Evaluation of Substituted Pyrazole-Based Kinase Inhibitors in One Decade (2011–2020): Current Status and Future Prospects

Discovery of novel cyclin-dependent kinase (CDK) and histone deacetylase (HDAC) dual inhibitors with potent in vitro and in vivo anticancer activity

(2020) Chunhui Cheng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of CNS-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors

(2020) Zhili Xin et al.   ACS Medicinal Chemistry Letters

Synthesis and molecular docking study of new pyrazole derivatives as potent anti-breast cancer agents targeting VEGFR-2 kinase

(2020) Dina H. Dawood et al.   BIOORGANIC CHEMISTRY

Structural Basis of Activin Receptor-Like Kinase 2 (R206H) Inhibition by Bis-heteroaryl Pyrazole-Based Inhibitors for the Treatment of Fibrodysplasia Ossificans Progressiva Identified by the Integration of Ligand-Based and Structure-Based Drug Design Approaches

(2020) Tomohiro Sato et al.   ACS Omega

Uses of dimedone to synthesis pyrazole, isoxazole and thiophene derivatives with antiproliferative, tyrosine kinase and Pim-1 kinase inhibitions

(2020) Rafat Milad Mohareb et al.   MEDICINAL CHEMISTRY RESEARCH

Design, synthesis, biological activity evaluation of 3-(4-phenyl-1H-imidazol-2-yl)-1H-pyrazole derivatives as potent JAK 2/3 and aurora A/B kinases multi-targeted inhibitors

(2020) You-Guang Zheng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of SP-96, the first non-ATP-competitive Aurora Kinase B inhibitor, for reduced myelosuppression

(2020) Naga Rajiv Lakkaniga et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Selective targeting of the αC and DFG-out pocket in p38 MAPK

(2020) Sandra Röhm et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery and optimization of novel pyrazole-benzimidazole CPL304110, as a potent and selective inhibitor of fibroblast growth factor receptors FGFR (1–3)

(2020) Abdellah Yamani et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The paradox-breaking panRAF plus SRC family kinase inhibitor, CCT3833, is effective in mutant KRAS-driven cancers

(2020) G. Saturno et al.   ANNALS OF ONCOLOGY

Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study

(2019) Hamadeh Tarazi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases

(2019) Dahye Lee et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of 5-Aminopyrazole-4-carboxamide-based Bumped-Kinase Inhibitors for Cryptosporidiosis Therapy

(2019) Wenlin Huang et al.   JOURNAL OF MEDICINAL CHEMISTRY

DPD-Inspired Discovery of Novel LsrK Kinase Inhibitors: An Opportunity To Fight Antimicrobial Resistance

(2019) Silvia Stotani et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma

(2019) Xiaojing Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chloro and bromo-pyrazole curcumin Knoevenagel condensates augmented anticancer activity against human cervical cancer cells: design, synthesis, in silico docking and in vitro cytotoxicity analysis

(2019) Monika Chaudhary et al.   JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS

Bis-Heteroaryl Pyrazoles: Identification of Orally Bioavailable Inhibitors of Activin Receptor-Like Kinase-2 (R206H)

(2019) Katsuhiko Sekimata et al.   CHEMICAL & PHARMACEUTICAL BULLETIN

Deciphering the Allosteric Binding Mechanism of the Human Tropomyosin Receptor Kinase A (hTrkA) Inhibitors

(2019) Govindan Subramanian et al.   ACS Chemical Biology

Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14

(2019) Fleur M. Ferguson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of Potent, Selective, and Brain-Penetrant 1H-Pyrazol-5-yl-1H-pyrrolo[2,3-b]pyridines as Anaplastic Lymphoma Kinase (ALK) Inhibitors

(2019) Makoto Fushimi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling

(2019) Mark Zak et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The discovery of novel 3-aryl-indazole derivatives as peripherally restricted pan-Trk inhibitors for the treatment of pain

(2019) Hiromitsu Shirahashi et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Erdafitinib: First Global Approval

(2019) Anthony Markham   DRUGS

Molecular dynamics investigation on the Asciminib resistance mechanism of I502L and V468F mutations in BCR-ABL

(2019) Jiu-Yu Zhan et al.   JOURNAL OF MOLECULAR GRAPHICS & MODELLING

Design, synthesis, and antifibrosis evaluation of 4-(benzo-[c][1,2,5]thiadiazol-5-yl)-3(5)-(6-methyl- pyridin-2-yl)pyrazole and 3(5)-(6-methylpyridin- 2-yl)-4-(thieno-[3,2,-c]pyridin-2-yl)pyrazole derivatives

(2019) Wen-Jing Zhu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors

(2019) Wenhu Zhan et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model

(2019) Velma Ganga Reddy et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a potent p38α/MAPK14 kinase inhibitor: Synthesis, in vitro/in vivo biological evaluation, and docking studies

(2019) Mohammed I. El-Gamal et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3

(2019) Youri Oh et al.   JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Design, synthesis and biological evaluation of novel 1,3,4-trisubstituted pyrazole derivatives as potential chemotherapeutic agents for hepatocellular carcinoma

