- Development of radioiodinated pyrimidinopyridone derivatives as targeted imaging probes of activated p38α for single photon emission computed tomography
-
Objective: p38α, a member of the mitogen-activated protein kinase superfamily, is ubiquitously expressed in a variety of mammalian cells. Activated p38α induces inflammatory responses to external stimuli, suggesting that non-invasive detection of activate
- Hashimoto, Tomoyuki,Kondo, Naoya,Hirata, Masahiko,Temma, Takashi
-
p. 1293 - 1304
(2021/08/23)
-
- Design of pyrido[2,3-d]pyrimidin-7-one inhibitors of receptor interacting protein kinase-2 (RIPK2) and nucleotide-binding oligomerization domain (NOD) cell signaling
-
Receptor interacting protein kinase-2 (RIPK2) is an enzyme involved in the transduction of pro-inflammatory nucleotide-binding oligomerization domain (NOD) cell signaling, a pathway implicated in numerous chronic inflammatory conditions. Herein, a pyrido[
- Nikhar, Sameer,Siokas, Ioannis,Schlicher, Lisa,Lee, Seungheon,Gyrd-Hansen, Mads,Degterev, Alexei,Cuny, Gregory D.
-
-
- Discovery of Selective, Covalent FGFR4 Inhibitors with Antitumor Activity in Models of Hepatocellular Carcinoma
-
Hepatocellular carcinoma (HCC) accounts for a majority of primary liver cancer and is one of the most common forms of cancer worldwide. Aberrant signaling of the FGF19-FGFR4 pathway leads to HCC in mice and is hypothesized to be a driver in FGF19 amplifie
- Liu, Haibo,Niu, Deqiang,Tham Sjin, Robert Tjin,Dubrovskiy, Alex,Zhu, Zhendong,Mcdonald, Joseph J.,Fahnoe, Kelly,Wang, Zhigang,Munson, Mark,Scholte, Andrew,Barrague, Matthieu,Fitzgerald, Maria,Liu, Jinyu,Kothe, Michael,Sun, Fangxian,Murtie, Joshua,Ge, Jie,Rocnik, Jennifer,Harvey, Darren,Ospina, Beatriz,Perron, Keli,Zheng, Gang,Shehu, Elvis,D'Agostino, Laura Akullian
-
supporting information
p. 1899 - 1904
(2020/11/09)
-
- PROTEIN KINASE INHIBITORS AND USES THEREOF FOR THE TREATMENT OF DISEASES AND CONDITIONS
-
Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2) and/or receptor interacting kinase 3 (RIPK3). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 or RIPK3 could provide therapeutic benefit. Compounds that function as RIPK3 inhibitors provide therapeutic benefit in the treatment of inflammatory and degenerative conditions.
- -
-
Paragraph 0106; 0109; 0110
(2020/11/30)
-
- FGFR4 kinase inhibitor, preparation method and uses thereof
-
The present invention relates to a compound represented by a formula (I), or a pharmaceutically acceptable salt, a solvate, a polymorph or an isomer thereof, and uses in preparation of drugs for treatment of FGFR4 mediated diseases.
- -
-
Paragraph 0203-0204; 0206-0207
(2020/04/17)
-
- PYRIDO[2,3-D]PYRIMIDIN-7ONES AND RELATED COMPOUNDS AS INHIBITORS OF PROTEIN KINASES
-
Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds having the structures below (I) are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2). Compounds that are either dual RIPK2/ ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 could provide therapeutic benefit.
- -
-
Paragraph 0049-0050; 0006; 0007
(2018/12/13)
-
- Discovery of 2-((3-Acrylamido-4-methylphenyl)amino)-N-(2-methyl-5-(3,4,5-trimethoxybenzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-BMX-078) as a Highly Potent and Selective Type II Irreversible Bone Marrow Kinase in the X Chromosome (BMX) Kinase Inhibitor
-
BMX is a member of TEC family nonreceptor tyrosine kinase and is involved in a variety of critical physiological and pathological processes. Through combination of irreversible inhibitor design and type II inhibitor design approaches, we have discovered a highly selective and potent type II irreversible BMX kinase inhibitor compound 41 (CHMFL-BMX-078), which exhibited an IC50 of 11 nM by formation of a covalent bond with cysteine 496 residue in the DFG-out inactive conformation of BMX. It displayed a high selectivity profile (S score(1) = 0.01) against the 468 kinases/mutants in the KINOMEscan evaluation and achieved at least 40-fold selectivity over BTK kinase. Given the fact that BMX mediated signaling pathway is still not fully understood, compound 41 would serve as a useful pharmacological tool to elucidate the detailed mechanism of BMX mediated signaling pathways.
