The Experts below are selected from a list of 39 Experts worldwide ranked by ideXlab platform
Martin R. Bryce - One of the best experts on this subject based on the ideXlab platform.
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THERMAL FRAGMENTATION REACTIONS OF 1,4,2-DITHIAZINES AND 1,4,2,5-DITHIADIAZINES IN THE PRESENCE OF DIENOPHILES : SYNTHESIS OF 1,4-DITHIINE DerivativeS . X-RAY CRYSTAL STRUCTURES OF A 1,4,2-DITHIAZINE 1,1-DIOXIDE AND A 1,4,2,5- DITHIADIAZINE DERIVATIV
Journal of the Chemical Society Perkin Transactions 1, 1997Co-Authors: Martin R. Bryce, Shimon Yoshida, Andrei S. Batsanov, Judith A. K. HowardAbstract:The reaction of 5,6-dimethyl-3-(4-bromophenyl)-1,4,2-dithiazine 1b with dimethyl acetylenedicarboxylate (DMAD) at 180 °C in o-dichlorobenzene affords a mixture of thiophene Derivative 5 and Isothiazole Derivative 6: the former probably via the zwitterionic adduct 3 and dithiine Derivative 4, neither of which are isolable; the latter by sulfur extrusion from 1b. Reaction of norbornene with 1b affords dithiine Derivative 7. Oxidation of 1b with meta-chloroperoxybenzoic acid yields the 1,1-dioxide Derivative 8, the X-ray crystal structure of which is reported. The efficient synthesis of 3-aryl-6-methylthio-1,4,2,5-dithiadiazine Derivatives 12a–c by ring expansion of 1,4,2-dithiazolium salts 11a–c with an iodine–ammonia reagent is described. Reaction of 12c with DMAD at 180 °C affords the stable dithiine Derivative 14, probably via the intermediate 1,4,2-dithiazine 13. Electrochemical oxidation of 12a–c is irreversible, yielding 1,4,2,5-dithiadiazinium cation radicals at potentials [E ox = 1.55–1.73 V (vs. Ag/AgCl)] which are sensitive to the electronic nature of the para-substituent on the aryl ring. The X-ray crystal structure of 12b is reported.
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Synthetic, structural and electrochemical studies on the 1,2-dithiole-3-thione system: Preparation and reactions of the 5,6-dihydro-1,2-dithiolo[4,5-b][1,4]dithiin-3-ium cation
Tetrahedron, 1992Co-Authors: Martin R. Bryce, Gordon R. Davison, Adrian J. Moore, Michael B. Hursthouse, K. M. Abdul MalikAbstract:Abstract The synthesis, X-ray crystal structure and some reactions of 1,2-dithiole-3-thione Derivative 8 are reported. The structure of thione 8 is characterised by a remarkable three-dimensional network of close, non-bonded, S---S interactions. Compound 8 is efficiently converted into the 1,2-dithiolium cation salt 11 by sequential reaction with meta-chloroperoxybenzoic acid and sodium iodide. Cation salt 11 reacts with aqueous ammonia in the presence of iodine to afford Isothiazole Derivative 18 in high yield; the mechanism proposed for this reaction proceeds via 1,2,3-dithiazine Derivative 17. The solution electrochemistry of the title thione, and related compounds, has been studied by cyclic voltammetry.
Francesco Guerrera - One of the best experts on this subject based on the ideXlab platform.
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Antiviral Chemistry & Chemotherapy 18:277–283 Isothiazole Derivatives as antiviral agents
2016Co-Authors: Adriana Garozzo, Christian Cc Cutri, Christophe Pannecouque, Angelo Castro, Francesco Guerrera, Erik De ClercqAbstract:We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-Isothiazole-carbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3-methylthio-5-(4-OBn-phenyl)-4-Isothiazolecarbo-nitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a new Isothiazole Derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol-3-yl]-O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be activ
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Isothiazole Derivatives as antiviral agents
Antiviral chemistry & chemotherapy, 2007Co-Authors: Adriana Garozzo, Christian Cc Cutri, Christophe Pannecouque, Angelo Castro, Francesco Guerrera, Erik De ClercqAbstract:We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5phenylisothiazol-3-yl) disulphanyl-4-Isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol -3-yl)-O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (III B ) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3methylthio-5-(4-OBn-phenyl)-4-Isothiazolecarbonitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a new Isothiazole Derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol3-yl]-O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (III B ) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be active against rhinoviruses 2, 39, 86 and 89, Coxsackie B1 and measles virus.
