678975-17-2Relevant academic research and scientific papers
A scalable synthesis of an atropisomeric drug substance via buchwald-hartwig amination and bruylants reactions
Liu, Yugang,Prashad, Mahavir,Shieh, Wen-Chung
, p. 239 - 245 (2014)
A practical, chromatography-free synthesis for a chemokine receptor antagonist NIBR-1282 (1) is described. Highlights of this scalable synthesis include (1) Buchwald-Hartwig amination reaction using (t-Bu)3P as the ligand and 5-12 mol % of water as an additive affording 6 with yield increase of more than 2-fold; (2) a variant of the Bruylants reaction for the synthesis of a-methyl amine 10 via aminotriazole 15a, instead of classical amino nitrile 8; and (3) development of a crystallization-induced, atropisomer transformation leading to predominantly one atropisomer 1. The new approach was employed for the manufacturing of kilogram quantities of the target active pharmaceutical ingredient.
Reduced cardiac side-effect potential by introduction of polar groups: Discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is active in vivo
Thoma, Gebhard,Beerli, Christian,Bigaud, Marc,Bruns, Christian,Cooke, Nigel G.,Streiff, Markus B.,Zerwes, Hans-Guenter
, p. 2000 - 2005 (2008/12/21)
Introduction of polar groups in a series of potent CCR5 antagonists which are very likely to adversely affect the conduction system in the heart led to the identification of NIBR-1282 which did not show adverse effects when tested in an isolated rabbit heart ex vivo model. Administration of NIBR-1282 in combination with a non-efficacious dose of CsA led to significant prolongation of kidney allograft survival in cynomolgus monkeys.
