34126-99-3Relevant academic research and scientific papers
Covalent inhibition of the histamine H3 receptor
Wágner, Gábor,Mocking, Tamara A.M.,Kooistra, Albert J.,Slynko, Inna,ábrányi-Balogh, Péter,Keser u, Gy?rgy M.,Wijtmans, Maikel,Vischer, Henry F.,de Esch, Iwan J.P.,Leurs, Rob
supporting information, (2019/12/25)
Covalent binding of G protein-coupled receptors by small molecules is a useful approach for better understanding of the structure and function of these proteins. We designed, synthesized and characterized a series of 6 potential covalent ligands for the histamine H3 receptor (H3R). Starting from a 2-amino-pyrimidine scaffold, optimization of anchor moiety and warhead followed by fine-tuning of the required reactivity via scaffold hopping resulted in the isothiocyanate H3R ligand 44. It shows high reactivity toward glutathione combined with appropriate stability in water and reacts selectively with the cysteine sidechain in a model nonapeptide equipped with nucleophilic residues. The covalent interaction of 44 with H3R was validated with washout experiments and leads to inverse agonism on H3R. Irreversible binder 44 (VUF15662) may serve as a useful tool compound to stabilize the inactive H3R conformation and to study the consequences of prolonged inhibition of the H3R.
Arylpiperazine-containing pyrimidine 4-carboxamide derivatives targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant
Kim, Jong Yup,Kim, Deukjoon,Kang, Suk Youn,Park, Woo-Kyu,Kim, Hyun Jung,Jung, Myung Eun,Son, Eun-Jung,Pae, Ae Nim,Kim, Jeongmin,Lee, Jinhwa
scheme or table, p. 6439 - 6442 (2010/11/18)
Pyrimidine usually has good pharmacokinetic properties as a drug substance and considerable efforts have been devoted to develop pyrimidine derivatives into drug candidates. Arylpiperazine-containing pyrimidine 4-carboxamide derivatives were synthesized and evaluated for binding to serotonin receptors and transporter. Pyrimidine derivatives showed good antidepressant activity in FST (forced swimming test) animal model and also displayed no appreciable inhibitory activity against hERG channel blocking assay. Herein SAR studies of pyrimidine derivatives targeting serotonin receptors and transporter will be disclosed.
Acetylenes. Part 2. 2-Methylpyrimidin-4(3H)-ones and 4-amino-6-(1-hydroxyalkyl)-2-methylpyrimidines from alka-2,3-dienoates and 4-hydroxyalk-2-ynenitriles, respectively
Roberts, Ralph R.,Landor, Stephen R.,Bolessa, Evon A.
, p. 3021 - 3024 (2007/10/02)
Ethyl alka-2,3-dienoates and 4-tetrahydropyranyloxyalk-2-ynenitriles provide a 3-atom fragment when reacted with acetamidine in tetrahydrofuran, to furnish-2-methylpyrimidin-4(3H)-ones and 4-amino-2-methyl-6-(1-tetrahydropyranyloxyalkyl)pyrimidines, respectively (60-70% yield). The latter, with hydrochloric acid/ethanol, gave the corresponding 4-amino-6-(1-hydroxyalkyl-2-methylpyrimidines as their hydrochloride salts.
