- Preparation method and medical application of benzisothiazole and benzothiophene
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The invention discloses a preparation method and medical application of benzisothiazole and benzothiophene, and telates to the field of pharmaceutical chemistry. According to the invention, benzisothiazole and benzothiophene are the first type of HIF-2 agonists; compared with a compound M1001 found by the applicant in the earlier stage, the invention has better HIF-2 agonist activity, and has remarkable enhancement activity on expression of mRNA and protein of EPO, VGEF, Glut1, NDRG1 and the like at the downstream of HIF-2, so that the invention can be used for preparing drugs for treating and/or preventing chronic kidney diseases/chronic renal anemia, dyslipidemia and high cholesterol caused by abnormal expression of HIF-2; and the method has a good industrialization prospect.
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Paragraph 0166-0169; 0209-0212
(2021/08/19)
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- 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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- INHIBITORS OF THE YAP/TAZ-TEAD INTERACTION AND THEIR USE IN THE TREATMENT OF CANCER
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The invention relates to compounds of formula (I): wherein R1; R2, R3, R4, R5 and are as defined in the description. The compounds of formula (I) are inhibitors of the YAP/TAZ-TEAD interaction and thu
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Paragraph 0096; 0106
(2020/04/21)
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- Novel compounds that are inhibitors of YAP/TAZ-TEAD interaction and their use in the treatment of malignant mesothelioma
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These compounds are useful as inhibitors of the YAP/TAZ-TEAD interaction.
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Paragraph 0729-0731
(2020/02/01)
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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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- Acetylenyl-pyrazolo-pyrimidine derivatives
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The present invention relates to compounds of formula (I): wherein R1 to R3, A, M, L, E, G, and J are as defined in the description and claims. The invention also relates to a process for the manufacture of such compounds, pharmaceutical compositions containing them, and methods for treating CNS disorders.
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Page/Page column 28
(2008/06/13)
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- Biphenyl- and terphenyl-based recyclable organic trivalent iodine reagents
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Biphenyl- and terphenyl-based recyclable trivalent iodine reagents, such as 4-bromo-4′-(diacetoxyiodo)biphenyl, 4,4′-bis(diacetoxyiodo)biphenyl, 1,4-bis[4-(diacetoxyiodo)phenyl]benzene, 4-bromo-4′-[(hydroxy)(tosyloxy)iodo]biphenyl, 4,4′-bis[(hydroxy)(tosyloxy)iodo]biphenyl, were simply prepared and their reactivities for the oxidative rearrangement of ketones to esters, TEMPO-mediated oxidation of alcohols to aldehydes or ketones, oxidative dealkylation of N-alkylsulfonamides to sulfonamides, and α-tosyloxylation of ketones were compared with p-(diacetoxyiodo)toluene and p-[(hydroxy)(tosyloxy)iodo]toluene to show the same reactivities and, moreover, the biphenyl- and terphenyl-based iodoarenes formed were recovered by simple filtration of the reaction mixture in every reaction. Thus, these biphenyl- and terphenyl-based trivalent iodine reagents can be used as the recyclable reagents.
- Moroda, Atsushi,Togo, Hideo
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p. 12408 - 12414
(2007/10/03)
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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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- Oxidatively sonochemical dealkylation of various N-alkylsulfonamides to free sulfonamides and aldehydes
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Various N-alkylsulfonamides were easily dealkylated to give the corresponding free sulfonamides in moderate to good yields in the presence of (diacetoxyiodo)benzene and iodine under ultrasonic irradiation. Application of this methodology to various N-prot
- Katohgi, Masashi,Togo, Hideo
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p. 7481 - 7486
(2007/10/03)
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- Novel sonochemical dealkylation of N-alkylsulfonamides in the presence of (diacetoxyiodo)benzene and iodine
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Various N-alkylsulfonamides were easily dealkylated in moderate to good yields by the ultrasonic irradiation in the presence of (diacetoxyiodo)benzene and iodine.
- Katohgi, Masashi,Yokoyama, Masataka,Togo, Hideo
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p. 1055 - 1057
(2007/10/03)
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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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