870281-85-9

Usage

Uses

Used in Pharmaceutical Industry:
(S)-tert-butyl (1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbaMate is used as a reagent for the discovery of phosphoinositide 3-kinase (PI3K) b/d inhibitors. These inhibitors are of significant interest for the treatment of phosphatase and tensin homolog (PTEN) deficient tumors, as they can help regulate the PI3K/AKT/mTOR signaling pathway, which is often dysregulated in cancer cells. By targeting this pathway, (S)-tert-butyl (1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbaMate contributes to the development of novel therapeutic agents for cancer treatment.

Upstream product

• 62-53-3 aniline 
• 870281-83-7 2-fluoro-6-nitro-N-phenyl-benzamide 
• 45121-22-0 Boc-D-Abu 
• 385-02-4 6-fluoro-2-nitrobenzoic acid 
• 24424-99-5 di-tert-butyl dicarbonate 
• 34306-42-8 Boc-Abu 
• 7304-32-7 2-fluoro-5-nitrobenzoic acid 
• 434-76-4 2-amino-6-fluorobenzoic acid 
• 1417456-04-2 2-amino-6-fluoro-N-phenyl-benzamide 
• 78755-94-9 5-fluoro-2H-benzo[d][1,3]-oxazine-2,4(1H)-dione 
• 870281-84-8 (S)-[1-(2-fluoro-6-nitro-benzoy)phenylaminocarbonyl]propyl carbamic acid tert-butyl ester 

Downstream Products

• 870281-86-0 (S)-2-(1-((9H-purin-6-yl-2,8-d2)amino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one 
• 870281-82-6 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-3,4-dihydroquinazolin-4-one 

Relevant academic research and scientific papers

Construction of N-Boc-2-Alkylaminoquinazolin-4(3H)-Ones via a Three-Component, One-Pot Protocol Mediated by Copper(II) Chloride that Spares Enantiomeric Purity

Chiral 2-alkylquinazolinones are key synthetic intermediates, but their preparation in high optical purity is challenging. Thus, a multicomponent procedure integrating anthranilic acids, N-Boc-amino acids, and amines in the presence of methanesulfonyl chl

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.

A novel strategy for the manufacture of idelalisib: Controlling the formation of an enantiomer

A novel and scalable synthesis of 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone, idelalisib 1, has been developed. This strategy controls the desfluoro impurity of 13 during reduction of nitro intermediate 4, and also arrests the formation of the enantiomer during cyclisation of diamide 17, without affecting the neighbouring chiral centre. This process is demonstrated on a larger scale in the laboratory and achieved good chemical and chiral purities coupled with good yields.

HETEROARYL DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSTION FOR PREVENTING OR TREATING DISEASES ASSOCIATED WITH PI3 KINASES, CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a heteroaryl derivative or a pharmaceutically acceptable salt thereof, a preparation method therefor, and a pharmaceutical composition for preventing or treating diseases associated with PI3 kinases, containing the same as an active ingredient. The heteroaryl derivative according to the present invention has an excellent effect of selectively inhibiting PI3 kinases, thereby being useful in preventing or treating PI3 kinase diseases such as: cancers, autoimmune diseases, and respiratory diseases.

A preparation method of generation of ralli department intermediates (by machine translation)

The invention discloses a method for the preparation of generation of ralli department, aniline, N - Boc - L - 2 - aminobutyric acid, DCC, triethylamine, 2 - fluoro - 5 - nitrophenyl chloride as the raw material, through the condensation reaction, the ami

Substituted aminopyrimidine compounds and their method and use thereof

The invention relates to a new aminopyrimidine compound and an application thereof as a drug for treating disorder or diseases related to PI3-kinase abnormity in a free form or a pharmaceutically acceptable salt and preparation form. The invention also relates to a pharmaceutical composition which contains the new aminopyrimidine compound and an application of the pharmaceutical composition in treating mammal disorder or diseases and especially treating human disorder or diseases related to the PI3-kinase abnormity, such as treatment of immunity and inflammatory diseases of PI3-kinase regulation which plays a leading role in a leucocyte function and treatment of proliferative diseases which are related to PI3-kinase activity and include but not limited to leukaemia and solid tumor.

Discovery of a Phosphoinositide 3-Kinase (PI3K) β/δ Inhibitor for the Treatment of Phosphatase and Tensin Homolog (PTEN) Deficient Tumors: Building PI3Kβ Potency in a PI3Kδ-Selective Template by Targeting Nonconserved Asp856

Phosphoinositide 3-kinase (PI3K) β signaling is required to sustain cancer cell growth in which the tumor suppressor phosphatase and tensin homolog (PTEN) has been deactivated. This manuscript describes the discovery, optimization, and in vivo evaluation

Preparation method of Idelalisib intermediate

The invention relates to a preparation method of an Idelalisib intermediate. The method is a novel method for preparing a tert-butyl (S)-(1-(5-fluoro-4-carbonyl-3-phenyl-3, 4-dihydroquinazolin-2-yl)propyl)carbamate. The preparation method has the advantages of simple reaction steps, high yield, high optical purity and mass production.

Preparation method of (S)-2-(1-amino-propyl)-5-fluoro-3-phenyl-3H-quinazoline-4-one

The invention discloses a preparation method of (S)-2-(1-amino-propyl)-5-fluoro-3-phenyl-3H-quinazoline-4-one. According to the method, a compound represented as a formula (V) is subjected to cyclization under the action of trimethylchlorosilane, (S)-[1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydro-quinazoline-2-yl) propyl]-isobutyl carbamate is obtained and subjected to BOC (t-butyloxycarboryl) de-protection through acid, and a product is obtained. A synthetic route provided by the invention overcomes defects in the prior art, has the advantages of being mild in reaction condition of each step, stable in reaction and high in yield, and is particularly applicable to industrial large-scale production of a key intermediate 6 of Idelalisib.