- SPIRO NITROGEN-BRIDGED HETEROCYCLIC COMPOUNDS
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The invention relates to novel compounds (I) for treating diseases of the central and peripheral nervous system: STR1 including enantiomers, racemates and acid addition and quaternary salts thereof, wherein one of X and Y is O and the other of X and Y is N; Q is (CH 2) n or C(CH. sub.3) 2 where n is 1, 2 or 3 and the bridge--Q--is attached at one end to position 1 and at the other end to position 4 or 5, and R° is hydrogen, methyl or hydroxyl; in the moiety STR2 the line connecting Z and Y signifies a double bond when X--Z is O--C--R and Y is N, and a single bond when X--Z is N=C--R and Y is O; Z is C--R wherein R is selected from hydrogen, NH 2, NH-R" (R"=C 1-6-alkyl) , N(R") 2, R", C 2-6-alkenyl, C 2-6-alkynyl, C 3-7-cycloalkyl, R" substituted by hydroxy or by 1-6 halogen atoms, R"O-C 1-6-alkyl, carboxy-C 1-6-alkyl, R"OCO-C 1-6-alkyl, amino-C 1-6-alkyl, R"NH-C 1-6-alkyl, (R") 2 N-C 1-6-alkyl, 2-oxo-pyrrolidin-1-ylmethyl, aryl, diarylmethylol, and R" substituted by one or two aryl groups, wherein aryl denotes phenyl optionally substituted by 1-3 halogens, R", R"O and(or) CF 3. Also claimed are compounds wherein the line connecting Z and Y signifies the absence of a bond, X is O, Z is H and Y is NH 2, NO 2 or N 3. "
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- Cholinergic activity of acetylenic imidazoles and related compounds
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A series of acetylenic imidazoles related to oxotremorine (1a) were prepared and evaluated as cholinergic agents with in vitro binding assays and in vivo pharmacological tests in mice. 1-[4-(1H-Imidazol-1-yl)-2-butynyl]-2-pyrrolidinone (1b) was a cholinergic agonist with one-half the potency of oxotremorine. Analogues of 1b with a 5- or 2-methyl substituent in the imidazole ring (compounds 1c and 1g) were cholinergic partial agonists. Analogues of 1b with a methyl substituent at the 5-position in the pyrrolidinone ring (7b) or at the α-position in the acetylenic chain (8b) were antagonists. Various analogues of these imidazole acetylenes where the pyrrolidinone ring was replaced by an amide, carbamate, or urea residue were prepared. Several compounds which contained 5-methylimidazole as the amine substituent were partial agonists. The activities of the imidazole compounds are compared with those of the related pyrrolidine and dimethylamine analogues. Agonist and antagonist conformations for these compounds at muscarinic receptors are proposed.
- Moon,Chidester,Heier,Morris,Collins,Russell,Francis,Sage,Sethy
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p. 2314 - 2327
(2007/10/02)
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