Merck + Co., Inc.

Other

Purdue Research Foundation

Shieh-Shung T Chen

Byron H Arison

Raymond F White

George M Garrity

Edward S Inamine

Linda S Wicker

George A Doss

Brian R Petuch

Ali Shafiee

John G MacConnell

Magda M Gagliardi

Leeyuan Huang

Louis Kaplan

Francis J Dumont

Brian Heimbuch

Georgette Dezeny

Randall R Miller

Lydia T So

David J Mathre

Thomas R Beattie

Michel M Chartrain

Russell B Lingham

Robert A Reamer

Laszlo R Treiber

Jon D Polishook

Kevin M Byrne

Ching-jer Chang

Christopher Roberge

Lawrence F Colwell, Jr

Bei B Zhang

Sagrario Mochales

Ralph A Stearns

Bryon H Arison

Xiaohua Li

Amy M Hale

Amy M Bernick

Substituted 4-hydroxy-2-furoic acids are obtained by the fermentation of an asterriquinone, which is a natural product having a 2,5-dioxy-3,6-bis(indolyl)quinone structure. The compounds modulate insulin receptor tyrosine kinase activity and may be useful in the treatment of diabetes and other diseases or conditions characterized by impaired endogenous insulin production or an impaired response to endogenous insulin.

Antidiabetic 4-hydroxy-2-furoic acids

A biotransformation process for the production of hydroxylated derivatives of taxol and new derivatives of taxol and cephalomannine are described. A method for converting taxol to L-760,006 and L-760,007, and a method for converting cephalomanine to L-745,596 are provided.

Microbial transformation of taxol and cephalomannine

Biotransformation products of a fermentation with culture MA7074 are potent HIV protease inhibitors. These products are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.

Streptomyces sp. MA 7074 (ATCC 55605) used for microbial synthesis of

The present invention provides a process for the stereoselective reduction of phenylalkyl ketones to their corresponding (S)-hydroxy compounds. The process utilizes the novel microorganism Microbacterium MB 5614 to effectuate the chiral reduction. The present invention also provides said novel Microbacterium, which has been deposited with the ATCC and assigned the accession number ATCC 55557.

Microbial method

Cholesterol lowering compound

A process for reducing a phenylalkyl ketone to the corresponding (S)-hydroxy derivative is disclosed. The process comprises contacting the phenylalkyl ketone with Mucor hiemalis IFO 5834 and recovering the (S)-hydroxy derivative.

Reduction of phenylalkyl ketones to the corresponding (S)-hydroxy

New cholesterol lowering compounds are formed from the photochemical treatment of the zaragozic acids.

Cholesterol lowering compounds

Microbial transformation of a macrolide immunosuppressant by the microorganism Streptomyces sp., (Merck Culture Collection MA 6960) ATCC No. 55387 yields a compound of the structural formula (I): ##STR1## This compound is an immunosuppressant useful in a mammalian host for the treatment of autoimmune diseases, infectious diseases, the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.

Microbial transformation product having immunosuppressive activity

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthetase inhibitors and thus useful as cholesterol lowering agents, antifungal agents and cancer treatment agents.

Cholesterol lowering compounds produced by directed biosynthesis

Compounds of Structural Formula (I) ##STR1## are produced by directed biosynthesis. These compounds are squalene synthase inhibitors and thus useful as cholesterol lowering agents and antifungal agents. These compounds are also inhibitors of farnesyl protein transferase and farnesylation of the oncogene protein Ras and thus useful in treating cancer.

Directed biosynthesis of biologically active compounds

Described is a process for producing an immunosuppressant, 'demethimmunomycin' (L-683,7411) a C-31 demethylated analog of L-683,590 under fermentation conditions utilizing the microorganism, Actinoplanacete sp, (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.

Immunosuppressant agent

Described is a process for producing a new immunosuppressant, a C-19/C-22 cyclic hemiketal (Compound I) biotransformation analog of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces sp. (Merck Culture Collection MA6969) ATCC No. 55280. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

New cyclic FR-900520 microbial biotransformation agent

Described is a process for producing a new immunosuppressant, a C-19/C-22 cyclic hemiketal (Compound I) biotransformation analog of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces sp. (Merck Culture Collection MA6971) ATCC No. 55282. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

Cyclic FR-900520 microbial biotransformation agent

Described is a process for producing a new immunosuppressant, a C-31 desmethyl, C-19/C-22 cyclic hemiketal biotransformation analog (Compound I) of FR-900520, under novel fermentation conditions utilizing the novel microorganism, Streptomyces, lavendulae ATCC No. 55209. Also disclosed is the C-31 methylated derivative (Compound II) of Compound I produced by enzymatic methylation using 31-O-desmethylimmunomycin O-methyl transferase, (DIMT), a methyl transferase enzyme. The macrolide immunosuppressants are useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow, liver, lung, kidney and heart transplants.

C-31 desmethyl FR-900520 cyclic hemiketal immunosuppressant agent

This invention relates to compounds of structural formula (I): ##STR1## which are squalene synthase inhibitors and thus useful as cholesterol lowering agents. The compounds also exhibit antifungal activity and are inhibitors of farnesyl-protein transferase.

Growing community of inventors

Morganville, NJ, United States of America

Shieh-Shung T Chen