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US4165378A Expired / Lapsed US ⏱️ 0.0 years remaining

Guanidine derivatives of imidazoles and thiazoles

Assignee: Syngenta Ltd
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Filing: 1978-04-19
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Granted: 1979-08-21
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Expires: 1998-04-19
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Abstract

Abstract The invention relates to guanidine derivatives of imidazoles and thiazoles which are histamine H-2 antagonists and which inhibit the secretion of gastric acid, to methods for their manufacture, to pharmaceutical compositions containing them and to methods of using such guanidine derivatives and compositions. The guanidine derivatives are of the general formula I: <IMAGE> I in which X is S or NH, Y is O, S, or SO, m is 1 to 4 and n is suitably 1 to 4, R1 is hydrogen, halogen or alkyl, R2 is hydrogen, alkyl, alkanoyl or aroyl, A is a 3,4-dioxocyclobuten-1,2-diyl radical or C=Z in which Z is O, S, NCN, NNO2, CHNO2, NCONH2, C(CN)2, NCOR3, NCO2R3, NSO2R3 or NR4 in which R3 is alkyl or aryl and R4 is hydrogen or alkyl, B is alkoxy or alkylthio or NR5R6 in which R5 and R6 are independently hydrogen, alkyl, alkenyl, cycloalkyl, hydroxyalkyl, alkoxyalkyl, alkylaminoalkyl or dialkylaminoalkyl; and the salts thereof.

Inventors

  • 👤 David J. Gilman
  • 👤 James M. Wardleworth
  • 👤 Tobias O. Yellin

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-04 14:07
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/44; C07D209/48; C07D233/00; C07D233/54; C07D233/66; C07D233/88; C07D277/00; C07D277/02; C07D277/20; C07D277/32; C07D277/38; C07D277/44; C07D277/48

Claims Analysis

Total Claims: 20
Claim 1
Independent Claim 420 words
A guanidine derivative of the formula: ##STR24## in which X is a sulphur atom or NH radical; Y is an oxygen or sulphur atom or a sulphinyl radical; m is 1 to 4 and n is 1 to 4, provided that when Y is an oxygen atom or a sulphinyl radical n is 2 to 4; R 1 is a hydrogen or halogen atom or an alkyl radical of 1 to 6 carbon atoms; R 2 is a hydrogen atom, an alkyl radical of 1 to 10 carbon atoms, an alkanoyl radical of 1 to 6 carbon atoms or an aroyl radical of 7 to 11 carbon atoms; A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C═Z in which Z is an oxygen or sulphur atom or a radical of the formula NCN, NNO 2 , CHNO 2 , NCONH 2 , C(CN) 2 , NCOR 3 , NCO 2 R 3 , NSO 2 R 3 or NR 4 in which R 3 is an alkyl radical of 1 to 6 carbon atoms or an aryl radical of 6 to 12 carbon atoms and R 4 is a hydrogen atom or an alkyl radical of 1 to 6 carbon atoms; B is an alkoxy or alkylthio radical of 1 to 6 carbon atoms or a radical of the formula NR 5 R 6 in which R 5 and R 6 , which may be the same or different, are hydrogen atoms, alkyl radicals of 1 to 10 carbon atoms, alkenyl radicals of 3 to 10 carbon atoms in which the double bond is separated from the nitrogen atom of NR 5 R 6 by at least one carbon atom, cycloalkyl radicals of 3 to 8 carbon atoms, (primary hydroxy)alkyl radicals of 2 to 6 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms, alkoxyalkyl radicals of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms, alkylaminoalkyl radicals of 3 to 10 carbon atoms in which the nitrogen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms; or dialkylaminoalkyl radicals of 4 to 10 carbon atoms in which the nitrogen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms; and the pharmaceutically acceptable acid-addition salts thereof.
Claim 2
Dependent Claim 420 words
A guanidine derivative of the formula: ##STR24## in which X is a sulphur atom or NH radical; Y is an oxygen or sulphur atom or a sulphinyl radical; m is 1 to 4 and n is 1 to 4, provided that when Y is an oxygen atom or a sulphinyl radical n is 2 to 4; R 1 is a hydrogen or halogen atom or an alkyl radical of 1 to 6 carbon atoms; R 2 is a hydrogen atom, an alkyl radical of 1 to 10 carbon atoms, an alkanoyl radical of 1 to 6 carbon atoms or an aroyl radical of 7 to 11 carbon atoms; A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C═Z in which Z is an oxygen or sulphur atom or a radical of the formula NCN, NNO 2 , CHNO 2 , NCONH 2 , C(CN) 2 , NCOR 3 , NCO 2 R 3 , NSO 2 R 3 or NR 4 in which R 3 is an alkyl radical of 1 to 6 carbon atoms or an aryl radical of 6 to 12 carbon atoms and R 4 is a hydrogen atom or an alkyl radical of 1 to 6 carbon atoms; B is an alkoxy or alkylthio radical of 1 to 6 carbon atoms or a radical of the formula NR 5 R 6 in which R 5 and R 6 , which may be the same or different, are hydrogen atoms, alkyl radicals of 1 to 10 carbon atoms, alkenyl radicals of 3 to 10 carbon atoms in which the double bond is separated from the nitrogen atom of NR 5 R 6 by at least one carbon atom, cycloalkyl radicals of 3 to 8 carbon atoms, (primary hydroxy)alkyl radicals of 2 to 6 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms, alkoxyalkyl radicals of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms, alkylaminoalkyl radicals of 3 to 10 carbon atoms in which the nitrogen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms; or dialkylaminoalkyl radicals of 4 to 10 carbon atoms in which the nitrogen atom is separated from the nitrogen atom of NR 5 R 6 by at least two carbon atoms; and the pharmaceutically acceptable acid-addition salts thereof.
Claim 3
Dependent Claim 172 words
A compound of claim 1 wherein X is a sulphur atom or an NH radical; Y is a sulphur atom or a sulphinyl radical; m is 1 to 4 and n is 1 to 4, provided that when Y is a sulphinyl radical n is 2 to 4; R 1 is a hydrogen or bromine atom or methyl radical; R 2 is a hydrogen atom, or a methyl, n-butyl, acetyl, propionyl or benzoyl radical; A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C═Z in which Z is an oxygen or sulphur atom or a radical of the formula NCN, NNO 2 , CHNO 2 , NCONH 2 , C(CN) 2 , NCO 2 CH 3 , NSO 2 -p-tolyl or NCH 3 ; B is a methoxy, ethoxy or methylthio radical or a radical of the formula NR 5 R 6 in which R 5 and R 6 are independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-hexyl, allyl, cyclohexyl, 2-hydroxyethyl, 3-hydroxypropyl, 2-methoxyethyl and 2-dimethylaminoethyl radicals.
Claim 4
Dependent Claim 11 words
A compound of claim 1 wherein X is a sulphur atom.
Claim 5
Dependent Claim 11 words
A compound of claim 3 wherein Y is a sulphur atom.
Claim 6
Dependent Claim 12 words
A compound of claim 4 wherein R 1 is a hydrogen atom.
Claim 7
Dependent Claim 12 words
A compound of claim 5 were R 2 is a hydrogen atom.
Claim 8
Dependent Claim 13 words
A compound of claim 6 where A is C═Z wherein Z is NCN.
Claim 9
Dependent Claim 22 words
A compound of claim 7 where B is NR 5 R 6 wherein R 5 is methyl and R 6 is methyl.
Claim 10
Dependent Claim 121 words
A compound of claim 1 where X is a sulphur atom; Y is a sulphur atom; m is 1 to 4; n is 1 to 4; R 1 is a hydrogen atom; R 2 is a hydrogen atom or a methyl rdical; A is C═Z wherein Z is a sulphur atom or a radical of the formula NCN, NNO 2 , NCONH 2 , NCOR 3 , NCO 2 R 3 or NSO 2 R 3 in which R 3 is a phenyl radical; and B is a radical of the formula NR 4 R 5 wherein R 4 and R 5 are independently selected from the group consisting of hydrogen and lower alkyl radicals of 1 to 4 carbon atoms.
Claim 11
Dependent Claim 87 words
A compound of claim 1 where X is a sulphur atom; Y is a sulphur atom; m is 1 to 4; n is 1 to 4; R 1 is hydrogen; R 2 is hydrogen; A is C═Z where Z is a sulphur atom or a radical of the formul NCN; and B is a radical of the formula NR 4 R 5 wherein R 4 and R 5 are independently selected from the group consisting of hydrogen and lower alkyl radicals of 1 to 4 carbon atoms.
Claim 12
Dependent Claim 15 words
A compound of claim 4 where m is 1 and n is 1 to 2.
Claim 13
Dependent Claim 8 words
A compound of claim 1 which is 2-quanidino-4-[2-(2-cyano-3-ethylguanidino)ethylthiomethyl]thiazole.
Claim 14
Dependent Claim 8 words
A compound of claim 1 which is 2-guanidino-4-[2-(2-cyano-3-methylguanidino)ethylthiomethyl]thiazole.
Claim 15
Dependent Claim 8 words
A compound of claim 1 which is 2-guanidino-4-[2-(2-nitroguanidino)ethylthiomethyl]thiazole.
Claim 16
Dependent Claim 8 words
A compound of claim 1 which is 2-guanidino-4-[2-(2-cyanoguanidino)ethylthiomethyl]thiazole.
Claim 17
Dependent Claim 8 words
A compound of claim 1 which is 2-guanidino-4-[2-(2-cyano-3-(2-hydroxyethyl)guanidino)ethylthiomethyl]thiazole.
Claim 18
Dependent Claim 27 words
A pharmaceutical composition to inhibit gastric acid secretion comprising a therapeutically effective amount of a compound of claim 1 to inhibit said secretion in a pharmaceutical carrier.
Claim 19
Dependent Claim 27 words
A pharmaceutical composition to inhibit gastric acid secretion comprising a therapeutically effective amount of a compound of claim 13 to inhibit said secretion in a pharmaceutical carrier.
Claim 20
Dependent Claim 21 words
A method of inhibiting gastric acid secretion in a living animal comprising administering to the animal a composition of claim 17.

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1982-08-20 1983-02-19 1983-08-21 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1986-08-20 1987-02-19 1987-08-21 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1990-08-20 1991-02-19 1991-08-21 $7700.00 Window Closed / Lapsed

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