Pharmaceutically useful benzo(β)pyranes and pyranopyridines

Claim 2

A benzo[b]pyrane or pyranopyridine of formula ##STR8## wherein either A) V denotes R 1 --C, T denotes R 2 --C and W denotes H--C, wherein R 1 signifies hydrogen, halogen, ethynyl, hydroxy, cyano or the groups of formulae --NR 6 R 8 , --CO 2 R 6 or --CONR 6 R 7 and R 2 signifies hydrogen, halogen, (C 1-4 )alkoxy, hydroxy or the group of formula --NR 6 R 8 -- whereby R 6 and R 7 independently of one another denote hydrogen or a (C 1-4 )alkyl group and R 8 signifies hydrogen, a (C 1-4 )alkyl group, a formyl, an acetyl or a trifluoroacetyl group--or one of R 1 and R 2 signifies nitro and the other of R 1 and R 2 is defined as above, or B) V denotes N or the corresponding N-Oxide, T denotes R 2 --C wherein R 2 has the significance given above and W denotes HC, or C) V denotes R' 1 --C, T denotes H--C and W denotes N, wherein R 1 ' signifies hydrogen, a cyano or nitro group or D) V denotes N, T denotes H--C and W denotes N, R 3 and R 4 independently of one another, denote hydrogen or a (C 1-4 )alkyl group or R 3 and R 4 together signify a group --(CH 2 )n--, whereby n is 2, 3, 4 or 5, R 5 signifies hydrogen or OR 8 , wherein R 8 is defined as above, R 9 and R 10 respectively denote hydrogen or methyl or together signify an oxo- or a thio-group, m is 1,2 or 3, X signifies O or NR 11 , whereby R 11 signifies hydrogen, a (C 1-4 )alkyl-, formyl-, acetyl- or hydroxymethyl group, Y=CH, C-halogen, N, C-formyl or C-hydroxymethyl and Z=CH 2 , O, S, CH-halogen or NR 6 , wherein R 6 is defined as above and their N-Oxides, their pharmacologically acceptable acid addition salts and quaternary ammonium salts.

Claim 3

A benzo[b]pyrane or pyranopyridine according to claim 1 of formula ##STR9## wherein either A a ) V a denotes R 1 a --C, T a denotes R 2 a --C and W a denotes H--C, wherein R 1 a signifies hydrogen, cyano, halogen, --NR 6 R 8 ethynyl or a group --CO 2 R 6 or --CONR 6 R 7 and R 2 a signifies hydrogen, methoxy, hydroxy or a group of formula --NR 6 R 8 , wherein R 6 , R 7 and R 8 have the significance given in claim 1, or one of R 1 a and R 2 b denotes nitro and the other of R 1 a and R 2 b is defined as above, or B a ) V a denotes N or the corresponding N-Oxide, T a denotes R 2 a --C wherein R 2 a has the significance given above and W a denotes H--C, or C a ) V a denotes R 1 a' --C, T a denotes H--C and W a denotes N, wherein R 1 a signifies hydrogen, cyano or nitro or D a ) V a denotes N, T a denotes H--C and W a denotes N R 3 a and R 4 a respectively signify hydrogen or (C 1-4 )alkyl or R 3 a and R 4 a together form a group of formula --(CH 2 )n a , wherein n a signifies 2,3 or 4 R 9 a and R 10 a respectively signify hydrogen or methyl or together signify an oxo group, m a =1 or 2 X a denotes O or NR 11 , wherein R 11 possesses the definition given in claim 1, Y a denotes CH, C-halogen, C-hydroxymethyl, C-formyl or N and Z a denotes O, NR 6 , wherein R 6 possesses the definition given in claim 1, CH 2 , CH-halogen or --S-- and their N-oxides, their pharmacologically acceptable acid addition salts and quaternary ammonium salts.

Claim 4

A benzo[b]pyrane or pyranopyridine according to claim 1 of formula ##STR10## A b ) V b denotes R 1 b --C, T b denotes R 2 b --C, wherein R 1 b signifies hydrogen, ethynyl, cyano or a group of formula --NR 6 R 8 , --CO 2 R 6 or --CONR 6 R 7 and R 2 b signifies hydrogen, hydroxy or a group of formula --NR 6 R 8 wherein R 6 , R 7 and R 8 have the significances given in claim 1, or one of R 1 b and R 2 b signifies nitro and the other of R 1 b and R 2 b is defined as above, or B b ) V b denotes N or the corresponding N-Oxide, T b denotes R 2 b --C, wherein R 2 b has the significance given above, R 3 b and R 4 b respectively signify hydrogen or (C 1-4 )alkyl, or R 3 b and R 4 b together signify a group of formula --(CH 2 ) n b --, wherein n signifies 2,3 or 4, m b denotes 1, or 2, and X b denotes O or NR 11 , whereby R 11 possesses the definition given in claim 1, Y b denotes CH, C-halogen, C-hydroxymethyl, C-formyl or N and Z b denotes CH 2 , CH-halogen, O, S or NR 6 , wherein R 6 possesses the definition given in claim 1, and their N-oxides, their pharmacologically acceptable acid addition salts and quaternary ammonium salts.

