- Indazole formamide compound as well as preparation method and application thereof
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The invention belongs to the field of chemical medicines, and particularly relates to an indazole formamide compound as well as a preparation method and application thereof. The invention provides anindazole carboxamide compound or a pharmaceutically acce
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Paragraph 0035; 0037-0038
(2021/02/16)
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- Polyheterocyclic substituted pyrimidines or pyridylamine derivatives Composition and medical application thereof
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The invention discloses a polycyclic substituted pyrimidine or pyridine amine derivative, and the structure is shown in a formula (I). The invention further discloses a pharmaceutically acceptable salt of the derivative, a solvate, a stereoisomer, a prodrug, a pharmaceutical composition and and an application thereof in medicine. The compounds of the present invention have significant adenosine A. 2A Receptor and/or adenosine A2B The receptor antagonism activity is very practical.
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Paragraph 0303-0305
(2021/09/26)
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- Discovery and Structure-Activity Relationships of Quinazolinone-2-carboxamide Derivatives as Novel Orally Efficacious Antimalarials
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A phenotypic high-throughput screen allowed discovery of quinazolinone-2-carboxamide derivatives as a novel antimalarial scaffold. Structure-activity relationship studies led to identification of a potent inhibitor 19f, 95-fold more potent than the origin
- Laleu, Beno?t,Akao, Yuichiro,Ochida, Atsuko,Duffy, Sandra,Lucantoni, Leonardo,Shackleford, David M.,Chen, Gong,Katneni, Kasiram,Chiu, Francis C. K.,White, Karen L.,Chen, Xue,Sturm, Angelika,Dechering, Koen J.,Crespo, Benigno,Sanz, Laura M.,Wang, Binglin,Wittlin, Sergio,Charman, Susan A.,Avery, Vicky M.,Cho, Nobuo,Kamaura, Masahiro
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p. 12582 - 12602
(2021/09/13)
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- Derivative based on PARP inhibitor Niraparib and a preparation method and use thereof
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The invention discloses a derivative based on a PARP inhibitor Niraparib. The derivative has a structure shown in a formula I as shown in the description, wherein R1 is selected from alkyl, alkoxy, cycloalkyl, aryl alkyl, cycloalkyl alkyl, heterocyclyl, a
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Paragraph 0029; 0037-0043
(2019/10/29)
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- SINGLE MOLECULE COMPOUNDS PROVIDING MULTI-TARGET INHIBITION OF PARP AND OTHER PROTEINS AND METHODS OF USE THEREOF
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The invention relates to compounds useful for inhibiting PARP and at least one other protein and to methods of treating diseases including cancer by administration of a compound(s) of Formula I-V (or pharmaceutically acceptable salts thereof) as defined herein.
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Paragraph 0160
(2019/01/10)
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- Chemoselective reduction and self-immolation based FRET probes for detecting hydrogen sulfide in solution and in cells
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Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter. Based on the mechanism of chemoselective azido reduction and self-immolation, five fluorescence resonance energy transfer (FRET) probes for the detection of H2S were designed and synthesized. The effect of functional substitution of the self-immolative moiety on azido reduction and quinone-methide rearrangement were investigated. Their fluorescence responses and chemoselectivity for H2S detection were evaluated in solutions and in cells. This strategy may provide a general route for designing H 2S probes with many commercially available FRET pairs. the Partner Organisations 2014.
- Chen, Bifeng,Wang, Peng,Jin, Qingqing,Tang, Xinjing
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supporting information
p. 5629 - 5633
(2014/07/22)
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- Development of a fit-for-purpose large-scale synthesis of an oral PARP inhibitor
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Compound (1) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed,
- Wallace, Debra J.,Baxter, Carl A.,Brands, Karel J. M.,Bremeyer, Nadine,Brewer, Sarah E.,Desmond, Richard,Emerson, Khateeta M.,Foley, Jennifer,Fernandez, Paul,Hu, Weifeng,Keen, Stephen P.,Mullens, Peter,Muzzio, Daniel,Sajonz, Peter,Tan, Lushi,Wilson, Robert D.,Zhou, George,Zhou, Guoyue
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scheme or table
p. 831 - 840
(2012/07/03)
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- PHARMACEUTICALLY ACCEPTABLE SALTS OF 2-{4-[(3S)-PIPERIDIN-3- YL]PHENYL} -2H-INDAZOLE-7-CARBOXAMIDE
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The present invention relates to pharmaceutically acceptable salts of an amide substituted indazole which are inhibitors of the enzyme poly(ADP-ribose)polymerase (PARP), previously known as poly(ADP-ribose)synthase and poly(ADP-ribosyl)transferase. The compounds of the present invention are useful as mono-therapies in tumors with specific defects in DNA-repair pathways and as enhancers of certain DNA -damaging agents such as anticancer agents and radiotherapy. Further, the compounds of the present invention are useful for reducing cell necrosis (in stroke and myocardial infarction), down regulating inflammation and tissue injury, treating retroviral infections and protecting against the toxicity of chemotherapy.
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Page/Page column 35
(2009/09/04)
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- Design, synthesis and identification of novel colchicine-derived immunosuppressant
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Synthesis and biological evaluation of various colchicine analogues through the mixed-lymphocyte reaction (MLR), lymphoproliferation, and inhibitory effects on the inflammatory genes are described. In addition, a new series of immunosuppressive agents developed on the structural basis of colchicine, as well as their structure-activity relationships is reported. The most potent analogue 20a exhibited an excellent immunosuppressive activity on in vivo skin-allograft model, which is comparable to that of cyclosporin A.
- Chang, Dong-Jo,Yoon, Eun-Young,Lee, Geon-Bong,Kim, Soon-Ok,Kim, Wan-Joo,Kim, Young-Myeong,Jung, Jong-Wha,An, Hongchan,Suh, Young-Ger
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scheme or table
p. 4416 - 4420
(2010/04/05)
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- Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors
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We disclose the development of a novel series of 2-phenyl-2H-indazole-7- carboxamides as poly(ADP-ribose) polymerase (PARP) 1 and 2 inhibitors. This series was optimized to improve enzyme and cellular activity, and the resulting PARP inhibitors display antiproliferation activities against BRCA-1 and BRCA-2 deficient cancer cells, with high selectivity over BRCA proficient cells. Extrahepatic oxidation by CYP450 1A1 and 1A2 was identified as a metabolic concern, and strategies to improve pharmacokinetic properties are reported. These efforts culminated in the identification of 2-{4-[(3S)-piperidin-3-yl] phenyl}-2H-indazole-7-carboxamide 56 (MK-4827), which displays good pharmacokinetic properties and is currently in phase I clinical trials. This compound displays excellent PARP 1 and 2 inhibition with IC50 = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.
- Jones, Philip,Altamura, Sergio,Boueres, Julia,Ferrigno, Federica,Fonsi, Massimiliano,Giomini, Claudia,Lamartina, Stefania,Monteagudo, Edith,Ontoria, Jesus M.,Orsale, Maria Vittoria,Palumbi, Maria Cecilia,Pesci, Silvia,Roscilli, Giuseppe,Scarpelli, Rita,Schultz-Fademrecht, Carsten,Toniatti, Carlo,Rowley, Michael
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experimental part
p. 7170 - 7185
(2010/07/04)
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- AMIDE SUBSTITUTED INDAZOLE AND BENZOTRIAZOLE DERIVATIVES AS POLY(ADP-RIBOSE)POLYMERASE (PARP) INHIBITORS
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The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts or tautomers thereof which are inhibitors of poly (ADP-ribose) polymerase (PARP) and thus useful for the treatment of cancer, inflammatory diseases, reperfusio
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Page/Page column 77
(2008/06/13)
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- BICYCLIC DERIVATIVES AS PPAR MODULATORS
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The present invention is directed to compounds represented by the following structural formula, Formula (I), and stereoisomers, pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R2 is selected from the group consisting of C0-C8 alkyl and C1-4- heteroalkyl; (b) X is selected from the group consisting of a single bond, O, S, S(O)2 and N; (c) U is an aliphatic linker wherein one carbon atom of the aliphatic linker is optionally replaced with O, NH or S, and wherein such aliphatic linker is optionally substituted with from one to four substituents each independently selected from R30; (d) Y is selected from the group consisting of C, O, S, NH and a single bond; and (e) E is C(R3)(R4)A or A.
