1. A compound represented by the structural formula
or a pharmaceutically acceptable salt or solvate thereof, wherein:
the dotted line represents an optional double bond;
a is 0 to 2;
b is 0 to 2;
n is 2;
p is 1, 2 or 3;
r is 0, 1, 2, or 3;
with the proviso that the sum of p and r is 3;
M1 is N;
M2 is C(R3);
X is a bond or C1\u2013C6 alkylene;
Y is \u2014C(O)\u2014, \u2014C(S)\u2014, \u2014(CH2)q\u2014, \u2014NR4C(O)\u2014, \u2014C(O)NR4\u2014, \u2014C(O)CH2\u2014, \u2014SO2\u2014, \u2014N(R4)\u2014, \u2014NH\u2014C(\u2550N\u2014CN)\u2014 or \u2014C(\u2550N\u2014CN)\u2014NH\u2014; with the provisos that when M1 is N, Y is not \u2014NR4C(O)\u2014 or \u2014NH\u2014C(\u2550N\u2014CN)\u2014; when M2 is N, Y is not \u2014C(O)NR4\u2014 or \u2014C(\u2550N\u2014CN)\u2014NH\u2014; and when Y is \u2014N(R4)\u2014, M1 is CH and M2 is C(R3);
q is 1 to 5, provided that when both M1 and M2 are N, q is 2 to 5;
Z is a bond, C1\u2013C6 alkylene, C1\u2013C6 alkenylene, \u2014C(O)\u2014, \u2014CH(CN)\u2014, \u2014SO2\u2014 or \u2014CH2C(O)NR4\u2014;
R1 is
Q is \u2014N(R8)\u2014, \u2014S\u2014 or \u2014O\u2014;
k is 0, 1, 2, 3 or 4;
k1 is 0, 1, 2 or 3;
k2 is 0, 1 or 2;
R is H, C1\u2013C6 alkyl, halo(C1\u2013C6)alkyl-, C1\u2013C6 alkoxy, (C1\u2013C6)alkoxy-(C1\u2013C6)alkyl-, (C1\u2013C6)-alkoxy-(C1\u2013C6)alkoxy, (C1\u2013C6)alkoxy-(C1\u2013C6)alkyl-SO0-2, R32-aryl(C1\u2013C6)alkoxy-, R32-aryl(C1\u2013C6)alkyl-, R32-aryl, R32-aryloxy, R32-heteroaryl, (C3\u2013C6)cycloalkyl, (C3\u2013C6)cycloalkyl-(C1\u2013C6)alkyl, (C3\u2013C6)cycloalkyl-(C1\u2013C6)alkoxy, (C3\u2013C6)cycloalkyl-oxy-, R37-heterocycloalkyl, R37-heterocycloalkyl-oxy-, R37-heterocycloalkyl-(C1\u2013C6)alkoxy, N(R30)(R31)\u2014(C1\u2013C6)alkyl-, \u2014N(R30)(R31), \u2014NH\u2014(C1\u2013C6)alkyl-O\u2014(C1\u2013C6)alkyl, \u2014NHC(O)NH(R29); R29\u2014S(O)0-2\u2014, halo(C1\u2013C6)alkyl-S(O)0-2\u2014, N(R30)(R31)\u2014(C1\u2013C6)alkyl-S(O)0-2\u2014 or benzoyl;
R8 is H, C1\u2013C6 alkyl, halo(C1\u2013C6)alkyl-, (C1\u2013C6)alkoxy-(C1\u2013C6)alkyl-, R32-aryl(C1\u2013C6)alkyl-, R32-aryl, R32-heteroaryl, (C3\u2013C6)cycloalkyl, (C3\u2013C6)cycloalkyl-(C1\u2013C6)alkyl, R37-heterocycloalkyl, N(R30)(R31)\u2014(C1\u2013C6)alkyl-, R29\u2014S(O)2\u2014, halo(C1\u2013C6)alkyl-S(O)2\u2014, R29\u2014S(O)0-1\u2014(C2\u2013C6)alkyl-, halo(C1\u2013C6)alkyl-S(O)0-1\u2014(C2\u2013C6)alkyl-;
R2 is a six-membered heteroaryl ring having 1 or 2 heteroatoms independently selected from N or N\u2014O, with the remaining ring atoms being carbon; a five-membered heteroaryl ring having 1, 2, 3 or 4 heteroatoms independently selected from N, O or S, with the remaining ring atoms being carbon; R32-quinolyl; R32-aryl; heterocycloalkyl; (C3\u2013C6)cycloalkyl; C1\u2013C6 alkyl; hydrogen; thianaphthenyl;
