Sandoz Gmbh

Novartis Ag

Novartis Tiergesundheit Ag

Pietro Bollinger

Hans Kobel

Dieter Seebach

Roland M Wenger

Soo Young Ko

Brigitte Besemer-Rosenwirth

Rene P Traber

Jorg Schnyder

Hans U Gubler

Johann J Bolsterli

Mahavir Prashad

Yugang Liu

Bernhard Riss

Peter C Hiestand

Trevor G Payne

Janet Dawson King

Jonathan King

Vincent Schmid

Friedrich Schuerch

Ren&eacute;P Traber

The present invention relates to novel aza-thia-benzoazulene derivatives of formula I as defined in the claims, their preparation, the use of these novel compounds for the preparation of pharmaceutical compositions, the use of these novel compounds and compositions for managing arthritis and arthritis-related conditions as well as in the treatment of pain in animals and humans. More particularly, the present invention relates to pharmaceutical, preferably veterinary compositions and methods for reducing inflammation and pain associated with acute inflammation of body parts, particularly joints, due to injury or due to arthritic conditions or other disease conditions.

Organic compounds

It has been found that nonimmunosuppressive, cyclophilin-binding cyclosporins are useful in the treatment and prevention of AIDS and AIDS-related disorders. Such cyclosporins include novel Ciclosporin derivatives modified at the 4- and/or 5-positions.

Cyclosporin fermentation process

Cyclosporins

Nonimmunosuppressant cyclosporin derivatives having cyclophilin-binding activity, for example, the compound, �MeIle!.sup.4 -ciclosporin, are useful in inhibiting HIV-1 replication in treating AIDS and AIDS related disorders.

Cyclosporins wherein the residue at the 1-position (typically -MeBmt- or -dihydro-MeBmt-) is 3'O-acylated or 3'-oxo or -C.sub.1-4 alkoxyimino substituted, or wherein the residue at the 2-position is .beta.-O-acyl or .beta.-oxo substituted, or wherein the residue at the 2-position is -Ile-, or wherein the residue at the 11-position is -MeAls-, -MeIle- or -MealloIle- as well as various naturally occurring cyclosporins/dihydro-derivatives thereof, are useful in reversing resistance to chemotherapy, in particular resistance to cytostatic or anti-neoplastic therapy. Various of these cyclosporins and intermediates for their production are novel. Intermediates wherein the residue (e.g. -MeBmt-, -dihydro-MeBmt- etc.) at the 1-position is 8'-alkoxy or 7'-desmethyl-7'-hydrocarbyl substituted are novel and useful as immunosuppressants, anti-inflammatory and anti-parasitic agents.

Cyclosporins and their use as pharmaceuticals

.alpha.-[10-oxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene]-carboxyli c acids, or physiologically-hydrolysable and -acceptable esters or pharmaceutically acceptable salts thereof are useful for effecting monokine inhibition, in particular interleukin-1 release or secretion inhibition, as a therapeutic means other than anti-inflammatory or anti-pyretic means.

.alpha.-[10-oxy-4H-benzo[4,5]cycloheptal[1,2-b]thiophen-4-ylidene]-carboxyl ic acids, or physiologically-hydrolysable and -acceptable esters or pharmaceutically acceptable salts thereof are useful for effecting monokine inhibition, in particular interleukin-1 release or secretion inhibition, as a therapeutic means other than anti-inflammatory or anti-pyretic means.

Treating tissue calcium depletion or degenerative processes in bone or

.alpha.-[5H-dibenzo[a,d]cyclohepten-5-ylidene]-carboxylic acids e.g. of formula I ##STR1## wherein R.sub.1 is H, C.sub.1-4 alkyl or phenyl-(C.sub.1-4 alkyl), R.sub.2 is H or C.sub.1-4 alkyl and ring A is unsubstituted or halo- or hydroxy-substituted, as well as the physiologically-hydrolysable and -acceptable esters thereof have valuable pharmaceutical, in particular anti-inflammatory, antipyretic and analgesic properties.

4H-benzo(4,5)cyclohepta(1,2-B)thiophene derivatives

Novel cyclosporins having an -Allylgly- residue in the 2-position and/or a -(D)-Ser- residue in the 8-position and process for their production. The novel cyclosporins are useful as pharmaceuticals, e.g. as immunosuppressive and anti-inflammatory agents.

Novel cyclosporins

The present invention concerns prostaglandins having a cyclopropane ring in the 2,3 position.

Growing community of inventors

Bottmingen, Switzerland

Pietro Bollinger