Chen, Liu Zeng; Shu, Hai Yang; Wu, Jing; Yu, Yun Long; Ma, Duo; Huang, Xin; Liu, Ming Ming; Liu, Xin Hua; Shi, Jing Bo published the artcile< Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis>, Application In Synthesis of 3959-07-7, the main research area is pyrazolopyrimidine thienopyrimidine preparation SAR antiinflammatory iNOS inhibitor arthritis; Anti-inflammatory activity; Arthritis; Drug-like properties; Thieno[3,2-d]pyrimidine; iNOS inhibitory activity.
In order to discover and develop drug-like anti-inflammatory agents against arthritis, based on “”Hit”” authours found earlier and to overcome drawbacks of toxicity, twelve series of total 89 novel pyrimidine, pyrazolo[4,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives were designed, synthesized and screened for their anti-inflammatory activity against NO and toxicity for normal liver cells (LO2). Relationships of balance toxicity and activity have been summarized through multi-steps, and title compounds (E)-N-(4-methylbenzyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimidin-4-amine, (E)-4-((2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimidin-4-yl)amino)phenol were found to show lower toxicity (against LO2: IC50 = 2934, 2301μM, resp.) and potent effect against NO release (IR = 98.3, 97.67%, at 10μM, resp.). Furthermore, compound (E)-N-(4-methylbenzyl)-2-(3,4,5-trimethoxystyryl)thieno[3,2-d]pyrimidin-4-amine showed potent iNOS inhibitory activity with value of IC50 is 0.96μM and could interfere stability and formation of the active dimeric iNOS. It’s anti-inflammatory activity in vivo was assessed by AIA rat model. Furthermore, the results of metabolic stability, CYP, PK study in vivo, acute toxicity study and subacute toxicity assessment indicated this compound had good drug-like properties for treatment.
European Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 3959-07-7 belongs to class bromides-buliding-blocks, and the molecular formula is C7H8BrN, Application In Synthesis of 3959-07-7.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary