Ayerst, Mckenna & Harrison, Inc.

American Home Products Corporation

Tibor Bogri

Jehan F Bagli

Nedumparambil A Abraham

Bozidar Palameta

Katherine Voith

Adi Treasurywala

Luis E Borella

.alpha.-Cyanoacrylic acid lower alkyl esters, and their corresponding amides, characterized by having a heterocyclic containing mercapto radical as one .beta.-substituent and an alkylthio, alkenylthio or a heterocyclic containing mercapto radical as another .beta.-substituent are useful for treating ulcers and for suppressing gastric acid secretion.

Pyridinyl substituted ketenemercaptal derivatives

2-(1-Piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions of the derivatives are disclosed. The derivatives exhibit dopamine-receptor stimulating activity in a mammal and are useful for treating hyperprolactinemia, galactorrhea, amenorrhea, impotence, Parkinsonism, diabetes, acromegaly, hypertension and other central nervous system disorders.

2-(1-Piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives

2-(4-Hydroxyalkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions of the derivatives are disclosed. The derivatives exhibit dopamine-receptor stimulating activity in a mammal and are useful for treating hyperprolactinemia, galactorrhea, amenorrhea, impotence, Parkinsonism, diabetes, acromegaly, hypertension and other central nervous system disorders.

2-(4-Hydroxyalkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives

2-(4-Substituted alkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions of the derivatives are disclosed. The derivatives exhibit dopamine-receptor stimulating activity in a mammal and are useful for treating hyperprolactinemia, galactorrhea, amenorrhea, impotence, Parkinsonism, diabetes, acromegaly, hypertension and other central nervous system disorders.

2-(4-Substituted alkyl-1-piperazinyl)-2,4,6-cycloheptatrien-1-one

Aldose reductase inhibitors of the formula ##STR1## in which R.sup.1 is CH.sub.2 COOR.sup.4 wherein R.sup.4 is hydrogen or lower alkyl; R.sup.2 is COOR.sup.5 wherein R.sup.5 is hydrogen or lower alkyl; and R.sup.3 is lower alkoxy, benzyloxy or CH.sub.2 COOR.sup.6 wherein R.sup.6 is hydrogen or lower alkyl; with the provisos that when R.sup.4 is hydrogen then R.sup.5 and R.sup.6 is hydrogen; and that when R.sup.4 is lower alkyl then R.sup.5 and R.sup.6 are lower alkyl with R.sup.4 and R.sup.6 being the same lower alkyl; are useful for treating diabetic complications.

4,7-Dihydro-4,7-dioxi-1H-cyclohepta[b]pyridine derivatives

Aldose reductase inhibitors of the formula ##STR1## in which R.sup.1 is COOH and R.sup.2 is hydrogen, 8-halo or 6-hydroxy, or R.sup.1 is CON(R.sup.3)-CH.sub.2 COOH wherein R.sup.3 is lower alkyl and R.sup.2 is hydrogen or 8-halo are useful for treating diabetic complications.

4,9-Dihydro-4,9-dioxo-1H-cyclohepta[b]pyridine derivatives

2-(1-Piperazinyl)-cycloheptimidazole derivatives are disclosed. The foregoing compounds are useful antihypertensive agents.

2(1-Piperazinyl)-cycloheptimidazole antihypertensive composition and

Disclosed herein are 1,2-dihydro-2-oxo(or 2-thioxo)cyclohepta[b]-pyrrole-1-acetic acid derivatives having optional substitution at positions 3, on the cycloheptatriene ring and on the acetic acid side chain. The compounds are aldose reductase inhibitors and thus are useful for treating diabetic complications.

Cyclohepta[b]pyrrole derivatives

2-(1-Piperazinyl)-cycloheptimidazole derivatives

Tropone derivatives characterized by having a derivative of oxamic acid at positions 2 and or 5 are disclosed. In addition, the tropone nucleus can be optionally further substituted. The foregoing compounds are useful for preventing or treating allergic conditions in a mammal. Methods for the preparation and use of said compounds are disclosed.

