140660-31-7

Upstream product

• 89-84-9 2',4'-dihydroxy-4-acetophenone 
• 75-65-0 tert-butyl alcohol 

Downstream Products

• 912545-13-2 2,4-bis-benzyloxy-5-tert-butyl-benzoic acid 
• 747414-06-8 1-(2,4-bis(benzyloxy)-5-tert-butylphenyl)ethanone 
• 140660-15-7 7-(4-acetyl-2-tert-butyl-5-hydroxyphenoxy)-2-cyano-2-methylheptane 

Relevant academic research and scientific papers

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)

4,5-Diarylisoxazole Hsp90 chaperone inhibitors: Potential therapeutic agents for the treatment of cancer

Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure - activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by ～50%.

ISOXAZOLE COMPOUNDS AS INHIBITORS OF HEAT SHOCK PROTEINS

Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R1, is a group of formula (IA): -Ar1-(Alk1)p-(Z)r-(Alk2)S-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1and Alk2 are optionally substituted divalent Cl-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, -S-, -(C=O)-, -(C=S)-, -SO2-, -C(=O)O-, -C(=O)NRA-, -C(=S)NRA-, - SO2NRA-, -NRAC(=O)-, -NRASO2- or -NRA- wherein RA is hydrogen or Cl-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk1)p-(Z)r-(Alk2)s-Q wherein Q, Alk1, Alk2, Z, p, r and s are as defined above in relation to group (IA); and R3 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl; or a carboxyl, carboxamide, or carboxyl ester group.

Anti-AIDS agents. 60. Substituted 3′R,4′R-di-O-(-)-camphanoyl- 2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP) analogues as potent anti-HIV agents

Synthesis of positional isomers is a commonly used technique in drug design. Accordingly, based on prior SAR studies of 3′R,4′R-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK, 1) analogues, a series of mono- and disubstituted chromone derivatives of 3′R,4′R-di-O-(-)camphanoyl- 2′,2′-dimethyldihydropyrano[2,3-f]chromone (DCP, 4) were designed and synthesized. Together with 1 and 4-methyl DCK (2), all newly synthesized DCP analogues (4-21) were screened for anti-HIV-1 activity against a non-drug-resistant strain in H9 lymphocytes and a multiple reverse transcriptase (RT) inhibitor-resistant strain in the MT4 cell line. Several DCP analogues (4, 5, 7, 8, 13, and 17) exhibited extremely high anti-HIV activity in the nondrug-resistant strain assay, with EC50 values ranging from 0.00032 to 0.0057 μM and remarkable therapeutic indexes (TI) ranging from 5.6 × 103 to 1.16 × 105, which were similar to those of 2 (EC50 0.0059 μM, TI > 6.6 × 103) and better than those of 1 (EC50 0.049 μM, TI > 328). Even more promisingly, some DCP analogues also showed activity against a multi-RT inhibitor-resistant strain, HIV-1 RTMDR1, whereas most DCK analogues did not. The most significant compound was 8, with an EC50 value of 0.06 μM and TI of 718 against the multi-RT inhibitor-resistant HIV-1 strain. Compounds 9 and 10 also showed good activity with an EC50 value of 0.14 μM, and TIs of 272 and >111, respectively. 2-Ethyl DCP (8) exhibited the best anti-HIV activity in both assays. Further development of 8-related compounds as clinical trial candidates is warranted.

Leukotriene B4 Receptor Antagonists: The LY255283 Series of Hydroxyacetophenones

A series of hydroxyacetophenones was prepared for evaluation as leukotriene B4 (LTB4) receptor antagonists, culminating in 1-oxy>phenyl>ethanone (compound 35, LY255283).Using an assay for inhibition of specific LTB4 binding to human PMN, we found that substitution of a nonpolar substituent in the 5-position was required for activity.Best activity was realized with hydrogen in the 3-position, hydroxyl in the 2-position, short chain alkyl ketone in the 1-position, and a six- or eight-carbon chain linking the oxygen in the 4-position with an unsaturated terminal function.Compound 35, having an IC50 of 87 nM in the binding assay, was chosen for further preclinical evaluation.