Compounds based on the ergoline ring system: ##STR1## have a suprising variety of pharmaceutical activities. For example, lysergic and isolysergic acid are 8-carboxy-6-methyl-9-ergolenes. (The trivial name "Ergoline" is given to the above structure and the 9,10 double bonded compound-related to lysergic acid-is called a 9-ergolene rather than a 9,10-didehydroergoline). The amides of lysergic acid, many of which have valuable and unique pharmacologic properties, include the naturally occurring oxytocic alkaloids -- ergocornine, ergokryptine, ergonovine, ergocristine, ergosine, ergotamine, etc. -- and synthetic oxytocics such as methergine as well as the synthetic hallucinogen -- lysergic acid diethylamide or LSD. The amides of 6-methyl-8-carboxyergoline, known generically as dihydroergot alkaloids, are oxytoxic agents of lower potency and also lower toxicity than the ergot alkaloids themselves. Recently, it has been found by Clemens, Semonsky, Meites, and their various co-workers that many ergot-related drugs have activity as prolactin inhibitors including ergocornine, dihydroergocornine, 2-bromo-.alpha.-ergokryptine and d-6-methyl-8-cyanomethylergoline. References embodying some of the newer findings in the field of ergoline chemistry are the following: Nagasawa and Meites, Proc. Soc. Exp't'l. Biol. Med, 135 469 (1970); Lutterbeck et al., Brit. Med. J., 228, (July 24, 1971); Heuson et al., Europ J. Cancer, 353 (1970); Coll. Czech, Chem. Commun., 33, 577 (1968); Nature, 221, 666 (1969); Seda et al., J. Reprod. Fert., 24 263 (1971); Mantle and Finn, id, 441; Semonsky and co-workers, Coll. Czech. Chem. Comm., 36, 2200 (1971); Schaar and Clemens, Endocr., 90, 285-8 (1972); Clemens and Schaar, Proc. Soc. Exp, Biol Med., 139, 659-662 (1972), Bach and Kornfeld, Tetrahedron Letters, 3225 (1974) and Sweeney, Clemens, Kornfeld and Poore, 64th Annual Meeting, American Association Cancer Research, April 1973. Recently issued patents in the field of ergoline derivatives or lysergic acid derivatives include the following: U.S. Pat. Nos. 3,704,233, 3,709,891, 3,585,201, 3,666,762, 3,586,683, 3,717,640, 3,592,816, 3,732,231, 3,717,640, 4,001,242, etc. -- see also Patent Office Classification Files 260-256.4 and 260-285.5.
8-Arylergolines have not heretofore been described. However, 2,3-dihydro-6-methyl-8-hydroxy-8-phenyl-9-ergolene is disclosed in U.S. Pat. No. 2,861,074 and in J. Org. Chem., 25, 142 (1960).
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