945016-63-7

Usage

Uses

Used in Pharmaceutical Development:
3-(2-chloropyrimidin-4-yl)-1H-indole is used as a key intermediate in the synthesis of pharmaceuticals for its potential to modulate biological targets and pathways. Its structural characteristics allow for the design of drugs that can interact with specific receptors or enzymes, contributing to the development of new therapeutic agents.
Used in Agrochemical Research:
In the agrochemical industry, 3-(2-chloropyrimidin-4-yl)-1H-indole is utilized as a starting material or a building block in the creation of novel agrochemicals. Its properties may be harnessed to develop pesticides, herbicides, or other crop protection agents that can effectively control pests and diseases while minimizing environmental impact.
Used as a Research Tool in Biological Studies:
3-(2-chloropyrimidin-4-yl)-1H-indole serves as a valuable research tool in the investigation of biological processes and interactions. Its unique chemical structure allows scientists to probe the mechanisms of various biological systems, potentially leading to a better understanding of disease pathways and the discovery of new therapeutic targets.
The specific applications and uses of 3-(2-chloropyrimidin-4-yl)-1H-indole may be further refined and expanded based on ongoing research and development efforts, as its properties and reactivity in different chemical contexts are explored.

Upstream product

• 882562-58-5 3-(2-chloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole 
• 586-96-9 Nitrosobenzene 
• 37968-69-7 2-chloro-4-ethynylpyrimidine 
• 120-72-9 indole 
• 3934-20-1 2,6-Dichloropyrimidine 
• 129271-98-3 1-(phenylsulfonyl)-1H-indol-3-ylboronic acid 

Downstream Products

• 1032452-86-0 2-chloro-4-(1'-methyl-1H-indol-3-yl)pyrimidine 
• 289628-76-8 4-(1H-indol-3-yl)pyrimidin-2-amine 
• 1421372-34-0 N- (4-fluoro-2-methoxy-5-nitrophenyl)-4-(1H-indol-3-yl)pyrimidin-2-amine 
• 1421373-74-1 C₂₈H₃₁N₇O₂ 
• 1421373-71-8 EB₁₀₄ 
• 1421373-68-3 C₂₉H₃₃N₇O₂ 
• 1421373-66-1 N-(2-(N-(2-(dimethylamino)ethyl)-N-methylamino)-4-methoxy-5-((4-(1-methyl-1H-indole-3-yl)pyrimidine-2-yl)amino)phenyl)acrylamide methanesulfonate 
• 1421373-65-0 [N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)propen-2-amide] 
• 1421373-52-5 N-(5-(4-(1H-indol-3-yl)pyrimidin-2-ylamino)-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl)acrylamide 
• 1421373-36-5 3-chloro-N-(2-{[2-(dimethylamino)ethyl](methyl)amino}-4-methoxy-5-{[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl]amino}phenyl)propanamide 
• 1421373-35-4 tert-butyl (2-((5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)-2-nitrophenyl)(methyl)amino)ethyl)(methyl)carbamate 
• 1421373-34-3 tert-butyl (2-((2-amino-5-methoxy-4-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)(methyl)carbamate 
• 1421373-33-2 tert-butyl N-[2-[[5-methoxy-4-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]-2-(prop-2-enoylamino)phenyl](methyl)amino]ethyl]-N-methylcarbamate 
• 1421373-32-1 N₁-(4-(1H-indol-3-yl)pyrimidin-2-yl)-N₄-(2-(dimethylamino)ethyl)-2-methoxy-N₄-methyl-5-nitrobenzene-1,4-diamine 

Relevant academic research and scientific papers

Structure-Based design of Marine-derived Meridianin C derivatives as glycogen synthase kinase 3β inhibitors with improved oral bioavailability: From aminopyrimidyl-indoles to the sulfonyl analogues

Glycogen synthase kinase 3β (GSK-3β) has become an attractive target for the treatment of diabetes. Compound I is an indole-based GSK-3β inhibitor designed from the Meridianin C, a marine natural product (MNP) isolated from Aplidium meridianum. However, this compound has a moderate inhibitory activity toward GSK-3β (IC50 = 24.4 μM), moderate glucose uptake (38%), and especially, a low oral bioavailability (F = 11.4%). In the present study, applying the structure-based design strategy, a series of derivatives modified on the indole moiety were synthesized based on the lead compound I, followed by evaluating their cytotoxic activity, antihyperglycemic activity, and kinase inhibitory activity. Among this series, compound 6x with a sulfonyl group displayed the highest glucose uptake (83.5%) in muscle L6 cells, showing much higher inhibitory activity against GSK-3β (IC50 = 5.25 μM). Molecular docking indicated that compound 6x was properly inserted into the ATP-binding binding pocket of GSK-3β with a higher docking score (-8.145 kcal/mol) compared with that of compound I (-6.950 kcal/mol), interpreting the higher kinase inhibitory activity toward GSK-3β. Remarkably, compound 6x showed favorable drug-like properties, including significantly better oral bioavailability (F = 47.4%) and no two-week acute toxicity at a dose of 1 g/kg. Our findings suggest that these MNP-derived sulfonyl indole derivatives could be used as lead compounds for the development of anti-hyperglycemic drugs.

