Taro Terauchi

Bio: Taro Terauchi is an academic researcher from Eisai. The author has contributed to research in topics: Single bond & Alkyl. The author has an hindex of 12, co-authored 35 publications receiving 549 citations.

Pyrazole compound and medicinal composition containing the same

Abstract: A novel compound having excellent JNK inhibitory activity. It is a compound represented by the following general formula or a salt thereof. (I) In the formula, R1 represents -(CO)h-(NRa)j-(CRb=CRc)k-Ar (wherein Ra, Rb, and Rc each independently represents hydrogen, halogeno, hydroxy, optionally substituted C1-6 alkyl, etc.); Cy means a 5- or 6-membered aromatic heterocycle; and V's each independently means -L-X-Y [wherein L means a single bond, optionally substituted C1-6 alkylene, etc.; X means a single bond, -A- (wherein A represents NR2, O, CO, S, SO, or SO2), etc.; and Y means hydrogen, halogeno, nitro, etc.].

Discovery of (1R,2S)-2-{[(2,4-Dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006): A Potent and Efficacious Oral Orexin Receptor Antagonist

Abstract: The orexin/hypocretin receptors are a family of G protein-coupled receptors and consist of orexin-1 (OX1) and orexin-2 (OX2) receptor subtypes. Orexin receptors are expressed throughout the central nervous system and are involved in the regulation of the sleep/wake cycle. Because modulation of these receptors constitutes a promising target for novel treatments of disorders associated with the control of sleep and wakefulness, such as insomnia, the development of orexin receptor antagonists has emerged as an important focus in drug discovery research. Here, we report the design, synthesis, characterization, and structure-activity relationships (SARs) of novel orexin receptor antagonists. Various modifications made to the core structure of a previously developed compound (-)-5, the lead molecule, resulted in compounds with improved chemical and pharmacological profiles. The investigation afforded a potential therapeutic agent, (1R,2S)-2-{[(2,4-dimethylpyrimidin-5-yl)oxy]methyl}-2-(3-fluorophenyl)-N-(5-fluoropyridin-2-yl)cyclopropanecarboxamide (E2006), an orally active, potent orexin antagonist. The efficacy was demonstrated in mice in an in vivo study by using sleep parameter measurements.

2-iminopyrrolidine derivatives

Abstract: 2-Iminopyrrolidine derivatives represented by the general formula (I) or salts thereof: (I) wherein B is a benzene or pyridine ring, or the like; R101 to R103 are each hydrogen, halogeno, C1-6 alkyl, or the like; R5 is hydrogen, C1-6 alkyl, C1-6 alkoxy C1-6 alkyl, or the like; R6 is hydrogen, C1-6 alkyl, C1-6 alkyloxycarbonyl, or the like; Y1 is a single bond, -CH2-, or the like; Y2 is a single bond, -CO-, or the like; and Ar is hydrogen, a group represented by the general formula (II): (II) (wherein R10 to R14 are each hydrogen, C1-6 alkyl, hydroxyl, C1-6 alkoxy, or the like, or R11 and R12 or R12 and R13 may be united to form a 5- to 8-membered heterocycle), or the like.

Novel 1h-indazole compound

Abstract: A novel 1H-indazole compound having excellent JNK inhibitory activity. It is a compound represented by the following general formula (I), a salt thereof, or a hydrate of either: (I) wherein R means C6-14 aromatic cyclic hydrocarbon group; R , R , and R each independently means hydrogen, halogeno, cyano, etc.; L means a single bond, C1-6 alkylene, etc.; X means a single bond, a group represented by -CO-NH- or -NH-CO-, etc.; and Y means C3-8 cycloalkyl, a C6-14 aromatic cyclic hydrocarbon group, a 5- to 14-membered aromatic heterocyclic group, etc.

Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum

Abstract: Excess activation of glutamate receptors and production of free radicals including nitric oxide may result in severe and irreversible damage to the mammalian central nervous system (CNS), but endogenous defense systems that protect neurons from these insults are poorly understood. Here, we purified and isolated a neuroprotective substance, which has been named “serofendic acid,” from a lipophilic fraction of FCS based on the ability to protect rat primary cortical neurons against nitric oxide cytotoxicity. Mass spectrometry and NMR spectroscopy revealed the chemical structure of serofendic acid (15-hydroxy-17-methylsulfinylatisan-19-oic acid) as a sulfur-containing atisane-type diterpenoid, which is unique among known endogenous substances. Synthetic serofendic acid exhibited potent protective actions on cortical neurons against cytotoxicity of a nitric oxide donor as well as of glutamate, although it did not show appreciable influences on glutamate receptor-mediated responses in these neurons. Electron spin resonance analysis demonstrated that serofendic acid had no direct scavenging activity on nitric oxide radicals but was capable of inhibiting the generation of hydroxyl radical, a presumed “executor” radical in the nitric oxide-mediated neurotoxic cascade. These findings suggest that serofendic acid is a low-molecular-weight bioactive factor that promotes survival of CNS neurons, probably through the attenuation of free radical-mediated insults.

The "Cyclopropyl Fragment" is a Versatile Player that Frequently Appears in Preclinical/Clinical Drug Molecules.

Abstract: Recently, there has been an increasing use of the cyclopropyl ring in drug development to transition drug candidates from the preclinical to clinical stage. Important features of the cyclopropane ring are, the (1) coplanarity of the three carbon atoms, (2) relatively shorter (1.51 A) C–C bonds, (3) enhanced π-character of C–C bonds, and (4) C–H bonds are shorter and stronger than those in alkanes. The present review will focus on the contributions that a cyclopropyl ring makes to the properties of drugs containing it. Consequently, the cyclopropyl ring addresses multiple roadblocks that can occur during drug discovery such as (a) enhancing potency, (b) reducing off-target effects, (c) increasing metabolic stability, (d) increasing brain permeability, (e) decreasing plasma clearance, (f) contributing to an entropically more favorable binding to the receptor, (g) conformational restriction of peptides/peptidomimetics to prevent proteolytic hydrolysis, and (h) altering drug pKa to reduce its P-glycoprotein e...

Compositions useful as inhibitors of protein kinases

Abstract: The present invention provides a compound of formula I: or a pharmaceutically acceptable salt or mixtures thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK mammalian protein kinase, and more particularly inhibitors of GSK-3 mammalian protein kinase. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.

Enantioselective synthesis of sulfoxides: 2000-2009.

Abstract: 1.2.2. Davis Oxaziridines 4305 1.2.3. Metal Complexes in Enantioselective Oxidation 4305 1.3. New Applications 4307 1.3.1. Chiral Sulfinate Method 4307 1.3.2. Oxidation with Chiral Oxaziridines 4309 1.3.3. Oxidation Using Metal Complexes 4310 1.4. New Systems 4313 1.4.1. C-S Bond Formation 4314 1.4.2. Organic Oxidants 4315 1.4.3. Oxidations Catalyzed by Metal Complexes 4316 1.5. Diastereoselective Oxidations 4330 1.6. Heterogenized Systems 4332 1.7. Summary 4335 2. Biological Oxidations 4336 2.

Modulators of atp-binding cassette transporters

Abstract: The present invention relates to modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator, compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.