- TRIAZINE DERIVATIVE HAVING EGFR INHIBITORY ACTIVITY, PREPARATION METHOD THEREFOR AND USE THEREOF
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Disclosed are a triazine derivative having EGFR inhibitory activity, a preparation method therefor and use thereof. In particular, disclosed are an EGFR inhibitor having a structure of formula (I), a preparation method therefor, a pharmaceutical composition containing same, use thereof for preparing the EGFR inhibitor, and use thereof in preparing medicaments for treating and/or preventing cancers, tumors or metastatic diseases at least partially related to insertion, deletion or other mutation of EGFR exon 20, and in particular use thereof in preparing medicaments for treating and/or preventing hyperproliferative diseases and diseases inducing cell death disorders. The definition of each substituent of formula (I) is the same as that in the description.
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Page/Page column 33
(2022/02/24)
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- NOVEL COMPOUNDS USEFUL AS POLY(ADP-RIBOSE) POLYMERASE (PARP) INHIBITORS
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The present invention provides novel poly(ADP-ribose) polymerase (PARP) inhibitors, methods of preparing them, pharmaceutical compositions containing them and methods for the treatment, prevention and/or amelioration of PARP mediated diseases or disorders using them. In particular, the compounds described herein are useful for the treatment of carcinoma of the breast, ovarian cancer, carcinoma of the liver, carcinoma of the lung, small cell lung cancer, esophageal cancer, gall bladder cancer, pancreatic cancer and stomach cancer.
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Paragraph 223
(2021/11/06)
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- NEW PROPANAMINE DERIVATIVES FOR TREATING PAIN AND PAIN RELATED CONDITIONS
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The present invention relates to new compounds of general formula (I) that show dual activity towards α2δ subunit of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit, and to the noradrenaline transporter (NET). The invention is also rel
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Page/Page column 66; 67
(2019/02/13)
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- PHARMACEUTICAL COMPOUNDS
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This invention relates to compounds that are agonists of the muscarinic M1 receptor or M1 and M4 receptors and which are useful in the treatment of muscarinic M1 or M1/M4 receptor mediated
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Paragraph 0734; 0735; 0736
(2018/04/26)
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- SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
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The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer, wherein A, R2, R3, R10, E1, E2, E3, Y, and Z are as defined herein.
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Page/Page column 286
(2017/08/01)
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- AZAINDOLE COMPOUNDS AS MODULATORS OF RORC
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The present invention encompasses compounds of the formula (I), wherein the variables are defined herein which are suitable for the modulation of RORC and the treatment of diseases related to the modulation of RORC. The present invention also encompasses processes of making compounds of formula (I) and pharmaceutical preparations containing them.
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Page/Page column 43; 44
(2015/02/25)
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- Lead optimization of 1,4-azaindoles as antimycobacterial agents
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In a previous report, we described the discovery of 1,4-azaindoles, a chemical series with excellent in vitro and in vivo antimycobacterial potency through noncovalent inhibition of decaprenylphosphoryl-β-d-ribose-2′- epimerase (DprE1). Nevertheless, high mouse metabolic turnover and phosphodiesterase 6 (PDE6) off-target activity limited its advancement. Herein, we report lead optimization of this series, culminating in potent, metabolically stable compounds that have a robust pharmacokinetic profile without any PDE6 liability. Furthermore, we demonstrate efficacy for 1,4-azaindoles in a rat chronic TB infection model. We believe that compounds from the 1,4-azaindole series are suitable for in vivo combination and safety studies.
- Shirude, Pravin S.,Shandil, Radha K.,Manjunatha,Sadler, Claire,Panda, Manoranjan,Panduga, Vijender,Reddy, Jitendar,Saralaya, Ramanatha,Nanduri, Robert,Ambady, Anisha,Ravishankar, Sudha,Sambandamurthy, Vasan K.,Humnabadkar, Vaishali,Jena, Lalit K.,Suresh, Rudrapatna S.,Srivastava, Abhishek,Prabhakar,Whiteaker, James,McLaughlin, Robert E.,Sharma, Sreevalli,Cooper, Christopher B.,Mdluli, Khisi,Butler, Scott,Iyer, Pravin S.,Narayanan, Shridhar,Chatterji, Monalisa
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p. 5728 - 5737
(2014/08/05)
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- Azaindoles: Noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo
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We report 1,4-azaindoles as a new inhibitor class that kills Mycobacterium tuberculosis in vitro and demonstrates efficacy in mouse tuberculosis models. The series emerged from scaffold morphing efforts and was demonstrated to noncovalently inhibit decaprenylphosphoryl-β-D-ribose2′-epimerase (DprE1). With "drug-like" properties and no expectation of pre-existing resistance in the clinic, this chemical class has the potential to be developed as a therapy for drug-sensitive and drug-resistant tuberculosis.