(2018) Marwa F. Harras et al.   BIOORGANIC CHEMISTRY

Synthesis, in vitro antiproliferative activity, and kinase inhibitory effects of pyrazole-containing diarylureas and diarylamides

(2018) Mohammed I. El-Gamal et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Part II: New candidates of pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors

(2018) Shadia A. Galal et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Part III: Novel checkpoint kinase 2 (Chk2) inhibitors; design, synthesis and biological evaluation of pyrimidine-benzimidazole conjugates

(2018) Shadia A. Galal et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

(2018) Khalid Karrouchi et al.   MOLECULES

Kinase inhibitors: the road ahead

(2018) Fleur M. Ferguson et al.   NATURE REVIEWS DRUG DISCOVERY

A comprehensive review of protein kinase inhibitors for cancer therapy

(2018) Radhamani Kannaiyan et al.   Expert Review of Anticancer Therapy

Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1

(2018) Joseph Schoepfer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Synthesis of aminopyrazole analogs and their evaluation as CDK inhibitors for cancer therapy

(2018) Sandeep Rana et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis, in vitro anticancer evaluation, kinase inhibitory effects, and pharmacokinetic profile of new 1,3,4-triarylpyrazole derivatives possessing terminal sulfonamide moiety

(2018) Mohammed S. Abdel-Maksoud et al.   JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Synthesis and Evaluation of 3-Substituted-4-(quinoxalin-6-yl) Pyrazoles as TGF-β Type I Receptor Kinase Inhibitors

(2018) Li-Min Zhao et al.   MOLECULES

Kinase Inhibitory Activities and Molecular Docking of a Novel Series of Anticancer Pyrazole Derivatives

(2018) Eman Nossier et al.   MOLECULES

Part I: Design, synthesis and biological evaluation of novel pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors with studying their activities alone and in combination with genotoxic drugs

(2017) Shadia A. Galal et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1

(2017) Andrew A. Wylie et al.   NATURE

Synthesis, in vitro antiproliferative and antiinflammatory activities, and kinase inhibitory effects of a new series of 1,3,4-triarylpyrazole derivatives

(2016) Mohammed El-Gamal   Anti-Cancer Agents in Medicinal Chemistry

Discovery of N -(benzyloxy)-1,3-diphenyl-1 H -pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK

(2016) Xian-Hai Lv et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Potent, selective and orally bioavailable leucine-rich repeat kinase 2 (LRRK2) inhibitors

(2016) Thomas J. Greshock et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis, and biological activity of 4-(imidazo[1,2- b ]pyridazin-3-yl)-1 H -pyrazol-1-yl-phenylbenzamide derivatives as BCR–ABL kinase inhibitors

(2016) Liming Hu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors

(2016) Wenhu Zhan et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, synthesis and biological evaluation of N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1 H -pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors

(2016) V. Ganga Reddy et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties

(2016) Mahmoud M. Gamal El-Din et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design and synthesis of a new series of highly potent RAF kinase-inhibiting triarylpyrazole derivatives possessing antiproliferative activity against melanoma cells

(2016) Mohammad Ashrafuddin Khan et al.   Future Medicinal Chemistry

Design, synthesis, and in vitro antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents

(2016) Mahmoud M. Gamal El-Din et al.   JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Discovery of [5-Amino-1-(2-methyl-3H-benzimidazol-5-yl)pyrazol-4-yl]-(1H-indol-2-yl)methanone (CH5183284/Debio 1347), An Orally Available and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor

(2016) Hirosato Ebiike et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel p38α MAP kinase inhibitors identified from yoctoReactor DNA-encoded small molecule library

(2016) L. K. Petersen et al.   MedChemComm

Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1H)-pyrazole Derivatives as JAKs Inhibitors

(2016) Xuewu Liang et al.   ACS Medicinal Chemistry Letters

Novel arylazopyrazole inhibitors of cyclin-dependent kinases

(2015) Radek Jorda et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis, and biological activity of phenyl-pyrazole derivatives as BCR–ABL kinase inhibitors

(2015) Liming Hu et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Identification of N-(1H-pyrazol-4-yl)carboxamide inhibitors of interleukin-1 receptor associated kinase 4: Bicyclic core modifications

(2015) Jongwon Lim et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors

(2015) Huiyong Hu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences in the orientation of the pyrazole N1-substituent

(2015) Vassilios Bavetsias et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran–pyrazole derivatives as anticancer agents

(2015) Somaia S. Abd El-Karim et al.   BIOORGANIC CHEMISTRY

Tetrahydroindazoles as Interleukin-2 Inducible T-Cell Kinase Inhibitors. Part II. Second-Generation Analogues with Enhanced Potency, Selectivity, and Pharmacodynamic Modulation in Vivo

(2015) Jason D. Burch et al.   JOURNAL OF MEDICINAL CHEMISTRY

Potent and Selective Amidopyrazole Inhibitors of IRAK4 That Are Efficacious in a Rodent Model of Inflammation

