Sterling Drug Inc.

Sterling Winthrop Inc.

Sanofi

Sanofi Sa

Malcolm R Bell

Virendra Kumar

Thomas E D'Ambra

Rudolf Oesterlin

Chakrapani Subramanyam

John J Court

Ranjit C Desai

Richard P Dunlap

Dennis J Hlasta

Susan J Ward

Andrew W Zalay

Neil Warren Boaz

Albert J Mura, Jr

Lee H Latimer

Karl O Gelotte

John L Herrmann, Jr

Manohar T Saindane

Edward R Bacon

John P Mallamo

Philip M Carabateas

Michael A Eissenstat

Robert G Christiansen

John A Carlson

Robert P Farrell

Pierre Casellas

Francis Barth

Christian Congy

Chester J Opalka, Jr

Murielle Rinaldi

James H Ackerman

Donald C Schlegel

Richard E Philion

Didier Oustric

Harry P Schane, Jr

Vahan Akullian

Edward Richard Bacon

The use of human CB.sub.2 receptor-specific agonists of formula (I) or (I') for preparing immunomodulating drugs is disclosed. In formulae (I) and (I'), R.sub.1 is a group selected from --CH.sub.2 CHR.sub.10 NR.sub.6 R.sub.11, --(CH.sub.2).sub.2 NR'.sub.6 R'.sub.11, --CHR.sub.9 CH.sub.2 NR'.sub.6 R'.sub.11, --(CH.sub.2).sub.n Z and --COR.sub.8 ; R'.sub.1 is a --CH.sub.2 CHR.sub.10 NR.sub.6 R.sub.11 or --(CH.sub.2).sub.2 NR'.sub.6 R'.sub.11 group; R.sub.2 and R'.sub.2 are hydrogen, halogen or C.sub.1-4 alkyl; R.sub.3 is hydrogen, C.sub.1-4 alkyl or a group selected from --CH.sub.2 CHR.sub.10 NR.sub.6 R.sub.11, --(CH.sub.2).sub.2 NR'.sub.6 R'.sub.11 and --COR.sub.8 ; R'.sub.3 is a .dbd.CR.sub.6 R.sub.8 group; R.sub.4 has one of the meanings given for R.sub.5 or is a --COR.sub.8 group; R.sub.5 is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, a halogen atom, a CF.sub.3 group, an OCF.sub.3 group or C.sub.1-4 alkylthio; R'.sub.5 has one of the meanings given for R.sub.5 and is in the 5 or 6 position of the indene ring; R.sub.6 is hydrogen or C.sub.1-4 alkyl; R'.sub.6 is C.sub.1-4 alkyl; R.sub.7 has one of the meanings given for R.sub.5 or R.sub.7 and R.sub.9 together form a --Y--CH.sub.2 -- group attached to the indole ring in the 7 position by a group Y; R.sub.8 is phenyl substituted one to four times by a substituent selected from halogen, C.sub.1-4 alkyl or C.sub.1-4 alkoxy; a polycyclic ring selected from naphth-1-yl, naphth-2-yl, 1,2,3,4-tetrahydronaphth-1-yl, 1,2,3,4-tetrahydronaphth-5-yl, anthryl, benzofuryl, benzothien-2-yl, benzothien-3-yl, 2-, 3-, 4- or 8-quinolyl, said polycyclic rings optionally being substituted once or twice by a substituent selected from C.sub.1-4 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, halogen, cyano, hydroxyl, trifluoromethyl and imidazol-1-yl; R.sub.10 and R.sub.11 together are a group selected from --CH.sub.2 --O--CH.sub.2 --CR.sub.12 R.sub.13 -- and --(CH.sub.2).sub.p --CR.sub.12 R.sub.13 --, wherein the carbon atom substituted by R.sub.12 and R.sub.13 is attached to the nitrogen atom; R'.sub.11 is C.sub.1-4 alkyl; or R'.sub.11 and R'.sub.6, taken together with the nitrogen atom to which they are attached, form a group selected from morpholin-4-yl, thiomorpholin-4-yl, piperidin-1-yl and pyrrolidin-1-yl; each of R.sub.12 and R.sub.13 is independently hydrogen or C.sub.1-4 alkyl; n is 2, 3, 4 or 5; p is 2 or 3; Z is a methyl group or a halogen atom; and Y is a methylene group or an oxygen atom.

