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Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid.

Abstract：

:Cyclic phosphatidic acid (CPA) is a naturally occurring analog of lysophosphatidic acid (LPA) in which the sn-2 hydroxy group forms a five-membered ring with the sn-3 phosphate. Here, we describe the synthesis of R-3-CCPA and S-3-CCPA along with their pharmacological properties as inhibitors of lysophospholipase D/autotaxin, agonists of the LPA(5) GPCR, and blockers of lung metastasis of B16-F10 melanoma cells in a C57BL/6 mouse model. S-3CCPA was significantly more efficacious in the activation of LPA(5) compared to the R-stereoisomer. In contrast, no stereoselective differences were found between the two isomers toward the inhibition of autotaxin or lung metastasis of B16-F10 melanoma cells in vivo. These results extend the potential utility of these compounds as potential lead compounds warranting evaluation as cancer therapeutics.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Gupte R,Siddam A,Lu Y,Li W,Fujiwara Y,Panupinthu N,Pham TC,Baker DL,Parrill AL,Gotoh M,Murakami-Murofushi K,Kobayashi S,Mills GB,Tigyi G,Miller DD

doi

10.1016/j.bmcl.2010.09.115

subject

Has Abstract

pub_date

2010-12-15 00:00:00

pages

7525-8

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(10)01424-1

journal_volume

20

pub_type

杂志文章

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