- Synthetic models related to methoxalen and menthofuran-cytochrome P450 (CYP) 2A6 interactions. Benzofuran and coumarin derivatives as potent and selective inhibitors of CYP2A6
-
Human microsomal cytochrome P450 (CYP) 2A6 contributes extensively to nicotine detoxication but also activates tobacco-specific procarcinogens to mutagenic products. We prepared a series of benzofuran and coumarin derivatives that have inhibitory effects on the activity of human CYP2A6. The reported compounds methoxalen and menthofuran had potent inhibitory effects on the activity of CYP2A6 with IC50 values of 0.47 μM and 1.27 μM, respectively. Synthetic benzofuran (4-methoxybenzofuran: IC50=2.20 μM) and coumarin (5-methoxycoumarin: IC50=0.13 μM and 6-methoxycoumarin: IC50=0.64 μM) derivatives, which have more selective effects than those of methoxalen and menthofuran, exhibited comparable activities against CYP2A6. These compounds can be used as a lead compounds in the design of CYP2A6 inhibitor drugs to reduce smoking and tobacco-related cancers.
- Yamaguchi, Yuki,Akimoto, Ichie,Motegi, Kyoko,Yoshimura, Teruki,Wada, Keiji,Nishizono, Naozumi,Oda, Kazuaki
-
-
Read Online
- New heteroaryl carbamates: Synthesis and biological screening in vitro and in mammalian cells of wild-type and mutant HIV-protease inhibitors
-
New heteroaryl HIV-protease inhibitors bearing a carbamoyl spacer were synthesized in few steps and high yield, from commercially available homochiral epoxides. Different substitution patterns were introduced onto a given isopropanoyl-sulfonamide core that can have either H or benzyl group. The in vitro inhibition activity against recombinant protease showed a general beneficial effect of both carbamoyl moiety and the benzyl group, ranging the IC50 values between 11 and 0.6 nM. In particular, benzofuryl and indolyl derivatives showed IC50 values among the best for such structurally simple inhibitors. Docking analysis allowed to identify the favorable situation of such derivatives in terms of number of interactions in the active site, supporting the experimental results. The inhibition activity was also confirmed in HEK293 mammalian cells and was maintained against protease mutants. Furthermore, the metabolic stability was comparable with that of the commercially available inhibitors.
- Tramutola, Francesco,Armentano, Maria Francesca,Berti, Federico,Chiummiento, Lucia,Lupattelli, Paolo,D'Orsi, Rosarita,Miglionico, Rocchina,Milella, Luigi,Bisaccia, Faustino,Funicello, Maria
-
-
Read Online
- Facile entry to 4- and 5-hydroxybenzofuran and to their amino derivatives
-
An innovative one-step procedure for the synthesis of 4-hydroxybenzofuran and an improved synthesis of 5-hydroxybenzofuran is reported. Such compounds were also transformed into their amino derivatives via Smiles rearrangement with good to high overall yields. Copyright Taylor & Francis Group, LLC.
- Bonini, Carlo,Cristiani, Graziella,Funicello, Maria,Viggiani, Licia
-
-
Read Online
- Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand
-
Mutant huntingtin (mHTT) protein carrying the elongated N-Terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington's disease (HD) pathology. A high-Affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD therapeutic development and disease progression. To identify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural activity studies; lead optimization of aggregate-binding affinity, unbound fractions in brain, permeability, and low efflux culminated in the discovery of compound 1, which exhibited target engagement in autoradiography (ARG) studies in brain slices from HD mouse models and postmortem human HD samples. PET imaging studies with 11C-labeled 1 in both HD mice and WT nonhuman primates (NHPs) demonstrated that the right-hand-side labeled ligand [11C]-1R (CHDI-180R) is a suitable PET tracer for imaging of mHTT aggregates. [11C]-1R is now being advanced to human trials as a first-in-class HD PET radiotracer.
- Prime, Michael E.,Liu, Longbin,Lee, Matt R.,Khetarpal, Vinod,Brown, Christopher J.,Johnson, Peter D.,Miranda-Azpiazu, Patricia,Chen, Xuemei,Clark-Frew, Daniel,Coe, Samuel,Davis, Randall,Dickie, Anthony,Ebneth, Andreas,Esposito, Simone,Gadouleau, Elise,Gai, Xinjie,Galan, Sebastien,Green, Samantha,Greenaway, Catherine,Giles, Paul,Halldin, Christer,Hayes, Sarah,Herbst, Todd,Herrmann, Frank,He?mann, Manuela,Jia, Zhisheng,Kiselyov, Alexander,Kotey, Adrian,Krulle, Thomas,Mangette, John E.,Marston, Richard W.,Menta, Sergio,Mills, Matthew R.,Monteagudo, Edith,Nag, Sangram,Nibbio, Martina,Orsatti, Laura,Schaertl, Sabine,Scheich, Christoph,Sproston, Joanne,Stepanov, Vladimir,Svedberg, Marie,Takano, Akihiro,Taylor, Malcolm,Thomas, Wayne,Toth, Miklós,Vaidya, Darshan,Vanr?s, Katarina,Weddell, Derek,Wigginton, Ian,Wityak, John,Mrzljak, Ladislav,Munoz-Sanjuan, Ignacio,Bard, Jonathan A.,Dominguez, Celia
-
-
Read Online
- 2-Nitrofurans as dienophiles in Diels-Alder reactions
-
α-Nitrofuran derivatives are studied in Diels-Alder reactions under thermal conditions. In contrast to α-acylfurans, they proved to be efficient dienophiles.
- Rosa, Claudia Della,Kneeteman, María N.,Mancini, Pedro M.E.
-
-
Read Online
- Synthesis, characterization, and properties of a benzofuran-based cage-shaped borate: Photo activation of Lewis acid catalysts
-
A cage-shaped borate with benzofuran moieties was synthesized. This borate showed a higher degree of catalytic activity for Mukaiyama-aldol type reactions than a simple benzene-based cage-shaped borate induced by self-aggregation. Moreover, the exposure of the complex to black-light irradiation enhanced the catalytic activity.
- Konishi, Akihito,Yasunaga, Ryosuke,Chiba, Kouji,Yasuda, Makoto
-
-
Read Online
- TRICYCLIC SUBSTITUTED PIPERIDINE DIONE COMPOUND
-
Disclosed is a series of tricyclic substituted piperidine dione compounds, and applications thereof in the preparation of medicines for treating diseases related to CRBN protein; specifically disclosed are the derivative compound represented by formula (I) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0101-0102
(2021/07/17)
-
- Immunoproteasome Inhibitor-Doxorubicin Conjugates Target Multiple Myeloma Cells and Release Doxorubicin upon Low-Dose Photon Irradiation
-
Proteasome inhibitors are established therapeutic agents for the treatment of hematological cancers, as are anthracyclines such as doxorubicin. We here present a new drug targeting approach that combines both drug classes into a single molecule. Doxorubicin was conjugated to an immunoproteasome-selective inhibitor via light-cleavable linkers, yielding peptide epoxyketone-doxorubicin prodrugs that remained selective and active toward immunoproteasomes. Upon cellular uptake and immunoproteasome inhibition, doxorubicin is released from the immunoproteasome inhibitor through photoirradiation. Multiple myeloma cells in this way take a double hit: immunoproteasome inhibition and doxorubicin-induced toxicity. Our strategy, which entails targeting of a cytotoxic agent, through a covalent enzyme inhibitor that is detrimental to tumor tissue in its own right, may find use in the search for improved anticancer drugs.
- Dekker, Patrick M.,Florea, Bogdan I.,Maiorana, Santina,Maurits, Elmer,Neefjes, Jacques J. C.,Overkleeft, Herman S.,Van De Graaff, Michel J.,Van Der Zanden, Sabina Y.,Van Kasteren, Sander I.,Wander, Dennis P. A.
-
supporting information
p. 7250 - 7253
(2020/08/06)
-
- Method suitable for large-scale production of B-RAF kinase dimer inhibitor
-
The invention relates to a method for large-scale production of a B-RAF kinase dimer inhibitor 1-((1S, 1aS, 6bS)-5-((7-oxo-5, 6, 7, 8-tetrahydro-1, 8-diazanaphthalene-4-yl) oxy)-1a, 6b-dihydro-1H-cyclopropyl [b] benzofuran-1-yl)-3-(2, 4, 5- trifluorophenyl) urea (hereinafter sometimes referred to as a compound 1). The method enables impurities or by-products to be controlled to 0.05% or less without the use of expensive column chromatography operations. Thus, the method greatly reduces cost and is suitable for large-scale production.
