- Synthesis and structure-activity relationships of new (5R,8R,10R)-ergoline derivatives with antihypertensive or dopaminergic activity
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A series of new (5R,8R,10R)-ergoline derivatives was synthesized, and their antihypertensive and dopaminergic activities were tested in conscious spontaneously hypertensive rats and in rats with unilateral 6- hydroxydopamine-induced lesions of the substantia nigra. (5R,8R,10R)-6- Alkyl-8-ergolinemethanols, prepared from the corresponding ergolinecarboxylates, were converted to the tosylates, which were treated with various five-membered heterocycles containing nitrogen atoms to afford the new ergolines. (5R,8R,10R)-8-(1,2,4-Triazol-1-ylmethyl)-6-methylergoline (4s, maleate: BAM-1110) exhibited potent dopaminergic activity, about 18- fold greater than that of bromocriptine mesylate. (5R,8R,10R)-8-(1,2,4- Triazol-1-ylmethyl)-6-propylergoline (8b, fumarate: BAM-1602) showed extremely potent dopaminergic activity, being about 220 and 1.15 times more active than bromocriptine mesylate and pergolide mesylate, respectively. Several compounds exhibited potent antihypertensive activity. Structure- activity relationships for antihypertensive and dopaminergic activities are discussed.
- Ohno,Adachi,Koumori,Mizukoshi,Nagasaka,Ichihara,Kato -
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p. 1463 - 1473
(2007/10/02)
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- EPIMERIZATION OF ESTERS OF STEREOISOMERIC 8-ERGOLINECARBOXYLIC ACIDS ON CARBON C(8)
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Esters of 8β-ergolinecarboxylic acids, I-XI, exposed to strong bases, such as lithium diisopropylamide, in polar aprotic solvents gave enolates, which were decomposed by suitable proton donors to a mixture of epimers.This contained, apart from the starting 8β-esters, the corresponding 8α-esters, Ia-IVa and VIa-XIa (65-80percent) and Va (about 16percent).Exposure of 8α-ester XIIa to these conditions produced epimerization on C(8) (about 54percent) and, to a small extent, isomerization on C(10), affording ester I(c. 1percent) and Ia (c. 5percent).
- Benes, Jan,Cerny, Antonin,Miller, Vladimir,Kudrnac, Stanislav
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p. 1333 - 1340
(2007/10/02)
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- Ergot derivatives
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Compounds and process for making same are disclosed, the compounds having the formula (I): STR1 wherein R1 represents methyl, phenyl, piperidino, 1-pyrrolidinyl, morpholino or 4-methyl-1-piperazinyl, alkyl or alkoxy having from 1 to 4 carbon atoms, amino, substituted amino of the formula NHR' (wherein R' is alkyl having from 1 to 4 carbon atoms, cycloalkyl, a benzyl, or phenyl) or substituted amino of the formula NR" R"' (wherein R" and R"' both represent alkyl having from 1 to 4 carbon atoms); R2 represents a hydrogen atom, alkyl having from 1 to 4 carbon atoms, or phenyl; R3 represents a fluorine atom, cyano, difluoromethyl, difluorobromomethyl, trifluoromethyl, methylthio, methylsulphonyl, sulphonamido, an alkoxy having from 1 to 4 carbon atoms, an alkanoyl having from 2 to 5 carbon atoms, or benzoyl; R4 represents a hydrocarbon having from 1 to 4 carbon atoms; R5 represents a hydrogen atom or methoxy; R6 represents a hydrogen or halogen atom or methyl; and R7 represents a hydrogen atom or methyl. The 2-cyano derivatives are especially preferred. The compounds are useful as antihypertensive agents.
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- 6-N-Propyl-8-methoxymethyl or methylmercaptomethylergolines and related compounds
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6-n-Propyl (ethyl or allyl)-8β-methoxy-(methylsulfinyl, methylsulfonyl, or methylmercapto) methylergolines, 8-ergolenes or 9-ergolenes, useful as prolactin inhibitors and in the treatment of Parkinsonism.
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