1402838-08-7

Usage

Uses

Used in Pharmaceutical Industry:
2-(1-trityl-1H-imidazol-4-yl)benzaldehyde is used as an intermediate in the synthesis of NLG919-d10 (N630002) for the development of potent indoleamine-2,3-dioxygenase (IDO) pathway inhibitors. These inhibitors are crucial in the treatment of immunosuppression associated with cancer, as they help modulate the immune response and improve the effectiveness of cancer therapies.
Used in Cancer Treatment:
2-(1-trityl-1H-imidazol-4-yl)benzaldehyde is used as a key component in the creation of IDO pathway inhibitors, which are essential for the treatment of various types of cancer. By targeting the IDO pathway, these inhibitors can help reduce immunosuppression and enhance the body's ability to fight cancer cells, leading to improved treatment outcomes for patients.
Used in Research and Development:
2-(1-trityl-1H-imidazol-4-yl)benzaldehyde is also used in research and development for the study of the IDO pathway and its role in cancer immunosuppression. 2-(1-trityl-1H-imidazol-4-yl)benzaldehyde can be utilized in the design and synthesis of new IDO inhibitors, contributing to the advancement of cancer treatment strategies and the development of more effective therapies.

Upstream product

• 40138-16-7 2-formylbenzene boronic acid 
• 87941-55-7 4-bromo-1-(triphenylmethyl)-1H-imidazole 
• 76-83-5 trityl chloride 
• 96797-15-8 N-trityl-4⁽⁵⁾-iodoimidazole 

Downstream Products

• 1402836-61-6 2-(5H-imidazo[5,1-α]isoindol-5-yl)-1-(2-nitrophenyl)ethanone 
• 1402838-89-4 rac-1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanone 
• 1402836-79-6 (Z)-1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethan-1-one oxime 
• 1029684-41-0 2-(1H-imidazol-4⁽⁵⁾-yl)benzaldehyde 

Relevant academic research and scientific papers

Preparation method of (2-(1H-imidazole-4-yl)phenyl)methanol

The invention belongs to the technical field of medicinal chemistry, and particularly discloses a preparation method of (2-(1H-imidazole-4-yl)phenyl)methanol. Amino of 4-iodine-1H-imidazole is protected by a triphenylmethyl protecting group and reacts wit

Design and synthesis of indoleamine 2,3-dioxygenase 1 inhibitors and evaluation of their use as anti-tumor agents

Indoleamine 2,3-dioxygenase (IDO) 1 is the key enzyme for regulating tryptophan metabolism and is an important target for interrupting tumor immune escape. In this study, we designed four series of compounds as potential IDO1 inhibitors by attaching various fragments or ligands to indole or phenylimidazole scaffolds to improve binding to IDO1. The compounds were synthesized and their inhibitory activities against IDO1 and tryptophan 2,3-dioxygenase were evaluated. The cytotoxicities of the compounds against two tumor cell lines were also determined. Two compounds with a phenylimidazole scaffold (DX-03-12 and DX-03-13) showed potent IDO1 inhibition with IC50 values of 0.3–0.5 μM. These two IDO1 inhibitors showed low cell cytotoxicity, which indicated that they may exert their anti-tumor effect via immune modulation. Compound DX-03-12 was investigated further by determining the in vivo pharmacokinetic profile and anti-tumor efficacy. The pharmacokinetic study revealed that DX-03-12 had satisfactory properties in mice, with rapid absorption, moderate plasma clearance (～36% of hepatic blood flow), acceptable half-life (～4.6 h), and high oral bioavailability (～96%). Daily oral administration of 60 mg/kg of compound DX-03-12 decreased tumor growth by 72.2% after 19 days in a mouse melanoma cell B16-F10 xenograft model compared with the untreated control. Moreover, there was no obvious weight loss in DX-03-12-treated mice. In conclusion, compound DX-03-12 is a potent lead compound for developing IDO1 inhibitors and anti-tumor agents.

Discovery of clinical candidate (1 R,4 r)-4-((R)-2-((S)-6-Fluoro-5 H-imidazo[5,1-A[isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a potent and selective inhibitor of indoleamine 2,3-dioxygenase 1

A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties.