(2015) William T. McElroy et al.   ACS Medicinal Chemistry Letters

Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

(2015) Honghe Wan et al.   ACS Medicinal Chemistry Letters

Pyrazole derivatives as potent inhibitors of c-Jun N-terminal kinase: Synthesis and SAR studies

(2014) Anuradha Doma et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAFV600E inhibitors

(2014) Shu-Fu Wang et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors

(2014) Byung Sun Park et al.   BIOORGANIC & MEDICINAL CHEMISTRY

4-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5(3)-(6-methylpyridin-2-yl)imidazole and -pyrazole derivatives as potent and selective inhibitors of transforming growth factor-β type I receptor kinase

(2014) Cheng Hua Jin et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Discovery and optimization of indazoles as potent and selective interleukin-2 inducible T cell kinase (ITK) inhibitors

(2014) Richard M. Pastor et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Property- and Structure-Guided Discovery of a Tetrahydroindazole Series of Interleukin-2 Inducible T-Cell Kinase Inhibitors

(2014) Jason D. Burch et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural Insights into FGFR Kinase Isoform Selectivity: Diverse Binding Modes of AZD4547 and Ponatinib in Complex with FGFR1 and FGFR4

(2014) Julie A. Tucker et al.   STRUCTURE

Synthesis, molecular modeling and biological evaluation of cinnamic acid derivatives with pyrazole moieties as novel anticancer agents

(2014) Wei-Ming Zhang et al.   RSC Advances

Structure of Aurora B–INCENP in complex with barasertib reveals a potential transinhibitory mechanism

(2014) Fabio Sessa et al.   Acta Crystallographica Section F-Structural Biology Communications

Discovery of N -[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2- b ]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1 H -pyrazole-5-carboxamide (TAK-593), a highly potent VEGFR2 kinase inhibitor

(2013) Naoki Miyamoto et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole–benzimidazole derivatives as potent Aurora A/B kinase inhibitors

(2013) Youguang Zheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole linked analogues

(2013) Jonathan M. Large et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Antiproliferative Diarylpyrazole Derivatives as Dual Inhibitors of the ERK Pathway and COX-2

(2013) Mohammed I. El-Gamal et al.   Chemical Biology & Drug Design

Discovery of Highly Potent, Selective, and Brain-Penetrant Aminopyrazole Leucine-Rich Repeat Kinase 2 (LRRK2) Small Molecule Inhibitors

(2013) Anthony A. Estrada et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases

(2012) Michael L. Curtin et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Synthesis, biological evaluation, and molecular docking studies of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives as anticancer agents

(2012) Xi Li et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

AZD4547: An Orally Bioavailable, Potent, and Selective Inhibitor of the Fibroblast Growth Factor Receptor Tyrosine Kinase Family

(2012) P. R. Gavine et al.   CANCER RESEARCH

Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors

(2012) Emily J. Hanan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Ruxolitinib

(2012) Ruben A. Mesa et al.   NATURE REVIEWS DRUG DISCOVERY

Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors

(2012) Tao Wang et al.   ACS Medicinal Chemistry Letters

Design, Synthesis, and Antiproliferative Activity of 3,4-Diarylpyrazole-1-carboxamide Derivatives Against Melanoma Cell Line

(2011) Mohammed I. El-Gamal et al.   ARCHIV DER PHARMAZIE

The secret life of kinases: functions beyond catalysis

(2011) Jens Rauch et al.   Cell Communication and Signaling

Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors

(2011) Cheng Hua Jin et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies

(2011) Won-Kyoung Choi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Design, synthesis and biological evaluation of pyrazole derivatives as potential multi-kinase inhibitors in hepatocellular carcinoma

(2011) Elena Strocchi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structure-based design, synthesis and biological evaluation of N-pyrazole, N′-thiazole urea inhibitors of MAP kinase p38α

(2011) Matthäus Getlik et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Investigation of the Differences in Activity between Hydroxycycloalkyl N1 Substituted Pyrazole Derivatives As Inhibitors of B-Raf Kinase by Using Docking, Molecular Dynamics, QM/MM, and Fragment-BasedDe NovoDesign: Study of Binding Mode of Diastereomer Compounds

(2011) Julio Caballero et al.   Journal of Chemical Information and Modeling

Tri- and Tetrasubstituted Pyrazole Derivates: Regioisomerism Switches Activity from p38MAP Kinase to Important Cancer Kinases

(2011) Bassam Abu Thaher et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Phase I study to assess the safety, pharmacokinetics and efficacy of barasertib (AZD1152), an Aurora B kinase inhibitor, in Japanese patients with advanced acute myeloid leukemia

(2011) Kosuke Tsuboi et al.   LEUKEMIA RESEARCH

Crizotinib

(2011) Alice T. Shaw et al.   NATURE REVIEWS DRUG DISCOVERY

AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3β activation and RNA polymerase II inhibition

(2010) L Santo et al.   ONCOGENE

Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway

(2009) K. Thress et al.   MOLECULAR CANCER THERAPEUTICS

Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines

(2009) M. S. Squires et al.   MOLECULAR CANCER THERAPEUTICS