Counde O'yang
Hoffmann-La Roche
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Publication
Featured researches published by Counde O'yang.
British Journal of Pharmacology | 2006
Keith R. Bley; Anindya Bhattacharya; Don V Daniels; Joel R Gever; Alam Jahangir; Counde O'yang; Steven Smith; Dinesh Srinivasan; Anthony P. D. W. Ford; Mary-Frances Jett
Prostacyclin (PGI2) possesses various physiological functions, including modulation of nociception, inflammation and cardiovascular activity. Elucidation of these functions has been hampered by the absence of selective IP receptor antagonists. Two structurally distinct series of IP receptor antagonists have been developed: 4,5‐dihydro‐1H‐imidazol‐2‐yl)‐[4‐(4‐isopropoxy‐benzyl)‐phenyl]‐amine (RO1138452) and R‐3‐(4‐fluoro‐phenyl)‐2‐[5‐(4‐fluoro‐phenyl) ‐benzofuran‐2‐ylmethoxycarbonylamino]‐propionic acid (RO3244794). RO1138452 and RO3244794 display high affinity for IP receptors. In human platelets, the receptor affinities (pKi) were 9.3±0.1 and 7.7±0.03, respectively; in a recombinant IP receptor system, pKi values were 8.7±0.06 and 6.9±0.1, respectively. Functional antagonism of RO1138452 and RO3244794 was studied by measuring inhibition of carbaprostacyclin‐induced cAMP accumulation in CHO‐K1 cells stably expressing the human IP receptor. The antagonist affinities (pKi) of RO1138452 and RO3244794 were 9.0±0.06 and 8.5±0.11, respectively. Selectivity profiles for RO1138452 and RO3244794 were determined via a panel of receptor binding and enzyme assays. RO1138452 displayed affinity at I2 (8.3) and PAF (7.9) receptors, while RO3244794 was highly selective for the IP receptor: pKi values for EP1 (<5), EP3 (5.38), EP4 (5.74) and TP (5.09). RO1138452 (1–10 mg kg−1, i.v.) and RO3244794 (1–30 mg kg−1, i.v.) significantly reduced acetic acid‐induced abdominal constrictions. RO1138452 (3–100 mg kg−1, p.o.) and RO3244794 (0.3–30 mg kg−1, p.o.) significantly reduced carrageenan‐induced mechanical hyperalgesia and edema formation. RO3244794 (1 and 10 mg kg−1, p.o.) also significantly reduced chronic joint discomfort induced by monoiodoacetate. These data suggest that RO1138452 and RO3244794 are potent and selective antagonists for both human and rat IP receptors and that they possess analgesic and anti‐inflammatory potential.
BJUI | 2004
David R. Blue; Donald V. Daniels; Joel R Gever; Mary-Frances Jett; Counde O'yang; H.M. Tang; Timothy J. Williams; Anthony P. D. W. Ford
To describe the preclinical pharmacology of Ro 115–1240, a peripherally acting selective α1A/1L‐adrenoceptor (AR) partial agonist, compared with the α1A/1L‐AR full agonist amidephrine, as AR agonists have some utility in the treatment of stress urinary incontinence (SUI) but are limited by undesirable cardiovascular and central nervous system side‐effects.
Journal of Medicinal Chemistry | 2013
Fernando Padilla; Niala Bhagirath; Shaoqing Chen; Eric Chiao; David Michael Goldstein; Johannes Cornelius Hermann; Jonathan Hsu; Joshua Kennedy-Smith; Andreas Kuglstatter; Cheng Liao; Wenjian Liu; Lee Edwin Lowrie; Kin Chun Luk; Stephen M. Lynch; John Menke; Linghao Niu; Timothy D. Owens; Counde O'yang; Aruna Railkar; Ryan Craig Schoenfeld; Michelle Slade; Sandra Steiner; Yun-Chou Tan; Armando G. Villaseñor; Ce Wang; Jutta Wanner; Wenwei Xie; Daigen Xu; Xiaohu Zhang; Mingyan Zhou
We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.
Journal of Medicinal Chemistry | 2017
Ying Huang; Jeff Zhang; Zhengtian Yu; Hailong Zhang; Youzhen Wang; Andreas Lingel; Wei Qi; X. Justin Gu; Kehao Zhao; Michael Shultz; Long Wang; Xingnian Fu; Yongfeng Sun; Qiong Zhang; Xiangqing Jiang; Jiang-wei Zhang; Chunye Zhang; Ling Li; Jue Zeng; Lijian Feng; Chao Zhang; Yueqin Liu; Man Zhang; Lijun Zhang; Mengxi Zhao; Zhenting Gao; Xianghui Liu; Douglas D. Fang; Haibing Guo; Yuan Mi
Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2MUT preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.
Synthetic Communications | 2006
Aaron E. Bunnell; Counde O'yang; Andra Petrica; Michael Soth
Abstract The C‐3 position of isoindazoles is readily functionalized by metalation with lithium diisopropylamide followed by reaction with a variety of electrophiles.
Archive | 1999
Richard Leo Cournoyer; Paul Francis Keitz; Counde O'yang; Dennis Mitsugu Yasuda
Archive | 2005
Nidhi Arora; Roland Joseph Billedeau; Nolan James Dewdney; Tobias Gabriel; David Michael Goldstein; Counde O'yang; Michael Soth
Archive | 2004
Counde O'yang; Ryan Craig Schoenfeld
Archive | 1998
Keith R. Bley; Robin Douglas Clark; Alam Jahangir; Bruce A. Kowalczyk; Francisco Javier Lopez-Tapala; Alexander Victor Muehldorf; Counde O'yang; Thomas Weitao Sun
Archive | 2006
Nidhi Arora; Roland Joseph Billedeau; Nolan James Dewdney; Tobias Gabriel; David Michael Goldstein; Counde O'yang; Michael Soth; Teresa Alejandra Trejo-Martin