Parke-davis Company

Warner-lambert Company

Warner Lambert LLC

Ernest D Nicolaides

Francis John Tinney

Elizabeth Ann Lunney

Eugene Leroy Wittle

James S Kaltenbronn

Joseph Thomas Repine

Theodore H Haskell

Marland P Hutt, Jr

Peter W Woo

Alfred Campbell

Mildred Catherine Rebstock

W Howard Roark

Marland Paul Hutt

Thomas F Mich

James C French

Michael Andrew Stier

James P Hudspeth

Gin G Huang

Dana E DeJohn

Thomas F Mick

This invention concerns novel renin-inhibitory peptides containing proline which are useful for treating renin associated hypertension and for treating hyperaldosteronism. Intermediates and processes for preparing both the intermediates and the novel peptides, pharmaceutical compositions, and methods of treatment are included. Also included is a method of diagnosis of renin-associated hypertension using the compounds of the invention.

Proline-containing renin inhibitors

The invention concerns novel renin-inhibitory peptides which are useful for treating renin associated hypertension and for treating hyperaldosteronism. Novel intermediates, processes for preparing both the intermediates and the novel peptides, pharmaceutical compositions, and methods of treatment are included.

Renin inhibitors

Modified oxytocin-vasopressin di- or tri-peptides wherein an amide group is replaced by a group selected from ##STR1## --CH.sub.2 NH--, --CH.sub.2 O--, --CH.sub.2 S--, --CH.sub.2 SO--, --CH.sub.2 SO.sub.2 --, --CH.sub.2 CH.sub.2 -- and --CH.dbd.CH-- are described as well as methods for their manufacture, pharmaceutical compositions and methods for treatment, especially of cognitive disorders, depression, morphine dependency and parkinsonism by adjunctive therapy.

Modified tripeptides

Novel organic amide compounds which are N-[6-[(acylaminoacylamino or aminoacylamino)phenyl]-1,2-dihydro-2-oxonicotinyl] penicillin compounds having broad spectrum antibacterial utility are provided by (a) reacting the free amino acid of the appropriate penicillin or the acid salt or silylated derivative or complex thereof with a reactive derivative of the corresponding N-6-[(acylaminoacylamino or aminoacylamino)-phenyl]-1,2-dihydro-2-oxonicotinic acid or (b) reacting the free amino acid 6-aminopenicillanic acid or a related compound or the acid salt or silylated derivative thereof with a reactive derivative of the corresponding D-N-[6-[(acylaminoacylamino or aminoacylamino) phenyl]-1,2-dihydro-2-oxonicotinyl]-2-substituted glycine. Pharmaceutical compositions containing said compounds and methods for treating infections using said compositions are also disclosed.

Antibacterial amide compounds and means for using the same

Novel organic amide compounds which are N-[2-[(acylaminoacylamino or aminoacylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl] penicillin compounds having broad spectrum antibacterial utility are provided by (a) reacting the free amino acid of the appropriate penicillin or the acid salt or silylated derivative or complex thereof with a reactive derivative of the corresponding N-2-[(acylaminoacylamino or aminoacylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid or (b) reacting the free amino acid of 6-aminopenicillamic acid or a related compound or the acid salt or silylated derivative thereof with a reactive derivative of the corresponding D-N-[2-[(acylaminoacylamino or aminoacylamino)phenyl]-4-hydroxy-5-pyrimidinylcarbonyl]-2-substituted glycine. Pharmaceutical compositions containing said compounds and methods for treating infections using said compositions are also disclosed.

Novel antibacterial amide compounds and process means for producing the

A new decapeptide having the formula, pGlu-His-Trp-Ser-Tyr-Gly-Leu-NO.sub.2 Arg-Pro-Gly(NH.sub.2); salts thereof; production thereof by reacting pGlu-His-Trp-Ser-Tyr(N.sub.3) with Gly-Leu-NO.sub.2 Arg-Pro-Gly(NH.sub.2), by reacting pGlu-His-Trp-Ser-Tyr-Gly(N.sub.3) with Leu-NO.sub.2 Arg-Pro-Gly(NH.sub.2), or by reacting pGlu-His-Trp-Ser-Tyr-Gly-Leu(N.sub.3) with NO.sub.2 Arg-Pro-Gly(NH.sub.2); certain peptide intermediates and their salts used in the production thereof; and the use thereof in the preparation of luteinizing hormone releasing factor.

Pyroglutamyl-histidyl-tryptophanyl-seryl-tyrosyl hydrazides

New nonapeptides having the formula R-Trp-Ser(benzyl)-Tyr(benzyl)-D-Phe-Leu-Arg(X)-Pro-Gly-Y wherein X is a protective group, R is pGlu, protected His(benzyl), protected Ser(benzyl) or protected Cys(benzyl), and Y is lower alkoxy, amino, lower alkylamino or di(lower alkyl)amino.

