1. A compound of Formula I
wherein
n is 0, 1, 2, or 3;
m is 0, 1, 2, or 3;
p is 1 or 2;
q is 0, 1, 2, 3, or 4;
Y is a bond, C\u2550O, or S(O)t; wherein t is 0, 1, or 2;
R1 is selected from a group consisting of: hydroxy, C1-C6 alkyl, aryl, C2-C6 alkenyl, C1-C6 haloalkyl, C1-C6 alkylheterocyclic, C3-C8 cycloalkyl, C1-C6 alkylcycloalkyl; C1-C6 alkylaryl, heterocyclyl, C1-C6 alkylalcohol, C1-C6 alkoxy, aryloxy, \u2014OC2-C6 alkenyl, \u2014OC1-C6 haloalkyl, \u2014OC1-C6 alkylheterocyclic, \u2014OC3-C8 cycloalkyl, \u2014OC1-C6 alkylcycloalkyl, \u2014NR7R8 and \u2014OC1-C6 alkylaryl, \u2014O-heterocyclic, \u2014OC1-C6 alkylheterocyclic, CI-C6 alkyl-O\u2014C(O)NR7R8, C1-C6 alkyl-NR7C(O)NR7R8, and C0-C6 alkylCOOR11; provided that R1 is not hydroxy when Y is S(O)t; and wherein each cycloalkyl, aryl and heterocyclic group is optionally substituted with 1 to 3 groups independently selected from oxo, hydroxy, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 alkylalcohol, CONR11R12, NR11SO2R12, NR11COR12, C0-C3 alkylNR11R12, C1-C3 alkylCOR11, C0-C6 alkylCOOR11, cyano, C1-C6 alkylcycloalkyl, phenyl, \u2014OC1-C6 alkylcycloalkyl, \u2014OC1-C6 alkylaryl, \u2014OC1-C6 alkylheterocyclic, and C1-C6 alkylaryl;
each R2 is bound only to a carbon atom and is a group independently selected from the group consisting of: hydrogen, hydroxy, halogen, oxo, C2-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C6 haloalkyl, CONR11R12, \u2014NR11SO2R12, \u2014NR11COR12, C0-C6 alkylNR11R12, C0-C6 alkylCOR1, C0-C6 alkylCOOR11, cyano, nitro, C0-C6 alkylcycloalkyl, phenyl, C0-C6 alkylaryl, heterocyclyl, C3-C8 cycloalkyl, and C1-C6 haloalkyl; and wherein two independently selected R2 groups are optionally gem-disubstituted;
R3a and R3b are independently selected from the group consisting of: hydrogen, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, and C1-C6 haloalkyl;
R4 is a group represented by the formula \u2014NR4aR4b wherein;
R4a is a heterocyclic, C1-C6 alkylheterocyclic, or C2-C6 alkenylheterocyclic group wherein each heterocyclic group is optionally substituted with 1 to 3 groups independently selected from the group consisting of: oxo, hydroxyl, halogen, \u2014NR11R12, C1-C6 alkyl, C1-C6 alkenyl, C0-C6 alkylCN, C1-C6 alkoxy, C1-C6 alkylalcohol, C1-C6 haloalkyl, \u2014OC(O)NR11R12, C1-C6 alkylNR11R12 wherein the C1-C6 alkyl group is optionally substituted with \u2014OR10 or C(O)OR10, C0-C6 alkylNO2, C0-C6 alkylNR11SO2R12, C0-C6 alkylC(O)NR11R12, C0-C6 alkylNR11C(O)R12, C0-C6 alkylNR11C(O)OR12, C0-C6 alkylNR11C(O)NR10R12, C0-C6 alkylNR11CHR10CO2R12, C0-C6 alkylC(O)OR11, C0-C6 alkylSO2NR11R12, C0-C6 alkylS(O)tR11, C3-C8 cycloalkyl, C1-C6 alkylcycloalkyl, and C0-C6 alkylheterocyclic wherein the heterocycle of the C0-C6 alkylheterocyclic group is optionally substituted with halo, C1-C6 alkyl, oxo, \u2014CO2R11 and \u2014NR11R12; and
R4b is selected from the group consisting of: C1-C6 alkylaryl, C2-C6 alkenylaryl, C2-C6 alkynylaryl, C1-C6 alkylheterocyclic, C2-C6 alkenylheterocyclic, C1-C6 alkylcycloalkyl, C1-C6 alkyl-O\u2014C1-C6 alkylaryl, wherein each cycloalkyl, aryl, or heterocyclic group is optionally substituted with 1-3 groups independently selected from the group consisting of:
hydroxy, oxo, \u2014SC1-C6 alkyl, C1-C6 alkyl, C1-C6 alkenyl, C1-C6 alkynyl, C1-C6 haloalkyl, halogen, C1-C6 alkoxy, aryloxy, C1-C6 alkenyloxy, C1-C6 haloalkoxyalkyl, C0-C6 alkylNR11R12, \u2014OC1-C6 alkylaryl, nitro, cyano, C1-C6 haloalkylalcohol, and C1-C6 alkyl alcohol;
R5 is selected from a group consisting of: hydrogen, hydroxy, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, aryloxy, \u2014OC2-C6 alkenyl, \u2014OC1-C6 haloalkyl, C1-C6 haloalkyl, C3-C8 cycloalkyl, C1-C6 alkylaryl, C1-C6 alkylheterocyclic, C2-C6 alkenylaryl, C2-C6 alkenylheterocyclic, aryl, heterocyclic, cyano, nitro, C0-C6 alkylNR7R8, C0-C6 alkylCOR7, C0-C6 alkylCO2R7, C0-C6 alkylCONR7R8, CONR7SO2R8, \u2014NR7SO2R8, \u2014NR7COR8, \u2014N\u2550CR7R8, \u2014OCONR7R8, \u2014S(O)tR7, \u2014SO2NR7R8, C0-C5CH2OH, \u2014OC1-C6 alkylheterocyclic, and \u2014OC1-C6 alkylaryl wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclic group or subgroup is optionally substituted with oxo, alkyloxy, aryloxy; and wherein any two R5 groups may combine to form an optionally substituted 5, 6, or 7-member fused ring with the phenyl ring (A-ring) to which they are attached, wherein the 5, 6, or 7-member fused ring is saturated, partially unsaturated, or fully unsaturated and optionally contains 1, 2, or 3 heteroatoms independently selected from O, N, and S;
R6 is independently selected from a group consisting of: hydrogen, C1-C6 alkyl, C2-C6 alkenyl, hydroxy, COR7, C1-C6 alkoxy, aryloxy, \u2014OC2-C6 alkenyl, \u2014OC1-C6 haloalkyl, C1-C6 alkylNR7R8, C3-C8 cycloalkyl, heterocyclic, aryl, C1-C6 alkyl-O\u2014C(O)NR7R8, C1-C6 alkyl-NR7C(O)NR7R8 and C1-C6 alkylcycloalkyl;
R7 and R8 are each independently selected from a group consisting of: hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, \u2014OC1-C6 alkyl, C1-C6 haloalkyl, \u2014O-aryl, \u2014OC3-C8 cycloalkyl, \u2014O-heterocyclic, \u2014NR7R8, \u2014C1-C6 alkylcycloalkyl, \u2014OC1-C6 alkylcycloalkyl, \u2014OC1-C6 alkylheterocyclic, C1-C6 alkylheterocyclic, \u2014O C1-C6 alkylaryl, C3-C8 cycloalkyl, heterocyclic, aryl, and C1-C6 alkylaryl, wherein each alkyl, cycloalkyl, heterocyclic or aryl group is optionally substituted with 1-3 groups independently selected from hydroxy, CN, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, and \u2014NR11R12, or R7 and R8 combine to form a nitrogen containing heterocyclic ring which having 0, 1, or 2 additional heteroatoms selected from oxygen, nitrogen and sulfur and wherein the nitrogen-containing heterocycle is optionally substituted with oxo or C1-C6 alkyl;
R10, R11 and R12 are independently selected from a group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkenyl, C3-C8 cycloalkyl, heterocyclic, aryl, C1-C6 alkylaryl, wherein each alkyl, aryl, cycloalkyl, and heterocyclic group is optionally substituted with 1-3 groups independently selected from halogen, C1-C6 alkylheterocyclic, and C1-C6 haloalkyl, or R11 and R12 combine to form a nitrogen containing heterocyclic ring which may have 0, 1, or 2 additional heteroatoms selected from oxygen, nitrogen or sulfur and is optionally substituted with oxo, C1-C6 alkyl, COR7, and \u2014SO2R7;
or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixture of diastereomers thereof.