Troponyl-oxamic acid derivatives for treating allergic conditions

A process for preparing 11-deoxyprostaglandin E.sub.1, E.sub.2 and E.sub.3 and analogs thereof is realized by treating an appropriate di(lower)alkyl 3-(optionally substituted)-2-formylcyclopropane-1,1-dicarboxylate with an ylid prepared from a Wittig reagent of formula (AlkO).sub.2 POCH.sub.2 CO--(c)-CH.sub.3 in which Alk is an alkyl containing one to three carbon atoms and (c) is either (CH.sub.2).sub.q wherein q is an integer from 1 to 6 or cis CH.sub.2 CH.dbd.CH(CH.sub.2).sub.r wherein r is an integer from 0 to 3 to obtain the corresponding compound of formula: ##STR1## in which R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl, R.sup.4 is lower alkyl and (c) is as defined herein. The latter compound is reduced with an alkali metal borohydride to yield the corresponding alcohol derivative. Condensation of this alcohol derivative or preferably its corresponding tetrahydropyran-2-yl ether derivative with a triester of formula CH(COOR.sup.6).sub.2 --(a)-(CH.sub.2)pCOOR in which R and R.sup.6 are lower alkyl, (a) is CH.sub.2 CH.sub.2, cis CH.dbd.CH or C.tbd.C and p is an integer from 2 to 4, gives the corresponding cyclopentanonetriester of formula ##STR2## in which (a), (c), p, R, R.sup.4 and R.sup.6 are as defined herein, R.sup.5 is hydrogen or tetrahydropyran-2-yl, respectively, and R.sup.7 is hydrogen or lower alkyl; the lactonized form of the cyclopentanonetriester being obtained from said alcohol derivative in which R.sup.2 is CH.sub.2 OR.sup.3 wherein R.sup.3 is lower alkanoyl. In the instance when R.sup.5 is tetrahydropyran-2-yl the cyclopentanonetriester is treated with an acid to give the corresponding compound in which R.sup.5 is hydrogen. The instant compound is then treated with a base under aqueous conditions, followed by optional esterification and acylation to give the desired 11-deoxy-prostaglandin derivatives of formula ##STR3## in which (a), (c) and p, are as defined herein, (b) is trans CH.dbd.CH, R is hydrogen or lower alkyl, R.sup.1 is hydrogen or lower alkanoyl and R.sup.2 is hydrogen, lower alkyl or CH.sub.2 OR.sup.3 wherein R.sup.3 is hydrogen or lower alkanoyl. The derivatives possess prostaglandin-like biological activity and methods for their use are given.

11 Hydroxy methyl 11-deoxyprostaglandin E.sub.1

Tropone derivatives substituted with an amino-, thio- or oxy-derivative of oxalic acid or acetic acid are disclosed. In addition, the tropone nucleus can be optionally further substituted. The foregoing compounds are useful for preventing or treating allergic conditions in a mammal. Methods for the preparation and use of the compounds are disclosed.

Tropone derivatives

Prostaglandin derivatives of the formula ##STR1## in which R.sup.4, R.sup.5, R.sup.6 and R.sup.7 each are hydrogen or lower alkyl, X is hydroxy and Y is hydrogen or X and Y together are oxo, Z is CH.sub.2 CH.sub.2 or trans CH.dbd.CH, m is an integer from one to three and n is an integer from two to five, with the proviso that at least one of R.sup.4, R.sup.5 or R.sup.6 is hydrogen, are disclosed together with a process for their preparation. The compounds in which Z is CH.sub.2 CH.sub.2 and the process are new. The new derivatives possess hypotensive, antihypertensive, bronchospasmolytic, gastric acid secretion inhibiting, abortifacient, estrus synchronizing and ovulation regulating properties. These compounds also inhibit the aggregation of platelets and promote the disaggregation of aggregated platelets. Methods for their use are also disclosed.

5-Unsaturated prostanoic acid derivatives

Cyclohepta[b]pyridine-2-carboxylic acid derivatives characterized by having a 4,7-dihydro-4,7-dioxo-1H-cyclohepta-[b]pyridine nucleus substituted at position 2 with a carboxylic acid or carboxylic acid ester are disclosed. In addition, the nucleus can be optionally further substituted at positions 1, 5,6 and 8. The foregoing compounds are useful for preventing or treating allergic conditions in a mammal. Methods for the preparation and use of the compounds are disclosed.

Growing community of inventors

Montreal, Canada

Tibor Bogri