937366-57-9

Usage

Uses

Used in Pharmaceutical Industry:
3-(2,5-dichloropyrimidin-4-yl)-1H-indole is used as a key intermediate in the synthesis of pyrimidine derivatives for the development of EGFR modulators. These modulators are crucial for the prevention or treatment of various types of cancer, with a particular focus on non-small cell lung cancer.
In the context of cancer treatment, EGFR modulators have emerged as valuable agents due to their ability to target the epidermal growth factor receptor, which plays a critical role in cell growth and proliferation. By modulating the activity of EGFR, these compounds can effectively inhibit the growth of cancer cells and potentially lead to improved therapeutic outcomes for patients suffering from cancer.

Upstream product

• 882562-40-5 3-(2,5-dichloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole 
• 120-72-9 indole 
• 5750-76-5 2,4,5-trichloropyrimidine 
• 129271-98-3 1-(phenylsulfonyl)-1H-indol-3-ylboronic acid 
• 937366-54-6 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole 

Downstream Products

• 1356962-34-9 5-Chloro-4-(1H-indol-3-yl)-N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)pyrimidin-2-amine 
• 1356962-20-3 AZD3436 
• 1421372-65-7 2-{[5-amino-2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]amino}-4-(1H-indol-3-yl)pyrimidine-5-carbonitrile 
• 1421372-68-0 2-{[5-amino-4-(2-dimethylaminoethyl-methylamino)-2-methoxyphenyl]amino}-4-(1-methylindol-3-yl)pyrimidine-5-carbonitrile 
• 1421372-83-9 N-[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine 
• 1421372-84-0 5-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1H-indol-3-yl)pyrimidin-2-amine 
• 1421373-39-8 C₂₈H₂₇ClN₆O₂ 
• 1421373-54-7 N-[5-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl]prop-2-enamide 
• 1421373-55-8 C₂₉H₃₃N₇O₂ 
• 1421373-58-1 C₂₉H₃₂ClN₇O₂ 
• 1421373-59-2 C₃₀H₃₂N₈O₂ 
• 1421373-60-5 C₂₉H₃₀N₈O₂ 
• 1421373-61-6 C₂₈H₃₀ClN₇O₂ 
• 1421373-62-7 N-(5-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide 

Relevant academic research and scientific papers

Discovery of SY-5609: A Selective, Noncovalent Inhibitor of CDK7

CDK7 has emerged as an exciting target in oncology due to its roles in two important processes that are misregulated in cancer cells: cell cycle and transcription. This report describes the discovery of SY-5609, a highly potent (sub-nM CDK7 Kd) and selective, orally available inhibitor of CDK7 that entered the clinic in 2020 (ClinicalTrials.gov Identifier: NCT04247126). Structure-based design was leveraged to obtain high selectivity (>4000-times the closest off target) and slow off-rate binding kinetics desirable for potent cellular activity. Finally, incorporation of a phosphine oxide as an atypical hydrogen bond acceptor helped provide the required potency and metabolic stability. The development candidate SY-5609 displays potent inhibition of CDK7 in cells and demonstrates strong efficacy in mouse xenograft models when dosed as low as 2 mg/kg.

AMINOPYRIMIDINE COMPOUNDS

Disclosed herein are aminopyrimidine compounds that inhibit FGFR and methods of treating diseases and/or conditions (e.g., cancer) with the aminopyrimidine compounds disclosed herein.

CDK inhibitor based on organic arsine as well as preparation method and application of CDK inhibitor

The invention provides a CDK inhibitor based on organic arsine as well as a preparation method and application of the CDK inhibitor. Specifically, the invention providese compounds of Formula I, or stereoisomers or tautomers thereof, or pharmaceutically acceptable salts, hydrates or solvates thereof; and the invention also discloses a preparation method and application thereof. Definitions of allgroups in the formula are shown in the specification.

Selective Covalent Targeting of Mutated EGFR(T790M) with Chlorofluoroacetamide-Pyrimidines

Covalent modification of disease-associated proteins with small molecules is a powerful approach for achieving an increased and sustained pharmacological effect. To reduce the potential risk of nonselective covalent modification, molecular design of covalent inhibitors is critically important. We report herein the development of a targeted covalent inhibitor for mutated epidermal growth factor receptor (EGFR) (L858R/T790M) using α-chlorofluoroacetamide (CFA) as the reactive group. The chemically tuned weak reactivity of CFA was suitable for the design of third-generation EGFR inhibitors that possess the pyrimidine scaffold. The structure-activity relationship study revealed that CFA inhibitor 18 (NSP-037) possessed higher inhibition selectivity to the mutated EGFR over wild-type EGFR when compared to clinically approved osimertinib. Mass-based chemical proteomics analyses further revealed that 18 displayed high covalent modification selectivity for the mutated EGFR in living cells. These findings highlight the utility of CFA as a warhead of targeted covalent inhibitors and the potential application of the CFA-pyrimidines for treatment of non-small-cell lung cancer.

Pyrimidine amine compound, and preparation method and application thereof

The invention discloses a polycyclic compound, and a preparation method and an application thereof. The invention provides the polycyclic compound represented by formula I, or a pharmaceutically acceptable salt thereof. The compound has a relatively good inhibition effect on CDK7.

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.).

Cyclin-dependent kinase inhibitors and application thereof

The invention relates to compounds used as cyclin-dependent kinase inhibitors and application thereof, belonging to the field of medical chemistry. Specifically, the invention provides the compound asshown in a formula I which is described in the specification, or isomers, pharmaceutically acceptable salts, solvates, crystals or prodrugs thereof, preparation methods thereof, pharmaceutical compositions containing the compounds, and application of the compounds or the compositions to treatment of cancer, tissue hyperplasia diseases or inflammatory diseases. The compounds of the invention havegood inhibitory activity to CDK7 and are highly expected to be developed into a therapeutic agent for cancer, tissue hyperplasia diseases and inflammatory diseases.

INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)

The present invention provides novel compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase (e.g., CDK7), and therefore induce cellular apoptosis and/or inhibit transcription in the subject.

INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)

The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g., cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

2 - (2, 4, 5 - SUBSTITUTED -ANILINO) PYRIMIDINE DERIVATIVES AS EGFR MODULATORS USEFUL FOR TREATING CANCER

The present invention relates to certain 2-(2,4,5-substituted-anilino) pyrimidine compounds and pharmaceutically acceptable salts thereof which may be useful in the treatment or prevention of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (for example the L858R activating mutant, the Exonl9 deletion activating mutant and the T790M resistance mutant). Such compounds and salts thereof may be useful in the treatment or prevention of a number of different cancers. The invention also relates to pharmaceutical compositions comprising said compounds and salts thereof, especially useful polymorphic forms of these compounds and salts, intermediates useful in the manufacture of said compounds and to methods of treatment of diseases mediated by various different forms of EGFR using said compounds and salts thereof.