58752-86-6

Upstream product

• 79-37-8 oxalyl dichloride 
• 4331-54-8 4-methylcyclohexanecarboxylic acid 
• 934-67-8 trans-4-methylcyclohexanecarboxylic acid 

Downstream Products

• 220203-27-0 ethyl (4-methylcyclohexanecarbonyl)acetate 
• 60940-94-5 (trans)-4-methylcyclohexane-1-carboxamide 
• 1191064-35-3 C₂₄H₃₉N₅O₄S 
• 1403776-28-2 C₁₉H₂₂FN₃O₂ 
• 1403776-21-5 C₁₉H₂₂ClN₃O₂ 
• 1403776-08-8 C₂₀H₂₅N₃O₂ 
• 1414848-89-7 N-(1-acetyl-5-(4-methylcyclohexanecarbonyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)benzamide 
• 1315192-90-5 5-(3,3-dimethyl-but-1-ynyl)-3-[N-(4-methyl-cyclohexanecarbonyl)-N'-(2,2,2-trifluoro-acetyl)-hydrazino]-thiophene-2-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Variously substituted 2-oxopyridine derivatives: Extending the structure-activity relationships for allosteric modulation of the cannabinoid CB2 receptor

We previously reported the 2-oxopyridine-3-carboxamide derivative EC21a as the first small synthetic CB2R positive allosteric modulator which displayed antinociceptive activity in vivo in an experimental mouse model of neuropathic pain. Herein, we extended the structure-activity relationships of EC21a through structural modifications regarding the p-fluoro benzyl moiety at position 1 and the amide group in position 3 of the central core. The characterization in vitro was assessed through radioligand binding experiments and functional assays (GTPγS, cAMP, βarrestin2). Among the new compounds, the derivatives A1 (SV-10a) and A5 (SB-13a) characterized respectively by fluorine atom or by chlorine atom in ortho position of the benzylic group at position 1 and by a cycloheptane-carboxamide at position 3 of the central core, showed positive allosteric behavior on CB2R. They enhanced the efficacy of CP55,940 in [35S]GTPγS assay, and modulated CP55,940-dependent βarrestin2 recruitment and cAMP inhibition. The obtained results extend our knowledge of the structural requirements for interaction with the allosteric site of CB2R.

BENZOTHIAZOLE COMPOUNDS AND USES THEREOF

The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus

Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 μg/mL (acetazolamide) to MIC = 0.007 μg/mL (22) and 1 μg/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative α-carbonic and γ-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.

SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF

Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

Synthesis and evaluation of mefway analogs as ligands for serotonin 5HT1A receptors

18F-Mefway (N-{2-[4-(2′methoxyphenyl)piperazinyl]ethyl}-N-(2-pyridyl)-N-(4′18F-fluoro-methylcyclohexane)carboxamide) was developed and evaluated for use as a PET ligand for imaging 5-HT1A receptors. Ongoing studies of sup

Synthesis, photo-sensitive and electrochemical properties of rod-like aromatic aldehyde with azo bridge

Eight new rod-like liquid crystal molecules composed by a long rigid core of three six-member rings (cyclohexane ring or benzene ring), azo, ester and terminal aldehyde groups have been prepared. These rod-like liquid crystalline molecules were designed to construct new structures to further study photo-isomerization in their mesophases. All the compounds have been characterized based on their basic spectral data, differential scanning calorimeter (DSC) and hot stage polarizing optical microscope (HS-POM). The result showed that all the molecules, even those with the shortest terminal methyl group, have liquid crystalline properties. Their mesophases are nematic within the temperature ranges from 85 to 145°C. They exhibit photo-sensitivities not only in methanol solutions but also in a mesophase when exposed to UV light. The highest occupied orbital (HOMO) and the lowest unoccupied orbital (LUMO) and the differences between the frontier molecular orbitals (Eg) of these compounds were determined by cyclic voltammetry. The effect of even-odd carbon number of the terminal straight alkyl chain on the UV spectral data and the Eg were observed. The difference between the Eg of these compounds are in excellent agreement with the difference of their maximum absorption wavelength in UV spectra.

1,2,4 -TRIAZOLES AS ALLOSTERIC MODULATORS OF MGLU5 RECEPTOR ACTIVITY FOR THE TREATMENT OF SCHIZOPHRENIA OF DEMENTIA

This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.

SUBSTITUTED TRIAZOLES AND THEIR USE FOR TREATMENT AND/OR PREVENTION NEUROLOGICAL AND PSYCHIATRIC DISORDERS

This invention relates to compounds of formula (I), their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.

Phenolic esters of O-desmethylvenlafaxine with improved Oral bioavailability and brain uptake

O-Desmethylvenlafaxine (desvenlafaxine, ODV) is a recently approved antidepressant which in some clinical studies failed to meet a satisfactory end-point. The aim of this study was to prepare a series of phenolic esters of ODV and evaluate their potential as ODV prodrugs with improved brain uptake. Fifteen phenolic esters (compounds 1a-o) were synthesized and their pharmacokinetic profiles evaluated in rat. The four compounds producing the highest relative bioavailability of ODV in rat (compounds 1c, 1e, 1n, 1o) were then studied to evaluate their brain uptake. Of these four compounds, compound 1n (the piperonylic acid ester of ODV) demonstrated the highest Cmax of ODV both in the rat hypothalamus and total brain. Finally the pharmacokinetics of 1n were evaluated in beagle dog where the increase in relative bioavailability of ODV was found to be as great as in rat. This high relative bioavailability of ODV coupled with its good brain penetration make 1n the most promising candidate for development as an ODV prodrug.

INHIBITORS OF SERINE PALMITOYLTRANSFERASE

This invention provides compounds of the formula (I) useful in the inhibition or modulation of serine palmitoyl transferase and their use in methods of treatment or amelioration of type 2 diabetes, type 1 diabetes, insulin resistance, the effects of obesity, metabolic syndrome (sometimes referred to as Syndrome X), impaired glucose tolerance, Cushing's disease, cardiovascular disease, prothrombotic conditions, myocardial infarction, hypertension, congestive heart failure, cardiomyopathy, atherosclerosis, dyslipidemia, sepsis, liver damage, retinal degenerative disorders, cachexia, emphysema, hepatitis C infections, HIV infections and inflammatory disorders and useful in methods for raising HDL plasma levels in a mammal. The compounds of this invention can also be used to prevent damage or loss of pancreatic islet beta cells (such as in the case of pancreatic beta cell apoptosis, including those related to insulin-dependent diabetes mellitus).