Imidazole compounds and medicinal use thereof
View Patent ↗Imidazole compounds represented by general formula (I): wherein each symbol is as defined in the specification, and salts thereof, and a pharmaceutical composition containing same are provided. These compounds are useful in treating the diseases curable based on a hypoglycemic action, and the diseases curable based on a cGMP-PDE inhibitory action, a smooth muscle relaxing action, a bronchodilating action, a vasodilating action, a smooth muscle cell inhibitory action and an allergy inhibitory action.
1. An imidazole compound of the formula:
wherein
R 2 is a lower alkyl;
R 3 is chlorine;
R 4 is (1) a lower alkenyl optionally substituted by aryl or heterocyclic group, (2) aryl optionally substituted by lower alkenyl, (3) lower alkyl, or (4) heterocyclic group optionally substituted by halogen;
R 6 is lower alkenyl optionally substituted by phenyl, or lower alkynyl optionally substituted by phenyl; and
L is ethylene,
where aryl is defined as unsubstituted aryl or alkyl-substituted aryl, or a salt thereof.
2. The imidazole compound of claim 1 which is:
(5) (E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-methylimidazol-5-yl)-N-((4-methylbenzene)sulfonyl)-2-propenamide,
(6) (2E)-3-(4-chloro-1-(2-4-(phenylethynyl)benzyl)-2-methylimidazol-5-yl)-N-(((E)-2-phenylethenyl)sulfonyl)-2-propenamide,
(34) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-methylimidazol-5-yl)-N-((4-methylbenzene)sulfonyl)-2-propenamide,
(35)(E)-3-(4-chloro-1′-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-methylimidazol-5-yl)-N-(((E)-2-phenylethenyl)sulfonyl)-2-propenamide,
(41) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-methylimidazol-5-yl)-N-(1-pentanesulfonyl)-2-propenamide,
(42) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-methylimidazol-5-yl)-N-((E)-1-penten-1-ylsulfonyl)-2-propenamide,
(43) (E)-N-(1-butanesulfonyl)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-methylimidazol-5-yl)-2-propenamide,
(44) (E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-methylimidazol-5-yl)-N-(1-pentanesulfonyl)-2-propenamide,
(45) (E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-methylimidazol-5-yl)-N-((E)-1-penten-1-ylsulfonyl)-2-propenamide,
(46) (E)-N-(1-butanesulfonyl)-3-(4-chloro-1-(2-chloro-4-(2-phenylethynyl)benzyl)-2-methylimidazol-5-yl)-2-propenamide,
(54) (E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-((E)-2-phenylethenesulfonyl)-2-propenamide,
(55) (E)-3-(4-chloro-1-(2-chloro-4-phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-((4-methylbenzene)sulfonyl)-2-propenamide,
(56) (E)-N-(1-butanesulfonyl)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-2-propenamide,
(57) (E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-(1-pentanesulfonyl)-2-propenamide,
(58) (E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-((E)-1-penten-1-ylsulfonyl)-2-propenamide,
(59) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-ethylimidazol-5-yl)-N-((E)-2-phenylethenesulfonyl)-2-propenamide,
(60) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-ethylimidazol-5-yl)-N-(4-methylbenzenesulfonyl)-2-propenamide,
(61) (E)-N-(1-butanesulfonyl)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-ethylimidazol-5-yl)-2-propenamide,
(62) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-ethylimidazol-5-yl)-N-(1-pentanesulfonyl)-2-propenamide, or
(63) (E)-3-(4-chloro-1-(2-chloro-4-((E)-2-phenylethenyl)benzyl)-2-ethylimidazol-5-yl)-N-((E)-1-penten-1-ylsulfonyl)-2-propenamide,
or a salt thereof.
3. The imidazole compound of claim 1 , which is:
(E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-methylimidazol-5-yl)-N-((4-methylbenzene)sulfonyl)-2-propenamide,
(E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-((4-methylbenzene)sulfonyl)-2-propenamide,
(E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-(1-pentanesulfonyl)-2-propenamide or
(E)-3-(4-chloro-1-(2-chloro-4-(phenylethynyl)benzyl)-2-ethylimidazol-5-yl)-N-((E)-1-penten-1-ylsulfonyl)-2-propenamide,
or a salt thereof.
4. A pharmaceutical composition containing the imidazole compound of claim 2 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable organic or inorganic excipient.
5. A pharmaceutical preparation containing the imidazole compound of claim 2 , or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable organic or inorganic excipient, which is used as an agent for the treatment of diabetes, polycystic ovary syndrome, atherosclerosis, hyperglycemia, or hypertension.
6. A method of treating a disease in a patient treatable with a pharmaceutical compound having hypoglycemic activity selected from the group consisting of diabetes, polycystic ovary syndrome, atherosclerosis, hyperglycemia, osteoporosis, and hypertension, which comprises administering to the patient the hypoglycemically active imidazole compound of claim 2 or a pharmaceutically acceptable salt thereof.