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      Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review

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          Abstract

          At present more than 250 FDA approved chlorine containing drugs were available in the market and many pharmaceutically important drug candidates in pre-clinical trials. Thus, it is quite obvious to expect that in coming decades there will be an even greater number of new chlorine-containing pharmaceuticals in market. Chlorinated compounds represent the family of compounds promising for use in medicinal chemistry. This review describes the recent advances in the synthesis of chlorine containing heterocyclic compounds as diverse biological agents and drugs in the pharmaceutical industries for the inspiration of the discovery and development of more potent and effective chlorinated drugs against numerous death-causing diseases.

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          Highlights

          • The applications of chlorine in medicinal chemistry is one of the fastest growing hot research areas in the chemistry community.

          • More than 250 FDA approved chloro-containing drugs are in the market.

          • This review summarizes nearly 130 FDA approved drugs against diverse biological agents.

          • Discussions of the SAR of potent drugs were included.

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          Most cited references109

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          Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1).

          Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).
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                Author and article information

                Contributors
                Journal
                Eur J Med Chem
                Eur J Med Chem
                European Journal of Medicinal Chemistry
                Elsevier Masson SAS.
                0223-5234
                1768-3254
                10 April 2019
                1 July 2019
                10 April 2019
                : 173
                : 117-153
                Affiliations
                [a ]School of Chemistry, Chemical Engineering and Life Science, School of Materials Science and Engineering, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070, PR China
                [b ]Department of Chemistry, Sri Jayachamarajendra College of Engineering, Mysuru, 570006, Karnataka, India
                [c ]Department of Chemistry, Pooja Bhagavath Memorial Mahajana Education Centre, Mysuru, 570016, Karnataka, India
                [d ]Biotechnology Research Group, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
                Author notes
                []Corresponding author. rakeshasg@ 123456gmail.com
                [∗∗ ]Corresponding author. qinhuali@ 123456whut.edu.cn
                Article
                S0223-5234(19)30297-1
                10.1016/j.ejmech.2019.03.063
                7111421
                30995567
                43496c27-b960-4171-bb5e-3643483719e6
                © 2019 Elsevier Masson SAS. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 3 December 2018
                : 30 March 2019
                : 31 March 2019
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                synthesis,chlorinated compounds,biological applications,sar

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