Patent DK-10684-A (DK)
Inventor: BUYNISKI JOSEPH P
IPC: A61K/
Filed: 1984-01-10
Abstract: A pharmaceutical preparation for treating peptic ulcer comprises pepstatin and a histamine H2 receptor antagonist of the formula <IMAGE> in which p denotes 1 or 2, R1 denotes hydroxyl or NR2R3, R2 and R3 each, independently of the other, denote 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 R2 is hydrogen, R3 can 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, in which the pyridyl ring can contain a substituent selected from (lower)alkyl, (lower)alkoxy, hydroxyl, amino and halogen, amino, (lower)alkylamino, di(lower)alkylamino, hydroxyl, (lower)alkoxy, 2,3-dihydroxypropyl, cyano, amidino, (lower)alkylamidino, A'-(CH2)m'Z'(CH2)n'-, phenyl, phenyl(lower)alkyl, substituted phenyl or substituted phenyl(lower)alkyl, in which the phenyl ring can contain one or two substituents which are selected, independent of each other, from (lower)alkyl, hydroxyl, (lower)alkoxy and halogen, or a substituent selected from methylenedioxy, trifluoromethyl and di(lower)alkylamino, or R2 and R3 together can be -CH2CH2X(CH2)r-, r is an integer from 1 to 3 inclusive, X is methylene, sulphur, oxygen or N-R4, with the proviso that when r is 1, X is methylene, R4 is hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, (lower)alkanoyl or benzoyl, m and m' are each, independently of the other, an integer from 0 to 2 inclusive, n and n' are each, independently of the other, an integer from 2 to 4 inclusive, Z and Z' are each, independently of the other, sulphur, oxygen or methylene, A and A' are each, independently of the other, phenyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, triadiazolyl, oxadiazolyl, furyl, thienyl or pyridyl, with the proviso that A and A', independently of each other can contain one or two substituents, with the first substituent being selected from (lower)alkyl, hydroxyl, trifluoromethyl, halogen, amino, hydroxymethyl, (lower)alkoxy, <IMAGE> the second being selected from (lower)alkyl, hydroxyl, trifluoromethyl, halogen, amino, hydroxymethyl and (lower)alkoxy, q is an integer from 0 to 6 inclusive, R14 and R15 are, independently of each other hydrogen or (lower)alkyl, or, if R14 is hydrogen, R15 can also be (lower)alkanoyl or benzoyl, or R14 and R15 can together be ethylene, and R5 and R6 each, independently of the other, denote hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, (lower)alkoxy(lower)alkyl, cyclo(lower)alkyl, phenyl or phenyl(lower)alkyl, with the proviso that R5 and R6 cannot both be cyclo(lower)alkyl or phenyl, or R5 and R6, together with the nitrogen atom to which they are linked, can denote pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, hydroxypiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino, or a non- toxic, pharmaceutically acceptable salt, hydrate or solvate thereof. The simultaneous administration of the two constituents reduces the quantity of histamine H2 receptor antagonist which is required for treatment, with the tendency for side effects to occur being decreased.