41085-27-2

Usage

Preparation

Preparation from 2-hydroxy-6-methylbenzonitrile and methylmagnesium bromide in ethyl ether–tetrahydrofuran mixture at 50° (67%).

Upstream product

• 6161-64-4 1-(2-methoxy-6-methylphenyl)ethanone 
• 567-61-3 2-hydroxy-6-methylbenzoic acid 
• 917-54-4 methyllithium 
• 6555-40-4 ethyl 2-hydroxy-6-methylbenzoate 
• 75-16-1 methylmagnesium bromide 
• 2835-97-4 2-amino-3-methylphenol 
• 577-16-2 2-Methylacetophenone 
• 53005-44-0 2-methoxy-6-methyl-benzonitrile 
• 108-39-4 3-methyl-phenol 
• 22061-78-5 2-bromo-3-methylphenol 
• 97674-02-7 tributyl(1-ethoxyvinyl)stannane 
• 54884-55-8 2-methoxy-6-methyl-benzaldehyde 
• 2944-49-2 2,3-dimethylanisole 
• 118-90-1 ortho-methylbenzoic acid 

Downstream Products

• 105508-77-8 1-(2-Methoxymethoxy-6-methyl-phenyl)-ethanone 
• 1026483-39-5 (E)-3-(2-Chloro-phenyl)-1-(2-hydroxy-6-methyl-phenyl)-propenone 
• 1154740-59-6 2-bromo-1-(2-hydroxy-6-methylphenyl)ethan-1-one 
• 1354928-64-5 C₁₈H₁₄O₄ 
• 924300-58-3 C₁₅H₁₃NO₃ 
• 105508-81-4 3-Hydroxy-3-(2-methoxymethoxy-6-methyl-phenyl)-butyric acid tert-butyl ester 
• 1025952-31-1 1-(2-chloro-phenyl)-3-(2-hydroxy-6-methyl-phenyl)-propane-1,3-dione 
• 444814-17-9 2-(2-chlorophenyl)-5-methyl-4H-chromen-4-one 
• 702684-42-2 (+)-3-methyl-2-{(1S)-1-{[(1R)-1-phenylethyl]amino}ethyl}phenol 
• 702684-44-4 (+)-[(1S)-1-(2-hydroxy-6-methylphenyl)ethyl]amine 
• 155164-50-4 1-(2-benzyloxy-6-methyl-phenyl)-ethanone 

Relevant academic research and scientific papers

Total syntheses of gerberinol i and the pterophyllins 2 and 4 using the Casnati-Skatteb?l reaction under different conditions

The concise and efficient total syntheses of the naturally-occurring coumarin derivatives gerberinol I, and the pterophyllins 2 and 4, from 5-methyl-4-hydroxycoumarin as a common precursor employing different Casnati-Skatteb?l reaction conditions, are reported. The synthesis of the key intermediate coumarin was achieved by the organocatalytic condensation of acetylacetone and crotonaldehyde followed by a LiCl-assisted cyclization, CuCl2-promoted aromatization and a final Et2CO3-mediated cyclization. A Casnati-Skatteb?l formylation under high-temperature conditions afforded gerberinol I, whereas milder conditions resulted in an unstable 3-formyl-4-hydroxycoumarin derivative, which was subjected to a basic alumina-mediated one pot O-alkylation with chloroacetone and intramolecular aldolization to furnish pterophyllin 4. Wittig methylenation of the latter conveniently afforded pterophyllin 2.

