Author: claimsbot

1. A method for conserving electrical power in a telecommunications facility containing a plurality of like electrically powered hardware resources for transporting call traffic through the facility, said method comprising:
(a) monitoring a traffic load being experienced by the facility;
(b) selecting one or more of the hardware resources in response to the monitored traffic load, such that the selected hardware resources have a capacity sufficient to reliably transport the monitored traffic load thereover; and
(c) consolidating call traffic in the selected hardware resources.
2. The method of claim 1, wherein said consolidating comprises:
transferring call traffic from non-selected hardware resources to selected hardware resources.
3. The method of claim 2, further comprising:
(d) powering down one or more non-selected hardware resources such that electrical power consumption by a powered down hardware resource is at least one of interrupted or reduced.
4. The method of claim 2, wherein the facility is a mobile switch center.
5. The method of claim 4, wherein the hardware resources are media gateways.
6. The method of claim 2, wherein the facility is a central office.
7. The method of claim 6, wherein the hardware resources are telecommunication switches.
8. The method of claim 2, wherein each hardware resource is a distinct hardware module with a set capacity to transport call traffic thereover, and a plurality of the hardware modules are combined into a piece of telecommunications equipment.
9. The method of claim 3, wherein the step (d) is automatically executed.
10. The method of claim 2, further comprising:
(d) providing a human perceivable output which identifies non-selected hardware resources available for powering down such that electrical power consumption by a powered down hardware resources is at least one of interrupted or reduced.
11. The method of claim 2, further comprising:
dynamically altering the selection of hardware resources and consolidation of traffic therein in response to the monitored traffic load.
12. The method of claim 11, wherein as the monitored traffic load decreases, fewer hardware resources are selected and call traffic is further consolidated in the fewer selected hardware resources thereby freeing more non-selected hardware resources from the burden of transporting call traffic thereover.
13. The method of claim 11, wherein as the monitored traffic load increases, more hardware resources are selected to raise the capacity of the selected hardware resources and accommodate said increase.
14. A telecommunications facility comprising:
a plurality of like hardware resources that selectively transport call traffic thereover; and
a functional entity operative to:
(i) monitor a traffic load being experienced by the facility;
(ii) select one or more of the hardware resources in response to the monitored traffic load, such that the selected hardware resources have a capacity sufficient to reliably transport the monitored traffic load thereover; and
(iii) consolidate call traffic in the selected hardware resources thereby freeing non-selected hardware resources from the burden of transporting call traffic thereover.
15. The telecommunications facility of claim 14, further comprising:
a human perceivable output which identifies non-selected hardware resources available for powering down such that electrical power consumption by a powered down hardware resources is at least one of interrupted or reduced.
16. The telecommunications facility of claim 14, wherein one or more of the hardware resources includes a power state selection interface that allows a power state of the hardware resource to be automatically selected from at least one of a powered on state in which the hardware resource is operational and receiving electrical power therefor and a powered down state in which the electrical power consumption by the hardware resource is at least one of interrupted or reduced.
17. The telecommunications facility of claim 16, wherein one or more of the hardware resources including the power state selection interface are automatically powered on and down via the interface based upon them being selected or not selected by the functional entity.
18. The telecommunications facility of claim 14, wherein the functional entity comprises a central processing unit running a software program to execute the operative monitoring, selection and consolidation.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

What is claimed is:

1. A compound of the formula I:
49
or a pharmaceutically acceptable salt thereof, wherein
R1 is
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, O, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino, N(R)C(O)R, OC(O)-amino and OC(O)-mono- or dialkylamino, or
C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
aryl, heteroaryl, heterocyclyl, aryl (C1-C6) alkyl-, heteroaryl (C1-C6)alkyl-, or heterocyclyl(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, OH, SH, CN, NO2, NR105R105, CO2R, N(R)COR, N(R)SO2R, C(O)(C1-C4) alkyl, SO2-amino, SO2-monoalkylamino, SO2-dialkylamino, C(O)-amino, C(O)-monoalkylamino, C(O)-dialkylamino, SO2(C1-C4) alkyl,
C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino,
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino and C1-C3 alkyl, and
C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo;
R and R independently are hydrogen, C1-C10 alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl;
R2 are the same or different and are H or C1-C6 alkyl optionally substituted with with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, halogen, OH, SH, CON, CF3, C1-C3 alkoxy, and NR105R105;
RC and RC are independently hydrogen, (CR245R250)0-4-aryl, (CR245R250)0-4-heteroaryl, (CR245R250)0-4-heterocyclyl, (CR245R250)0-4-aryl-heteroaryl, (CR245R250)0-4-aryl-heterocyclyl, (CR245R250)0-4-aryl-aryl, (CR245R250)0-4-heteroaryl-aryl, (CR245R250)0-4-heteroaryl-heterocyclyl, (CR245R250)0-4-heteroaryl-heteroaryl, (CR245R250)0-4-heterocyclyl-heteroaryl, (CR245R250)0-4-heterocyclyl-heterocyclyl, (CR245R2SO)0-4-heterocyclyl-aryl, CH(aryl)2, CH(heteroaryl)2, CH(heterocyclyl)21CH(aryl)(heteroaryl), (CH2)0-1CH((CH2)0-6OH)(CH2)0-1-aryl, (CH2)0-1CH(CH2)0-1OH)(CH2)0-1-heteroaryl, CH(-aryl or -heteroaryl)CO(C1-C4 alkyl), (C1-C6 alkyl)O(C1-C6 alkyl)-OH; CH2NHCH2CH(OCH2CH3)2, (CH2)0-6
C(NR235)(NR235R240), C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R110, R120 and R130,
C2-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, R110, R120, R130, OCONR235R240, S(O)0-2(C1-C6 alkyl), SH, and S(O)2NR235R240,
(CH2)0-3(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, CO2H, and CO2(C1-C4 alkyl), or
cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR215, O, and S(O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group is optionally substituted with one or two groups that are independently R205, O, CONR235R240, or SO2(C1-C4 alkyl), or
C2-C10 alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R210;

R200 at each occurrence is independently selected from OH, NO2, halogen, CO2H, CN, (CH2)0-4CONR220R225, (CH2)0-4CO(C1-C12 alkyl), (CH2)0-4CO(C2-C12 alkenyl), (CH2)0-4CO(C2-C12 alkynyl), (CH2)0-4CO(C3-C7 cycloalkyl), (CH2)0-4CO-aryl, (CH2)0-4CO-heteroaryl, (CH2)0-4CO-heterocyclyl, (CH2)0-4COOR215, (CH2)0-4SO2NR22OR225, (CH2)0-4SO(C1-C8 alkyl), (CH2)0-4SO2(C1-C12 alkyl), (CH2)0-4SO2(C3-C7 cycloalkyl), (CH2)0-4N(H or R215)COOR215, (CH2)0-4N(H or R215)CON(R215)2, (CH2)0-4NCSN(R21)2, (CH2)0-4N(H or R215)COR220, (CH2)0-4NR22OR225, (CH2)0-4CO(C1-Calkyl), (CH2)0-4OP(O)(OR240)2, (CH2)0-4OCON(R215)2, (CH2)0-4OCSN(R215)2, (CH2)0-4O(R215), (CH2)0-4O(R215)COOH, (CH2)0-4S(R215), (CH2)0-4O(C1-C6) alkyl optionally substituted with 1, 2, or 3 F, C3-C7 cycloalkyl, (CH2)0-4N(H or R215)SO2R220, (CH2)0-4C3-C7 cycloalkyl,
C1-C10 alkyl optionally substituted with 1, 2, or 3 independently selected R205 groups,
C2-C10 alkenyl and C2-C10 alkynyl, each of which is optionally substituted with 1 or 2 independently selected R205 groups, wherein
the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein

the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210;

R205 at each occurrence is independently selected from C1-C6 alkyl, halogen, OH, O-phenyl, SH, SC1-C6 alkyl, CN, CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) or N(C1-C6 alkyl)(C1-C6 alkyl);
R210 at each occurrence is independently selected from halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, NR220R225, OH, CN, CO(C1-C4 alkyl), SO2NR235R240, CONR235R240, SO2(C1-C4 alkyl), O, or
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;

R215 at each occurrence is independently selected from C1-C6 alkyl, (CH2)0-2-(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and (CH2)0-2-(heteroaryl), (CH2)0-2-(heterocyclyl), wherein
the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R210;

R220 and R225 at each occurrence are independently selected from H, C3-C7 cycloalkyl, (C1-C2 alkyl)-(C3-C7 cycloalkyl), (C1-C6 alkyl)-O(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, and
C1-C10 alkyl optionally substituted with OH, NH2 or halogen, wherein
the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R270 groups

R235 and R240 at each occurrence are independently H, or C1-C6 alkyl;
R245 and R250 at each occurrence are independently selected from H, C1-C4 alkyl, C1-C4 alkylaryl, C1-C4 alkylheteroaryl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, (CH2)0-4C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and phenyl; or
R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from O, S, SO2, and NR220;
R255 and R260 at each occurrence are independently selected from H, (CH2)1-2S(O)0-2(C1-C6 alkyl), (C1-C4 alkyl)-aryl, (C1-C4 alkyl)-heteroaryl, (C1-C4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, (CH2)1-4R265(CH2)0-4-aryl, (CH2)1-4-R265(CH2)0-4-heteroaryl, (CH2)1-4R265(CH2)0-4-heterocyclyl, and
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and (CH2)0-4C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein
each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein

each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;

R265 at each occurrence is independently O, S or N(C1-C6 alkyl)-;
R270 at each occurrence is independently R205, halogen C1-C6 alkoxy, C1-C6 haloalkoxy, NR235R240, OH, CN, CO(C1-C4 alkyl), SO2NR235R240, CONR235R240, SO2(C1-C4 alkyl), O, or
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or (CH2)0-4C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;

RN is R100, SO2R100, (CRR)1-6R100, C(O)(CRR)0-6R100, C(O)(CRR)1-6OR100, C (O)(CRR)1-6SR100, C(O)(CRR)1-6C(O)R100, C(O)(CRR)1-6SO2R100 or C(O)(CRR)1-6NR100R100;
R100 and R100 independently represent aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, -heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, CH (CH2)0-2OR150(CH2)0-2-aryl, CH(CH2)0-2OR150(CH2)0-2-heterocyclyl or CH(CH2)0-2OR150(CH2)0-2-heteroaryl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from
OR, NO2, C1-C6 alkyl, halogen, CN, OCF3, CF3, (CH2)0-4OP(O)(OR)(OR), (CH2)0-4CONR105R105, (CH2)0-4O(CH2)0-4CONR102R102, (CH2)0-4CO(C1-C12 alkyl), (CH2)0-4CO(C2-C12 alkenyl), (CH2)0-4CO(C2-C12 alkynyl), (CH2)0-4CO(CH2)0-4(C3-C7 cycloalkyl), (CH2)0-4R110, (CH2)0-4R120, (CH2)0-4R130, (CH2)0-4COR110, (CH2)0-4COR120, (CH2)0-4COR130, (CH2)0-4COR140, (CH2)0-4COOR150, (CH2)0-4SO2NR105R105, (CH2)0-4SO(C1-C8 alkyl), (CH2)0-4SO2(C1-C12 alkyl), (CH2)0-4SO2(CH2)0-4(C3-C7 cycloalkyl), (CH2)0-4N(R150)COOR150, (CH2)0-4N(R150)CON(R150)2, (CH2)0-4N(R150)CSN(R150)2, (CH2)0-4N(R150)COR105, (CH2)0-4NR105R105, (CH2)0-4R140, (CH2)0-4OCO(C1-C6 alkyl), (CH2)0-4OP(O)(OR110)2, (CH2)0-4OCON(R150)2, (CH2)0-4OCSN(R150)2, (CH2)0-4O(R150), (CH2)0-4OR150COOH, (CH2)0-4S(R150), (CH2)0-4N(R150)SO2R105, (CH2)0-4 C3-C7 cycloalkyl, (C2-C10)alkenyl, and (C2-C10)alkynyl, or

R100 is C1-C10 alkyl optionally substituted with 1, 2, or 3 R115 groups, or
R100 is (C1-C6 alkyl)OC1-C6 alkyl) or (C1-C6 alkyl)-S(C1-C6 alkyl), each of which is optionally substituted with 1, 2, or 3 R115 groups, or
R100 is C3-C8 cycloalkyl optionally substituted with 1, 2, or 3 R115 groups;
W is (CH2)0-4, S(O)0-2, N(R135), CR(OH) or C(O);
R102 and R102 independently are hydrogen, or
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups that are independently halogen, aryl or R110;

R105 and R105 independently represent H, R110, R120, C3-C7 cycloalkyl, (C1-C2 C3-C7 cycloalkyl), (C1-C6 alkyl)O(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkyl chain with one double bond and one triple bond, or
C1-C6 alkyl optionally substituted with OH or NH2; or,
C1-C6 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, or

R105 and R105 together with the atom to which they are attached form a 3 to 7 membered carbocylic ring, where one member is optionally a heteratom selected from O, S(O)0-2, N(R135), the ring being optionally substituted with 1, 2 or 3 independently selected R140 groups;
R115 at each occurrence is independently halogen, OH, CO2R102, C1-C6 thioalkoxy, CO2-phenyl, NR150R135, SO2(C1-C8 alkyl), C(O)R180, R180, CONR105R105, SO2NR105R105, NHCO(C1-C6 alkyl), NHCOR110, NHCOR120, NHC(O)OH, NHC(O)OR, NHC(O)O-phenyl, OC(O)(C1-C6 alkyl), OC(O)-amino, OC(O)-mono- or dialkylamino, OC(O)-phenyl, O(C1-C6 alkyl) CO2H, NHSO2(C1-C6 alkyl), C1-C6 alkoxy or C1-C6 haloalkoxy;
R135 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, (CH2)0-2-(aryl), (CH2)0-2-(heteroaryl) or (CH2)0-2-(heterocyclyl);
R140 is heterocyclyl optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C1-C6) alkylamino, di (C1-C6) alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino (C1-C6) alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di (C1-C6)alkylamino(C1-C6)alkyl, and O;
R145 is C1-C6 alkyl or CF3;
R150 is hydrogen, C3-C7 cycloalkyl, (C1-C2 alkyl)-(C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, R110, R120, or
C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from OH, NH2, C1-C3 alkoxy, R110, and halogen;

R150 is C3-C7 cycloalkyl, (C1-C3 alkyl)-(C3-C7 cycloalkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, R110, R120, or
C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from OH, NH2, C1-C3 alkoxy, R110, and halogen;

R155 is C3-C7 cycloalkyl, (C1-C2 alkyl)-(C3-C7 cycloalkyl) C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl with one double bond and one triple bond, R110, R120, or
C1-C6 alkyl optionally substituted with 1, 2, 3, or 4 groups independently selected from OH, NH2, C1-C3 alkoxy, and halogen;

R180 is selected from morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S,S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3, or 4 groups independently selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, hydroxy, cyano, nitro, amino, mono(C1-C6)alkylamino, di(C1-C6)alkylamino, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, amino(C1-C6)alkyl, mono(C1-C6)alkylamino(C1-C6)alkyl, di (C1-C6)alkylamino(C1-C6)alkyl, and O;
R110 is aryl optionally substituted with 1 or 2 R125 groups;
R125 at each occurrence is independently halogen, amino, mono- or dialkylamino, OH, CN, SO2NH2, SO2NHC1-C6 alkyl, SO2N(C1-C6 alkyl)2, SO2(C1-C4 alkyl), CONH2, CONHC1-C6 alkyl, or CON(C1-C6 alkyl)2, or
C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups that are independently selected from C1-C3 alkyl, halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, and mono- and dialkylamino, or
C1-C6 alkoxy optionally substituted with one, two or three of halogen;

R120 is heteroaryl, which is optionally substituted with 1 or 2 R125 groups; and
R130 is heterocyclyl optionally substituted with 1 or 2 R125 groups; and
X is NH, O, or S.
2. A compound according to claim 1 wherein
R2 at each occurrence is H; and
R1 is C1-C6 alkyl-aryl, C1-C6 alkyl-heteroaryl, or C1-C6 alkyl-heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, OH, SH, CN, NO2, NR105R105, CO2R, N(R)COR, or N(R)SO2R, C(O)(C1-C4) alkyl, SO2-amino, SO2-mono or dialkylamino, C(O)-amino, C(O)-mono or dialkylamino, SO2(C1-C4) alkyl, or
C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen, or
C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino, or
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino and C1-C3 alkyl, or
C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo, or

R1 is C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, O, SH, CN, CF3, C1-C3 alkoxy, S(C1-C3)alkyl, amino, mono- or dialkylamino, N(R)C(O)R, OC(O)-amino and OC(O)-mono- or dialkylamino.
3. A compound according to claim 2 wherein
RC is H or is C1-C6 alkyl optionally substituted with with one, two or three substituents independently selected from the group consisting of C1-C3 alkyl, halogen, OH, SH, CON, CF3, C1-C3 alkoxy, and NR105R105.
4. A compound according to claim 3 wherein
RN is C(O)(CRR)0-6R100;
R100 represents aryl, heteroaryl, or heterocyclyl, where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from
OR, NO2, C1-C6 alkyl, halogen, CN, OCF3, CF3, (CH2)0-4OP(O)(OR)(OR), (CH2)0-4CONR105R105, (CH2)0-4O(CH2)0-4CONR102R102, (CH2)0-4CO(C1-C12 alkyl), (CH2)0-4CO(C2-C12 alkenyl), (CH2)0-4CO(C2-C12 alkynyl), (CH2)0-4CO(CH2)0-4 (C3-C7 cycloalkyl), (CH2)0-4R110, (CH2)0-4R120, (CH2)0-4R130, (CH2)0-4COR110, (CH2)0-4COR120, (CH2)0-4COR130, (CH2)0-4COR140, (CH2)0-4COOR150, (CH2)0-4SO2NR105R105, (CH2)0-4SO(C1-C8 alkyl), (CH2)0-4SO2(C1-C12 alkyl), (CH2)0-4SO2(CH2)0-4-(C3-C7 cycloalkyl), (CH2)0-4N(R150)COOR150, (CH2)0-4N(R150)CON(R150)2, (CH2)0-4N(R150)CSN(R150)2, (CH2)0-4N(R150)COR105, (CH2)0-4NR105R105, (CH2)0-4R140, (CH2)0-4CO(C1-C6 alkyl), (CH2)0-4OP(O)(OR110)2, (CH2)0-4OCON(R15O)2, (CH2)0-4OCSN(R150)2, (CH2)0-4O(R150), (CH2)0-4OR150COOH, (CH2)0-4S(R150), (CH2)0-4N(R150)SO2R105, (CH2)0-4C3-C7 cycloalkyl, (C2-C10)alkenyl, or (C2-C10)alkynyl.
5. A compound according to claim 3 wherein
RN is C(O)(CRR)0-6R100; and
R100 is C1-C10 alkyl optionally substituted with 1, 2, or 3 R115 groups.
6. A compound according to claim 4 wherein
RN is C(O)-aryl or C(O)-heteroaryl where the ring portions of each are optionally substituted with 1, 2, or 3 groups independently selected from
OR, NO2, C1-C6 alkyl, halogen, CN, OCF3, CF3, (CH2)0-4CONR105R105, (CH2)0-4O(CH2)0-4CONR102R102, (CH2)0-4CO(C1-C12 alkyl), (CH2)0-4CO(C2-C12 alkenyl), (CH2)0-4CO(C2-C12 alkynyl), (CH2)0-4R110, (CH2)0-4R120, (CH2)0-4R130, (CH2)0-4COR110, (CH2)0-4COR120, (CH2)0-4COR130, (CH2)0-4COR140, (CH2)0-4COOR150, (CH2)0-4SO2NR105R105, (CH2)0-4SO(C1-C8 alkyl) (CH2)0-4SO2(C1-C12 alkyl), (CH2)0-4N(R150)COOR150, (CH2)0-4N(R150)CON(R150)2, (CH2)0-4N(R150)COR105, (CH2)0-4NR105R105, (CH2)0-4R140, (CH2)0-4OCO(C1-C6 alkyl), (CH2)0-4OCON(R150)2, (CH2)0-4O(R150), (CH2)0-4N(R150)SO2R105, (CH2)0-4 C3-C7 cycloalkyl, (C2-C10)alkenyl, or (C2-C10)alkynyl.
7. A compound according to claim 5 wherein
RN is C(O)C1-C10 alkyl optionally substituted with 1, 2, or 3 of halogen, OH, CO2R102, C1-C6 thioalkoxy, CO2-phenyl, NR105R105, SO2(C1-C8 alkyl), C(O)R180, R180, CONR105R105, SO2NR105R105, NHCO(C1-C6 alkyl), NHCO-R110, NHCOR120, NHC(O)OH, NHC(O)OR, NHC(O)O-phenyl, OC(O)(C1-C6 alkyl), OC(O)-amino, OC(O)-mono- or dialkylamino, OC(O)-phenyl, O(C1-C6 alkyl)-CO2H, NHSO2(C1-C6 alkyl), C1-C6 alkoxy or C1-C6 haloalkoxy.
8. A compound according to claim 6 wherein
RC is (CH2)-aryl, (CH2)-heteroaryl, or
C2-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C6 alkyl, halogen, OH, O-phenyl, SH, SC1-C6 alkyl, CN, CF3, C1-C6 alkoxy, and NH2, wherein
each aryl and heteroaryl is optionally substituted with 1, 2, or 3 groups selected from OH, NO2, halogen, CO2H, CN, (CH2)0-4CONR220R225, (CH2)0-4CO(C1-C12 alkyl), and (CH2)0-4SO2NR220R225.
9. A compound according to claim 7 wherein
RC is (CH2)-aryl, (CH2)-heteroaryl, or
C2-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from C1-C6 alkyl, halogen, OH, O-phenyl, SH, SC1-C6 alkyl, CN, CF3, C1-C6 alkoxy, and NH2, wherein
each aryl and heteroaryl is optionally substituted with 1, 2, or 3 groups selected from OH, NO2, halogen, CO2H, CN, (CH2)0-4CONR220R225, (CH2)0-4CO(C1-C12 alkyl), and (CH2)0-4SO2NR22OR225.
10. A compound according to claim 8 or 9 selected from the grou consisting of:
N-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethoxy)-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-1-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethoxy)-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethoxy)-propylcarbamoyl-2-(butane-1-sulfonyl)-ethyl-nicotinamide,
N-1-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propylcarbamoyl-2-(butane-1-sulfonyl)-ethyl-nicotinamide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 1-benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethoxy)-propyl-amide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 1-benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propyl-amide,
N-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylamino)-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-1-(3,5-Difluoro-benzyl)-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-1-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylamino)-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-1-(3,5-Difluoro-benzyl)-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-1-Benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylamino)-propylcarbamoyl-2-(butane-1-sulfonyl)-ethyl-nicotinamide,
N-2-(Butane-1-sulfonyl)-1-1-(3,5-difluoro-benzyl)-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propylcarbamoyl-ethyl-nicotinamide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 1-benzyl-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylamino)-propyl-amide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 1-(3,5-difluoro-benzyl)-2-hydroxy-3-isobutylcarbamoyl-3-(2-methoxy-ethylsulfanyl)-propyl-amide,
N-1-Benzyl-2-hydroxy-3-(2-hydroxy-ethylamino)-3-phenethylcarbamoyl-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-3-Benzylcarbamoyl-1-(3,5-difluoro-benzyl)-2-hydroxy-3-(2-methoxy-ethylsulfanyl)-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-1-1-Benzyl-2-hydroxy-3-(2-hydroxy-ethylamino)-3-phenethylcarbamoyl-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-3-Benzylcarbamoyl-1-(3,5-difluoro-benzyl)-2-hydroxy-3-(2-methoxy-ethylsulfanyl)-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-1-Benzyl-2-hydroxy-3-(2-hydroxy-ethylamino)-3-phenethylcarbamoyl-propylcarbamoyl-2-(butane-1-sulfonyl)-ethyl-nicotinamide,
N-1-3-Benzylcarbamoyl-1-(3,5-difluoro-benzyl)-2-hydroxy-3-(2-methoxy-ethylsulfanyl)-propylcarbamoyl-2-(butane-1-sulfonyl)-ethyl-nicotinamide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 1-benzyl-2-hydroxy-3-(2-hydroxy-ethylamino)-3-phenethylcarbamoyl-propyl-amide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 3-benzylcarbamoyl-1-(3,5-difluoro-benzyl)-2-hydroxy-3-(2-methoxy-ethylsulfanyl)-propyl-amide,
N-1-(3,5-Difluoro-benzyl)-2-hydroxy-3-(2-methanesulfonyl-ethoxy)-3-phenethylcarbamoyl-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-3-Benzylcarbamoyl-3-(3-cyano-propoxy)-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl-5-methyl-N,N-dipropyl-isophthalamide,
N-1-1-(3,5-Difluoro-benzyl)-2-hydroxy-3-(2-methanesulfonyl-ethoxy)-3-phenethylcarbamoyl-propylcarbamoyol-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-1-3-Benzylcarbamoyl-3-(3-cyano-propoxy)-1(3,5-difluoro-benzyl)-2-hydroxy-propylcarbamoyl-2-(heptane-4-sulfonyl)-ethyl-nicotinamide,
N-2-(Butane-1-sulfonyl)-1-1-(3,5-difluoro-benzyl)-2-hydroxy-3-(2-methanesulfonyl-ethoxy)-3-phenethylcarbamoyl-propylcarbamoyl-ethyl-nicotinamide,
N-1-3-Benzylcarbamoyl-3-(3-cyano-propoxy)-1-(3,5-difluoro-benzyl)-2-hydroxy-propylcarbamoyl-2-(butane-1-sulfonyl)-ethyl-nicotinamide,
2-Methanesulfonylamino-thiazole-4-carboxylic acid 1-(3,5-difluoro-benzyl)-2-hydroxy-3-(2-methanesulfonyl-ethoxy)-3-phenethylcarbamoyl-propyl-amide, and
2-Methanesulfonylamino-thiazole-4-carboxylic acid 3-benzylcarbamoyl-3-(3-cyano-propoxy)-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl-amide.
11. A method for the treatment or prevention of Alzheimer’s disease, mild cognitive impairment Down’s syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, other degenerative dementias, dementias of mixed vascular and degenerative origin, dementia associated with Parkinson’s disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration, diffuse Lewy body type of Alzheimer’s disease compriseing administration of a therapeutically effective amount of a compound or salt according to claim 1, to a patient in need thereof.
12. A method of treatment as in claim 11, wherein the patient is a human.
13. A method of treatment according to claim 11, wherein the disease is dementia.
14. A method for making a compound of claim 1.
15. An intermediate of the formula III:
50
wherein R1 is
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, O, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino, N(R)C(O)R, OC(O)-amino and OC(O)-mono- or dialkylamino, or
C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
aryl, heteroaryl, heterocyclyl, aryl (C1-C6) alkyl-, heteroaryl (C1-C6) alkyl-, or heterocyclyl(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, OH, SH, CN, NO2, NR105R105, CO2R, N(R)COR, N(R)SO2R, C(O)(C1-C4) alkyl, SO2-amino, SO2-monoalkylamino, SO2 dialkylamino, C(O)-amino, C(O)-monoalkylamino, C(O)-dialkylamino, SO2(C1-C4) alkyl,
C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino,
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino and C1-C3 alkyl, and
C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo; and

R and R independently are hydrogen, C1-C10 alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl.
16. An intermediate of the formula IV:
51
wherein
R1 is
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, O, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino, N(R)C(O)R, OC(O)-amino and OC(O)-mono- or dialkylamino, or
C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
aryl, heteroaryl, heterocyclyl, aryl (C1-C6) alkyl-, heteroaryl(C1-C6)alkyl-, or heterocyclyl(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, OH, SH, CN, NO2, NR105R105, CO2R, N(R)COR, N(R)SO2R, C(O)(C1-C4) alkyl, SO2-amino, SO2-monoalkylamino, SO2-dialkylamino, C(O)-amino, C(O)-monoalkylamino, C(O)-dialkylamino, SO2(C1-C4) alkyl,
C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C2-C6 alkyl and mono- or dialkylamino,
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino and C1-C3 alkyl, and
C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo;
R and R independently are hydrogen, C1-C10 alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl; and
RC is hydrogen, (CR245R250)0-4-aryl, (CR245R250)0-4-heteroaryl, (CR245R250)0-4-heterocyclyl, (CR245R2so)0-4-aryl-heteroaryl, (CR245R250)0-4-aryl-heterocyclyl, (CR245R250)0-4-aryl-aryl, (CR245R250)0-4-heteroaryl-aryl, (CR245R250)0-4-heteroaryl-heterocyclyl, (CR245R250)0-4-heteroaryl-heteroaryl, (CR245R250)0-4-heterocyclyl-heteroaryl, (CR245R250)0-4-heterocyclyl-heterocyclyl, (CR245R250)0-4-heterocyclyl-aryl, CH(aryl)2, CH(heteroaryl)2, CH(heterocyclyl)2, CH(aryl)(heteroaryl), (CH2)0-1CH((CH2)0-6OH)(CH2)0-1-aryl, (CH2)0-1CH((CH2)0-6OH)(CH2)0-1-heteroaryl, CH(-aryl or -heteroaryl)-COO(C1-C4 alkyl), (C1-C6 alkyl)-O(C1-C6 alkyl)-OH; CH2NHCH2CH(OCH2CH3)2,
(CH2)0-6C(NR235)(NR235R240), C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R110, R120 and R130,
C2-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, R110, R120, R130, OCONR235R240, S(O)0-2(C1-C6 alkyl), SH, and S(O)2NR235R240,
(CH2)0-3(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, CO2H, and CO2(C1-C4 alkyl), or
cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR215, O, and S(O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group is optionally substituted with one or two groups that are independently R205, O, CONR235R240, or SO2(C1-C4 alkyl), or
C2-C10 alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein
each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R210;

R200 at each occurrence is independently selected from OH, NO2, halogen, CO2H, CN, (CH2)0-4CONR220R225, (CH2)0-4CO(C1-C12 alkyl), (CH2)0-4CO(C2-C12 alkenyl), (CH2)0-4CO(C2-C12 alkynyl), (CH2)0-4CO(C3-C7 cycloalkyl), (CH2)0-4CO-aryl, (CH2)0-4CO-heteroaryl, (CH2)0-4CO-heterocyclyl, (CH2)0-4COOR215, (CH2)0-4SO2NR220R225, (CH2)0-4SO(C1-C8 alkyl), (CH2)0-4SO2(C1-C12 alkyl), (CH2)0-4SO2(C3-C7 cycloalkyl), (CH2)0-4N(H or R215)COOR215, (CH2)0-4N(H or R215)CON(R215)2, (CH2)0-4NCSN(R215)2, (CH2)0-4N(H or R215)COR220(CH2)0-4NR220R225, (CH2)0-4OCO(C1-C6 alkyl), (CH2)0-4P(O)(OR240)2(CH2)0-4OCON(R215)2, (CH2)0-4OCSN(R215)2, (CH2)0-4O(R215), (CH2)0-4O(R215)COOH, (CH2)0-4S(R215), (CH2)0-4O(C1-C6) alkyl optionally substituted with 1, 2, or 3 F, C3-C7 cycloalkyl, (CH2)0-4N(H or R215)SO2R220, (CH2)0-4C3-C7 cycloalkyl,
C1-C10 alkyl optionally substituted with 1, 2, or 3 independently selected R205 groups,
C2-C10 alkenyl and C2-C10 alkynyl, each of which is optionally substituted with 1 or 2 independently selected R205 groups, wherein
the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein

the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210;

R205 at each occurrence is independently selected from C1-C6 alkyl, halogen, OH, O-phenyl, SH, SC1-C6 alkyl, CN, CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) or N(C1-C6 alkyl)(C1-C6 alkyl);
R210 at each occurrence is independently selected from halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, NR220R225, OH, CN, CO(C1-C4 alkyl), SO2 NR235R240, CONR235R240, SO2(C1-C4 alkyl), O, or
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;

R215 at each occurrence is independently selected from C1-C6 alkyl, (CH2)0-2-(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and (CH2)0-2-(heteroaryl), (CH2)0-2-(heterocyclyl), wherein
the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R210;

R220 and R225 at each occurrence are independently selected from H, C3-C7 cycloalkyl, (C1-C2 alkyl)-(C3-C7 cycloalkyl), (C1-C6 alkyl)-O(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, and
C1-C10 alkyl optionally substituted with OH, NH2 or halogen, wherein
the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R270 groups

R235 and R240 at each occurrence are independently H, or C1-C6 alkyl;
R245 and R250 at each occurrence are independently selected from H, C1-C4 alkyl, C1-C4 alkylaryl, C1-C4 alkylheteroaryl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, (CH2)0-4C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and phenyl; or
R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from O, S, SO2, and NR220;
R255 and R260 at each occurrence are independently selected from H, (CH2)1-2S(O)0-2(C1-C6 alkyl), (C1-C4 alkyl) -aryl, (C1-C4 alkyl)-heteroaryl, (C1-C4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, (CH2)14R265(CH2)0-4-aryl, (CH2)1-4R265(CH2)0-4-heteroaryl, (CH2)1-4R265(CH2)0-4-heterocyclyl, and
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and (CH2)0-4C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein
each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein

each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;

R265 at each occurrence is independently O, S or N(C1-C6 alkyl)-;
R270 at each occurrence is independently R205, halogen C1-C6 alkoxy, C1-C6 haloalkoxy, NR235R240, OH, CN, CO(C1-C4 alkyl), SO2NR235R240, CONR235R240, SO2(C1-C4 alkyl), O, or
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or (CH2)0-4C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups.
17. An intermediate of the formula V:
52
wherein
R1 is
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, O, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino, N(R)C(O)R, OC(O)-amino and OC(O)-mono- or dialkylamino, or
C2-C6 alkenyl or C2-C6 alkynyl, each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, and mono- or dialkylamino, or
aryl, heteroaryl, heterocyclyl, aryl (C1-C6) alkyl-, heteroaryl (C1-C6) alkyl-, or heterocyclyl(C1-C6)alkyl-, where the ring portions of each are optionally substituted with 1, 2, 3, or 4 groups independently selected from halogen, OH, SH, CN, NO2, NR105R105, CO2R, N(R)COR, N(R)SO2R, C(O)(C1-C4) alkyl, SO2-amino, SO2-monoalkylamino, SO2-dialkylamino, C(O)-amino, C(O)-monoalkylamino, C(O)-dialkylamino, SO2(C1-C4) alkyl,
C1-C6 alkoxy optionally substituted with 1, 2, or 3 groups which are independently selected from halogen,
C3-C7 cycloalkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino,
C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, mono- or dialkylamino and C1-C3 alkyl, and
C2-C10 alkenyl or C2-C10 alkynyl each of which is optionally substituted with 1, 2, or 3 groups independently selected from halogen, OH, SH, CN, CF3, C1-C3 alkoxy, amino, C1-C6 alkyl and mono- or dialkylamino; and the heterocyclyl group is optionally further substituted with oxo;
R and R independently are hydrogen, C1-C10 alkyl, C1-C10 alkylaryl or C1-C10 alkylheteroaryl; and
RC and RC are independently hydrogen, (CR245R250)0-4-aryl, (CR245R250)0-4-heteroaryl, (CR245R250)0-4-heterocyclyl, (CR245R250)0-4-aryl-heteroaryl, (CR245R250)0-4-aryl-heterocyclyl, (CR245R250)0-4-aryl-aryl, (CR245R250)0-4 heteroaryl-aryl, (CR245R250)0-4-heteroaryl-heterocyclyl, (CR245R250)0-4-heteroaryl-heteroaryl, (CR245R250)0-4-heterocyclyl-heteroaryl, (CR245R250)0-4-heterocyclyl-heterocyclyl, (CR245R250)0-4-heterocyclyl-aryl, CH(aryl)2, CH(heteroaryl)2, CH(heterocyclyl)2, CH(aryl)(heteroaryl), (CH2)0-1CH((CH2)0-6OH)(CH2)0-1-aryl, (CH2)0-1CH ((CH2)0-6OH) (CH2)0-1-heteroaryl, CH(-aryl or -heteroaryl)-COO(C1-C4 alkyl), (C1-C6 alkyl)-O(C1-C6 alkyl)-OH; CH2NHCH2CH(OCH2CH3)2, (CH2)0-6
C(NR235)(NR235R240), C1-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R110, R120 and R130,
C2-C10 alkyl optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, R110, R120, R130, OCONR235R240, S(O)0-2(C1-C6 alkyl), SH, and S(O)2NR235R240,
(CH2)0-3(C3-C8) cycloalkyl wherein the cycloalkyl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of R205, CO2H, and CO2(C1-C4 alkyl), or
cyclopentyl, cyclohexyl, or cycloheptyl ring fused to aryl, heteroaryl, or heterocyclyl wherein one, two or three carbons of the cyclopentyl, cyclohexyl, or cycloheptyl is optionally replaced with a heteroatom independently selected from NH, NR215, O, and S(O)0-2, and wherein the cyclopentyl, cyclohexyl, or cycloheptyl group is optionally substituted with one or two groups that are independently R205, O, CONR235R240, or SO2(C1-C4 alkyl), or
C2-C10 alkenyl or C2-C10 alkynyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein
each aryl and heteroaryl is optionally substituted with 1, 2, or 3 R200, and wherein each heterocyclyl is optionally substituted with 1, 2, 3, or 4 independently selected R210;

R200 at each occurrence is independently selected from OH, NO2, halogen, CO2H, CN, (CH2)0-4CONR220R225, (CH2)0-4CO(C1-C12 alkyl), (CH2)0-4CO(C2-C12 alkenyl), (CH2)0-4CO(C2-C12 alkynyl), (CH2)0-4CO(C3-C7 cycloalkyl), (CH2)0-4CO-aryl, (CH2)0-4CO-heteroaryl, (CH2)0-4CO-heterocyclyl, (CH2)0-4COOR215, (CH2)0-4SO2NR220R225, (CH2)0-4SO(C1-C8 alkyl), (CH2)0-4SO2(C1-C12 alkyl), (CH2)0-4SO2(C3-C7 cycloalkyl), (CH2)0-4N(H or R215)COOR215, (CH2)0-4N(H or R215)CON(R215)2, (CH2)0-4NCSN(R215)2, (CH2)0-4N(H or R215)COR220(CH2)0-4NR220R225, (CH2)0-4OCO(C1-C6 alkyl), (CH2)0-4OP(O)(OR240)2, (CH2)0-4OCON(R215)2, (CH2)0-4OCSN(R215)2, (CH2)0-4O (R215), (CH2)0-4O (R215)COOH, (CH2)0-4S(R215), (CH2)0-4O(C1-C6) alkyl optionally substituted with 1, 2, or 3 F, C3-C7 cycloalkyl, (CH2)0-4N(H or R215)SO2R220, (CH2)0-4C3-C7 cycloalkyl,
C1-C10 alkyl optionally substituted with 1, 2, or 3 independently selected R205 groups,
C2-C10 alkenyl and C2-C10 alkynyl, each of which is optionally substituted with 1 or 2 independently selected R205 groups, wherein
the aryl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein

the heterocyclyl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R210;

R205 at each occurrence is independently selected from C1-C6 alkyl, halogen, OH, O-phenyl, SH, SC1-C6 alkyl, CN, CF3, C1-C6 alkoxy, NH2, NH(C1-C6 alkyl) or N(C1-C6 alkyl)(C1-C6 alkyl);
R210 at each occurrence is independently selected from halogen, C1-C6 alkoxy, C1-C6 haloalkoxy, NR220R225, OH, CN, CO(C1-C4 alkyl), SO2NR235R240, CONR235R240, SO2(C1-C4 alkyl), O, or
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups;

R215 at each occurrence is independently selected from C1-C6 alkyl, (CH2)0-2(aryl), C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and (CH2)0-2-(heteroaryl), (CH2)0-2-(heterocyclyl), wherein
the aryl group at each occurrence is optionally substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein
the heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R210;

R220 and R225 at each occurrence are independently selected from H, C3-C7 cycloalkyl, (C1-C2 alkyl)-(C3-C7 cycloalkyl), (C1-C6 alkyl)-O(C1-C3 alkyl), C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl chain with one double bond and one triple bond, -aryl, -heteroaryl, and -heterocyclyl, and
C1-C10 alkyl optionally substituted with OH, NH2 or halogen, wherein
the aryl, heterocyclyl and heteroaryl groups at each occurrence are optionally substituted with 1, 2, or 3 independently selected R270 groups

R235 and R240 at each occurrence are independently H, or C1-C6 alkyl;
R245 and R250 at each occurrence are independently selected from H, C1-C4 alkyl, C1-C4 alkylaryl, C1-C4 alkylheteroaryl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, (CH2)0-4C3-C7 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, and phenyl; or
R245 and R250 are taken together with the carbon to which they are attached to form a carbocycle of 3, 4, 5, 6, or 7 carbon atoms, where one carbon atom is optionally replaced by a heteroatom selected from O, S, SO2, and NR220;
R255 and R260 at each occurrence are independently selected from H, (CH2)1-2S(O)0-2(C1-C6 alkyl), (C1-C4 alkyl)-aryl, (C1-C4 alkyl)-heteroaryl, (C1-C4 alkyl)-heterocyclyl, -aryl, -heteroaryl, -heterocyclyl, (CH2)14R265(CH2)0-4-aryl, (CH2)1-4R265(CH2)0-4-heteroaryl, (CH2)1-4R265(CH2)0-4-heterocyclyl, and
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and (CH2)0-4C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 independently selected R205 groups, wherein
each aryl or phenyl is optionally substituted with 1, 2, or 3 groups that are independently R205, R210, or
C1-C6 alkyl substituted with 1, 2, or 3 groups that are independently R205 or R210, and wherein

each heterocyclyl is optionally substituted with 1, 2, 3, or 4 R210;

R265 at each occurrence is independently O, S or N(C1-C6 alkyl)-;
R270 at each occurrence is independently R205, halogen C1-C6 alkoxy, C1-C6 haloalkoxy, NR235R240, OH, CN, CO(C1-C4 alkyl), SO2NR235R240, CONR235R240, SO2(C1-C4 alkyl), O, or C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or (CH2)0-4C3-C7 cycloalkyl, each of which is optionally substituted with 1, 2, or 3 R205 groups.