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Page/Page column 88
(2008/06/13)
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- Novel phenylalanine derivatives
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Specific phenylalanine derivatives and analogues thereof have an antagonistic activity to α4 integrin. They are used as therapeutic agents for various diseases concerning α4 integrin.
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Page/Page column 30
(2010/02/14)
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- Synthesis of novel analogs of aromatic peptide nucleic acids (APNAs) with modified conformational and electrostatic properties
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Aromatic peptide nucleic acid analogs having an N-(2-aminobenzyl)glycine backbone (APNA 1) were previously identified as promising new leads for the design of polyaromatic DNA mimics. Structural modifications of 1, which lock the aromatic backbone into a
- Fader, Lee D.,Myers, Eddie L.,Tsantrizos, Youla S.
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p. 2235 - 2246
(2007/10/03)
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- Electrosynthesis of dibenzonaphthyridine derivatives from 2,2-(2-nitrobenzyl)-2-substituted-acetonitriles
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An indirect electrochemical procedure involving an ex-cell two-phase process is proposed to produce dibenzonaphthyridine derivatives from 2,2-(2-nitrobenzyl)-2-substituted-acetonitriles in dichloromethane. The selective reduction of both nitro groups into amino groups using Cp2Ti+ in aqueous acidic medium avoids a cyclization of hydroxylamine intermediates as observed by direct electrolysis.
- Jan, Thierry,Dupas, Béatrice,Floner, Didier,Moinet, Claude
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p. 5949 - 5952
(2007/10/03)
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- Palladium-Catalyzed Synthesis of Indoles by Reductive N-Heteroannulation of 2-Nitrostyrenes
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A palladium-phosphine catalyzed reductive N-heteroannulation of 2-nitrostyrenes, in the presence of carbon monoxide, producing indoles has been developed. Indoles were obtained, in moderate to excellent yield, from substituted 2-nitrostyrenes having either electron-withdrawing (NO2 and CO2-Me) or electron-donating (Br, OH, Me, OMe, and OTf) substituents on the aromatic ring. Best results were obtained using palladium diacetate (6 mol percent) together with triphenylphosphine (24 mol percent) as the catalytic system, under 4 atm of carbon monoxide in acetonitrile at 70 °C. Other palladium(II) and palladium(0) complexes also catalyze the reaction.
- So?derberg, Bjo?rn C.,Shriver, James A.
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p. 5838 - 5845
(2007/10/03)
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- Heterocyclic amines having central nervous system activity
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Tricyclic nitrogen containing compounds, having central nervous system activity of the following structural formula: STR1 and pharmaceutically acceptable salts thereof wherein R1, R2, and R3 are independently hydrogen, C1-6 alkyl, alkenyl, or alkynyl, C3-10 cycloalkyl, or R1 and R2 are joined to form a C3-7 cyclic amine which can contain additional heteroatoms; X is hydrogen, C1-6 alkyl halogen, hydroxy, alkoxy, cyano, carboxamide, carboxyl, or carboalkoxyl; A is SO2, N, CH, CH2, CHCH3, C=O, C=S, C-SCH3, C=NH, C-NH2, C-NHCH3, C--NHCOOCH3, or C--NHCN. B is CH2, CH, C=O, N, NH or N--CH3 ; n is 0 or 1; and D is CH, CH2, C=O, O, N, NH or N--CH3. These new compounds are suitable for treating schizophrenia, Parkinson's disease, anxiety, depression or as compounds for lowering blood pressure in animal or human hosts.
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- Diacid-containing benzimidazole compounds for treatment of neurotoxic injury
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A class of diacid-containing benzimidazole compounds is described for treatment to reduce neurotoxic injury associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a
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