912545-04-1

Basic information

• Product Name: 2,4-bis(benzyloxy)-5-chlorobenzoic acid
• Synonyms: 2,4-bis(benzyloxy)-5-chlorobenzoic acid
• CAS NO: 912545-04-1
• Molecular Weight: 368.817
• Mol File: 912545-04-1.mol

Chemical Properties

• CAS DataBase Reference: 2,4-bis(benzyloxy)-5-chlorobenzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,4-bis(benzyloxy)-5-chlorobenzoic acid(912545-04-1)
• EPA Substance Registry System: 2,4-bis(benzyloxy)-5-chlorobenzoic acid(912545-04-1)

Safety Data

• Hazardous Substances Data: 912545-04-1(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
2,4-bis(benzyloxy)-5-chlorobenzoic acid is used as a building block in organic synthesis for the creation of complex molecules and pharmaceutical drugs. Its unique structure allows for the development of a wide range of compounds with diverse applications in the chemical and pharmaceutical industries.
Used in Pharmaceutical Development:
In the pharmaceutical industry, 2,4-bis(benzyloxy)-5-chlorobenzoic acid is used as a precursor in the synthesis of various drug molecules. Its presence in the molecular structure can contribute to the drug's efficacy, stability, and other pharmacological properties.
Used in Material Science:
2,4-bis(benzyloxy)-5-chlorobenzoic acid may also find applications in material science, where its chemical structure could be leveraged to develop new materials with specific properties for various applications.
Used in Molecular Engineering:
2,4-bis(benzyloxy)-5-chlorobenzoic acid has potential uses in molecular engineering, where its structural features can be utilized to design and construct molecules with tailored functions and interactions for specialized applications.

Upstream product

• 705963-54-8 1-[2,4-bis(benzyloxy)-5-chlorophenyl]ethan-1-one 
• 90110-32-0 1-(5-chloro-2,4-dihydroxyphenyl)ethan-1-one 
• 95-88-5 4-Chlororesorcinol 
• 67828-44-8 5-chloro-2,4-dihydroxy-benzoic acid 
• 67828-69-7 methyl 5-chloro-2,4-dihydroxybenzoate 
• 100-39-0 benzyl bromide 
• 2150-47-2 methyl 2,4-dihydroxybenzoate 

Downstream Products

• 1020065-89-7 (2,4-bis-benzyloxy-5-chlorophenyl)-(1,3-dihydroisoindol-2-yl)methanone 

Relevant articles and documents

SUBSTITUTED PYRIDINONE-CONTAINING TRICYCLIC COMPOUNDS, AND METHODS USING SAME

The present invention includes substituted pyridinone-containing tricyclic compounds, and compositions comprising the same, that can be used to treat or prevent hepatitis B virus (HBV) infection in a patient. In certain embodiments, the compounds and compositions of the invention inhibit and/or reduce HBsAg secretion.

Design, synthesis and pharmacological evaluation of N-(5-chloro-2,4-dihydroxybenzoyl)-(R)-N-arylmethyl-1,2,3,4-tetrahydro-3-isoquinolinecarboxamides as potent Hsp90 inhibitors

Using diverse arylmethyl groups to replace the benzyl moiety of the lead Hsp90 inhibitor 1 (N-(5-chloro-2,4-dihydroxybenzoyl)-(R)-N-benzyl-1,2,3,4-tetrahydro-3-iso quinolinecarboxamide), thirty four derivatives (10–43) were developed, and exhibited improved Hsp90 inhibitory and antiproliferative activities. SAR analysis indicated that the southeastern aryl substitutions influenced their antiproliferative activities obviously, with the para-pyridyl group (41) outperforming all other substitution patterns. In this regard, compound 41 was selected for further evaluation. CETSA melt and ITDRFCETSA (isothermal dose-response fingerprint) curves for Hsp90α further proved that 41 interacted with intracellular Hsp90α powerfully. Compared with the lead compound 1, docking and MD refinement of the Hsp90α-41 complex revealed a favorable H-bonding interaction between the side-chain of Tyr139 and the pyridine moiety of 41, which is the first time to be used for resorcinol-based Hsp90 inhibitors. With broad-spectral antitumor activity, compound 41 induced time- and dose-dependent growth inhibition and G0/G1 cell cycle arrest on human breast cancer MDA-MB-453 cell line. In addition, flow cytometry and Western blot analyses confirmed that 41 induced apoptosis of human breast cancer MDA-MB-453 cell line. Via degradation of IKKs and suppression of IKKs activity, compound 41 inhibited TNF-α-induced NF-κB activation. The overall properties warrant compound 41 a promising Hsp90 inhibitor and further biological characterizations. This study provides insights into the chemical evolution of Hsp90 inhibitors, and may facilitate the design of next generation Hsp90 inhibitors for the antitumor drug development.

Tetrahydroisoquinoline-3-carboxylic acid heat shock protein 90 inhibitor and application thereof

The invention discloses a tetrahydroisoquinoline-3-carboxylic acid heat shock protein 90 inhibitor. The heat shock protein 90 inhibitor is a compound with a formula (I), or is an optical isomer, a diastereoisomer or a despinner mixture, or a pharmaceutically acceptable salt, a solvate or a predrug. The invention further discloses the application of the inhibitor to preparation of a medicine used for preventing or treating a heat shock protein 90 related disease. The experiment proves that the tetrahydroisoquinoline-3-carboxylic acid heat shock protein 90 inhibitor has a remarkable effect of inhibiting various tissues like tumor cells from the mammary gland and respiratory and reproductive systems, the toxicity to the normal hepatocyte of human is low, and the druggability is relatively good. The tetrahydroisoquinoline-3-carboxylic acid heat shock protein 90 inhibitor has a broad clinical application prospect.

