3921-30-0Relevant articles and documents
Ferraro et al.
, p. 2055,2058 (1965)
ORGANOPHOSPHATE DERIVATIVES
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Paragraph 00130, (2019/02/15)
Provided herein are organophosphates and pharmaceutical compositions comprising said compounds.
Fatty alcohol phosphates are subtype-selective agonists and antagonists of lysophosphatidic acid receptors
Virag, Tamas,Elrod, Don B.,Liliom, Karoly,Sardar, Vineet M.,Parrill, Abby L.,Yokoyama, Kazuaki,Durgam, Gangadhar,Deng, Wenlin,Miller, Duane D.,Tigyi, Gabor
, p. 1032 - 1042 (2007/10/03)
A more complete understanding of the physiological and pathological role of lysophosphatidic acid (LPA) requires receptor subtype-specific agonists and antagonists. Here, we report the synthesis and pharmacological characterization of fatty alcohol phosphates (FAP) containing saturated hydrocarbon chains from 4 to 22 carbons in length. Selection of FAP as the lead structure was based on computational modeling as a minimal structure that satisfies the two-point pharmacophore developed earlier for the interaction of LPA with its receptors. Decyl and dodecyl FAPs (FAP-10 and FAP-12) were specific agonists of LPA2 (EC50 = 3.7 ± 0.2 μM and 700 ± 22 nM, respectively), yet selective antagonists of LPA3 (Ki = 90 nM for FAP-12) and FAP-12 was a weak antagonist of LPA1. Neither LPA1 nor LPA3 receptors were activated by FAPs; in contrast, LPA2 was activated by FAPs with carbon chains between 10 and 14. Computational modeling was used to evaluate the interaction between individual FAPs (8 to 18) with LPA2 by docking each compound in the LPA binding site. FAP-12 displayed the lowest docked energy, consistent with its lower observed EC50. The inhibitory effect of FAP showed a strong hydrocarbon chain length dependence with C12 being optimum in the Xenopus laevis oocytes and in LPA3-expressing RH7777 cells. FAP-12 did not activate or interfere with several other G-protein-coupled receptors, including S1P-induced responses through S1P1.2,3.5 receptors. These data suggest that FAPs are ligands of LPA receptors and that FAP-10 and FAP-12 are the first receptor subtype-specific agonists for LPA2.
Counterion affinity orders in aqueous micellar solutions of sodium decyl phosphate and sodium dodecyl sulfate determined by changes in23Na NMR relaxation rates: A surprising dependence on head group charge
Romsted, Laurence S.,Yoon, Choon-Ock
, p. 989 - 994 (2007/10/02)
Changes in quadrupole relaxation rates of 23Na on addition of the Cl- salts of Na+, K+, Rb+, Cs+, TMA+, and TEA+ ions were used to determine the relative affinities of these cations for micelles composed of the decyl phosphate monoanion, DPH- (pH 5.3), the decyl phosphate dianion, DP2- (pH 12.6), and their 1:1 mixture (pH 7.8) at 35 °C. Similar experiments were run in sodium dodecyl sulfate (SDS) micelles at 35 and 60 °C for comparison. The affinity of alkali metal ions for decyl phosphate micelles clearly increases with cation size at all three pH's. The alkali metal cations show significantly less affinity than TMA+ and TEA+ for DPH- micelles and than TMA+ for SDS micelles. In DP2- micelles, the affinity order of the alkali metals remains the same, but surprisingly, TMA+ and TEA+ fail to displace Na+ from the micellar interface. The 1:1 mixture ef DPH- and DP2- shows intermediate behavior. These changes in affinity order with head group charge can be interpreted qualitatively by assuming that alkali metal ions are hydrated at the surface of decyl phosphate micelles but that they interact much more strongly with divalent than monovalent phosphate head groups, perhaps by site binding to the dianionic phosphate head group through an intervening water molecule. These results are compared with affinity orders of monovalent cations in solutions of micelles, vesicles, polyelectrolytes, DNA, and ion-exchange resins.
