183741-80-2Relevant articles and documents
ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE 1 (ENPP-1) INHIBITORS AND USES THEREOF
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Paragraph 0613, (2019/03/17)
Disclosed herein are methods and compounds of augmenting and enhancing the production of type I IFNs in vivo. In some embodiments, the compounds disclosed herein are ENPP-1 inhibitors, pharmaceutical compositions, and methods for the treatment of cancer or a viral infection.
Mitigation of Acetylcholine Esterase Activity in the 1,7-Diazacarbazole Series of Inhibitors of Checkpoint Kinase 1
Gazzard, Lewis,Williams, Karen,Chen, Huifen,Axford, Lorraine,Blackwood, Elizabeth,Burton, Brenda,Chapman, Kerry,Crackett, Peter,Drobnick, Joy,Ellwood, Charles,Epler, Jennifer,Flagella, Michael,Gancia, Emanuela,Gill, Matthew,Goodacre, Simon,Halladay, Jason,Hewitt, Joanne,Hunt, Hazel,Kintz, Samuel,Lyssikatos, Joseph,Macleod, Calum,Major, Sarah,Médard, Guillaume,Narukulla, Raman,Ramiscal, Judi,Schmidt, Stephen,Seward, Eileen,Wiesmann, Christian,Wu, Ping,Yee, Sharon,Yen, Ivana,Malek, Shiva
, p. 5053 - 5074 (2015/07/02)
Checkpoint kinase 1 (ChK1) plays a key role in the DNA damage response, facilitating cell-cycle arrest to provide sufficient time for lesion repair. This leads to the hypothesis that inhibition of ChK1 might enhance the effectiveness of DNA-damaging therapies in the treatment of cancer. Lead compound 1 (GNE-783), the prototype of the 1,7-diazacarbazole class of ChK1 inhibitors, was found to be a highly potent inhibitor of acetylcholine esterase (AChE) and unsuitable for development. A campaign of analogue synthesis established SAR delineating ChK1 and AChE activities and allowing identification of new leads with improved profiles. In silico docking using a model of AChE permitted rationalization of the observed SAR. Compounds 19 (GNE-900) and 30 (GNE-145) were identified as selective, orally bioavailable ChK1 inhibitors offering excellent in vitro potency with significantly reduced AChE activity. In combination with gemcitabine, these compounds demonstrate an in vivo pharmacodynamic effect and are efficacious in a mouse p53 mutant xenograft model.
Discovery of a novel series of thienopyrimidine as highly potent and selective PI3K inhibitors
Han, Fangbin,Lin, Songwen,Liu, Peng,Liu, Xiujie,Tao, Jing,Deng, Xiaobing,Yi, Chongqin,Xu, Heng
supporting information, p. 434 - 438 (2015/04/27)
Inhibition of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway provides a promising new approach for cancer therapy. Through a rational design, a novel series of thienopyrimidine was discovered as highly pote
TRPV4 ANTAGONISTS
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Page/Page column 78-79, (2013/03/26)
The present invention relates to spirocarbamate compounds of Formula (I) in which R1, (R2)Y, R3, R4, X and A have the meanings given in the specification. The invention further provides pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and relates to their use of these compounds as TRPV4 antagonists in treating or preventing conditions associated with TRPV4 imbalance.
AZACARBOLINE DERIVATIVES, PREPARATION METHOD THEREOF AND THERAPEUTIC USE OF SAME
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Page/Page column 46, (2011/08/04)
The invention relates to novel azacarbonlines having formula (I), wherein: R3, R4 represent independently H; hal; CF3; substituted oxy, optionally substituted alkoxy; optionally substituted amino; substituted carbonyl; optionally substituted carboxyl; optionally substituted amide; sulphur, such as optionally substituted sulphones, sulphoxides or sulphides; linear, branched or cyclic C1-C10 alkyl optionally comprising an optionally substituted heteroatom; optionally substituted linear, branched or cyclic C2-C7 alkenyl; optionally substituted linear or branched C2-C6 alkynyl; optionally substituted aryl or heteroaryl; of which may be optionally substituted; in the form of a base or an acid addition salt. The invention also relates to the use of same in therapeutics for the treatment of cancer and to synthesis methods.
Preparation of azaindolines and benzoyl substituted azaindolines: Precursors of triazabenzo[cd]azulen-9-one PDE4 inhibitors
Badland, Matthew,Devillers, Ingrid,Durand, Corinne,Fasquelle, Véronique,Gaudillire, Bernard,Jacobelli, Henry,Manage, Ajith C.,Pevet, Isabelle,Puaud, Jocelyne,Shorter, Anthony J.,Wrigglesworth, Roger
supporting information; experimental part, p. 5292 - 5296 (2011/10/30)
The syntheses of various substituted azaindolines are described. Azaindolines were identified as potential key intermediates towards new PDE4 inhibitors.
ANTIDIABETIC AZAINDOLES AND DIAZAINDOLES
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Page/Page column 73-74, (2009/03/07)
Azaindoles and diazaindoles having aromatic substituents on the 5-membered ring are agonists or partial agonists of the PPAR receptor and are useful in the treatment and control of type 2 diabetes and of symptoms of diabetes, including hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and obesity that are often associated with type 2 diabetes.
Azabenzodiazepines as pde4 inhibitors
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Page/Page column 8, (2010/02/11)
Compounds of formula (I): characterized in that:R1 represents a group selected from hydrogen atom, methyl, methoxy, hydroxy, amino, dimethylamino, acetamido, pyrrolidin-1-yl, and hydroxymethyl;R2 represent a group selected from phenyl, pyridyl, pyrimidyl, quinolyl, isoquinolyl, indolyl, pyrolyl, [1,2,3]-triazolyl, benzo[c]isoxazolyl, thienyl, pyrazolyl, isothiazolyl, imidazolyl, benzofuranyl, pyrazolo[5,1-c][1,2,4]triazyl each of these groups being optionally substituted from 1 to 3 groups, identical or different independently of each other, selected from halogen, trifluoromethyl, (C1-C4)alkyl, (C1-C4)alkoxy, hydroxy, amino, acetamido, tert-butyloxycarbonylamino, cycloalkylcarbonylamino, sulfonamide, nitro, acetylmethoxy, cyclopentyloxy; optionally, their optical isomers, and addition salts thereof with a pharmaceutically acceptable acid or base, and their use as active ingredient in pharmaceutical composition useful for treating diseases involving therapy by inhibition of PDE4.
Synthesis of 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones via directed lithiation of 2-substituted 5-aminopyridine derivatives
Rewcastle, Gordon W.,Denny, William A.,Winters, R. Thomas,Colbry, Norman L.,Showalter, H. D. Hollis
, p. 2221 - 2226 (2007/10/03)
Directed lithiation of Boc or pivaloyl derivatives of 2-substituted 5-aminopyridines with BuLi-TMEDA in diethyl ether at -10°C gave 4-lithio derivatives which were quenched with CO2 to give the analogous C-4 carboxylic acids. Hydrolysis of the protecting groups with either TFA or aqueous KOH gave 2-substituted 5-aminopyridine-4-carboxylic acids which were converted to 6-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones by reaction with formamide or, more optimally, formamidine acetate. Boc protected aminopyridines provided the best overall results, with synthesis of these derivatives best achieved by direct reaction of the aminopyridine with di-tert-butyl dicarbonate in the absence of added base.