- Liang, Xiaofei,Lv, Fengchao,Wang, Beilei,Yu, Kailin,Wu, Hong,Qi, Ziping,Jiang, Zongru,Chen, Cheng,Wang, Aoli,Miao, Weili,Wang, Wenchao,Hu, Zhenquan,Liu, Juan,Liu, Xiaochuan,Zhao, Zheng,Wang, Li,Zhang, Shanchuan,Ye, Zi,Wang, Chu,Ren, Tao,Wang, Yinsheng,Liu, Qingsong,Liu, Jing
-
p. 1793 - 1816
(2017/03/17)
-
- Inhibitors of the fibroblast growth factor receptor
-
Described herein are inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of FGFR-4.
- -
-
Page/Page column 48
(2017/08/01)
-
- Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia
-
Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream mediators such as STAT5, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM), and MEG-01 (GI50 = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.
- Liang, Xiaofei,Liu, Xiaochuan,Wang, Beilei,Zou, Fengming,Wang, Aoli,Qi, Shuang,Chen, Cheng,Zhao, Zheng,Wang, Wenchao,Qi, Ziping,Lv, Fengchao,Hu, Zhenquan,Wang, Li,Zhang, Shanchun,Liu, Qingsong,Liu, Jing
-
p. 1984 - 2004
(2016/03/22)
-
- PREPARATION AND USE OF NOVEL PROTEIN KINASE INHIBITORS
-
The invention provides novel compounds and methods of using such compounds to treat or prevent cancer.
- -
-
Paragraph 151
(2016/11/14)
-
- Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones
-
In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9,10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing.
- Zhang, Jing,Lu, Dai,Wei, Han-Xun,Gu, Yongli,Selkoe, Dennis J.,Wolfe, Michael S.,Augelli-Szafran, Corinne E.
-
p. 2138 - 2141
(2016/04/20)
-
- PHARMACEUTICAL COMPOUNDS
-
The present invention relates to compounds that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.
- -
-
Page/Page column 87; 88
(2015/02/25)
-
- INHIBITORS OF THE FIBROBLAST GROWTH FACTOR RECEPTOR
-
Described herein are inhibitors of FGFR-4, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of FGFR-4.
- -
-
Paragraph 0166; 0167
(2015/07/22)
-
- KINASE INHIBITORS FOR THE TREATMENT OF DISEASE
-
The invention relates to compounds and their use in the treatment of disease. Novel irreversible inhibitors of wild-type and mutant forms of EGFR, FGFR, ALK, ROS, JAK, BTK, BLK, ITK, TEC, and/or TXK and their use for the treatment of cell proliferation disorders are described.
- -
-
Page/Page column 85
(2015/02/02)
-
- Pyridopyrimidinone derivatives as potent and selective c-jun N-terminal kinase (JNK) inhibitors
-
A novel series of 2-aminopyridopyrimidinone based JNK (c-jun N-terminal kinase) inhibitors were discovered and developed. Structure-activity relationships (SARs) were systematically developed utilizing biochemical and cell based assays and in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) studies. Through the optimization of lead compound 1, several potent and selective JNK inhibitors with high oral bioavailability were developed. Inhibitor 13 was a potent JNK3 inhibitor (IC50 = 15 nM), had high selectivity against p38 (IC50 > 10 μM), had high potency in functional cell based assays, and had high stability in human liver microsome (t1/2 = 76 min), a clean CYP-450 inhibition profile, and excellent oral bioavailability (%F = 87). Moreover, cocrystal structures of compounds 13 and 22 in JNK3 were solved at 2.0 ?. These structures elucidated the binding mode (Type-I binding) and can pave the way for further inhibitor design of this pyridopyrimidinone scaffold for JNK inhibition.
- Zheng, Ke,Park, Chul Min,Iqbal, Sarah,Hernandez, Pamela,Park, Hajeung,Lograsso, Philip V.,Feng, Yangbo
-
supporting information
p. 413 - 418
(2015/04/27)
-
- PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS
-
This disclosure relates to compounds, methods for their preparation, pharmaceutical compositions including these compounds and methods for the treatment of cellular proliferative disorders, including, but not limited to, cancer.
