SAQUINAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C38H50N6O5
Molecular Weight	670.8408
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)NC(=O)[C@@H]1C[C@@H]2CCCC[C@@H]2CN1C[C@@H](O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(N)=O)NC(=O)C4=CC=C5C=CC=CC5=N4

InChI

InChIKey=QWAXKHKRTORLEM-UGJKXSETSA-N

InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C38H50N6O5
Molecular Weight	670.8408
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Saquinavir (brand names Invirase and Fortovase) is an antiretroviral drug used together with other medications to treat or prevent HIV/AIDS. Saquinavir is an inhibitor of HIV protease. HIV protease is an enzyme required for the proteolytic cleavage of viral polyprotein precursors into individual functional proteins found in infectious HIV. Saquinavir is a peptide-like substrate analog that binds to the protease active site and inhibits the activity of the enzyme. Saquinavir inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature noninfectious virus particles. The most frequent adverse events with saquinavir in either formulation are mild gastrointestinal symptoms, including diarrhea, nausea, loose stools & abdominal discomfort. Invirase is better tolerated than Fortovase.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 protease 30	Inhibitor 7468	HIV Infection	0.4 nM [IC50]
Protease 7	Inhibitor 7468	HIV Infection	0.4 nM [IC50]
Human immunodeficiency virus type 2 pol protein 2	Inhibitor 7468	HIV Infection	0.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV Infection 19	Primary	Human immunodeficiency virus type 2 pol protein Protease Human immunodeficiency virus type 1 protease	Approved 7883	FORTOVASE

PubMed

Title	Date	PubMed
Saquinavir soft gelatin capsule: a comparative safety review.	2001	11347724
Comparison of P-triglyceride levels among patients with human immunodeficiency virus on randomized treatment with ritonavir, indinavir or ritonavir/saquinavir.	2001	11345223
Generation of a flexible cell line with regulatable, high-level expression of HIV Gag/Pol particles capable of packaging HIV-derived vectors.	2001 Apr	11319923
An open-label randomized trial to evaluate different therapeutic strategies of combination therapy in HIV-1 infection: design, rationale, and methods of the initio trial.	2001 Apr	11306154
Impact of HIV type 1 protease, reverse transcriptase, cleavage site, and p6 mutations on the virological response to quadruple therapy with saquinavir, ritonavir, and two nucleoside analogs.	2001 Apr 10	11350662
Differences in the intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport.	2001 Apr 13	11371681
Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance liquid chromatography.	2001 Apr 13	11355843
Determination of interaction kinetic constants for HIV-1 protease inhibitors using optical biosensor technology.	2001 Apr 15	11401294
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.	2001 Apr 15	11391173
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.	2001 Apr 15	11391165
[Improving the pharmacokinetics of protease inhibitors in a more innovative manner. HIV drugs administered in a more clever way].	2001 Apr 2	11373769
Antiretrovirals: simultaneous determination of five protease inhibitors and three nonnucleoside transcriptase inhibitors in human plasma by a rapid high-performance liquid chromatography--mass spectrometry assay.	2001 Aug	11477320
Pharmacokinetics and resistance mutations affect virologic response to ritonavir/saquinavir-containing regimens.	2001 Aug	11477313
Antiviral drugs: current state of the art.	2001 Aug	11418355
Comparison of virologic, immunologic, and clinical response to five different initial protease inhibitor-containing and nevirapine-containing regimens.	2001 Aug 1	11468423
Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals.	2001 Aug 1	11468422
HIV-protease inhibitors contribute to P-glycoprotein efflux function defect in peripheral blood lymphocytes from HIV-positive patients receiving HAART.	2001 Aug 1	11468419
[Resistance to protease inhibitors].	2001 Feb	11428058
Pharmacology and clinical experience with saquinavir.	2001 Feb	11336588
Large hepatic mitochondrial DNA deletions associated with L-lactic acidosis and highly active antiretroviral therapy.	2001 Feb 16	11273225
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
Synergistic antiviral effect of PEG-asparaginase (ONCASPAR), with protease inhibitor alone and in combination with RT inhibitors against HIV-1 infected T-cells: a model of HIV-1-induced T-cell lymphoma.	2001 Jan-Feb	11286117
Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model.	2001 Jul	11483925
Predictors of protease inhibitor-associated adverse events.	2001 Jul	11478584
HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro.	2001 Jul	11476984
Combination therapy with saquinavir soft gelatin capsules in children with human immunodeficiency virus infection.	2001 Jul	11465838
CMVR diagnoses and progression of CD4 cell counts and HIV viral load measurements in HIV patients on HAART.	2001 Jul	11423459
Capillary electrophoretic separation of protease inhibitors used in human immunodeficiency virus therapy.	2001 Jul 13	11486877
High-performance liquid chromatographic assay to determine the plasma levels of HIV-protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir and saquinavir) and the non-nucleoside reverse transcriptase inhibitor (nevirapine) after liquid-liquid extraction.	2001 Jul 15	11486821
Synthesis of a chiral aziridine derivative as a versatile intermediate for HIV protease inhibitors.	2001 Jul 26	11463313
The effects of antiretroviral protease inhibitors on serum lipid levels in HIV-infected patients.	2001 Jun	11424549
The effect of fluconazole on ritonavir and saquinavir pharmacokinetics in HIV-1-infected individuals.	2001 Jun	11422025
Prognostic factors of combined viral load and CD4+ cell count responses under triple antiretroviral therapy, Aquitaine cohort, 1996-1998.	2001 Jun 1	11404538
Design and synthesis of a conformationally restricted trans peptide isostere based on the bioactive conformations of saquinavir and nelfinavir.	2001 Jun 1	11374993
Selection by AZT and rapid replacement in the absence of drugs of HIV type 1 resistant to multiple nucleoside analogs.	2001 Jun 10	11429122
Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.	2001 Jun 15	11417878
The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design.	2001 Jun 15	11396919
A comprehensive account on the role of efflux transporters in the gastrointestinal absorption of 13 commonly used substrate drugs in humans.	2001 Mar	11396754
Challenges of antiretroviral treatment in transient and drug-using populations: the SUN study.	2001 Mar	11313025
Sequencing of protease inhibitor therapy: insights from an analysis of HIV phenotypic resistance in patients failing protease inhibitors.	2001 Mar 30	11316998
The interaction of saquinavir (soft gelatin capsule) with ketoconazole, erythromycin and rifampicin: comparison of the effect in healthy volunteers and in HIV-infected patients.	2001 May	11417442
Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors.	2001 May	11322888
Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines.	2001 May	11316764
Clinical outcome among HIV-infected patients starting saquinavir hard gel compared to ritonavir or indinavir.	2001 May 25	11399982
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.	2001 May 5	11393736
Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir.	2001 May 7	11337155
[Drug interactions with antiretroviral agents].	2001 May-Jun	11475806
Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro.	2001 Sep	11448730
Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5.	2001 Sep 14	11454872
Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR.	2001 Sep 7	11466304

