64507-07-9

Upstream product

• 4864-01-1 2-methoxy-5-(trifluoromethyl)-benzoic acid 

Downstream Products

• 64506-92-9 β-{4-[2-(2-methoxy-5-trifluoromethylbenzamido)-ethyl]-phenyl}-propionic acid 
• 1187465-17-3 (Z)-N-(5-tert-butyl-3-(2-sulfamoylethyl)thiazol-2(3H)-ylidene)-2-methoxy-5-(trifluoromethyl)benzamide 
• 1140918-65-5 N-(3-tert-butyl-1-((tetrahydrofuran-3-yl)methyl)-1H-pyrazol-5-yl)-2-methoxy-5-(trifluoromethyl)benzamide 
• 933982-96-8 2-hydroxy-5-(trifluoromethyl)benzamide 
• 1416255-32-7 (2,5-dimethyl-1-benzofuran-3-yl)[2-methoxy-5-(trifluoromethyl)phenyl]methanone 
• 1416255-74-7 (2,5-dimethyl-1-benzofuran-3-yl)[2-hydroxy-5-(trifluoromethyl)phenyl]methanone 
• 1140917-70-9 2-methoxy-N-{2-[(2R)-tetrahydrofuran-2-ylmethyl]-2,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl}-5-(trifluoromethyl)benzamide 
• 1140918-01-9 N-{(3E)-5-tert-butyl-1-methyl-2-[(2R)-tetrahydrofuran-2-ylmethyl]-1,2-dihydro-3H-pyrazol-3-ylidene}-2-methoxy-5-(trifluoromethyl)benzamide 
• 1075243-83-2 N-[(5Z)-4-butyl-2-(2-fluoro-1,1-dimethylethyl)isothiazol-5(2H)-ylidene]-2-methoxy-5-(trifluoromethyl)benzamide 
• 1065640-10-9 (Z)-tert-butyl 3-((5-tert-butyl-2-(2-methoxy-5-(trifluoromethyl)benzoylimino)thiazol-3(2H)-yl)methyl)azetidine-1-carboxylate 
• 934495-04-2 Ethyl 3-[2-methoxy-5-(trifluoromethyl)phenyl]-3-oxopropanoate 

Relevant academic research and scientific papers

ARYL AND HETEROARYL-CARBOXAMIDE SUBSTITUTED HETEROARYL COMPOUNDS AS TYK2 INHIBITORS

Novel carboxamide substituted compounds of Formula (I) are disclosed; as well as processes for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Tyrosine Kinase 2 (Tyk2).

Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model

Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50 = 3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole)were evaluated in comparison to MY 5445 (4b)in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment.

One-Pot Domino Friedel-Crafts Acylation/Annulation between Alkynes and 2-Methoxybenzoyl Chlorides: Synthesis of 2,3-Disubstituted Chromen-4-one Derivatives

A highly regioselective synthesis of 2,3-disubstituted chromen-4-one derivatives is accomplished from readily available internal alkynes and 2-methoxybenzoyl chlorides. The reaction proceeds via a domino intermolecular Friedel-Crafts acylation/intramolecular vinyl carbocation trapping (or oxa-Michael addition)/demethylation reaction sequence. This Lewis acid promoted method features relatively mild reaction conditions to synthesize a variety of 2,3-disubstituted chromen-4-one derivatives in one pot with up to 93% yield. The chromen-2-one (coumarin) product was obtained when 2,6-dimethoxybenzoyl chloride was used as a starting material via an electrophilic aromatic substitution/rearrangement process.

Color Tuning of Efficient Electroluminescence in the Blue and Green Regions Using Heteroleptic Iridium Complexes with 2-Phenoxyoxazole Ancillary Ligands

A rational molecular design strategy for tuning the emission color of phosphorescent complexes by functionalization of the bis(2-phenylpyridine)(2-(2′-oxyphenyl)-2-oxazoline/oxazole)iridium(III) framework is reported. Five new complexes (2-6) have been synthesized in good yields and characterized by cyclic voltammetry, absorption, and photoluminescence studies, by time-dependent density functional theory (TD-DFT) calculations, and by single-crystal X-ray diffraction studies for complexes 2, 4, and 6. An interesting feature of the complexes is that the HOMO is localized on the Ir d-orbitals and the phenoxylate part of the “ancillary” ligand, while the LUMO is located on the pyridyl ring of the ppy ligands. A few other complexes containing 2′-oxyphenyl-2-oxazoline/oxazole ancillary ligands have been reported previously; however, until now there has not been a systematic investigation into manipulating this unusual frontier orbital distribution to tune the emissive properties. It is shown that exchanging the phenylpyridine (ppy) ligand for 2,4-difluoro-ppy gives a blue shift of 21-22 nm (from 1 to 2 and from 4 to 5), and the introduction of electron-withdrawing substituents (SO2Me, CF3) onto the phenoxylate ring of the (2′-oxyphenyl)-2-oxazole ligand results in a further blue shift of 13-20 nm. Combining these functionalizations gives sky-blue emission with λmaxPL 476 and 479 nm for complexes 5 and 6 in dichloromethane solution. The solution quantum yields of all the complexes are within the range ΦPL 0.42-0.73. The observed lifetimes (τobs = 1.52-3.01 μs) and spectral profiles are indicative of phosphorescence from a mixture of ligand-centered and MLCT excited states. (TD-)DFT calculations are in close agreement with the observed photophysical and electrochemical properties of the complexes. Phosphorescent organic light-emitting diodes have been fabricated using complexes 2, 3, 5, and 6 as the emitter, doped in a 4,4′-bis(N-carbazolyl)biphenyl host, giving efficient emission in the blue-green region. Notably, complex 5 gives λmaxEL 480 nm with a maximum brightness of 26150 cd m-2.

Aryl hetaryl ketones and thioketones as efficient inhibitors of peptidyl-prolyl cis-trans isomerases

A series of 18 differently substituted new aryl hetaryl ketones and thioketones were synthesized in four to six steps from commercial starting materials. The new ketones were evaluated as inhibitors of the peptidyl-prolyl cis-trans isomerase hPin1 with Ki values ranging in the one-digit micromolar to sub-micromolar numbers. A crystal structure revealed the non-planar arrangement of the aryl residues at the carbonyl compound and supports the hypothesis that the new compounds might mimic the transition state of the enzymatic conversion.

NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS

Disclosed herein are compounds of formula (I) wherein R1, R2, R3, R25a, R26a, X, and n are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and pharmaceutical compositions are also described

NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS

The present application relates to thiazolylidene containing compounds of formula (I) wherein R1, R2, R3, R4, L2 and A are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

Pyrazole derivatives, compositions containing such compounds and methods of use

Pyrazoles having a naphthyl group attached are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

Substituted salicylanilides as inhibitors of two-component regulatory systems in bacteria

A new class of inhibitors of the two-component regulatory systems (TCS) of bacteria was discovered based on the salicylanilide screening hits, closantel (1) and tetrachlorosalicylanilide (9). A systematic SAR study versus a model TCS, KinA/Spo0F, demonstrated the importance of electron- attracting substituents in the salicyloyl ring and hydrophobic groups in the anilide moiety for optimal activity. In addition, derivatives 8 and 16, containing the 2,3-dihydroxybenzanilide structural motif, were potent inhibitors of the autophosphorylation of the KinA kinase, with IC50s of 2.8 and 6.3 μM, respectively. Compound 8 also inhibited the TCS mediating vancomycin resistance (VanS/VanR) in a genetically engineered Enterococcus faecalis cell line at concentrations subinhibitory for growth. Closantel (1), tetrachlorosalicylanilide (9), and several related derivatives (2, 7, 10, 11, 20) had antibacterial activity against the drug-resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF).