1615255-01-0

Basic information

• Product Name: (S)-tert-butyl (1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)carbamate
• Synonyms: (S)-tert-butyl (1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)carbamate
• CAS NO: 1615255-01-0
• Molecular Weight: 427.931
• Mol File: 1615255-01-0.mol

Chemical Properties

• CAS DataBase Reference: (S)-tert-butyl (1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)carbamate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-tert-butyl (1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)carbamate(1615255-01-0)
• EPA Substance Registry System: (S)-tert-butyl (1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)carbamate(1615255-01-0)

Safety Data

• Hazardous Substances Data: 1615255-01-0(Hazardous Substances Data)

Upstream product

• 13734-41-3 t-Boc-L-valine 
• 2148-56-3 2-chloro-6-aminobenzoic acid 
• 62-53-3 aniline 

Downstream Products

• 1615256-54-6 (S)-2-(1-amino-2-methylpropyl)-5-chloro-3-phenylquinazolin-4(3H)-one 

Relevant articles and documents

Synthesis and biological evaluation of novel purinyl quinazolinone derivatives as PI3Kδ-specific inhibitors for the treatment of hematologic malignancies

Phosphatidylinositol 3-kinases (PI3Ks) mediate intracellular signal transduction. Aberrant PI3K signaling is associated with oncogenesis and disease progression in solid tumors and hematologic malignancies. Idelalisib (1), a first-in-class PI3Kδ inhibitor for the treatment of hematologic malignancies, was developed, but its sales were limited by black box warnings due to unexpected adverse effects. Therefore, to overcome these adverse events, various quinazolinone derivatives were synthesized and evaluated in vitro based on their inhibitory activity against the PI3K enzyme and the viability of cell lines such as MOLT and SUDHL. Among them, 6f (IC50 = 0.39 nM) and 6m (IC50 = 0.09 nM) showed excellent enzyme activity, and 6m displayed an approximately four-fold higher selectivity for PI3Kγ/δ compared with Idelalisib (1). Furthermore, in vivo PK experiments with 6f and 6m revealed that 6f (AUClast = 81.04 h*ng/mL, Cmax = 18.34 ng/mL, Tmax = 0.5 h, t1/2 = 10.2 h in 1 mpk dose) had improved PK compared with 1. Finally, further experiments will be conducted with 6f selected as a candidate, and the potential for it to be developed as a treatment with good efficacy for hematologic malignancies will be determined.

PHOSPHATIDYLINOSITOL 3-KINASE INHIBITORS

The present disclosure provides phosphatidylinositol 3-kinase (PI3K) inhibitors of formula (I), or pharmaceutically acceptable salts thereof, in which n, m, R1, R2, and R3 are as defined herein. These compounds are useful for treatment of conditions mediated by one or more PI3K isoforms, such as PI3Kδ. The present disclosure further provides pharmaceutical compositions that include a compound of formula (I), or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by one or more PI3K isoforms, such as PI3Kδ.