- Shirude, Pravin S.,Shandil, Radha,Sadler, Claire,Naik, Maruti,Hosagrahara, Vinayak,Hameed, Shahul,Shinde, Vikas,Bathula, Chandramohan,Humnabadkar, Vaishali,Kumar, Naveen,Reddy, Jitendar,Panduga, Vijender,Sharma, Sreevalli,Ambady, Anisha,Hegde, Naina,Whiteaker, James,McLaughlin, Robert E.,Gardner, Humphrey,Madhavapeddi, Prashanti,Ramachandran, Vasanthi,Kaur, Parvinder,Narayan, Ashwini,Guptha, Supreeth,Awasthy, Disha,Narayan, Chandan,Mahadevaswamy, Jyothi,Vishwas,Ahuja, Vijaykamal,Srivastava, Abhishek,Prabhakar, Kr,Bharath, Sowmya,Kale, Ramesh,Ramaiah, Manjunatha,Choudhury, Nilanjana Roy,Sambandamurthy, Vasan K.,Solapure, Suresh,Iyer, Pravin S.,Narayanan, Shridhar,Chatterji, Monalisa
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supporting information
p. 9701 - 9708
(2014/01/06)
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- Discovery and bioactivity of 4-(2-arylpyrido[3′,2′:3,4] pyrrolo[1,2-f][1,2,4]triazin-4-yl) morpholine derivatives as novel PI3K inhibitors
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PI3K is a promising therapeutic target for cancer. With PI-103 as the lead compound, we designed and synthesized 4-(2-arylpyrido[3′,2′:3,4] pyrrolo[1,2-f][1,2,4]triazin-4-yl)morpholine derivatives. 9, 10a, 10d, 10e had the IC50 against PI3Kα comparable with PI-103. All of the compounds showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several cancer cell lines.
- Wang, Jia,Wang, Xiang,Chen, Yanhong,Chen, Simeng,Chen, Guang,Tong, Linjiang,Meng, Linghua,Xie, Yuyuan,Ding, Jian,Yang, Chunhao
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scheme or table
p. 339 - 342
(2012/03/11)
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- GSK-3BETA INHIBITOR
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For the purpose of providing a GSK-3β inhibitor containing a 2-aminopyridine compound or a salt thereof or a prodrug thereof useful as an agent for the prophylaxis or treatment of a GSK-3β-related pathology or disease, the present invention provides a GSK-3β inhibitor containing a compound represented by the formula (IA): wherein each symbol is as defined in the specification. or a salt thereof or a prodrug thereof.
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Page/Page column 32
(2011/04/13)
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- Chemical development of the casein kinase i - Epsilon inhibitor: 3-(3-fluorophenyl)sulfanyl-1 H -pyrrolo[3,2- b pyridine-2-carboxylic acid amide
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The development of a scalable process for 3-arylsulfanyl-1H-pyrrolo[3,2- bpyridine-2-carboxylic acid amides (1), potent casein kinase I inhibitors, is described. The rapid identification of suitable reaction conditions expedited the lab scale synthesis of drug substances for early toxicological evaluations. Further improvements were made to achieve a safe and cost-effective process to meet increasing demands for drug substances to support clinical studies. This paper describes the synthesis at multikilogram scale.
- Huang, Bao-Guo,Kubiak, Gregory,Shay, John J.,Pemberton, Clive,Peers, James,Hanna, Reda G.,Powers, Matthew R.,Gamboa, Juan A.,Gelormini, Ann M.,Yarabe, Hyacinthe,Rudisill, Duane E.
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experimental part
p. 1040 - 1045
(2011/12/21)
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- 3' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein Q, R1, R4, m and Ar are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 136-137
(2009/04/25)
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- Substituted 1H-pyrrolo[3,2-b, 3,2-c, and 2,3-c]pyridine-2-carboxamides and related analogs as inhibitors of casein kinase lepsilon
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The present invention discloses and claims compounds of formula (I) as inhibitors of human casein kinase IF, and methods of using said compounds of formula (I) for treating central nervous system diseases and disorders including mood disorders and sleep disorders. Pharmaceutical compositions comprising compounds of formula (I) and methods for the preparation of compounds of formula (I) are also disclosed and claimed.