- -
-
Paragraph 0067-0068
(2020/08/18)
-
- Stable crystalline form A of B-RAF kinase dimer inhibitor
-
The invention relates to a stable crystalline form A of a B-RAF kinase dimer inhibitor 1-((1S, 1aS, 6bS)-5-((7-oxo-5, 6, 7, 8-tetrahydro-1, 8-diazanaphthalene-4-yl) oxy)-1a, 6b-dihydro-1H-cyclopropyl[b] benzofuran-1-yl)-3-(2, 4, 5- trifluorophenyl) urea (hereinafter sometimes referred to as a compound 1), a preparation method of the crystalline Form A and therapeutic use of the crystalline Form A.
- -
-
Paragraph 0059; 0074-0075
(2020/08/18)
-
- STABLE SOLID DISPERSIONS OF B-RAF KINASE DIMER INHIBITOR, METHODS OF PREPARATION, AND USES THEREFOR
-
Disclosed herein is a physically stable solid dispersion comprising Compound 1, i.e., the B-RAF kinase dimer inhibitor 1- ( (1S, 1aS, 6bS) -5- ( (7-oxo-5, 6, 7, 8-tetrahydro-1, 8-naphthyridin-4-yl) oxy) -1a,6b-dihydro-1H-cyclopropa [b] benzofuran-1-yl) -3- (2, 4, 5-trifluorophenyl) urea and a specific stabilizing polymer, the method for preparing the same, and the uses of the solid dispersion. Also disclosed herein is the crystalline form of Compound 1.
- -
-
Page/Page column 0179; 0193-0194
(2020/08/13)
-
- Amorphous B-RAF kinase dimer inhibitor
-
The invention relates to a stable amorphous form of a B-RAF kinase dimer inhibitor 1-((1S, 1aS, 6bS)-5-((7-oxo-5, 6, 7, 8-tetrahydro-1, 8-diazanaphthalene-4-yl) oxy)-1a, 6b-dihydro-1H-cyclopropyl [b]benzofuran-1-yl)-3-(2, 4, 5- trifluorophenyl) urea (hereinafter sometimes referred to as a compound 1), a prepration method of the amorphous compound and therapeutic use of the amorphous compound.
- -
-
Paragraph 0069; 0083; 0084
(2020/08/18)
-
- Palladium-Catalyzed Hydroxylation of Aryl Halides with Boric Acid
-
Boric acid, B(OH)3, is proved to be an efficient hydroxide reagent in converting (hetero)aryl halides to the corresponding phenols with a Pd catalyst under mild conditions. Various phenol products were obtained in good to excellent yields. This transformation tolerates a broad range of functional groups and molecules, including base-sensitive substituents and complicated pharmaceutical (hetero)aryl halide molecules.
- Song, Zhi-Qiang,Wang, Dong-Hui
-
supporting information
p. 8470 - 8474
(2020/11/18)
-
- Polymer-supported eosin Y as a reusable photocatalyst for visible light mediated organic transformations
-
A novel polymer-supported recyclable photocatalyst has been developed for visible light mediated oxidation reactions. The organic dye eosin Y was loaded on macroporous commercially available Amberlite IRA 900 chloride resin and exploited as a photocatalyst for visible light mediated oxidation of thioethers to sulfoxides and phenylboronic acids to phenols under open atmospheric air. Varieties of functional groups were well tolerated during oxidation. The catalyst is recyclable for six cycles without significant loss in its efficiency. Furthermore, gram-scale oxidation of sulfides to sulfoxides has been demonstrated to prove the commercial viability of the method.
- Sridhar, Arunasalam,Rangasamy, Rajmohan,Selvaraj, Mari
-
p. 17974 - 17979
(2019/12/02)
-
- BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS
-
Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII); or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.