- -
-
Page/Page column 52; 53
(2014/10/04)
-
- HETEROARYL COMPOUNDS AND USES THEREOF
-
The present invention relates to compounds useful as inhibitors of protein kinases, containing a cysteine residue in the ATP binding site. The invention further provides for pharmaceutically acceptable compositions comprising therapeutically effective amounts of one or more of the protein kinase inhibitor compounds and methods of using said compositions in the treatment of cancers and carcinomas.
- -
-
Paragraph 00719
(2014/09/29)
-
- INHIBITORS OF THE FIBROBLAST GROWTH FACTOR RECEPTOR
-
Described herein are inhibitors of FGFR, pharmaceutical compositions including such compounds, and methods of using such compounds and compositions to inhibit the activity of tyrosine kinases.
- -
-
Page/Page column 30; 31
(2014/02/15)
-
- KINASE INHIBITORS
-
Provided herein are kinase inhibiting compounds and methods of using the same.
- -
-
Paragraph 0466-0468
(2014/11/11)
-
- Discovery of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7- oxo-7,8-dihydro-pyrido[2,3- d ]pyrimidine-6-carbonitrile (7x) as a potent inhibitor of cyclin-dependent kinase 4 (CDK4) and AMPK-related kinase 5 (ARK5)
-
The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure-activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-cyclopentyl-2-[4-(4-methyl- piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6- carbonitrile (7x), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30-100 nM. In vitro kinase profiling revealed that 7x is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARK5 kinases. Here, we report the synthesis, structure-activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound.
- Reddy, M. V. Ramana,Akula, Balireddy,Cosenza, Stephen C.,Athuluridivakar, Saikrishna,Mallireddigari, Muralidhar R.,Pallela, Venkat R.,Billa, Vinay K.,Subbaiah, D. R. C. Venkata,Bharathi, E. Vijaya,Vasquez-Del Carpio, Rodrigo,Padgaonkar, Amol,Baker, Stacey J.,Reddy, E. Premkumar
-
p. 578 - 599
(2014/03/21)
-
- SUBSTITUTED PYRIDO[2,3-D]PYRIMIDIN-7(8H)-ONES AND THERAPEUTIC USES THEREOF
-
Compounds useful as antiproliferative agents according to Formula (I), wherein n, A, R1, R2, and Ar1 are as defined herein, and salts thereof; antibody conjugates, pharmaceutical compositions, methods of treatment, and syn
- -
-
Page/Page column 62
(2011/07/07)
-
- Discovery of 6-(2,4-difluorophenoxy)-2-[3-hydroxy-1-(2-hydroxyethyl) propylamino]-8-methyl-8 H -pyrido[2,3- d ]pyrimidin-7-one (pamapimod) and 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2 H -pyran-4-ylamino)pyrido[2,3- d ]pyrimidin-7(8 H)-one (R1487) as orally bioavailable and highly selective inhibitors of p38α mitogen-activated protein kinase
-
The development of a new series of p38α inhibitors resulted in the identification of two clinical candidates, one of which was advanced into a phase 2 clinical study for rheumatoid arthritis. The original lead, an lck inhibitor that also potently inhibited p38α, was a screening hit from our kinase inhibitor library. This manuscript describes the optimization of the lead to p38-selective examples with good pharmacokinetic properties.
