Cyclic GMP phosphodiesterase inhibitors. 2. Requirement of 6-substitution of quinazoline derivatives for potent and selective inhibitory activity.

doi:10.1021/JM00039A024

Paper

Cyclic GMP phosphodiesterase inhibitors. 2. Requirement of 6-substitution of quinazoline derivatives for potent and selective inhibitory activity.

Published Jun 24, 1994 · Y. Takase, T. Saeki, N. Watanabe

Journal of medicinal chemistry

Q1 SJR score

95

Citations

3

Influential Citations

Full textSemantic Scholar

Abstract

We synthesized various 4-[[3,4-(methylenedioxy)benzyl]amino]quinazolines substituted at the 5- to 8-positions and evaluated their inhibitory activities toward cyclic GMP phosphodiesterase (cGMP-PDE) from porcine aorta. Monosubstitution at the 6-position was essential for the inhibitory activity, and the preferred substituents were compact and hydrophobic: methoxy (3b, IC50 = 0.23 microM), methyl (3c, 0.10 microM), chloro (3d, 0.019 microM), thiomethyl (3f, 0.031 microM), and cyano (3p, 0.090 microM) groups. Compounds 3b-d,f,p lacked inhibitory activity toward other PDE isozymes (all IC50 values > 100 microM), and their relaxing activities in porcine coronary arteries were well correlated with the inhibitory activities toward cGMP-PDE (r = 0.88, p < 0.05). One of these compounds, 3b, elevated the intracellular cGMP level in isolated porcine coronary arteries without causing any change in the cAMP level. We consider that this series of compounds dilates coronary arteries via potent and specific inhibition of cGMP-PDE.

In Vitro Study

Highly Cited

Study Snapshot

6-substitution of quinazoline derivatives is essential for potent and selective inhibition of cGMP-PDE, which dilates coronary arteries and acts as a selective cGMP-PDE inhibitor.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Sign up to use Study Snapshot

Consensus is limited without an account. Create an account or sign in to get more searches and use the Study Snapshot.

Create an account

Paper

Cyclic GMP phosphodiesterase inhibitors. 2. Requirement of 6-substitution of quinazoline derivatives for potent and selective inhibitory activity.

Sign up to use Study Snapshot

References

Citations

Quinazoline scaffold as a target for combating microbial resistance: Synthesis and antimicrobial profiling of quinazoline derivatives

Quinazoline derivatives show potential as antimicrobial agents against drug-resistant pathogens, offering a promising avenue for developing novel antibiotics.

Role of autophagy and proteostasis in neurodegenerative diseases: Exploring the therapeutic interventions

Targeting autophagy and proteostasis may help mitigate neurodegenerative diseases by preventing protein accumulation and maintaining cellular health.

One pot facile visible-light promoted synthesis of quinazolinones via Csp3-H oxidation in aqueous media

This study demonstrates a one-pot, solar-powered method for efficient, sustainable synthesis of quinazolinones in aqueous media, with high to excellent yields and a wide substrate scope.

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

PDE5 inhibitors show promise as disease-modifying agents, with recent advances in allosteric inhibitors offering unprecedented selectivity and potential for diverse therapeutic applications.

[Formulation Studies and Application of Their Experimental Techniques to Drug Discoveries].

This research demonstrates the potential of a competing agent to improve bioavailability of drugs, leading to the discovery of a phosphodiesterase type 5 inhibitor and various other pharmaceutical products.

Visible-light promoted catalyst-free (VLCF) multi-component synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids: evaluation of in vitro anticancer activity, molecular docking, MD simulation and DFT studies

Visible-light-promoted catalyst-free synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids shows promising anticancer activity and potential for clinical trials.

Identification of a novel ALDH1A3‐selective inhibitor by a chemical probe with unrelated bioactivity: An approach to affinity‐based drug target discovery

Affinity-based binder identification identified a novel ALDH1A3-selective inhibitor, providing insights for novel drug discovery and cancer stem cell targeting.

Computational design, synthesis and biological evaluation of PDE5 inhibitors based on N2,N4-diaminoquinazoline and N2,N6-diaminopurine scaffolds.

This study identified 25 new PDE5 inhibitors with a PDE5 IC50 of 0.15 M and improved solubility, validating our computationally driven approach.