Substituted 1,2,5-thiadiazole derivatives
AssigneeBristol-Myers Company
InventorsRonnie R. Crenshaw, Aldo A. Algieri
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Abstract
Histamine H.sub.2 -antagonists of the formula ##STR1## wherein p is 1 or 2; R.sup.1 is hydroxy, amino, substituted amino or a 5- to 9-membered fully saturated nitrogen-containing heterocyclic ring attached via its nitrogen atom; m is an integer of from 0 to 2; n is an integer of from 2 to 4; Z is sulfur, oxygen or methylene; and A is an optionally substituted phenyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, furyl, thienyl or pyridyl ring; and nontoxic pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof are novel anti-ulcer agents. Intermediates and processes for their preparation are disclosed.
Claims5
A compound of the formula ##STR60## wherein p is 1 or 2;
- n is an integer of from 2 to 4, inclusive;
- R.sup.2 and R.sup.3 each are independently hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, cyclo(lower)alkyl(lower)alkyl, hydroxy(lower)alkyl, (lower)alkoxy(lower)alkyl, (lower)alkylthio(lower)alkyl, 2-fluoroethyl, 2,2,2-trifluoroethyl or cyano(lower)alkyl, or, when R.sup.2 is hydrogen, R.sup.3 may also be cyclo(lower)alkyl, amino(lower)alkyl, (lower)alkylamino(lower)alkyl, di(lower)alkylamino(lower)alkyl, pyrrolidino(lower)alkyl, piperidino(lower)alkyl, morpholino(lower)alkyl, piperazino(lower)alkyl, pyridyl(lower)alkyl, substituted pyridyl(lower)alkyl wherein the pyridyl ring may contain one substituent selected from (lower)alkyl, (lower)alkoxy, hydroxy, amino and halogen, amino, (lower)alkylamino, di(lower)alkylamino, hydroxy, (lower)alkoxy, 2,3-dihydroxypropyl, cyano, amidino, (lower)alkylamidino, A'--(CH.sub.2).sub.m' Z'(CH.sub.2).sub.n' --, phenyl, phenyl(lower)alkyl, substituted phenyl or substituted phenyl(lower)alkyl, wherein the phenyl ring may contain one or two substituents independently selected from (lower)alkyl, hydroxy, (lower)alkoxy and halogen or one substituent selected from methylenedioxy, trifluoromethyl and di(lower)alkylamino;
- or R.sup.2 and R.sup.3, taken together, may be --CH.sub.2 CH.sub.2 X(CH.sub.2).sub.r --;
- r is an integer of from 1 to 3, inclusive;
- X is methylene, sulfur, oxygen or N-R.sup.4, provided that, when r is 1, X is methylene;
- R.sup.4 is hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, (lower)alkanoyl or benzoyl;
- m' is an integer of from zero to 2, inclusive;
- n' is an integer of from 2 to 4, inclusive;
- Z' is sulfur, oxygen or methylene;
- A' is phenyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, furyl, thienyl or pyridyl;
- provided that A' may contain one or two substituents, the first substituent being selected from (lower)alkyl, hydroxy, trifluoromethyl, halogen, amino, hydroxymethyl, (lower)alkoxy, ##STR61## and the second substituent being selected from (lower)alkyl, hydroxy, trifluoromethyl, halogen, amino, hydroxymethyl and (lower)alkoxy;
- q is an integer of from 0 to 6, inclusive;
- R.sup.14 and R.sup.15 independently are hydrogen or (lower)alkyl, or, if R.sup.14 is hydrogen, R.sup.15 also may be (lower)alkanoyl or benzoyl, or R.sup.14 and R.sup.15, taken together, may be ethylene;
- and
- R.sup.5 and R.sup.6 each are independently hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, (lower)alkoxy(lower)alkyl, cyclo(lower)alkyl, phenyl or phenyl(lower)alkyl, provided that R.sup.5 and R.sup.6 may not both be cyclo(lower)alkyl or phenyl;
- or R.sup.5 and R.sup.6, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, hydroxypiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino;
- or a salt, hydrate, solvate or N-oxide thereof.
Dependencies are inferred from the claim text.