- Goldstein, David M.,Soth, Michael,Gabriel, Tobias,Dewdney, Nolan,Kuglstatter, Andreas,Arzeno, Humberto,Chen, Jeffrey,Bingenheimer, William,Dalrymple, Stacie A.,Dunn, James,Farrell, Robert,Frauchiger, Sandra,La Fargue, Joann,Ghate, Manjiri,Graves, Bradford,Hill, Ronald J.,Li, Fujun,Litman, Renee,Loe, Brad,McIntosh, Joel,McWeeney, Daniel,Papp, Eva,Park, Jaehyeon,Reese, Harlan F.,Roberts, Richard T.,Rotstein, David,San Pablo, Bong,Sarma, Keshab,Stahl, Martin,Sung, Man-Ling,Suttman, Rebecca T.,Sjogren, Eric B.,Tan, Yunchou,Trejo, Alejandra,Welch, Mary,Weller, Paul,Wong, Brian R.,Zecic, Hasim
-
experimental part
p. 2255 - 2265
(2011/06/21)
-
- A type-ii kinase inhibitor capable of inhibiting the T315I "Gatekeeper" mutant of Bcr-Abl
-
The second generation of Bcr-Abl inhibitors nilotinib, dasatinib, and bosutinib developed to override imatinib resistance are not active against the T315I "gatekeeper" mutation. Here we describe a type-II T315I inhibitor 2 (GNF-7), based upon a 3,4-dihydr
- Choi, Hwan Geun,Ren, Pingda,Adrian, Francisco,Sun, Fangxian,Lee, Hyun Soo,Wang, Xia,Ding, Qiang,Zhang, Guobao,Xie, Yongping,Zhang, Jianming,Liu, Yi,Tuntland, Tove,Warmuth, Markus,Manley, Paul W.,Mestan, Jürgen,Gray, Nathanael S.,Sim, Taebo
-
experimental part
p. 5439 - 5448
(2010/11/05)
-
- AZABICYCLO DERIVATIVES AS ANTI-INFLAMMATORY AGENTS
-
The present invention relates to novel azabicyclo derivatives of Formula (I) as anti-inflammatory agents which are useful for inhibition and prevention of inflammation and associated pathologies including inflammatory and autoimmune diseases such as sepsi
- -
-
Page/Page column 22
(2009/03/07)
-
- KINASE INHIBITORS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES
-
The present invention relates to novel kinase inhibitors and modulator compounds useful for the treatment of various diseases. More particularly, the invention is concerned with such compounds, kinase/compound adducts, methods of treating diseases, and methods of synthesis of the compounds. Preferrably, the compounds are useful for the modulation of kinase activity of Raf kinases and disease polymorphs thereof. Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanoma, colorectal cancer, ovarian cancer, papillary thyroid carcinoma, non small cell lung cancer, and mesothelioma. Compounds of the present invention also find utility in the treatment of rheumatoid arthritis and retinopathies including diabetic retinal neuropathy and macular degeneration.
- -
-
Page/Page column 87-88
(2008/06/13)
-
- SUBSTITUTED 6-PHENYL-PYRIDO [2,3-D] PYRIMIDIN-7-ONE DERIVATIVES AS KINASE INHIBITORS AND METHODS FOR USING THE SAME
-
Compounds of formula (I): wherein R1, R2, R3 and R4 are as defined herein. Also disclosed are methods of making the compounds, pharmaceutical compositions, methods of using the compounds for treatment of p38 MAP
- -
-
Page/Page column 41-42
(2008/12/05)
-
- ANTI-INFLAMMATORY AGENTS
-
The present invention relates to pyrido-pyrimidin-2yl-aminomethyl-dioxolyl derivatives as anti-inflammatory agents. The compounds of this invention were useful for inhibition and prevention of inflammation and associated pathologies including inflammatory and autoimmune diseases such as sepsis, rheumatoid arthritis, inflammatory bowel disease, type-1 diabetes, asthma, chronic obstructive pulmonary disorder, organ transplant rejection and psoriasis. This invention also relates to pharmacological compositions containing the compounds of the present invention and the methods of treating sepsis, rheumatoid arthritis, inflammatory bowel disease, type-1 diabetes, asthma, chronic obstructive pulmonary disorder, organ transplant rejection and psoriasis, and other inflammatory and/or autoimmune disorders, using the compounds.
- -
-
Page/Page column 22
(2008/12/06)
-
- ENZYME MODULATORS AND TREATMENTS
-
Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, hyperproliferative diseases, cancer, and diseases characterized by hypervascularization are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein ab1 kinase protein, bcr-ab1 kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein comprises the step of contacting said kinase protein with the novel compounds.
