10562-70-6Relevant academic research and scientific papers
Direct Exploitation of the Ethynyl Moiety in Calcium Carbide Through Sealed Ball Milling
Hosseini, Abolfazl,Schreiner, Peter R.
, p. 4339 - 4346 (2020/07/04)
Ball milling of calcium carbide (CaC2) enables the reaction of its ethynyl moiety with organic electrophiles. This was realized simply by co-milling CaC2 with organic substrates in a sealed jar without the need for an additive or a catalyst. Various ketones including those bearing α-hydrogens were ethynylated in good yields at short reaction times. Aryl halides are also amenable substrates for this protocol as they furnish aryl ethynes through a benzyne intermediate. This method offers a practical and cheap alternative to the established procedures for introducing ethynyl functionalities.
Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding
Deng, Hui,Kooijman, Sander,Van Den Nieuwendijk, Adrianus M. C. H.,Ogasawara, Daisuke,Van der Wel, Tom,Van Dalen, Floris,Baggelaar, Marc P.,Janssen, Freek J.,Van Den Berg, Richard J. B. H. N.,Den Dulk, Hans,Cravatt, Benjamin F.,Overkleeft, Herman S.,Rensen, Patrick C. N.,Van der Stelt, Mario
supporting information, p. 428 - 440 (2017/04/26)
Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.
Pd(II)-catalyzed highly regio-and stereoselective assembly of C-C double bonds: An efficient method for the synthesis of 2,4-dihalo-1,3,5-trienes from alkynols
Jiang, Huanfeng,Gao, Yang,Wu, Wanqing,Huang, Yubing
supporting information, p. 238 - 241 (2013/03/13)
A highly efficient method for the synthesis of 2,4-dihalo-1,3,5-trienes from alkynols was developed. This chemistry allows access to multiple conjugated double bonds in a single step with high stereoselectivity.
Analogues of oxybutynin. Synthesis and antimuscarinic and bladder activity of some substituted 7-amino-1-hydroxy-5-heptyn-2-ones and related compounds
Carter,Noronha-Blob,Audia,Dupont,McPherson,Natalie Jr.,Rzeszotarski,Spagnuolo,Waid,Kaiser
, p. 3065 - 3074 (2007/10/02)
Oxybutynin chloride [4-(diethylamino)-2-butynyl α-cyclohexyl-α-hydroxybenzeneacetate hydrochloride, Ditropan] is widely used for the relief of symptoms in neurogenic bladder. This is a result of its combined anticholinergic, antispasmodic, and local anesthetic activities. In a study directed toward development of agents possessing the beneficial properties of oxybutynin, but having a longer duration of action, a series of metabolically more stable keto analogues of the parent ester, i.e. substituted 7-amino-1-hydroxy-5-heptyn-2-ones along with some analogues and derivatives, was prepared and evaluated for in vitro and in vivo antimuscarinic action in guinea pig preparations. Several members of the series were potent antimuscarinics having a longer duration of activity than that of oxybutynin in a guinea pig cystometrogram model. On the basis of its in vitro and in vivo antimuscarinic activity, coupled with a 5-fold greater duration of action than that of oxybutynin, 1-cyclobutyl-7-(dimethylamino)-1-hydroxy-1-phenyl-5-heptyn-2-one (14b) was selected for clinical evaluation.
