About: Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety

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About: Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety
Creator	Chen, Shen-En Akaji, Kenichi Freire, Ernesto Hayashi, Yoshio Kawasaki, Yuko Kiso, Yoshiaki Konno, Sho Takayama, Kentaro Thanigaimalai, Pillaiyar Yakushiji, Fumika Yamamoto, Takehito Kakiuchi, Rie Nakada, Kiyohiko Yamazaki, Yuri
Source	Elsevier; Medline; PMC
abstract	Abstract We describe here the design, synthesis and biological evaluation of a series of molecules toward the development of novel peptidomimetic inhibitors of SARS-CoV 3CLpro. A docking study involving binding between the initial lead compound 1 and the SARS-CoV 3CLpro motivated the replacement of a thiazole with a benzothiazole unit as a warhead moiety at the P1′ site. This modification led to the identification of more potent derivatives, including 2i, 2k, 2m, 2o, and 2p, with IC50 or K i values in the submicromolar to nanomolar range. In particular, compounds 2i and 2p exhibited the most potent inhibitory activities, with K i values of 4.1 and 3.1nM, respectively. The peptidomimetic compounds identified through this process are attractive leads for the development of potential therapeutic agents against SARS. The structural requirements of the peptidomimetics with potent inhibitory activities against SARS-CoV 3CLpro may be summarized as follows: (i) the presence of a benzothiazole warhead at the S1′-position; (ii) hydrogen bonding capabilities at the cyclic lactam of the S1-site; (iii) appropriate stereochemistry and hydrophobic moiety size at the S2-site and (iv) a unique folding conformation assumed by the phenoxyacetyl moiety at the S4-site.
has issue date	2013-01-15(xsd:dateTime)
bibo:doi	10.1016/j.bmc.2012.11.017
bibo:pmid	23245752
has license	els-covid
sha1sum (hex)	43a01f3a7935d879533de01ab397fb4e5ae641fe
schema:url	https://doi.org/10.1016/j.bmc.2012.11.017
resource representing a document's title	Design and synthesis of new tripeptide-type SARS-CoV 3CL protease inhibitors containing an electrophilic arylketone moiety
has PubMed Central identifier	PMC7127713
has PubMed identifier	23245752
schema:publication	Bioorganic & Medicinal Chemistry
resource representing a document's body	covid:43a01f3a7935d879533de01ab397fb4e5ae641fe#body_text
is schema:about of	named entity 'site' named entity 'SARS-CoV' named entity 'series' named entity 'moiety' named entity 'conformation' named entity 'motivated' named entity 'pro' named entity 'development' named entity 'moiety' named entity 'TRIPEPTIDE' named entity 'DESIGN' named entity 'ASSUMED' named entity 'DOCKING' named entity 'PRESENCE OF' named entity 'SARS' named entity 'CYCLIC' named entity 'ATTRACTIVE' named entity 'LEADS' named entity 'PEPTIDOMIMETIC' named entity 'ACTIVITIES' named entity 'REQUIREMENTS' named entity 'FOLLOWS' named entity 'THERAPEUTIC AGENTS' named entity 'SERIES' named entity 'SIZE' named entity 'PEPTIDOMIMETICS' named entity 'REPLACEMENT' named entity 'LED' named entity 'BENZOTHIAZOLE' named entity 'LACTAM' named entity 'NANOMOLAR' named entity 'POSITION' named entity 'CONTAINING' named entity 'MOLECULES' named entity 'POTENTIAL' named entity 'TYPE' named entity 'VALUES' named entity 'SARS-COV' named entity 'SYNTHESIS' named entity 'NEW' named entity 'PROTEASE INHIBITORS' named entity 'MOIETY' named entity 'IDENTIFICATION' named entity 'STEREOCHEMISTRY' named entity 'HYDROGEN BONDING' named entity 'CONFORMATION' named entity '3.1' named entity 'DESIGN' named entity 'STRUCTURAL' named entity 'INCLUDING' named entity 'MOIETY' named entity 'BIOLOGICAL EVALUATION' named entity 'LEAD COMPOUND' named entity 'DESCRIBE' named entity 'FOLDING' named entity 'HERE' named entity 'SARS-COV' named entity '28I' named entity 'INHIBITORY' named entity 'SITE' named entity 'INITIAL' named entity 'PARTICULAR' named entity 'UNIT' named entity 'INHIBITORS' named entity 'PRO' named entity 'SYNTHESIS' named entity 'HYDROPHOBIC' named entity 'INVOLVING'

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