About: Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies

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About: Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies
Creator	Chen, Shen-En Akaji, Kenichi Freire, Ernesto Hayashi, Yoshio Koiwai, Yuji Konno, Sho Naser-Tavakolian, Aurash Schön, Arne Taguchi, Akihiro Takayama, Kentaro Thanigaimalai, Pillaiyar Yakushiji, Fumika Yamamoto, Takehito
Source	Elsevier; Medline; PMC
abstract	Abstract We report the design and synthesis of a series of dipeptide-type inhibitors with novel P3 scaffolds that display potent inhibitory activity against SARS-CoV 3CLpro. A docking study involving binding between the dipeptidic lead compound 4 and 3CLpro suggested the modification of a structurally flexible P3 N-(3-methoxyphenyl)glycine with various rigid P3 moieties in 4. The modifications led to the identification of several potent derivatives, including 5c–k and 5n with the inhibitory activities (K i or IC50) in the submicromolar to nanomolar range. Compound 5h, in particular, displayed the most potent inhibitory activity, with a K i value of 0.006 μM. This potency was 65-fold higher than the potency of the lead compound 4 (K i = 0.39 μM). In addition, the K i value of 5h was in very good agreement with the binding affinity (16 nM) observed in isothermal titration calorimetry (ITC). A SAR study around the P3 group in the lead 4 led to the identification of a rigid indole-2-carbonyl unit as one of the best P3 moieties (5c). Further optimization showed that a methoxy substitution at the 4-position on the indole unit was highly favorable for enhancing the inhibitory potency.
has issue date	2013-10-31(xsd:dateTime)
bibo:doi	10.1016/j.ejmech.2013.07.037
bibo:pmid	23994330
has license	els-covid
sha1sum (hex)	a2c3b7432fa3849f33885eaa61bf78bd67bba6bc
schema:url	https://doi.org/10.1016/j.ejmech.2013.07.037
resource representing a document's title	Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies
has PubMed Central identifier	PMC7115411
has PubMed identifier	23994330
schema:publication	European Journal of Medicinal Chemistry
resource representing a document's body	covid:a2c3b7432fa3849f33885eaa61bf78bd67bba6bc#body_text
is schema:about of	named entity 'isothermal titration calorimetry' named entity 'indole' named entity 'potency' named entity 'derivatives' named entity 'METHOXY' named entity 'ISOTHERMAL TITRATION CALORIMETRY' named entity 'FOLD' named entity 'LEAD COMPOUND' named entity 'LEAD' named entity 'UNIT' named entity 'STUDY' named entity 'ENHANCING' named entity 'OPTIMIZATION' named entity 'VARIOUS' covid:arg/a2c3b7432fa3849f33885eaa61bf78bd67bba6bc named entity 'INCLUDING' named entity 'ADDITION' named entity 'OBSERVED' named entity 'TYPE' named entity 'COMPOUND' named entity 'BINDING' named entity 'POTENCY' named entity 'DISPLAY' named entity 'SAR' named entity 'SARS-COV' named entity 'NOVEL' named entity 'AGREEMENT' named entity 'MODIFICATION' named entity 'DOCKING' named entity 'BEST' named entity 'FLEXIBLE' named entity 'PRO' named entity 'GROUP' named entity 'PARTICULAR' named entity 'SCAFFOLDS' named entity 'DESIGN' named entity 'LED' named entity 'BINDING AFFINITY' named entity 'POSITION' named entity 'SERIES' named entity 'SYNTHESIS' named entity 'ARTICLE' named entity 'ORIGINAL' named entity 'DIPEPTIDE' named entity 'INHIBITORY ACTIVITY' named entity 'CARBONYL' named entity 'INDOLE' named entity 'HIGHER' named entity 'INVOLVING' named entity 'REPORT' named entity 'INHIBITORS' named entity 'NANOMOLAR' named entity 'ACTIVITIES' named entity 'VERY GOOD' named entity 'RANGE' named entity 'VALUE' named entity 'SUBSTITUTION' named entity 'INHIBITORY' named entity 'IDENTIFICATION' named entity 'FAVORABLE' named entity 'RIGID' named entity 'ONE OF' named entity 'potent' named entity 'carbonyl' named entity 'inhibitory' named entity '4-position' named entity 'lead compound' named entity 'highly' named entity 'led'

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