Chuk Chui Man
Boehringer Ingelheim
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Publication
Featured researches published by Chuk Chui Man.
Journal of Medicinal Chemistry | 2009
Anne B. Eldrup; Fariba Soleymanzadeh; Steven John Taylor; Ingo Muegge; Neil A. Farrow; David B. Joseph; Keith McKellop; Chuk Chui Man; Alison Kukulka; Stéphane De Lombaert
Inhibition of soluble epoxide hydrolase (sEH) is hypothesized to lead to an increase in circulating levels of epoxyeicosatrienoic acids, resulting in the potentiation of their in vivo pharmacological properties. As part of an effort to identify inhibitors of sEH with high and sustained plasma exposure, we recently performed a high throughput screen of our compound collection. The screen identified N-(3,3-diphenyl-propyl)-nicotinamide as a potent inhibitor of sEH. Further profiling of this lead revealed short metabolic half-lives in microsomes and rapid clearance in the rat. Consistent with these observations, the determination of the in vitro metabolic profile of N-(3,3-diphenyl-propyl)-nicotinamide in rat liver microsomes revealed extensive oxidative metabolism and a propensity for metabolite switching. Lead optimization, guided by the analysis of the solid-state costructure of N-(3,3-diphenyl-propyl)-nicotinamide bound to human sEH, led to the identification of a class of potent and selective inhibitors. An inhibitor from this class displayed an attractive in vitro metabolic profile and high and sustained plasma exposure in the rat after oral administration.
Bioorganic & Medicinal Chemistry Letters | 2009
Brian Nicholas Cook; Jörg Bentzien; Andre White; Peter Allen Nemoto; Ji Wang; Chuk Chui Man; Fariba Soleymanzadeh; Hnin Hnin Khine; Mohammed A. Kashem; Stanley Kugler; John P. Wolak; Gregory P. Roth; Stephane De Lombaert; Steven S. Pullen; Hidenori Takahashi
Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhibitors through structure-based design where high-resolution crystal structural information was used to optimize interactions within the kinase specificity pocket of the enzyme to improve both potency and selectivity.
Bioorganic & Medicinal Chemistry Letters | 2010
Ho Yin Lo; Chuk Chui Man; Roman Wolfgang Fleck; Neil A. Farrow; Richard H. Ingraham; Alison Kukulka; John R. Proudfoot; Raj Betageri; Tom Kirrane; Usha R. Patel; Rajiv Sharma; Mary Ann Hoermann; Alisa Kabcenell; Stephane De Lombaert
A novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles.
Tetrahedron Letters | 2008
Ho Yin Lo; Jörg Bentzien; Andre White; Chuk Chui Man; Roman Wolfgang Fleck; Steven S. Pullen; Hnin Hnin Khine; Josephine King; Joseph R. Woska; John P. Wolak; Mohammed A. Kashem; Gregory P. Roth; Hidenori Takahashi
Archive | 2006
Roman Wolfgang Fleck; Xin Guo; Ho Yin Lo; Chuk Chui Man
Archive | 2005
Joerg Martin Bentzien; Brian Nicholas Cook; Xiang Li; Ho Yin Lo; Chuk Chui Man; Ingo Andreas Mugge; Peter Allen Nemoto; Steven S. Pullen; Doris Riether; Gregory P. Roth; Fariba Soleymanzadeh; Hidenori Takahashi; Ji Wang; Andre White; Renee M. Zindell
Archive | 2005
Joerg Martin Bentzien; Brian Nicholas Cook; Xiang Li; Ho Yin Lo; Chuk Chui Man; Ingo Andreas Mugge; Steven S. Pullen; Gregory P. Roth; Fariba Soleymanzadeh; Hidenori Takahashi; Ji Wang; Andre White; Renee M. Zindell; Doris Riether; Peter Allen Nemoto; Xin Yao; John E. Mangette
Archive | 2008
Asitha Abeywardane; Brian Nicholas Cook; Stephane De Lombaert; Michel J. Emmanuel; Xin Guo; Ming-Hong Hao; Jin Mi Kim; Ho Yin Lo; Chuk Chui Man; Tina Marie Morwick; Peter Allen Nemoto; Kevin Chungeng Qian; Hidenori Takahashi; Steven John Taylor
Archive | 2011
Angela Berry; Zhidong Chen; Stephane De Lombaert; Michel J. Emmanuel; Pui Leng Loke; Chuk Chui Man; Tina Marie Morwick; Hidenori Takahashi
Archive | 2008
Xin Guo; Ho Yin Lo; Chuk Chui Man; Hidenori Takahashi