a new generation of 1,5,10,10a - cztemethod of producing new derivative of 1,5,10,10a - trowodorotiazolo / 3,4 - b - izochinoliny etrahydrothiazolo / 3,4 - b - isoquinoline

摘要

Thiazolo (3,4-b) isoquinolines of formula (I) as the racemate or isomers and their acid addition salts are novel cpds. (where A = 3-pyridyl, 4-pyridyl or 5-isoquinolyl; when A = 3-pyridyl then X1 = H, halo, dimethylamino or cyano, X2 = H or F and X3 = H or nitro at least two of X1, X2 and X3 = H or X1 and X2 together = methylene -dioxy and X3 = H; when A = 4-pyridyl or 5-isoquinolyl then X1, X2, X3 = H). Cpds. are analgesics and antipyretics with some anti-inflammatory activity. They have low toxicity (LD50 300 to 3000 mg/kg). They may be administered orally, parenterally or rectally in daily doses of 50-1000 mg for adults, e.g. in treatment of chronic or acute pain, rheumatism, dental pain, neurological pain or visceral pain. (I) include 3-(3-pyridyl-imino)-1,5,10,10a-tetrahydrothiazolo (3,4-b) isoquinoline and 3-(5-isoquinolylimino)-1,5,10,10a-tetrahydro-thiazolo (3,4-b) isoquinolines. Cpds. are prepd. by cyclisation of 3 hydroxymethyl-N-(A)-tetrahydro isoquinolylcarbothioamides or by reaction of A-NH2 with 3-chloro-, alkylthio or benzylthio-tetrahydrothiazolo (3,4-b) isoquinolinium salts.