Novel Tetrahydropyrido[4,3-d]pyrimidines as Potent Inhibitors of Chaperone Heat Shock Protein 90

Heat shock protein 90 (Hsp90) is a potential target for oncology therapeutics. Some inhibitors have shown antitumor effects in clinical trials, spurring the discovery of small molecule Hsp90 inhibitors. Here, we describe the structural optimization studies of a hit compound, tetrahydropyrido[4,3-d]pyrimidine-based Hsp90 inhibitor 15, which exhibits inhibitory activity against Hsp90. A series of analogues were synthesized, and their structure-activity and structure-property relationships were analyzed. These explorations led to the discovery of compound 73, which exhibited potent in vitro activities, good physicochemical properties, favorable ADME properties, and a potent antitumor effect in an HCT116 xenograft model. Furthermore, 73 exhibited no ocular toxicity in a rat retinal damage model, suggesting it is a relatively safe Hsp90 inhibitor. As a promising antitumor agent, 73 was progressed for further preclinical evaluation.

Design and synthesis of N-(5-chloro-2,4-dihydroxybenzoyl)-(R)-1,2,3,4-tetrahydroisoquinoline-3-carboxamides as novel Hsp90 inhibitors

Heat shock protein 90 (Hsp90) is an attractive chemotherapeutic target for antitumor drug development. Herein, we reported the design and synthesis of two series of novel N-(5-chloro-2,4-dihydroxybenzoyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamides as Hsp90 inhibitors using (S)-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) (A1-13) and (R)-Tic (B1-13) as scaffold, respectively. Cellular thermal shift assay (CETSA) screening showed that compounds B1-13 with (R)-Tic scaffold exhibited potent ability to stabilize Hsp90α. Compound B7 showed not only the most potent ability to induce thermal stabilization of Hsp90α but also the strongest cytotoxicity. The IC50 values of B7 were 0.98 μM and 1.74 μM against the proliferation of human breast cancer MDA-MB-231 and human cervical cancer HeLa cell lines, respectively. Moreover, CETSA melt and ITDRFCETSA (isothermal dose-response fingerprint) curves confirmed that B7 bound to Hsp90α in 293T cells. Western blotting results indicated that B7 induced the degradation of Hsp90 clients CDK4, Her2, Cdc-2 and C-raf. In addition, docking and Molecular dynamics (MD) refinement of the B7-Hsp90 complex showed that the binding model of B7 to Hsp90 was similar with that of 8-benzyladenines. The overall properties warrant compound B7 a promising lead for the development of Hsp90 inhibitor antitumor drugs.

Phenyl 1, 2 - isoxazole or phenyl 1, 2 - pyrazole compound and use thereof (by machine translation)

The invention discloses the following formula of phenyl 1, 2 - different oxazole or 1, 2 - pyrazole compounds with use. Through the biological activity tests show that, the compound inhibiting heat shock protein 90 activity. Therefore, the invention phenyl 1, 2 - different oxazole or 1, 2 - pyrazole compounds can be used as a heat shock protein 90 inhibitor for the treatment of cancer. (by machine translation)

RESORCINOL N-ARYL AMIDE COMPOUNDS, FOR USE AS PYRUVATE DEHYDROGENASE KINASE INHIBITORS

A compound of formula I: or a pharmaceutically acceptable salt thereof, wherein: Y is –CONR1- or optionally substituted arylene or optionally substituted heteroarylene; R1 is H, Cl, F, CH3 or CF3; 10 each R4 is independently H, CH3 or F; R5 is H or CH3; and each R2 and R6 is independently (Alk)n-Rn-(Alk)n-Rn-(Alk)n-X; The compounds of the invention are useful as resorcinol N-aryl amide (NAA) compounds, which are suitable for use as PDK inhibitors, for example for 15 inhibition of cancer cell proliferation.

Discovery of potent N-(isoxazol-5-yl)amides as HSP90 inhibitors

HSP90 is ubiquitously overexpressed in a broad spectrum of human cancers and has been recognized as an attractive target for cancer treatment. Here, we described the fragment screening, synthesis and structure-activity relationship studies of small molecule inhibitors with 4,5-diarylisoxazole scaffold targeting HSP90. Among them, the compound N-(3-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-((4-morpholinopiperidin-1-yl)methyl)phenyl)isoxazol-5-yl)cyclopropanecarboxamide (108) showed high affinity for binding to HSP90 (FP binding assay, IC50 Combining double low line 0.030 μM) and inhibited the proliferation of various human cancer cell lines with averaging GI50 about 88 nM. Compound 108 exhibited its functional inhibition of HSP90 by depleting key signaling pathways and concomitantly elevating of HSP70 and HSP27 in U-87MG cells. Further in vivo studies showed that compound 108 strongly suppressed the tumor growth of human glioblastoma xenograft model U-87MG with T/C Combining double low line 18.35% at 50 mg/kg q3w/2.5w. Moreover, compound 108 also exhibited good pharmacokinetic properties. Together, our study implicates that compound 108 is a promising candidate of HSP90 inhibitor and is currently advanced to preclinical study.

Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1- ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design

Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) are currently generating significant interest in clinical development as potential treatments for cancer. In a preceding publication (DOI: 10.1021/jm100059d) we describe Astex's approach to screening fragments against Hsp90 and the subsequent optimization of two hits into leads with inhibitory activities in the low nanomolar range. This paper describes the structure guided optimization of the 2,4-dihydroxybenzamide lead molecule 1 and details some of the drug discovery strategies employed in the identification of AT13387 (35), which has progressed through preclinical development and is currently being tested in man.

PHARMACEUTICAL COMPOUNDS

The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof: wherein the bicyclic group: is selected from the structures C1, C5 and C6: wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims. The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity.