Bristol-Myers Squibb Compnay

Cumbre Pharmaceuticals Inc.

Cumbre IP Ventures, L.p.

Global Alliance for Tb Drug Development

Charles Z Ding

Zhenkun Ma

Katerina Leftheris

John T Hunt

Yafei Jin

In Ho Kim

Rajeev S Bhide

Jing Li

Karnail S Atwal

Soong-Hoon Kim

Peter T W Cheng

Susan Harran

Timothy F Herpin

Keith P Minor

Jamie C Longgood

Keith D Combrink

Hao Zhang

Pratik Devasthale

Shung C Wu

Genliang Lu

Toomas Mitt

Xiang-Yang Ye

Wei Wang

Francis N Ferrara

Jiancheng Wang

Yong He

William Alexander Denny

Saleem Ahmad

David L Green

John E Lloyd

George C Rovnyak

Philip D Stein

Brian Desmond Palmer

Gary J Grover

Andrew Mark Thompson

Adrian Blaser

Dinos P Santafianos

Hamish Scott Sutherland

Iveta Kmentova

Lawrnce G Hamann

Timothy W Morris

Minsoo Song

Dianjun D Chen

A Simon Lynch

Jamie Carol Longgood

Andrew M Thompson

Keith Combrink

Diajun D Chen

Compounds are provided which have the structure wherein

Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method

The compounds include substituted rifamycin derivatives in which a quinolone carboxylic acid pharmacophore is covalently bonded to a benzoxazinorifamycin or a spiropiperidinorifamycin. The rifamycin derivatives are useful as antimicrobial agents and are effective against a number of human and veterinary Gram positive and Gram negative pathogens. The advantage of the inventive compounds is that both the rifamycin and quinolone antibacterial pharmacophores are co-delivered with matched pharmacokinetics to the targeted pathogens of interests. Delivery of multiple antibacterial pharmacophores simultaneously to the targeted pathogens has the maximum chance of achieving synergy and minimizing the development of resistance to the antibiotics given.

Quinolone carboxylic acid-substituted rifamycin derivatives

Substituted rifamycin derivatives in which a nitroimidazole, nitrothiazole or nitrofuran pharmacophore is covalently bonded to a rifamycin, methods of using the rifamycin derivatives, and pharmaceutical compositions containing the rifamycin derivatives are disclosed. Methods of synthesizing these substituted rifamycin derivatives are also disclosed. The rifamycin derivatives possess antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases.

Nitroheteroaryl-containing rifamycin derivatives

The current invention provides a series of bicyclic nitroimidazole-substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild-type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as

Bicyclic nitroimidazole-substituted phenyl oxazolidinones

Compounds are provided which are useful as antidiabetic agents and antiobesity agents and have the structure wherein m is 0, 1 or 2; n is 0, 1 or 2;

Substituted heterocyclic derivatives are provided which have the structure wherein Zis (CH)or C&#x2550;O; In addition, a method is provided for treating diabetes, Type 2 diabetes, insulin resistance, hyperglycemia, hyperinsulinemia, elevated blood levels of fatty acids or glycerol, hyperlipidemia, obesity, hypertriglyceridemia, Syndrome X, or atherosclerosis, wherein the substituted heterocyclic derivatives are administered in a therapeutically effective amount to a patient.

The invention relates to rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms, specifically, the rifamycin derivatives having an oxime group at the C-11 position.

Rifamycin C-11 oxime derivatives effective against drug-resistant microbes

Rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms are claimed in this invention. The inventive rifamycin derivatives are uniquely designed in that they have a rifamycin moiety covalently linked to a linker group through the C-3 carbon of the rifamycin moiety and the linker is, in turn covalently linked to a therapeutic moiety or antibacterial agent/pharmacophore. The therapeutic moiety can be a quinolone, an oxazolidinone, a macrolide, an aminoglycoside, a tetracycline core or a structure/pharmacophore associated with an antibacterial agent.

Rifamycin derivatives effective against drug-resistant microbes

The present invention relates to rifamycin 3-iminomethylenyl (&#x2014;CH&#x2550;N&#x2014;) derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. The claimed rifamycin derivative has a rifamycin moiety covalently linked to a linker through an iminomethylenyl (&#x2014;CH&#x2550;N&#x2014;) group at the C-3 carbon of the rifamycin moiety and the linker is, in turn, covalently linked to a quinolone structure or its pharmacophore within the DNA gyrase and topoisomerase IV inhibitor family. The inventive rifamycins are novel and exhibit activity against both rifampin and ciprofloxacin-resistant microorganisms.

Rifamycin imino derivatives effective against drug-resistant microbes

Novel rifamycin derivatives of formula I (both hydroquinone and corresponding quinone (C-C) forms): or their salts, hydrates or prodrugs thereof,wherein: a preferred R comprises hydrogen, acetyl; L is a linker, a preferred linker group elements selected from any combination of 1 to 5 groups shown FIG., provided L is not wherein Ris H, methyl or alkyl. The inventive compounds exhibit valuable antibiotic properties. Formulations having these compounds can be used in the control or prevention of infectious diseases in mammals, both humans and non-humans. In particular, the compounds exhibit a pronounced antibacterial activity, even against multiresistant strains of microbes.

Rifamycin derivatives

Rifamycin derivatives having the following structure of general formula I (both hydroquinone and corresponding quinone (C-C) forms): or its salts, hydrates or prodrugs thereof; wherein a preferred Rcomprises hydrogen or acetyl and a prefered Rcomprises hydrogen, methyl or other lower alkyls; wherein asterik (*) denotes the carbon bearing the chiral center, wherein absolute configuration is assigned as R or S. Methods of preparation of the aforementioned rifamycin derivatives are also described. The compounds exhibit antimicrobial activities, including activities against drug-resistant microorganisms.

(R/S) rifamycin derivatives, their preparations and pharmaceutical compositions

Compounds having the formula (I), and pharmaceutically acceptable salts thereof,are useful for modulating mitochondrial FFATPase activity and treating ischemic conditions including myocardial infarction, congestive heart failure, and cardiac arrhythmias.

(1-phenyl-2-heteoaryl)ethyl-guanidine compounds as inhibitors of mitochondrial F1F0 ATP hydrolase

Compounds are provided which are useful as antidiabetic agents and antiobesity agents and have the structurewherein m is 0, 1 or 2; n is 0, 1 or 2;

Thiadioxobenzodiazepine inhibitors of farnesyl protein transferase

Disclosed are quinoline and benzazepine derivatives that inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogenic protein Ras. Thus, the compounds are useful as anti-cancer agents. The compounds are also useful in the treatment of diseases other than cancer.

Inhibitors of farnesyl protein transferase

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Plano, TX, United States of America

Charles Z Ding