95691-32-0

Upstream product

• 7464-46-2 p-nitrophenyl p-methoxybenzoate 
• 121-97-1 4-Methoxypropiophenone 
• 18362-51-1 1,3-bis(4'-methoxyphenyl)propane-1,3-dione 
• 74-88-4 methyl iodide 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 100-66-3 methoxybenzene 
• 100-09-4 4-methoxybenzoic acid 
• 100-07-2 4-methoxy-benzoyl chloride 
• 614-45-9 tert-Butyl peroxybenzoate 

Downstream Products

• 1307315-20-3 C₂₃H₁₉NO₄ 
• 1307315-21-4 C₂₄H₂₁NO₅ 
• 1307315-14-5 1,2,4-tris(4-hydroxyphenyl)-3-methyl-1H-pyrrole 
• 1307315-30-5 C₂₆H₂₅NO₃ 
• 1307315-26-9 C₁₉H₁₉NO₂ 
• 1307315-23-6 C₂₂H₂₃NO₄ 
• 263717-50-6 3,5-bis(4-methoxyphenyl)-4-methyl-1-phenyl-1H-pyrazole 

Relevant academic research and scientific papers

Copper-catalyzed methylation of 1,3-diketones with tert-butyl peroxybenzoate

Copper-catalyzed radical methylation of 1,3-diketones with tert-butyl peroxybenzoate in air is described, providing a general pathway to α-methyl 1,3-diketones in moderate to good yields. This protocol has been scaled up to 50?g, and one of the synthesized products can be used in the synthesis of medicine, Rosuvastatin.

Method for preparing 2-methyl-1,3-dicarbonyl derivative

The invention discloses a method for preparing a 2-methyl-1,3-dicarbonyl derivative. A 1,3-dicarbonyl derivative serves as an initiator, raw materials are easy to obtain, and a great variety of raw materials are available. The product obtained through the method has high type diversity and can be used directly or used for other further reactions. Besides, only organic peroxides and a catalytic amount of inorganic copper salt are used, so that cost is low. According to the method, a reaction is conducted in air, reaction conditions are mild, pollution is small, reaction time is short, the yield of the target product is high, reaction operation and aftertreatment are easy, and the method is suitable for industrial production.

Antiproliferative novel isoxazoles: Modeling, virtual screening, synthesis, and bioactivity evaluation

A series of novel isoxazole derivatives were efficiently synthesized through the adaptation/modification of an in situ synthetic procedure for pyrazoles. All novel compounds were tested against four different cell lines to evaluate their antiproliferative activity. Based on the Hela cells results of this study and previous work, a classification model to predict the anti-proliferative activity of isoxazole and pyrazole derivatives was developed. Random Forest modeling was used in view of the development of an accurate and reliable model that was subsequently validated. A virtual screening study was then proposed for the design of novel active derivatives. Compounds 9 and 11 demonstrated significant cytostatic activity; the fused isoxazole derivative 18 and the virtually proposed compound 2v, were proved at least 10 times more potent as compared to compound 9, with IC50 values near and below 1 μM. In conclusion, a new series of isoxazoles was exploited with some of them exhibiting promising cytostatic activities. Further studies on the substitution pattern of the isoxazole core can potentially provide compounds with cytostatic action at the nM scale. In this direction the in silico approach described herein can also be used to screen existing databases to identify derivatives with anticipated activity.

Synthesis and investigations on the oxidative degradation of C3/C5-Alkyl-1,2,4-triarylpyrroles as ligands for the estrogen receptor

In this study, we synthesized 1,2,4-triarylpyrroles as ligands for the estrogen receptor (ER). Two pyrrole series were prepared with either C3-alkyl or C3/C5-dialkyl residues. Compounds from both series were susceptible to oxidative degradation-dialkylated compounds (t1/2=33-66h) to a higher extent than their monoalkylated congeners (t1/2=140-211h). Nevertheless, stability was sufficient for determination of in vitro ER binding affinity. The most active agonist in hormone-dependent, ERα-positive MCF-7/2a and U2-OS/α cells was 1,2,4-tris(4-hydroxyphenyl)-3-propyl-1H-pyrrole (6d) (MCF-7/2a: EC50=70nM; U2-OS/α: EC50=1.6nM). A corresponding inactivity in U2-OS/β cells demonstrated the high ERα selectivity. This trend was confirmed in a competition experiment using estradiol (E2) and purified hERα and hERβ proteins (relative binding affinity (RBA) calculated for 6d: RBA(ERα)=1.85%; RBA(ERβ) 0.01%). Generally, C3/C5-dialkyl substitution led to reduction of activity, possibly due to lower stability. Triarylpyrroles with C3-alkyl or C3/C5-dialkyl residues were synthesized as ligands for the estrogen receptor (ER). The compounds exhibited transcription activation selectively for ERα but only marginally displaced estradiol from its binding site. The compounds were susceptible to oxidative degradation-dialkylated compounds to a higher extent than their monoalkylated congeners. The reasons for instability were elucidated; thus, by changing the substitution pattern, it will be possible to generate stable triarylpyrroles.

Free radical ring expansion and chain extension of 1,3-diketones

Free radical-promoted one carbon ring expansion and chain extension of 1,3-diketones including 1,3-diarylpropane-1,3-diones and 2-aroyl-3,4-dihydro-2H- naphalen-1-one to generate corresponding 1,4-diketones are described.

Enantioselective borohydride reduction catalyzed by optically active cobalt complexes

The highly enantioselective borohydride reduction of aromatic ketones or imines to the corresponding alcohols was developed in the presence of a catalytic amount of an optically active cobalt(II) complex catalyst. This enantioselective reduction is carried out using a precisely premodified borohydride with alcohols such as tetrahydrofurfuryl alcohol, ethanol and methanol. High optical yields are obtained by choosing the appropriate alcohol as modifiers and a suitable β-ketoiminato ligand of the catalyst. The enantioselective borohydride reduction has been successfully applied to the preparation of optically active 1,3-diols, the stereoselective reduction of diacylferrocenes, and dynamic and/or kinetic resolution of 1,3-dicarbonyl compounds.

Estrogen receptor modulators

Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

Pyrazole ligands: Structure - Affinity/activity relationships and estrogen receptor-α-selective agonists

We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ERα than on the ERβ subtype (Sun et al. Endocrinology 1999, 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ERα-selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions. Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ERα. The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ERα with high affinity (ca. 50% that of estradiol), and it has a 410-fold binding affinity preference for ERα. It also activates gene transcription only through ERα. Thus, this compound represents the first ERα-specific agonist. We investigated the molecular basis for the exceptional ERα binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling. These investigations suggest that the pyrazole triols prefer to bind to ERα with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ERα has a smaller residue than ERβ. These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ERα.