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Synthesis of new 3-methylthio-5-aryl-4-Isothiazolecarbonitriles with broad antiviral spectrum.
Antiviral research, 2002Co-Authors: Christian Cc Cutri, Adriana Garozzo, M. A. Siracusa, A. Castro, Gianna Tempera, M. C. Sarva, Francesco GuerreraAbstract:Abstract The Isothiazole Derivative 3-methylthio-5-(4-OBn-phenyl)-4-Isothiazolecarbonitrile, coded IS - 50 , which in previous studies had exhibited a broad antipicornavirus spectrum of action, was selected as the model for the synthesis of a new series of 3-methylthio-5-aryl-4-Isothiazolecarbonitriles. These compounds were prepared in good yield (from 66 to 82%) by alkylation of 3-methylthio-5-(4-hydroxyphenyl)-4-Isothiazolecarbonitrile with suitable bromides in the presence of acetone; only the 4-cyanophenoxy Derivatives were obtained in a yield of less than 30%. All the compounds were screened against a panel of 17 representative human rhinovirus (HRV) serotypes belonging to both A and B groups, enteroviruses polio 1, ECHO 9 and Coxsackie B1, cardiovirus EMC, measles virus, and herpes simplex virus type 1 (HSV-1). Our results demonstrate that HRV 86 (group A) and HRVs 39 and 89 (group B) are the rhinovirus serotypes more susceptible to the action of these compounds. Isothiazole Derivatives with a longer intermediate alkyl chain exhibited good activity against polio 1 and ECHO 9. The compound bearing a butyl group between the two phenoxy rings showed the lowest IC 50 against Coxsackie B1 and measles viruses. No activity against HSV-1 was detected with any of the compounds screened.
Judith A. K. Howard - One of the best experts on this subject based on the ideXlab platform.
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THERMAL FRAGMENTATION REACTIONS OF 1,4,2-DITHIAZINES AND 1,4,2,5-DITHIADIAZINES IN THE PRESENCE OF DIENOPHILES : SYNTHESIS OF 1,4-DITHIINE DerivativeS . X-RAY CRYSTAL STRUCTURES OF A 1,4,2-DITHIAZINE 1,1-DIOXIDE AND A 1,4,2,5- DITHIADIAZINE DERIVATIV
Journal of the Chemical Society Perkin Transactions 1, 1997Co-Authors: Martin R. Bryce, Shimon Yoshida, Andrei S. Batsanov, Judith A. K. HowardAbstract:The reaction of 5,6-dimethyl-3-(4-bromophenyl)-1,4,2-dithiazine 1b with dimethyl acetylenedicarboxylate (DMAD) at 180 °C in o-dichlorobenzene affords a mixture of thiophene Derivative 5 and Isothiazole Derivative 6: the former probably via the zwitterionic adduct 3 and dithiine Derivative 4, neither of which are isolable; the latter by sulfur extrusion from 1b. Reaction of norbornene with 1b affords dithiine Derivative 7. Oxidation of 1b with meta-chloroperoxybenzoic acid yields the 1,1-dioxide Derivative 8, the X-ray crystal structure of which is reported. The efficient synthesis of 3-aryl-6-methylthio-1,4,2,5-dithiadiazine Derivatives 12a–c by ring expansion of 1,4,2-dithiazolium salts 11a–c with an iodine–ammonia reagent is described. Reaction of 12c with DMAD at 180 °C affords the stable dithiine Derivative 14, probably via the intermediate 1,4,2-dithiazine 13. Electrochemical oxidation of 12a–c is irreversible, yielding 1,4,2,5-dithiadiazinium cation radicals at potentials [E ox = 1.55–1.73 V (vs. Ag/AgCl)] which are sensitive to the electronic nature of the para-substituent on the aryl ring. The X-ray crystal structure of 12b is reported.
Christian Cc Cutri - One of the best experts on this subject based on the ideXlab platform.
