The present invention relates to a thiazole derivative represented by the formula I, pharmaceutically acceptable acid addition salt thereof, and a process for preparation thereof ##STR3## wherein R.sub.1 represents --COOR.sub.4, ##STR4## or cyano wherein R.sub.4 represents hydrogen or lower alkyl, and
R.sub.5 and R.sub.6 may be same or different and represent hydrogen, lower alkyl, aryl, amino-lower alkyl, N-lower alkylamino-lower alkyl, N,N-di-lower alkylamino-lower alkyl or R.sub.5 and R.sub.6 are joined to form N-containing heterocyclic group; PA1 R.sub.5 and R.sub.6 may be same or different and represent hydrogen, lower alkyl, aryl, amino-lower alkyl, N-lower alkylamino-lower alkyl, N,N-di-lower alkylamino-lower alkyl or R.sub.5 and R.sub.6 are joined to form N-containing heterocyclic group;
R.sub.2 represents hydrogen or lower alkyl; and PA0 R.sub.3 represents N-containing heterocyclic group. PA0 R.sub.2 represents hydrogen or lower alkyl; and PA0 R.sub.3 represents N-containing heterocyclic group. PA0 methyl 4-methyl-5-(4-pyridinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(4-pyridinyl)-thiazole-2-carboxamide; PA0 N,4-dimethyl-5-(4-pyridinyl)-thiazole-2-carboxamide; PA0 4-methyl-5-(4-pyridinyl)-thiazole-2-carboxanilide; PA0 4-methyl-N-aminomethyl-5-(4-pyridinyl)-thiazole-2-carboxamide; PA0 4-methyl-N-(2-methylaminoethyl)-5-(4-pyridinyl)-thiazole-2-carboxamide; PA0 4-methyl-N-(2-dimethylaminoethyl)-5-(4-pyridinyl)-thiazole-2-carboxamide; PA0 N,N-diethyl-4-methyl-5-(4-pyridinyl)-thiazone-2-carboxamide; PA0 2',6'-dimethyl-4-methyl-5-(4-pyridinyl)-thiazole-2-carboxamide; PA0 1-[4-methyl-5-(4-pyridinyl)-2-thiazolylcarbonyl]-piperidine; PA0 2-cyano-4-methyl-5-(4-piperidinyl)-thiazole; PA0 methyl 4-methyl-5-(4-pyridazinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(4-pyridazinyl)-thiazole-2-carboxamide; PA0 1-[4-methyl-5-(4-pyridazinyl)-2-thiazolylcarbonyl]-piperazine; PA0 2-cyano-4-methyl-5-(4-pyridazinyl)-thiazole; PA0 methyl 4-methyl-5-(4-quinolinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(4-quinolinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(4-quinolinyl)-thiazole; PA0 methyl 4-methyl-5-(3-methyl-4-pyridinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(3-methyl-4-pyridinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(3-methyl-4-pyridinyl)-thiazole; PA0 methyl 4-methyl-5-(3-acetyl-4-pyridinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(3-acetyl-4-pyridinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(3-acetyl-4-pyridinyl)-thiazole; PA0 methyl 4-methyl-5-(3-chloro-4-pyridinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(3-chloro-4-pyridinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(3-chloro-4-pyridinyl)-thiazole; PA0 methyl 4-methyl-5-(3-formyl-4-pyridinyl)-2-carboxylate; PA0 4-methyl-5-(3-formyl-4-pyridinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(3-formyl-4-pyridinyl)-thiazole; PA0 methyl 4-methyl-5-(3-cyano-4-pyridinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(3-cyano-4-pyridinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(3-cyano-4-pyridinyl)-thiazole; PA0 methyl 4-methyl-5-(6-methoxy-4-quinolinyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(6-methoxy-4-quinolinyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(6-methoxy-4-quinolinyl)-thiazole; PA0 methyl 4-methyl-5-(2-thiazolyl)-thiazole-2-carboxylate; PA0 4-methyl-5-(2-thiazolyl)-thiazole-2-carboxamide; PA0 2-cyano-4-methyl-5-(2-thiazolyl)-thiazole;
Some thiazole derivatives having a cardiotonic activity are known as described in Japanese Patent Applications laid open under Nos. 134417/1982, 16889/1984 and 193878/1984 and so on. Meanwhile, thiazole derivatives in general are prepared by a method as described in Japanese Patent Applications laid open under Nos. 34241/1982, 49969/1974 and so on. That is, a thioamide is reacted with an .alpha.-halocarbonyl compound to form a compound of thiazole derivative. The known thiazole derivatives having a cardiotonic activity is prepared by this well known method.
However, there is no teaching in the prior art of any cardiotonically active compounds having any chemical structure comparable to or suggestive of instantly claimed compound.
Further, such known technique is unsuitable for synthesizing the compound of the formula I.
USPTO Backgrounds
USPTO Backgrounds