- -
-
Page/Page column 379; 380
(2018/03/25)
-
- COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER
-
Disclosed herein is a pharmaceutical combination for use in the prevention, delay of progression or treatment of cancer, wherein the pharmaceutical combination exhibits a synergistic efficacy. The pharmaceutical combination comprises a humanized antagonist monoclonal antibody against PD- and a RAF inhibitor. Also disclosed herein is a combination for use in the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject a therapeutically effective amount of a humanized antagonist monoclonal antibody against PD-1 and a therapeutically effective amount of a RAF inhibitor.
- -
-
Paragraph 0091
(2018/09/25)
-
- FORMULATIONS FOR 2-HETEROARYL SUBSTITUTED BENZOFURANS
-
Processes and compositions for 2-heteroaryl substituted benzofuran derivatives are described. The 2-heteroaryl substituted benzofuran derivatives may be suitable for preparing radiolabeled 2-heteroaryl substituted benzofuran derivatives for imaging amyloid deposits in living patients.
- -
-
Page/Page column 23
(2017/06/12)
-
- Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile
-
In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control β-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H … π interactions with Trp105 and Phe178 residues compared to the control β-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation.
- Bian, Jinlei,Li, Xiang,Wang, Nan,Wu, Xingsen,You, Qidong,Zhang, Xiaojin
-
-
- Chemoselective oxidation of aryl organoboron systems enabled by boronic acid-selective phase transfer
-
We report the direct chemoselective Brown-type oxidation of aryl organoboron systems containing two oxidizable boron groups. Basic biphasic reaction conditions enable selective formation and phase transfer of a boronic acid trihydroxyboronate in the presence of boronic acid pinacol (BPin) esters, while avoiding speciation equilibria. Spectroscopic investigations validate a base-promoted phase-selective discrimination of organoboron species. This phenomenon is general across a broad range of organoboron compounds and can also be used to invert conventional protecting group strategies, enabling chemoselective oxidation of BMIDA species over normally more reactive BPin substrates. We also demonstrate the selective oxidation of diboronic acid systems with chemoselectivity predictable a priori. The utility of this method is exemplified through the development of a chemoselective oxidative nucleophile coupling.
- Molloy, John J.,Clohessy, Thomas A.,Irving, Craig,Anderson, Niall A.,Lloyd-Jones, Guy C.,Watson, Allan J. B.
-
p. 1551 - 1559
(2017/02/10)
-
- MALEATE SALTS OF A B-RAF KINASE INHIBITOR, CRYSTALLINE FORMS, METHODS OF PREPARATION, AND USES THEREFORE
-
The invention relates to 5- ( ( (1R, 1aS, 6bR) -1- (6- (trifluoromethyl) -1H-benzo [d] imidazol-2-yl) -1a,6b-dihydro-1H-cyclopropa [b] benzofuran-5-yl) oxy) -3, 4-dihydro-1, 8-naphthyridin-2 (1H) -one (Compound 1) maleate salts, in particular the sesqui-maleate salt and its crystalline forms, methods of preparation, pharmaceutical compositions, and therapeutic uses for treatment of diseases or disorders mediated by BRAF or other kinases.
- -
-
Paragraph 0156
(2016/11/02)
-
- Expanding the Strained Alkyne Toolbox: Generation and Utility of Oxygen-Containing Strained Alkynes
-
We report synthetic methodology that permits access to two oxacyclic strained intermediates, the 4,5-benzofuranyne and the 3,4-oxacyclohexyne. In situ trapping of these intermediates affords an array of heterocyclic scaffolds by the formation of one or more new C-C or C-heteroatom bonds. Experimentally determined regioselectivities were consistent with predictions made using the distortion/interaction model and were also found to be greater compared to selectivities seen in the case of trapping experiments of the corresponding N-containing intermediates. These studies demonstrate the synthetic versatility of oxacyclic arynes and alkynes for the synthesis of functionalized heterocycles, while further expanding the scope of the distortion/interaction model. Moreover, these efforts underscore the value of harnessing strained heterocyclic intermediates as a unique approach to building polycyclic heteroatom-containing frameworks.
- Shah, Tejas K.,Medina, Jose M.,Garg, Neil K.
-
supporting information
p. 4948 - 4954
(2016/05/10)
-
- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS
-
Novel tricyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
- -
-
Page/Page column 97
(2015/07/07)
-
- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OSTEOPOROSIS
-
Novel tricyclic compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
- -
-
Page/Page column 96
(2015/07/07)
-
- FUSED TRICYCLIC UREA COMPOUNDS AS RAF KINASE AND/OR RAF KINASE DIMER INHIBITORS
-
Provided are certain fused tricyclic urea compounds and salts thereof, compositions thereof, and methods of use therefor.
- -
-
Page/Page column 47; 48
(2015/01/16)
-
- FUSED TRICYCLIC AMIDE COMPOUNDS AS MULTIPLE KINASE INHIBITORS
-
Provided are fused tricyclic amide compounds, pharmaceutical compositions comprising at least one such fused tricyclic compound, processes for the preparation thereof, and the use thereof in therapy. Disclosed herein are certain tricyclic amide compounds that can be useful for inhibiting multiple (specifically BRAF and/or EGFR-T790M) kinases and for treating disorders mediated thereby.
- -
-
Page/Page column 56; 57
(2015/01/16)
-
- PYRAZINES AS DELTA OPIOID RECEPTOR MODULATORS
-
Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R1, R2, R3, L, X, and Y are defined herein.
- -
-
Page/Page column 18
(2011/05/08)
-
- NEW BENZOFURANS SUITABLE AS PRECURSORS TO COMPOUNDS THAT ARE USEFUL FOR IMAGING AMYLOID DEPOSITS
-
The present invention relates to novel derivatives that are suitable as precursors to compounds that are useful for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. The compounds deriving from these precursors are useful in methods of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease by positron emission tomography (PET) as well as measuring clinical efficacy of Alzheimer's disease therapeutic agents. Furthermore, the present invention also discloses the precursor compounds in crystalline form.
- -
-
Page/Page column 14; 29
(2010/04/06)
-
- Thermolysis of 4-(ω-hydroxyalkyl)-2,6-di-tert-butylphenols
-
The process of thermolysis of tert-butylated hydroxyalkyl phenols includes de-tert-butylation, etherification, and fragmentation of the hydroxyalkyl group. On the basis of the proposed schemes of the mechanism of thermal de-tert-butylation the path of the search for catalysts for the synthesis of 4-hydroxyalkylphenols is defined and transformations of the by-products into biologically active substances were considered.
- Krysin,Egorova,Vasil'Ev
-
experimental part
p. 275 - 283
(2010/07/15)
-
- S1P RECEPTOR MODULATING COMPOUNDS AND USE THEREOF
-
The present invention relates to compounds of the general formula (I) that have activity as SlP receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate SlP receptor activity. The compounds may be used as immunomodulators, e.g., for treating or preventing diseases such as autoimmune and related immune disorders including systemic lupus erythematosus, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, type I diabetes, uveitis, psoriasis, myasthenia gravis, rheumatoid arthritis, non-glomerular nephrosis, hepatitis, Behcet's disease, glomerulonephritis, chronic thrombocytopenic purpura, hemolytic anemia, hepatitis and Wegner's granuloma; and for treating other conditions.
- -
-
Page/Page column 43; 91
(2008/06/13)
-
- 9-Azabicyclo[3.3.1]nonane derivatives
-
The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula I, wherein each of the substituents is given the definition as set forth in the specification and claims, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
- -
-
Page/Page column 21/2
(2010/11/27)
-
- 9-AZABICYCLO [3 . 3 . 1] NONANE DERIVATIVES AS MONOAMINE REUPTAKE INHIBITORS
-
The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula (I), wherein R1 is H or C1-5alkyl; X is O or NR2, wherein R2 is H, C1-5alkyl or C2-5acyl and Ar is C6-10aryl or a 5-10 membered heteroaryl ring system, both being optionally substituted with one to three of R3-R5 independently selected from halogen, C1-5alkyl, C1-5alkoxy, C3-6cycloalkyl, C2-5alkenyl, C2-5alkynyl, CN, NO2, hydroxy, phenyl, phenoxy and phenylC1-2alkoxy, wherein said C1-5alkyl and C1-5alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC1-2alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R3-R5 at adjacent positions together form a methylenedioxy or propylene unit, with the proviso that the compounds exo-9-methyl-3-phenoxy-9-azabicyclo[3.3.1]nonane and N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine are excluded, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
- -
-
Page/Page column 40
(2010/11/26)
-
- Therapeutic diphenyl ether ligands
-
This invention is directed to compounds of formula Ia, Ib or Ic and to pharmaceutical compositions thereof: or a prodrug thereof and a pharmaceutically acceptable carrier, wherein the R groups are defined in the specification; and, in which the dashed line represents an optional double bond. The invention is also directed to methods of treating, diagnosing, and preventing disorders of the central nervous system that are associated with 5HT receptors, including obesity, attention deficit disorder, migraine, depression, epilepsy, anxiety, Alzheimer's disease, withdrawal from drug abuse, pain, schizophrenia, stress-related disorders, panic disorder, sleep disorders, phobias, obsessive compulsive disorder, post-traumatic-stress syndrome, immune system depression, stress-induced gastrointestinal dysfunction, stress-induced cardiovascular dysfunction, and sexual dysfunction.
