- N-(Biphenyl-3-ylmethyl)ethanamines as G protein-biased agonists of 5-HT7R
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There has been much attention to biased ligands of G protein-coupled receptors (GPCRs) for potential pharmacological benefits. Recently, we reported N-((6-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)methyl)ethanamine 1 as G protein-biased agonist of 5-HT7R, which could be used as a chemical probe for the study on treatment discovery of autism spectrum disorder. Herein, we describe the synthesis of derivatives of the compound 1 and their biological evaluations in both G protein and β-arrestin signaling pathway. Total 16 compounds were synthesized and evaluated, and the compounds 3c, 3f, 3i, and 3p could be called as G protein-biased agonists like the compound 1. Among the four compounds, the compound 3c was the best in efficacy with an Emax value of 73% and the compound 3f was the most potent agonist with an EC50 value of 0.094 μM.
- Kim, Doyoung,Lee, Jieon,Kwag, Rina,Kim, Hyunbin,Oh, Hyunji,Moon, Bongjin,Kim, Hak Joong,Seong, Jihye,Jeon, Byungsun,Kang, Taek,Choo, Hyunah
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supporting information
p. 73 - 77
(2021/11/10)
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- GLYCINE COMPOUND
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[Problem] The present invention provides a compound which is useful as an active ingredient of a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases. [Means for Solution] The present inventors have conducted intensive studies on a compound having a VAP-1 inhibitory activity, and as a result, they have found that a compound of the present invention or a salt thereof exhibits an excellent VAP-1 inhibitory activity and is useful for preventing and/or treating VAP-1-related diseases, in particular, diabetic nephropathy or diabetic macular edema, thereby completing the present invention. The present invention further relates to a pharmaceutical composition, in particular, a pharmaceutical composition for preventing and/or treating VAP-1-related diseases, which comprises the compound of the present invention or a salt thereof, and an excipient.
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Page/Page column 16
(2012/07/28)
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- Reactions of N-Chlorobenzylalkylamines with Sodium Methoxide in Methanol. Steric Effects in Elimination Reactions
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Reactions of N-chlorobenzylalkylamines in which the alkyl group is Me, Et, i-Pr, t-Bu, and sec-Bu with MeONa-MeOH have been investigated kinetically.The eliminations are quantitative and regiospecific, producing only benzylidenealkylamines.The reactions are first order in base and first order in substrate, and an E2 mechanism is evident.The relative rates of elimination at 25 deg C are 1/0.5/0.3/0.2/0.01 for Me/Et/i-Pr/sec-Bu/t-Bu alkyl substituents, respectively.The results are attributed to repulsive interaction between the alkyl group and the base in the transition state.Hammett ρ and kH/kD values decreased, but the ΔH(excit.) and ΔS(excit.) values increased with bulkier alkyl substituents.Changes in the transition-state parameters with the substrate steric effect are interpreted with variation in structure of the imine-forming transition states.
- Cho, Bong Rae,Maeng, Jun Ho,Yoon, Jong Chan,Kim, Tae Rin
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p. 4752 - 4756
(2007/10/02)
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- Benzylamines: Synthesis and evaluation of antimycobacterial properties
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The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described. The most active compounds in this test, N-methyl-3-chlorobenzylamine (MIC 10.2 μg/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 μg/mL), and N-butyl-3,5-difluorobenzylamine (MIC 6.4 μg/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties. The combination of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M. tuberculosis H 37 Ra.
- Meindl,Von Angerer,Schonenberger,Ruckdeschel
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p. 1111 - 1118
(2007/10/02)
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