Patents

Sample Use Guides

In Vivo Use Guide

1000 mg (with ritonavir 100 mg) PO q12hr, or in combination with ritonavir-enhanced lopinavir Treatment-naïve patients: Initial dose: 500 mg PO BID plus ritonavir 100 mg BID x 7 days, THEN increase to 1000mg/100mg PO BID

Route of Administration: Oral

In Vitro Use Guide

In vitro antiviral activity of saquinavir was assessed in lymphoblastoid and monocytic cell lines and in peripheral blood lymphocytes. Saquinavir inhibited HIV activity in both acutely and chronically infected cells. IC50 and IC90 values (50% and 90% inhibitory concentrations) were in the range of 1 to 30 nM and 5 to 80 nM, respectively. In the presence of 40% human serum, the mean IC50 of saquinavir against laboratory strain HIV-1 RF in MT4 cells was 37.7± 5nM representing a 4-fold increase in the IC50 value. In cell culture, saquinavir demonstrated additive to synergistic effects against HIV-1 in combination with reverse transcriptase inhibitors (didanosine, lamivudine, nevirapine, stavudine, zalcitabine and zidovudine) without enhanced cytotoxicity. Saquinavir in combination with the protease inhibitors amprenavir, atazanavir, or lopinavir resulted in synergistic antiviral activity. Saquinavir displayed antiviral activity in vitro against HIV-1 clades A-H (IC50 ranged from 0.9 to 2.5 nM). The IC50 and IC90 values of saquinavir against HIV-2 isolates in vitro ranged from 0.25 nM to 14.6 nM and 4.65 nM to 28.6 nM respectively.

Substance Class	Chemical Created by `admin` on `Mon Oct 21 19:47:03 UTC 2019` Edited by `admin` on `Mon Oct 21 19:47:03 UTC 2019`
Record UNII	L3JE09KZ2F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SAQUINAVIR

Official Name

English

RO 31-8959/000

Code

English

SAQUINAVIR [JAN]

Common Name

English

SAQUINAVIRUM [WHO-IP LATIN]

Common Name

English

SAQUINAVIR [ORANGE BOOK]

Common Name

English

SAQUINAVIR [VANDF]

Common Name

English

SAQUINAVIR [USAN]

Common Name

English

SAQUINAVIR [HSDB]

Common Name

English

RO-31-8959/000

Code

English

BUTANEDIAMIDE, N(SUP 1)-(3-(3-(((1,1-DIMETHYLETHYL)AMINO)CARBONYL)OCTAHYDRO-2(1H)-ISOQUINOLINYL)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-2-((2-QUINOLINYLCARBONYL)AMINO)-, (3S-(2(1R*(R*),2S*),3.ALPHA.,4A.BETA.,8A.BETA.))-

Common Name

English

(S)-N-((IS)-I-((1R)-2-((3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)OCTAHYDRO-2(1H)-ISOQUINOLYL)-1-HYDROXYETHYL)PHENETHYL)-2-QUINALDAMIDOSUCCINAMIDE

Common Name

English

SAQUINAVIR [USP]

Common Name

English

SAQUINAVIR [WHO-IP]

Common Name

English

SAQUINAVIR [WHO-DD]

Common Name

English

SAQUINAVIR [EMA EPAR]

Common Name

English

(S)-N-((.ALPHA.S)-.ALPHA.-((1R)-2-((3S,4AS,8AS)-3-(TERT-BUTYLCARBAMOYL)OCTAHYDRO-2(1H)-ISOQUINOLYL)-1-HYDROXYETHYL)PHENETHYL)-2-QUINALDAMIDOSUCCINAMIDE

Common Name

English

SAQUINAVIR [INN]

Common Name

English

SAQUINAVIR [MART.]

Common Name

English

SCH-52852

Code

English

SAQUINAVIR [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175889