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US 6,476,022 B1Granted
Oxathiepino[6,5-b]dihydropyridines, and related compositions and methods
AssigneeOrtho-McNeil Pharmaceutical, Inc.
InventorsJohn H. Dodd, James R. Henry, Kenneth C. Rupert, James L. Bullington, Daniel A. Hall
Life of this patent
Estimating the term…
Abstract
This invention provides novel oxathiepino[6,5-b]dihydropyridines. These compounds are useful as calcium channel antagonists with cardiovascular, antiasthmatic and antibronchoconstriction activity. Thus, this invention also provides pharmaceutical compositions, as well as methods, for preventing and treating disorders such as hypersensitivity, allergy, asthma, bronchospasm, dysmenorrhea, esophageal spasm, glaucoma, premature labor, urinary tract disorders, gastrointestinal motility disorders and cardiovascular disorders.
Claims40
A compound of Formula I,
- or a pharmaceutically acceptable salt thereof, wherein
- (a) R1, R2, R3, R4 and R5 are independently selected from the group consisting of H, OH, halogen, cyano, NO2, alkyl, C1-8 alkoxy, C1-8 alkylsulfonyl, C1-4 carboalkoxy, C1-8 alkylthio, difluoromethoxy, difluoromethylthio, and trifluoromethyl, or an oxadiazole (formed by R1 and R2);
- (b) R6 is selected from the group consisting of H, C1-5 straight or branched alkyl, aryl, 3-piperidyl, N-substituted 3-piperidyl, N-substituted 2-pyrrolidinyl methylene and substituted alkyl, wherein
- said N-substituted 3-piperidyl and said N-substituted 2-pyrrolidinyl methylene may be substituted with C1-8 straight or branched chain alkyl or benzyl, and said substituted alkyl may be substituted with C1-8 alkoxy, C2-8 alkanoyloxy, phenylacetyloxy, benzoyloxy, hydroxy, halogen, p-tosyloxy, mesyloxy, amino, carboalkoxy or NR′R″, wherein
- (i) R′ and R″ are independently selected from the group consisting of H, C1-8 straight or branched alkyl, C3-7 cycloalkyl, phenyl, benzyl and phenethyl, or
- (ii) R′ and R″ together form a heterocyclic ring selected from the group consisting of piperidino, pyrrolidino, morpholino, thiomorpholino, piperazino, and an N-substituted piperazino ring, said N-substituted piperazino ring being substituted with H, C1-8 straight or branched alkyl, benzyl, benzhydryl, phenyl or substituted phenyl (substituted with NO2, halogen, C1-8 straight or branched chain alkyl, C1-8 alkoxy and/or trifluoromethyl);
- (c) R7 is selected from the group consisting of H, amino, alkyl, aryl, trifluoromethyl, alkoxymethyl, 2-thieno and 3-thieno;
- (d) R9 is oxygen or sulfur;
- and
- (e) n is an integer from 1 to 4.
7 more elements
The compound of Formula (II), wherein
- (a) R1, R2, R3, R4 and R5 are independently selected from the group consisting of hydrogen, OH, halogen, cyano, NO2, alkyl, C1-8 alkoxy, C1-8 alkylsulfonyl, C1-4 carboalkoxy, C1-8 alkylthio, difluoromethoxy, difluoromethylthio, and trifluoromethyl, or an oxadiazole (formed by R1 and R2);
- (b) R7 is selected from the group consisting of H, amino, alkyl, aryl, trifluoromethyl, alkoxymethyl, 2-thieno and 3 -thieno;
- (c) R8 is selected from the group consisting of -alkyl-OH, alkylamine, lactone, cyclic carbonate, alkyl-substituted cyclic carbonate, aryl-substituted cyclic carbonate, -aryl-C(O)OR′, -alkyl-aryl-C(O)OR′, -alkyl-OC(O)R′, -alkyl-C(O)R′, -alkyl-C(O)OR′, -alkyl-N(R′)C(O)R′, and -alkyl-N(R′)C(O)OR′, wherein
- R′ and R″ are independently selected from the group consisting of hydrogen, amino, alkyl, aryl, aryl-fused cycloalkyl and a 5 or 6 membered saturated or unsaturated heterocyclyl having one nitrogen or one nitrogen and either a second nitrogen, a sulfur or an oxygen, the amino, alkyl, aryl, aryl-fused cycloalkyl and heterocyclyl being optionally substituted with halogen, cyano, NO2, lactone, amino, alkylamino, aryl-substituted alkylamino, amido, carbamate, cyclic carbonate, alkyl, halogen-substituted alkyl, arylalkyl, alkoxy, heterocyclyl and/or aryl (the aryl being optionally substituted with OH, halogen, cyano, NO2, alkyl, amino, dimethylamino, alkoxy, alkylsulfonyl, C1-4;
- carboalkoxy, alkylthio and/or trifluoromethyl);
- and
- (d) R9 is oxygen or sulfur.
4 more elements
Dependencies are inferred from the claim text.