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Antiviral Chemistry & Chemotherapy 18:277–283 Isothiazole Derivatives as antiviral agents
2016Co-Authors: Adriana Garozzo, Christian Cc Cutri, Christophe Pannecouque, Angelo Castro, Francesco Guerrera, Erik De ClercqAbstract:We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-Isothiazole-carbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3-methylthio-5-(4-OBn-phenyl)-4-Isothiazolecarbo-nitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a new Isothiazole Derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol-3-yl]-O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be activ
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Isothiazole Derivatives as antiviral agents
Antiviral chemistry & chemotherapy, 2007Co-Authors: Adriana Garozzo, Christian Cc Cutri, Christophe Pannecouque, Angelo Castro, Francesco Guerrera, Erik De ClercqAbstract:We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5phenylisothiazol-3-yl) disulphanyl-4-Isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol -3-yl)-O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (III B ) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3methylthio-5-(4-OBn-phenyl)-4-Isothiazolecarbonitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5phenylisothiazol-3-yl)-O-ethyl thiocarbonate as the model for the synthesis of a new Isothiazole Derivative, S-[4-cyano-5-(4-OBn-phenyl)isothiazol3-yl]-O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (III B ) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be active against rhinoviruses 2, 39, 86 and 89, Coxsackie B1 and measles virus.
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Synthesis of new 3-methylthio-5-aryl-4-Isothiazolecarbonitriles with broad antiviral spectrum.
Antiviral research, 2002Co-Authors: Christian Cc Cutri, Adriana Garozzo, M. A. Siracusa, A. Castro, Gianna Tempera, M. C. Sarva, Francesco GuerreraAbstract:Abstract The Isothiazole Derivative 3-methylthio-5-(4-OBn-phenyl)-4-Isothiazolecarbonitrile, coded IS - 50 , which in previous studies had exhibited a broad antipicornavirus spectrum of action, was selected as the model for the synthesis of a new series of 3-methylthio-5-aryl-4-Isothiazolecarbonitriles. These compounds were prepared in good yield (from 66 to 82%) by alkylation of 3-methylthio-5-(4-hydroxyphenyl)-4-Isothiazolecarbonitrile with suitable bromides in the presence of acetone; only the 4-cyanophenoxy Derivatives were obtained in a yield of less than 30%. All the compounds were screened against a panel of 17 representative human rhinovirus (HRV) serotypes belonging to both A and B groups, enteroviruses polio 1, ECHO 9 and Coxsackie B1, cardiovirus EMC, measles virus, and herpes simplex virus type 1 (HSV-1). Our results demonstrate that HRV 86 (group A) and HRVs 39 and 89 (group B) are the rhinovirus serotypes more susceptible to the action of these compounds. Isothiazole Derivatives with a longer intermediate alkyl chain exhibited good activity against polio 1 and ECHO 9. The compound bearing a butyl group between the two phenoxy rings showed the lowest IC 50 against Coxsackie B1 and measles viruses. No activity against HSV-1 was detected with any of the compounds screened.
Kazuko Yonemori - One of the best experts on this subject based on the ideXlab platform.
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Design and synthesis of selective CDK8/19 dual inhibitors: Discovery of 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]Isothiazole Derivatives.
Bioorganic & medicinal chemistry, 2017Co-Authors: Koji Ono, Hiroshi Banno, Masanori Okaniwa, Takaharu Hirayama, Naoki Iwamura, Yukiko Hikichi, Saomi Murai, Maki Hasegawa, Yuka Hasegawa, Kazuko YonemoriAbstract:To develop a novel series of CDK8/19 dual inhibitors, we employed structure-based drug design using docking models based on a library compound, 4,5-dihydroimidazolo[3',4':3,4]benzo[1,2-d]Isothiazole 16 bound to CDK8. We designed various [5,6,5]-fused tricyclic scaffolds bearing a carboxamide group to maintain predicted interactions with the backbone CO and NH of Ala100 in the CDK8 kinase hinge region. We found that 4,5-dihydrothieno[3',4':3,4]benzo[1,2-d]Isothiazole Derivative 29a showed particularly potent enzymatic inhibitory activity in both CDK8/19 (CDK8 IC50: 0.76nM, CDK19 IC50: 1.7nM). To improve the physicochemical properties and kinase selectivity of this compound, we introduced a substituted 3-pyridyloxy group into the scaffold 8-position. The resulting optimized compound 52h showed excellent in vitro potency (CDK8 IC50: 0.46nM, CDK19 IC50: 0.99nM), physicochemical properties, and kinase selectivity (only 5 kinases showed