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Page/Page column 13
(2008/06/13)
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- Excited state tautomerization of azaindole
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Fluorescent tryptophan analogs, like azatryptophan, offer an advantage for exploring protein and peptide structure and dynamics. The chromophoric moieties, azaindole, of the azatryptophan analogs are investigated for their potential as fluorescent probes. The photophysical properties of 4-azaindole (4AI) and 5-azaindole (5AI) and their tautomers are characterized through computational and experimental methods. Both 4AI and 5AI undergo excited state tautomerization in the presence of 1 M NaOH. The protonated forms of 4AI and 5AI have a fluorescence emission of 415 and 410 nm, respectively, while the tautomers of 4AI and 5AI have a fluorescent emission of 480 and 450 nm, respectively. Gas phase computations (B3LYP/6-31+G**) show that the N1H azaindole tautomer is lower in energy in the ground state by as much as 12.5 kcal mol-1, while the N″H azaindole tautomer is lower in energy in the excited state by as much as 18.1 kcal mol-1. Solvent effects on the tautomer energy differences were computed using the isodensity polarized continuum model (IPCM). The polarity of the solvent helps to reduce the energy difference between the tautomers in the ground state by as much as 5.8 kcal mol-1, but not enough to reverse the ground state tautomer preference. The Royal Society of Chemistry 2005.
- Cash, Michael T.,Schreiner, Peter R.,Phillips, Robert S.
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p. 3701 - 3706
(2007/10/03)
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- Discovery and in vitro evaluation of potent TrkA kinase inhibitors: Oxindole and aza-oxindoles
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The discovery, synthesis, potential binding mode, and in vitro kinase profile of 3-(3-bromo-4-hydroxy-5-(2′-methoxyphenyl)-benzylidene)-5-bromo- 1,3-dihydro-pyrrolo[2,3-b]pyridin-2-one, 3-[(1-methyl-1H-indol-3-yl)methylene]- 1,3-dihydro-2H-pyrrolo[3,2-b]-pyridin-2-one as potent TrkA inhibitors are discussed.
- Wood, Edgar R.,Kuyper, Lee,Petrov, Kimberly G.,Hunter III, Robert N.,Harris, Philip A.,Lackey, Karen
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p. 953 - 957
(2007/10/03)
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- Synthesis of 2-aryl-1-hydroxyazaindoles and 2-arylazaindoles via oxidation of o-hydroxyaminostyrylpyridines
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2-Aryl-1-hydroxyazaindoles (pyrrolopyridin-1-ols) are prepared via an oxidation/cyclization of o-hydroxyaminostyrylpyridines with DDQ. Reduction of the N-OH bond affords the corresponding 2-arylazaindoles (1H-pyrrolopyridines). The scope of the cyclization is explored via (i) the condensation of 4-methyl-3-nitropyridine with various aryl aldehydes to afford 2-aryl substituted 6-azaindoles and, (ii) the synthesis of 2-phenyl-4-, 5- and 7-azaindoles.
- Kuzmich, Daniel,Mulrooney, Carol
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p. 1671 - 1678
(2007/10/03)
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- Substituted aza-oxindole derivatives
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Substituted aza-oxindole derivatives useful as cyclin dependent kinase 11 inhibitors, for preventing/reducing the severity of epithelial cytotoxicity side-effects (e.g., alopecia, plantar-palmar syndrome, mucositis) induced by chemoptherapy and/or radiati
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- 3-(anilinomethylene) oxindoles
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The present invention relates generally to novel amine substituted oxindole compounds and compositions. Such compounds and compositions have utility as pharmacological agents in treating diseases or conditions alleviated by the inhibition or antagonism of
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Page column 71-72
(2010/02/04)
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- Oxindolylquinazoline derivatives as angiogenesis inhibitors
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The invention relates to compounds of formula (I) and salts thereof as further defined herein, wherein ring Z is a 6-membered heterocyclic ring containing 1 to 3 nitrogen atoms, and the use of such compounds and salts to inhibit the effects of VEGF and FGF, and in the treatment of a number of disease states including cancer and rheumatoid arthritis.
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- Pyridylcarbamates, process and intermediates for their preparation, and their use
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A pyridylcarbamate compound of the formula I STR1 wherein R' is hydrogen; opt. subst. alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, alkylcarbonyl and alkoxycarbonyl; R" is opt. subst. alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl; or is hydrogen when V is nitrogen; V is O, S or N; X is cyano; nitro; halogen; opt. subst. alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, or an opt. subst. bridge which is bonded to two adjacent C atoms of the pyridyl ring; n is 0, 1, 2 or 3; R is halogen; OH; SH; NH; CHO; CO2 H; CONH2 ; opt. subst. alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or hetaryl, each being bonded directly or via O, S, N, CO2 or CONH; or together with X and the pyridyl ring to which they are bonded an opt. subst. bicyclus, its manufacture, and pesticidal and fungicidal compositions containing I.
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- A One-pot Synthesis of 3-Nitro- and 3,5-Dinitro-2-picolines
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3-Nitro- and 3,5-dinitro-2-picoline were each prepared in a one-pot synthesis in high yield by treatment of the respective 2-chloro-3-nitro- and 2-chloro-3,5-dinitropyridines with diethyl sodiomalonate, followed by hydrolysis and decarboxylation with 50percent sulfuric acid.
- Liu, Mao-Chin,Lin, Tai-Shun,Sartorelli, Alan C.
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p. 2965 - 2970
(2007/10/02)
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