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Basic Characteristics of Mutations
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Mutation Site
|
G140S |
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Mutation Site Sentence
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The [3.2.2]-bridged tricyclic system was identified as an advantageous chemotype, with representatives exhibiting excellent antiviral activity against both wild-type viruses and the G140S/Q148H resistant virus that arises in response to therapy with raltegravir and elvitegravir. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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IN |
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Standardized Encoding Gene
|
gag-pol:155348
|
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Genotype/Subtype
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HIV-1 |
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Viral Reference
|
-
|
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Functional Impact and Mechanisms
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Disease
|
HIV Infections
|
|
Immune
|
- |
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Target Gene
|
-
|
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Clinical and Epidemiological Correlations
|
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Clinical Information
|
- |
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Treatment
|
raltegravir (RAL);elvitegravir (EVG);INSTIs |
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Location
|
- |
|
Literature Information
|
|
PMID
|
32389483
|
|
Title
|
Design, synthesis and SAR study of bridged tricyclic pyrimidinone carboxamides as HIV-1 integrase inhibitors
|
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Author
|
Patel M,Naidu BN,Dicker I,Higley H,Lin Z,Terry B,Protack T,Krystal M,Jenkins S,Parker D,Panja C,Rampulla R,Mathur A,Meanwell NA,Walker MA
|
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Journal
|
Bioorganic & medicinal chemistry
|
|
Journal Info
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2020 Jul 1;28(13):115541
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Abstract
|
The design, synthesis and structure-activity relationships associated with a series of bridged tricyclic pyrimidinone carboxamides as potent inhibitors of HIV-1 integrase strand transfer are described. Structural modifications to these molecules were made in order to examine the effect on potency towards wild-type and clinically-relevant resistant viruses. The [3.2.2]-bridged tricyclic system was identified as an advantageous chemotype, with representatives exhibiting excellent antiviral activity against both wild-type viruses and the G140S/Q148H resistant virus that arises in response to therapy with raltegravir and elvitegravir.
|
|
Sequence Data
|
-
|