Nonapeptides and methods for their production

New octapeptides having the formula Prot Grp-R-Trp-Ser-Tyr-R.sub.2 -Leu-Arg-Pro-R.sub.3 ; salts thereof; wherein R is Gln, Gln (bzl), His (bzl), Ser (bzl), Pro, Leu, Tyr (bzl), Ile, Cys (bzl) or Phe, R.sub.2 is D-Phe, D-Ala, D-Leu, D-Trp, D-Tyr, D-Tyr (Me), D-Ser, D-Met, D-Arg, D-Val, D-His, D-Gln, D-Phs, D-Thr, D-Pro, D-Me.sub.5 Phe or D-Asn and R.sub.3 is NH.sub.2, NH(lower alkyl), N-(lower alkyl).sub.2, NH-benzyl, NHCH.sub.2 CH.sub.2 N-(lower alkyl).sub.2 or NH-CH.sub.2 CH.sub.2 SO.sub.2 NH-benzyl; methods for their production; certain peptide intermediates and their salts used in the production thereof; and the use of said octapeptides as luteinizing hormone releasing factor antagonists.

Octapeptides and methods for their production

New octapeptides having the formula X-R.sup.1 -Trp-Ser(benzyl)-Tyr(benzyl)-R.sup.2 -Leu-Arg(R)-Pro-R.sup.3 -Y wherein X is a protective group, R is hydrogen or a protective group, R.sup.1 is a single bond, Gln, D-Leu or D-Val, R.sup.2 is D-Phe or D-Ala, R.sup.3 is a single bond or Gly and Y is lower alkoxy, amino, lower alkylamino or di(lower alkyl)amino.

New heptapeptides having the formula X-R-His(benzyl)-His(benzyl)--R.sup.1 --R.sup.2 --Trp--Ala--Y wherein X is a protective group, R is Pro or Gln; R.sup.1 and R.sup.2 are Ser(benzyl) or Tyr(benzyl) and Y is lower alkoxy, amino, lower alkylamino or di(lower alkyl)-amino.

New heptapeptides and methods for their production

New hexapeptides having the formula X-R-Trp-His(benzyl)-Tyr(benzyl)-Ser(benzyl)-R.sup.1 -Ala-Y wherein X is t-butoxycarbonyl or benzyloxycarbonyl, R is a single bond, His, His(benzyl) or Gln; R.sup.1 is a single bond or Pro and Y is lower alkoxy, amino, lower alkylamino or di(lower alkyl)amino with the proviso that the total number of amino acid units when R and R.sup.1 are combined is one.

Hexapeptides and methods for their production

New nonapeptides having the formula pGlu-D-Phe-Trp-Tyr(benzyl)-Ser(benzyl)-D-Ala-Leu-Orn-Pro-Y and Y is amino, lower alkylamino or di(lower alkyl)amino.

New pentapeptides having the formula X-R-Tyr-(benzyl)-Ser(benzyl)-R.sup.1 -Y wherein X is t-butoxycarbonyl or benzyloxycarbonyl, R is a single amino acid fragment, a dipeptide fragment or tripeptide fragment utilizing amino acids selected from the group consisting of Pro, Aze, His-(benzyl) and Trp; R.sup.1 is a single bond or a single amino acid fragment or a dipeptide fragment utilizing amino acids selected from the group consisting of Ala, Trp and His and Y is lower alkoxy, hydrazino, amino, lower alkylamino or di(lower alkyl)amino with the proviso that the total number of amino acid units when R and R.sup.1 are combined is three.

New pentapeptides and methods for their production

New pentapeptides having the formula X-R-Ser-(benzyl)-Tyr(benzyl)-R.sup.1 -Y wherein X is t-butoxycarbonyl or benzyloxycarbonyl, R is a single amino acid fragment or a dipeptide fragment utilizing amino acids selected from the group consisting of Aze, His(benzyl) and Trp; R.sup.1 is a single amino acid fragment or a dipeptide fragment utilizing amino acids selected from the group consisting of Ala, Leu and Pro and Y is lower alkoxy, hydrazino, amino, lower alkylamino or di(lower alkyl)amino with the priviso that the total number of amino acid units when R and R.sup.1 are combined is three.

New tetrapeptides having the formula A-R.sub.1 -Tyr(benzyl)-Ser(benzyl)-D-Ala-R.sub.2 wherein A is t-butoxycarbonyl, cyclohexylcarbonyl, benzyloxycarbonyl and p-nitrobenzyloxycarbonyl; R.sub.1 is L-His(benzyl), D-Pro, or L-Trp; Tyr(benzyl) is D-Tyr-(benzyl) or L-Tyr(benzyl); Ser(benzyl) is D-ser(benzyl) or L-Ser(benzyl) and R.sub.2 is lower alkoxy, hydrazino, amino, lower alkylamino or di(lower alkyl)amino.

Growing community of inventors

Ann Arbor, MI, United States of America

Ernest D Nicolaides