128200-13-5Relevant academic research and scientific papers
Novel 5-HT3 antagonists: Indol-3-ylspiro(azabicycloalkane-3,5'(4'H)- oxazoles)
Swain,Baker,Kneen,Herbert,Moseley,Saunders,Seward,Stevenson,Beer,Stanton,Watling,Ball
, p. 1019 - 1031 (2007/10/02)
The synthesis and biochemical evaluation of a series of spirofused indole oxazoline 5-HT3 antagonists is described in which the oxazoline ring acts as a bioisosteric replacement for esters and amides. The effect of substitution about the indole ring has shown the steric limitations of the aromatic binding site. Incorporation of a variety of azabicyclic systems within the rigid spirofused framework has allowed the definition of a binding model which incorporates a number of known antagonists and agonists. In this model steric constraints limit substitution around the indole ring although there is some bulk tolerance at the 1- and 2-positions. The importance of constraining the basic nitrogen within an azabicyclic system is underlined by comparison with the monocyclic piperidine. The highest affinity was observed for those compounds in which the basic nitrogen occupies a bridgehead position, the most potent analogue in this group being the azabicyclic [3.3.1] system (pIC50 = 8.95), suggesting lipophilic interactions may play a role in increasing affinity. A suggested model for agonist binding is included in which the basic nitrogens are superimposed and the 5-hydroxyl group of 5-HT is superimposed on the H-bond-accepting atom of the heterocyclic linking group.
3-[N-aroyl(or thioaroyl)aminomethyl]-3-quinuclidinols
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, (2008/06/13)
3-[N-Aroyl(or thioaryol)aminoalkyl]-3-quinuclidinols corresponding to the formula: STR1 wherein X is O or S, and Ar is phenyl, substituted phenyl, indole, indazole or pyrimidine; optical isomers and the pharmaceutically acceptable acid addition salts and solvates thereof. These compounds have gastric emptying, antiemetic, anxiolytic and selective serotonin modulating or inhibiting activity.
SPIRO NITROGEN-BRIDGED HETEROCYCLIC COMPOUNDS
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, (2008/06/13)
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. "
SYNTHESIS OF INDOLE OXAZOLINES; NOVEL 5-HT3 ANTAGONISTS
Swain, Christopher J.,Kneen, Clare,Herbert, Richard,Baker, Raymond
, p. 3183 - 3186 (2007/10/02)
The synthesis of a novel series of spiro fused indole oxazolines is reported, the spiro centre being generated via addition of an azabicyclic amino alcohol to an indole imidate.The azabicyclic amino alcohol was generated from the corresponding cyanohydrin by borane reduction, which alsoserved to protect the highly nucleophilic azabicyclic nitrogen.In the case of the unsymmetrical azabicyclic system 10, stereocontrolled cyanohydrin formation was achieved.Selective alkylation of the indole nitrogen was facilitated by borane protection of the azabicyclic nitrogen.