Effect of the Chromone Core Substitution of Dirchromone on the Resultant Biological Activities

Dirchromone is a bioactive vinyl sulfoxide-bearing chromone first isolated from the shrub Dirca palustris. Altogether, 32 of its derivatives were prepared to assess the effect of substitution of its chromone core upon activities against cancer cell lines, Gram-positive bacteria, and fungi (such as Candida albicans). All compounds were synthesized following a synthetic strategy involving Pummerer and soft-enolization Baker-Venkataraman rearrangements. Substituent position changes induced little variability on the activities tested. There was no correlation between cytotoxic and antibacterial effects, suggesting different underlying mechanisms of action. In particular, hydroxy group and cyanide substituents diminished cytotoxicity, with the latter featuring enhanced antibacterial activity. Higher homologues of 6-alkoxydirchromones also exhibited progressively emerging antifungal activity. Other modifications had moderate effects on cytotoxicity with some derivatives leading to increased potency. This behavior highlights the robustness of the natural dirchromone pharmacophore toward decoration, thus paving the way for more elaborate future drug design.

NEW ANTIBACTERIAL COMPOUNDS

The present invention relates to novel antibacterial compounds, pharmaceutical compositions containing them and their use as antimicrobials.

Effects of structural modifications on the metal binding, anti-amyloid activity, and cholinesterase inhibitory activity of chalcones

As the number of individuals affected with Alzheimer's disease (AD) increases and the availability of drugs for AD treatment remains limited, the need to develop effective therapeutics for AD becomes more and more pressing. Strategies currently pursued include inhibiting acetylcholinesterase (AChE) and targeting amyloid-β (Aβ) peptides and metal-Aβ complexes. This work presents the design, synthesis, and biochemical evaluation of a series of chalcones, and assesses the relationship between their structures and their ability to bind metal ions and/or Aβ species, and inhibit AChE/BChE activity. Several chalcones were found to exhibit potent disaggregation of pre-formed N-biotinyl Aβ1-42 (bioAβ42) aggregates in vitro in the absence and presence of Cu2+/Zn2+, while others were effective at inhibiting the action of AChE.

Chromenones as potent bradykinin B1 antagonists

A series of fused 6,6-bicyclic chromenones was investigated for activity against the bradykinin B1 receptor. SAR studies based on a pharmacophore model revealed compounds with high affinity for both human and rabbit B1. These compounds demonstrated favorable pharmacokinetic properties and 5-chlorochromenone 15 was efficacious in a carrageenan-induced mechanical hyperalgesia model for chronic pain.

Synthesis of ortho-acylphenols through the palladium-catalyzed ketone-directed hydroxylation of arenes

ortho-Acylphenols are an important structural motif found in a diversity of bioactive molecules ranging from natural products to drugs (Figure 1). Moreover, they also serve as versatile building blocks for the synthesis of various pharmaceuticals, such as warfarin, as well as agrichemicals, flavors, and fragrances. Classic approaches to the synthesis of o-acylphenols generally involve a two-step process: acylation of phenols followed by Fries rearrangement of the resulting phenyl esters (Scheme 1a). On the other hand, direct C-acylation of phenols has also been known under more forcing conditions. Although effective, these approaches are often complicated by the formation of undesired p-substituted products when bulky acyl groups need to be introduced, as well as the limited variety of ketones that can be generated.

INHIBITORS OF VIRAL REPLICATION, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES

The present invention relates to compounds of formula (1) as claimed in claim 1, their use in the treatment or the prevention of viral disorders, including HIV. (Formula I)

Synthesis, structure-activity relationship of novel substituted 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates as potential anti-mycobacterial and anticancer agents

Series of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 7a-7zb, 8a-8d and 9a-9d were synthesized and screened for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) and cytotoxicity against three human cancer cell lines including A549, SK-N-SH and HeLa. The results indicate that six compounds are more potent and 7za is most effective anti-mycobacterial derivative compared to the standard drugs Ethambutol and Ciprofloxacin. However, 12 compounds exhibited cytotoxicity against human neuroblastoma cell line; amongst them the compound 7v is most effective compared to the standard drug Doxorubicin. This is the first report assigning in vitro anti-mycobacterial, anticancer and structure-activity relationship for this new class of 4H-chromen-1,2,3,4-tetrahydropyrimidine-5- carboxylates.

Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]

Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis.

Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3, 4-dihydrospiro[chromene-2,4′-piperidine] analogs

In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol- 2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID 50 = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC 50 (mouse) = 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg).