641569-97-3

Basic information

• Product Name: 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester
• Synonyms: 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester;Benzoic acid, 4-Methyl-3-[[4-(3-pyridinyl)-2-pyriMidinyl]aMino]-, ethyl ester;Ethyl 4-Methyl-3-((4-(pyridin-3-yl)pyriMidin-2-yl)aMino)benzoate;Ethyl 4-methyl-3-((4-(pyridin-3-yl)
• CAS NO: 641569-97-3
• Molecular Formula: C19H18N4O2
• Molecular Weight: 334.37
• Mol File: 641569-97-3.mol

Chemical Properties

• Boiling Point: 546.1 °C at 760 mmHg
• Flash Point: 284.1 °C
• Appearance: /
• Density: 1.233
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• CAS DataBase Reference: 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester(641569-97-3)
• EPA Substance Registry System: 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester(641569-97-3)

Safety Data

• Hazardous Substances Data: 641569-97-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Synthesis:
4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester is used as an intermediate in the synthesis of Nilotinib-d6 (N465303), which is a labeled analogue of Nilotinib. Nilotinib is a tyrosine kinase inhibitor that is primarily used in the treatment of chronic myelogenous leukemia (CML). 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester plays a crucial role in the development of this therapeutic agent, contributing to its efficacy and potential for targeted cancer treatment.
Used in Smo Inhibitor Preparation:
In the pharmaceutical industry, 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester is also utilized in the preparation of Smoothened (Smo) inhibitors. Smo inhibitors are a class of drugs that target the Smo protein, which is involved in the Hedgehog signaling pathway. This pathway plays a critical role in cell differentiation and tissue development, and its dysregulation has been linked to various cancers. By inhibiting Smo, these compounds can potentially slow down or halt tumor growth, making them valuable in the development of anticancer drugs.
Used in Synthesis and Application of Related Compounds:
4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester is employed in the synthesis of other related compounds that may have various applications in the pharmaceutical and chemical industries. Its unique structure and functional groups make it a versatile building block for the development of new molecules with potential therapeutic or industrial uses. 4-Methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]benzoic acid ethyl ester's role in these syntheses highlights its importance in the broader context of chemical research and drug discovery.

Upstream product

• 641569-95-1 C₁₁H₁₅N₃O₂ 
• 55314-16-4 3-(N,N-dimethylamino)-1-(pyridin-3-yl)prop-2-en-1-one 
• 41191-92-8 3-amino-4-methylbenzoic acid ethyl ester 
• 483324-01-2 2-chloro-4-(pyridin-3-yl)pyrimidine 
• 19013-15-1 ethyl 4-methyl-3-nitro-benzoate 
• 96-98-0 4-methyl-3-nitrobenzoic acid 
• 147962-81-0 ethyl 3-bromo-4-methylbenzoate 
• 66521-66-2 4-pyridin-3-ylpyrimidin-2-ylamine 
• 7697-26-9 3-bromo-4-methylbenzoic acid 
• 350-03-8 methyl-3-pyridylketone 
• 2458-12-0 3-amino-p-toluic acid 
• 641569-96-2 3-guanidino-4-methylbenzoic acid ethyl ester nitrate 

Downstream Products

• 1205540-16-4 N-(3-bromo-5-(trifluoromethyl)phenyl)-4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)benzamide 
• 641570-12-9 C₂₀H₁₆N₆OS 

Relevant articles and documents

Method for preparing N-(5-carboxyl-2-methylphenyl)-4-(3-pyridine)-2-pyrilamine

The invention discloses a method for preparing N-(5-carboxyl-2-methylphenyl)-4-(3-pyridine)-2-pyrilamine. The method specifically comprises the following steps: step 1, carrying out ethyl esterification reaction on 3-nitro-4-methyl benzoic acid serving as an initial raw material to generate a compound 2; step 2, reducing nitro of the compound 2 through hydrogenation reduction reaction in the presence of palladium on carbon to generate a compound 3; step 3, reacting the compound 3 with a nitrile amine aqueous solution, and then carrying out base exchange to obtain a compound 4; step 4, carrying out cyclization between the compound 4 and a compound 6 to obtain a compound 7; and step 5, hydrolyzing the compound 7 under the action of an alkaline to generate a compound 8, namely N-(5-carboxyl-2-methylphenyl)-4-(3-pyridine)-2-pyrilamine. The method overcomes the defects that in the prior art such as long reaction time, low yield, high cost, difficulty for industrial production, and the like. A preparation method, which is high in yield, is environmentally-friendly, and is suitable for industrial production, is provided.

