- Novel syntheses of dithiosalicylide
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Treatment of 3H-1,2-benzodithiol-3-one or 3H-1,2-benzodithiol-3-one 1-oxide with triphenylphosphine affords a good yield of dithiosalicylide. These reactions provide practical methods for the preparation of interesting cleft-shaped molecules.
- Mitra, Kaushik,Gates, Kent S.
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Read Online
- A BODIPY-based fluorescent sensor for the detection of Pt2+ and Pt drugs
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A BODIPY-based fluorescent sensor PS with an NO4S2 podand ligand was studied for the selective detection of Pt2+ over 21 cations as well as selected platinum drugs in aqueous medium. The platinum sensor PS shows 28-fold, 22-fold and 14-fold fluorescence turn-on enhancements to Pt2+, cisplatin and nedaplatin, and was thereby employed to detect platinum drugs in A-549 human lung cancer cells.
- Bian, Qingyuan,Kong, Fred Ka-Wai,Leung, Ken Cham-Fai,Ng, Maggie,Tang, Fung-Kit,Tse, Anfernee Kai-Wing,Tse, Yu-Chung,Yam, Vivian Wing-Wah,Zhu, Jiaqian
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p. 2695 - 2698
(2020/03/13)
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- Benzothiophene-2-carboxamide derivatives as SENPs inhibitors with selectivity within SENPs family
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The SUMO (small ubiquitin-related modifier)-specific proteases (SENPs) are responsible for the cleavage of SUMO from its target proteins, thus play important roles in the dynamic SUMOylation and deSUMOylation processes. SENPs are related to a variety of human diseases including cancer and represent a new class of potential therapeutic targets with mechanism of action that is likely to be different from that of current clinically used drugs. However, potent inhibitors that are selective within the SENPs family members still remain a challenge due to their high homology. In order to demonstrate the feasibility of developing selective inhibitors within the SENPs family, we chose SENP1/2/5 as representatives, aiming to identify inhibitors with selectivity among the members. Starting from a hit compound ZCL951 from virtual screening, a series of benzothiophene-2-carboxamide inhibitors were designed based on the protein structures of SENP1, 2, and 5. First, an unoccupied hydrophobic pocket was first identified which led to IC50 as low as 0.56 μM. Furthermore, the ethylacetate 77 gave both submicromolar inhibitory activity and 33-fold selectivity for SENP2 versus SENP5. They are the most potent and selective nonpeptidic inhibitor reported so far for the SENPs family, as far as we are aware. Their structure-activity relationship was also discussed.
- Wang, Zhongli,Liu, Yunqi,Zhang, Jianchen,Ullah, Shafi,Kang, Ning,Zhao, Yaxue,Zhou, Huchen
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- Discovery of Benzoazepinequinoline (BAQ) Derivatives as Novel, Potent, Orally Bioavailable Respiratory Syncytial Virus Fusion Inhibitors
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A novel benzoazepinequnoline (BAQ) series was discovered as RSV fusion inhibitors. BAQ series originated from compound 2, a hit from similarity-based virtual screening. In SAR exploration, benzoazepine allowed modifications in the head moiety. Benzylic sulfonyl on benzoazepine and 6-Me on quinoline were crucial for good anti-RSV activity. Although the basic amine in the head portion was crucial for anti-RSV activity, the attenuated basicity was required to reduce Vss. Introducing oxetane to the head portion led to discovery of compound 1, which demonstrated single-digit nM anti-RSV activity against different RSV strains, reasonable oral exposure in plasma, and 78-fold higher exposure in lung. Compound 1 also displayed 1 log viral reduction in a female BALB/c mice RSV model by b.i.d. oral dosing at 12.5 mg/kg. A single resistant mutant at L138F in fusion protein proved compound 1 to be a RSV fusion inhibitor.
- Zheng, Xiufang,Liang, Chungen,Wang, Lisha,Wang, Baoxia,Liu, Yongfu,Feng, Song,Wu, Jim Zhen,Gao, Lu,Feng, Lichun,Chen, Li,Guo, Tao,Shen, Hong C.,Yun, Hongying
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p. 10228 - 10241
(2018/11/23)
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- Synthesis and anti-bacterial activity of a library of 1,2-benzisothiazol-3(2H)-one (BIT) derivatives amenable of crosslinking to polysaccharides
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1,2-Benzisothiazol-3(2H)-one (BIT) is one of the most common chemical biocides in industrial products, with a heterocyclic structure and a wide range of antimicrobial activity. A library of BIT derivatives was synthesized and characterized, from which 18 compounds were selected, tested for anti-bacterial activity relative to the parent molecule and amenable of coupling to plant polysaccharides in general and to galactomannans (GM) in particular, widely used as rheology modifiers, but with limited “biostability”. Four sites on the BIT core were targeted: the nitrogen and the oxygen atoms on the heterocyclic ring, the C5 and the C6 positions on the aromatic ring, where functional groups were introduced. The ultimate aim of this work is to establish whether by covalently linking a biocide to GM polymers, their “biostability” can be improved.
- Viani, Fiorenza,Rossi, Bianca,Panzeri, Walter,Merlini, Luca,Martorana, Alessandra M.,Polissi, Alessandra,Galante, Yves M.
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p. 1745 - 1761
(2017/03/08)
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- Hybrid molecule from Farnesylthiosalicylic acid-diamine and phenylpropenoic acid as Ras-related signaling inhibitor with potent antitumor activities
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Novel series of Farnesylthiosalicylic acid-diamine/phenylpropenoic acid hybrids were designed and synthesized. Their in vitro growth inhibitory assays showed that most compounds displayed strong antiproliferation activity against seven cancer cells. Especially, the new hybrid 12f, by the conjugation of 10a with ferulic acid, could selectively suppress the proliferation of tumor cells and display significantly lower toxicities to normal cells than its intermediate 10a. Furthermore, 12f dose-dependently induced SMMC-7721 cell apoptosis. Additionally, our observations demonstrated that 12f inhibited both Ras-related signaling and phosphorylated NF-κB synergistically, which may be advantageous to the strong antitumor activities of 12f. Our findings suggest that these novel hybrids may hold a great promise as therapeutic agents for the intervention of human cancers.
- Ling, Yong,Wang, Zhiqiang,Wang, Xuemin,Li, Xianghua,Wang, Xinyang,Zhang, Wei,Dai, Hong,Chen, Li,Zhang, Yihua
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p. 145 - 152
(2015/01/30)
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- Synthesis and biological evaluation of novel farnesylthiosalicylic acid derivatives for cancer treatment
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Novel farnesylthiosalicylic acid (FTS) derivatives were synthesized by coupling with different substituted diamines. Their in vitro growth inhibitory activities against seven human cancer cell lines were evaluated. The results revealed that the synthetic farnesylthiosalicylamides displayed significant antitumor activities compared to the positive control FTS. Especially, compound 8f exhibited the strongest antitumor activities with IC50 values of 6.20-7.83 μM, which were one- to threefold less than those of sorafenib and six- to tenfold less than that of FTS against each cell line in vitro. Furthermore, 8f could inhibit the Ras-related signaling pathway and induce SMMC-7721 cell apoptosis superior to FTS in a dose-dependent manner. These data indicate that 8f may hold greater promise as therapeutic agent for the intervention of human cancers.
- Ling, Yong,Wang, Xuemin,Zhu, Hongyan,Wang, Zhiqiang,Xu, Chenjun,Wang, Xinyang,Chen, Li,Zhang, Wei
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p. 327 - 333
(2014/05/20)
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- Synthesis and biological evaluation of farnesylthiosalicylamides as potential anti-tumor agents
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Fourteen hybrids of farnesylthiosalicylic acid (FTS) with various diamines were synthesized and biologically evaluated. It was found that FTS-monoamide molecules (10a-g) displayed strong anti-proliferative activity against seven human cancer cell lines, superior to FTS and FTS-bisamide compounds (11a-g). The mono-amide 10f was the most active, with IC50s of 3.78-7.63 μM against all tested cancer cells, even more potent than sorafenib (9.12-22.9 μM). In addition, 10f induced SMMC-7721 cell apoptosis, down-regulated the expression of Bcl-2 and up-regulated Bax and caspase-3. Furthermore, 10f had the improved aqueous solubility relative to FTS. Finally, treatment with 10f dose-dependently inhibited the Ras-related signaling pathways in SMMC-7721 cells. Collectively, 10f could be a promising candidate for the intervention of human cancers.
