51802-78-9Relevant articles and documents
N-Aryl pyrrolidinonyl oxadiazoles as potent mGluR5 positive allosteric modulators
Packiarajan, Mathivanan,Mazza Ferreira, Christine G.,Hong, Sang-Phyo,White, Andrew D.,Chandrasena, Gamini,Pu, Xiaosui,Brodbeck, Robbin M.,Robichaud, Albert J.
, p. 5658 - 5662 (2012/09/22)
A novel series of N-aryl pyrrolidinonyl oxadiazoles were identified as mGluR5 positive allosteric modulators (PAMs). Optimization of the initial lead compound 6a led to the identification of the 12c (-) enantiomer as a potent compound with acceptable in vitro clearance, CYP, hERG and PK properties. Para substituted N-aryl pyrrolidinonyl oxadiazoles are mGluR5 PAMs while the meta and ortho substituted N-aryl pyrrolidinonyl oxadiazoles are negative allosteric modulators (NAMs). Para fluoro substitution on the N-aryl group and meta chloro or methyl substituents on the aryl oxadiazole moiety are optimal for mGluR5 PAM efficacy. The existence of an exquisitely sensitive 'PAM to NAM switch' within this chemotype making it challenging for simultaneous optimization of potency and drug-like properties.
The discovery of a selective, high affinity A2B adenosine receptor antagonist for the potential treatment of asthma
Zablocki, Jeff,Kalla, Rao,Perry, Thao,Palle, Venkata,Varkhedkar, Vaibhav,Xiao, Dengming,Piscopio, Anthony,Maa, Tenning,Gimbel, Art,Hao, Jia,Chu, Nancy,Leung, Kwan,Zeng, Dewan
, p. 609 - 612 (2007/10/03)
Adenosine has been suggested to play a role in asthma, possibly via activation of A2B adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A2B AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A2B AdoR antagonist with good selectivity (A2B AdoR Ki = 50 nM, selectivity A1 > 200: A2A > 200: A3 > 167).
NEW COMPOUNDS
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Page 151, (2010/02/06)
The present invention relates to new compounds of formula I, (I) a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said compounds and to the use of said compounds in therapy.