1628047-84-6

Usage

Uses

1. Pharmaceutical Industry:
tert-butyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-bromobenzoate is used as an intermediate in the synthesis of apoptosis-inducing agents for the development of anticancer drugs. Its application is particularly relevant in the production of Venetoclax (A112430), a potent and selective BCL-2 inhibitor. Venetoclax demonstrates significant antitumor activity while sparing platelets, making it a valuable addition to cancer treatment options.
2. Oncology Research:
In the field of oncology, tert-butyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-bromobenzoate is used as a key component in the development of novel therapeutic strategies targeting cancer cell apoptosis. Its role in the synthesis of BCL-2 inhibitors highlights its potential in contributing to the advancement of cancer treatment and improving patient outcomes.
3. Drug Development:
As a chemical intermediate, tert-butyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-bromobenzoate plays a vital role in the drug development process. Its unique structure and properties make it a valuable building block for the creation of new and innovative pharmaceutical compounds with potential applications in various therapeutic areas, including oncology.

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 105931-73-5 1-bromo-3-fluoro-4-iodobenzene 
• 98549-88-3 5-hydroxypyrrolo[2,3-b]pyridine 
• 889858-12-2 4-bromo-2-fluoro-benzoic acid tert-butyl ester 

Downstream Products

• 1235865-77-6 [2-((1H-pyrrolo [2,3-b]pyridin-5-yl)oxy)-4-(4-((4’-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1’-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid] 
• 1257044-40-8 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)benzamide 

Relevant academic research and scientific papers

Discovery of potent and selective Bcl-2 inhibitors with acyl sulfonamide skeleton

The antiapoptotic protein B-cell lymphoma 2 (Bcl-2), overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, a series of novel derivatives with acyl sulfonamide skeleton was designed, synthesized, and evaluated as Bcl-2 inhibitors by means of bioisosteric replacement. Among them, compound 24g demonstrated equal efficient inhibition activity against RS4;11 cell line compared to positive control ABT-199. Moreover, it showed improved selectivity for Bcl-2/Bcl-xL inhibitory effects, the result of which was consistent with platelet toxicity studies. In vitro and in vivo pharmacokinetic properties of compound 24g had a significantly improved profiles. Taken together, those results suggested it as a promising candidate for development of novel therapeutics targeting Bcl-2 in cancer.

Venetoclax and dihydroartemisinin compound and preparation method and application thereof

The invention belongs to the technical field of medicines, and relates to a Venetoclax and dihydroartemisinin compound, pharmaceutically acceptable salts, hydrates and optical isomers thereof, a pharmaceutical composition taking the compound as an active component, and an application of the compound in preparation of medicines for treating cancers. The structure of the Venetoclax and dihydroartemisinin compound is as shown in a general formula I in the specification, wherein L is as described in the claims and the specification.

Method for synthesizing key intermediate of venetoclax

The invention relates to the technical field of medicine synthesis, in particular to a method for synthesizing a key intermediate of venetoclax. The method comprises the following steps: with 4-bromo-2-fluorobenzoic acid (I) as a raw material, carrying ou

Development of a Convergent Large-Scale Synthesis for Venetoclax, a First-in-Class BCL-2 Selective Inhibitor

The process development of a new synthetic route leading to an efficient and robust synthetic process for venetoclax (1: the active pharmaceutical ingredient (API) in Venclexta) is described. The redesigned synthesis features a Buchwald-Hartwig amination to construct the core ester 23c in a convergent fashion by connecting two key building blocks (4c and 26), which is then followed by a uniquely effective saponification reaction of 23c using anhydrous hydroxide generated in situ to obtain 2. Finally, the coupling of the penultimate core acid 2 with sulfonamide 3 furnishes drug substance 1 with consistently high quality. The challenges and solutions for the key Pd-catalyzed C-N cross-coupling will also be discussed in detail. The improved synthesis overcomes many of the initial scale-up challenges and was accomplished in 46% overall yield from 3,3-dimethyldicyclohexanone (6), more than doubling the overall yield of the first generation route. The new process was successfully implemented for producing large quantities of 1 with >99% area purity.

Bcl-2 INHIBITORS

Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases including cancers and treating autoimmune disease, and a pharmaceutical composition comprising the same.

SOLID STATE FORMS OF VENETOCLAX AND PROCESSES FOR PREPARATION OF VENETOCLAX

Solid state forms of Venetoclax, pharmaceutical compositions thereof, and uses thereof are disclosed. Also disclosed are processes for the preparation of Venetoclax.

Processes For The Preparation Of An Apoptosis-Inducing Agent

Provided herein is a process for the preparation of an apoptosis-inducing agent, and chemical intermediates thereof. Also provided herein are novel chemical intermediates related to the process provided herein.