2. A compound of claim 1 wherein p is 1.
3. A compound according to claim 1 wherein n, m, and q are independently 0, or 1.
4. A compound according to claim 1 wherein p is 1, n is 0, Y is C(O), and R1 is selected from a group consisting of: hydroxy, hydrogen, C1-C6 alkyl, C0-C6 alkylcycloalkyl, C0-C6 alkylheterocyclic, C1-C6 haloalkyl, C0-C6 alkylaryl, \u2014Oaryl, \u2014OC1-C6 haloalkyl, \u2014OC1-C6 alkylcycloalkyl, \u2014OC3-C8 cycloalkyl, \u2014OC1-C6 alkylcycloalkylNR7R8, \u2014OC1-C6 alkyl, \u2014OC0-C6 alkylaryl, \u2014OC1-C6 alkylcyano, \u2014OC1-C6 alkylCO2R11, \u2014OC3-C8 cycloalkylCO2R11, \u2014OC1-C6 alkylhydroxy, \u2014OC1-C6 alkylNR7R8 and \u2014OC1-C6 alkylheterocyclic; and wherein each alkyl, cycloalkyl, aryl, or heterocyclic is optionally substituted with 1 or 2 groups selected from halogen, C0-C3 alkylalcohol, C0-C3 alkylamine, C0-C3 alkylCOOH, C0-C3 alkylCONH2, C0-C3 alkylcyano, and
C0-C3 alkylC(O)OC1-C3 alkyl.
5. A compound according to claim 1 wherein p is 1, n is 0, Y is a bond, and R1 is selected from a group consisting of: C1-C6 alkyl, C0-C6 alkylcycloalkyl, C1-C6 alkylheterocyclic, C2-C6 haloalkyl, C0-C6 alkylaryl, C1-C6 alkylcycloalkylNR7R8, C1-C6 alkylcyano, C1-C6 alkylCO2R11, C1-C6 alkylcycloalkylCO2R11, C1-C6 alkylalcohol, and C1-C6 alkylNR7R8; and wherein each alkyl, cycloalkyl, aryl, or heterocyclic is optionally substituted with 1 or 2 groups selected from halogen, C0-C3 alkylalcohol, C0-C3 alkylamine, C0-C3 alkylCOOH, C0-C3 alkylCONH2, and C0-C3 alkylcyano.
6. A compound compound according to claim 1 wherein p is 1, R3a and R3b are both hydrogen and R4 is NR4aR4b; wherein R4b is 3,5-bistrifluoromethylbenzyl and R4a is selected from the group consisting of:
wherein each R is independently selected from the group consisting of: halogen, C0-C6 alkylalcohol, hydrogen, C1-C6 alkyl, C1-C6 alkoxy C0-C6 alkylcycloalkyl, C0-C6 alkylheterocyclic, C1-C6 alkylCN, C1-C6 haloalkyl, C0-C6 alkylNR11R12, C1-C6 alkylC(O)NR11R12, and C1-C6 alkylC(O)OR11.
7. A compound selected from the group consisting of:
(S)-5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepine-1-carboxylic acid tetrahydro-pyran-4-yl ester,
(S)-2-{5-(3,5-Bis-trifluoromethyl-benzyl)-(1-cyclopentylmethyl-7-methyl-8-trifluoromethyl-2,3,4, 5-tetrahydro-1H-benzobazepin-5-yl)-amino-tetrazol-2-yl}-ethanol,
(S)-2-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl}-ethanol,
(+\u2212)-9-(3,5-Bis-trifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino-2,2-difluoro-6,7,8,9-tetrahydro-1,3-dioxa-5-aza-cycloheptafindene-5-carboxylic acid isopropyl ester,
(+\u2212)-Isopropyl 5-(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino-8-chloro-2,3,4, 5-tetrahydrobenzobazepine-1-carboxylate,
(+\u2212)-isopropyl 5-(3,5-bistrifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-8-chloro-2,3,4,5-tetrahydrobenzobazepine-1-carboxylate,
(+\u2212) isopropyl -6-(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino-2,3,6,7,8,9-hexahydro-1H-10-aza-cycloheptaeindene-10-carboxylate,
(+\u2212)-isopropyl 5-(3,5-bistrifluoromethyl-benzyl)-(5-methyl-1H-pyrazol-3-yl)-amino-8-chloro-2,3,4,5-tetrahydrobenzobazepine-1-carboxylate,
+\u2212)-isopropyl 5-(3,5-bistrifluoromethyl-benzyl)-(5-methyl-isoxazol-5-yl)-amino-8-chloro-2,3,4,5-tetrahydrobenzobazepine-1-carboxylate,)
(S)-6-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-21-1-tetrazol-5-yl)-amino-4-methyl-2,3,6,7,8,9-hexahydro-1H-10-aza-cycloheptaeindene-10-carboxylic acid isopropyl ester,
(S)-isopropyl 5-(3,5-bistrifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-8,9-dimethyl-2,3,4,5-tetrahydrobenzobazepine-1-carboxylate,
(S)-isopropyl 5-{(3,5-Bis-trifluoromethyl-benzyl)-2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl-amino}-8,9-dimethyl-2,3,4,5-tetrahydrobenzobazepine-1-carboxylate,
(S)-9-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-2,3,6,7,8,9-hexahydro-1H-5-aza-cycloheptafindene-5-carboxylic acid tert-butyl ester,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(5-cyclopentylmethyl-1,2,3,5,6,7,8,9-octahydro-5-aza-cycloheptafinden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(5-cyclopentylmethyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cycloheptafinden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-5-{9-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cycloheptafinden-5-yl)-3,3-dimethyl-pentanoic acid,
(S)-5-(9-{(3,5-Bis-trifluoromethyl-benzyl)-2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl-amino}-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cycloheptafinden-5-yl)-3,3-dimethyl-pentanoic acid,
(3,5-Bis-trifluoromethyl-benzyl)-(1-cyclopentylmethyl-2,3,4,5,7,8,9,10-octahydro-1H-naphtho2,3-bazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-6-{(3,5-Bis-trifluoromethyl-benzyl)-2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl-amino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cycloheptaeindene-10-carboxylic acid isopropyl ester,
