14869-41-1Relevant articles and documents
Novel bicyclic pyrazoles as potent ALK2 (R206H) inhibitors for the treatment of fibrodysplasia ossificans progressiva
Yamamoto, Hirofumi,Sakai, Naoki,Ohte, Satoshi,Sato, Tomohiro,Sekimata, Katsuhiko,Matsumoto, Takehisa,Nakamura, Kana,Watanabe, Hisami,Mishima-Tsumagari, Chiemi,Tanaka, Akiko,Hashizume, Yoshinobu,Honma, Teruki,Katagiri, Takenobu,Miyazono, Kohei,Tomoda, Hiroshi,Shirouzu, Mikako,Koyama, Hiroo
, (2021)
Mutant activin receptor-like kinase-2 (ALK2) is associated with the pathogenesis of fibrodysplasia ossificans progressiva, making it an attractive target for therapeutic intervention. We synthesized a new series of bicyclic pyrazoles and evaluated their mutant ALK2 enzyme inhibitory activities, leading to the identification of 8 as the most potent inhibitor. This compound showed moderate microsomal metabolic stability and human ether-a-go-go related gene (hERG) safety. In C2C12 cells carrying mutant ALK2 (R206H), 8 efficiently inhibited the bone morphogenetic protein (BMP)-induced alkaline phosphatase activity.
Preparation method of levocetirizine
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Paragraph 0024, (2020/06/17)
The invention provides a preparation method of levocetirizine. The preparation method comprises following steps: carrying out a reaction on a compound represented by a formula (I) under the action ofa reduction system and L-tartaric acid to obtain a compound represented by a formula (II); and reacting the compound shown in a formula (II) with a compound shown in a formula (III) under the action of NaH, N,N-dimethyl formamide and tetrabutyl ammonium bromide to obtain levocetirizine. The levocetirizine is prepared by taking the compound shown by the formula (I) and the compound shown by the formula (III) as raw materials, at first, the compound shown by the formula (I) is de-protected and then racemized to obtain the compound shown by the formula (II); and the compound shown by the formula(II) and the compound shown by the formula (III) carry out reactions to obtain levocetirizine. The provided method is short in reaction route, the yield can reach 54% or above, and the purity can reach 99.65% at most.
One-pot, regiospecific assembly of (E)-benzamidines from δ- and γ-amino acids via an intramolecular aminoquinazolinone rearrangement
Schroeder, Chad E.,Neuenswander, Sarah A.,Yao, Tuanli,Aubé, Jeffrey,Golden, Jennifer E.
supporting information, p. 3950 - 3955 (2016/06/06)
The efficient generation of novel, N-linked benzamidines resulting from a regiospecific rearrangement of quinazolinones is described. This methodology study explored reaction parameters including the effect of changing solvent and temperature, as well as varying electronic substituents on the structural core. The transformation was extensively optimized in terms of reaction conditions and scope, resulting in a protocol that consistently affords diversely functionalized amidines in high yield. The process permits regional structural derivatization that was previously inaccessible, and the multistep process was also reduced to a telescoped, five-step sequence that efficiently affords pharmacologically unique (E)-benzamidoamidines from N-BOC protected γ- and δ-amino acids.