G.d. Searle & Company

Robert W Hamilton

Barnett S Pitzele

Michael John Clare

Donald W Hansen, Jr

Kurt J Rorig

Stella S Yu

Daniel R Pilipauskas

Alan E Moormann

Chi-Dean Liang

James R Deason

Harman S Lowrie

Richard E Henderson

The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is hydrogen, lower alkyl, hydroxy, --OCO.sub.2 lower alkyl, lower alkoxy, --O(CH.sub.2).sub.n -phenyl with the phenyl optionally substituted by halogen, --NO.sub.2, --CN, --NH.sub.2 or lower alkyl wherein n is 1 to 4; R.sup.2 and R.sup.3 represent lower alkyl, halogen, or lower alkoxy, or either one of R.sup.2 or R.sup.3 is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 may be the same or different and represent hydrogen or lower alkyl; R.sup.10 is selected from the gorup consisting of

Pyridyl and pyrimidinyl substituted tyrosyl dipeptide amides

The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is hydrogen, lower alkyl, hydroxy, --OCO.sub.2 lower alkyl, lower alkoxy, --O(CH.sub.2).sub.n --phenyl with the phenyl optionally substituted by halogen, --NO.sub.2, --CN, --NH.sub.2 or lower alkyl wherein n is 1 to 4; R.sup.2 and R.sup.3 represent lower alkyl, halogen, or lower alkoxy, or either one of R.sup.2 or R.sup.3 is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 may be the same or different and represent hydrogen or lower alkyl; R.sup.10 is selected from the group consisting of

Substituted dipeptide amides #3

Fluorenyl substituted tyrosyl dipeptide amides which are useful in

The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is hydrogen, lower alkyl, hydroxy, --OCO.sub.2 lower alkyl, lower alkoxy, --O(CH.sub.2).sub.n -phenyl with the phenyl optionally substituted by halogen, --NO.sub.2, --CN, --NH.sub.2 or lower alkyl wherein n is 1 to 4; R.sup.2 and R.sup.3 represent lower alkyl, halogen, or lower alkoxy, or either one of R.sup.2 or R.sup.3 is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 may be the same or different and represent hydrogen or lower alkyl; R.sup.10 is selected from the group consisting of

Phenyl substituted dipeptide amides

This invention relates to compounds of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is ##STR2## where X is oxygen or sulfur, Y is oxygen or nitrogen, and R.sup.11 represents straight or branched chain lower alkenyl having 2-6 carbon atoms, or phenyl, benzyl, and their equivalents such as nitro, halogen, or lower alkyl or lower alkoxy substituted phenyl or benzyl; wherein R.sup.2 and R.sup.3 may be the same or different and represent straight or branched chain lower alkyl having 1-6 carbon atoms, wherein R.sup.4 -R.sup.9 may be the same or different and represent hydrogen, or straight or branched chain lower alkyl having 1-6 carbon atoms; wherein C.sub.w is an asymmetric carbon atom when R.sup.7 and R.sup.8 are not the same and may be racemic or have the D or L configuration; and wherein C.sup.v is an asymmetric carbon atom and may be racemic or may have the D or L configuration. The compounds of this invention are useful because they possess analgesic activity in mammals.

O-substituted tyrosyl dipeptide amides

This invention encompasses compounds of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is lower alkoxy or --O--(CH.sub.2).sub.n -phenyl where the phenyl may be optionally substituted with halogen, --NO.sub.2, --CN, --NH.sub.2 or lower alkyl wherein n is 1 to 4; R.sup.2 and R.sup.3 represent lower alkyl, halogen, lower alkoxy or one of R.sup.2 or R.sup.3 is hydrogen and the other is lower alkyl, lower alkoxy, or halogen; R.sup.4, R.sup.5, R.sup.7, R.sup.8, and R.sup.9 represent hydrogen or lower alkyl, R.sup.6 represents hydrogen, lower alkyl, lower alkenyl, or --(CH.sub.2).sub.m -cycloalkyl wherein m is 1 to 4 and the cycloalkyl has 3 to 8 carbon atoms; R.sup.10 is --(CH.sub.2).sub.p -phenyl wherein p is 1 to 4; and v represents an asymmetric carbon that may be racemic or have the D or L Configuration; w represents an asymmetric carbon when R.sup.7 and R.sup.8 are not the same that may be racemic or have the D or L configuration. This invention also encompasses compounds where R.sup.1 is hydroxy, provided at least one of R.sup.4, R.sup.5, R.sup.6 or R.sup.9 is lower alkyl. The compounds of this invention are useful analgesic agents.

N-terminally substituted dipeptide amides

This invention relates to novel 3-thiophene-substituted tryosyl dipeptide amides of the formula: ##STR1## and the pharmaceutically acceptable addition salts thereof, wherein R.sup.1 is --OH, benzyloxy, or --OCH.sub.3 ; wherein R.sub.2 and R.sub.3 may be the same or different and represent lower alkyl of 1-6 carbon atoms; wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 may be the same or different and represent hydrogen or lower alkyl of 1-6 carbon atoms; wherein 'v' represents an asymmetric carbon atom that may be racemic or that may have the D or L configuration; and wherein 'w' represents an asymmetric carbon atom that has the D configuration. These compounds are useful as analgesic agents.

3-thiophene-substituted tyrosyl dipeptide amides

The invention relates to compounds of the formula: ##STR1## which are useful cardiovascular agents.

N-(aralkoxybenzyl)-4(benzhydryl) piperidines

This invention relates to novel substituted (azacycloalk-2-yl)iminophenols that are useful in the treatment of diarrhea.

Substituted (azacycloalk-2-yl)iminophenols and esters thereof

This invention relates to the novel use of certain aromatic substituted amidines as antidiarrheals.

2-[(Aminophenyl and amidophenyl)amino]-1-azacycloalkanes having

N.sup.6 -2-hydroxypropylaryl-substituted adenosines and adenines represented by the formula ##STR1## wherein R.sub.1 is selected from the group consisting of naphthyl, phenyl, substituted phenyl or biphenyl; and R.sub.2 is hydrogen or 1-.beta.-ribosyl; and the pharmaceutically acceptable salts thereof. The compounds are anti-hypertensive agents.

N.sup.6 -[(2-Hydroxypropyl)aryl]adenosines

The present invention relates to compounds of the formula ##STR1## having the [(X-substituted)phenyl]phenylmethyl moiety attached to the 2, 3, or 4 position of the piperidine ring and wherein X is hydrogen, halo, trifluoromethyl, (lower alkyl) containing 1-7 carbon atoms, or (lower alkoxy) containing 1-7 carbon atoms, A represents alkylene containing 1-3 carbon atoms, and R.sub.1 and R.sub.2 represent (lower alkyl) containing 1-7 carbon atoms or R.sub.1 and R.sub.2 together with N represent piperidino or morpholino and the pharmaceutically acceptable salts thereof. The compounds of this invention are prepared by the reaction of an appropriate [(X-substituted)phenyl]phenylmethylpiperidine with an appropriate 1-halo-2-dialkylaminoalkane. The compounds of this invention are useful as anti-arrythmic agents.

[(Substituted )phenyl]phenylmethyl-1-(dialkylaminoalkyl)piperidines

4-{[4-(Diphenylmethyl)-1-piperidinyl]methyl}benzenamines useful by reason of their vasodilating activity are disclosed.

4-{[4-(Diphenylmethyl)-1-piperidinyl]methyl}benzenamines

Aminoalkyl esters and amides of 4,5-dihydrobenz[g]indazole-3-carboxylic acids and related compounds are described herein. They are useful as anti-ulcer agents, anti-arrhythmic agents, anti-bacterial agents, anti-protozoal agents, anthelmintics, anti-fungal agents, anti-algal agents and anti-inflammatory agents. The compounds are prepared from the appropriate carboxylic acid, alkyl ester, or acid chloride.

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Wilmette, IL, United States of America

Robert W Hamilton