wherein said six-membered heteroaryl ring or said five-membered heteroaryl ring is optionally substituted by R6;
R3 is H, halogen, C1\u2013C6 alkyl, \u2014OH, (C1\u2013C6)alkoxy or \u2014NHSO2\u2014(C1\u2013C6)alkyl;
R4 is independently selected from the group consisting of hydrogen, C1\u2013C6 alkyl, C3\u2013C6 cycloalkyl, (C3\u2013C6)cycloalkyl(C1\u2013C6)alkyl, R33-aryl, R33-aryl(C1\u2013C6)alkyl, and R32-heteroaryl;
R5 is hydrogen, C1\u2013C6 alkyl, \u2014C(O)R20, \u2014C(O)2R20, \u2014C(O)N(R20)2, (C1\u2013C6)alkyl-SO2\u2014, or (C1\u2013C6)alkyl-SO2\u2014NH\u2014;
or R4 and R5, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl ring;
R6 is 1 to 3 substituents independently selected from the group consisting of \u2014OH, halogen, C1\u2013C6 alkyl-, C1\u2013C6 alkoxy, C1\u2013C6 alkylthio, \u2014CF3, \u2014NR4R5, \u2014CH2\u2014NR4R5, \u2014NHSO2R22, \u2014N(SO2R22)2, phenyl, R33-phenyl, NO2, \u2014CO2R4, \u2014CON(R4)2,
R7 is \u2014N(R29)\u2014, \u2014O\u2014 or \u2014S(O)0-2\u2014;
R12 is independently selected from the group consisting of C1\u2013C6 alkyl, hydroxyl, C1\u2013C6 alkoxy, or fluoro, provided that when R12 is hydroxy or fluoro, then R12 is not bound to a carbon adjacent to a nitrogen; or two R12 substituents form a C1 to C2 alkyl bridge from one ring carbon to another non-adjacent ring carbon; or R12 is \u2550O;
R13 is independently selected from the group consisting of C1\u2013C6 alkyl, hydroxyl, C1\u2013C6 alkoxy, or fluoro, provided that when R13 is hydroxy or fluoro then R13 is not bound to a carbon adjacent to a nitrogen; or two R13 substituents form a C1 to C2 alkyl bridge from one ring carbon to another non-adjacent ring carbon; or R13 is \u2550O;
R20 is independently selected from the group consisting of hydrogen, C1\u2013C6 alkyl, or aryl, wherein said aryl group is optionally substituted with from 1 to 3 groups independently selected from halogen, \u2014CF3, \u2014OCF3, hydroxyl, or methoxy; or when two R20 groups are present, said two R20 groups taken together with the nitrogen to which they are bound can form a five or six membered heterocyclic ring;
R22 is C1\u2013C6 alkyl, R34-aryl or heterocycloalkyl;
R24 is H, C1\u2013C6 alkyl, \u2014SO2R22 or R34-aryl;
R25 is independently selected from the group consisting of C1-C6 alkyl, halogen, \u2014CN, \u2014NO2, \u2014CF3, \u2014OH, C1\u2013C6 alkoxy, (C1\u2013C6)alkyl-C(O)\u2014, aryl-C(O)\u2014, \u2014C(O)OR29, \u2014N(R4)(R5), N(R4)(R5)\u2014C(O)\u2014, N(R4)(R5)\u2014S(O)1-2\u2014, R22\u2014S(O)0-2\u2014, halo-(C1\u2013C6)alkyl- or halo-(C1\u2013C6)alkoxy-(C1\u2013C6)alkyl-;
R29 is H, C1\u2013C6 alkyl, C3\u2013C6 cycloalkyl, R35-aryl or R35-aryl(C1\u2013C6)alkyl-;
R30 is H, C1\u2013C6 alkyl-, R35-aryl or R35-aryl(C1\u2013C6)alkyl-;
R31 is H, C1\u2013C6 alkyl-, R35-aryl, R35-aryl(C1\u2013C6)alkyl-, R35-heteroaryl, (C1\u2013C6)alkyl-C(O)\u2014, R35-aryl-C(O)\u2014, N(R4)(R5)\u2014C(O)\u2014, (C1\u2013C6)alkyl-S(O)2\u2014 or R35-aryl-S(O)2\u2014;
or R30 and R31 together are \u2014(CH2)4-5\u2014, \u2014(CH2)2\u2014O\u2014(CH2)2\u2014 or \u2014(CH2)2\u2014N(R38)\u2014(CH2)2\u2014 and form a ring with the nitrogen to which they are attached;
R32 is 1 to 3 substituents independently selected from the group consisting of H, \u2014OH, halogen, C1\u2013C6 alkyl, C1\u2013C6 alkoxy, R35-aryl-O\u2014, \u2014SR22, \u2014CF3, \u2014OCF3, \u2014OCHF2, \u2014NR39R40, phenyl, R33-phenyl, NO2, \u2014CO2R39, \u2014CON(R39)2, \u2014S(O)2R22, \u2014S(O)2N(R20)2, \u2014N(R24)S(O)2R22, \u2014CN, hydroxy-(C1\u2013C6)alkyl-, \u2014OCH2CH2OR22, and R35-aryl(C1\u2013C6)alkyl-O\u2014, or two R32 groups on adjacent carbon atoms together form a \u2014OCH2O\u2014 or \u2014O(CH2)2O\u2014 group;
R33 is 1 to 3 substituents independently selected from the group consisting of C1\u2013C6 alkyl, halogen, \u2014CN, \u2014NO2, \u2014CF3, \u2014OCF3, \u2014OCHF2 and \u2014O\u2014(C1\u2013C6)alkyl;
R34 is 1 to 3 substituents independently selected from the group consisting of H, halogen, \u2014CF3, \u2014OCF3, \u2014OH and \u2014OCH3;
R35 is 1 to 3 substituents independently selected from hydrogen, halo, C1\u2013C6 alkyl, hydroxy, C1\u2013C6 alkoxy, phenoxy, \u2014CF3, \u2014N(R36)2, \u2014COOR20 and \u2014NO2;
R36 is independently selected form the group consisting of H and C1\u2013C6 alkyl;
R37 is 1 to 3 substituents independently selected from hydrogen, halo, C1\u2013C6 alkyl, hydroxy, C1\u2013C6 alkoxy, phenoxy, \u2014CF3, \u2014N(R36)2, \u2014COOR20, \u2014C(O)N(R29)2 and \u2014NO2, or R37 is one or two \u2550O groups;
R38 is H, C1\u2013C6 alkyl, R35-aryl, R35-aryl(C1\u2013C6)alkyl-, (C1\u2013C6)alkyl-SO2 or halo(C1\u2013C6)alkyl-SO2\u2014;
R39 is independently selected from the group consisting of hydrogen, C1\u2013C6 alkyl, C3\u2013C6 cycloalkyl, (C3\u2013C6)cycloalkyl(C1\u2013C6)alkyl, R33-aryl, R33-aryl(C1\u2013C6)alkyl, and R32-heteroaryl; and
R40 is hydrogen, C1\u2013C6alkyl, \u2014C(O)R20, \u2014C(O)2R20, \u2014C(O)N(R20)2, (C1\u2013C6)alkyl-SO2\u2014, or (C1\u2013C6)alkyl-SO2\u2014NH\u2014;
or R39 and R40, together with the nitrogen to which they are attached, form an azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl ring.
