4463-59-6Relevant articles and documents
Design and synthesis of new potent 5-HT7 receptor ligands as a candidate for the treatment of central nervous system diseases
Drabczyk, Anna K.,Latacz, Gniewomir,Ja?kowska, Jolanta,Ku?aga, Damian,Pla?uk, Damian,Rózga, Karolina,Sata?a, Grzegorz
, (2021/10/29)
Owing to their multifunctional pharmacological profiles (including dual 5-HT1A/5-HT7 action), arylpiperazine derivatives are widely used for treating central nervous system diseases including the depression or neuropathic pain. Herein we describe the design, synthesis and evaluation of biological activity of novel 5-HT7 ligands derived of 2,4,6-triamino-1,3,5-triazine. The studied compounds showed affinity and high selectively towards 5-HT7 receptor with the two most active compounds 34 (Ki = 61 nM), 22 (Ki = 109 nM) showing good metabolic stability and moderate affinity to CYP3A4 isoenzyme. Compound 22 had high hepatotoxicity at a concentration below 50 μM, while compound 34 showed low hepatotoxicity even at a concentration above 50 μM.
Palladium-Catalyzed meta-C-H Allylation of Arenes: A Unique Combination of a Pyrimidine-Based Template and Hexafluoroisopropanol
Bag, Sukdev,Dutta, Uttam,Jayarajan, Ramasamy,Maiti, Debabrata,Mondal, Arup,Porey, Sandip,Sunoj, Raghavan B.,Surya, K.
supporting information, p. 12453 - 12466 (2020/08/06)
Controlling remote selectivity and delivering novel functionalities at distal positions in arenes are an important endeavor in contemporary organic synthesis. In this vein, template engineering and mechanistic understanding of new functionalization strategies are essential for enhancing the scope of such methods. Herein, meta-C-H allylation of arenes has been achieved with the aid of a palladium catalyst, pyrimidine-based auxiliary, and allyl phosphate. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) was found as a critical solvent in this transformation. The role of HFIP throughout the catalytic cycle has been systematically studied. A broad substrate scope with phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl ester, phenylacetic acid, hydrocinnamic acid, and 2-phenylbenzoic acid derivatives has been demonstrated. Interestingly, conformationally flexible arenes have also been selectively allylated at the meta-position using allyl phosphate. A combination of 1H NMR, 31P NMR, ESI-MS, kinetic experiments, and density functional theory (DFT) computations suggested that reaction proceeds through a ligand-assisted meta-C-H activation, allyl addition forming a Pd-?-allyl complex which is then followed by a turnover determining the C-C bond formation step leading to the meta-allylated product.
Synthesis and Investigation of S-Substituted 2-Mercaptobenzoimidazoles as Inhibitors of Hedgehog Signaling
Gr??le, Simone,Susanto, Steven,Sievers, Sonja,Tavsan, Emel,Nieger, Martin,Jung, Nicole,Br?se, Stefan
supporting information, p. 931 - 935 (2017/09/22)
Due to the arising resistance of common drugs targeting the Hedgehog signaling pathway, the identification of new compound classes with inhibitory effect is urgently needed. We were able to identify S-alkylated 2-mercaptobenzoimidazoles as a new compound
