- Compound for preparing PRC2 inhibitor, and preparation method and application thereof
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The invention discloses a compound for preparing a PRC2 inhibitor, and a preparation method and application thereof. According to the method disclosed by the invention, a series of oximes can be simply and efficiently obtained, then a series of benzylamin
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Paragraph 0014; 0066; 0070-0072; 0098; 0102-0104
(2021/06/23)
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- Redox-Neutral Coupling between Two C(sp3)?H Bonds Enabled by 1,4-Palladium Shift for the Synthesis of Fused Heterocycles
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The intramolecular coupling of two C(sp3)?H bonds to forge a C(sp3)?C(sp3) bond is enabled by 1,4-Pd shift from a trisubstituted aryl bromide. Contrary to most C(sp3)?C(sp3) cross-dehydrogenative couplings, this reaction operates under redox-neutral conditions, with the C?Br bond acting as an internal oxidant. Furthermore, it allows the coupling between two moderately acidic primary or secondary C?H bonds, which are adjacent to an oxygen or nitrogen atom on one side, and benzylic or adjacent to a carbonyl group on the other side. A variety of valuable fused heterocycles were obtained from easily accessible ortho-bromophenol and aniline precursors. The second C?H bond cleavage was successfully replaced with carbonyl insertion to generate other types of C(sp3)-C(sp3) bonds.
- Rocaboy, Ronan,Anastasiou, Ioannis,Baudoin, Olivier
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p. 14625 - 14628
(2019/09/16)
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- Synthesis of Functionalized Dihydrobenzofurans by Direct Aryl C?O Bond Formation under Mild Conditions
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A method for the synthesis of dihydrobenzofurans by a direct aryl C?O bond formation is described. A mechanistic pathway for the reaction, distinct from previously described similar transformations, allows for mild reaction conditions that are expected to be compatible with functionalized substrates.
- Alvarado, Joseph,Fournier, Jeremy,Zakarian, Armen
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supporting information
p. 11625 - 11628
(2016/10/24)
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- Discovery and structure-activity relationship of novel 2,3- dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2 h)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 Inhibitors
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Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3′,4′-dihydroxybenzylidene 58 (IC50 = 0.531 μM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4′-hydroxyl/4′-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66-68, 70, 72, and 73; IC50 values from 0.718 to 0.079 μM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (-)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors.
- Patel, Maulik R.,Bhatt, Aaditya,Steffen, Jamin D.,Chergui, Adel,Murai, Junko,Pommier, Yves,Pascal, John M.,Trombetta, Louis D.,Fronczek, Frank R.,Talele, Tanaji T.
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p. 5579 - 5601
(2014/08/05)
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- Nonsteroidal dissociated glucocorticoid agonists containing azaindoles as steroid A-ring mimetics
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Syntheses and structure-activity relationships (SAR) of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain azaindole moieties as A-ring mimetics and display various degrees of in vitro dissociation between gene trans
- Riether, Doris,Harcken, Christian,Razavi, Hossein,Kuzmich, Daniel,Gilmore, Thomas,Bentzien, J?rg,Pack, Edward J.,Souza, Donald,Nelson, Richard M.,Kukulka, Alison,Fadra, Tazmeen N.,Zuvela-Jelaska, Ljiljana,Pelletier, Josephine,Dinallo, Roger,Panzenbeck, Mark,Torcellini, Carol,Nabozny, Gerald H.,Thomson, David S.
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experimental part
p. 6681 - 6698
(2010/12/19)
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- Studies toward the discovery of the next generation of antidepressants. 3. Dual 5-HT1A and serotonin transporter affinity within a class of N-aryloxyethylindolylalkylamines
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N-Aryloxylethylindolealkylamines (5) having dual 5-HT transporter and 5-HT1A affinity are described. These compounds represent truncated analogues of our previously reported piperidinyl derivatives (3). Compounds in this investigation were found to have more similar affinities and functional activities for the 5-HT1A receptor and 5-HT transporter. Though 5-HT1A antagonism is not consistently observed throughout series 5, several molecular features were found to be essential to obtain high and balanced activities. The proper placement of a heteroatom in the aryl ring and the length of the linkage used to tether the indole moiety had significant influence on 5-HT1A and 5-HT transporter affinities. Introduction of a halogen into the aryl ring usually lowered intrinsic activity and in some cases led to full 5-HT1A antagonists. Compounds 33 and 34 were observed to be full 5-HT1A antagonists with Ki values of approximately 30 nM for the 5-HT1A receptor and Ki values of 5 and 0.5 nM for the 5-HT transporter, respectively. Unfortunately, similar to our previous series (3), compounds in this report also had high affinity for the α1 receptor.
- Mewshaw, Richard E.,Zhou, Dahui,Zhou, Ping,Shi, Xiaojie,Hornby, Geoffrey,Spangler, Taylor,Scerni, Rosemary,Smith, Deborah,Schechter, Lee E.,Andree, Terrance H.
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p. 3823 - 3842
(2007/10/03)
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- ARYLPIPERAZINYL-CYCLOHEXYL INDOLE DERIVATIVES FOR THE TREATMENT OF DEPRESSION
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Compounds are provided which are useful for the treatment of serotonin-affected neurological disorders which comprise (I) wherein: Ra, R1, R2 and R3 are each, independently, hydrogen, or a substituent selected from halogen, CF3, alkyl, alkoxy, MeSO2, amino or aminocarbonyl (each optionally substituted by one or two groups selected from alkyl and benzyl) carboxy, or alkoxycarbonyl; or two adjacent of Ra and R1-4 together can form a 5-7 membered carbocyclic or heterocyclic ring which is optionally substituted by a substituent defined above; R4 is hydrogen, halogen, or alkyl; R5 is hydrogen, alkyl, arylalkyl, or aryl; R6 is hydrogen, halogen, CF3, CN, carbamide, alkoxy or benzyloxy; X1, X2 and X3 are each carbon or one of X1, X2 or X3 may be nitrogen; Y is CH or nitrogen; and Z is carbon or nitrogen; or pharmaceutically acceptable salts thereof.
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- GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
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Compounds of Formula (IA) and Formula (IB) wherein R1, R2, R3, R4, R5, and R6 are as defined herein for Formula (IA) or Formula (IB), or a tautomer, prodrug, solvate,or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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Page/Page column 139-140
(2010/02/07)
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