- Discovery of potent colony-stimulating factor 1 receptor inhibitors by replacement of hinge-binder moieties
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Tumor-associated macrophages (TAMs) are predominantly associated with tumor growth. Colony-stimulating factor 1 receptor (CSF1R) acts as a key regulator of TAM survival and differentiation and is a molecular target for cancer therapies. Herein, novel CSF1
- Lee, Jung Wuk,Park, Jiwon,Kim, Jina,Kim, Jihyung,Choi, Changyu,Min, Kyung Hoon
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- NOVEL INHIBITORS OF MAP4K1
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The invention relates to novel inhibitors of MAP4K1 (HPK1) useful for the treatment of diseases or disorders characterised by dysregulation of the signal transduction pathways associated with MAPK activation, including hyperproliferative diseases, diseases of immune system dysfunction, inflammatory disorders, neurological diseases, and cardiovascular diseases. The invention further relates to pharmaceutical compositions comprising the same and methods of treatment of said diseases and disorders. The inhibitors are of formula (I) wherein the definitions for A, D, E, F, R5, R6, R7, Z, ring Q, n, x and y are as given in the application.
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Page/Page column 67
(2018/12/13)
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- Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad-Spectrum Antiproliferative Activity
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Herein we report the discovery of compound 6 [KST016366; 4-((2-(3-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)ureido)benzo[d]thiazol-6-yl)oxy)picolinamide] as a new potent multikinase inhibitor through minor structural modification of our
- El-Damasy, Ashraf Kareem,Cho, Nam-Chul,Nam, Ghilsoo,Pae, Ae Nim,Keum, Gyochang
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supporting information
p. 1587 - 1595
(2016/08/28)
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- ISOQUINOLINE-5-CARBOXAMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
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A compound selected from the group consisting of an isoquinoline-5-carboxamide derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate and a solvate thereof is effective for the prevention or treatment of diseases associated with abnormal cell growth, which are caused by abnormal activation of a protein kinases.
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Paragraph 0089
(2015/06/03)
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- ISOQUINOLINE-5-CARBOXAMIDE DERIVATIVE HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASE
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A compound selected from the group consisting of an isoquinoline-5-carboxamide derivative of formula (I), a pharmaceutically acceptable salt, an isomer, a hydrate and a solvate thereof is effective for the prevention or treatment of diseases associated with abnormal cell growth, which are caused by abnormal activation of a protein kinases.
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Paragraph 0188-0190
(2015/07/15)
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- THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
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Paragraph 0246; 0247; 0248
(2015/01/06)
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- FUSED TRICYCLIC UREA COMPOUNDS AS RAF KINASE AND/OR RAF KINASE DIMER INHIBITORS
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Provided are certain fused tricyclic urea compounds and salts thereof, compositions thereof, and methods of use therefor.
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Page/Page column 80; 81
(2015/01/16)
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- SUBSTITUTED PYRIMIDINYL AND PYRIDINYL-PYRROLOPYRIDINONES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
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The present invention relates to substituted pyrimidinyl- and pyridinylpyrrolopyridinone compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular RET family kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions containing these compounds.
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Page/Page column 40
(2014/05/24)
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- THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases
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Page/Page column 37
(2013/07/19)
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- Discovery of 3-[2-(imidazo[1,2- b ]pyridazin-3-yl)ethynyl]-4-methyl- N -{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant
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In the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors, the T315I gatekeeper mutant has emerged as resistant to all currently approved agents. This report describes the structure-guided design of a novel series of potent pan-inhibitors of BCR-ABL, including the T315I mutation. A key structural feature is the carbon-carbon triple bond linker which skirts the increased bulk of Ile315 side chain. Extensive SAR studies led to the discovery of development candidate 20g (AP24534), which inhibited the kinase activity of both native BCR-ABL and the T315I mutant with low nM IC 50s, and potently inhibited proliferation of corresponding Ba/F3-derived cell lines. Daily oral administration of 20g significantly prolonged survival of mice injected intravenously with BCR-ABLT315I expressing Ba/F3 cells. These data, coupled with a favorable ADME profile, support the potential of 20g to be an effective treatment for CML, including patients refractory to all currently approved therapies.
- Huang, Wei-Sheng,Metcalf, Chester A.,Sundaramoorthi, Raji,Wang, Yihan,Zou, Dong,Thomas, R. Mathew,Zhu, Xiaotian,Cai, Lisi,Wen, David,Liu, Shuangying,Romero, Jan,Qi, Jiwei,Chen, Ingrid,Banda, Geetha,Lentini, Scott P.,Das, Sasmita,Xu, Qihong,Keats, Jeff,Wang, Frank,Wardwell, Scott,Ning, Yaoyu,Snodgrass, Joseph T.,Broudy, Marc I.,Russian, Karin,Zhou, Tianjun,Commodore, Lois,Narasimhan, Narayana I.,Mohemmad, Qurish K.,Iuliucci, John,Rivera, Victor M.,Dalgarno, David C.,Sawyer, Tomi K.,Clackson, Tim,Shakespeare, William C.
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experimental part
p. 4701 - 4719
(2010/10/03)
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- COMPOUNDS AND COMPOSITIONS USEFUL FOR THE TREATMENT OF MALARIA
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The invention provides a class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent malaria.
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Page/Page column 26-27
(2010/01/07)
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- COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
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The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated kinase activity, particularly diseases or disorders that involve abnormal activation of Abl, Bcr-Abl, Bmx, BTK, b-RAF, c RAF, CSK, cSRC, Fes, FGFR3, Flt3, IKKα, IKKβ, JNK1α1, JNK2α2, Lck, Met, MKK4, MKK6, p70S6K, PAK2, PDGFRα, PKA, PKCα, PKD2, ROCK-II, Ros, Rsk1, SAPK2α, SAPK2β, SAPK3, SAPK4, SGK, Syk, Tie2 and TrkB kinases.
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Page/Page column 31-32
(2008/06/13)
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