UC-781

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H18ClNO2S
Molecular Weight	335.848
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)=CCOC1=CC(NC(=S)C2=C(C)OC=C2)=CC=C1Cl

InChI

InChIKey=YZHIXLCGPOTQNB-UHFFFAOYSA-N

InChI=1S/C17H18ClNO2S/c1-11(2)6-8-21-16-10-13(4-5-15(16)18)19-17(22)14-7-9-20-12(14)3/h4-7,9-10H,8H2,1-3H3,(H,19,22)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21969851 | https://www.ncbi.nlm.nih.gov/pubmed/22900504 | https://www.ncbi.nlm.nih.gov/pubmed/14693562

N-(4-Chloro-3-((3-Methyl-2-Butenyl)Oxy)Phenyl)-2-Methyl-3-Furancarbothioamide (also known as UC-781) is a thiocarboxanilide non-nucleoside reverse transcriptase inhibitor patented by Uniroyal Chemical Company, Inc. for prevention of HIV transmission. UC-781 is a potent inhibitor of reverse transcriptase-dependent pyrophosphorolysis, and purportedly restores the chain-terminating activity of zidovudine (AZT) against AZT-resistant virus. In clinical trials single and 7-day topical rectal exposure of UC-781 was safe with no significant adverse events, no detected UC-781 plasma drug levels, no significant mucosal changes, and high participant acceptability. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy.

Originator

Approval Year

PubMed

Title	Date	PubMed
Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781.	2008-12	19089644
Preclinical safety assessments of UC781 anti-human immunodeficiency virus topical microbicide formulations.	2007-05	17353240
Slow-, tight-binding HIV-1 reverse transcriptase non-nucleoside inhibitors highly active against drug-resistant mutants.	2007-04	17323401
Pradimicin A, a carbohydrate-binding nonpeptidic lead compound for treatment of infections with viruses with highly glycosylated envelopes, such as human immunodeficiency virus.	2007-01	17050611
In vitro microbicidal activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 against NNRTI-resistant human immunodeficiency virus type 1.	2006-05	16611904
Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase.	2006-02	16298131
Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate and UC781 has synergistic and complementary effects against human immunodeficiency virus type 1 infection.	2005-05	15855503
Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis.	2005-05	15718224
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	15848161
Mannose-specific plant lectins from the Amaryllidaceae family qualify as efficient microbicides for prevention of human immunodeficiency virus infection.	2004-10	15388446
In vitro comparison of topical microbicides for prevention of human immunodeficiency virus type 1 transmission.	2004-10	15388443
A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides.	2004-10	15388420
In vitro evaluation of nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 as human immunodeficiency virus microbicides.	2004-01	14693562
Novel human immunodeficiency virus (HIV) inhibitors that have a dual mode of anti-HIV action.	2003-10	14506017
Inhibition of human immunodeficiency virus by a new class of pyridine oxide derivatives.	2003-09	12937000
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	11384232
Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors.	2000-05	10779379
Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors.	2000-04-10	10777142
Human immunodeficiency virus type 1 reverse transcriptase dimer destabilization by 1-[Spiro[4"-amino-2",2" -dioxo-1",2" -oxathiole-5",3'-[2', 5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]]]-3-ethylthy mine.	2000-02-15	10684624
Unique anti-human immunodeficiency virus activities of the nonnucleoside reverse transcriptase inhibitors calanolide A, costatolide, and dihydrocostatolide.	1999-08	10428899
Crystal structures of HIV-1 reverse transcriptase in complex with carboxanilide derivatives.	1998-10-13	9772165
Preclinical studies on thiocarboxanilide UC-781 as a virucidal agent.	1998-07-09	9677161
A proline-to-histidine substitution at position 225 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) sensitizes HIV-1 RT to BHAP U-90152.	1998-06	9634074
1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitors with anti-HIV-1 activity.	1998-03	9517942
A novel mutation (F227L) arises in the reverse transcriptase of human immunodeficiency virus type 1 on dose-escalating treatment of HIV type 1-infected cell cultures with the nonnucleoside reverse transcriptase inhibitor thiocarboxanilide UC-781.	1998-02-10	9491916
Characteristics of the Pro225His mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase that appears under selective pressure of dose-escalating quinoxaline treatment of HIV-1.	1997-11	9343170
Efficacy, pharmacokinetics, and in vivo antiviral activity of UC781, a highly potent, orally bioavailable nonnucleoside reverse transcriptase inhibitor of HIV type 1.	1997-06-10	9171223
Models which explain the inhibition of reverse transcriptase by HIV-1-specific (thio)carboxanilide derivatives.	1997-05-19	9177293
Highly potent oxathiin carboxanilide derivatives with efficacy against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus isolates.	1997-04	9087499
Chemical barriers to human immunodeficiency virus type 1 (HIV-1) infection: retrovirucidal activity of UC781, a thiocarboxanilide nonnucleoside inhibitor of HIV-1 reverse transcriptase.	1997-04	9060662
Anti-HIV and anti-HBV activity and resistance profile of 2',3'-dideoxy-3'-thiacytidine (3TC) and its arylphosphoramidate derivative CF 1109.	1996-08-14	8753770
Highly favorable antiviral activity and resistance profile of the novel thiocarboxanilide pentenyloxy ether derivatives UC-781 and UC-82 as inhibitors of human immunodeficiency virus type 1 replication.	1996-08	8700148
Identification of novel thiocarboxanilide derivatives that suppress a variety of drug-resistant mutant human immunodeficiency virus type 1 strains at a potency similar to that for wild-type virus.	1996-06	8726019

Patents

Sample Use Guides

In Vivo Use Guide

0.1%, 0.25%

Route of Administration: Topical

Name

Type

Language

UC-781

Common Name

English

NSC-675186

Preferred Name

English

N-(4-CHLORO-3-((3-METHYL-2-BUTENYL)OXY)PHENYL)-2-METHYL-3-FURANCARBOTHIOAMIDE

Systematic Name

English

3-FURANCARBOTHIOAMIDE, N-(4-CHLORO-3-((3-METHYL-2-BUTENYL)OXY)PHENYL)-2-METHYL-

Systematic Name

English

3-FURANCARBOTHIOAMIDE, N-(4-CHLORO-3-((3-METHYL-2-BUTEN-1-YL)OXY)PHENYL)-2-METHYL-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C97453