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US 6,642,222 B2Granted
Pyrano, piperidino, and thiopyrano compounds and methods of use
AssigneeAbbott Laboratories
InventorsWilliam A. Carroll, Konstantinos A. Agrios, Robert J. Altenbach, Irene Drizin, Michael E. Kort
Life of this patent
Estimating the term…
Abstract
The present invention provides novel compounds of formula I which may be useful in hyperpolarizing cell membranes, opening potassium channels, relaxing smooth muscle cells, and inhibiting bladder contractions.
Claims72
A compound having formula I
- or a pharmaceutically acceptable salt thereof, wherein
- n is 0-1;
- m is 1-2;
- A is selected from the group consisting of NR2, O, and S;
- A′ is selected from the group consisting of NR3, O, S and CR4R5;
- D is selected from the group consisting of CH2 and C(O);
- D′ is selected from the group consisting of CH2, C(O), S(O), and S(O)2;
- R1 is selected from the group consisting of aryl and heterocycle;
- R2 and R3 are independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heterocyclealkyl, hydroxy, hydroxyalkyl, —NZ1Z2, and (NZ1Z2)alkyl wherein Z1 and Z2 are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, aryl, arylalkyl, and formyl;
- R4 and R5 are independently selected from the group consisting of hydrogen and alkyl;
- or
- R4 and R5 together with the carbon atom to which they are attached form a 3-6 membered carbocyclic ring;
- R6 and R7 are independently selected from the group consisting of hydrogen and alkyl;
- or
- R6 and R7 together with the carbon atom to which they are attached form a 3-6 membered carbocyclic ring;
- and
- R8 is alkyl, and
- R9 is independently selected from the group consisting of hydrogen and alkyl;
- or
- R8 and R9 together with the carbon atom to which they are attached form a 3-6 membered carbocyclic ring;
- with the proviso that when D is CH2 then D′ is other than CH2;
- and
- with the proviso that when D′ is S(O) or S(O)2 then A′ is CR4R5.
20 more elements
A compound selected from the group consisting of
- 5-(3-bromo-4-methylphenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(3-iodo-4-methylphenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(3,4-dibromophenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-[4-chloro-3-(trifluoromethyl)phenyl]-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-[4-fluoro-3-(2-furyl)phenyl]-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(5-bromo-4-fluoro-2-hydroxyphenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(4-methyl-3-nitrophenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(4-bromo-3-chlorophenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(3-bromo-4-chlorophenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-[3-iodo-4-(trifluoromethyl)phenyl]-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-[3-bromo-4-(trifluoromethyl)phenyl]-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- 5-(4-fluoro-3-isopropenylphenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione;
- and
- 5-(4-fluorophenyl)-5,10-dihydro-1H,3H-dipyrano[3,4-b:4,3-e]pyridine-4,6(7H,9H)-dione.
11 more elements
A compound selected from the group consisting of
- 9-(3-bromo-4-methylphenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(3-iodo-4-methylphenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(4-fluoro-3-iodophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(3,4-dibromophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(3,4-dichlorophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-[4-chloro-3-(trifluoromethyl)phenyl]-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(3-bromo-4-chlorophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(4-methyl-3-nitrophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-[3-(2-furyl)-4-methylphenyl]-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-[4-fluoro-3-(2-furyl)phenyl]-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (9S)-9-(4-fluoro-3-iodophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (9R)-9-(4-fluoro-3-iodophenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (9R)-9-(3-bromo-4-methylphenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (9S)-9-(3-bromo-4-methylphenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (+) 9-(3-iodo-4-methylphenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- and
- (−) 9-(3-iodo-4-methylphenyl)-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione.
14 more elements
A compound selected from the group consisting of
- (trans)-9-(3-bromo-4-fluorophenyl)-3-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (cis)-9-(3-bromo-4-fluorophenyl)-3-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (cis)-9-(3-bromo-4-fluorophenyl)-3-ethyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (trans)-9-(3-bromo-4-fluorophenyl)-3-ethyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (cis)-9-(3-bromo-4-fluorophenyl)-3-propyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (trans)-9-(3-bromo-4-fluorophenyl)-3-propyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- 9-(3-bromo-4-fluorophenyl)-3,3-dimethyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- (+) (cis)-9-(3-bromo-4-fluorophenyl)-3-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione;
- and
- (−) (cis)-9-(3-bromo-4-fluorophenyl)-3-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione.
7 more elements
Dependencies are inferred from the claim text.