1008451-58-8

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-2-Methoxynicotinaldehyde is used as a reactant for the preparation of insulin-like growth factor 1 receptor (IGF-1R) inhibitors, specifically GTx-134. 4-Chloro-2-Methoxynicotinaldehyde plays a crucial role in the development of novel therapeutic agents targeting IGF-1R, which is implicated in various cancers and has potential applications in the treatment of these diseases.
The IGF-1R inhibitors, such as GTx-134, are designed to modulate the IGF-1R signaling pathway, which is often dysregulated in cancer cells, leading to uncontrolled cell growth and proliferation. By targeting this pathway, 4-Chloro-2-Methoxynicotinaldehyde contributes to the development of innovative cancer treatments that can potentially improve patient outcomes and survival rates.

Upstream product

• 72141-44-7 4-chloro-2-methoxypyridine 
• 109-72-8 n-butyllithium 
• 107-31-3 Methyl formate 
• 108-18-9 diisopropylamine 
• 68-12-2 N,N-dimethyl-formamide 
• 64-17-5 ethanol 
• 140-29-4 phenylacetonitrile 

Downstream Products

• 1823-00-3 3-benzyl-5-trichloromethyl-[1,2,4]oxadiazole 

Relevant academic research and scientific papers

Development of a Stereoselective and Scalable Synthesis for the Potent Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor, BMT-297376; N-((R)-1-((cis)-4-(3-(Difluoromethyl)-2-methoxypyridin-4-yl)cyclohexyl)propyl)-6-methoxynicotinamide

The current work describes a stereoselective and scalable route to N-((R)-1-((cis)-4-(3-(difluoromethyl)-2-methoxypyridin-4-yl)cyclohexyl)propyl)-6-methoxynicotinamide (1) from readily available 1,4-dioxaspiro[4.5]decan-8-one. The developed process encompasses an efficient 1,4-trans-selective synthesis of (trans)-4-(3-(difluoromethyl)-2-methoxypyridin-4-yl)cyclohexyl methanesulfonate as the key intermediate and the use of Ellman sulfinamine methodology to install an alkyl amine in a stereoselective manner. Various synthetic routes were screened to accomplish a stereoselective and scalable protocol to access the title compound (1). This advancement enabled a competent route to the title compound in an enantioselective, safe, cost-effective, and scalable manner.

Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors

IDO1 inhibitors have shown promise as immunotherapies for the treatment of a variety of cancers, including metastatic melanoma and renal cell carcinoma. We recently reported the identification of several novel heme-displacing IDO1 inhibitors, including the clinical molecules linrodostat (BMS-986205) and BMS-986242. Both molecules contain quinolines that, while being present in successful medicines, are known to be potentially susceptible to oxidative metabolism. Efforts to swap this quinoline with an alternative aromatic system led to the discovery of 2,3-disubstituted pyridines as suitable replacements. Further optimization, which included lowering ClogP in combination with strategic fluorine incorporation, led to the discovery of compound 29, a potent, selective IDO1 inhibitor with robust pharmacodynamic activity in a mouse xenograft model.

INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.

DERIVATIVES OF OXADIAZOLE AND PYRIDAZINE, THEIR PREPARATION AND THEIR APPLICATION IN THERAPEUTICS

The invention relates to compounds of formula (I): in which: n is equal to 0 or 1; D represents an oxygen atom or a bond; W represents a nitrogen atom or a -CH- group; X1 represents a nitrogen atom or a -CH=CH- group; X2 represents an oxygen atom or a nitrogen atom; X3 represents an oxygen atom or a nitrogen atom; one of X1, X2, X3 being other than a nitrogen atom, X2 and X3 not being an oxygen atom at the same time; R1, R2 are absent or represent, (i) independently of one another, a hydrogen atom or a (C1 -C4)alkyl group, (ii) R1 and R2 may form, with the carbon atom to which they are attached, a -(C3-C10)cycloalkyl- group; Y represents a -(C3-C10)cycloalkyl-, aryl or aryloxy group, said groups being optionally substituted with one or more substituents chosen from a halogen atom or a (C1 -C6)alkoxy group; Z1 is absent or represents an -NH- function; Z2 and Z3 are as defined in the description. The invention also relates to a process for preparing compounds of formula (I), compositions containing them and their application in therapeutics.