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US 2001/0036950 A1Published application
Potassium channel openers
OwnerWilliam A. Carroll, Irene Drizin +3inventors
InventorsWilliam A. Carroll, Irene Drizin, Mark W. Holladay, James P. Sullivan, Henry Q. Zhang
Life of this patent
Estimating the term…
Abstract
Compounds having the formula 1 are useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Claims41
A compound of Formula I
- 8
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof
- wherein
- R1 is alkyl;
- R2 is selected from the group consisting of aryl and heteroaryl;
- the aryl or heteroaryl are optionally substituted;
- n is 0-2;
- A is selected from the group consisting of hydrogen, alkyl, and —X—R3;
- R3 is alkyl or haloalkyl;
- X is —C(O)— or —S(O)p—;
- p is 1-2;
- R4 and R5 are independently selected from the group consisting of hydrogen, alkyl and haloalkyl;
- or
- R1 and R5 together with the ring to which they are attached form a 5-, 6- or 7-membered sulfur-containing ring with 1-2 double bonds and 0-2 oxo substituents;
- or
- A and R4 together with the ring to which they are attached form a ring selected from the group consisting of a 5-, 6-, or 7-membered carbocyclic ring with 1-2 double bonds and 0-1 oxo substituents and a 5-, 6- or 7-membered sulfur-containing ring with 1-2 double bonds and 0-2 oxo substituents, provided that at least one of R1 and R5 or A and R4 forms a ring.
13 more elements
A compound selected from the group consisting of
- 3,4,6,7,8,10-hexahydro-10-phenyl-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 3,4,6,7,8,10-hexahydro-10-(3-nitrophenyl)-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-cyanophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano [3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 3,4,6,7,8,10-hexahydro-10-[3-(trifluoromethyl)phenyl]-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-bromophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-fluorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-chlorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 3,4,6,7,8,10-hexahydro-10-[4-(trifluoromethyl)phenyl]-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(4-bromophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3,4-dichlorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-chloro-4-fluorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-bromo-4-fluorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3,4-difluorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-[3-fluoro-5-(trifluoromethyl)phenyl]-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-[4-fluoro-3-(trifluoromethyl)phenyl]-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 3,4,6,7,8,10-hexahydro-10-(4-methyl-3-nitrophenyl)2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(4-chloro-3-fluorophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(4-chloro-3-nitrophenyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 3,4,6,7,8,10-hexahydro-1 0-(3,4,5-trifluorophenyl)-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(3-pyridyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano[3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 10-(4-pyridyl)-3,4,6,7,8,10-hexahydro-2H-thiopyrano [3,2-b]quinolin-9(5H)-one, 1,1-dioxide;
- 9-(3-cyanophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 9-(3-nitrophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 9-(3,4-dichlorophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 9-[4-fluoro-3-(trifluoromethyl)phenyl]-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 3,4,5,6,7,9-hexahydro-9-(4-methyl-3-nitrophenyl)thieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 9-(3,4-difluorophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 9-(4-chloro-3-nitrophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 9-(3-bromo-4-fluorophenyl)-3,4,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(2H)-one, 1,1-dioxide;
- 4-(3-cyanophenyl)-4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-5(1H)-quinolinone;
- 4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-4-(3-nitrophenyl)-5(1H)-quinolinone;
- 4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-4-[4-(trifluoromethyl)phenyl]-5(1H)-quinolinone;
- 4-(3,4-dichlorophenyl)-4,6,7, 8-tetrahydro-2-methyl-3-(methylsulfonyl)-5(1H)-quinolinone;
- 4,6,7,8-tetrahydro-2-methyl-4-(4-methyl-3-nitrophenyl)-3-(methylsulfonyl)-5(1H)-quinolinone;
- 4-(4-chloro-3-nitrophenyl)-4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-5(1H)-quinolinone;
- 4-(3-bromo-4-fluorophenyl)-4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-5(1H)-quinolinone;
- 4-(4-chloro-3-fluorophenyl)-4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-5(1H)-quinolinone;
- 4-(3,4,5-trifluorophenyl)-4,6,7,8-tetrahydro-2-methyl-3-(methylsulfonyl)-5(1H)-quinolinone;
- 9-(3-cyano)-3,4,5,6,7,9-hexahydrocyclopenta[b]thiopyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 9-(3,4-dichlorophenyl)-3,4,5,6,7,9-hexahydrocyclopenta[b]thio-pyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 9-(4-chloro-3-nitrophenyl)-3,4,5,6,7,9-hexahydrocyclopenta[b]thio-pyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 9-(3-chloro-4-fluorophenyl)-3,4,5,6,7,9-hexahydrocyclopenta[b]thio-pyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 9-(3-bromo-4-fluorophenyl)-3,4,5,6,7,9-hexahydrocyclopenta[b]thio-pyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 9-(4-fluoro-3-trifluoromethyl)-3,4,5,6,7,9-hexahydrocyclopenta[b]thiopyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 9-(4-methyl-3-nitro)-3,4,5,6,7,9-hexahydrocyclopenta[b]thio-pyrano[2,3-e]pyridin-8(2H)-one, 1,1-dioxide;
- 8-(4-chloro-3-nitrophenyl)-3,5,6,8-tetrahydro-2H-cyclopenta[b]thieno[2,3-e]pyridin-7(4H)-one, 1,1-dioxide;
- 8-(3-bromo-4-fluorophenyl)-3,5,6,8-tetrahydro-2H-cyclopenta[b]thieno[2,3-e]pyridin-7(4H)-one, 1,1-dioxide;
- 8-(3,4-dichlorophenyl)-3,4,5,8-tetrahydro-6-methyl-1,1-dioxido-2H-thiopyrano[3,2-b]pyridin-7-yl]ethanone;
- 1-[8-(4-chloro-3-nitrophenyl)-3,4,5,8-tetrahydro-6-methyl-1,1-dioxido-2H-thiopyrano[3,2-b]pyridin-7-yl]ethanone;
- and
- 10-(4-chloro-3-nitrophenyl)-3,4,6,7,1 0-hexahydro-2H, 5H-bisthiopyrano[3,2-b:2′,3′-e]pyridine, 1,1,9,9-tetraoxide, or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
48 more elements
A compound of formula II
- 9
- or a pharmaceutically acceptable salt, ester, amide or prodrug thereof
- wherein
- R2 is selected from the group consisting of aryl and heteroaryl;
- the aryl or heteroaryl are optionally substituted;
- n is 1 or 2;
- X is selected from the group consisting of —CH2—, —C(O)—, —S(O)—, or —S(O)2—;
- and
- n′ and n″ are independently 1-3.
6 more elements
Dependencies are inferred from the claim text.