- Ling, Yong,Wang, Zhiqiang,Zhu, Hongyan,Wang, Xuemin,Zhang, Wei,Wang, Xinyang,Chen, Li,Huang, Zhangjian,Zhang, Yihua
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p. 374 - 380
(2014/01/17)
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- SEVEN-MEMBERED SULFONAMIDES AS MODULATORS OF RAR-RELATED ORPHAN RECEPTOR-GAMMA (RORγ, NR1F3)
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The invention provides modulators for the orphan nuclear receptor RORγ and methods for treating RORγ mediated diseases by administration of these novel RORγ modulators to a human or a mammal in need thereof. Specifically, the present invention provides compounds of Formula (1) and the enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof as well as pharmaceutical compositions comprising said compounds as an active ingredient.
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Page/Page column 62
(2013/05/22)
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- Synthesis of some 1,3,4-thiadiazole derivatives as inhibitors of Entamoeba histolytica
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In the quest for potent anti-amoebic agents, some 1,3,4-thiadiazole derivatives were synthesized and characterized by spectral data. The purity of the compounds was confirmed by elemental analysis. All the compounds were screened in vitro against HM1:IMSS strain of Entamoeba histolytica by microdilution method. The results revealed that compounds 1 (IC50 = 0.670 μM), 3 (IC50 = 1.60 μM) and 8 (IC50 = 0.522 μM) had much better anti-amoebic activity than the reference drug metronidazole (IC50 = 1.80 μM). Further, cytotoxicity of the compounds having IC50 value less than metronidazole was assessed by MTT assay on human breast cancer MCF-7 cell line and all the compounds were found low cytotoxic in the concentration range of 2.5-250 μM. Preliminary results indicate that these three compounds (1, 3 and 8) may be subjected to further investigations and it may be hoped that the present study will stimulate efforts towards the development of novel effective anti-amoebic agents.
- Siddiqui, Shadab Miyan,Salahuddin, Attar,Azam, Amir
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p. 1305 - 1312
(2013/04/10)
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- COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS DISEASE
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The invention relates to the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2 and X are as defined in the description and claims, which are useful for the treatment or prophylaxis of RSV infection.
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Paragraph 0102; 0103
(2013/04/13)
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- COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF RESPIRATORY SYNCYTIAL VIRUS DISEASE
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A compound of formula (I) as well as pharmaceutically acceptable salt thereof, wherein R1, R2 and X are as defined in description and in claims, can be used as a medicament.
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Page/Page column 15
(2013/04/25)
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- NOVEL INTERMEDIATES OF VORICONAZOLE AND PREPARATION METHOD OF VORICONAZOLE USING THE SAME
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The present invention provides a compound of formula 2 and a compound of formula 4 which are a novel intermediate of voriconazole and a process for the preparation of voriconazole using the same. The novel intermediates of the present invention are environmentally-friendly due to no emission of irritative and offensive odor unique to thiols and enable the production of voriconazole with high purity and high yield.
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Page/Page column 9
(2012/05/04)
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- Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives
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A series of 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives has been prepared and subsequently evaluated with regards to the inhibition of 5-LOX/COX. Structure optimization furnished derivatives with promising in vitro activity as dual 5-LOX/COX inhibitors with submicromolar IC50 values for inhibition of 5-LOX and COX-1, respectively.
- Hansen, Finn K.,Khankischpur, Mehdi,Tolaymat, Ibrahim,Mesaros, Renata,Dannhardt, Gerd,Geffken, Detlef
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experimental part
p. 5031 - 5034
(2012/08/28)
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- DBU-Mediated cleavage of aryl- and heteroaryl disulfides
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The capacity of the nitrogen nucleophile, 1,8-diazabicyclo[5.4.0]undec-7- ene (DBU) to reduce aryl- and heteroaryl disulfides to the corresponding mercaptans is demonstrated. While dicarboxylated disulfide analogues afford the mono-DBU disulfide salts, as confirmed by X-ray crystallography, the corresponding methyl esters are cleaved normally. ARKAT-USA, Inc.
- Nyoni, Dubekile,Lobb, Kevin A.,Kaye, Perry T.,Caira, Mino R.
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experimental part
p. 245 - 252
(2012/05/31)
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- Molecular design, synthesis and bioactivity of glycosyl hydrazine and hydrazone derivatives: Notable effects of the sugar moiety
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Assuming that the water solubility of our previous hydrazone derivatives would improve after modification with sugars while keeping or modulating their notable biological activities, we designed and synthesized some glycosyl hydrazine and hydrazone derivatives. Bioassay results indicated that the antitumor activity of our previously prepared hydrazones reduced or disappeared after modification with sugars. On the contrary, some glycosyl derivatives displayed much better antifungal activity against selected fungi. Obviously, a small sugar can change the biological activity of hydrazones significantly.
- Cui, Zining,Yang, Xinling,Shi, Yanxia,Uzawa, Hirotaka,Cui, Jingrong,Dohi, Hirofumi,Nishida, Yoshihiro
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scheme or table
p. 7193 - 7196
(2012/02/02)
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- Rational tuning of the rigidity of a ligand scaffold: synthesis of diphenylsulfide-linked bis(oxazoline) ligands and their application in asymmetric allylic alkylation
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The scaffold rigidity of bis(oxazoline) ligands was rationally tuned on the basis of literature information. Diphenylsulfide-linked bis(oxazoline) ligands with a flexible scaffold were efficiently synthesized to test our hypothesis. The improved enantioselectivity in palladium-catalyzed asymmetric allylic alkylation reaction was achieved as we expected.
- Du, Xian,Liu, Han,Du, Da-Ming
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experimental part
p. 241 - 246
(2010/05/17)
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- Synthesis and cannabinoid activity of a variety of 2,3-substituted 1-benzo[b]thiophen derivatives and 2,3-substituted benzofuran: Novel agonists for the CB1 receptor
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An exploratory chemical effort has been undertaken to develop a novel series of compounds as selective CB1 agonists. It is hoped that compounds of this type will have clinical utility in pain control and cerebral ischaemia following stroke or traumatic head injury. We report here medicinal chemistry studies directed towards the investigation of several classes of 1-benzo[b]thiophen and benzofuran derivatives as novel CB1 agonists. We have discovered a novel series of compounds, which contain a 1-benzo[b]thiophen or a benzofuran group as the central aromatic group. Our investigation of this series of compounds has enhanced our understanding of the importance of binding sites within the CB1 receptor for favourable CB1 potency. Our understanding of these factors allowed us to modify the structure of a 1-benzothiophen derivative and improve its potency at the CB1 receptor. CSIRO 2008.
- Moloney, Gerard P.,Angus, James A.,Robertson, Alan D.,Stoermer, Martin J.,Robinson, Michael,Lay, Lucy,Wright, Christine E.,McRae, Ken,Christopoulos, Arthur
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p. 484 - 499
(2008/12/20)
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- 1,3-Dipolar cycloadditions of acetylenic sulfones in solution and on solid supports
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(Chemical Equation Presented) Several representative acetylenic sulfones were immobilized on a polymer support derived from Merrifield resin by means of ester linkers that were used to couple free carboxylic acid groups on the solid support with benzylic hydroxyl functions on the arylsulfonyl moieties of the acetylenes. Several examples of reversed ester linkers, using Merrifield resin directly, were also successfully prepared. The 1,3-dipolar cycloadditions of the solid-supported acetylenic sulfones were investigated with a series of 1,3-dipoles, including benzyl azide, ethyl diazoacetate, diazomethane, as well as representative nitrile oxides, nitrile imines, nitrile ylides, nitrones, azomethine imines, azomethine ylides, munchnones, and sydnones. In general, analogous cycloadditions were also performed with acetylenic sulfones in solution phase for comparison. The cycloadditions typically afforded good to excellent yields of the desired products in both solution and solid phase, although the latter reactions sometimes required more vigorous conditions. Except in the case of benzyl azide and diazo compounds, where mixtures of regioisomers were obtained, the other 1,3-dipoles reacted with high regioselectivity and afforded essentially unique regioisomers. Cleavage of the products from the resin was smoothly effected by alkaline hydrolysis, while several attempts at reductive desulfonylation with sodium amalgam or samarium diiodide-HMPA resulted in N-O or C-O scission, in addition to cleavage from the polymer. The method provides access to a number of important classes of heterocycles, including variously substituted and functionalized triazoles, pyrazoles, 1,2-oxazoles, pyrroles, as well as their dihydro and bicyclic analogues. The success of the cycloadditions on polymer supports paves the way to future investigations of sequential transformations leading to libraries of useful heterocycles.
- Gao, Detian,Zhai, Huimin,Parvez, Masood,Back, Thomas G.
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p. 8057 - 8068
(2008/12/22)
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- Therapeutic Compounds
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The present invention provides compounds of formula (I), or pharmaceutically acceptable salts or solvates thereof, methods for their preparation, methods for their use, and pharmaceutical formulations comprising them.
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Page/Page column 28
(2008/06/13)
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- A new Zn/TiCl4/LiAlH4 mediated approach to 2-aryl- or 2-alkyl-substituted benzothiophenes via intramolecular cyclization
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Methyl 2-(substituted benzoylthio)benzoates undergo intramolecular ring cyclizations in the presence of Zn/TiCl4/LiAlH4 to give the corresponding 2-aryl- or alkylsubstituted benzothiophenes in good yields. Georg Thieme Verlag Stuttgart.
- Hyung, Jae Jeong,Un, Young Yoon,Sang, Hun Jang,Yoo, Un-Aeh,Su, Nam Kim,Ba, Tai Truong,Sung, Chul Shin,Yoon, Yong-Jin,Okram, Mukherjee Singh,Lee, Sang-Gyeong
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p. 1407 - 1410
(2008/02/13)
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- Synthesis of 4,4-disubstituted-4H-benzo[d][1,3]oxathiin-2-ones, a new class of compounds
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4,4-Dialkyl and 4,4-diaryl-4H-benzo[d][1,3]oxathiin-2-ones were synthesized by the reaction of 2-(mercapto-phenyl)-dialkyl- (or diaryl)-methanol with CDI in excellent yield. The 2-(mercaptophenyl)-dialkyl- (or diaryl)-methanols were prepared by the reaction of commercially available methylthiosalicylate with an ppropriate alkyl or aryl Grignard reagent. Copyright Taylor & Francis Group, LLC.
- Kamila, Sukanta,Khan, Omair,Zhang, Hongming,Biehl, Edward R.
