Ayerst, Mckenna & Harrison, Inc.

American Home Products Corporation

Francesco Bellini

Kazimir Sestanj

Nedumparambil A Abraham

Adi Treasurywala

Hans U Immer

Steven Fung

Leslie G Humber

Jehan F Bagli

Marvin M Kobric

Michael Kraml

Nedumparampil A Abraham

Herein disclosed are N-naphthoylglycine derivatives having aldose reductase inhibiting activity. The derivatives are useful for treating, diabetic complications.

N-naphthoylglycine derivatives

Herein disclosed are N-naphthoylglycine derivatives having aldose reductase inhibiting activity. The derivatives are useful for treating diabetic complications.

Disclosed herein are tolrestat amides and methods of preparation. The amides are new aldose reductase inhibitors useful for the treatment or prevention of diabetic complications.

N[[5-(trifluoromethyl)-6-methoxy-1-naphthalenyl]-thioxomethyl]-N

Disclosed herein are new aldose reductase inhibitors of the formula ##STR1## wherein n is an integer from 1 to 5 and X is a chalcogen, and methods of preparation. The derivatives are useful for treating or preventing diabetic complications.

N-[6-methoxy-5-(perfluoroalkyl)-1-naphtholyl]-N-methylglycines and their

N-Naphthoylglycine derivatives

Disclosed herein are antisecretory agents represented by the formula ##STR1## wherein R.sup.1 is hydrogen and R.sup.2 is lower alkylthio, (2-thienylmethyl)thio or SCH.sub.2 -- COOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl, or R.sup.1 and R.sup.2 are independently a lower alkylthio or (2-thienylmethyl)thio, or R.sup.1 and R.sup.2 together with the carbon atom to which they are attached form a 2-imidazolidinylidene; and R.sup.3 and R.sup.4 are each the same lower alkyl, or R.sup.3 and R.sup.4 together with the carbon atoms to which they are attached form a cyclohexane wherein said carbon atom is a spiro atom in common with the cyclohexane ring and the adjoining dioxane ring.

Antisecretory agents derived from meldrum's acid

A process and intermediates for preparing 6-(lower alkoxy)-5-(trifluoromethyl)-1-naphthalenecarboxylic acid derivatives are disclosed. The derivatives are useful for preparing aldose reductase inhibitors. With reference to the process, 1,1,1-trifluoro-5-(2-methylphenyl)-2,3-pentadione 3-oxime is cyclized to give a key intermediate 3,4-dihydro-1-hydroxy-5-methyl-1-(trifluoromethyl)-2(1H)-naphthalenone oxime; and 3,4-dihydro-1-hydroxy-5-methyl-1-(trifluoromethyl)-2(1H)-naphthalenone is aromatized to 5-methyl-1-(trifluoromethyl)-2-naphthalenol with a dehydrating agent.

5-Methyl-1-(trifluoromethyl)-2-naphthalenol, process for its preparation

Disclosed herein are new aldose reductase inhibitors of the formula ##STR1## wherein R is ##STR2## wherein R.sup.1 is lower alkyl; R.sup.2 is halo and R.sup.3 is hydrogen, or R.sup.2 and R.sup.3 each is a substituent at positions 3, 4, 5 or 6 of the naphthalene ring selected from the group consisting of lower alkoxy, trihalomethyl, and halo; and R.sup.4 is lower alkyl. The derivatives are useful for treating or preventing diabetic complications.

Naphthalenylthiazole derivatives

6-(Lower alkoxy)-5-(trifluoromethyl)-1-naphthalenecarboxaldehydes

Herein disclosed are N-(naphthalenylthioxomethyl)aminoacid derivatives having aldose reductase inhibiting activity. The derivatives are useful for treating diabetic complications.

N-(Naphthalenylthioxomethyl)aminoacid derivatives

Aldose reductase inhibitors of the formula ##STR1## wherein R.sup.1 and R.sup.2 each is lower alkyl, or a therapeutically acceptable salt thereof with an organic or inorganic base, are useful for treating diabetic complications.

N-[[6-(Lower

Herein is described a process for preparing the decapeptide Pry-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2 ([D-Trp.sup.6 ]-LH-RH) by coupling Pyr-His-Trp-NHNH.sub.2 with H-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH.sub.2. [D-Trp.sup.6 ]-LH-RH had been established to be an efficient agent for causing release of lutenizing hormone and follicle-stimulating hormone in mammals.

Preparation of (D-Trp .sup.6)-LH-RH via the heptapeptide

Peptides of formula I ##STR1## in which X is (CH.sub.2).sub.2, S--CH.sub.2 or CH.sub.2 --S or a therapeutically acceptable acid addition salt thereof are disclosed. The peptides of formula I are useful as agents for the treatment of acromegaly and the management of diabetes in a mammal. Compositions and methods for the preparation of the peptides of formula I are also disclosed.

Growing community of inventors

Mount Royal, Canada

Francesco Bellini