To determine the maximum tolerated dose of CI-1012 in late-stage HIV-1-infected patients. To determine the antiretroviral activity of CI-1012 when added to combination therapy. To assess the multiple-dose pharmacokinetic characteristics of CT-1012 when added to combination therapy. To assess the effect of CI-1012 on the pharmacokinetics of other antiretroviral agents.

Start Date-

Sponsor / Collaborator

Parke-Davis & Co. Ltd.

NCT00002196 / CompletedPhase 1

A Phase I Multiple Oral, Rising-Dose, Tolerance and Pharmacokinetic Trial of CI-1012 in HIV-1-Infected Volunteers.

The purpose of this study is to see if it is safe and effective to give CI-1012 to HIV-infected patients who do not have any symptoms of the disease. This study also examines how the body handles CI-1012.

Start Date-

Sponsor / Collaborator

Parke-Davis & Co. Ltd.

100 Clinical Results associated with CI-1012

100 Translational Medicine associated with CI-1012

100 Patents (Medical) associated with CI-1012

Literatures (Medical) associated with CI-1012

01 Feb 2001·Antiviral ResearchQ2 · MEDICINE

Inhibition of the early phase of HIV replication by an isothiazolone, PD 161374

Q2 · MEDICINE

Article

Author: Rocco Gogliotti ; Thomas McQuade ; Stephen Gracheck ; Lamia Sharmeen ; Andrea Heldsinger ; John Domagala

A new class of substituted 2'-benzisothiazolone represented by PD 161374 was discovered with antiviral activity against retroviruses similar to previously described nucleocapsid inhibitor PD 159206 (DIBA-4). In T cell culture, the 50% inhibitory concentrations (EC(50)) of PD 161374 and PD 159206 were on average 2.5 microM (ranges of 1.2-13.5 microM) without any cytotoxic effect up to 100 microM. PD 161374 inhibited acute HIV infection and it was effective when added during the early phase of HIV infection. However, very modest effects were observed in chronically infected H9 cells and the HIV latency model line OM-10.1. Direct PCR analysis of infected cells demonstrated that PD 161374 delayed the appearance of completed HIV-cDNA products including 2LTR circles. Together all these results suggest that PD 161374 exerts its antiviral effect at pre-integration steps in the early phase of the virus life cycle. When combined with a protease inhibitor, PD 161374 did not show any antagonism and combination with a reverse transcriptase inhibitor (AZT) resulted in a synergistic effect.

01 May 1997·Drug design and discovery

2,2'-Dithiobisbenzamides and 2-benzisothiazolones, two new classes of antiretroviral agents: SAR and mechanistic considerations.

Article

Author: Mack, D ; Gogliotti, R ; Tummino, P ; Song, Y ; McQuade, T ; Musa, K ; Sanchez, J P ; Loo, J ; Hupe, D ; Harvey, P ; Reily, M ; Sharmeen, L ; Scholten, J ; Stier, M A ; Saunders, J ; Domagala, J M

Substituted 2,2'-dithiobisbenzamides and 2-benzisothiazolones were prepared and shown to possess low microM activity with high therapeutic indices against HIV-1, HIV-2 and SIV in cell culture. The mechanism of antiviral action was determined to be directed toward the nucleocapsid protein (NCp7), which contains two zinc fingers and plays vital roles in the viral life cycle. The "active sulfides" of this study cause the extrusion of zinc from these zinc fingers. Structure-activity relationships of the 2,2'-dithiobisbenzamides reveal that the disulfide bond and the ortho benzamide functional groups are essential for activity, with the best compounds having a carboxylic acid, carboxamide, or sulfonamide substituent. The 2-benzisothiazolones are formed from the disulfides both chemically and in vivo and their SAR mimics that of the 2,2'-dithiobisbenzamides. The antiviral activity of the disulfides may require cyclization to the isothiazolones. Two agents, PD 159206 and PD 161374, which showed good antiviral activity, physical properties, and excellent pharmacokinetics in mice, were selected for advanced studies.

100 Deals associated with CI-1012

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Phase 2	US	National Institutes of Health	-
HIV Infections	Phase 2	US	Pfizer Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis