Drug Discovery against Psoriasis: Identification of a New Potent FMS-like Tyrosine Kinase 3 (FLT3) Inhibitor, 1-(4-((1H-Pyrazolo[3,4-d]pyrimidin-4-yl)oxy)-3-fluorophenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea, That Showed Potent Activity in a Psoriatic Animal Model was written by Li, Guo-Bo;Ma, Shuang;Yang, Ling-Ling;Ji, Sen;Fang, Zhen;Zhang, Guo;Wang, Li-Jiao;Zhong, Jie-Min;Xiong, Yu;Wang, Jiang-Hong;Huang, Shen-Zhen;Li, Lin-Li;Xiang, Rong;Niu, Dawen;Chen, Ying-Chun;Yang, Sheng-Yong. And the article was included in Journal of Medicinal Chemistry in 2016.Category: isoxazole This article mentions the following:
Psoriasis is a chronic T-cell-mediated autoimmune disease, and FMS-like tyrosine kinase 3 (FLT3) has been considered as a potential mol. target for the treatment of psoriasis. In this investigation, structural optimization was performed on a lead compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3- (trifluoromethyl)phenyl)urea, which showed a moderate inhibitory activity against FLT3. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship anal. led to the discovery of a number of potent FLT3 inhibitors. One of the most active compounds, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-fluorophenyl)-3-(5-tert-butylisoxazol-3-yl)urea (I), was then chosen for in-depth anti-psoriasis studies because this compound displayed the highest potency in a preliminary anti-psoriasis test. Compound I exhibited significant anti-psoriatic effects in the K14-VEGF transgenic mouse model of psoriasis, and no recurrence was found 15 days later after the last administration. Detailed mechanisms of action of compound I were also investigated. Collectively, compound I could be a potential drug candidate for psoriasis treatment. In the experiment, the researchers used many compounds, for example, 3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9Category: isoxazole).
3-(tert-Butyl)isoxazol-5-amine (cas: 59669-59-9) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. Isoxazoles are commonly used as enaminoketone or β-diketone surrogate. The electrophilic cyclization of various 2-alkynone O-methyl oximes with a wide range of substrates such as ICl, I2, Br2, PhSeBr, etc. provides a variety of 3,4,5-trisubstituted isoxazoles in good to excellent yields.Category: isoxazole
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem