56924-11-9Relevant articles and documents
New dual 5-HT1A and 5-HT7 receptor ligands derived from SYA16263
Ofori, Edward,Onyameh, Edem K.,Gonela, Uma M.,Voshavar, Chandrashekhar,Bricker, Barbara,Swanson, Tracy L.,Eshleman, Amy J.,Schmachtenberg, Jennifer L.,Bloom, Shelley H.,Janowsky, Aaron J.,Ablordeppey, Seth Y.
, (2021)
We have previously reported that dual 5-HT1A and 5-HT7 receptor ligands might find utility as treatment options for various CNS related conditions including cognitive and anxiolytic impairments. We have also more recently reported that SYA16263 has antipsychotic-like properties with an absence of catalepsy in animal models ascribed to its ability to recruit β-arrestin to the D2 receptor. However, SYA16263 also binds with very high affinity to 5-HT1AR (Ki = 1.1 nM) and a moderate affinity at 5-HT7R (Ki = 90 nM). Thus, it was of interest to exploit its pharmacophore elements in designing new dual receptor ligands. Using SYA16263 as the lead molecule, we have conducted a limited structure-affinity relationship (SAFIR) study by modifying various structural elements in the arylalkyl moiety, resulting in the identification of a new dual 5-HT1AR and 5-HT7R ligand, 6-chloro-2-methyl-2-(3-(4-(pyridin-2-yl)piperazin-1-yl)propyl)-2,3-dihydro-1H-inden-1-one (21), which unlike SYA16263, has a sub-nanomolar (5-HT1AR, Ki = 0.74 nM) and a low nanomolar (5-HT7R, Ki = 8.4 nM) affinity for these receptors. Interestingly, 21 is a full agonist at 5-HT1AR and antagonist at the 5-HT7R, functional characteristics which point to its potential as an antidepressant agent.
SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
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Paragraph 0855-0856, (2015/02/25)
Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.
Novel phenylpiperazine derivatives as dual cytokine regulators with TNF-α suppressing and IL-10 augmenting activity
Hanano, Tokushi,Adachi, Kunitomo,Aoki, Yoshiyuki,Morimoto, Hiroshi,Naka, Yoichi,Hisadome, Masao,Fukuda, Tetsuko,Sumichika, Hiroshi
, p. 875 - 879 (2007/10/03)
Phenylpiperazine derivatives were synthesized as dual cytokine regulators with TNF-α suppressing and IL-10 augmenting activity. Lead optimization led to compound 5k having the potent regulatory activity and demonstrating remarkable protective effects against the lethal challenge of LPS in mice, suggesting that 5k would be a promising drug candidate for the treatment of TNF-α associated diseases including septic shock. (C) 2000 Elsevier Science Ltd. All rights reserved.
Rapid and efficient synthesis of high-purity fluorine-18 labeled haloperidol and spiperone via the nitro precursor in combination with a new HPLC separation method
Hashizume, Kazunari,Hashimoto, Naoto,Miyake, Yoshihiro
, p. 681 - 687 (2007/10/03)
We have completed a convenient synthesis of fluorine-18 labeled butyrophenone neuroleptics from their nitro precursors. Thus, we have developed an efficient single-columm HPLC system using a C18-bonded vinyl alcohol copolymer gel (octadecyl polymer, ODP) column and strongly alkaline solvent systems for purifying of the 18F-labeled butyrophenone neuroleptics obtained by a single-stp 18F-for-nitro exchange reaction. The method has been applied to the synthesis of two typical butyrophenone neuroleptics ([18F]haloperidol and [18F]spiperone) with high purity in high yield. With information concerning the optimized conditions for the 18F-for-nitro exchange reaction, the synthetic method would be useful for synthesizing various 18F-labeled compounds.