1. A method of delivering a gas mixture containing an effective amount of nitric oxide, in combination with oxygen, to an infected site of a patient to reduce pathogen levels comprising the steps of:
providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen;
mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen;
providing a bathing unit around the infected site of the patient, the bathing unit forming a seal with the infected site of the patient;
transporting the gas mixture to the bathing unit so as to bathe the infected site of the patient with the gas mixture.
2. The method of claim 1, wherein the pathogen is at least one selected from the group consisting of a bacterium, a virus, a fungus, a parasite, an arthropod and a protozoan.
3. The method of claim 1, wherein the pathogen is an antibiotic-resistant bacteria.
4. The method of claim 3, wherein the antibiotic-resistant bacteria is at least one selected from the group consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Escherichia coli, Salmonella, Klebsiella, Enterococci, and combinations thereof.
5. The method of claim 1, further comprising the step of evacuating at least a portion of the nitric oxide gas is evacuated from the bathing unit.
6. The method according to claim 1, further comprising the step of removing at least a portion of the nitric oxide contained within the gas mixture that is evacuated from the bathing unit.
7. The method according to claim 1, further comprising the step of controlling the flow rate of gas mixture into and out of the bathing unit.
8. The method according to claim 1, further comprising the step of agitating the gas mixture within the bathing unit.
9. The method according to claim 1, further comprising the step of directing the flow of gas mixture onto the infected site of the patient.
10. The method of claim 1, wherein the infected site is a wound.
11. The method of claim 10, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
12. The method of claim 1, wherein the infected site is an abscess.
13. The method of claim 1, wherein the infected site is a lesion.
14. The method of claim 1, wherein the gas mixture is delivered to the infected site at a pressure greater than 1 atmosphere.
15. A method to promote healing of an area of the body of a patient with a wound, the method comprising the steps of: providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; and mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering gas mixture to the area of the body so as to bathe the wound with the gas mixture; and wherein the wound is infected by at least one type of pathogen.
16. The method of claim 15, wherein the pathogen is at least one selected from the group consisting of a bacterium, a virus, a fungus, a parasite, an arthropod and a protozoan.
17. The method of claim 15, wherein the pathogen is an antibiotic-resistant bacteria.
18. The method of claim 15, wherein the antibiotic-resistant bacteria is at least one selected from the group consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Escherichia coli, Salmonella, Klebsiella, Enterococci, and combinations thereof.
19. The method of claim 15, wherein the gas mixture is delivered to the area using a bathing unit surrounding the area.
20. The method of claim 15, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
21. The method of claim 15, further comprising the step of refreshing the area with a fresh supply of the gas mixture.
22. The method of claim 15, wherein the step of refreshing utilizes an agitator.
23. The method of claim 15, wherein a jet of the gas mixture is delivered to the wound.
24. The method of claim 15, wherein the source of nitric oxide is a pressurized cylinder containing nitric oxide gas.
25. The method of claim 15, wherein the source of oxygen is a pressurized cylinder containing oxygen.
26. The method of claim 15, further comprising the step of monitoring the concentration of nitric oxide bathing the area.
27. The method of claim 15, further comprising the step of monitoring the concentration of nitrogen dioxide bathing the area.
28. The method of claim 15, further comprising the step of monitoring the concentration of oxygen bathing the area.
29. The method of claim 17, further comprising the step of evacuating the gas mixture from the area.
30. The method of claim 15, wherein the gas mixture is delivered to the wound at a pressure greater than 1 atmosphere.
31. A method to promote healing of a lesion, the method comprising the steps on identifying the lesion on the body of a patient; providing a flow-controlled source of gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering the gas mixture to the lesion on the body of the patient; and wherein the lesion is infected by at least one type of pathogen.
32. The method of claim 31, wherein the pathogen is at least one selected from the group consisting of a bacterium, a virus, a fungus, a parasite, an arthropod and a protozoan.
33. The method of claim 31, wherein the pathogen is an antibiotic-resistant bacteria.
34. The method of claim 33, wherein the antibiotic-resistant bacteria is at least one selected from the group consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Escherichia coli, Salmonella, Klebsiella, Enterococci, and combinations thereof.
35. The method of claim 31, further comprising the step of sealing the gas mixture.
36. The method of claim 31, further comprising the step of diluting the gas mixture.
37. The method of claim 31, wherein the nitric oxide gas flows from a pressurized cylinder containing nitric oxide gas.
38. The method of claim 31, wherein the oxygen gas flows from a pressurized cylinder containing oxygen gas.
39. The method of claim 31, further comprising the step of adjusting the pressure of the gas mixture delivered to the lesion.
40. The method of claim 31, further comprising evacuating the gas mixture at a flow rate substantially equal to a flow rate of the gas mixture delivered to the lesion.
41. The method of claim 31, wherein the lesion is a wound.
42. The method of claim 41, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
43. The method of claim 31, wherein the lesion is an abscess.
44. The method of claim 31, wherein the gas mixture is delivered to the lesion at a pressure greater than 1 atmosphere.
45. A method to promote healing of a lesion, the method comprising the steps of: identifying the lesion in the body of a patient; providing a flow-controlled source of gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering the gas mixture to the lesion in the body of the patient; and wherein the lesion is infected by at least one type of pathogen.
46. The method of claim 45, wherein the pathogen is at least one selected from the group consisting of a bacterium, a virus, a fungus, a parasite, an arthropod and a protozoan.
47. The method of claim 45, wherein the pathogen is an antibiotic-resistant bacteria.
48. The method of claim 47, wherein the antibiotic-resistant bacteria is at least one selected from the group consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Escherichia coli, Salmonella, Klebsiella, Enterococci, and combinations thereof.
49. The method of claim 45 further comprising the step of diluting the gas mixture.
50. The method of claim 45, wherein the source of nitric oxide gas is a pressurized cylinder containing nitric oxide gas.
51. The method of claim 45, wherein the source of oxygen gas is a pressurized cylinder containing oxygen gas.
52. The method of claim 45, further comprising the step of adjusting the pressure of the gas mixture delivered to the lesion.
53. The method of claim 45, further comprising evacuating the gas mixture at a flow rate substantially equal to a flow rate of the gas mixture delivered to the lesion.
54. The method of claim 45, wherein the lesion is a wound.
55. The method of claim 54, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
56. The method of claim 45, wherein the lesion is an abscess.
57. The method of claim 45, wherein the gas mixture is delivered to the lesion at a pressure greater than 1 atmosphere.
58. A method to promote healing of a lesion on or in the body of a patient, the method comprising the steps of: providing a source of gas containing nitric oxide and a source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; diluting the gas mixture; and delivering the diluted gas mixture to the lesion; wherein the lesion is infected by at least one type of pathogen.
59. The method of claim 58, wherein the pathogen is at least one selected from the group consisting of a bacterium, a virus, a fungus, a parasite, an arthropod and a protozoan.
60. The method of claim 58, wherein the pathogen is an antibiotic-resistant bacteria.
61. The method of claim 60, wherein the antibiotic-resistant bacteria is at least one selected from the group consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Escherichia coli, Salmonella, Klebsiella, Enterococci, and combinations thereof.
62. The method of claim 58, wherein the step of mixing the gas containing nitric oxide with the gas containing oxygen is performed using a gas blender.
63. The method of claim 58, wherein the gas mixture delivered to the lesion is flow controlled.
64. The method of claim 58, wherein the step of diluting the gas mixture further comprises the step of delivering a dilutant gas to a sealed area over the lesion.
65. The method of claim 58, further comprising the step of monitoring the concentration of nitric oxide being delivered.
66. The method of claim 65, further comprising the step of monitoring the concentration of oxygen being delivered.
67. The method of claim 58, wherein the lesion is a wound.
68. The method of claim 67, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
69. The method of claim 58, wherein the lesion is an abscess.
70. The method of claim 58, wherein the gas mixture is delivered to the lesion at a pressure greater than 1 atmosphere.
71. A method of treating an infected site by exposure to a gas mixture containing nitric oxide and oxygen, comprising the steps of providing a source of gas containing nitric oxide and a source of gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; delivering the gas mixture to the infected site so as to bathe the infected site with the gas mixture; and wherein the infected site is infected by at least one type of pathogen.
72. The method of claim 71, wherein the pathogen is at least one selected from the group consisting of a bacterium, a virus, a fungus, a parasite, an arthropod and a protozoan.
73. The method of claim 71, wherein the pathogen is an antibiotic-resistant bacteria.
74. The method of claim 73, wherein the antibiotic-resistant bacteria is at least one selected from the group consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumoniae, Escherichia coil, Salmonella, Klebsiella, Enterococci, and combinations thereof.
75. The method of claim 71, wherein the gas mixture is delivered to the infected site using a bathing unit surrounding the infected site.
76. The method of claim 71, further comprising the step of refreshing the infected site with a fresh supply of the gas mixture.
77. The method of claim 71, wherein a jet of the gas mixture is delivered to the infected site.
78. The method of claim 71, wherein the source of nitric oxide gas is a pressurized cylinder containing nitric oxide gas.
79. The method of claim 71, wherein the source of oxygen gas is a pressurized cylinder containing oxygen gas.
80. The method of claim 71, further comprising the step of monitoring the concentration of nitric oxide bathing the infected site.
81. The method of claim 71, further comprising the step of monitoring the concentration of oxygen bathing the infected site.
82. The method of claim 71, further comprising the step of monitoring the concentration of nitrogen dioxide bathing the infected site.
83. The method of claim 71, further comprising the step of evacuating the gas mixture from the area surrounding the infected site.
84. The method of claim 71, further comprising the step of stripping nitric oxide from the evacuated gas mixture.
85. The method of claim 71, further comprising the step of stripping nitrogen dioxide from the evacuated gas mixture.
86. The method of claim 71, wherein the infected site is a wound.
87. The method of claim 86, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
88. The method of claim 71, wherein the infected site is an abscess.
89. The method of claim 71, wherein the infected site is a lesion.
90. The method of claim 71, wherein the gas mixture is delivered to the infected site at a pressure greater than 1 atmosphere.
91. A method of treating an infected site by exposure to a gas mixture comprising the steps of: providing a source of gas containing nitric oxide and a source of gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; delivering the gas mixture to the infected site so as to bathe the infected site with the gas mixture; evacuating the gas mixture from the area surrounding the infected site; and stripping nitric oxide from the evacuated gas mixture.
92. The method of claim 91, wherein the infected site is a wound.
93. The method of claim 92, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
94. The method of claim 91, wherein the infected site is an abscess.
95. The method of claim 91, wherein the infected site is a lesion.
96. The method of claim 91, wherein the gas mixture is delivered to the infected site at a pressure greater than 1 atmosphere.
97. A method of treating an infected site with a gas mixture comprising the steps of: providing a source of gas containing nitric oxide and a source of gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; delivering the gas mixture to the infected site so as to bathe the infected site with the gas mixture; evacuating the gas mixture from the area surrounding the infected site; and stripping nitric dioxide from the evacuated gas mixture.
98. The method of claim 97, wherein the step of refreshing utilizes an agitator.
99. The method of claim 97, wherein the infected site is a wound.
100. The method of claim 99, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
101. The method of claim 97, wherein the infected site is an abscess.
102. The method of claim 97, wherein the infected site is a lesion.
103. The method of claim 97, wherein the gas mixture is delivered to the infected site at a pressure greater than 1 atmosphere.
104. A method of treating an infected site comprising the steps of: identifying the infected site on or in a human; providing a flow-controlled source of gas containing nitric oxide and a flow-controlled source of gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering the gas mixture to at least a portion of the infected site.
105. The method of claim 104, further comprising the step of sealing the gas mixture.
106. The method of claim 104, further comprising the step of diluting the gas mixture with a dilutant gas.
107. The method of claim 104, wherein the flow-controlled source of nitric oxide gas flows from a pressurized cylinder containing nitric oxide gas.
108. The method of claim 104, further comprising the step of adjusting the pressure of the gas mixture delivered to the infected site.
109. The method of claim 104, further comprising evacuating the gas mixture at a flow rate substantially equal to a flow rate of the gas mixture delivered to the infected site.
110. The method of claim 104, wherein the step of refreshing utilizes an agitator.
111. The method of claim 104, wherein the infected site is a wound.
112. The method of claim 111, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
113. The method of claim 104, wherein the infected site is an abscess.
114. The method of claim 104, wherein the gas mixture is delivered to the infected site at a pressure greater than 1 atmosphere.
115. A method of treating an infected site by exposure to a gas mixture comprising the steps of: providing a source of gas containing nitric oxide and a source of gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; diluting the gas mixture with a dilutant gas; delivering the diluted gas mixture to at least a portion of the infected site.
116. The method of claim 115, wherein the step of mixing the gas containing nitric oxide with the gas containing oxygen is performed using a gas blender.
117. The method of claim 115, wherein the gas mixture delivered to the infected site is flow controlled.
118. The method of claim 115, wherein the step of diluting the gas mixture further comprises the step of delivering the dilutant gas to a sealed area over the infected site.
119. The method of claim 115, further comprising the step of monitoring the concentration of nitric oxide being delivered.
120. The method of claim 115, further comprising the step of refreshing the gas mixture utilizing an agitator.
121. The method of claim 115, wherein the infected site is a wound.
122. The method of claim 121, wherein the wound is at least one selected from the group consisting of a surgical wound, a trauma wound and a burn.
123. The method of claim 115, wherein the infected site is an abscess.
124. A method of delivering a gas mixture to an infected site of a patient to reduce pathogen levels comprising the steps of: providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; providing a bathing unit around the infected site of the patient, the bathing unit forming a seal with the infected site of the patient; transporting the gas mixture to the bathing unit so as to bathe the infected site of the patient with the gas mixture; controlling the flow rate of the gas mixture into and out of the bathing unit; agitating the gas mixture within the bathing unit; directing the flow of gas mixture onto the infected site of the patient; actively or passively evacuating at least a portion of the gas mixture from the bathing unit; and removing at least a portion of the nitric oxide contained within the gas mixture that is evacuated from the bathing unit.
125. A method to promote healing of an area of the body of a patient with a wound, the method comprising the steps of: providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering the gas mixture to the area of the body so as to bathe the wound; wherein the gas mixture is delivered to the area using a bathing unit surrounding the area; wherein the gas mixture bathing the area is refreshed utilizing an agitator; wherein the wound is infected by at least one type of pathogen; wherein the source of gas containing nitric oxide is a pressurized cylinder containing nitric oxide gas; wherein the source of gas containing oxygen is a pressurized cylinder containing oxygen; wherein the concentration of nitric oxide bathing the area is monitored; wherein the concentration of nitrogen dioxide bathing the area is monitored; wherein the concentration of oxygen bathing the area is monitored; and wherein the gas mixture is evacuated from the area.
126. A method to promote healing of a lesion, the method comprising the steps of: identifying the lesion on the body of a patient; providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering the gas mixture to the lesion on the body of the patient; wherein the lesion is infected by at least one type of pathogen; wherein the delivery area of the gas mixture is sealed to prevent contact with air in the atmosphere; wherein the source of gas containing nitric oxide is a pressurized cylinder; wherein the source of gas containing oxygen is a pressurized cylinder; wherein the pressure of the gas mixture delivered to the lesion is adjusted; and wherein the gas mixture is evacuated at a flow rate substantially equal to the flow rate that the gas mixture is delivered to the lesion.
127. A method of treating an infected site by exposure to a gas mixture comprising the steps of: providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; and delivering the gas mixture to the infected site so as to bathe the infected site with the gas mixture; wherein the infected site is infected by at least one type of pathogen; wherein the gas mixture is delivered to the infected site using a bathing unit surrounding the infected site; wherein the gas mixture bathing the infected site is refreshed with a fresh supply of the gas mixture; wherein a jet of gas mixture is delivered to the infected site; wherein the source of gas containing nitric oxide is a pressurized cylinder; wherein the source of gas containing oxygen is a pressurized cylinder; wherein the concentration of nitric oxide bathing the infected site is monitored; wherein the concentration of oxygen bathing the infected site is monitored; wherein the concentration of nitrogen dioxide bathing the infected site is monitored; wherein the gas mixture bathing the infected site is evacuated; wherein nitric oxide is stripped from the evacuated gas mixture; and wherein nitrogen dioxide is stripped from the evacuated gas mixture.
128. A method of treating an infected site with a gas containing 10,000 ppm nitric oxide, in combination with 20% oxygen, comprising the steps of providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; delivering the gas mixture to the infected site so as to bathe the infected site with the gas mixture; evacuating the gas mixture from the area surrounding the infected site; stripping nitric dioxide from the evacuated gas mixture; and refreshing the gas mixture utilizing an agitator.
129. A method of treating an infected site comprising the steps of: identifying the infected site on or in a human; providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; delivering the gas mixture to at least a portion of the infected site; sealing the delivery area to prevent contact with air in the atmosphere; wherein the source of the gas containing nitric oxide is a pressurized cylinder; wherein the source of the gas containing oxygen is a pressurized cylinder; wherein the pressure of the gas mixture delivered to the infected site is adjusted; evacuating the gas mixture at a flow rate substantially equal to the flow rate of the gas mixture delivered to the infected site; refreshing the gas mixture bathing the infected site utilizing an agitator.
130. A method of treating an infected site by exposure to gas mixture comprising the steps of: providing a flow-controlled source of a gas containing nitric oxide and a flow-controlled source of a gas containing oxygen; mixing the gas containing nitric oxide with the gas containing oxygen, wherein the gas mixture contains at least about 10,000 ppm nitric oxide and at least about 20% oxygen; diluting the gas mixture; delivering the diluted gas mixture to at least a portion of the infected site; wherein the step of diluting the gas mixture is performed using a gas blender; wherein the gas mixture delivered to the infected site is flow controlled; wherein the step of diluting the gas mixture further comprises the step of delivering the gas mixture to a sealed area over the infected site; monitoring the concentration of nitric oxide being delivered; monitoring the concentration of oxygen being delivered; and refreshing the gas mixture bathing the infected site utilizing an agitator.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A method of returning information from a database search comprising:
creating an index list with positional counters in nodes for a first subindex;
maintaining for each entry an aggregate value of information in a second subindex for entries before each entry;
traversing the index list and obtaining a first aggregate value for all entries before a first value of the first subindex;
traversing the index list and obtaining a second aggregate value for a first entry after the first value of the first subindex;
subtracting the first aggregate value from the second aggregate value to identify the aggregate of the second subindex for entries with the same value in the first subindex;
returning to the user a response based on the subtracting.
2. The method of claim 1, wherein the aggregate value is a sum of values in the second subindex.
3. The method of claim 2, further comprising determining the number of items with the first value, and using the aggregate sum and number of items to determine an average.
4. The method of claim 1, wherein the aggregate value is a sum of squares of values in the second subindex.
5. The method of claim 1, wherein the index information is maintained in a B*tree index.
6. A database system for implementing the method of claim 1.
7. The database of claim 6, wherein the aggregate value is a sum of values in the second subindex.
8. The database of claim 7, further comprising determining the number of items with the first value, and using the aggregate sum and number of items to determine an average.
9. The database of claim 6, wherein the aggregate value is a sum of squares of values in the second subindex.
10. The database of claim 6, wherein the index information is maintained in a B*tree index.