142374-19-4Relevant articles and documents
1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists: Modifications of the arylpropylpiperidine side chains
Lynch, Christopher L.,Willoughby, Christopher A.,Hale, Jeffrey J.,Holson, Edward J.,Budhu, Richard J.,Gentry, Amy L.,Rosauer, Keith G.,Caldwell, Charles G.,Chen, Ping,Mills, Sander G.,MacCoss, Malcolm,Berk, Scott,Chen, Liya,Chapman, Kevin T.,Malkowitz, Lorraine,Springer, Martin S.,Gould, Sandra L.,DeMartino, Julie A.,Siciliano, Salvatore J.,Cascieri, Margaret A.,Carella, Anthony,Carver, Gwen,Holmes, Karen,Schleif, William A.,Danzeisen, Renee,Hazuda, Daria,Kessler, Joseph,Lineberger, Janet,Miller, Michael,Emini, Emilio A.
, p. 119 - 123 (2003)
The 4-(3-phenylprop-1-yl)piperidine moiety of the 1,3,4-trisubstituted pyrrolidine CCR5 antagonist 1 was modified with electron deficient aromatics as well as replacement of the benzylic methylene with sulfones, gem-difluoromethylenes and alcohols in an effort to balance the antiviral potency with reasonable pharmacokinetics.
Discovery of a Novel, Highly Potent, and Selective Thieno[3,2- d]pyrimidinone-Based Cdc7 Inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Antitumor Agent
Kurasawa, Osamu,Miyazaki, Tohru,Homma, Misaki,Oguro, Yuya,Imada, Takashi,Uchiyama, Noriko,Iwai, Kenichi,Yamamoto, Yukiko,Ohori, Momoko,Hara, Hideto,Sugimoto, Hiroshi,Iwata, Kentaro,Skene, Robert,Hoffman, Isaac,Ohashi, Akihiro,Nomura, Toshiyuki,Cho, Nobuo
, p. 1084 - 1104 (2020/02/05)
In our pursuit of developing a novel, potent, and selective cell division cycle 7 (Cdc7) inhibitor, we optimized the previously reported thieno[3,2-d]pyrimidinone analogue I showing time-dependent Cdc7 kinase inhibition and slow dissociation kinetics. These medicinal chemistry efforts led to the identification of compound 3d, which exhibited potent cellular activity, excellent kinase selectivity, and antitumor efficacy in a COLO205 xenograft mouse model. However, the issue of formaldehyde adduct formation emerged during a detailed study of 3d, which was deemed an obstacle to further development. A structure-based approach to circumvent the adduct formation culminated in the discovery of compound 11b (TAK-931) possessing a quinuclidine moiety as a preclinical candidate. In this paper, the design, synthesis, and biological evaluation of this series of compounds will be presented.
6-bromo-3-(piperidine-4-yl)imidazo[1,2-a]pyridine preparation method
-
Paragraph 0006; 0007, (2019/12/25)
The invention relates to a 6-bromo-3-(piperidine-4-yl)imidazo[1,2-a]pyridine preparation method. A purpose of the present invention is mainly to solve the technical problem that no suitable industrialsynthesis method exists in the prior art. According to the technical scheme, the method comprises five steps, and comprises: generating a compound 2 from a compound 1 and Boc2O in chloroform under the action of triethylamine; adding dichloromethane, oxalyl chloride and dimethyl sulfoxide into the compound 2, and oxidizing to obtain a compound 3; carrying out a reaction on the compound 3 and a bromination reagent phenyltrimethylammonium tribromide (PTAB) in tetrahydrofuran to obtain a compound 4; carrying out a reaction on the compound 4 and 2-amino-5-bromopyridine in ethyl alcohol to obtain acompound 5; and finally obtaining a compound 6 from the compound 5 under the action of ethyl acetate hydrochloride. According to the present invention, the obtained compound can be used as the intermediate or product for synthesis of a plurality of drugs.
