Time filter

Source Type

Singapore, Singapore

Liu Y.,Kosan Biosciences Inc. | Li Y.,Kosan Biosciences Inc. | Myles D.C.,Kosan Biosciences Inc. | Claypool M.,Kosan Biosciences Inc. | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2010

A series of derivatives of the amine of 9-dihydro-9-O-ethylamino-N- desmethyl-N-isopropyl erythromycin A derivatives were synthesized as motilin agonists. The compounds were developed for potency without showing antibacterial activity and inhibition of the hERG potassium channel. The formamide of the amide series was found to show the optimal combination of properties relative to carbamates, ureas, thioureas, and amines. This prompted an investigation of heterocyclic isosteres for the amide. In this series the triazole had the optimal combination of properties. From the study, two compounds met the criteria for detailed pharmacokinetic studies. © 2010 Elsevier Ltd. All rights reserved. Source

Duncton M.A.J.,Evotec | Duncton M.A.J.,Rigel Inc
MedChemComm | Year: 2011

The addition of a radical to a heteroaromatic base is commonly referred to as a Minsici reaction. Such reactions constitute a broad-set of selective CH-functionalization processes. This review describes some of the major applications of Minisci reactions and related processes to medicinal or biological chemistry, and highlights some potential developments within this area. © 2011 The Royal Society of Chemistry. Source

This invention is directed to compounds of formula (I): where n, m, Y, R

trans-2-(Trifluoromethyl)cyclopropylboronic acid N-methyliminodiacetic acid (MIDA) ester 5 was synthesized as a pure diastereomer from vinylboronic acid MIDA ester and (trifluoromethyl)diazomethane in a single step. An X-ray study confirmed the trans-stereochemistry around the cyclopropyl ring. Use of 5 in Suzuki reactions, with a variety of aryl or heteroaryl coupling partners, provided trans-2-(trifluoromethyl)cyclopropyl products in moderate to excellent yields (17-90%). © 2013 American Chemical Society. Source

Owyang A.M.,XOMA | Owyang A.M.,Rigel Inc | Issafras H.,XOMA | Corbin J.,XOMA | And 9 more authors.
mAbs | Year: 2011

Interleukin-1β (IL-1β) is a potent mediator of inflammatory responses and plays a role in the differentiation of a number of lymphoid cells. In several inflammatory and autoimmune diseases, serum levels of IL-1β are elevated and correlate with disease development and severity. The central role of the IL-1 pathway in several diseases has been validated by inhibitors currently in clinical development or approved by the FDA. However, the need to effectively modulate IL-1β-mediated local inflammation with the systemic delivery of an efficacious, safe and convenient drug still exists. To meet these challenges, we developed XOMA 052 (gevokizumab), a potent anti-IL-1β neutralizing antibody that was designed in silico and humanized using Human Engineering™ technology. XOMA 052 has a 300 femtomolar binding affinity for human IL-1β and an in vitro potency in the low picomolar range. XOMA 052 binds to a unique IL-1β epitope where residues critical for binding have been identified. We have previously reported that XOMA 052 is efficacious in vivo in a diet-induced obesity mouse model thought to be driven by low levels of chronic inflammation. We report here that XOMA 052 also reduces acute inflammation in vivo, neutralizing the effect of exogenously administered human IL-1β and blocking peritonitis in a mouse model of acute gout. Based on its high potency, novel mechanism of action, long half-life and high affinity, XOMA 052 provides a new strategy for the treatment of a number of inflammatory, autoimmune and metabolic diseases in which the role of IL-1β is central to pathogenesis. © 2011 Landes Bioscience. Source

Discover hidden collaborations