US 2006/0148805 A1Published application

Opthalmic compositions for treating ocular hypertension

OwnerMeng Hsin Chen, James Doherty +4inventors

InventorsMeng Hsin Chen, James Doherty, Luping Liu, Swaminathan Natarajan, Dong-Ming Shen, Min Shu

Life of this patent

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Abstract

This invention relates to the use of potent potassium channel blockers or a formulation thereof in the treatment of glaucoma and other conditions which leads to elevated intraoccular pressure in the eye of a patient. This invention also relates to the use of such compounds to provide a neuroprotective effect to the eye of mammalian species, particularly humans.

Claims15

Dependent claims

A compound of the structural formula I:

or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
wherein,
M, M1, and M2, independently are CH or N;
W represents
R represents hydrogen, or C1-6 alkyl;
X represents —(CHR7)p—, or a bond;
Y represents —(CH2)r—, —CO(CH2)n—, —SO2—, —O—, —S—, —CH(OR′)—, or CONR′;
R′ represents hydrogen, C1-10 alkyl, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
or, R′ and R6 taken together with the intervening N atom of CONR′ of Y to form a 4-10 membered carbocyclic or heterocyclic ring optionally interrupted by 1-3 atoms of O, S, C(O) or NR, and optionally having 1-4 double bonds, and optionally substituted by 1-3 groups selected from Ra;
Q represents N, CRy, or O, wherein R2 is absent when Q is O;
Ry represents H, C1-10 alkyl, C1-6 alkylSR, —(CH2)nO(CH2)mOR,
—(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —N(R)2, —COOR, or —(CH2)nC6-10 aryl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-5 groups selected from Ra;
or, R2-Q-R3 form a 3-15 membered carbocyclic or heterocyclic ring or fused ring, optionally interrupted by 1-3 atoms of O, S, C(O) or NR, and optionally having 1-5 double bonds, and optionally substituted by 1-3 groups selected from Ra;
Rw represents H, C1-6 alkyl, —C(O)C1-6 alkyl, —C(O)OC1-6 alkyl, —SO2N(R)2, —SO2C1-6 alkyl, —SO2C6-10 aryl, NO2, CN or —C(O)N(R)2;
R2 represents hydrogen, C1-10 alkyl, C1-6 alkylSR, —(CH2)nO(CH2)mOR, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —N(R)2, —COOR, or —(CH2)nC6-10 aryl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
R3 represents hydrogen, C1-10 alkyl, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —(CH2)nCOOR, —(CH2)nC6-10 aryl, —(CH2)nNHR8, —(CH2)nN(R)2, —(CH2)nNHCOOR, —(CH2)nN(R8)CO2R, —(CH2)nN(R8)COR, —(CH2)nNHCOR, —(CH2)nCONH(R8), aryl, —(CH2)nC1-6 alkoxy, CF3, —(CH2)nSO2R, —(CH2)nSO2N(R)2, —(CH2)nCON(R)2, —(CH2)nCONHC(R)3, —(CH2)nCOR8, nitro, cyano or halogen, said alkyl, alkoxy, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups of Ra;
R4 and R5 independently represent hydrogen, C1-6 alkoxy, OH, OCOR3, C1-6 alkyl, COOR, SO3H, O(CH2)nN(R)2, O(CH2)nCO2R, C1-6 alkylcarbonyl, S(O)qRy, (CH2)nOPO(OH)2, O(CH2)nOPO(OH)2, N(R)2, CF3, nitro, cyano or halogen where said alkyl, and alkoxy, are optionally substituted with 1-7 groups of Ra;
R6 represents hydrogen, C1-10 alkyl, —(CH2)nC6-10 aryl, —(CH2)nC5-10 heteroaryl, (C6-10 aryl)O—, —(CH2)nC3-10 heterocyclyl, —(CH2)nC3-8 cycloalkyl, —COOR, —C(O)CO2R, said aryl, heteroaryl, heterocyclyl and alkyl optionally substituted with 1-3 groups selected from Ra;
R7 represents hydrogen, C1-6 alkyl, —(CH2)nCOOR or —(CH2)nN(R)2,
R8 represents —(CH2)nC3-8 cycloalkyl, —(CH2)n 3-10 heterocyclyl, C1-6 alkoxy or —(CH2)nC5-10 heteroaryl, said heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
R9 represents C1-10 alkyl, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC6-10 aryl, —(CH2)nC5-10 heteroaryl, or —N(R)2 wherein said alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted with 1-3 groups selected from Ra;
Ra represents F, Cl, Br, I, CF3, N(R)2, NO2, CN, —COR8, —CONHR8, —CON(R8)2, —O(CH2)nCOOR, —NH(CH2)nOR, —COOR, —OCF3, —NHCOR, —SO2R, —SO2NR2, —SR, (C1-C6 alkyl)O—, —(CH2)nO(CH2)mOR, —(CH2)nC1-6 alkoxy, (aryl)O—, —OH, (C1-C6 alkyl)S(O)m—, H2N—C(═NH)—, (C1-C6 alkyl)C(O)—, (C1-C6 alkyl)OC(O)NH—, —(C1-C6 alkyl)NRw(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)O(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)S(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)-C3-10 heterocyclyl-Rw, —(CH2)n-Z1-C(=Z2)N(R)2, —(C2-6 alkenyl)NRw(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)O(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)S(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)-C3-10 heterocyclyl-Rw, —(C2-6 alkenyl)-Z1-C(=Z2)N(R)2, —(CH2)nSO2R, —(CH2)nSO3H, —(CH2)nPO(OR)2, —(CH2)nOPO(OR)2, —O(CH2)nSO2R, —O(CH2)nPO(OR)2, —O(CH2)nOPO(OR)2, cyclohexyl, morpholinyl, piperidyl, pyrrolidinyl, thiophenyl, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, isothiazolyl, C2-6 alkenyl, and C1-C10 alkyl, said alkyl, alkenyl, alkoxy, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, and isothiazolyl optionally substituted with 1-3 groups selected from C1-C6 alkyl, COOR, SO3H, OH, F, Cl, Br, I, and —O(CH2)nCH(OH)CH2SO3H;
Z1 and Z2 independently represents NRw, O, CH2, or S;
m is 0-3;
n is 0-3;
q is 0-2;
r is 0-6 and
p is 0-2.

