Author: Kanojia, Ramesh M. ; Moore, John B. Jr. ; Williams, Louella ; Falotico, Robert ; Tobia, Alfonso J. ; McNally, James J. ; Press, Jeffery B. ; Lever, O. William Jr.

A series of isoquinolin-3-ol derivatives (II) was prepared as analogues of the clinical cardiotonic agent bemarinone (ORF 16600, I). Although in many respects the structural requirements for the cardiotonic activity of II are similar to those of bemarinone, certain differences between the series were noted. Our structure-activity studies show that II is less sensitive to alkoxy-substitution effects than is I, and more significantly, 4-substitution of II by alkyl groups, halogen, or alkanecarboxylic acid derivatives enhances cardiotonic activity in II in contrast to I, wherein analogous substitution eliminated activity. A linear correlation between contractile force (CF) increase and cyclic nucleotide phosphodiesterase fraction III (PDE-III) inhibition by the title compounds was determined. The isoquinoline derivatives were characteristically short-acting cardiotonic agents with good potency and selectivity.

01 Aug 1987·Journal of Medicinal ChemistryQ1 · MEDICINE

Synthesis and cardiotonic activity of a series of substituted 4-alkyl-2(1H)-quinazolinones

Q1 · MEDICINE

Article

Author: Bandurco, Victor T. ; Reed, Marianne S. ; Kanojia, Ramesh M. ; Levine, Seymour D. ; Mulvey, Dennis M. ; Bell, Stanley C. ; Schwender, Charles F. ; Combs, Donald W. ; Appollina, Mary A.

The synthesis, cardiac fraction III cyclic nucleotide phosphodiesterase (PDE-III) inhibition, and positive inotropic activity of a series of 2(1H)-quinazolinones are reported. A general synthesis of the series involved the cyclization of 2-aminoacetophenones with potassium cyanate in acetic acid. Modifications at the 4-position of the quinazoline nucleus were best achieved by formation of the intermediate N1-acyl-N3-phenylurea from the substituted phenyl isocyanate and appropriate carboxamide. PPA was used to ring close to the quinazoline product. Generally the SAR for the series paralleled the five-point model previously published for PDE-III inhibition. The most active analogue of the series was 5,6-dimethoxy-4-methyl-2(1H)-quinazolinone (1) (ORF 16600), which had about twice the intravenous potency of amrinone. Compound 1 is currently under development as an orally active cardiotonic.

100 Deals associated with Bemarinone hydrochloride

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Heart Failure	Phase 1	-	Johnson & Johnson	-

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

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

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


No Data

Bemarinone hydrochloride

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation