32263-64-2Relevant academic research and scientific papers
Convincing Catalytic Performance of Oxo-Tethered Ruthenium Complexes for Asymmetric Transfer Hydrogenation of Cyclic α-Halogenated Ketones through Dynamic Kinetic Resolution
Touge, Taichiro,Nara, Hideki,Kida, Michio,Matsumura, Kazuhiko,Kayaki, Yoshihito
supporting information, p. 3070 - 3075 (2021/05/05)
A highly efficient dynamic kinetic resolution of cyclic halohydrins was achieved by the asymmetric transfer hydrogenation of racemic α-haloketones. Bifunctional oxo-tethered Ru(II) catalysts could promote the reduction without deterioration of halogens. By structural tuning of the catalyst, chiral alcohols having halogen, ester, carboxamide, and sulfone functions were obtained variably with excellent diastereo- and enantioselectivities (up to >99:1 d.r. and >99.9 ee), which provided a concise synthetic approach to a dopamine D3 receptor ligand, (+)-PHNO.
The evaluation of 1-tetralone and 4-chromanone derivatives as inhibitors of monoamine oxidase
Cloete, Stephanus J.,N’Da, Clarina I.,Legoabe, Lesetja J.,Petzer, Anél,Petzer, Jacobus P.
, p. 491 - 507 (2020/10/02)
Abstract: Monoamine oxidase (MAO) is of much clinical relevance, and inhibitors of this enzyme are used in the treatment for neuropsychiatric and neurodegenerative disorders such as depression and Parkinson’s disease. The present study synthesises and evaluates the MAO inhibition properties of a series of 33 1-tetralone and 4-chromanone derivatives in an attempt to discover high-potency compounds and to expand on the structure–activity relationships of MAO inhibition by these classes. Among these series, eight submicromolar MAO-A inhibitors and 28 submicromolar MAO-B inhibitors are reported, with all compounds acting as specific inhibitors of the MAO-B isoform. The most potent inhibitor was a 1-tetralone derivative (1h) with IC50 values of 0.036 and 0.0011?μM for MAO-A and MAO-B, respectively. Interestingly, with the reduction of 1-tetralones to the corresponding alcohols, a decrease in MAO inhibition potency is observed. Among these 1-tetralol derivatives, 1p (IC50 = 0.785?μM) and 1o (IC50 = 0.0075?μM) were identified as particularly potent inhibitors of MAO-A and MAO-B, respectively. Potent compounds such as those reported here may act as leads for the future development of MAO-B specific inhibitors. Graphic abstract: The present study describes the MAO inhibitory activities of a series of 1-tetralone and 4-chromanone derivatives. Numerous high-potency MAO-B specific inhibitors were identified.[Figure not available: see fulltext.].
An Electrophilic Trifluoromethylthiolation of Silylenol Ethers and β-Naphthols with Diethylaminosulfur Trifluoride and (Trifluoromethyl)trimethylsilane
Saravanan, Perumal,Anbarasan, Pazhamalai
supporting information, p. 2894 - 2899 (2018/08/17)
An efficient and general trifluoromethylthiolation of silylenol ethers and β-naphthols have been accomplished employing the combination of diethylaminosulfur trifluoride (DAST) and (trifluoromethyl)trimethylsilane (CF3TMS) as source of electrophilic trifluoromethylthio moiety for the synthesis of α-trifluoromethylthiolated carbonyl compounds and β-naphthols in good yields. Important features of this method include wide functional group tolerance and use of readily available DAST/CF3TMS. Potential of the methodology was demonstrated via the synthesis of α-trifluoromethylthiolated (+)-4-cholesten-3-one and naphthoquinone. (Figure presented.).
SULFONAMIDE DERIVATIVES AND PHARMACEUTICAL APPLICATIONS THEREOF
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Paragraph 00295, (2015/11/09)
Provided herein are sulfonamide derivatives or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and their uses for treating Alzheimer's disease. Also provided herein are pharmaceutical compositions containing such compounds, and use of such compounds or pharmaceutical compositions thereof for managing or treating 5-HT6 receptor-mediated diseases, especially in the manufacture of a medicament for managing or treating Alzheimer's disease.
The Synthesis and Evaluation of C7-Substituted α-Tetralone Derivatives as Inhibitors of Monoamine Oxidase
Legoabe, Lesetja J.,Petzer, Anél,Petzer, Jacobus P.
, p. 895 - 904 (2015/10/06)
Based on a previous report that α-tetralone (3,4-dihydro-2H-naphthalen-1-one) is a promising scaffold for the design of highly potent inhibitors of the enzyme, monoamine oxidase, the present study investigates the monoamine oxidase inhibitory properties of a synthetic series of fifteen C7-substituted α-tetralone derivatives. Arylalkyloxy substitution on C7 of the α-tetralone moiety yielded compounds with high inhibition potencies toward the human monoamine oxidase-B isoform with all compounds possessing IC50 values in the submicromolar range (0.00089-0.047 μm). The C7-substituted α-tetralones also were highly potent monoamine oxidase-A inhibitors with thirteen (of fifteen) compounds possessing IC50 values in the submicromolar range (0.010-0.741 μm). The α-tetralones were, however, in each instance selective for monoamine oxidase-B over the monoamine oxidase-A isoform. Dialyses of enzyme-inhibitor mixtures show that, while a representative inhibitor acts as a reversible monoamine oxidase-A inhibitor, inhibition of monoamine oxidase-B is not readily reversed by dialysis. Using a molecular modeling approach, possible binding orientations and interactions of selected α-tetralones with the active sites of the monoamine oxidases are also proposed. This study suggests that C7-substituted α-tetralones are promising monoamine oxidase inhibitors and may represent lead compounds for the development of therapies for Parkinson's disease and depression. C7-Substituted α-tetralones act as high potency reversible inhibitors of human MAO-A and MAO-B. This class of compounds represent promising leads for the development of therapies for Parkinson's disease and depression.
Synthesis of the dopamine D2/D3 receptor agonist (+)-PHNO via supercritical fluid chromatography: Preliminary PET imaging study with [3-11C]-(+)PHNO
Shoup, Timothy M.,McCauley, John P.,Lee Jr., David F.,Chen, Rui,Normandin, Marc D.,Bonab, Ali A.,El Fakhri, Georges,Vasdev, Neil
supporting information, p. 682 - 685 (2014/01/23)
Carbon-11 labeled (+)-4-[1-11C]propyl-3,4,4a,5,6,10b-hexahydro- 2H-naphtho[1,2-b][1,4]oxazin-9-ol ([1-11C]-(+)-PHNO) is a dopamine D3-preferring agonist radiopharmaceutical used for medical imaging by positron emission tomography (PET). We report the synthesis of (+)-PHNO using supercritical fluid chromatography for enantiomeric resolution of its norpropyl derivative, HNO, followed by propylation. (+)-HNO was used to prepare the radiolabeling precursor, (+)-trans-4-acetyl-9-triisopropylsilyloxy-2,3,4a,5,6, 10b-hexahydro-4H-naphth[1,2b][1,4]oxazine, in 12 steps. Modifications to the labeling procedure were made to ensure consistent preparation of [3- 11C]-(+)-PHNO via [11C]CH3I. A preliminary PET imaging study was carried out with this tracer in an attempt to image dopamine receptors in brown adipose tissue (brown fat) in vivo.
Structure-activity relationship study of tricyclic necroptosis inhibitors
Jagtap, Prakash G.,Degterev, Alexei,Choi, Sungwoon,Keys, Heather,Yuan, Junying,Cuny, Gregory D.
