Synthesis and biological evaluation of .omega.-homologues of prostaglandin E1

Dajani, Esam Z.; Rozek, Leonard F.; Sanner, John H.; Miyano, Masateru

doi:10.1021/jm00230a005

Cited by 9 publications

(3 citation statements)

References 4 publications

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“…The mixture was filtered, and the filtrate was stripped of solvent under reduced pressure. Recrystallization of the residue from H20 afforded 1.9 g (80%) of 23 (±)-Methyl 7-(4-Hydroxy-2-methoxy-5-oxocyclopent-lene)heptanoate (25). To a solution of 2.4 g (10 mmol) of 23 in 35 mL of MeOH was added 10 mL of acetone dimethyl acetal and 4 mL of 1 % methanolic HC1.…”

Section: Methodsmentioning

confidence: 99%

“…About 4 mL of ether was added and the mixture was allowed to stand at room temperature for 48 h. The solidified mixture was taken up in benzene containing 1 % triethylamine and the solution was washed successively with dilute K2C03 and H20, dried (Na2S04), and stripped of solvent under reduced pressure. The residue crystallized upon addition of ether to give 2.2 g (80%) of a white solid 25, mp 92 °C. Anal.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogs

Collins¹,

Dajani²,

Driskill³

et al. 1977

J. Med. Chem.

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The preparation and gastric antisecretory activity of a series of 15-deoxy-16-hydroxyprostaglandin analogues are described. The compounds were tested intravenously in histamine-stimulated Heidenhain pouch dogs in relation to the reference standards PGE1 and PGE1 methyl ester (PGE1ME). The parent compound of this seris, (+/-)-15-deoxy-16alpha,beta-hydroxyprostaglandin E1 methyl ester (3), was found to be equipotent to the reference standard PGE1ME. Methylation at C-16 of 3 produced 8 which was found to be some 40 times more potent than PGE1. In sharp contrast, addition of two methyl groups to 3 at C15 or C17 markedly reduced the antisecretory action. The 16-ethyl analogue of 3 also showed reduced potency. Removal or epimerization of the C-11 hydroxy group of 8 reduced the activity. Likewise, hydrogenation or changing the stereochemistry of the 13,14 double bond from trans to cis decreased the activity. On the other hand, omega-homologation of 8 or the introduction of a cis-5,6 double bond did not affect the potency. From these studies, it appears that 8, 16, and 17 possess optimum gastric antisecretory effects in this series.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogs

Collins¹,

Dajani²,

Driskill³

et al. 1977

J. Med. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…la, 59414-23-2; If, 82093-19-4; 2a, 107-02-8; 2b, 78-85-3; 2c, 4170-30-3; 2d, 104-55-2; 2e, 80466-34-8; 3a, 82093-20-7; 3b, 82093-21-8; 3c, 82093-22-9; 3d, 82093-23-0; 3e, 82093-24-1; cis-3f, 82093-25-2; trans-M, 82093-26-3; 4, 953-21-9; 5, 82093-27-4; zinc chloride, 7646-85-7; boron trifluoride etherate, 109-63-7. 3a,6,7,7a-Tetrahydro-l.ff-mdene-4-carboxylic Acid Received February 4,1982 In an extention of an co-modified prostaglandin project,1 we required the optically active [[[2-(bicyclo[2.2.1]heptan-2-yl)ethyl]carbonyl]methylene]triphenylphosphorane (1). This phosphorane would be prepared readily from Commercial3 "99% pure" 3 was treated with 1 equiv of (+)-a-methylbenzylamine in ether.…”

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confidence: 99%