Butyrophenone Analogues Research Articles

Potential atypical antipsychotics: synthesis, binding affinity and SAR of new heterocyclic bioisosteric butyrophenone analogues as multitarget ligands

A series of 15 heterocyclic butyrophenone analogues was synthesized as potential multi-target ligands. The compounds were assayed for their in vitro human D2 and 5-HT2A receptor affinity, and those compounds exhibiting the highest affinities were evaluated for binding affinity on D1, D3, 5-HT1A, 5-HT2C and 5-HT6 receptors.

ChemInform Abstract: Butyrophenone Analogues in the Carbazole Series as Potential Atypical Antipsychotics: Synthesis and Determination of Affinities at D2, 5-HT2A, 5-HT2B and 5-HT2C Receptors.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis and binding affinity of new pyrazole and isoxazole derivatives as potential atypical antipsychotics

We describe the synthesis and binding affinities on D 2, 5-HT 2A and 5-HT 2C receptors of 6-aminomethyl-6,7-dihydro-1 H-indazol-4(5 H)-ones and 6-aminomethyl-6,7-dihydro-3-methyl-benzo[ d]isoxazol-4(5 H)-ones, as conformationally constrained butyrophenone analogues. One of the new compounds showed good in vitro binding features, and a Meltzer’s ratio characteristic of an atypical antipsychotic profile.

Butyrophenone analogues in the carbazole series as potential atypical antipsychotics: synthesis and determination of affinities at D 2, 5-HT 2A, 5-HT 2B and 5-HT 2C receptors

We describe practical and efficient routes for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4 H-carbazol-4-ones using the Fischer indole synthesis or palladium-catalysed cyclization methodologies, as well as their affinities for D 2, 5-HT 2A and 5-HT 2C receptors, and their activity at the 5-HT 2B receptor. The most active compounds, 4b (QF 2003B) and 4c (QF 2004B), with a p K i (5-HT 2A/D 2) ratio of 1.28 show a potential antipsychotic profile according to Meltzer's classification.

ChemInform Abstract: Butyrophenone Analogues in the Carbazole Series: Synthesis and Determination of Affinities at D2 and 5‐HT2A Receptors.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Butyrophenone analogues in the carbazole series: Synthesis and determination of affinities at D 2 and 5-HT 2A receptors

We describe a practical and efficient route for synthesis of 2-aminomethyl-1,2,3,9-tetrahydro-4 H-carbazol-4-ones using an effective Fisher indole methodology. The most active compounds, 4b ( QF 2003B) and 4c ( QF 2004B), with pKi ( 5- HT 2A D 2 ) ratio of 1.28 show an antipsychotic profile according to Meltzer's classification.

ChemInform Abstract: New CNS Agent Precursors. A Simple and Efficient Route for Synthesis of 6‐Aminomethyl‐4,5,6,7‐tetrahydrobenzofuran‐4‐ones as Conformationally Constrained Butyrophenone Analogues.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

New CNS agent precursors. A simple and efficient route for synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as conformationally constrained butyrophenone analogues

Starting from 3,4,5-trimethoxybenzoic acid, we described a practical and efficient five-step synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as new CNS agent precursors in an overall yield of 20%.

New cyclic butyrophenone derivatives in the indole series as potential atypical antipsychotics. A simple and practical synthesis of 6-aminomethyl-tetrahydroindol-4-ones and their affinites for D 2 and 5-HT 2A receptors

A simple and efficient synthesis of novel 6-aminomethyl-tetrahydroindol-4-ones, which are butyrophenone analogues of molindone, is described. These compounds exhibit potent affinities for D 2 and 5-HT 2A receptors in vitro. The most active compounds, 6d (QF 0408B) and 6e (QF 0409B), with pK i (5-HT 2A/D 2) ratios of 1.32 and 1.17 respectively, show an antipsychotic profile according to Meltzer's classification.

ChemInform Abstract: Butyrophenone Analogues: Synthesis of 2‐Methyl‐3‐ethyl‐5‐aminoethyl‐4, 5,6,7‐tetrahydroindol‐4‐ones, and Their Affinities for D1, D2 and 5‐ HT2A Receptors.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Butyrophenone analogues: Synthesis of 2-methyl-3-ethyl-5-aminoethyl-4,5,6,7-tetrahydroindol-4-ones, and their affinities for d 1, d 2 and 5-ht 2a receptors

Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, ( 1) and 2-methyl-3-ethyl-5-(4- o-methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetrahydroindol-4-one ( 2) as butyrophenone analogues of the neuroleptic molindone. The affinities of these compounds for D 1 and D 2 dopamine and 5-HT 2A serotonin receptors were evaluated in vitro. The affinity of 1 for D 2 receptors is less than that of molindone (pKi's 6.23 and 7.48 respectively) and that of 2 similar (pK i 7.55). Both compounds bind to 5-HT 2A receptors, the affinity of 2 being significantly greater than that of molindone (pK i's of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively).

2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1.

2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or to the 4-substituted piperazine moiety of fluanisone but is lost if the 2-phenylpyrrole is combined with the 4-substituted piperidine moiety of haloperidol. The 2-phenylpyrrole analogue 1 of sultopride is in vitro 0.25 and in vivo 3 times as potent as the parent compound. Its binding to the dopamine D-2 receptors is, in analogy to the substituted benzamides, strongly sodium-dependent. The 2-(4-fluorophenyl)pyrrole analogue 5 of fluanisone is superior in vitro as well as in vivo to the corresponding benzamide 7 and the butyrophenone fluanisone. The increase in activity is not only due to a higher affinity for the D-2 receptors but also to an enhanced oral absorption (ratio po/ip = 4.5 vs 40 for the benzamide and 60 for fluanisone). Compound 5 is further characterized by a high selectivity for the D-2 receptors, in contrast to the benzamide and butyrophenone analogues (ratio D-2/alpha 1 = 60, 2.0, and 0.3, respectively). The binding to the D-2 receptors has little dependence on sodium. The 2-phenylpyrrole 5 shares with the benzamide 7 a low potential to induce catalepsy, which is in contrast to haloperidol. So, 5-(4-fluorophenyl)-2-[[4-(2-methoxyphenyl)-1-piperazinyl]methyl]pyrrole (5) is the prototype of a new class of sodium-independent dopamine D-2 antagonists, which may be particularly useful as potential antipsychotics with a low propensity to induce acute extrapyramidal side effects.

Synthesis and neuroleptic activity of some trans-(2-aminomethyl)-cyclopentyl aryl ketones

This article describes the synthesis of a series of butyrophenone analogues in which the propyl chain is partially included in a cyclopentane ring. These trans-(2-aminomethyl)cyclopentyl aryl ketones are obtained by reacting (2-bromomethyl)cyclopentyl phenyl ketone or (2-bromomethyl)cyclopentyl p-fluorophenyl ketone with the corresponding heterocyclic amine. The potential neuroleptic activity of these compounds is reported.

Synthesis of new haloperidol analogues and characterization of their interactions with alpha-adrenoceptors in rat parotid slices and human platelet membranes.

1 The synthesis of several butyrophenone analogues of haloperidol is described. 2 The effects of these compounds on alpha-adrenoceptors were evaluated by examining their ability to reduce alpha 1-stimulated K+ release from rat parotid slices and to displace [3H]-phentolamine from human platelet membrane alpha 2-adrenoceptors. 3 The affinity of haloperidol and its analogues for alpha 1-receptors was found to be 1 to 2 orders of magnitude greater than that for alpha 2-adrenoceptors. These observations suggest that most of the alpha-adrenoceptor activity of butyrophenones results from their interaction with alpha 1-adrenoceptors. 4 The relatively high affinity of the butyrophenones for alpha 1-adrenoceptors suggests that they may be useful as probes in studies of alpha 1-adrenoceptors in these and other tissues.