2. A compound of claim 1 wherein a is 0, and the optional double bond is not present.
3. A compound of claim 2 wherein M2 is C(R3) wherein R3 is hydrogen or fluorine, b is 0, r is 1, and p is 2.
4. A compound of claim 3 wherein X is a bond.
5. A compound of claim 4 wherein Y is \u2014C(O)\u2014.
6. A compound of claim 5 wherein Z is straight or branched C1\u2013C3 alkyl.
7. A compound of claim 6 wherein R2 is a six-membered heteroaryl ring, optionally substituted with one R6 substituent.
8. A compound of claim 7 wherein R2 is pyrimidyl, R6\u2212pyrimidyl, pyridyl R6\u2212pyridyl or pyridazinyl and R6 is \u2014NH2.
9. A compound of claim 8 wherein R2 is
10. A compound of claim 2 wherein R1 is
11. A compound of claim 10 wherein R is (C1\u2013C6)alkyl, (C1\u2013C6)alkoxy, (C1\u2013C6)alkoxy(C1\u2013C6)alkoxy, (C1\u2013C6)alkylthio, heteroaryl or R32-aryl; R25 is halogen or \u2014CF3; and k and k1 are 0 or 1.
12. A compound of claim 11 wherein R is \u2014CH3, \u2014CH2CH3, \u2014OCH3, \u2014OCH2CH3, \u2014OCH2CH2CH3, \u2014OCH((CH3)2, \u2014CH2CH3, \u2014SCH3, \u2014SCH2CH3, pyridyl, pyrimidyl, pyrazinyl, furanyl, oxazolyl or R32-phenyl.
13. A compound of claim 12 wherein R2 is
14. A compound of claim 1 selected from the group consisting of
15. A pharmaceutical composition comprising an effective amount of a compound of claim 1 and a pharmaceutically effective carrier.
16. A method of treating nasal congestion obesity, somnolence, narcolepsy, attention deficit hyperactivity disorder, Alzheimer’s disease, and schizophrenia comprising administering to a patient in need of such treatment an effective amount of a compound of claim 1.
17. A pharmaceutical composition comprising an effective amount of a compound of claim 1, and an effective amount of H1 receptor antagonist, and a pharmaceutically effective carrier.
18. A method of treating nasal congestion comprising administering to a patient in need of such treatment an effective amount of a compound of claim 1 in combination with an H1 receptor antagonist.
19. The method of claim 18 wherein said H1 receptor antagonist is selected from: astemizole, azatadine, azelastine, acrivastine, brompheniramine, cetirizine, chlorpheniramine, clemastine, cyclizine, carebastine, cyproheptadine, carbinoxamine, descarboethoxyloratadine, diphenhydramine, doxylamine, dimethindene, ebastine, epinastine, efletirizine, fexofenadine, hydroxyzine, ketotifen, loratadine, levocabastine, meclizine, mizolastine, mequitazine, mianserin, noberastine, norastemizole, picumast, pyrilamine, promethazine, terfenadine, tripelennamine, temelastine, trimeprazine or triprolidine.
20. The method of claim 19 wherein said H1 receptor antagonist is selected from: loratadine, descarboethoxyloratadine, fexofenadine or cetirizine.
21. The method of claim 20 wherein said H1 receptor antagonist is selected from: loratadine or descarboethoxyloratadine.
22. The compound having the structure
The claims below are in addition to those above.
All refrences to claims which appear below refer to the numbering after this setence.
1. An adjustable light beam device for an aimable vehicle lamp assembly, comprising:
a lamp housing having a channel member with an outer portion and an inner portion; and
a tube component positioned within the inner portion of the channel member in which the tube component is adjustably movable along the inner portion of the channel member.
2. The adjustable light beam device of claim 1 further comprising at least one slot formed within the inner portion of the channel member; and
at least one resilient snap member of the tube component which is positionable within the at least one slot for slidable movement along the at least one slot.
3. The adjustable light beam device of claim 2 further comprising at least one blocking member formed in the inner portion of the channel member such that the blocking member is positioned for engagement with the resilient snap member to resist movement of the tube component in one direction.
4. The adjustable light beam device of claim 3 wherein the channel member has a hollow elongated configuration extending between a top opening and a bottom opening and wherein the at least one blocking member horizontally extends across the slot and is transverse to the top and bottom opening of the channel member.
5. The adjustable light beam device of claim 3 wherein the tube component has a flanged section to resist slidable movement of the tube component in another direction upon abutment of the flanged section with one end of the channel member.
6. The adjustable light beam device of claim 5 wherein the tube component further comprises a light clipping member extending across an interior portion of the tube component, and wherein the light clipping member includes a tapered hole extending from a wide opening to a narrow opening.
7. The adjustable light beam device of claim 2 wherein the at least one slot includes a plurality of slots formed within the inner portion of the channel member and wherein the at least one resilient snap member includes a plurality of resilient snap members which are correspondingly positionable into the slots for slidable movement along the inner portion of the channel member.
8. The adjustable light beam device of claim 7 further comprising a plurality of blocking members correspondingly formed in the plurality of slots such that the blocking members are positioned to engage with a corresponding one of the plurality of resilient snaps to resist movement of the tube component in one direction.
9. The adjustable light beam device of claim 8 wherein the plurality of blocking members are substantially equally spaced apart from one another and the resilient snaps are substantially equally spaced apart from one another.
10. The adjustable light beam device of claim 8 wherein each of the plurality of blocking members horizontally extends across a width of a corresponding one of the plurality of slots.
11. The adjustable light beam device of claim 10 wherein the resilient snaps have a lateral extension portion which extends outward from a body of the tube component such that the lateral extension portions of the snaps are correspondingly engageable with the blocking members formed in the slots of the channel member to resist movement of the tube component in the one direction.
12. The adjustable light beam device of claim 11 wherein the resilient snaps further comprise an arched portion extending down from the lateral extension portion to a bottom end of the tube component.
13. The adjustable light beam device of claim 8 further comprising a plurality of rib members on an outer wall of the tube component to provide a tight fit with the inner portion of the channel member.
14. The adjustable light beam device of claim 13 wherein the tube component further comprises a flanged section to resist slidable movement of the tube component in another direction upon abutment with one end of the channel member.
15. The adjustable light beam device of claim 13 wherein the tube component further comprises a light clipping member extending across an interior portion of the tube component, and wherein the light clipping member includes a tapered hole extending from a wide opening to a narrow opening.
16. The adjustable light beam device of claim 1 wherein the channel member has a plurality of thread members formed on the inner portion for mating engagement with another plurality of thread members formed on an outer body portion of the tube component such that the tube component is able to move within the channel member upon rotational movement of the tube component.
17. A method of adjusting a light beam diameter in a vehicle lamp assembly, comprising:
positioning a channel member, with an outer portion and an inner portion, of a lamp housing proximate to a light source capable of emitting a beam of light;
positioning a tube component within the inner portion of the channel member such that the tube component is able to be adjustably moved along the inner portion of the channel member; and
varying a diameter of the beam of light as the tube component is moved along the inner portion of the channel.
18. The method of claim 17 further comprising positioning a plurality of resilient snap members of the tube component into corresponding slots formed in the inner portion of the channel member;
slidably moving the resilient snap members along the corresponding slots; and
engaging the resilient snap members of the tube component with corresponding blocking members formed in the slots to resist movement of the tube component in one direction.
19. The method of claim 18 further comprising moving a flange member of the tube component to abut with an end of the channel member to resist movement of the tube component in another direction.
20. The method of claim 19 further comprising providing a light clipping member, having a light blocking section and a tapered hole, to extend across an interior portion of the tube component.