Claim 5

A compound according to claim 1 selected from: trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclohex-1-enyloxy)-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(4-iodo-3-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enylamino)-2H-1-benzopyran-6-carbonitrile (+)-(3R,4S)-trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile (-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[2-oxofuran-4(5H)-ylamino]-2H-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[2-oxo-furan-4(5H)-yloxy]-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[N-methyl-N-(3-oxo-cyclopent-1-enyl)amino-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[N-methyl-N-(2-oxo-furan-4(5H)-yl)amino]-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[N-methyl-N-(N-methyl-2-oxo-pyrrzol-4(5H)-yl)amino-]2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-[2-oxothiophen-4(5H)-yloxy]-2H-1-benzopyran-6-carbonitrile trans-4-[N-formyl-[N-(3-oxo-cyclopent-1-enyl)amino]-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-4-[N-(2-hydroxymethyl-3-oxo-cyclopent-1-enyl)amino]-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-4-(2-formyl-3-oxo-cyclopent-1-enyl-amino)-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile trans-4-[N-(2-fluoro-3-oxo-cyclopent-1-enyl)-amino]-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile trans-4-[N-(2-chloro-3-oxo-cyclopent-1-enyl)-amino]-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile trans-4-[N-(2-bromo-3-oxo-cyclopent-1-enyl)-amino-]3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 3-amino-[N-(trans-3,4-dihydro-2,2-dimethyl-3-hydroxy-6-nitro-2H(1)-benzopyran-4-yl)]-cyclopent-2-en-1-one trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[N-methyl-N-(2-oxo-furan-4(5H)-yl)-amino]-2H-1-benzopyran-6-carboxylic acid-methylester trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-[N-methyl-N-(2-oxo-furan-4(5H)-yl)-amino]-2H-1-benzopyran-6-carboxylic acid-dimethylamide trans-2,2-diethyl-3,4-dihydro-3-hydroxy-4-(3-oxo-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile trans-3,4-dihydro-3-hydroxy-4-(3-oxo-cyclopent-1-enyloxy)-spiro[2H-1-benzopyran-2,1'-cyclohexan]-6-carbonitrile trans-3,4-dihydro-2,2-dimethyl-4-(3-oxo-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile 3-amino-N-(trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-pyrano[3,2-c]pyridin-4-yl)cyclopent-2-en-1-one 3-amino-N-(trans-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-pyrano[3,2-c]pyridin-4-yl)cyclopent-2-en-1-on-N-oxide trans-N-acetyl-2,2-diethyl-7-amino-3,4-dihydro-3-hydroxy-4-(3-oxo-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile 3-(trans-N-acetyl-6-amino-3,4-dihydro-3-hydroxy-7-nitro-2,2-dimethyl-2H-1-benzopyran-4-oxy)-cyclopent-2-en-1-on

Claim 6

The compound according to claim 1, which is (-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile.

Claim 7

A pharmaceutical composition useful in the treatment of raised blood pressure, vascular disorders, disorders in which a reduction in the tension of the smooth muscles is therapeutically useful, asthma, and obstructive disorders of the respiratory system comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier therefor.

Claim 8

A method of preventing or treating raised blood pressure, vascular disorders, and disorders in which a reduction in the tension of the smooth muscles is therapeutically useful which comprises administering to a subject in need of said treatment a therapeutically effective amount of a compound of claim 1.

Claim 9

A method of preventing or treating of asthma and obstructive disorders of the respiratory system which comprises administering to a subject in need of said treatment a therapeutically effective amount of a compound of claim 1.

Claim 10

A method for the prophylactic treatment of obstructive or inflammatory airways disease in a subject in need thereof, which comprises administering to said subject a prophylactically effective amount of a compound selected from the group consisting of: compounds of formula I according to claim 1 their N-oxides as well as the pharmaceutically acceptable acid addition and quaternary ammonium salts thereof.

Claim 11

A method according to claim 8 wherein the compound administered is (-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enylox-2H-1-benzopyran-6-carbonitrile.

Claim 17

A pharmaceutical composition: in unit dosage form and comprising a compound of formula I, its N-oxide and its salt according to claim 1, as active ingredient in an amount of from 0.1 to 2 mg/unit dosage, together with one or more pharmaceutically acceptable diluents or carriers therefor; or in liquid form and suitable or adapted for administration in spray or other liquid particulate form and comprising a compound of formula I, its N-oxide and its salt according to claim 1, as active ingredient, together with one or more pharmaceutically acceptable diluents or carriers therefor.

Claim 18

A composition according to claim 16 comprising (-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile as active ingredient.

Claim 19

A composition according to claim 16 or 17 in oral unit dosage form.

Claim 20

A composition according to claim 18 comprising (-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-cyclopent-1-enyloxy)-2H-1-benzopyran-6-carbonitrile as active ingredient in an amount of from 0.1 to 1 mg/unit dosage.