Molecular requirements for the expression of antiplatelet effects by synthetic structural optimized analogues of the anticancer drugs imatinib and nilotinib

Background: Platelets play important roles in cancer progression and metastasis, as well as in cancer-associated thrombosis (CAT). Tyrosine kinases are implicated in several intracellular signaling pathways involved in tumor biology, thus tyrosine kinase inhibitors (TKIs) represent an important class of anticancer drugs, based on the concept of targeted therapy. Purpose: The objective of this study is the design and synthesis of analogues of the TKIs imatinib and nilotinib in order to develop tyrosine kinase inhibitors, by investigating their molecular requirements, which would express antiplatelet properties. Methods: Based on a recently described by us improved approach in the preparation of imatinib and/or nilotinib analogues, we designed and synthesized in five-step reaction sequences, 8 analogues of imatinib (I–IV), nilotinib (V, VI) and imatinib/nilotinib (VII, VIII). Their inhibitory effects on platelet aggregation and P-selectin membrane expression induced by arachidonic acid (AA), adenosine diphosphate (ADP) and thrombin receptor activating peptide-6 (TRAP-6), in vitro, were studied. Molecular docking studies and calculations were also performed. Results: The novel analogues V–VIII were well established with the aid of spectroscopic methods. Imatinib and nilotinib inhibited AA-induced platelet aggregation, exhibiting IC50 values of 13.30 μΜ and 3.91 μΜ, respectively. Analogues I and II exhibited an improved inhibitory activity compared with imatinib. Among the nilotinib analogues, V exhibited a 9-fold higher activity than nilotinib. All compounds were less efficient in inhibiting platelet aggregation towards ADP and TRAP-6. Similar results were obtained for the membrane expression of P-selectin. Molecular docking studies showed that the improved antiplatelet activity of nilotinib analogue V is primarily attributed to the number and the strength of hydrogen bonds. Conclusion: Our results show that there is considerable potential to develop synthetic analogues of imatinib and nilotinib, as TKIs with antiplatelet properties and therefore being suitable to target cancer progression and metastasis, as well as CAT by inhibiting platelet activation.

Smo inhibitor as well as synthesis method and application thereof

The invention discloses an Smo inhibitor as well as a synthesis method and application thereof. A structural formula of the Smo inhibitor is shown by a formula (I) as shown in the specification. The invention also discloses the synthesis method and the application of the Smo inhibitor. According to the invention, nilotinib is optimized into the dual-targeted inhibitor being active against Smo andBcr-Abl, and the inhibitor can overcome the tolerance problem caused by single-targeted drugs, has the advantages of improving anti-tumor efficacy and reducing toxic or side effects, and provides a reference for future research on dual-targeted anti-hematologic malignant drugs.

Investigations into the potential role of metabolites on the anti-leukemic activity of imatinib, nilotinib and midostaurin

The efficacy and side-effects of drugs do not just reflect the biochemical and pharmacodynamic properties of the parent compound, but often comprise of cooperative effects between the properties of the parent and active metabolites. Metabolites of imatinib, nilotinib and midostaurin have been synthesised and evaluated in assays to compare their properties as protein kinase inhibitors with the parent drugs. The N-desmethylmetabolite of imatinib is substantially less active than imatinib as a BCR-ABL1 kinase inhibitor, thus providing an explanation as to why patients producing high levels of this metabolite show a relatively low response rate in chronic myeloid leukaemia (CML) treatment. The hydroxymethylphenyl and N-oxide metabolites of imatinib and nilotinib are only weakly active as BCR-ABL1 inhibitors and are unlikely to play a role in the efficacy of either drug in CML. The 3-(R)-HO-metabolite of midostaurin shows appreciable accumulation following chronic drug administration and, in addition to mutant forms of FLT3, potently inhibits the PDPK1 and VEGFR2 kinases (IC50 values 100 nM), suggesting that it might contribute to drug efficacy in acute myeloid leukaemia patients. The case studies discussed here provide further examples of how the synthesis and characterisation of metabolites can make important contributions to understanding the clinical efficacy of drugs.

Preparing method for 4-methyl-3-[[4-(3-pyridyl)-2-pyrimidyl]amidogen]ethyl benzoate

The invention relates to a preparing method for 4-methyl-3-[[4-(3-pyridyl)-2-pyrimidyl]amidogen]ethyl benzoate and belongs to the technical field of compound synthesis. The preparing method comprises the following steps of using triacetyl pyridine as a beginning raw material, condensing a product generated after urea loop closing and carbonyl chloro substitution with 3-amino-4-methyl ethyl benzoate to generate a key intermediate (I). Compared with an existing synthetic method, the preparing method is moderate in reacting condition and high in yield and has practical value. In addition, the raw material of the preparing method is cheap, easy to obtain and low in price. A synthetic route of the preparing method is as follow in the specification.

Design, synthesis and biological evaluation of pyridin-3-yl pyrimidines as potent Bcr-Abl inhibitors

A series of pyridin-3-yl pyrimidines was synthesized and evaluated for their Bcr-Abl inhibitory and anticancer activity. The preliminary results indicated that some compounds were promising anticancer agents. Compounds A2, A8, and A9 exhibited potent Bcr-Abl inhibitory activity, suggesting that aniline containing halogen substituents might be important for biological activity. Molecular docking was carried out to investigate the binding mode of them with Bcr-Abl. Details of synthesis and SAR studies of these compounds are described. A series of phenylaminopyrimidines was designed and synthesized as potent Bcr-Abl inhibitors. The screening of these rationally designed compounds for antitumor activity had identified three candidate leads which could be further optimized to improve the anticancer activities.

INHIBITORS OF TYROSINE KINASES

The invention relates to compounds of formula (I) Wherein the substituents R1, R2 and R4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, especially a neoplastic disease, in particular leukaemia, and a method for the treatment of such disease.