Refinement of covalent EGFR inhibitor AZD9291 to eliminate off-target activity

Non-small-cell lung cancer (NSCLC) is a major disease that accounts for 85% of all lung cancer cases which claimed around 1.8 billion lives worldwide in 2020. Tyrosine kinase inhibitors (TKIs) that target EGFR have been used for the treatment of NSCLC, but often develop drug resistance, and the covalent inhibitor AZD9291 has been developed to tackle the problem of drug resistance mediated by the T790M EGFR mutation; however, there is a side effect of hyperglycemia that may be due to off-target activity. This study examines analogs of AZD9291 by chemical proteomics, identifying analogs that maintain T790M-EGFR engagement while showing reduced cross-reactivity with off-targets.

Structural modifications on indole and pyrimidine rings of osimertinib lead to high selectivity towards L858R/T790M double mutant enzyme and potent antitumor activity

EGFR inhibitors represent a significant milestone for treatment of non-small cell lung cancer, however, they suffer from the acquired drug resistance. Utilizing osimertinib as the lead compound, this work has explored the structural modifications on the indole and pyrimidine rings of osimertinib to generate novel osimertinib derivatives. The in vitro enzymatic and cellular studies showed that the derivatives possessed high selectivity towards double mutant EGFR and potent antitumor activity. Particularly, compound 6b-1, the most active compound, exhibited excellent inhibitory activity against double mutant EGFR (IC50 = 0.18 nM) and wild-type EGFR (IC50 = 2.89 nM) as well as H1975 cells (IC50 = 1.44 nM). Western blot analysis showed that 6b-1 completely inhibited double mutant EGFR and Erk phosphorylation. In vivo test using xenograft model indicated that compound 6b-1 had better antitumor efficacy than osimertinib. More importantly, 6b-1 displayed many advantages in the pharmacokinetic study, including better oral bioavailability and metabolism character.

Alkynyl-containing AZD9291 derivative, preparation method and application thereof

The invention relates to an alkynyl-containing AZD9291 derivative, a preparation method and application thereof. The structural general formula (I) of the alkynyl-containing AZD9291 derivative is shown as the specification. Compared with the prior art, an AZD9291 analogue is synthesized and alkynyl is introduced, so that not only is the property of the AZD9291 analogue retained, but also the property of alkynyl is improved, the in-vitro antitumor activity is enhanced, and a good inhibition effect is achieved on a variety of tumor cells, and the alkynyl-containing AZD9291 derivative is an idealmedicine for treating diseases caused by EGFR mutation.

Preparation method of 4-(1-cyclopropyl-1H-indole-3-yl)-N-phenylpyrimidine-2-amine derivative

The invention relates to a preparation method of a 4-(1-cyclopropyl-1H-indole-3-yl)-N-phenylpyrimidine-2-amine derivative. The structural formula of the derivative is shown in the descriptions of theinvention. Specifically, the invention relates to a preparation method of a 4-(1-cyclopropyl-1H-indole-3-yl)-N-phenylpyrimidine-2-amine derivative with a compound structure as shown in a general formula (IV). According to the method, defects in the prior art are overcome, cost is greatly reduced, an obtained product is good in purity, high in yield and strong in process operability, and process safety is also greatly improved. Therefore, the preparation method and the application thereof are suitable for industrial application.

Deuterated pyrimidine derivative and application thereof

The invention discloses a deuterated pyrimidine derivative and application thereof, and belongs to the field of medicines. The deuterated pyrimidine derivative and a pharmaceutically acceptable salt thereof have good activity of selectively inhibiting an

2 - (2,Anilino) pyrimidine compound and application thereof (by machine translation)

The invention relates to certain 2 - (2,anilino) pyrimidine compounds represented by the following formula I and application thereof. These compounds or salts thereof show a higher inhibition of EGFR than wild-type EGFR in the form of an activated or drug resistant mutant. Since the toxicity associated with the wild-type EGFR inhibition is reduced, it is expected that such a compound or salt thereof has excellent pharmacodynamic properties, higher metabolic stability, better blood-brain barrier permeability, and more suitable for use as a therapeutic agent, particularly for the treatment of cancer. , These compounds or salts thereof can be used to prepare EGFR-mediated diseases, in particular non-small cell lung cancer, for the treatment of certain mutated forms. (by machine translation)

Compound, containing conjugated dienamide structure, preparation method, pharmaceutical composition and application thereof

The invention relates to a compound containing a conjugated allene amide structure and a preparation method, a medicine composition and application thereof, in particular to a compound containing a conjugated allene amide structure shown in a formula (I), and a preparation method, a medicine composition and application thereof in preparation of an EGFR (epidermal growth factor receptor) inhibitoror a medicine for preventing and/or treating EGFR-related diseases, especially cancers. (The formula (I) is shown in the description.).

Preparation method for antagonizing drug-resistance anti-tumor EGFR (Epidermal Growth Factor Receptor) inhibitor

The invention relates to a preparation method for an antagonizing drug-resistance anti-tumor EGFR (Epidermal Growth Factor Receptor) inhibitor. Specifically, the invention relates to a preparation method for a 4-(1-cyclopropyl-1H-indole-3-yl)-N-phenylpyrimidine-2-amine derivative of a compound structure shown in a general formula (IV). According to the method, defects in the prior art are overcome; cost is greatly shortened; an obtained product has high purity, high yield and high technical maneuverability; and technical safety is greatly improved. Therefore, the preparation method disclosed by the invention and the application of the preparation method are suitable for industrial application.

2-(2, 4, 5-substituted aniline) pyrimidine derivative

The invention relates to a 2-(2, 4, 5-substituted aniline) pyrimidine derivative, and more specifically discloses a compound represented by formula I or a pharmaceutically acceptable salt thereof, anda preparation method and applications of the compound represented by formula I and the pharmaceutically acceptable salt of the compound, wherein R1 to R9 are used for representing groups defined in the invention.