1. Academic Validation
  2. Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P1 Receptor Modulator

Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P1 Receptor Modulator

  • J Med Chem. 2016 Dec 22;59(24):11138-11147. doi: 10.1021/acs.jmedchem.6b01433.
Michael G Yang 1 Zili Xiao 1 T G Murali Dhar 1 Hai-Yun Xiao 1 John L Gilmore 1 David Marcoux 1 Jenny H Xie 1 Kim W McIntyre 1 Tracy L Taylor 1 Virna Borowski 1 Elizabeth Heimrich 1 Yu-Wen Li 1 Jianlin Feng 1 Alda Fernandes 1 Zheng Yang 1 Praveen Balimane 1 Anthony M Marino 1 Georgia Cornelius 1 Bethanne M Warrack 1 Arvind Mathur 1 Dauh-Rurng Wu 1 Peng Li 1 Anuradha Gupta 1 Bala Pragalathan 1 Ding Ren Shen 1 Mary Ellen Cvijic 1 Lois D Lehman-McKeeman 1 Luisa Salter-Cid 1 Joel C Barrish 1 Percy H Carter 1 Alaric J Dyckman 1
Affiliations

Affiliation

  • 1 Research and Development, Bristol-Myers Squibb Company , Princeton, New Jersey 08543-4000, United States.
Abstract

We describe a highly efficient route for the synthesis of 4a (BMS-986104). A key step in the synthesis is the asymmetric hydroboration of trisubstituted alkene 6. Particularly given the known difficulties involved in this type of transformation (6 → 7), the current methodology provides an efficient approach to prepare this class of compounds. In addition, we disclose the efficacy of 4a in a mouse EAE model, which is comparable to 4c (FTY720). Mechanistically, 4a exhibited excellent remyelinating effects on lysophosphatidylcholine (LPC) induced demyelination in a three-dimensional brain Cell Culture assay.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-120633
    LPL Receptor Modulator