67751-23-9

Usage

Uses

Used in Pharmaceutical Industry:
1,1-DIMETHOXY-4-DIMETHYLAMINOBUT-3-EN-2-ONE is used as a chemical intermediate for the preparation of substituted anthranilic amide derivatives. These derivatives have potential applications as VEGF modulators, which can be employed against cancer and other disorders by targeting the VEGF pathway and modulating angiogenesis, a critical process in tumor growth and progression.

InChI:InChI=1/C8H15NO3/c1-9(2)6-5-7(10)8(11-3)12-4/h5-6,8H,1-4H3/b6-5-

Upstream product

• 6342-56-9 Pyruvic aldehyde dimethyl acetal 
• 68-12-2 N,N-dimethyl-formamide 
• 1188-33-6 N,N-dimethylformamide diethyl diacetal 
• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 5815-08-7 tert-Butoxybis(dimethylamino)methane 

Downstream Products

• 111573-59-2 pyrazole-3-carboxaldehyde dimethylacetal 
• 180869-38-9 4-(dimethoxymethyl)-N-methylpyrimidin-2-amine 
• 165807-05-6 4-(dimethoxymethyl)pyrimidin-2-amine 
• 27258-32-8 1-methyl-1H-pyrazole-3-carbaldehyde 
• 27258-33-9 1-methyl-1H-pyrazole-5-carbaldehyde 
• 180869-36-7 4-dimethoxymethyl-2-methylsulfanylpyrimidine 
• 165807-06-7 2-Aminopyrimidine-4-carboxaldehyde 
• 180869-44-7 2-acetamidopyrimidine-4-carboxaldehyde 
• 165806-48-4 5-(2-Aminopyrimidin-4-yl)-4-(4-fluorophenyl)-1-[3-(4-Morpholinyl)propyl]imidazole 
• 193747-11-4 2-propylthiopyrimidine-4-carboxaldehyde dimethyl acetal 
• 878760-47-5 4-(dimethoxymethyl)-2-(trifluoromethyl)pyrimidine 
• 890082-26-5 (4-dimethoxymethyl-pyrimidin-2-yl)-(2-methoxy-phenyl)amine 
• 25746-87-6 acetal dimethylique du pyrimidine-4 carboxaldehyde 
• 156825-33-1 4-(dimethoxymethyl)-2-(2-pyridyl)pyrimidine 

Relevant academic research and scientific papers

A PESTICIDALLY ACTIVE MIXTURE COMPRISING PYRAZOLOPYRIDINE ANTHRANILAMIDE COMPOUND, OXIDES OR SALTS THEREOF

The present invention relates to a pesticidal active mixture comprising pyrazolopyridine anthranilamide compound of formula (I), oxides or a salt thereof, Formula (I) wherein, R1, R2, R3, R4, Z and E are as defined in the description, and at least one insecticidally active compound (II) or at least one fungicidally active compound (III).

Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor

Myeloid cell leukemia 1 (Mcl-1) has emerged as an attractive target for cancer therapy. It is an antiapoptotic member of the Bcl-2 family of proteins, whose upregulation in human cancers is associated with high tumor grade, poor survival, and resistance to chemotherapy. Here we report the discovery of our clinical candidate S64315, a selective small molecule inhibitor of Mcl-1. Starting from a fragment derived lead compound, we have conducted structure guided optimization that has led to a significant (3 log) improvement of target affinity as well as cellular potency. The presence of hindered rotation along a biaryl axis has conferred high selectivity to the compounds against other members of the Bcl-2 family. During optimization, we have also established predictive PD markers of Mcl-1 inhibition and achieved both efficient in vitro cell killing and tumor regression in Mcl-1 dependent cancer models. The preclinical candidate has drug-like properties that have enabled its development and entry into clinical trials.

A Conformational Restriction Strategy for the Identification of a Highly Selective Pyrimido-pyrrolo-oxazine mTOR Inhibitor

The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conformational restriction approach to explore a novel chemical space for the generation of TORKi. Structure-activity relationship (SAR) studies led to the identification of compound 12b with a ～450-fold selectivity for mTOR over class I PI3K isoforms. Pharmacokinetic studies in male Sprague Dawley rats highlighted a good exposure after oral dosing and a minimum brain penetration. CYP450 reactive phenotyping pointed out the high metabolic stability of 12b. These results identify the tricyclic pyrimido-pyrrolo-oxazine moiety as a novel scaffold for the development of highly selective mTOR inhibitors for cancer treatment.

Macrocyclic MCL-1 inhibitors and methods of use

The present disclosure provides for compounds of Formula (I) wherein A2, A3, A4, A6, A7, A8, A15, RA, R5, R9, R10A, R10B, R11, R12, R13, R14, R16, W, X, and Y have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents for the treatment of diseases and conditions, including cancer. Also provided are pharmaceutical compositions comprising compounds of Formula (I).

PYRAZOLOPYRIDINE-DIAMIDES, THEIR USE AS INSECTICIDE AND PROCESSES FOR PREPARING THE SAME.

The present invention provides novel pyrazolopyridine-diamides of Formula (I), wherein, the definition of W1, W2, A1, A2, A3, B1, B2, D, Z1, E, R1, R2, R3, R4, m and n is as described in the description. The present invention also relates to the composition, combination, use and method of application of the compounds of Formula (I).

Molecular Basis for the N-Terminal Bromodomain-and-Extra-Terminal-Family Selectivity of a Dual Kinase-Bromodomain Inhibitor

As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-?-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-κB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38α. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.

NEW AMMONIUM DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6 and Y are as defined in the description. Medicaments.

Synthetic method of tert-butyl-7-hydroxy-7,8-dihydro-4H-pyrazolo [1,5-a][1,4] diazepin-5-(6H)-carboxylate

The invention relates to a synthetic method of tert-butyl-7-hydroxy-7,8-dihydro-4H-pyrazolo [1,5-a][1,4] diazepin-5-(6H)-carboxylate and mainly solves the technical problems of low perfect ratio of a route, difficulty in reaction control, inconvenience in experiment operation and the like in the conventional synthetic process. Tert-butyl-7-hydroxy-7,8-dihydro-4H-pyrazolo [1,5-a][1,4] diazepin-5-(6H)-carboxylate is prepared from 1,1-dimethoxypropane-2-one serving as a starting material through six steps of reactions. The equation is shown in the specification. The obtained product diazepine is a useful intermediate or product for synthesis of various drugs.

ARGININE METHYLTRANSFERASE INHIBITORS AND USES THEREOF

Described herein are compounds of Formula (S-I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

NEW HYDROXYESTER DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Compounds of formula (1) wherein R1, R2, R3, R4, R5, R6, R7, R13, Ra, Rb, A and n are as defined in the description. Medicaments containing them