25 more elements

A compound which is:

1-(1-Benzyl-6-methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
1-(1-benzyl-5-methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
1-(5-Methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
Methyl[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]acetate,
Methyl[2-(2,2-dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]acetate,
[2-(2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]acetic acid,
2-[2-(2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N,N-bis(3-methylbutyl)acetamide,
1-(Diethoxymethyl)-6-methoxy-1H-benzimidazole,
1-(diethoxymethyl)-5-methoxy-1H-benzimidazole,
1-(6-Methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
N,N-Dibutyl-2-[2-(2,2-dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]acetamide,
2-[2-2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N,N-diisobutylacetamide,
2-[2-(2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N,N-dipropylacetamide,
N-(Cyclopropylmethyl)-2-[2-2,2-dimethylpropanoyl)-5-methoxy-1H-benzimidazol 1-yl]-N-propylacetamide,
2-[2-(2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N-ethyl-N-(3-methylbutyl)acetamide,
N-Butyl-2-[2-(2,2-dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N-ethylacetamide,
N-Cyclohexyl-2-[2-(2,2-dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N-ethylacetamide,
2-[2-(2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-N-ethyl-N-1,3-thiazol-2-ylacetamide,
[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]acetic acid,
2-[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N,N-bis(3-methylbutyl)acetamide,
N,N-Dibutyl-2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]acetamide,
2-[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N,N-diisobutylacetamide,
2-[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N,N-dipropylacetamide,
N-(Cyclopropylmethyl)-2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-propylacetamide,
2-[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-ethyl-N-(3-methylbutyl)acetamide,
N-Butyl-2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-ethylacetamide,
N-Cyclohexyl-2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-ethylacetamide,
2-[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-ethyl-N-1,3-thiazol-2-ylacetamide,
N-(3,3-Dimethylbutyl)-2-[2-2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-ethylacetamide,
1-[2-(2,2-Dimethylpropanoyl)-5-methoxy-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one, 1-[2-(2,2-Dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one,
1-(1-Benzyl-5-methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
1-(1-Benzyl-6-methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
1-[1-(3,3-Dimethylbutyl)-5-methoxy-1H-benzimidazol-2-yl]-2,2-dimethylpropan-1-one,
1-[1-(3,3-Dimethylbutyl)-6-methoxy-1H-benzimidazol-2-yl]-2,2-dimethylpropan-1-one,
N,N-Dibutyl-2-[2-(2,2-dimethylpropyl)-5-methoxy-1H-benzimidazol-1-yl]acetamide,
N,N-Dibutyl-2-[2-(2,2-dimethylpropyl)-6-methoxy-1H-benzimidazol-1-yl]acetamide,
1-[2-(2,2-Dimethylpropyl)-5-methoxy-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one,
1-[2-(2,2-Dimethylpropyl)-6-methoxy-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one,
1-[5-Methoxy-2-(2-phenylethyl)-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one,
1-[6-Methoxy-2-(2-phenylethyl)-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one,
1-(5-Methoxy-2-phenyl-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
1-(6-Methoxy-2-phenyl-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
