A. H. Robins Company, Incorporated

William J Welstead, Jr

David A Walsh

Young S Lo

Henry W Moran

Ibrahim M Uwaydah

Dwight A Shamblee

Robert F Boswell

Joseph C Nolan

Albert D Cale, Jr

Ying-Ho Chen

Reevis S Alphin

Warren N Dannenburg

Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula:

Compounds having one or more aminosulfonyloxy radicals useful as

Compounds having one or more aminosulfaonyloxy radicals useful as

This invention relates to an improved process for the preparation of 3-phenoxy-1-azetidinecarboxamides of Formula I which are useful ##STR1## in the treatment of epileptic seizures. Under Formula I, n is 1 to 3, X is H, halogen, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, acetyl, or aminocarbonyl, and R is H or methyl. This process involves heating a 3-phenoxyazetidine with urea to obtain the Formula I compound. Urea is inexpensive and easily removed by washing the solid Formula I product with water.

Urea fusion process for the synthesis of

A process is described wherein pyrido[1,4]benzodiazepines having the formula: ##STR1## wherein Q is NR.sup.1 R.sup.2 or ##STR2## are prepared from unsubstituted pyridobenzodiazepinones by alkylation reaction with halo-alkyl-Q followed by acylation of the other nitrogen; breaking the ring with an aryl Grignard reagent and recyclizing to add the aryl radical and form the azepine ring. Novel intermediates are thereby disclosed.

Process for the preparation of aryl-pyrido(1,4) benzodiazepines

A pharmaceutical method for improving memory or correcting memory deficiency is disclosed, utilizing compounds having the formula: ##STR1## wherein m and n are zero and one and when m is zero, the dotted line represents a double bond; X is oxygen or sulfur; R.sup.1 and R.sup.2 are hydrogen, loweralkyl, phenyl or phenylloweralkyl, or R.sup.1 and R.sup.2 taken together may form a fused second ring with the nitrogen atoms having three or four methylene groups to which may be attached at any second ring carbon atom thereof, a loweralkyl or phenyl radical; R.sup.3 is hydrogen or loweralkyl; Ar is phenyl, pyridyl, furanyl, thienyl, methoxy-1H-benzotriazolyl, indolinyl, methoxyindolinyl, methoxypyrimidinyl, aminomethoxypyrimidinyl, 1,3-benzodioxolyl or naphthalenyl, the active optical isomers; and the pharmaceutically acceptable acid addition salts thereof.

Method for enhancing memory or correcting memory deficiency with

A pharmaceutical method for improving memory or correcting memory deficiency is disclosed, utilizing compounds having the formula: ##STR1## wherein n.sup.1, n.sup.2, n.sup.3, and n.sup.4 =0 to 3; R.sup.1, R.sup.2, R.sup.3, and R.sup.4 =H, loweralkyl or phenyl; R.sup.5 =H or loweralkyl; X=O or S; Ar=phenyl, substituted phenyl, pyridinyl, furanyl, thienyl, methoxy-1H-benzotriazolyl, indolinyl, methoxyindolinyl, methoxypyrimidinyl, amino-methoxypyrimadinyl, 1,3-benzodioxolyl, or naphthalenyl, and the pharmaceutically acceptable acid addition salts, hydrates and alcoholates thereof.

Method of enhancing memory or correcting memory deficiency with

Cis and trans-3-aryloxy-4-hydroxypyrrolidines and derivatives thereof having the formula: ##STR1## are disclosed wherein R.sub.1 is hydrogen, loweralkyl, benzyloxycarbonyl and N-loweralkylcarbamoyl; R.sub.2 is hydrogen, lower alkyl, cycloalkyl, phenylalkyl, benzyloxycarbonyl, carbamoyl, N-loweralkylcarbamoyl, N-diloweralkylcarbamoyl and parafluorobenzoyl-lower-alkyl; Ar is phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, 1-indenyl and 2-indenyl and pharmaceutically acceptable acid addition and quaternary salts thereof. The compounds have antidepressant, antihypertensive and antiarrythmic activity in animals.

Cis and trans-3-aryloxy-4-hydroxypyrrolidines used as anti-arrhythmics

Novel 2-amino-3-benzoylphenethylalcohols are provided having the formula: ##STR1## wherein; X is hydrogen, loweralkyl, loweralkoxy, halogen or trifluoromethyl, and

2-Amino-3-benzoyl-phenethylalcohols and intermediates therefor

Trans-4-(2-chlorophenoxy)-1-ethyl-3-pyrrolidinol and anti-depressant use

1-R-4-(omega-substituted alkyl)-3,3-diphenyl-2-pyrrolidinones of the formula ##STR1## wherein R is hydrogen, lower alkyl, cyclohexyl or benzyl, R.sup.1 is hydrogen, chloro, bromo, fluoro, trifluoromethyl or lower alkoxy, R.sup.2 is hydrogen, chloro, bromo, or fluoro, A is hydroxy, lower-alkylcarbonyloxy or lower-alkoxycarbonyl and n is 1, 2 or 3 having analgetic and antidiarrheal activity are disclosed. The pharmaceutically acceptable acid addition salts of the bases are within the scope of the present invention.

Heterocyclic antidiarrheal compositions & methods of use

3,4-Epoxypyrrolidines substituted in the 1-position with alkyl, cycloalkyl and phenylalkyl are disclosed which have pharmaceutical application in cataract prevention in animals and as intermediates in preparation of trans-3-aryloxy-4-hydroxypyrrolidines. The epoxypyrrolidines are prepared by a novel route involving chlorination of pyrrolines in aqueous medium.

1-Substituted-3,4-epoxypyrrolidines

A novel process for the preparation of 7-acylindolin-2-ones of the formula: ##STR1## wherein R is hydrogen, halogen, lower alkyl, lower alkoxy, or trifluoromethyl; R.sup.1 is lower alkyl, alkylphenyl, cycloalkyl, or aryl; and R.sup.2 is hydrogen, lower alkyl or benzyl is provided. The compounds are useful as intermediates in the preparation of 2-amino-3-acylphenylacetic acid compounds which possess pharmaceutical properties.

Intermediate and process for the preparation of 7-acylindolin-2-ones

Novel 2-amino-3-(5- and 6-)benzoylphenylacetic acids, esters and metal salts of the formula: ##STR1## wherein R is hydrogen or lower alkyl, R.sup.1 is hydrogen, lower-alkyl, sodium or potassium, R.sup.2 is hydrogen, halogen or lower alkoxy, X is hydrogen, lower alkyl, halogen, nitro or trifluoromethyl, Y is hydrogen, lower alkyl, halogen, nitro or trifluoromethyl, and Am is primary amino (--NH.sub.2) methylamino or dimethylamino. The compounds are prepared by hydrolysis of 4-(5- and 7-)benzoylindolin-2-ones to give the 2-amino-3-(5- and 6-)benzoylphenylacetic acids wherein amino is primary amino. The free acids are converted to the esters and metal salts. The calcium and magnesium salts are disclosed and are within the scope of the present invention. The compounds inhibit blood platelet aggregation.

Method of inhibiting blood platelet aggregation with 2-amino-3-(5- and

1,5-Disubstituted-1,2-dihydro-2H-1,4-benzodiazepin-2-ones of the formula ##STR1## wherein R is hydrogen or fluoro, R.sup.1 is hydrogen, fluoro chloro, bromo or trifluoromethyl, and n is 2 to 4, having anticonvulsant activity and useful as anti-anxiety agents, are disclosed.

1,5-Disubstituted-1,2-dihydro-2H-1,4-benzodiazepin-2-ones

Methods for using 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-1,2-dione and pharmaceutical compositions thereof in preventing diabetic complications are disclosed.

Growing community of inventors

Richmond, VA, United States of America

William J Welstead, Jr