GB1358522A - Thioamide compounds - Google Patents

Abstract

1358522 Thioamides SMITHKLINE CORP 21 Dec 1972 59009/72 Heading C2C The invention comprises novel compounds (I) (including salts and optical isomers thereof) of the general formula (I) in which: R 1 is 2-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 2-pyrazinyl, 2-pyrrolyl, 2-quinolyl, 2-thiazolyl or 4-thiazolyl; R 2 and R 3 are selected from the following groups: (a) R 2 is hydrogen, lower alkyl, lower alkenyl or -(CH 2 ) n -phenyl, in which n is 0 or 1; R 3 is di-lower alkylamino- CH 2 -NH, N-lower alkyl-N-phenylamino-CH 2 - NH, pyrrolidino-CH 2 -NH, piperidino-CH 2 -NH, morpholino-CH 2 -NH or N-lower alkylpiperazino-CH 2 -NH; (b) R 2 is hydrogen, lower alkyl, lower alkenyl or phenyl, said phenyl being optionally substituted by halogen, lower alkyl or lower alkoxy; R 3 is NH-(CH 2 ) n -cycloalkyl, in which n is 0 or 1 and cycloalkyl has 3 to 6 carbon atoms; (c) R 2 is in which m is 0 or 1 and R 4 and R 5 are lower alkyl or taken together with the nitrogen atom to which they are attached form a piperidino, pyrrolidino or N-lower alkylpiperazino ring; R 3 is or NH-(CH 2 ) n -cycloalkyl, in which R 6 and R 7 are hydrogen or lower alkyl, n is 0 or 1 and cycloalkyl has 3 to 6 carbon atoms; (d) R 2 is (CH 2 ) m -O-R 8 , in which m is 0,1 or 2 and R 8 is lower alkyl, allyl or cyclopropanemethyl; R 3 is NH-phenyl or NH-(CH 2 ) n -cycloalkyl, in which R 9 and R 10 are hydrogen or lower alkyl, n is 0 or 1 and cycloalkyl has 3 to 6 carbon atoms; (e) R 2 is hydrogen, lower alkyl, lower alkenyl, lower alkoxy, allyloxy, cyclopropanemethoxy, phenyl, benzyl or (CH 2 ) n -NR 11 R 12 , in which n is 0 or 1 and R 11 and R 12 are lower alkyl or taken together with the nitrogen atom to which they are attached form a piperidino, pyrrolidino, morpholino or N-lower alkylpiperazino ring; R 3 is NH-R 13 , in which R 13 is an allyl or propargyl group optionally substituted by methyl or ethyl groups, said R 13 having 3 to 6 carbon atoms; (f) R 2 is morpholinomethyl; R 3 is or NH-(CH 2 ) n -cycloalkyl, in which R 14 and R 15 are hydrogen or lower alkyl, n is 0 or 1 and cycloalkyl has 3 to 6 carbon atoms; (g) R 2 is (CH 2 ) m -R 16 , in which m is 0 or 1 and R 16 is dilower alkylamino, N-lower alkyl-N-phenylamino, piperidino, pyrrolidino, morpholino or N-lower alkyl-piperazino; R 3 is NH-CH 2 -R 16 (the term lower relates to groups having up to 4 carbons; heterocyclic groups may be nuclear substituted). They are made by standard methods. The invention also comprises a process of preparing (I) as defined under (d) by reacting R 1 CH 2 (CH 2 ) m OR 8 with a strong base and then with R<SP>1</SP>NCS where R<SP>1</SP> is lower alkyl, phenyl, or (CH 2 ) n -cycloalkyl and R 8 is lower alkyl, allyl or cyclopropylmethyl. The following compounds are also prepared: 2-dimethylamino-2-(2-pyridyl)-acetonitrile, 2- methoxymethyl-pyridine, methyl 2-bromo-2-(2- (2- pyridyl)-acetate, methyl 2-methoxy-2-(2-pyridyl)- acetate and 2-methoxy-2-(2-pyridyl)-acetamide and -acetonitrile. Pharmaceutical preparations especially inhibiting gastric acid secretion and preventing ulcer formation contain (I) as active ingredient. Administration may be orally, rectally or parenterally.