Imperial Chemical Industries Limited

Ici Americas, Inc.

Derrick M Mant

Tobias O Yellin

Karin M Kirkland

A guanidine derivative of the formula I: ##STR1## in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, ring X and D are a variety of radicals defined in the specification and A is a 3-8C alkylene chain which is substituted by a hydroxy radical and into which is optionally inserted, as part of the backbone of the chain, one or two groups selected from oxygen and sulphur atoms and NH and 1-6C N-alkyl radicals; and the pharmaceutically-acceptable acid additions salts thereof. Pharmaceutical compositions and methods of manufacture are also described. The compound of the formula I is a histamine H-2 antagonist and is therefore useful in ulcer therapy.

Guanidinopyrazolylamides, guanidimoimidazolylamides, compositions

The invention relates to oxadiazole derivatives which are histamine H-2 antagonists and which inhibit the secretion of gastric acid, to methods for their manufacture and to pharmaceutical compositions containing them. The oxadiazole derivatives are of the formula: ##STR1## in which Y is O, S, CH.sub.2 or a direct bond; m is 0 to 4 and n is 1 to 4, provided than when Y is S or O m is 1 to 4 and when Y is O n is 2 to 4; A is a 3,4-dioxocyclobuten-1,2-diyl radical or C.dbd.Z in which Z is O, S, NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.1, NCO.sub.2 R.sup.1, NSO.sub.2 R.sup.1 or NR.sup.2 in which R.sup.1 is alkyl or aryl and R.sup.2 is H or alkyl; B is alkoxy or alkylthio or NHR.sup.3 in which R.sup.3 is H or alkyl: and the salts thereof.

3-Chloroalkyl-5-guanidino-1,2,4-oxadiazoles

The invention relates to oxadiazole derivatives which are histamine H-2 antagonists and which inhibit the secretion of gastric acid, to methods for their manufacture and to pharmaceutical compositions containing them. The oxadiazole derivatives are of the formula: ##STR1## in which Y is O, S, CH.sub.2 or a direct bond; m is 0 to 4 and n is 1 to 4, provided that when Y is S or O m is 1 to 4 and when Y is O n is 2 to 4; A is a 3,4-dioxocyclobuten-1,2-diyl radical or C.dbd.Z in which Z is O, S, NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.1, NCO.sub.2 R.sup.1, NSO.sub.2 R.sup.1 or NR.sup.2 in which R.sup.1 is alkyl or aryl and R.sup.2 is H or alkyl; B is alkoxy or alkylthio or NHR.sup.3 in which R.sup.3 is H or alkyl: and the salts thereof.

5-Guanidino-1,2,4-oxadiazoles

The invention relates to a thiadiazole derivative of the formula I: ##STR1## in which Y is O, S, CH.sub.2, SO or a direct bond; m is 0 to 4 and n is 1 to 4 provided that when Y is S, O or SO m is 1 to 4, and when Y is O or SO n is 2 to 4; R.sup.1 is H or (C.sub.1-10)alkyl; A is 3,4-dioxocyclobuten-1,2-diyl or C.dbd.Z in which Z is O, S, NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.2, NCO.sub.2 R.sup.2, NSO.sub.2 R.sup.2 or NR.sup.3 in which R.sup.2 is (C.sub.1-6)alkyl or (C.sub.6-12)aryl and R.sup.3 is H or (C.sub.1-6)alkyl; B is (C.sub.1-6)alkoxy, (C.sub.1-6)alkylthio or NR.sup.4 R.sup.5 in which R.sup.4 and R.sup.5 are independently H, (C.sub.1-10)alkyl, C.sub.3-6 (alkenyl), (C.sub.3-6)alkynyl, (C.sub.2-6)(primary hydroxy)alkyl, (C.sub.2-6)(primary amino)alkyl or (C.sub.3-6)cycloalkyl or R.sup.4 and R.sup.5 are joined to form a 5- or 6- membered saturated ring optionally containing an additional O or NH: and the salts thereof.

3-Chloroalkyl-5-guanidino-1,2,4-thiadiazole compounds

The invention relates to oxadiazole derivatives which are histamine H-2 antagonists and which inhibit the secretion of gastric acid, to methods for their manufacture and to pharmaceutical compositions containing them. The oxadiazole derivatives are of the formula: ##STR1## in which Y is O, S, CH.sub.2 or a direct bond; m is 0 to 4 and n is 1 to 4, provided that when Y is S or O m is 1 to 4 and when Y is O n is 2 to 4; A is a 3,4-dioxocyclobuten-1,2-diyl radical or C=Z in which Z is O, S, NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.1, NCO.sub.2 R.sup.1, NSO.sub.2 R.sup.1 or NR.sup.2 in which R.sup.1 is alkyl or aryl and R.sup.2 is H or alkyl; B is alkoxy or alkylthio or NHR.sup.3 in which R.sup.3 is H or alkyl: and the salts thereof.

Antisecretory oxadiazoles and pharmaceutical compositions containing them

The invention relates to a thiadiazole derivative of the formula I: ##STR1## in which Y is O, S, CH.sub.2, SO or a direct bond; m is 0 to 4 and n is 1 to 4 provided that when Y is S, O or SO m is 1 to 4, and when Y is O or SO n is 2 to 4; R.sup.1 is H or (C.sub.1-10)alkyl; A is 3,4-dioxocyclobuten-1,2-diyl or C=Z in which Z is O, S, NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.2, NCO.sub.2 R.sup.2, NSO.sub.2 R.sup.2 or NR.sup.3 in which R.sup.2 is (C.sub.1-6)alkyl or (C.sub.6-12)aryl and R.sup.3 is H or C.sub.1-6)alkyl; B is (C.sub.1-6)alkoxy, (C.sub.1-6)alkylthio or NR.sup.4 R.sup.5 in which R.sup.4 and R.sup.5 are independently H, (C.sub.1-10)alkyl, C.sub.3-6 (alkenyl), (C.sub.3-6)alkynyl, (C.sub.2-6)(primary hydroxy)alkyl, (C.sub.2-6)(primary amino)alkyl or C.sub.3-6)cycloalkyl or R.sup.4 and R.sup.5 are joined to form a 5- or 6- membered saturated ring optionally containing an additional O or NH: and the salts thereof.

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Bramhall, United Kingdom

Derrick M Mant