Organic compounds -- part of the class 532-570 series – Organic compounds – Silicon containing
Patent
1995-09-18
1998-03-24
Shaver, Paul F.
Organic compounds -- part of the class 532-570 series
Organic compounds
Silicon containing
560 17, 560118, 560121, 562431, 562498, 562503, C07F 708
Patent
active
057314527
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel 7-thiaprostaglandins having the ability to inhibit cell migration and useful as a pharmaceutical, a method of production of the same, intermediates useful for their synthesis and applications.
BACKGROUND ART
Prostaglandins have diverse physiological activities such as inhibition of platelet aggregation, vasodilation, hypotension, suppression of the secretion of gastric acids, smooth muscle constriction, cytoprotection, and diuresis and are useful for the treatment or prevention of cardiac infarction, angia, artereosclerosis, hypertension, duodenal ulcers, oxytocia, and abortion. Among these, prostaglandin E, analogues have a potent inhibitory activity of platelet aggregation and a potent vasodilator activity and are already being used clinically.
It has been disclosed that 7-thiaprostaglandin E.sub.1 derivatives exhibit various activities such as inhibitation of platelet aggregation, hypotension, vasodilation, and a resultant action against thrombus, angia, cardiac infarction, arteriosclerosis, and metastatis of malignant tumors (Kokai) No. 53-68753, Japanese Unexamined Patent Publication (Kokai) No. 58-110562, Japanese Unexamined Patent Publication (Kokai) No. 59-29661, Japanese Unexamined Patent Publication (Kokai) No. 60-185761, Japanese Unexamined Patent Publication (Kokai) No. 61-204163!. Further, these 7-thiaprostaglandin E.sub.1 derivatives are known to be useful for 64-52721!.
On the other hand, enol butyrate of prostaglandin E.sub.1 are known as prostaglandin E.sub.1 analogues (Japanese Unexamined Patent Publication (Kokai) No. 5-213862). It is only shown, however, that they are stable even when prepared under high temperatures and that they can give a physiological activity equal to that of prostaglandin E.sub.1. No suggestion at all is made about the physiological activity of the compounds of the present invention given below.
By the way, in the past, as a method of production of prostaglandin E.sub.1 analogues, it was known that it was possible to synthesize prostaglandin E.sub.1 analogues by a two-component coupling type reaction of a cyclopentenone derivative having a side chain corresponding to an J. Weiss et al., J. Org. Chem. 44, 1439 (1978)!. Further, the method given below was known as an example of the synthesis by a two-component coupling type reaction using the organolithiocuprates of the .omega.-chain portion (1972), R. Pappo, P. W. Collins, Tetrahedron Lett. 4217, (1954), Kurozumi et al., Chem. Pharm. Bull. 35, 1102, (1982), C. K. Sih, J. Am. Chem. Soc. 97, 865, (1975), Sato et al., Japanese Unexamined Patent Publication (Kokai) No. 1-228933!.
Similarly, as a method of synthesis of 7-thiaprostaglandin E.sub.1 analogues, a two-component coupling reaction of cyclopentenone derivatives having an .alpha.-chain of the 7-thia-type and organolithiocuprates of the (1985)!.
Further, as a method of production of enol butyrate of prostaglandins, Japanese Unexamined Patent Publication (Kokai) No. 5-213862 described a method of production of the following formula (XII): ##STR2## According to this method, they are produced by, for example, protecting the hydroxyl group of the 1-iodo-3-hydroxy-1-octene, carrying out a reaction with alkyllithium to make 1-lithioalkene, then carrying out a reaction with a trialkylphosphine-copper (I) iodide complex to make organolithiocuprate, then carrying out 1,4-conjugate addition of the organolithiocuprate to the 4-hydroxy-2-(6-carbobutoxyhexyl)-2-cyclopentene-1-on with the protected hydroxyl group, then quenching by adding anhydrous butyric acid or a butyric acid halide to the reaction mixture.
On the other hand, it is known to synthesize the prostaglandin E.sub.1 derivative, misoprostol by the method of producing cuprate in situ from the vinylstannane type .omega.-chain portion using higher order cyanocuprates, then carrying out a 1,4-conjugate addition to a cyclopentenone derivative having a side chain corresponding to the (1988)!. This reference shows that it is possible to make just one of the two s
REFERENCES:
patent: 5159102 (1992-10-01), Tanaka et al.
Endo Noriaki
Ishii Koji
Kataoka Ken-ichiro
Minoshima Toru
Tanaka Hiroko
Shaver Paul F.
Teijin Limited
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