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关于吲烷 SHIP1 激动剂 AQX-1125 的合成研究。

Synthetic studies on the indane SHIP1 agonist AQX-1125.

机构信息

Department of Chemistry, Syracuse University, 1-014 Center for Science and Technology, Syracuse, NY 13244, USA.

Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

出版信息

Org Biomol Chem. 2022 May 18;20(19):4016-4020. doi: 10.1039/d2ob00555g.

DOI:10.1039/d2ob00555g
PMID:35506893
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9153081/
Abstract

AQX-1125 is an indane based SHIP1 agonist that has been evaluated in the clinic for the treatment of bladder pain syndrome/interstitial cystitis. To support our own studies on SHIP1 agonists as potential treatments for IBD and Crohn's disease, a new synthetic route to the SHIP1 agonist AQX-1125 has been developed. This sequence utilizes a hydroxy-acid intermediate which allows for ready differentiation of the C6 and C7 positions. The role of the C17 alkene in the biological activity of the system is also investigated, and this functional group is not required for SHIP1 agonist activity. While AQX-1125 shows SHIP1 agonist activity in enzyme assays, it does not show activity in cell based assays similar to other SHIP1 agonists, which limits the utility of this molecule.

摘要

AQX-1125 是一种基于茚满的 SHP1 激动剂，已在临床上用于治疗膀胱疼痛综合征/间质性膀胱炎。为了支持我们自己关于 SHP1 激动剂作为治疗 IBD 和克罗恩病的潜在治疗方法的研究，开发了一种新的 AQX-1125 SHP1 激动剂的合成途径。该序列利用了羟基酸中间体，这使得 C6 和 C7 位置的区分变得容易。该系统中 C17 烯烃在生物学活性中的作用也得到了研究，并且该官能团对于 SHP1 激动剂活性不是必需的。虽然 AQX-1125 在酶测定中显示出 SHP1 激动剂活性，但它在类似于其他 SHP1 激动剂的细胞测定中没有活性，这限制了该分子的用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/c40004e08263/nihms-1807794-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/e910755c8a09/nihms-1807794-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/1f114c2df7f5/nihms-1807794-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/6064a8f182d2/nihms-1807794-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/c97b7dd3dffe/nihms-1807794-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/685ab25e546b/nihms-1807794-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/c40004e08263/nihms-1807794-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/e910755c8a09/nihms-1807794-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/1f114c2df7f5/nihms-1807794-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/6064a8f182d2/nihms-1807794-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/c97b7dd3dffe/nihms-1807794-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/685ab25e546b/nihms-1807794-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7090/9153081/c40004e08263/nihms-1807794-f0006.jpg

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