Ciba-Geigy Corporation

Novartis Ag

Isidoros Vlattas

Gary Mark Coppola

Sidney Wolf Topiol

James Richard Wareing

John William Davies

Yu-Chin Li

Donald Mark Sperbeck

Travis Mathew Stams

Charles Francis Jewell, Jr

Compounds of the formula provide pharmacological agents which are inhibitors of PTPases, in particular, the compounds of formula I inhibit PTP-1B and TC PTP, and thus may be employed for the treatment of conditions associated with PTPase activity. The compounds of the present invention may also be employed for inhibition of other enzymes with a phosphotyrosine binding region such as the SH2 domain. Accordingly, the compounds of formula I may be employed for prevention or treatment of insulin resistance associated with obesity, glucose intolerance, diabetes mellitus, hypertension and ischemic diseases of the large and small blood vessels. The compounds of the present invention may also be employed in the treatment, prevention or control of a number of conditions that accompany Type 2 diabetes, including hyperlipidemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, irritable bowel syndrome, pancreatitis, adipose cell tumors and carcinomas such as liposarcoma, dyslipidemia, and other disorders where insulin resistance is indicated. In addition, the compounds of the present invention may be employed to treat or prevent cancer, osteoporosis, neurodegenerative and infectious diseases, and diseases involving inflammation and the immune system.

5-substituted 1,1-dioxo-1,2,5,-thiadiazolidin-3-one derivatives

1-(Carbamyl, thiocarbamyl, and iminocarbamyl)-indoline derivatives of the formula ##STR1## where each R.sub.1 is independently alkyl, alkoxy, acyloxy, hydroxy, halo or trifluoromethyl, n is 0, 1, 2 or 3, R.sub.2 and R.sub.3 are independently hydroxy, alkoxy, amino or substituted amino, R.sub.4 and R.sub.5 are independently hydrogen, alkyl or substituted alkyl, R.sub.6 is hydrogen, alkyl or substituted alkyl, and Y is O, S or N--R.sub.7 where R.sub.7 is hydrogen, alkyl, cyano or substituted alkyl, and salts thereof, which are useful as antihypertensive and cardioactive agents, methods of preparing the same, and pharmaceutical compositions thereof, are provided.

1-(carbamyl, thiocarbamyl, and iminocarbamyl)-indoline derivatives

Described are 5-diazacycloalkyltriazolo[2,3-c][1,3]benzodiazepines, for example compounds of the formula ##STR1## wherein R.sub.1 represents hydrogen, halogen, trifluoromethyl, lower alkylthio, lower alkoxy or lower alkyl; R.sub.2 represents hydrogen, lower alkyl or hydroxy-C.sub.2 -C.sub.7 alkyl wherein the hydroxy group is separated from the nitrogen atom by at least 2 carbon atoms; R.sub.3 represents hydrogen, lower alkyl, lower alkoxy, lower alkylthio, halogen or trifluoromethyl; and C.sub.n H.sub.2n represents ethylene. The synthesis, pharmaceutical compositions and methods of use as neuroleptic and/or antihistaminic agents are given.

Diazacycloalkyl-1,2,4-triazolo[2,3-c][1,3]benzodiazepines useful as

5-Diazacycloalkylimidazo[1,2-c][1,3]benzodiazepines, for example compounds of the formula ##STR1## in which e.g., R.sub.1, R.sub.2 and R.sub.4 are hydrogen, R.sub.3 is methyl and C.sub.n H.sub.2n is CH.sub.2 CH.sub.2, have neuroleptic and/or antihistaminic activity. The synthesis, pharmaceutical compositions and methods of treatment utilizing such compounds are described.

Imidazo[1,2-c][1,3]benzodiazepines

5-Diazacycloalkyl-imidazo[2,1-b][1,3,5] benzothiadiazepines, e.g. those of the formula ##STR1## R.sub.1, R.sub.2 =H or alkyl R.sub.4 =H, alkyl or HO--alkyl;

Process for preparing imidazobenzothiadiazepines

5-Diazacycloalkyl-imidazo[imidazo]2,1-b][1,3,5]benzothiadiazepines of the formula ##STR1## e.g. a compound of formula I wherein Ph=phenylene, m=2, n=3, R.sub.1 and R.sub.2 =H, and R.sub.3 =methyl, oxides and salts thereof, are neuroleptic agents.

Imidazobenzothiadiazepines

5-Diazacycloalkyl imidazo[1,2-c][1,3]benzodiazepines

5-Diazacycloalkylimidazo[1,2-c][1,3]benzodiazepines, for example compounds of the formula ##STR1## in which e.g., R.sub.1, R.sub.2 and R.sub.4 are hydrogen, R.sub.3 is methyl and C.sub.n H.sub.2n is CH.sub.2 CH.sub.2, have neurcleptic and/or antihistaminic activity. The synthesis, pharmaceutical compositions and methods of treatment utilizing such compounds are described.

5-Diazacycloalkylimidazo[1,2-c][1,3]benzodiazepines

5-Diazacycloalkyl-imidazo[2,1-b][1,3,5]benzothiadiazepines, e.g. those of the formula ##STR1## the N-oxides and salts thereof are neuroleptic agents, lacking extrapyramidal side-effects.

5(1-Piperazinyl(imidazo[2,1-b][1,3,5]benzothiadiazepines

7-[3.alpha.-(3-hydroxy-3-hydrocarbylpropyl, or -1-propenyl, or 1-propynyl)-4-hydroxy-tetrahydro-2.beta.-furyl]-heptanoic or 4-heptenoic acids, esters or salts thereof are stable, prostaglandin-like acting agents.

9-Oxaprostaglandins

7-[3.alpha.-(3-hydroxy-3-hydrocarbylpropyl, or -1-propenyl, or 1-propynyl)-4-hydroxy-tetrahydro-2.beta.-thienyl]-heptanoic or 5-heptenoic acids, sulfoxides, sulfones, esters or salts thereof are stable, prostaglandin-like acting and antiasthmatic agents.

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Summit, NJ, United States of America

Isidoros Vlattas