1056149-69-9

Basic information

• Product Name: (2E)-(N,N-dimethylamino)-2-butenoyl chloride
• Synonyms: (2E)-(N,N-dimethylamino)-2-butenoyl chloride
• CAS NO: 1056149-69-9
• Molecular Weight: 147.605
• Mol File: 1056149-69-9.mol

Chemical Properties

• CAS DataBase Reference: (2E)-(N,N-dimethylamino)-2-butenoyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: (2E)-(N,N-dimethylamino)-2-butenoyl chloride(1056149-69-9)
• EPA Substance Registry System: (2E)-(N,N-dimethylamino)-2-butenoyl chloride(1056149-69-9)

Safety Data

• Hazardous Substances Data: 1056149-69-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(2E)-(N,N-dimethylamino)-2-butenoyl chloride is used as an intermediate in the synthesis of pharmaceuticals for its strong acylating properties, enabling the production of various drugs and medicinal compounds.
Used in Agrochemical Industry:
(2E)-(N,N-dimethylamino)-2-butenoyl chloride is used as an intermediate in the synthesis of agrochemicals for its ability to form amides, esters, and other organic compounds, contributing to the development of pesticides and other agricultural products.
Used in Organic Chemistry:
(2E)-(N,N-dimethylamino)-2-butenoyl chloride is used as a reagent in organic chemistry for its strong acylating capabilities, allowing for the formation of various organic compounds and facilitating numerous chemical reactions.

Upstream product

• 1130155-48-4 (E)-4-(dimethylamino)-2-butenoic acid hydrochloride 
• 149586-32-3 (2E)-4-(dimethylamino)but-2-enoic acid 
• 79-37-8 oxalyl dichloride 

Downstream Products

• 257933-82-7 pelitinib 
• 848133-88-0 4-chloro-6-(5-(dimethylamino)-2-oxopent-3-enyl)-7-ethoxyquinoline-3-carbonitrile 
• 544417-30-3 (E)-N-{4-[4-(benzyloxy)-3-chloroanilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-buteneamide 
• 848134-35-0 C₃₃H₃₉ClN₆O₆ 

Relevant articles and documents

Design, synthesis, and biological evaluation of novel conformationally constrained inhibitors targeting EGFR

This letter describes the construction of conformationally constrained quinazoline analogues. Structure-activity relationship studies led to the identification of the lead compound 9n. Compound 9n exhibits effective in vitro activity against A431WT,overexpression and H1975 [L858R/T790M] cancer cell lines but is significantly less effective against EGFR negative cancer cell lines (SW620, A549, and K562). Compound 9n was also assessed for potency in enzymatic assays and in vivo antitumor studies. The results indicated that 9n is a potent kinase inhibitor against both wild-type and T790M mutant EGFR kinase. Meanwhile, an oral administration of 9n at a dose of 200 mg/kg produced a considerable antitumor effect in a A431 xenograft model, as compared to gefitinib. A preliminary pharmacokinetic study of 9n also indicates it has good pharmacokinetic properties, and therefore, it is a good starting point for further development.

Discovery of new quinazoline derivatives as irreversible dual EGFR/HER2 inhibitors and their anticancer activities – Part 1

Overexpression of EGFR and HER2 are observed in many breast, ovarian, colon and prostate cancers. The second and third generation irreversible EGFR/HER2 dual kinase inhibitors became popular after the approval of Afatinib by FDA to overcome the mutation related problem. To find efficacious drug candidates, a series of novel quinazoline derivatives were designed, synthesized and evaluated as dual EGFR/HER2 tyrosine kinase (TK) inhibitors. Selected twenty four compounds were reported here with significant inhibitory activities against EGFR/HER2 tyrosine kinases. Several compounds showed nanomolar IC50 values. In vitro studies of quinazoline derivatives were done on NCI-H1975, HCC827, A431, MDA MB-453 cell lines. The compounds 1a, 1d and 1v were found more potent compared to standard drug afatinib. In vivo efficacy study of 1d on nude mice NCI-H1975 tumour xenograft model was discussed.

Structure-Activity Relationship Study of Covalent Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors

Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are important molecular players in a variety of diseases, such as cancer. Currently available PI5P4K inhibitors are reversible small molecules, which may lack selectivity and sufficient cellular on-target activity. In this study, we present a new class of covalent pan-PI5P4K inhibitors with potent biochemical and cellular activity. Our designs are based on THZ-P1-2, a covalent PI5P4K inhibitor previously developed in our lab. Here, we report further structure-guided optimization and structure-activity relationship (SAR) study of this scaffold, resulting in compound 30, which retained biochemical and cellular potency, while demonstrating a significantly improved selectivity profile. Furthermore, we confirm that the inhibitors show efficient binding affinity in the context of HEK 293T cells using isothermal CETSA methods. Taken together, compound 30 represents a highly selective pan-PI5P4K covalent lead molecule.

Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach

Receptor tyrosine kinases represent one of the prime targets in cancer therapy, as the dysregulation of these elementary transducers of extracellular signals, like the epidermal growth factor receptor (EGFR), contributes to the onset of cancer, such as non-small cell lung cancer (NSCLC). Strong efforts were directed to the development of irreversible inhibitors and led to compound CO-1686, which takes advantage of increased residence time at EGFR by alkylating Cys797 and thereby preventing toxic effects. Here, we present a structure-based approach, rationalized by subsequent computational analysis of conformational ligand ensembles in solution, to design novel and irreversible EGFR inhibitors based on a screening hit that was identified in a phenotype screen of 80 NSCLC cell lines against approximately 1500 compounds. Using protein X-ray crystallography, we deciphered the binding mode in engineered cSrc (T338M/S345C), a validated model system for EGFR-T790M, which constituted the basis for further rational design approaches. Chemical synthesis led to further compound collections that revealed increased biochemical potency and, in part, selectivity toward mutated (L858R and L858R/T790M) vs nonmutated EGFR. Further cell-based and kinetic studies were performed to substantiate our initial findings. Utilizing proteolytic digestion and nano-LC-MS/MS analysis, we confirmed the alkylation of Cys797.

FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF

The present disclosure relates to a class of fused pyrimidine compounds of Formula I, their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these fused pyrimidine compounds, and to pharmaceutical compositions containing them.

(1H-INDOL-5-YL)ACRYLAMIDE DERIVATIVES AS INHIBITORS OF TEAD PROTEINS AND THE HIPPO-YAP1/TAZ SIGNALING CASCADE FOR THE TREATMENT OF CANCER

The invention relates to 1H-indolyl-acrylamide derivatives of formula (I): as inhibitors of the TEAD-dependent gene transcription and the HIPPO-YAP1/TAZ signaling cascade for use in methods of treatment of cancer, such as e.g. breast, ovarian, uterine, prostate, lung, gastric, colorectal, bladder, pancreatic and liver cancers, sarcomas, esophageal, head and neck cancers, uveal melanoma or glioma, and in particular in the treatment of patients who have exhibited resistance to prior anti-cancer therapy. The present description discloses the syntheses of exemplary compounds as well as pharmacological data thereof (e.g. pages 11 to 48; examples 1 to 51; tables). An exemplary compound is e.g. N-(1-(3-(trifluoromethyl)benzyl-1H-indol-5-yl)acrylamide ( example 1).

Quinazoline derivative, preparation method and pharmaceutical application thereof

The invention discloses a quinazoline derivative, a preparation method and pharmaceutical application thereof. The invention provides the quinazoline derivative which is a compound shown as formula Iin the specification, and also provides a pharmaceutical

Structure-Based Design of Selective, Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors

The ability of G protein-coupled receptor (GPCR) kinases (GRKs) to regulate desensitization of GPCRs has made GRK2 and GRK5 attractive targets for treating heart failure and other diseases such as cancer. Although advances have been made toward developing inhibitors that are selective for GRK2, there have been far fewer reports of GRK5 selective compounds. Herein, we describe the development of GRK5 subfamily selective inhibitors, 5 and 16d that covalently interact with a nonconserved cysteine (Cys474) unique to this subfamily. Compounds 5 and 16d feature a highly amenable pyrrolopyrimidine scaffold that affords high nanomolar to low micromolar activity that can be easily modified with Michael acceptors with various reactivities and geometries. Our work thereby establishes a new pathway toward further development of subfamily selective GRK inhibitors and establishes Cys474 as a new and useful covalent handle in GRK5 drug discovery.

INHIBITORS OF CYCLIN-DEPENDENT KINASES

Provided herein are inhibitors of cyclin-dependent kinases (CDKs), pharmaceutical compositions comprising said compounds, and methods for using said compounds for the treatment of diseases.

PROCESS FOR THE PREPARATION OF N-[4-[(3-CHLORO-4-FLUORO PHENYL) AMINO]-7-[[(3s-TETRAHYDRO-3-FURANYL]OXY]-6-QUINAZOLINYL]-4-(DIMETHYL AMINO)-(2E)-2-BUTENAMIDE (2Z)-2-BUTENEDIOATE (1 :2) AND ITS POLYMORPHS THEREOF

The present invention relates to an improved process for the preparation of N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[[(3S)-tetrahydro-3-furanyl]oxy]-6-quinazolinyl]-4-(dimethyl amino)-(2E)-2-butenamide (2Z)-2-butenedioate (1:2) represented by the following structural formula: