FTIR spectral study of intramolecular hydrogen bonding in thromboxane A2 receptor agonist (U-46619), prostaglandin (PG)E2, PGD2, PGF2 alpha, prostacyclin receptor agonist (carbacyclin), and their related compounds in dilute CCl4 solution: structure-activity relationships.
FTIR spectra measurements and full optimization curve analysis of their spectra were done to obtain parameters of the OH and C = O stretching vibration bands for intramolecular hydrogen bondings in thromboxane (TX)A2 receptor partial agonist (CTA2), prostaglandin (PG)E2, PGD2, PGF2 alpha, prostacyclin (PGI2) receptor agonist (carbacyclin), and their related compounds in dilute CCl4 solutions. For CTA2, PGE2, PGD2, and PGF2 alpha, cyclic intramolecular hydrogen bonds involving a 15-membered ring similar to that observed for the TXA2 receptor agonist (U-46619) were found between a carboxyl group of the alpha-side chain and a 15-hydroxyl group of the omega-side chain. The arrangement of these side chains was P-shaped, and the percentage of the intramolecular hydrogen-bonded molecules with the 15-membered ring in CCl4 solution showed a high value of ca. 80% for these compounds. In addition, it was found that the cyclic intramolecular hydrogen bonds involving the 13-, 12-, and 12-membered rings in PGE2, PGD2, and PGF2 alpha, respectively, are formed between the carboxyl group of the alpha-side chain and the 11-, 9-, and 9-hydroxyl groups of a cyclopentane ring, respectively, although the percentages of the intramolecular hydrogen-bonded molecules with these membered rings are very small. It was also found that the hydrogen bond is more easily formed in the order of the 11-, 9-, and 15-hydroxyl groups. For carbacyclin, the cyclic intramolecular hydrogen bond involving the 13-membered ring was found between the carboxyl group of the alpha-side chain and the 11-hydroxyl group. The percentage of the intramolecular hydrogen-bonded molecules showed the value of 58% for carbacyclin. On the basis of information on the side-chain conformations in CCl4, we examined the structure-activity relationships for U-46619 in place of TXA2, PGE2, PGD2, PGF2 alpha, and carbacyclin in place of PGI2.
Takasuka
M
M
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kishi
M
M
Yamakawa
M
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002251:Carbon Tetrachloride; D015237:Dinoprost / Q000737:chemistry*; D015232:Dinoprostone / Q000737:chemistry*; D004285:Dogs; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D006860:Hydrogen Bonding; D046911:Macromolecular Substances; D008958:Models, Molecular; D015394:Molecular Structure; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000737:chemistry*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000737:chemistry*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000737:chemistry
D001643:Bridged Bicyclo Compounds; D005229:Fatty Acids, Monounsaturated; D046911:Macromolecular Substances; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D012996:Solutions; C056566:S 145; C051394:prostaglandin D2 methyl ester; D013928:Thromboxane A2; C026678:carboprostacyclin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015237:Dinoprost; D002251:Carbon Tetrachloride; D011464:Epoprostenol; D015232:Dinoprostone; D015230:Prostaglandin D2