1-(2-Benzyl-5-methoxy-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
1-(2-Benzyl-6-methoxy-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
N,N-dibutyl-2-(2-isobutyryl-6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)acetamide,
N,N-dibutyl-2-(2-isobutyryl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)acetamide,
N,N-dibutyl-2-(2-isobutyryl-6-methoxy-1H-imidazo[4,5-b]pyridin-1-yl)acetamide,
N,N-dibutyl-2-(8-isobutyryl-2-methoxy-9H-purin-9-yl)acetamide,
N,N-dibutyl-2-(2-isobutyryl-6-methoxy-1H-imidazo[4,5-b]pyrazin-1-yl)acetamide,
N,N-dibutyl-2-(6-isobutyryl-3-methoxy-5H-imidazo[4,5-c]pyridazin-5-yl)acetamide,
N,N-dibutyl-2-(6-isobutyryl-3-methoxy-5H-imidazo[4,5-e][1,2,4]triazin-5-yl)acetamide,
N,N-dibutyl-2-[2-(2,2-dimethylpropanoyl)-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl]acetamide
N,N-dibutyl-2-(2-(2,2-dimethylpropanoyl)-6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)acetamide,
N,N-dibutyl-2-(2-(2,2-dimethylpropanoyl)-6-methoxy-1H-imidazo[4,5-b]pyridin-1-yl)acetamide,
N,N-dibutyl-2-(8-(2,2-dimethylpropanoyl)-2-methoxy-9H-purin-9-yl)acetamide,
N,N-dibutyl-2-(2-(2,2-dimethylpropanoyl)-6-methoxy-1H-imidazo[4,5-b]pyrazin-1-yl)acetamide,
N,N-dibutyl-2-(6-(2,2-dimethylpropanoyl)-3-methoxy-5H-imidazo[4,5-c]pyridazin-5-yl)acetamide,
N,N-dibutyl-2-(6-(2,2-dimethylpropanoyl)-3-methoxy-5H-imidazo[4,5-e][1,2,4]triazin-5-yl)acetamide,
2-[2-(2,2-dimethylpropanoyl)-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl]-N,N-bis(3-methylbutyl)acetamide,
2-(2-(2,2-dimethylpropanoyl)-6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(2-(2,2-dimethylpropanoyl)-6-methoxy-1H-imidazo[4,5-b]pyridin-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(8-(2,2-dimethylpropanoyl)-2-methoxy-9H-purin-9-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(2-(2,2-dimethylpropanoyl)-6-methoxy-1H-imidazo[4,5-b]pyrazin-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(6-(2,2-dimethylpropanoyl)-3-methoxy-5H-imidazo[4,5-c]pyridazin-5-yl)-N,N-bis(3-methylbutyl)acetamide,
2-[6-(2,2-dimethylpropanoyl)-3-methoxy-5H-imidazo[4,5-e][1,2,4]triazin-5-yl]-N,N-bis(3-methylbutyl)acetamide,
2-(2-isobutyryl-5-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-bis(3-methylbutyl)acetamide,
2-2 isobutyryl-6-methoxy-1H-imidazo[4,5-c]pyridin-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(2-isobutyryl-6-methoxy-1H-imidazo[4,5-b]pyridin-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(8-isobutyryl-2-methoxy-9H-purin-9-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(2-isobutyryl-6-methoxy-1H-imidazo[4,5-b]pyrazin-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(6-isobutyryl-3-methoxy-5H-imidazo[4,5-c]pyridazin-5-yl)-N,N-bis(3-methylbutyl)acetamide,
2-[6-(2,2-dimethylpropanoyl)-3-methoxy-5H-imidazo[4,5-e][1,2,4]triazin-5-yl]-N,N-bis(3-methylbutyl)acetamide,
1-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
2-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-N,N-dibutylacetamide,
2-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-N,N-bis(3-methylbutyl)acetamide,
2-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-N-butyl-N-ethylacetamide,
2-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-N,N-dipropylacetamide,
2-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-N-(tert-butyl)-N-ethylacetamide,
2-(2-benzoyl-6-methoxy-1H-benzimidazol-1-yl)-N-ethyl-N-1,3-thiazol-2-ylacetamide,
[6-methoxy-1-(3-methylbutyl)-1H-benzimidazol-2-yl](phenyl)methanone,
[1-(2-ethylbutyl)-6-methoxy-1H-benzimidazol-2-yl](phenyl)methanone,