- -
-
Page/Page column 354
(2008/06/13)
-
- AZABICYCLO DERIVATIVES AS ANTI-INFLAMMATORY AGENTS
-
The present invention relates to novel azabicyclo derivatives of Formula (I) as anti-inflammatory agents which are useful for inhibition and prevention of inflammation and associated pathologies including inflammatory and autoimmune diseases such as sepsi
- -
-
Page/Page column 33-34
(2008/06/13)
-
- Synthetic studies on novel Syk inhibitors. Part 1: Synthesis and structure-activity relationships of pyrimidine-5-carboxamide derivatives
-
Spleen tyrosine kinase (Syk) is a non-receptor-type tyrosine kinase which mediates diverse responses in haematopoietic cells. Therefore, Syk is an attractive therapeutic target, and in a study of Syk inhibitors as potentially new therapeutic agents, we di
- Hisamichi, Hiroyuki,Naito, Ryo,Toyoshima, Akira,Kawano, Noriyuki,Ichikawa, Atsushi,Orita, Akiko,Orita, Masaya,Hamada, Noritaka,Takeuchi, Makoto,Ohta, Mitsuaki,Tsukamoto, Shin-Ichi
-
p. 4936 - 4951
(2007/10/03)
-
- Pyridopyrimidinone derivatives for treatment of neurodegenerative disease
-
This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferatives disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2 (amino and thio)pyrido[2,3-d]pyrimidines and 2,4-di
- -
-
-
- PYRIDOPYRIMIDINE KINASE INHIBITORS
-
The present invention provides compounds of formula (0): as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (0) and provides methods of treat
- -
-
-
- 6-ALKOXY-PYRIDO-PYRIMIDINES AS P-38 MAP KINASE INHIBITORS
-
The present invention provides compounds of Formula (I), wherein R1 is alkyl, cycloalkyl, cycloakylalkyl, or -CH2-alkenyl, X1 is O, NH, N(alkyl), S or -C(=O), Z is N or CH; and R2 and R3 are as define
- -
-
-
- 6-Substituted pyrido-pyrimidines
-
The present invention provides compounds of the Formula I and II: wherein R1, R3, W, Z, X1, X2, Ar1, R8 and R9 are as defined herein, and methods and intermediates for their preparation and uses thereof.
- -
-
-
- Bicyclic pyridine and pyrimidine p38 kinase inhibitors
-
The present invention discloses compounds corresponding to formula wherein A, R, X, Y, R, R1 and R2 are as defined above, pharmaceutical formulations, methods of making and uses thereof.
- -
-
Page/Page column 15
(2010/01/31)
-
- 7-oxo-pyridopyrimidines (II)
-
The present invention provides compounds of the formula: a prodrug or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3 and Ar1 are those defined herein, and methods for preparation and uses thereof
- -
-
-
- Heteroalkylamino-substituted bicyclic nitrogen heterocycles
-
The invention provides compounds represented by the formula: wherein R1, R2, R3, R4, and n are as defined in the Summary of the Invention; and individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds, methods for their use as therapeutic agents, and methods of preparation thereof.
- -
-
-
- Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation
-
This invention provides pyridopyrimidines and 4-aminopyrimidines that are useful for treating cell proliferative disorders, such as cancer and restenosis. We have now discovered a group of 7,8-dihydro-2-(amino and thio)pyrido[2,3-d]pyrimidines and 2,4-dia
- -
-
-
- Bicyclic nitrogen heterocycles
-
Amino-substituted dihydropyrimido[4,5-d]pyrimidinones of the formula in which R1 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl, R2 represents lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl or lower cycloalkyl-lower alkyl, and R3 represents hydrogen, lower alkyl, aryl, aryl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, lower cycloalkyl, lower cycloalkenyl or lower cycloalkyl-lower alkyl, and pharmaceutically acceptable salts thereof are protein kinase inhibitors. They can be used in the treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular disorders, in the treatment of asthma, central nervous system disorders or diabetic complications or for the prevention of graft rejection following transplant surgery.
- -
-
-
- 2-Substituted aminopyrido[2,3-d]pyrimidin-7(8H)-ones. Structure-activity relationships against selected tyrosine kinases and in vitro and in vivo anticancer activity
-
While engaged in therapeutic intervention against a number of proliferative diseases, we have discovered the 2-aminopyrido[2,3- d]pyrimidin-7(8H)-ones as a novel class of potent, broadly active tyrosine kinase (TK) inhibitors. An efficient route was devel
- Klutchko, Sylvester R.,Hamby, James M.,Boschelli, Diane H.,Wu, Zhipei,Kraker, Alan J.,Amar, Aneesa M.,Hartl, Brian G.,Shen, Cynthia,Klohs, Wayne D.,Steinkampf, Randall W.,Driscoll, Denise L.,Nelson, James M.,Elliott, William L.,Roberts, Billy J.,Stoner, Chad L.,Vincent, Patrick W.,Dykes, Donald J.,Panek, Robert L.,Lu, Gina H.,Major, Terry C.,Dahring, Tawny K.,Hallak, Hussein,Bradford, Laura A.,Showalter, H. D. Hollis,Doherty, Annette M.
-
p. 3276 - 3292
(2007/10/03)
-