Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues

Z Ye; Y Gao; R K Bakshi; M H Chen; S P Rohrer; S D Feighner; S S Pong; A D Howard; A Blake; E T Birzin; L Locco; R M Parmar; W W Chan; J M Schaeffer; R G Smith; A A Patchett; R P Nargund

doi:10.1016/s0960-894x(99)00584-3

Modeling directed design and biological evaluation of quinazolinones as non-peptidic growth hormone secretagogues

Bioorg Med Chem Lett. 2000 Jan 3;10(1):5-8. doi: 10.1016/s0960-894x(99)00584-3.

Authors

Z Ye¹, Y Gao, R K Bakshi, M H Chen, S P Rohrer, S D Feighner, S S Pong, A D Howard, A Blake, E T Birzin, L Locco, R M Parmar, W W Chan, J M Schaeffer, R G Smith, A A Patchett, R P Nargund

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.

PMID: 10636230
DOI: 10.1016/s0960-894x(99)00584-3

Abstract

Quinazolinone derivatives were synthesized and evaluated as non-peptidic growth hormone secretagogues. Modeling guided design of quinazolinone compound 21 led to a potency enhancement of greater than 200-fold compared to human growth hormone secretagogue affinity of a screening lead 4.

Publication types

Comparative Study

MeSH terms

Animals
Binding Sites
Drug Design*
Human Growth Hormone / metabolism*
Humans
Inhibitory Concentration 50
Kinetics
Models, Molecular
Quinazolines / chemical synthesis*
Quinazolines / chemistry
Quinazolines / metabolism
Quinazolines / pharmacology*
Rats
Receptors, Cell Surface / agonists*
Receptors, Cell Surface / metabolism
Receptors, G-Protein-Coupled*
Receptors, Ghrelin
Secretory Rate / drug effects
Structure-Activity Relationship

Substances

Quinazolines
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Receptors, Ghrelin
Human Growth Hormone