- A scaffold replacement approach towards new sirtuin 2 inhibitors
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Sirtuins (SIRT1–SIRT7) are an evolutionary conserved family of NAD+-dependent protein deacylases regulating the acylation state of ε-N-lysine residues of proteins thereby controlling key biological processes. Numerous studies have found association of the aberrant enzymatic activity of SIRTs with various diseases like diabetes, cancer and neurodegenerative disorders. Previously, we have shown that substituted 2-alkyl-chroman-4-one/chromone derivatives can serve as selective inhibitors of SIRT2 possessing an antiproliferative effect in two human cancer cell lines. In this study, we have explored the bioisosteric replacement of the chroman-4-one/chromone core structure with different less lipophilic bicyclic scaffolds to overcome problems associated to poor physiochemical properties due to a highly lipophilic substitution pattern required for achieve a good inhibitory effect. Various new derivatives based on the quinolin-4(1H)-one scaffold, bicyclic secondary sulfonamides or saccharins were synthesized and evaluated for their SIRT inhibitory effect. Among the evaluated scaffolds, the benzothiadiazine-1,1-dioxide-based compounds showed the highest SIRT2 inhibitory activity. Molecular modeling studies gave insight into the binding mode of the new scaffold-replacement analogues.
- Seifert, Tina,Malo, Marcus,Kokkola, Tarja,Stéen, E. Johanna L.,Meinander, Kristian,Wallén, Erik A.A.,Jarho, Elina M.,Luthman, Kristina
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- ARYL SULFIDE DERIVATIVES AND ARYL SULFOXIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
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The present invention relates to aryl sulphide and aryl sulphoxide derivatives, to the use thereof as acaricides and insecticides for controlling animal pests and to processes and intermediates for preparation thereof. The aryl sulphide and aryl sulphoxid
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Paragraph 1672; 1673; 1674
(2016/06/13)
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- Aryl sulfide derivatives and aryl sulfoxide derivatives as acaricides and insecticides
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The invention relates to aryl sulfide derivatives and aryl sulfoxide derivatives, use thereof as acaricides and insecticides for controlling animal pests, and methods and intermediate products for the production thereof. The aryl sulfide derivatives and a
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Paragraph 1874; 1875; 1876; 187
(2016/10/08)
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- ARYL SULFIDE DERIVATIVES AND ARYL SULFOXIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
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The present invention relates to aryl sulphide and aryl sulphoxide derivatives, to their use as acaricides and insecticides for controlling animal pests and to processes and intermediates for their preparation. The aryl sulphide and aryl sulphoxide derivatives have the general structure (I) in which the respective radicals have the meanings given in the description.
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Paragraph 1055; 1056; 1057
(2015/12/23)
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- Optimization of heterocyclic substituted benzenesulfonamides as novel carbonic anhydrase IX inhibitors and their structure activity relationship
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In this study, starting from a lead compound discovered by virtual screening, a series of novel heterocyclic substituted benzenesulfonamides were designed and synthesized as new carbonic anhydrase IX (CA IX) inhibitors. Some compounds exhibited potent inh
- Gao, Rui,Liao, Sha,Zhang, Chen,Zhu, Weilong,Wang, Liyan,Huang, Jin,Zhao, Zhenjiang,Li, Honglin,Qian, Xuhong,Xu, Yufang
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p. 597 - 604
(2013/05/09)
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- SUBSTITUTED HETEROCYCLIC ACETAMIDES AS KAPPA OPIOID RECEPTOR (KOR) AGONISTS
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The present invention relates to a series of substituted compounds having the general formula (I), including their ste reoisomers and/or their pharmaceutically acceptable salts, wherein R1, R2, R3. R4, R5, and R6 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.
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Page/Page column 86
(2013/09/26)
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- BI-ARYL META-PYRIMIDINE INHIBITORS OF KINASES
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The invention provides biaryl meta-pyrimidine compounds having the general structure (A). The pyrimidine compounds of the invention are capable of inhibiting kinases, such as members of the Jak kinase family, and various other specific receptor and non receptor kinases.
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Page/Page column 190
(2008/06/13)
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- 2-PHENYL-INDOLES AS PROSTAGLANDIN D2 RECEPTOR ANTAGONISTS
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The present invention is directed to a compound of Formula (XVI) wherein R, R2, R3, R4, R5, R6, R7 and n are as defined herein, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, a pharmaceutically acceptable prodrug thereof, or a pharmac
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Page/Page column 85
(2008/06/13)
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- Design, synthesis, and biological evaluation of N-acetyl-2- carboxybenzenesulfonamides: A novel class of cyclooxygenase-2 (COX-2) inhibitors
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N-Acetyl-2-carboxybenzenesulfonamide (11), and a group of analogues possessing an appropriately substituted-phenyl substituent (4-F, 2,4-F 2, 4-SO2Me, 4-OCHMe2) attached to its C-4, or C-5 position, were synthesized for ev
- Chen, Qiao-Hong,Rao, P. N. Praveen,Knaus, Edward E.
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p. 2459 - 2468
(2007/10/03)
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- Imidazole derivatives with biphenylsulfonyl substitution method for preparing them and their use as a drug or diagnostic agent
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The invention relates to compounds of formula (I), wherein the symbols have the meanings indicated in the specification. The inventive compounds exhibit dramatic antiarrhythmic proprieties and contain a cardioprotective compound. They can preventively inh
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- Some new 1,2-benzothiazine derivatives with analgesic and anti-inflammatory activities
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Twenty-three new 7-halo-4-hydroxy-2H(or alkyl)-N-(3-aralkyl-2-thio-l-hydantoinyl)-2H- 1,2-benzothiazine-3-carboxamide 1,1-dioxide derivatives were synthesized through the condensation of 7-halo-4-hydroxy-2H(or alkyl)-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxides with 1-amino-2-thio-3-aralkyl-imidazolidine-4-one. The analgesic and anti-inflammatory activities of the synthesized compounds were investigated by acetic acid-induced writhing syndrome and carrageenan rat paw edema tests. In analgesic activities most compounds exhibited higher activities than acetylsalicylic acid, but in antiinflammatory activities most compounds except compounds 24, 36, 39 showed lower activities than indometacin.
- Kwon, Soon-Kyoung,Park, Myung-Sook
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p. 966 - 971
(2007/10/03)
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