5467-79-8Relevant articles and documents
Selective naphthalene H3 receptor inverse agonists with reduced potential to induce phospholipidosis and their quinoline analogs
Rodriguez Sarmiento, Rosa Maria,Nettekoven, Matthias H.,Taylor, Sven,Plancher, Jean-Marc,Richter, Hans,Roche, Olivier
, p. 4495 - 4500 (2009)
We reported earlier the refinement of our initial five-point pharmacophore model for the Histamine 3 receptor (H3R), with a new acceptor feature important for binding and selectivity against the other histamine receptor subtypes 1, 2 and 4. This approach was validated with a new series of H3R inverse agonists: the naphthalene series. In this Letter, we describe our efforts to overcome the phospholipidosis flag identified with our initial lead compound (1a). During the optimization process, we monitored the potency of our molecules toward the H3 receptor, their selectivity against H1R, H2R and H4R, as well as some key molecular properties that may influence phospholipidosis. Encouraged by the promising profile of the naphthalene series, we used our deeper understanding of the H3R pharmacophore model to lead us towards the quinoline series. This series is perceived to have intrinsic advantages with respect to its amphiphilic vector.
Regioselective Cyanation of Six-Membered N-Heteroaromatic Compounds Under Metal-, Activator-, Base- and Solvent-Free Conditions
Sarmah, Bikash Kumar,Konwar, Monuranjan,Bhattacharyya, Dipanjan,Adhikari, Priyanka,Das, Animesh
, p. 5616 - 5625 (2019/11/22)
A regioselective cyanation of heteroaromatic N-oxides with trimethylsilyl cyanide has been developed to obtain 2-substituted N-heteroaromatic nitrile without the requirement of any external activator-, metal-, base-, and solvent. The present protocol is a straightforward, one-pot heteroaromatic C?H cyanation process, and proceeds smoothly in conventional heating but also under microwave irradiation with shorter reaction times. This approach now allows access to a broad class of quinoline N-oxides and other heteroarene N-oxides with high to good yields and can also be scaled up to obtain gram quantities. Further application of this process was observed and utilized in late-stage cyanation of the anti-malarial drug quinine as well as transformation of the 2-cyanoazines to a series of biologically important molecules. Based on the experimental observations, a plausible mechanism has also been proposed highlighting the dual role of trimethylsilyl cyanide as a nitrile source and as an activating agent. (Figure presented.).
Hypervalent Iodine(III)-Mediated Regioselective Cyanation of Quinoline N-Oxides with Trimethylsilyl Cyanide
Xu, Feng,Li, Yuqin,Huang, Xin,Fang, Xinjie,Li, Zhuofei,Jiang, Hongshuo,Qiao, Jingyi,Chu, Wenyi,Sun, Zhizhong
supporting information, p. 520 - 525 (2018/12/13)
A regioselective cyanation of quinoline N-oxides with trimethylsilyl cyanide was developed by using (Diacetoxyiodo) benzene (PIDA) as mediated hypervalent iodine(III) reagent under metal-free and base-free reaction conditions to obtain 2-cyanoquinolines. The efficient PIDA reagent could play the role of an activator of the substrates and an accelerator of N?O bond cleavage. The reaction system featured a wide range of substrate suitability and high yields. The procedure was enlarged gram-scale to synthesize the tuberculosis (TB) inhibitor. Finally, according to some experimental results, a plausible mechanism for the cyanation reaction is proposed. (Figure presented.).
