166272-81-7

Usage

Uses

4-Chloro-3-hydroxybenzoic Acid Methyl Ester id used in the synthesis of antidepressants.

Upstream product

• 67-56-1 methanol 
• 34113-69-4 4-chloro-3-hydroxybenzoic acid 
• 40889-91-6 2-chloro-5-(trifluoromethyl)phenol 
• 913835-92-4 (2-chloro-5-(methoxycarbonyl)phenyl)boronic acid 
• 19438-10-9 methyl 3-hydroxybenzoate 

Downstream Products

• 1252762-50-7 Methyl 4-chloro-3-(phenylmethoxy)benzoate 
• 166272-92-0 methyl 3-tert-butoxy-4-chlorobenzoate 

Relevant academic research and scientific papers

NOVEL INHIBITORS OF MAP4K1

The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.

Synthesis and crystal structure of 5-chloro-3,4-dihydroxy-3-(2-hydroxyethyl) isobenzofuran-1(3H)-one

5-Chloro-3,4-dihydroxy-3-(2-hydroxyethyl)isobenzofuran-1(3H)-one (C10H9ClO5, Mr=244.63) has been synthesized using 2-chloro-5-trifluoromethylphenol as starting material through esterification, Friedel-Crafts acylation, hydrolysis, and cyclization reaction. The compound was characterized by infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and elemental analysis. The single crystal structure of the title compounds has been further determined by X-ray diffraction. The crystal belongs to the triclinic system, space group P1 with a=7.8111(16) ?, b=7.8164(16) ?, c=8.5660(17) ?, α=82.50(3)°, β=71.28(3)°, γ=68.22(3)°, V=459.93(16) ?3, Z=2, Dc=1.766 g/cm3, μ=0.418 mm?1, F(000)=252, the final R1=0.0792, and wR2(I>2σ(I))=0.2209. The existence of π-π conjunction effect resulted in correlative bond length shorter than typical bond length in the crystal. The title compound is assembled into a three-dimensional supramolecular structure by two intermolecular hydrogen bonds and one intramolecular hydrogen bond.

Structure-Based Design and Biological Characterization of Selective Histone Deacetylase 8 (HDAC8) Inhibitors with Anti-Neuroblastoma Activity

Histone deacetylases (HDACs) are important modulators of epigenetic gene regulation and additionally control the activity of non-histone protein substrates. While for HDACs 1-3 and 6 many potent selective inhibitors have been obtained, for other subtypes much less is known on selective inhibitors and the consequences of their inhibition. The present report describes the development of substituted benzhydroxamic acids as potent and selective HDAC8 inhibitors. Docking studies using available crystal structures have been used for structure-based optimization of this series of compounds. Within this study, we have investigated the role of HDAC8 in the proliferation of cancer cells and optimized hits for potency and selectivity, both in vitro and in cell culture. The combination of structure-based design, synthesis, and in vitro screening to cellular testing resulted in potent and selective HDAC8 inhibitors that showed anti-neuroblastoma activity in cellular testing.

Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics

In the present study, a series of benzamides, endowed with potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl)butoxy)-N-methylbenzamide (21) and its fluoro-substituted analogue (22) held the best pharmacological binding profiles. They not only presented potent activities for D2, 5-HT1A, and 5-HT2A receptors, but were also endowed with low activities for 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity of inducing weight gain and QT prolongation. In animal models, compounds 21 and 22 reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy induction. It thus provides potential candidates for further preclinical studies.

The Catalyst-Controlled Regiodivergent Chlorination of Phenols

Different catalysts are demonstrated to overcome or augment a substrate's innate regioselectivity. Nagasawa's bis-thiourea catalyst was found to overcome the innate para-selectivity of electrophilic phenol chlorination, yielding ortho-chlorinated phenols that are not readily obtainable via canonical electrophilic chlorinations. Conversely, a phosphine sulfide derived from 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) was found to enhance the innate para-preference of phenol chlorination.

Novel dihydroquinolizinones for the treatment and prophylaxis of hepatitis B virus infection

The invention provides novel compounds having the general formula: wherein R1, R2, R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds.

NOVEL DIHYDROQUINOLIZINONES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION

The invention provides novel compounds having the general formula (I) wherein R1, R2 R3, R4, R5 and R6 are as described herein, compositions including the compounds and methods of using the compounds in the treatment of the hepatitis B virus.

Ring Opening of Bicyclo[3.1.0]hexan-2-ones: A Versatile Synthetic Platform for the Construction of Substituted Benzoates

Described is the development of a highly efficient 2πdisrotatory ring-opening aromatization sequence using bicyclo[3.1.0]hexan-2-ones. This unprecedented transformation efficiently proceeds under thermal conditions and allows facile construction of uniquely substituted and polyfunctionalized benzoates. In the presence of either amines or alcohols formation of substituted anilines or ethers, respectively, is achieved. Additionally, the utility of this method was demonstrated in a short synthesis of sekikaic acid methyl ester. Cracked open: A highly efficient thermal 2πdisrotatory ring-opening aromatization sequence of bicyclo[3.1.0]hexan-2-ones is described. The transformation proceeds in sulfolane to give uniquely substituted benzoates. In the presence of either amines or alcohols, formation of substituted anilines or ethers, respectively, is achieved.

HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK

Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.

GAMMA-AMINO-BUTYRIC ACID DERIVATIVES AS GABAB RECEPTOR LIGANDS

Gamma-amino-butyric acid derivatives that are GABAB receptor ligands, pharmaceutical compositions comprising such derivatives, and methods of using such derivatives and pharmaceutical compositions thereof for treating diseases are disclosed.