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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H43N3O8SSi2
Molecular Weight 589.85
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TSAO-T

SMILES

CC1=CN([C@@H]2O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@]3(OS(=O)(=O)C=C3N)[C@H]2O[Si](C)(C)C(C)(C)C)C(=O)NC1=O

InChI

InChIKey=YMSLYTIPSGCZRM-DSPLJNTKSA-N
InChI=1S/C24H43N3O8SSi2/c1-15-12-27(21(29)26-19(15)28)20-18(34-38(10,11)23(5,6)7)24(16(25)14-36(30,31)35-24)17(33-20)13-32-37(8,9)22(2,3)4/h12,14,17-18,20H,13,25H2,1-11H3,(H,26,28,29)/t17-,18+,20-,24-/m1/s1

HIDE SMILES / InChI
Molecular Formula C24H43N3O8SSi2
Molecular Weight 589.85
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

TSAO-T {[1-[2′,5′-bis-O-(tert-butyldimethyl silyl)-β-D-ribofuranosyl]thymine]-3′-spiro-5′′-(4′′-amino-1′′,2′′-ox-athiole-2′′,2′′-dioxide)} is the prototype of a unique class of NNRTIs (non-nucleoside RT inhibitors) which has structures and mechanism of actions quite distinct from conventional NNRTIs. It was discovered in a collaborative effort between the Instituto de Química Médica, CSIC (Spain) and the Rega Institute for Medical Research, KU (Belgium). TSAO-T is endowed with a potent and specific activity against human immunodeficiency virus (HIV) type 1 and is targeted at the HIV-1 reverse transcriptase (RT). Inhibition of HIV-1 RT by TSAO-T was reversible and noncompetitive. TSAO-T does not act as a DNA chain terminator. It interacts with HIV-1 RT at a nonsubstrate (dNTP)-binding site.

Originator

Approval Year

Unknown
149124
PubMed

PubMed

TitleDatePubMed
Synthesis and anti-HIV1 biological activity of novel 5''-ATSAO compounds.
2008-04-15
Structure-activity relationships of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5' '-(4' '-amino-1' ',2' '-oxathiole-2' ',2' '-dioxide)thymine derivatives as inhibitors of HIV-1 reverse transcriptase dimerization.
2006-08-10
Discovery of TSAO derivatives with an unusual HIV-1 activity/resistance profile.
2006-08
Improving the antiviral efficacy and selectivity of HIV-1 reverse transcriptase inhibitor TSAO-T by the introduction of functional groups at the N-3 position.
2005-10-20
First synthesis and evaluation of the inhibitory effects of aza analogues of TSAO on HIV-1 replication.
2005-06-30
The N137 and P140 amino acids in the p51 and the P95 amino acid in the p66 subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are instrumental to maintain catalytic activity and to design new classes of anti-HIV-1 drugs.
2005-04-25
Novel [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2" -dioxide) derivatives with anti-HIV-1 and anti-human-cytomegalovirus activity.
2005-02-24
Synthesis of 3' '-substituted TSAO derivatives with anti-HIV-1 and anti-HIV-2 activity through an efficient palladium-catalyzed cross-coupling approach.
2002-08-29
Identification of a novel family of nucleosides that specifically inhibit HIV-1 reverse transcriptase.
2001-12-03
Identification of a putative binding site for [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)thymine (TSAO) derivatives at the p51-p66 interface of HIV-1 reverse transcriptase.
2001-06-07
TSAO-T analogues bearing amino acids at position N-3 of thymine: synthesis and anti-human immunodeficiency virus activity.
2000-01
Potential multifunctional inhibitors of HIV-1 reverse transcriptase. Novel [AZT]-[TSAO-T] and [d4T]-[TSAO-T] heterodimers modified in the linker and in the dideoxynucleoside region.
1999-12-16
Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.
1999-08
Abasic analogues of TSAO-T as the first sugar derivatives that specifically inhibit HIV-1 reverse transcriptase.
1998-11-05
Regiospecific synthesis and anti-human immunodeficiency virus activity of novel 5-substituted N-alkylcarbamoyl and N,N-dialkylcarbamoyl 1,2,3-triazole-TSAO analogues.
1998-11
Highly potent oxathiin carboxanilide derivatives with efficacy against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus isolates.
1997-04
Novel L-lyxo and 5'-deoxy-5'-modified TSAO-T analogs: synthesis and anti-HIV-1 activity.
1996-11
Synthesis and anti-HIV-1 activity of novel TSAO-T derivatives modified at the 2'- and 5'-positions of the sugar moiety.
1995-06
Synthesis and anti-HIV activity of [AZT]-[TSAO-T] and [AZT]-[HEPT] dimers as potential multifunctional inhibitors of HIV-1 reverse transcriptase.
1995-05-12
1,2,3-Triazole-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D- ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole 2",2"-dioxide) (TSAO) analogues: synthesis and anti-HIV-1 activity.
1994-11-25
Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants.
1994-07-05
Novel series of TSAO-T derivatives. Synthesis and anti-HIV-1 activity of 4-, 5-, and 6-substituted pyrimidine analogues.
1994-02-18
Human immunodeficiency virus type 1 drug-resistance patterns with different 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives.
1993-10
Human immunodeficiency virus type 1 (HIV-1) strains selected for resistance against the HIV-1-specific [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro- 5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]-beta-D-pentofurano syl (TSAO) nucleoside analogues retain sensitivity to HIV-1-specific nonnucleoside inhibitors.
1993-08-01
HIV-1-specific reverse transcriptase inhibitors show differential activity against HIV-1 mutant strains containing different amino acid substitutions in the reverse transcriptase.
1993-01
Human immunodeficiency virus type 1-specific [2',5'-bis-O-(tert- butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)-purine analogues show a resistance spectrum that is different from that of the human immunodeficiency virus type 1-specific non-nucleoside analogues.
1993-01
TSAO analogues. Stereospecific synthesis and anti-HIV-1 activity of 1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro -5''- (4''-amino-1'',2''-oxathiole 2'',2''-dioxide) pyrimidine and pyrimidine-modified nucleosides.
1992-08-07
3'-Spiro nucleosides, a new class of specific human immunodeficiency virus type 1 inhibitors: synthesis and antiviral activity of [2'-5'-bis-O-(tert-butyldimethylsilyl)-beta-D-xylo- and -ribofuranose]-3'-spiro-5"-[4"-amino-1",2"-oxathiole 2",2"-dioxide] (TSAO) pyrimidine nucleosides.
1992-07-24
Kinetics of inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase by the novel HIV-1-specific nucleoside analogue [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4"-amino-1",2"-oxathiole-2",2"-dioxide)thymine (TSAO-T).
1992-06-15
2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole-2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase.
1992-05-15
[2',5'-Bis-O-(tert-butyldimethylsilyl)]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide) (TSAO) derivatives of purine and pyrimidinenucleosides as potent and selective inhibitors of human immunodeficiency virus type 1.
1992-05

