- AMIDE COMPOUND HAVING BET PROTEOLYSIS-INDUCING ACTION AND MEDICINAL APPLICATION THEREOF
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The present invention aims to provide a compound that: has an excellent cytotoxic action on cancer cells, excellent induction of BET protein degradation in cancer cells, and an excellent binding-inhibiting action on BET protein and acetylated histone; and is effective as an anti-cancer agent, a BET protein degradation-inducing agent, or a BET protein inhibiting agent. A compound indicated in general formula (I) or a pharmacologically acceptable salt thereof. {In the formula, each symbol is as outlined in the Description.}
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Paragraph 0516-0518
(2020/01/31)
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- Efficient synthetic approach to substituted benzo[b]furans and benzo[b]thiophenes by iodine-promoted cyclization of enaminones
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An efficient synthetic approach to the substituted benzo[b]furan and benzo[b]thiophene scaffolds by iodine-mediated cyclization of the corresponding enaminones is described. This protocol was applied to a large series of these latter precursors to afford the respective benzoheterocycles substituted at the C-2 position by a carbonyl group functionality. A study of the factors that control this process reveals that the reactivity depends on the presence of electron-donor groups in the aryl ring of the aryloxycarbonylic and arylthiocarbonylic moieties.
- Labarrios, Ehecatl,Jerezano, Alberto,Jimenez, Fabiola,Del Carmen Cruz, Maria,Delgado, Francisco,Zepeda, L. Gerardo,Tamariz, Joaquin
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p. 954 - 971
(2014/08/05)
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- AMINOPYRIMIDINE DERIVATIVES AS LRRK2 MODULATORS
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Compounds of the formula (I): or pharmaceutically acceptable salts thereof, wherein A, X, R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for t
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Page/Page column 68
(2013/06/27)
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- Falcipain inhibitors: Optimization studies of the 2-pyrimidinecarbonitrile lead series
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Falcipain-2 and falcipain-3 are papain-family cysteine proteases of the malaria parasite Plasmodium falciparum that are responsible for host hemoglobin hydrolysis to provide amino acids for parasite protein synthesis. Different heteroarylnitrile derivatives were studied as potential falcipain inhibitors and therefore potential antiparasitic lead compounds, with the 5-substituted-2- cyanopyrimidine chemical class emerging as the most potent and promising lead series. Through a sequential lead optimization process considering the different positions present in the initial scaffold, nanomolar and subnanomolar inhibitors at falcipains 2 and 3 were identified, with activity against cultured parasites in the micromolar range. Introduction of protonable amines within lead molecules led to marked improvements of up to 1000 times in activity against cultured parasites without noteworthy alterations in other SAR tendencies. Optimized compounds presented enzymatic activities in the picomolar to low nanomolar range and antiparasitic activities in the low nanomolar range.
- Coterón, Jose M.,Catterick, David,Castro, Julia,Chaparro, María J.,Díaz, Beatriz,Fernández, Esther,Ferrer, Santiago,Gamo, Francisco J.,Gordo, Mariola,Gut, Jiri,De Las Heras, Laura,Legac, Jennifer,Marco, Maria,Miguel, Juan,Mu?oz, Vicente,Porras, Esther,De La Rosa, Juan C.,Ruiz, Jose R.,Sandoval, Elena,Ventosa, Pilar,Rosenthal, Philip J.,Fiandor, Jose M.
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supporting information; experimental part
p. 6129 - 6152
(2010/10/21)
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- NOVEL SAFRAMYCIN ANALOGS AS THERAPEUTIC AGENTS
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The present invention is directed to saframcyin analogs that are useful in the treatment of cancer. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.
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Page/Page column 59
(2008/06/13)
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- NOVEL SAFRAMYCIN ANALOGS AS THERAPEUTIC AGENTS
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The present invention is directed to saframcyin analogs that are useful in the treatment of cancer. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.
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Page/Page column 65
(2010/02/15)
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- Heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids as leukotriene biosynthesis inhibitors
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A novel series of heteroarylmethoxyphenylalkoxyiminoalkylcarboxylic acids was studied as leukotriene biosynthesis inhibitors. A hypothesis of structure-activity optimization by insertion of an oxime moiety was investigated using REV-5901 as a starting point. A systematic structure- activity optimization showed that the spatial arrangement and stereochemistry of the oxime insertion unit proved to be important for inhibitory activity. The promising lead, S-(E)-11, inhibited LTB4 biosynthesis in the intact human neutrophil with IC50 of 8 nM and had superior oral activity in vivo, in a rat pleurisy model (ED50 = 0.14 mg/kg) and rat anaphylaxis model (ED50 = 0.13 mg/kg). In a model of lung inflammation, S-(E)-11 blocked LTE4 biosynthesis (ED50 of 0.1 mg/kg) and eosinophil influx (ED50 of 0.2 mg/kg). S-(E)-11 (A-93178) was selected for further preclinical evaluation.
- Kolasa, Teodozyj,Gunn, David E.,Bhatia, Pramila,Woods, Keith W.,Gane, Todd,Stewart, Andrew O.,Bouska, Jennifer B.,Harris, Richard R.,Hulkower, Keren I.,Malo, Peter E.,Bell, Randy L.,Carter, George W.,Brooks, Clint D. W.
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p. 690 - 705
(2007/10/03)
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- Benzofuran compounds and their use
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Benzofuran compound represented by the formula: STR1 wherein STR2 represents a group capable of releasing a cation in which ....... represents a single or double bond: R1 represents an optionally substituted heterocyclic residue which may be attached to the oxygen atom through a carbon chain; R2 represents a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon residue, an optionally protected hydroxyl group or an optionally protected amino group; Y represents a di- or tri-valent aliphatic hydrocarbon residue having 1 to 8 carbon atoms; and the benzene ring of the benzofuran moiety may have further substituents; or a salt thereof, which has excellent hypoglycemic and hypolipidemic action.
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- Synthesis and characterization of the furo and thieno analogues of the triester of PQQ
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We report here the synthesis and properties of the furo and thieno analogues of 4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid (=PQQ), i.e. the furo- and thieno[2,3-f]quinoline-4,5-quinone (FQQ and TQQ, resp.) derivatives B and C, obtained as triesters. The triester of PQQ derivative A is much more stable than the triesters of B or C, and only the triester of A shows strong activity in nonenzymatic catalytic oxidations.
- Martin,Winkler
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p. 100 - 110
(2007/10/02)
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