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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
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...
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| Published in: | Journal of medicinal chemistry 2016-12, Vol.59 (24), p.11138-11147 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| container_end_page | 11147 |
| container_issue | 24 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 59 |
| creator | Yang, Michael G Xiao, Zili Dhar, T. G. Murali Xiao, Hai-Yun Gilmore, John L Marcoux, David Xie, Jenny H McIntyre, Kim W Taylor, Tracy L Borowski, Virna Heimrich, Elizabeth Li, Yu-Wen Feng, Jianlin Fernandes, Alda Yang, Zheng Balimane, Praveen Marino, Anthony M Cornelius, Georgia Warrack, Bethanne M Mathur, Arvind Wu, Dauh-Rurng Li, Peng Gupta, Anuradha Pragalathan, Bala Shen, Ding Ren Cvijic, Mary Ellen Lehman-McKeeman, Lois D Salter-Cid, Luisa Barrish, Joel C Carter, Percy H Dyckman, Alaric J |
| description | 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. |
| doi_str_mv | 10.1021/acs.jmedchem.6b01433 |
| format | article |
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G. Murali ; Xiao, Hai-Yun ; Gilmore, John L ; Marcoux, David ; Xie, Jenny H ; McIntyre, Kim W ; Taylor, Tracy L ; Borowski, Virna ; Heimrich, Elizabeth ; Li, Yu-Wen ; Feng, Jianlin ; Fernandes, Alda ; Yang, Zheng ; Balimane, Praveen ; Marino, Anthony M ; Cornelius, Georgia ; Warrack, Bethanne M ; Mathur, Arvind ; Wu, Dauh-Rurng ; Li, Peng ; Gupta, Anuradha ; Pragalathan, Bala ; Shen, Ding Ren ; Cvijic, Mary Ellen ; Lehman-McKeeman, Lois D ; Salter-Cid, Luisa ; Barrish, Joel C ; Carter, Percy H ; Dyckman, Alaric J</creator><creatorcontrib>Yang, Michael G ; Xiao, Zili ; Dhar, T. G. Murali ; Xiao, Hai-Yun ; Gilmore, John L ; Marcoux, David ; Xie, Jenny H ; McIntyre, Kim W ; Taylor, Tracy L ; Borowski, Virna ; Heimrich, Elizabeth ; Li, Yu-Wen ; Feng, Jianlin ; Fernandes, Alda ; Yang, Zheng ; Balimane, Praveen ; Marino, Anthony M ; Cornelius, Georgia ; Warrack, Bethanne M ; Mathur, Arvind ; Wu, Dauh-Rurng ; Li, Peng ; Gupta, Anuradha ; Pragalathan, Bala ; Shen, Ding Ren ; Cvijic, Mary Ellen ; Lehman-McKeeman, Lois D ; Salter-Cid, Luisa ; Barrish, Joel C ; Carter, Percy H ; Dyckman, Alaric J</creatorcontrib><description>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). 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Murali</creatorcontrib><creatorcontrib>Xiao, Hai-Yun</creatorcontrib><creatorcontrib>Gilmore, John L</creatorcontrib><creatorcontrib>Marcoux, David</creatorcontrib><creatorcontrib>Xie, Jenny H</creatorcontrib><creatorcontrib>McIntyre, Kim W</creatorcontrib><creatorcontrib>Taylor, Tracy L</creatorcontrib><creatorcontrib>Borowski, Virna</creatorcontrib><creatorcontrib>Heimrich, Elizabeth</creatorcontrib><creatorcontrib>Li, Yu-Wen</creatorcontrib><creatorcontrib>Feng, Jianlin</creatorcontrib><creatorcontrib>Fernandes, Alda</creatorcontrib><creatorcontrib>Yang, Zheng</creatorcontrib><creatorcontrib>Balimane, Praveen</creatorcontrib><creatorcontrib>Marino, Anthony M</creatorcontrib><creatorcontrib>Cornelius, Georgia</creatorcontrib><creatorcontrib>Warrack, Bethanne M</creatorcontrib><creatorcontrib>Mathur, Arvind</creatorcontrib><creatorcontrib>Wu, Dauh-Rurng</creatorcontrib><creatorcontrib>Li, Peng</creatorcontrib><creatorcontrib>Gupta, Anuradha</creatorcontrib><creatorcontrib>Pragalathan, Bala</creatorcontrib><creatorcontrib>Shen, Ding Ren</creatorcontrib><creatorcontrib>Cvijic, Mary Ellen</creatorcontrib><creatorcontrib>Lehman-McKeeman, Lois D</creatorcontrib><creatorcontrib>Salter-Cid, Luisa</creatorcontrib><creatorcontrib>Barrish, Joel C</creatorcontrib><creatorcontrib>Carter, Percy H</creatorcontrib><creatorcontrib>Dyckman, Alaric J</creatorcontrib><title>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</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>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). 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Murali</au><au>Xiao, Hai-Yun</au><au>Gilmore, John L</au><au>Marcoux, David</au><au>Xie, Jenny H</au><au>McIntyre, Kim W</au><au>Taylor, Tracy L</au><au>Borowski, Virna</au><au>Heimrich, Elizabeth</au><au>Li, Yu-Wen</au><au>Feng, Jianlin</au><au>Fernandes, Alda</au><au>Yang, Zheng</au><au>Balimane, Praveen</au><au>Marino, Anthony M</au><au>Cornelius, Georgia</au><au>Warrack, Bethanne M</au><au>Mathur, Arvind</au><au>Wu, Dauh-Rurng</au><au>Li, Peng</au><au>Gupta, Anuradha</au><au>Pragalathan, Bala</au><au>Shen, Ding Ren</au><au>Cvijic, Mary Ellen</au><au>Lehman-McKeeman, Lois D</au><au>Salter-Cid, Luisa</au><au>Barrish, Joel C</au><au>Carter, Percy H</au><au>Dyckman, Alaric J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2016-12-22</date><risdate>2016</risdate><volume>59</volume><issue>24</issue><spage>11138</spage><epage>11147</epage><pages>11138-11147</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><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.</abstract><pub>American Chemical Society</pub><doi>10.1021/acs.jmedchem.6b01433</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2908-4060</orcidid><orcidid>https://orcid.org/0000-0002-1050-2077</orcidid></addata></record> |
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| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| title | 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 |
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