Fused imidazole compounds with indoleamine 2,3-dioxygenase inhibition activity

The invention relates to fused imidazole compounds, and a preparation method and application thereof. The structure of the compounds is shown in a general formula I, wherein the definitions of each group are as described in the specification. The compounds are capable of selectively inhibiting indoleamine 2,3-dioxygenase (IDO). The compounds provided by the invention can be used as IDO inhibitorsfor the treatment and/or prevention of diseases with the pathological characteristics of IDO mediated tryptophan metabolism pathways, such as cancer, eye diseases, autoimmune diseases, psychological disorders, depression, anxiety and other diseases.

A class of indoleamine 2,3-dioxygenase regulating compound and uses in pharmacy

The invention relates to compounds, which are one or a variety of inhibitors of indoleamine 2,3-dioxygenase. The invention further provides a pharmaceutical component containing the compound, a preparation containing the compound, and uses of the indoleamine 2,3-dioxygenase inhibitors, wherein the indoleamine 2,3-dioxygenase inhibitors can be separately used or can be combined with other drugs soas to treat symptoms related to indoleamine 2,3-dioxygenase.

Imidazole derivative containing four-membered ring

The present invention relates to the field of drugs, particularly to an imidazole derivative containing a four-membered ring structure, a preparation method, a composition and uses thereof.

Chiral resolution, absolute configuration determination, and stereo-activity relationship study of IDO1 inhibitor NLG919

NLG919 (1) with two chiral carbon atoms on its chemical structure is a potent indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor. We developed an effective way to prepare all stereoisomers of 1, the key step being the chiral resolution of racemic intermediate 2. The optimal resolution solvent system was identified as dichloromethane and n-pentane or petroleum ether. Using (?)-di-p-toluoyl-D-tartaric acid as resolution reagent, optical pure (R)-2 (e.e. > 99%, yield = 70%) was obtained. The mechanism of chiral resolution was clarified through single-crystal X-ray diffraction of the diastereomeric salt. The absolute configurations of four stereoisomers of 1 were established through electronic circular dichroism spectra, quantum chemical calculation and transition metal method. Their IDO1 inhibitory activity was assessed by pharmacological experiments in vitro and in mouse, demonstrating that S configuration of C5 played an important role on the inhibition of IDO1, while the stereochemistry on C2′ exerted little effect on the IDO1 inhibitory activity in mouse.

Hydrazino-containing indoleamine 2,3-dioxygenase inhibitors

The present invention provides IDO inhibitors represented by a formula I and a formula II, and a preparation method thereof, wherein R1, R2 and a group X are defined in the specification. The invention further provides a pharmaceutical composition contain

Imidazole-containing condensed tricyclic compound and application thereof

The invention discloses an imidazole-containing condensed tricyclic compound adopting the structure as shown in the formula (I) or pharmaceutically acceptable salts, stereisomers or prodrug molecules thereof. The imidazole-containing condensed tricyclic compound has the IDO1 activity regulation function, can enhance T-cell activation through blocking immune checkpoints IDO1, is used for treating IDO1-mediated immunosuppression, and therefore, can become an effective medicine for treating malignant tumors. When used together with checkpoint protein anti-body drugs or other anti-cancer drugs, the imidazole-containing condensed tricyclic compound can enhance the anti-cancer effect. Meanwhile, the imidazole-containing condensed tricyclic compound has the potential of effectively treating IDO1 abnormity related immunosuppressive diseases and has a high application value.

Discovery of imidazoleisoindole derivatives as potent IDO1 inhibitors: Design, synthesis, biological evaluation and computational studies

Indoleamine-2,3-dioxygenase-1 (IDO1) is an attractive target for cancer immunotherapy. Herein, a series of novel imidazoleisoindole derivatives were prepared and evaluated for their ability to inhibit IDO1. Among these, derivative 11r was the most active compound with nanomolar potency in the Hela cell-based assay, while showed negligible cellular toxicity. UV-visible spectra study demonstrated that compounds 11p and 11r bound to IDO1 and coordinated with the heme iron. Furthermore, they could significantly promote T cell proliferation, increase IFN-γ production, and reduce the numbers of Foxp3+ regulatory T cells. Finally, induced fit docking (IFD) and quantum mechanics/molecular mechanics (QM/MM) calculation were performed to understand the interactions of these compounds to IDO1 protein, which provided a comprehensive guide for further structural modification and optimization.