(S)-6-{(3,5-Bis-trifluoromethyl-benzyl)-2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl-amino}-4-methyl-2,3,6,7,8,9-hexahydro-1H-10-aza-cycloheptaeindene-10-carboxylic acid isopropyl ester,
(S)-9-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-2,3,6,7,8,9-hexahydro-1H-5-aza-cycloheptafindene-5,carboxylic acid 2-carboxy-2-methyl-propyl ester,
(S)-1-{5-(3,5-Bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl)-3-furan-2-ylmethoxy)-propan-2-one,
2-{5-(3,5-Bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl}-1-phenyl-ethanol,
2-{5-(3,5-Bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl) -2-phenyl-ethanol,
(4-{5-(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-ylmethyl}-cyclohexyl)-acetic acid methyl ester,
(4-{5-(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-ylmethyl}-cyclohexyl)-acetic acid,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine hydrochloride,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-3-ylmethyl-8-trifluoromethyl-2;3,4,5-tetrahydro-1H-benzobazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-2-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-ethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl}-ethanol,
(S)5-{9-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cycloheptafinden-5-ylmethyl}-thiophene-2-carboxylic acid,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(5-pyridin-4-ylmethyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cycloheptafinden-9-yl)-amine,
(S)-(4-{9-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cycloheptafinden-5-ylmethyl}-cyclohexyl)-acetic acid,
(S)-2-{9-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cycloheptafinden-5-yl}-ethanol,
(S)-9-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(3,5-bis-trifluoromethyl-benzyl)-amino-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cycloheptafindene-5-carboxylic acid tert-butyl ester,
(S)-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(5-benzyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cycloheptafinden-9-yl)-(3,5-bis-trifluoromethyl-benzyl)-amine,
(S)-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(3,5-bis-trifluoromethyl-benzyl)-5-(3,3,3-trifluoro-propyl)-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cycloheptafinden-9-yl-amine,
(S)-5-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-2,3,4,5,7,8,9,10-octahydro-naphtho2,3-bazepin-1-yl}-3,3-dimethyl-pentanoic acid,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(1-cyclopentylmethyl-11-methyl-2,3,4,5,7,8,9,10-octahydro-1H-naphtho2,3-bazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-5-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-ylmethyl}-thiophene-2-carboxylic acid,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(1,7-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-1-thiazol-2-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-amine,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-7-methyl-1-(1-methyl-1H-imidazol-2-ylmethyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl-(2-methyl-2H-tetrazol-5-amine,
(S)-5-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-ylmethyl},
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-piperidin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-(4-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-ylmethyl}-piperidin-1-yl)-acetic acid ethyl ester,
(S)-(4-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-ylmethyl}-piperidin-1-yl)-acetic acid,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyrrolidin-2-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,
(S)-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-1-(2-benzyloxy-ethyl)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl-(3,5-bis-trifluoromethyl-benzyl)-amine,
(S)-2-{5-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(3,5-bis-trifluoromethyl-benzyl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl}-ethanol,
(S)-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(3,5-bis-trifluoromethyl-benzyl)-(7-methyl-1-thiazol-2-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-amine,
(S)-(2-{5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepin-1-yl}-ethoxy)-acetic acid,
(S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-7-methyl-1-(2H-tetrazol-5-ylmethyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl-amine,
(S)-5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepine-1-carboxylic acid 2-amino-ethyl ester,
(S)-5-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzobazepine-1-carboxylic acid 2-carboxy-2-methyl-propyl ester,
(S)-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(3,5-bis-trifluoromethyl-benzyl)-(1-cyclopropylmethyl-7-methyl-8-tri fluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-amine,
(S)-2-(2-Amino-ethyl)-2H-tetrazol-5-yl-(3,5-bis-trifluoromethyl-benzyl)-(1-cyclopropylmethyl-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzobazepin-5-yl)-amine hydrochloride, and pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixture of diastereomers thereof.
8. A method of modulating CETP activity comprising administering a therapeutically effective composition comprising a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixture of diastereomers thereof to a patient in need thereof.
9. The method of claim 8 wherein modulation of CETP activity results in a decrease in LDL-cholesterol.
10. A method of treating or preventing dyslipidemia comprising administering a therapeutically effective composition comprising a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate diastereomer, mixture of diastereomers thereof, to a patient in need thereof.
11. A method of treating or preventing atherosclerosis comprising administering a therapeutically effective composition comprising a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to a patient.
12. A method of lowering plasma LDL-cholesterol in a mammal comprising administering a therapeutically effective dose of a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to said mammal.
13. A method of treating andor preventing the pathological sequelae due to high levels of plasma LDL-cholesterol in a mammal comprising administering a therapeutically effective dose of a compound of Formula I, pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer, or mixture of diastereomers to said mammal.
14. A pharmaceutical composition comprising a compound according to claim 1 and at least one of: a carrier, diluent, and excipient.
15. Use of a compound according to claim 1 for the manufacture of a medicament for treating or preventing atherosclerosis in a mammal comprising administering an effective dose of a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate; diastereomer, or mixture of diastereomers thereof to said mammal.
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 transit time ultrasound sensor for measuring a fluid flow in a conduit, comprising:
(a) a rigid housing;
(b) an upstream transducer affixed to the housing;
(c) a downstream transducer spaced from the upstream transducer and affixed to the housing to define an acoustic path between the upstream transducer and the downstream transducer, the acoustic path intersecting the fluid flow in the conduit; and
(d) a solid acoustic couplant disposed in the acoustic path and shaped to define a measuring channel sized to receive a length of the conduit, the acoustic couplant having an acoustic velocity within 10% of an acoustic velocity of the fluid flow and an acoustic velocity of the conduit wall, and an acoustic impedance within 10% of an acoustic impedance of the fluid flow and an acoustic impedance of the conduit wall.
2. A transit time ultrasound sensor for measuring a fluid flow in a conduit, comprising:
(a) a rigid housing;
(b) a first transducer affixed to the housing;
(c) one of a reflector and a second transducer spaced from the first transducer in one of an upstream location and a downstream location relative to the first transducer and affixed to the housing to define an acoustic path between the first transducer and the one of the reflector and the second transducer;
(d) a conduit in the acoustic path, the conduit having a curvilinear cross sectional profile, the transducer sized to illuminate the curved cross sectional profile with acoustic energy; and
(e) a solid acoustic couplant in the acoustic path and contacting the first transducer and at least partially defining a measuring channel sized to match the curvilinear conduit cross sectional profile.
3. A transit time ultrasound sensor for the measurement of fluid flow in a conduit, the sensor comprising:
(a) a rigid housing;
(b) a first transducer affixed to the housing for generating an acoustic wave having a nominal period and a planar wave front;
(c) a second transducer spaced from the first transducer and affixed to the housing to define an acoustic path between the first transducer and the second transducer along which the wave front travels to reach the second transducer;
(d) a conduit in the acoustic path having a curvilinear wall; and
(e) a solid acoustic couplant in the acoustic path and contacting a portion of the curvilinear wail; at least a portion of the planar wave front along the acoustic path reaching the second transducer within one-quarter of the nominal period.
4. A transit time ultrasound sensor as in claims 2 or 3, wherein the solid acoustic couplant contacts the first transducer.
5. The transit time ultrasound sensor of claim 1, wherein the solid acoustic couplant contacts the upstream transducer.
6. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant is a plastic.
7. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant is uncompressed.
8. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant has an acoustic velocity within 5% of the acoustic velocity of the conduit.
9. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant has an acoustic velocity within 5% of the acoustic velocity of the fluid flow.
10. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant has an acoustic impedance within 5% of the acoustic impedance of the conduit.
11. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant has an acoustic impedance within 5% of the acoustic impedance of the fluid flow.
12. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant has a hardness between approximately 75 to 95 Shore A.
13. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the solid acoustic couplant encompasses at least 25% of a length of the acoustic path.
14. A transit time ultrasound sensor as in claims 1, 2 or 3, wherein the conduit is substantially free of deformation under contact with the solid acoustic couplant.
15. A transit time ultrasound sensor for measuring a fluid flow in a measuring channel having a channel wall, comprising:
(a) a rigid housing;
(b) a first transducer affixed to the housing; and
(c) a solid, resilient plastic acoustic couplant intermediate the first transducer and the measuring channel, the acoustic couplant having an acoustic velocity within 5% of an acoustic velocity of the fluid flow and an acoustic velocity of the channel wall, and the acoustic couplant having an acoustic impedance within 5% of an acoustic impedance of the fluid flow and an acoustic impedance of the channel wall, the first transducer defining an acoustic path.
16. The transit time ultrasound sensor of claim 15, wherein the acoustic couplant defines a portion of the measuring channel to have a curvilinear cross section.
17. The transit time ultrasound sensor of claim 15, wherein the acoustic couplant has a hardness between approximately 75 to 95 Shore A.
18. A transit time ultrasound sensor for the measurement of a blood flow in a conduit, the sensor configured with an acoustic path extending between an upstream location and a spaced apart downstream location, the acoustic path illuminating a blood flow in the conduit, the sensor comprising a solid acoustic couplant having a density between 0.9 gcm3 and 1.15 gcm3.
19. A transit time ultrasound sensor for the measurement of a blood flow in a conduit, the sensor configured with an acoustic path that illuminates a blood flow in the conduit, the sensor comprising a solid acoustic couplant having a density within 10% of a density of blood, an acoustic velocity within 10% of an acoustic velocity of blood and an acoustic impedance within 10% of an acoustic impedance of blood.
20. The transit time ultrasound sensor of claim 19, wherein the solid acoustic couplant is a plastic elastomer.
21. The transit time ultrasound sensor of claim 19, further comprising a transducer, wherein the transducer and the acoustic couplant illuminate a full field of the blood flow.
22. The transit time ultrasound sensor of claim 19, wherein the acoustic couplant has a curvilinear profile corresponding to a profile of a blood flow conduit.
23. The transit time ultrasound sensor of claim 19, wherein the acoustic couplant is one of a polyether block amide and a polyurethane.
24. A transit time ultrasound sensor for measuring a fluid flow, comprising:
(a) a frame;
(b) an upstream transducer connected to the frame;
(c) a downstream transducer spaced from the upstream transducer and connected to the frame; and
(d) a solid acoustic coupler disposed between the upstream transducer and the downstream transducer to define a measuring channel sized to receive a length of the conduit, the solid acoustic coupler having an acoustic velocity within 10% of an acoustic velocity of the fluid, an acoustic path defined between the upstream transducer and the downstream transducer.
25. The transit time ultrasound sensor of claim 24, wherein the solid acoustic coupler has an acoustic velocity within 10% of an acoustic velocity of a wall of the conduit.
26. The transit time ultrasound sensor of claim 24, wherein the solid acoustic coupler has an acoustic impedance within 10% of an acoustic impedance of the fluid.
27. The transit time ultrasound sensor of claim 24, wherein the solid acoustic coupler has an acoustic impedance within 10% of an acoustic impedance of a wall of the conduit.
28. The transit time ultrasound sensor of claim 24, wherein the solid acoustic coupler is a plastic.
29. The transit time ultrasound sensor of claim 24, wherein the solid acoustic coupler is a thermoplastic elastomer.
30. The transit time ultrasound sensor of claim 24, wherein the solid acoustic coupler is one of a polyether block amide and a polyurethane.