[1-(3,3-dimethylbutyl)-6-methoxy-1H-benzimidazol-2-yl](phenyl)methanone,
N-benzyl-2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-ethylacetamide,
2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)-N,N-bis(3-methylbutyl)acetamide,
N,N-dibutyl-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)acetamide,
N,N-diisobutyl-2-(2-isobutyryl-6-methoxy-H-benzimidazol-1-yl)acetamide,
2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)-N,N-dipropylacetamide,
N-(cyclopropylmethyl)-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)-N-propylacetamide,
N-ethyl-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)-N-(3-methylbutyl)acetamide,
N-butyl-N-ethyl-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)acetamide,
N-cyclohexyl-N-ethyl-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)acetamide,
N-butyl-2-[2-2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-propylacetamide,
1-(1-{2-[trans-2,5-dipropylpyrrolidin-1-yl]-2-oxoethyl}-6-methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
1-(1-{2-[cis-2,5-dipropylpyrrolidin-1-yl]-2-oxoethyl}-6-methoxy-1H-benzimidazol-2-yl)-2,2-dimethylpropan-1-one,
1-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
N-(3,3-dimethylbutyl)-N-ethyl-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)acetamide,
N-butyl-2-(2-isobutyryl-6-methoxy-1H-benzimidazol-1-yl)-N-propylacetamide,
N-(3,3-dimethylbutyl)-2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-propylacetamide,
2-[2-(2,2-dimethylpropanoyl)-6-methoxy-1H-benzimidazol-1-yl]-N-(2,2-dimethylpropyl)-N-ethylacetamide,
2-{2-[4-(hydroxymethyl)benzoyl]-6-methoxy-1H-benzimidazol-1-yl}-N,N-bis(3-methylbutyl)acetamide,
2-{2-[4-(hydroxymethyl)benzoyl]-6-methoxy-1H-benzimidazol-1-yl}-N,N-diisobutylacetamide,
N-(3,3-dimethylbutyl)-N-ethyl-2-{2-[4-(hydroxymethyl)benzoyl]-6-methoxy-1H-benzimidazol-1-ylacetamide,
2-{2-[(4-trans-hydroxycyclohexyl)carbonyl]-6-methoxy-1H-benzimidazol-1-yl}-N,N-bis(3-methylbutyl)acetamide,
N-(3,3-dimethylbutyl)-2-{2-[(4-trans-hydroxycyclohexyl)carbonyl]-6-methoxy-1H-benzimidazol-1-yl}-N-propylacetamide,
N-(3,3-dimethylbutyl)-N-ethyl-2-{2-[(4-trans-hydroxycyclohexyl)carbonyl]-6-methoxy-1H-benzimidazol-1-yl}acetamide,
N,N-bis(3,3-dimethylbutyl)-2-(2-[(4-trans-hydroxycyclohexyl)carbonyl]-6-methoxy-1H-benzimidazol-1-yl}acetamide,
2-{2-[(4-cis-hydroxycyclohexyl)carbonyl]-6-methoxy-1H-benzimidazol-1-yl}-N,N-bis(3-methylbutyl)acetamide,
2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)-N,N-bis(3-methylbutyl)acetamide,
N,N-dibutyl-2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)acetamide,
2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)-N,N-diisobutylacetamide,
N-(3,3-dimethylbutyl)-N-ethyl-2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)acetamide,
N-butyl-2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)-N-propylacetamide,
N-(3,3-dimethylbutyl)-2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)-N-propylacetamide,
N-ethyl-2-(2-{[4-(hydroxymethyl)-1-methylcyclohexyl]carbonyl}-6-methoxy-1H-benzimidazol-1-yl)-N-(3-methylbutyl)acetamide,
1-{1-[2-(1-adamantyl)-2-oxoethyl)-6-methoxy-1H-benzimidazol-2-yl}-2,2-dimethylpropan-1-one,
1-{1-[2-(1-adamantyl)-2-oxoethyl]-6-methoxy-1H-benzimidazol-2-yl}-2-methylpropan-1-one,
1-(2-benzyl-5-methoxy-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
1-(5-methoxy-2-phenyl-1H-benzimidazol-1-yl)-3,3-dimethylbutan-2-one,
1-(5-methoxy-2-(2-phenylethyl)-1H-benzimidazol-1-yl]-3,3-dimethylbutan-2-one,
or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof.