, p. 1886 - 1895 (2008/02/03)
Necroptosis is a regulated caspase-independent cell death mechanism that can be induced in multiple cell types and is characterized by morphological features resembling necrosis. Here we describe a series of tricyclic heterocycles (i.e., 3-phenyl-3,3a,4,5-tetrahydro-2H-benz[g]indazoles, 3-phenyl-2,3,3a,4-tetrahydro-[1]benzopyrano[4,3-c]pyrazoles, 3-phenyl-2,3,3a,4-tetrahydro[1]benzothiopyrano[4,3-c]pyrazoles, and 5,5-dioxo-3-phenyl-2,3,3a,4-tetrahydro[1]benzothiopyrano[4,3-c]pyrazoles], collectively termed Nec-3, that can potently inhibit necroptosis. For example, compounds 8, 22, 41, 53, and 55 inhibit necroptosis in an FADD-deficient variant of human Jurkat T cells treated for 24 h with TNF-α with EC50 values in the range 0.15-0.29 μM. Distinct from the previously described series of hydantoin-containing indole derivatives (Nec-1), the Nec-3 series exhibits specificity in inhibiting TNF-α-induced necroptosis. A structure-activity relationship (SAR) study revealed that the (3R,3aR)-rel-diastereomers were more active than the (3R,3aS)-rel-diastereomers for all four ring systems. Introduction of fluorine or methoxy to the 8-position of the tricyclic ring and a methoxy to the 4-position of the pendent phenyl ring increased activity. Amides at the 2-position of the tricyclic ring were best. The Nec-3 series provides new tools for elucidating caspase-independent cell death pathways and potentially lead compounds for therapeutic development.
COMPOUNDS, SCREENS, AND METHODS OF TREATMENT
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Page/Page column 203-204, (2008/06/13)
The present invention features compounds, pharmaceutical compositions, and methods for treating trauma, ischemia, stroke, degenerative diseases associated with cellular necrosis, and other conditions. Screening assays for identifying compounds useful for treating these conditions are also described.
Pyrazinyl-substituted naphthalene derivatives
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, (2008/06/13)
Compounds of the formula where R1 is of the formulae R2 is —R4, —O—R4, —O—S (O)2—R4, —NR4R5, R4—(CH2)b—NH(C═X)—(CH2)—, R4—(CH2)b—O(C═O)NH—(CH2)c—(C═O)NH—, R4(C═O)NH—(C═O)NH—, —(CH2)b—NH(C═X)—(CH2)c—R4, R4—(CH2)b—O(C═)—(CH2)c—, —(CH2)b—O(C═O)—(CH2)c—R4, —NH(C═X)NH—R4, R4—O(C═O)O—, —O(C═)NH—R4, R4—O(C═O)NH—, —(CH2)b—(C═0)—(CH2)c—R4, —NH—S(O)2—R4, —C(OH)R4R5, —CH(OH)—R4, —(C═O)—NR4R5, —CN, —NO2, substituted C1 to C6 alkyl, substituted or unsubstituted C1 to C6 alkenyl, or substituted or unsubstituted C1 to C6 alkynyl, said substituted moieties substituted with a moiety of the formulae —R4, —R4R5, —O—R4, or —S(O)d—R4. These compounds are useful psychotherapeutics and are potent serotonin (5-HT1) agonists and antagonists and may be used in the treatment of depression, anxiety, eating disorders, obesity, drug abuse, cluster headache, migraine, pain and chronic paroxysmal hemicrania and headache associated with vascular disorders, and other disorders arising from deficient serotonergic neurotranmission. The compounds can also be used as centrally acting antihypertensives and vasodilators.
Fused polycyclic 2-aminopyrimidine derivatives
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, (2008/06/13)
Fused polycyclic 2-aminopyrimidines of formula (1): wherein Ar is an optionally substituted aromatic or heteroaromatic group; X is a carbon or nitrogen atom; Y is a carbon or nitrogen atom; Z is a linker group; A together with X and Y forms an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group; and the salts, solvates, hydrates and N-oxides thereof are described. The compounds are potent and selective inhibitors of the protein tyrosine kinases p56lck and p59fyn and are of use in the prophylaxis and treatment of immune diseases, hyperproliferative disorders and other diseases in which inappropriate p56lck and/or p59fyn activity is believed to have a role.
