- Synthesis and pharmacological evaluation of N-benzyl substituted 4-bromo-2,5-dimethoxyphenethylamines as 5-HT2A/2C partial agonists
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N-Benzyl substitution of phenethylamine 5-HT2A receptor agonists has dramatic effects on binding affinity, receptor selectivity and agonist activity. In this paper we examine how affinity for the 5-HT2A/2C receptors are influenced by N-benzyl substitution of 4-bromo-2,5-dimethoxyphenethylamine derivatives. Special attention is given to the 2′ and 3′-position of the N-benzyl as such compounds are known to be very potent. We found that substitutions in these positions are generally well tolerated. The 2′-position was further examined using a range of substituents to probe the hydrogen bonding requirements for optimal affinity and selectivity, and it was found that small changes in the ligands in this area had a profound effect on their affinities. Furthermore, two ligands that lack a 2′-benzyl substituent were also found to have high affinity contradicting previous held notions. Several high-affinity ligands were identified and assayed for functional activity at the 5-HT2A and 5-HT2C receptor, and they were generally found to be less efficacious agonists than previously reported N-benzyl phenethylamines.
- Hansen, Martin,Jacobsen, Stine Engesgaard,Plunkett, Shane,Liebscher, Gudrun Eckhard,McCorvy, John D.,Br?uner-Osborne, Hans,Kristensen, Jesper Langgaard
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- HETEROCYCLIC COMPOUNDS AS AHR MODULATORS
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The present invention relates compounds of the general formula (I) or (III) which are ARH inhibitors, methods for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds and pharmaceutical compositions for the treatment or prevention of diseases, in particular cancer or conditions with dysregulated immune functions, or other conditions associated with aberrant AHR signalling, as a sole agent of in combination with other active ingredients. Such compounds may also be of utility in the expansion of hematopoietic stem cells (HSCs) and the use of HSCs in autologous or allogenic transplantation for the treatment of patients with inherited immunological and autoimmune diseases and diverse hematopoietic disorders.
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Page/Page column 14; 18; 19; 20; 26; 28
(2020/03/24)
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- COMPOUND HAVING ZNF143 INHIBITORY ACTIVITY AND USE THEREOF
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PROBLEM TO BE SOLVED: To provide a compound having a ZNF143 inhibitory activity as well as to provide a ZNF143 inhibitory agent and pharmaceutical composition containing the same. SOLUTION: Provided is a compound represented by formula (I) or a salt thereof as well as a ZNF143 inhibitory agent containing the same and a pharmaceutical composition having the same as an active ingredient. A-B-C-D (I)[A is H, a methyl group, a naphthyl group, a phenyl group or a nitrogen-containing heterocyclic ring; B is as shown below, and C is an amide bond or a heteroaromatic ring containing N and O; D is a substituted/unsubstituted phenyl group or a monocyclic heteroaromatic ring containing N or S; and C and D are both fused heterocyclic ring or the like optionally having a substituent group.]. SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPOandINPIT
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Paragraph 0090; 0138; 0139
(2016/10/27)
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- 2,6-dialkyl-4-(benzothiazol- or benzoxazol-4-yl-1,4-dihydropyridines
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2,6-dialkyl-4-(benzothiazol- or benzoxazol-7-yl)-1,4-dihydropyridines which exhibit positive inotropic action with largely neutral vascular behavior, of the formula STR1 in which R1 and R5 are identical or different and represent straight-chain or branched alkyl having up to 8 carbon atoms, R2 represents nitro or cyano, or R1 and R2 together form a lactone ring of the formula STR2 R3 represents a radical of the formula STR3 R4 -R7 are defined hereinafter and physiologically acceptable salts thereof.
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