- -
-
Page/Page column 34
(2010/10/20)
-
- Anilide derivative, production and use thereof
-
This invention is to provide a compound of the formula: wherein R1is an optionally substituted 5- to 6-membered ring; the ring A is an optionally substituted 6- to 7-membered ring; the ring B is an optionally substituted benzene ring; n is an integer of 1 or 2; Z is a chemical bond or a divalent group; R2is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula: ?wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium; and R5and R6are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, and R5and R6may bind to each other to form a cyclic group together with the adjacent phosphorus atom, or a salt thereof , which is useful for antagonizing CCR5 and also for the prevention and treatment of infectious disease of HIV.
- -
-
-
- Depigmenting cosmetic or dermatologic composition containing a benzofuran derivative and its use in depigmentating skin
-
A depigmenting cosmetic or dermatologic composition for use in bleaching the skin or treating pigmental spots contains in a vehicle suitable for topical application to the skin a benzofuran derivative having the formula STR1 wherein the OH function occupies position 5 or 6, R1 and R2, each independently, represent hydrogen or alkyl having 1-4 carbon atoms, n is 0 or 1, when n is 0, the C2 -C3 bond is a double bond, and when n is 1, the C2 -C3 bond is a single bond.
- -
-
-
- Endothelin receptor antagonists
-
Novel compounds of the formula I STR1 in which R 1, R 2, R 3 and X have the meaning indicated in claim 1, and their salts exhibit endothelin receptor-antagonistic properties.
- -
-
-
- Structures and Stereochemical Assignments of Some Novel Chiral Synthons Derived from the Biotransformation of 2,3- Dihydrobenzofuran and Benzofuran by Pseudomonas putida
-
Metabolism of 2,3-dihydrobenzofuran using intact cells of Pseudomonas putida UV4 gave mainly (3S)-3-hydroxy-2,3-dihydrobenzofuran which was in turn oxidized to an unstable intermediate, (3S,4R,5S)-3,4,5-trihydroxy-2,3,4,5-tetrahydrobenzofuran.Spontaneous dehydration of this cis,cis-triol occurred in the carbocyclic ring to give (3S)-3,5-dihydroxy 2,3-dihydrobenzofuran and in the heterocyclic ring to yield (4R,5S)-cis-4,5-dihydroxy-4,5-dihydrobenzofuran.Bacterial metabolism of benzofuran was found to occur in the carbocyclic ring to form (6S,7S)-cis-6,7-dihydroxy-6,7-dihydrobenzofuran and its dehydration product, 6-hydroxybenzofuran.Dioxygenase-catalysed cis-dihydrodiol formation in the heterocyclic ring of benzofuran (to give cis-2,3-dihydroxy-2,3-dihydrobenzofuran as a transient intermediate) is proposed to account for the appearance of (1R)-1,2-dihydroxy-1-(2'-hydroxyphenyl)ethane as a major metabolite of benzofuran. cis-4,5-Dihydroxy-4,5-dihydrobenzofuran and cis-6,7-dihydroxy-6,7-dihydrobenzofuran are potentially valuable chiral synthons which can be added to the small pool of bicyclic cis-dihydrodiol metabolites currently available for synthesis.
- Boyd, Derek R.,Sharma, Narain D.,Boyle, Rosemary,Malone, John F.,Chima, Jagdeep,Dalton, Howard
-
p. 1307 - 1324
(2007/10/02)
-