Sample Use Guides

In Vitro Use Guide
TSAO-T was highly inhibitory to HIV-1-induced cytopathicity in MT-4 cells and HIV-1-induced giant cell formation in CEM cells. Its 50% effective concentration was about 0.03 uM in both cell systems. TSAO-T was inhibitory to HIV-1 RT at an IC50 of 17 uM when poly(C) (dG) was used as the template/primer and radiola- beled dGTP as the natural substrate.
Substance Class Chemical
Created
by admin
on Mon Mar 31 19:51:36 GMT 2025
Edited
by admin
on Mon Mar 31 19:51:36 GMT 2025
Record UNII
WF66Y930KH
Record Status Validated (UNII)
Record Version
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Name Type Language
TSAO
Preferred Name English
TSAO-T
Common Name English
2,4(1H,3H)-PYRIMIDINEDIONE, 1-((5R,6R,8R,9R)-4-AMINO-9-(((1,1-DIMETHYLETHYL)DIMETHYLSILYL)OXY)-6-((((1,1-DIMETHYLETHYL)DIMETHYLSILYL)OXY)METHYL)-2,2-DIOXIDO-1,7-DIOXA-2-THIASPIRO(4.4)NON-3-EN-8-YL)-5-METHYL-
Systematic Name English
Code System Code Type Description
FDA UNII
WF66Y930KH
Created by admin on Mon Mar 31 19:51:36 GMT 2025 , Edited by admin on Mon Mar 31 19:51:36 GMT 2025
PRIMARY
CAS
141781-17-1
Created by admin on Mon Mar 31 19:51:36 GMT 2025 , Edited by admin on Mon Mar 31 19:51:36 GMT 2025
PRIMARY
PUBCHEM
65005
Created by admin on Mon Mar 31 19:51:36 GMT 2025 , Edited by admin on Mon Mar 31 19:51:36 GMT 2025
PRIMARY
DAILYMED
WF66Y930KH
Created by admin on Mon Mar 31 19:51:36 GMT 2025 , Edited by admin on Mon Mar 31 19:51:36 GMT 2025
PRIMARY
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Structure of TSAO-T
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