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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H11FN5O5P
Molecular Weight 331.197
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GS-9148

SMILES

NC1=C2N=CN([C@@H]3O[C@H](OCP(O)(O)=O)C=C3F)C2=NC=N1

InChI

InChIKey=MPSGQQOHTJUJKB-QUBYGPBYSA-N
InChI=1S/C10H11FN5O5P/c11-5-1-6(20-4-22(17,18)19)21-10(5)16-3-15-7-8(12)13-2-14-9(7)16/h1-3,6,10H,4H2,(H2,12,13,14)(H2,17,18,19)/t6-,10+/m0/s1

HIDE SMILES / InChI

Molecular Formula C10H11FN5O5P
Molecular Weight 331.197
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Approval Year

PubMed

PubMed

TitleDatePubMed
Design and profiling of GS-9148, a novel nucleotide analog active against nucleoside-resistant variants of human immunodeficiency virus type 1, and its orally bioavailable phosphonoamidate prodrug, GS-9131.
2008 Feb
Patents
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:32:30 GMT 2023
Edited
by admin
on Sat Dec 16 11:32:30 GMT 2023
Record UNII
A8OH1KW2TZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GS-9148
Code English
PHOSPHONIC ACID, ((((2R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-FLUORO-2,5-DIHYDRO-2-FURANYL)OXY)METHYL)-
Systematic Name English
PHOSPHONIC ACID, P-((((2R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-FLUORO-2,5-DIHYDRO-2-FURANYL)OXY)METHYL)-
Systematic Name English
GS9148
Code English
Code System Code Type Description
CAS
875608-25-6
Created by admin on Sat Dec 16 11:32:30 GMT 2023 , Edited by admin on Sat Dec 16 11:32:30 GMT 2023
PRIMARY
FDA UNII
A8OH1KW2TZ
Created by admin on Sat Dec 16 11:32:30 GMT 2023 , Edited by admin on Sat Dec 16 11:32:30 GMT 2023
PRIMARY
PUBCHEM
15958718
Created by admin on Sat Dec 16 11:32:30 GMT 2023 , Edited by admin on Sat Dec 16 11:32:30 GMT 2023
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
In another program, a novel nucleotide analog, phosphonomethoxy-2'-fluoro-2', 3'-dideoxydidehydroadenosine (GS-9148), was selected as an NRTI with an improved pharmacological and resistance profile. The prodrug of GS-9148 (GS-9131) exhibits potent antiretroviral activity both in primary cells and T-cell lines (EC50 = 25-200 nM), low cytotoxicity (CC50 > 50 iM) in multiple cell types, and shows no effect on mitochondrial DNA or lactate production in HepG2 cells. In phenotypic assays, the activity of GS-9148 was not affected by the K65R, L74V, or M184V mutations in RT (EC50 fold change <1). Viruses with 4 or more thymidine analog mutations showed 0.74 to 2.0-fold change in the susceptibility, a shift that was smaller than that of any other tested NRTI. Passage of HIV-1 in the presence of GS-9148 selected for a primary K70E mutation and two other RT mutations that together conferred <3-fold resistance to GS-9148.
Related Record Type Details
ACTIVE MOIETY