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p. 1419 - 1429
(2007/10/03)
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- Studies on the flash vacuum thermolysis of thiones of selected N-, O-, and S-heterocycles
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Thermal decomposition of thiones of selected N-, O- and S-heterocycles under flash vacuum thermolysis conditions was investigated. In the case of six-membered 4H-3,1-benzoxathiin-4-thione 6, the course of the reaction depended on the substitution pattern at C(2) (Scheme 3). Thus, the 2-unsubstituted derivative 6a led to the unstable product 2, which upon treatment with MeOH was converted quantitatively into methyl 2-mercaptobenzoate (7). The analogous thermolysis of the 2,2-dimethyl derivative 6b yielded 2-methyl-4H-1- benzothiopyran-4-thione (8) as a sole product. In the case of thiophthalide derivatives 15, a thermal rearrangement in the gas phase leading to the corresponding benzo[c]thiophen-1(3H)-ones 16 in high yields was observed (Scheme 6). Unexpectedly, thionation of 1,3-oxathiolan-5-one 17 with Lawesson's reagent under standard conditions led to 1,2-dithietane derivative 19, which, after the gas-phase thermolysis, underwent a ring enlargement to yield 3H-1,2-dithiole 20 (Scheme 7). The six-membered 4H-1,3-benzothiazine-4-thione 21 was shown to give three products: phenanthro[9,10-c]-1,2-dithiete (22), 3H-1,3-benzodithiole-3- thione (23), and N-(3H-1,2-benzodithiol-3-ylidene)prop-2-en-1-amine (24) (Scheme 8). The latter is the product of the initial reaction, whereas 22 and 23 are postulated to be formed as secondary products of the conversion of the intermediate 6-(thioxomethylene)cyclohexa-2,4-diene-1-thione (26) (Schemes 9 and 10).
- Drewnowski, Tomasz,Lesniak, Stanislaw,Mloston, Grzegorz,Siedlecka, Renata,Skarzewski, Jacek
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p. 991 - 999
(2007/10/03)
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- Sulfur containing compounds
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This invention is directed to novel and known stufur containing compounds and pharmaceutically acceptable salts thereof that have utility as antifungals and as antiproliferative agents against mammalian cells, in particular cancer cells and most particularly leukemia-derived cells. The invention provides a method for synthesizing certain of the sulfur containing compounds that is more efficient than previously known methods.
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Page/Page column 25
(2010/11/30)
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- The Selective Deprotection of Thioesters Using Titanium(IV) Chloride/Zinc
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A new method for deprotection of thioesters using TiCl4/Zn at 0-25 deg C is described. The procedure chemoselectively cleaves the S-CO bond in thioesters in the presence of other carbonyl functional groups and other protecting groups to cleanly produce thiols.
- Jin, Chung Keun,Jeong, Hyung Jae,Kim, Min Kyu,Kim, Ju Young,Yoon, Yong-Jin,Lee, Sang-Gyeong
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p. 1956 - 1958
(2007/10/03)
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- New and more potent antifungal bisulfides
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From a design principle described in an earlier paper, a new series of substituted aryl methyl disulfides have been prepared and tested against Aspergillus niger and Aspergillus flavus. Methyl p-nitrophenyl disulfide is more potent (by an order of magnitude) than the fungitoxic natural product (CH3SCH2S)2. With the present rationale in hand, one can anticipate which Polycarpamine is an effective antifungal agent. CSIRO 2000.
- Baerlocher, Felix Jakob,Baerlocher, Mark Otto,Langler, Richard Francis,MacQuarrie, Stephanie Lee,Marchand, Maurice Emile
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- Biological activity of alkyl 2-(acylthio)benzoates
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Of a series of synthetic alkyl 2-(acylthio)benzoate (1-20), all the derivatives except for n-butyl 2-butyrylthiobenzoate (18) and n-butyl 2-n- valerylthiobenzoate (20) showed clear phytogrowth-inhibitory activity. All the compounds tested except for methyl 2-butyrylthiobenzoate (3) exhibited cytotoxic activity on mouse splenic T cells. Strong phytogrowth-inhibition and cytotoxic activity were found with 1, 6, 11 and 16 with an acetylthio group at C-2, suggesting that the acetyl group seems to play an important role in both activities of alkyl 2(acylthio)benzoates. Among them, methyl 2- acetylthiobenzoate (1) was the strongest inhibitor. On the other hand, potent inhibition of prolyl endopeptidase was exhibited by 2, 7, 12 and 17 with a propionylthio group at C-2. These findings imply that a propionyl group might be useful for increasing the inhibitory activity against on prolyl endopeptidase.
- Matsumura, Eiko,Nishinaka, Takahiro,Tsujibo, Hiroshi,Hachiken, Hiroko,Miki, Yasuyoshi,Sakagami, Yoshikazu,Inamori, Yoshihiko
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p. 254 - 256
(2007/10/03)
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- No-donors, part 3: Nitrooxyacylated thiosalicylates and salicylates - Synthesis and biological activities
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Organic nitrates release nitric oxide when incubated with thiosalicylic acid. S-Nitrooxyacylated esters and amides of thiosalicylic acid, together with the corresponding salicylates, were synthesized in order to perform a first in vitro evaluation of these new nitrate-thiol-hybrid prodrugs. These prodrugs might release NO in vivo after biotransformation without the use of endogenous reductives. None of these prodrugs released NO spontaneously when dissolved in buffer solution, but they did activate soluble guanylyl cyclase and induced vasodilatation of phenylephrine-pretreated male Wistar rat aorta in a potency range between that of isosorbiddinitrate and glycerole trinitrate.
- Endres, Stefan,Hacker, Andreas,Noack, Eike,Kojda, Georg,Lehmann, Jochen
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p. 895 - 901
(2007/10/03)
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- Novel inhibitors of the prenylated protein methyltransferase reveal distinctive structural requirements
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Inhibitors of a prenylated protein methyltransferase were synthesized and evaluated. S-farnesyl-5-fluorothiosalicylic acid and the 5-chloro analog (but not the 4-fluoro, 4-chloro or 3-chloro analogs) were potent inhibitors, as was the parent compound S-farnesyl thiosalicylic acid (FTS), whose methyl ester was far less active. S-geranyl and S-geranylgeranyl thiosalicylic acids were more than ten times less potent than FTS.
- Marciano, Daniele,Aharonson, Ziporet,Varsano, Tal,Haklai, Roni,Kloog, Yoel
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p. 1709 - 1714
(2007/10/03)
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- Potassium fluoride on alumina: Synthesis of O-aryl N,N-dimethylthiocarbamates and their rearrangement into S-aryl N,N-dimethylthiocarbamates under microwave irradiation
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A series of O-aryl N,N-dimethyl thiocarbamates have been prepared by the reaction of dimethylthiocarbamoyl chloride with phenols absorbed on potassium fluoride on alumina. The rearrangement of O-aryl N,N-dimethylthiocarbamate into S-aryl N,N-dimethylthiocarbamate under microwave irradiation was also studied. The use of conductive support like graphite or silicon carbide allow these rearrangements although the O-aryl N,N-dimethylthiocarbamates have very low dielectric lost.
- Villemin, Didier,Hachemi, Messaoud,Lalaoui, Mekki
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p. 2461 - 2471
(2007/10/03)
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- Oxidative Cleavage of S-Arylmercaptoacetic Acids by Sodium Perborate: Kinetic and Correlation Study
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Kinetics of oxidation of twenty six S-arylmercaptoacetic acids (SAMA) (I) by sodium perborate (PB) have been studied in acid medium.The product of oxidation is the corresponding thiophenol.The rate data of meta- and para-substituted acids have been correlated with DSP equations.While the para-compounds correlate well with ?I and ?0R values, the meta-compounds correlate well with ?I and ?-R values.The reaction constants are negative and of smaller magnitudes.Further, the ortho-substituted acids show a good correlation with a triparametric equation involving Taft's ?I and ?0R and Charton's steric parameter ν.There is a considerable steric contribution to the total ortho-substituent effect.Based on these observations, mechanism involving the formation of protonated arylsulfinylacetic acid intermediate, followed by an intramolecular rearrangement leading to the product thiophenol has been proposed.
- Kabilan, S.,Pandiarajan, K.,Krishnasamy, K.,Sankar, P.
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p. 443 - 452
(2007/10/02)
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- Cyclic Nucleotide Phosphodiesterase Inhibition by Imidazopyridines: Analogues of Sulmazole and Isomazole as Inhibitors of the cGMP Specific Phosphodiesterase
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The synthesis and phosphodiesterase (PDE) inhibitory profile of a series of imidazopyridines, including sulmazole and isomazole, on separated PDE isoenzymes are described.The results show that both sulmazole and isomazole are weak inhibitors of PDE III, and their inotropic activity is unlikely to be due to PDE III inhibition alone.Surprisingly, both compounds were found to be significant inhibitors of the cGMP specific isoenzyme, PDE V, and a series of simple 2-substituted phenylimidazopyridines have been made to investigate the SAR of PDE activity.This has been shown to be sensitive to chain length, polarity, and the nature of the heteroatom linking group.Potent PDE V inhibitors, many of which are also significant inhibitors of PDE IV, have been identified.
- Coates, William J.,Connolly, Brendan,Dhanak, Dashyant,Flynn, Sean T.,Worby, Angela
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p. 1387 - 1392
(2007/10/02)
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- Diarylstrylquinoline diacids and pharmaceutical compositions thereof
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Compounds having the formula: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.
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- Dibenzocyclooctene-, Dibenzochalcocine-, and Diarenochalconinediones
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2,2'-Oxybis-, -thiobis-, and -methylenebisbenzoic esters 2a-c react with methyllithium in ether to give low yields of 5H-dibenzochalcocine-5,7(6H)-diones 6a, 7a, and dibenzocyclooctene-5,7(6H,12H)-dione (8), respectively.Very good yields of such heterocycles with oxygen (6a-h, 37), sulfur (7a-h, 38) and selenium (36) as key atom are obtained when diaryl ethers (21, 22, 25), -sulfides (27, 29, 30), and -selenides (33) that contain 2'-acetyl- (or -propionyl-) and 2-methoxycarbonyl groups are treated with sodium hydride in boiling toluene.Analogously are prepared the dibenzoxonine-11,13(6H,12H)diones 62a-c and 7H-benzonaphthothionine-7,9-(8H)-dione (65) which are expanded by one ring member.In the analogous reaction of a corresponding benzophenone derivative 35, spiro-3(2H),3'-dione (41) is formed in a tandem reaction. - Under phase transfer conditions the dibenzochalcocinediones 6, 7, 36 and also the corresponding nitrogen cycles 5 react to give mixtures of C- (42-45) and O-alkyl derivatives (46-49).Methyllithium and diisobutylaluminium hydride provide the carbinols 50-54.With bromine and SO2Cl2, respectively, the methylene group is mono- or dihalogenated to the products 56, 57; defined nitration was only possible for the oxacycle 6a.
- Hellwinkel, Dieter,Bohnet, Siegbert
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p. 1151 - 1174
(2007/10/02)
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- Benzothiet-2-ones: Synthesis, Reactions, and Comparison with Benzoxet-2-ones and Benzazetin-2-ones
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Benzothiet-2-one (5) is obtained as a neat solid, stable below -20 deg C(-45 deg C in solution), by flash vacuum pyrolysis of benzothiophene-2,3-dione (9).Naphthothiet-2-one (21) and naphthothiet-1-one (42) are obtained as stable crystalline solids in near-quantitative yields from the corresponding naphthothiophenediones 20 and 41.Naphthooxet-2-one (31) and naphthoazetin-2-one (36) were generated and observed by IR spectroscopy to be stable below -40 deg C and 0 deg C, respectively.The thietones, oxetones, and azetinones undergo rapid ring-opening reactions with methanol to give the corresponding carboxylic acid esters.They undergo thermal CO elimination with concomitant Wolff-type ring contraction to thioketenes (17, 25, 45), ketenes (30), and nitriles (37), respectively.The di-, oligo-, and polymerization of the thietones has been elucidated.Naphthothiet-1-one (42) reacts with 1-thiocarbonyl-1H-indene (45) to give cycloaddition product 46.Naphthothietones 21 and 42 react with dicyclohexylcarbodiimide to furnish 2-imino-1,3-thiazin-4-one derivatives 47 and 49.
- Wentrup, Curt,Bender, Harald,Gross, Gerhard
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p. 3838 - 3847
(2007/10/02)
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