CB.sub.2 Receptor agonist compounds

4-R.sup.4 -R.sup.5 -2-Saccharinylmethyl heterocyclic carboxylates, useful in the treatment of degenerative diseases, are prepared by reacting a 4-R.sup.4 -R.sup.5 -2-halomethylsaccharin with either a heterocyclic carboxylic acid in the presence of an acid-acceptor or the alkali metal salt of a heterocyclic carboxylic acid.

2-Saccharinylmethyl heterocyclic carboxylates useful as proteolytic

2-R.sub.2 --R.sub.4 -substituted-3-R.sub.3 --CO-1-�(C-attached-N-heteryl)-(Alk) .sub.n !-1H-indoles useful as analgesic, anti-rheumatic, anti-inflammatory or anti-glaucoma agents.

3-arylcarbonyl-1-(C-attached-N-heteryl)-1H-indoles

2-saccharinylmethyl heterocyclic carboxylates useful as proteolytic

2--R.sub.2 --R.sub.4 -substituted-3--R.sub.3 --CO--1--[(C-attached-N-heteryl)-(Alk).sub.n ]--1H-indoles useful as analgesic, anti-rheumatic, anti-inflammatory or anti-glaucoma agents.

3-arylcarbonyl-1(C-attached-N-heteryl)-1H-indoles

4-R.sup.4 -R.sup.5 -2-Saccharinylmethyl aryl carboxylates, useful in the treatment of degenerative diseases, are prepared by reacting a 4-R.sup.4 -R.sup.5 -2-halomethylsaccharin with an arylcarboxylic acid in the presence of an acid-acceptor.

2-saccharinylmethyl aryl carboxylates useful as proteolytic enzyme

A compound having the formula: ##STR1## wherein Ar, R.sup.4 and R.sup.5 are defined herein have pharmaceutical utility as proteolytic enzyme inhibitors.

2-R.sub.2 -R.sub.4 -substitutea-3-R.sub.3 -CO-1-[(C-attached-N-heteryl)(Alk).sub.n ]-1H-indoles useful as analgesic, anti-rheumatic, anti-inflammatory or anti-glaucoma agents.

4-R.sup.4 -R.sup.5 -Saccharinylmethyl aryl carboxylates, useful in the treatment of degenerative diseases, are prepared by reacting a 4-R.sup.4 -R.sup.5 -2-halomethylsaccharin with an arylcarboxylic acid in the presence of an acid-acceptor.

Tetrahydro 2-saccharinylmerthyl aryl carboxylates

2-saccharinylmethyl aryl carboxylate

Proteolytic enzyme inhibition method

2- and 3-Aminomethyl-6-arylcarbonyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazines , useful as analgesic agents, are prepared either by reaction of a 2- or 3-aminomethyl-2,3-dihydropyrrolo[1,2,3-de]-1,4-benzoxazine with an arylcarboxylic acid halide in the presence of a Lewis acid or by reaction of a 2- or 3-aminomethyl-4-amino-3,4-dihydro-2H-1,4-benzoxazine with a 1-lower-alkyl-3-aryl-1,3-diketone or with a .beta.-aryl-.beta.-ketopropionaldehyde under dehydrating conditions and heating the resulting hydrazone in an acid medium.

2- or 3-aminomethyl-4-amino-3,4-dihydro-2H-1,4-benzoxazine intermediates

5'-Alkylsulfonylsteroido[3,2-b]furans, for example 5'-methylsulfonyl-5.alpha.-pregn-2-en-20-yno[3,2-b]furan-17.beta.-ol having the structural formula, ##STR1## which are useful as antiandrogenic agents, and processes for preparation, method of use and compositions thereof are disclosed.

Antiandrogenic sulfonylsteroidofurans

Growing community of inventors

East Greenbush, NY, United States of America

Malcolm R Bell