129912-28-3Relevant articles and documents
PYRAZOLOPYRIDINE PYRAZOLOPYRIMIDINE AND RELATED COMPOUNDS
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Paragraph 1289; 1290, (2015/11/25)
In one aspect this invention relates generally to compounds of Formula: and sub-formulas thereof, or a tautomer of each thereof, a pharmaceutically acceptable salt of each thereof, or a pharmaceutically acceptable solvate of each of the foregoing, where X1, L1, L3, and R3 are described herein.
Discovery of (10 R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17- tetrahydro- 2H -8,4-(metheno)pyrazolo[4,3- h ][2,5,11]- benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations
Johnson, Ted W.,Richardson, Paul F.,Bailey, Simon,Brooun, Alexei,Burke, Benjamin J.,Collins, Michael R.,Cui, J. Jean,Deal, Judith G.,Deng, Ya-Li,Dinh, Dac,Engstrom, Lars D.,He, Mingying,Hoffman, Jacqui,Hoffman, Robert L.,Huang, Qinhua,Kania, Robert S.,Kath, John C.,Lam, Hieu,Lam, Justine L.,Le, Phuong T.,Lingardo, Laura,Liu, Wei,McTigue, Michele,Palmer, Cynthia L.,Sach, Neal W.,Smeal, Tod,Smith, Graham L.,Stewart, Albert E.,Timofeevski, Sergei,Zhu, Huichun,Zhu, Jinjiang,Zou, Helen Y.,Edwards, Martin P.
supporting information, p. 4720 - 4744 (2014/07/07)
Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and physical-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clinically reported ALK kinase domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity.
NOVEL HETEROCYCLIC COMPOUND, AND COMPOSITION FOR TREATING INFLAMMATORY DISEASES USING SAME
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Paragraph 0068; 0069, (2013/07/05)
The heterocyclic compound according to the present invention may treat and prevent inflammatory diseases and heal skin wounds, and particularly, have effects of recovering damaged skin barrier, reducing inflammation and pruritus in inflammatory skin disea
MACROCYCLIC DERIVATIVES FOR THE TREATMENT OF PROLIFERATIVE DISEASES
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Page/Page column 228-229, (2013/09/26)
The invention relates to compounds of formula (Φ) as further defined herein and to the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to the uses thereof. The compounds and salts of the present invention inhibit anaplastic lymphoma kinase (ALK) and/or EML4-ALK and are useful for treating or ameliorating abnormal cell proliferative disorders, such as cancer.
