Pfizer Corporation

Ian T Barnish

Peter E Cross

John C Danilewicz

Malcolm Morville

Keith James

David A Cox

Anthony G Evans

Nicholas Kenneth Terrett

Michael T Williams

Gillian M Samuels

Michael G Page

Roger P Dickinson

Martin James Wythes

Martin J Wythes

N-(1-(2-carboxyethyl35cloalkylcarbonyl)-beta-alanine derivatives for

The invention provides the substantially optically pure 2(S)-stereoisomeric form of compounds of the formulae: ##STR1## and the salts thereof, together with processes for their preparation. The compounds are intermediates for the preparation of antihypertensive agents.

Glutaric acid derivatives and preparation thereof

A series of novel spiro-substituted glutaramide derivatives have been prepared, including the pharmaceutically acceptable salts thereof and bioprecursors therefor, wherein the spiro-substituent completes a 5- or 6- membered carbocyclic ring and is located at the carbon atom adjacent to the carbamoyl group. These particular compounds are inhibitors of the neutral endopeptidase E.C.3,4.24.11 enzyme and are therefore useful in therapy as diuretic agents for the treatment of hypertension, heart failure, renal insufficiency and other disorders. Methods for preparing these compounds from known starting materials are provided.

Glutaramide diuretic agents

The invention provides the substantially optically pure 2(S)-steroisomeric form of compounds of the formulae: ##STR1## and the salts thereof, together with processes for their preparation. The compounds are intermediates for the preparation of antihypertensive agents.

A series of novel spiro-substituted glutaramide derivatives have been prepared, including the pharmaceutically acceptable salts thereof and bioprecursors therefor, wherein the spiro-substituent completes a 5- or 6-membered carbocycyclic ring and is located at the carbon atom adjacent to the carbamoyl group. These particular compounds are inhibitors of the neutral endopeptidase E.C.3.4.24.11 enzyme and are therefore useful in therapy as diuretic agents for the treatment of hypertension, heart failure, renal insufficiency and other disorders. Methods for preparing these compounds from known starting materials are provided.

Heterobicyclic glyoxylic acids, L- and DL-heterobicyclic glycines and their derivatives of the formulae ##STR1## and pharmaceutically acceptable cationic and acid addition salts thereof, wherein R is OR.sup.2 or NHR.sup.3 ;

Heterobicyclic keto- and amino-acids, esters and amides

Derivates of L- and DL-hydroxyphenylglycines of the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R is hydrogen or methyl, R.sup.1 is hydrogen, amino or alkoxy having from one to six carbon atoms and R.sup.2 is the residue of certain .alpha.-amino acids are useful in treating diseases and conditions which are characterized by reduced blood flow, oxygen availability or carbohydrate metabolism in the cardiovascular system. Derivatives of D-hydroxyphenylglycine of formula (II) are substantially inactive in treating such diseases and conditions.

Therapeutic process employing amides of L and DL phenylglycines

5-Substituted 2-pyrroleglyoxylic acids, L- and DI-5-substituted 2-pyrrolylglycines and their derivatives of the formulae ##STR1## and pharmaceutically acceptable cationic and acid addition salts thereof, wherein R is hydrogen or alkyl having from one to four carbon atoms;

5-Substituted 2-pyrroleglyoxylic acids, 5-substituted 2-pyrrolylglycines

The use of phenylglyoxylic acids and derivatives thereof in the treatment of ischemic heart disease and the hyperglycemia of diabetes.

Use of phenylglyoxylic acids and derivatives thereof in the treatment of

Phenylglyoxylic acids and derivatives thereof

L- and DL-isomers of compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof, wherein R is hydrogen or methyl; R.sup.1 is alkynyl, alkenyl or cycloalkyl, each having from three to seven carbon atoms or alkyl having from one to six carbon atoms which may optionally be substituted by one or more groups selected from hydroxy, alkoxy, carboxy, amino, monoalkylamino, dialkylamino, phenyl and phenoxy, any such phenyl or phenoxy being optionally substituted with one or more hydroxy, alkyl or alkoxy groups, said alkyl and alkoxy optional substituents having from one to six carbon atoms; provided that R.sup.1 is other than 4-hydroxy-.alpha.-carboxybenzyl or 4-methoxy-.alpha.-carboxybenzyl. Said compounds are useful in treating diseases and conditions characterized by reduced blood flow, oxygen availability or carbohydrate metabolism in the cardiovascular system. The D-isomers of the compounds of formula (II) are substantially inactive in treating such diseases and conditions.

Derivatives of L- and DL-4-hydroxyphenylglycine

L- and DL- Phenylglycines of the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R is hydrogen or methyl and R.sup.1 is NH.sub.2, OH or completes a carboxylic ester group, useful in treating certain cardiovascular diseases, diabetes and obesity.

Method of treatment with glycinamides

L- and DL- Phenylglycines to treat diseases or conditions attributable

L- and DL-Phenylglycines of the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R is hydrogen or methyl and R.sup.1 is NH.sub.2, OH or completes a carboxylic ester group, useful in treating certain cardiovascular diseases, diabetes and obesity.

Growing community of inventors

Ramsgate, United Kingdom

Ian T Barnish