Prostacyclin analogs

The double bond of butenolides reacts under Diels-Alder conditions and the resulting chiral bicycles have served as precursors of prostacycline analogs and chrysanthemic acids (250,251). The butenolide 248 was obtained by the procedure described by Ireland et al. (237). A bicyclo[4.3.0] ring system (254) was prepared by Diels-Alder reaction of 248 with butadiene in the presence of aluminum trichloride. Reduction of 254 (LiBH4) yielded the... 

P.W. Collins, S.W. Djuric, Synthesis of therapeutically useful prostaglandin and prostacyclin analogs, Chem. Rev. 93 (1993) 1533. 

K. Bannai, T. Toru, T. Oba, T. Tanaka, N. Okamaura, K. Watanabe, A. Hazato, S. Kurozumi, Synthesis of chemically stable prostacyclin analogs, Tetrahedron 39 (1983) 3807. 

Collins PW and Djuric SW (1993) Synthesis of therapeutically useful prostaglandins and prostacyclin analogs. Chem Rev 93, 1533-1564. 

Prostacyclin lowers peripheral, pulmonary, and coronary resistance. It has been used to treat both primary pulmonary hypertension and secondary pulmonary hypertension, which sometimes occurs after mitral valve surgery. A commercial preparation of prostacyclin (epoprostenol) is approved for treatment of primary pulmonary hypertension, in which it appears to improve symptoms and prolong survival. However, because of its extremely short plasma half-life, the drug must be administered as a continuous intravenous infusion through a central line. Several prostacyclin analogs with longer half-lives have been developed and treprostinil was recently approved for use in pulmonary hypertension (Horn, 2002). This drug is administered by continuous subcutaneous infusion. 

Kushiro M, Shikata K, Sugimoto H et al. (1998) Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat. Kidney Intern 53 1314-1320 Masugi M, Sato T (1934) Virchows Arch Pathol Anat Physiol Klin Med 293 615... 

Intramolecular Wittig-Horner reactions. Aristoff effected intramolecular cycli-zation of 1 to the prostacyclin analog 2 in high yield by treatment with KiCO, (I equiv.) and l8-crown-6 (2 equiv.) in toluene. Usual conditions for this reaction resulted in de-... 

Dumble LJ, Gibbons S, Tejpal N, Chou TC, Redgrave NG, Boyle MJ, Kahan BD. 15 AU81, a prostacyclin analog, potentiates immunosuppression and mitigates renal Injury due to cyclosporine.Transplantation 1993 55 1124-1128. 

Cyclization of l,oi-dihalo [or bis(tosyloxy)] alkanes with methyl methylthiomethyl sulfoxide in the presence of a base such as Bu"Li or KH gave three-, four-, five- and six-memboed 1-methylsulfinyl-l-methylthiocycloalkanes that are easily converted to Ae corresponding ketone by acid hydrolysis. This is applicable to the formation of the key intermediate for the synthesis of isocaibacyclin, a potent prostacyclin analog. ... 

In the synthesis of the novel prostacyclin analog (157) an aldehyde group was introduced at the 2-position by regiospecific ring opening of the epoxide (156) with the lithium anion of (154) and subsequent... 

Answer A. During fetal development, the ductus arteriosus is kept open by prostaglandins. For temporary maintenance of patency in the infant, the PGE1 analog alprostadil is used. Closure of the ductus in the infant can often be accomplished by IV indomethacin, which decreases PG synthesis by inhibiting COX. Epoprostenol is a prostacyclin analog used in primary pulmonary HTN. 

Examples of enantioselective hydrolysis of cyclic diesters by a-chymotrypsin are comparatively rare (10-14) (Table 11.1-7). Interestingly, the cyclopentanoid and the cyclohexenoid monoesters 11 and 12 have the opposite absolute configuration to those obtained by the pig liver esterase-catalyzed hydrolysis of the corresponding diesters (Table 11.1-1). The keto ester 14, which is a valuable building block for the synthesis of prostacyclin analogs, has been obtained from the corresponding a,a -keto diester via a-chymotrypsin-catalyzed hydrolysis followed by a decarboxylation of the keto acid. 

Epoprostenol is a prostacyclin analog that antagonizes the vasoconstrictor effect of thromboxanes. It is useful in the therapy of pulmonary hypertension. 

The advent of Macugen and Lucentis to treat age-related macular degeneration and endothelin antagonists (Tracleer, Thelin, Ambrisentan) and prostacyclin analogs (Epoprostenol, Treprostinil, Beraprost, Iloprost) to treat pulmonary arte-... 

Crutchley, D.J., Conanan, L.B. and Que, B.G. (1994) Effects of Prostacyclin Analogs on the Synthesis of Tissue Factor, Tumor Necrosis Factor-a and Interleukin-ip in Human Monocytic THP-1 Cells,/. Pharmacol. Exp. Ther. 277,446-451. 

Zardi EM, Zardi DM, Cacciapaglia F, Dobrina A, Amoroso A, Picardi A, Afeltra A (2005) Endothehal dysfunction and activation as an expression of disease role of prostacyclin analogs. Int Immunopharmacol 5 437-459... 

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