117 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/561,571Filed 25 Jun 2004
Priority: 1 Jul 2003
Published: 6 Jul 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 235/12
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2: radicals substituted by oxygen atoms
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61P 25/24
Drugs for disorders of the nervous system: antidepressants

Family

Application60/483,996Us provisional application · filed 1 Jul 2003
US 2006/0148805 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of the structural formula I:

or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture thereof:
wherein,
M, M1, and M2, independently are CH or N;
W represents
R represents hydrogen, or C1-6 alkyl;
X represents —(CHR7)p—, or a bond;
Y represents —(CH2)r—, —CO(CH2)n—, —SO2—, —O—, —S—, —CH(OR′)—, or CONR′;
R′ represents hydrogen, C1-10 alkyl, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
or, R′ and R6 taken together with the intervening N atom of CONR′ of Y to form a 4-10 membered carbocyclic or heterocyclic ring optionally interrupted by 1-3 atoms of O, S, C(O) or NR, and optionally having 1-4 double bonds, and optionally substituted by 1-3 groups selected from Ra;
Q represents N, CRy, or O, wherein R2 is absent when Q is O;
Ry represents H, C1-10 alkyl, C1-6 alkylSR, —(CH2)nO(CH2)mOR,
—(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —N(R)2, —COOR, or —(CH2)nC6-10 aryl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-5 groups selected from Ra;
or, R2-Q-R3 form a 3-15 membered carbocyclic or heterocyclic ring or fused ring, optionally interrupted by 1-3 atoms of O, S, C(O) or NR, and optionally having 1-5 double bonds, and optionally substituted by 1-3 groups selected from Ra;
Rw represents H, C1-6 alkyl, —C(O)C1-6 alkyl, —C(O)OC1-6 alkyl, —SO2N(R)2, —SO2C1-6 alkyl, —SO2C6-10 aryl, NO2, CN or —C(O)N(R)2;
R2 represents hydrogen, C1-10 alkyl, C1-6 alkylSR, —(CH2)nO(CH2)mOR, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —N(R)2, —COOR, or —(CH2)nC6-10 aryl, said alkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
R3 represents hydrogen, C1-10 alkyl, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC5-10 heteroaryl, —(CH2)nCOOR, —(CH2)nC6-10 aryl, —(CH2)nNHR8, —(CH2)nN(R)2, —(CH2)nNHCOOR, —(CH2)nN(R8)CO2R, —(CH2)nN(R8)COR, —(CH2)nNHCOR, —(CH2)nCONH(R8), aryl, —(CH2)nC1-6 alkoxy, CF3, —(CH2)nSO2R, —(CH2)nSO2N(R)2, —(CH2)nCON(R)2, —(CH2)nCONHC(R)3, —(CH2)nCOR8, nitro, cyano or halogen, said alkyl, alkoxy, heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups of Ra;
R4 and R5 independently represent hydrogen, C1-6 alkoxy, OH, OCOR3, C1-6 alkyl, COOR, SO3H, O(CH2)nN(R)2, O(CH2)nCO2R, C1-6 alkylcarbonyl, S(O)qRy, (CH2)nOPO(OH)2, O(CH2)nOPO(OH)2, N(R)2, CF3, nitro, cyano or halogen where said alkyl, and alkoxy, are optionally substituted with 1-7 groups of Ra;
R6 represents hydrogen, C1-10 alkyl, —(CH2)nC6-10 aryl, —(CH2)nC5-10 heteroaryl, (C6-10 aryl)O—, —(CH2)nC3-10 heterocyclyl, —(CH2)nC3-8 cycloalkyl, —COOR, —C(O)CO2R, said aryl, heteroaryl, heterocyclyl and alkyl optionally substituted with 1-3 groups selected from Ra;
R7 represents hydrogen, C1-6 alkyl, —(CH2)nCOOR or —(CH2)nN(R)2,
R8 represents —(CH2)nC3-8 cycloalkyl, —(CH2)n 3-10 heterocyclyl, C1-6 alkoxy or —(CH2)nC5-10 heteroaryl, said heterocyclyl, aryl or heteroaryl optionally substituted with 1-3 groups selected from Ra;
R9 represents C1-10 alkyl, —(CH2)nC1-6 alkoxy, —(CH2)nC3-8 cycloalkyl, —(CH2)nC3-10 heterocyclyl, —(CH2)nC6-10 aryl, —(CH2)nC5-10 heteroaryl, or —N(R)2 wherein said alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted with 1-3 groups selected from Ra;
Ra represents F, Cl, Br, I, CF3, N(R)2, NO2, CN, —COR8, —CONHR8, —CON(R8)2, —O(CH2)nCOOR, —NH(CH2)nOR, —COOR, —OCF3, —NHCOR, —SO2R, —SO2NR2, —SR, (C1-C6 alkyl)O—, —(CH2)nO(CH2)mOR, —(CH2)nC1-6 alkoxy, (aryl)O—, —OH, (C1-C6 alkyl)S(O)m—, H2N—C(═NH)—, (C1-C6 alkyl)C(O)—, (C1-C6 alkyl)OC(O)NH—, —(C1-C6 alkyl)NRw(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)O(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)S(CH2)nC3-10 heterocyclyl-Rw, —(C1-C6 alkyl)-C3-10 heterocyclyl-Rw, —(CH2)n-Z1-C(=Z2)N(R)2, —(C2-6 alkenyl)NRw(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)O(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)S(CH2)nC3-10 heterocyclyl-Rw, —(C2-6 alkenyl)-C3-10 heterocyclyl-Rw, —(C2-6 alkenyl)-Z1-C(=Z2)N(R)2, —(CH2)nSO2R, —(CH2)nSO3H, —(CH2)nPO(OR)2, —(CH2)nOPO(OR)2, —O(CH2)nSO2R, —O(CH2)nPO(OR)2, —O(CH2)nOPO(OR)2, cyclohexyl, morpholinyl, piperidyl, pyrrolidinyl, thiophenyl, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, isothiazolyl, C2-6 alkenyl, and C1-C10 alkyl, said alkyl, alkenyl, alkoxy, phenyl, pyridyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thienyl, furyl, and isothiazolyl optionally substituted with 1-3 groups selected from C1-C6 alkyl, COOR, SO3H, OH, F, Cl, Br, I, and —O(CH2)nCH(OH)CH2SO3H;
Z1 and Z2 independently represents NRw, O, CH2, or S;
m is 0-3;
n is 0-3;
q is 0-2;
r is 0-6 and
p is 0-2.

25 more elements

Facts

Application

10/561,571Filed 25 Jun 2004

Priority

1 Jul 2003

Published

6 Jul 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 235/12
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2: radicals substituted by oxygen atoms
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 9/06
Drugs for disorders of the cardiovascular system: antiarrhythmics
A61P 25/24
Drugs for disorders of the nervous system: antidepressants