TAFETINIB


Synonyms	SIM 010603 SIM-010603 Tafetinib
Status
Molecule Category	UNKNOWN
UNII	H4X2M2NN5N


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	KGSRYTUWXUESJK-FXBPSFAMSA-N
Smiles	CCN(CC)CCNC(=O)c1c(C)[nH]c2c1CCC/C2=C1/C(=O)Nc2ccc(F)cc21
InChI	InChI=1S/C24H29FN4O2/c1-4-29(5-2)12-11-26-23(30)20-14(3)27-22-16(20)7-6-8-17(22)21-18-13-15(25)9-10-19(18)28-24(21)31/h9-10,13,27H,4-8,11-12H2,1-3H3,(H,26,30)(H,28,31)/b21-17-

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C24H29FN4O2
Molecular Weight	424.52
AlogP	3.73
Hydrogen Bond Acceptor	3.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	6.0
Polar Surface Area	77.23
Molecular species	BASE
Aromatic Rings	2.0
Heavy Atoms	31.0

Reference

Journal : J. Med. Chem.

Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.

PubMed ID : 23098265

DOI : 10.1021/jm301085w

Year : 2012

Volume : 55

Issue : 24

First Page : 10797

Last Page : 10822

Authors : Musumeci F, Radi M, Brullo C, Schenone S.

Abstract : The recent launch onto the market of five VEGFR inhibitors indicates the therapeutic value of these agents and the importance of the research in the field of angiogenesis inhibitors for future oncologic therapy. In this Perspective we briefly report the inhibitors that are in clinical use, while we dedicate two wider sections to the compounds that are in clinical trials and to the new derivatives appearing in the literature. We especially consider the medicinal chemistry aspect of the topic and report the structure-activity relationship studies and the binding mode of some inhibitors as well as the biological data of the compounds discovered in the past 5 years.

Reference

Journal : J. Med. Chem.

Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.

PubMed ID : 23098265

DOI : 10.1021/jm301085w

Year : 2012

Volume : 55

Issue : 24

First Page : 10797

Last Page : 10822

Authors : Musumeci F, Radi M, Brullo C, Schenone S.

Reference

Journal : J. Med. Chem.

Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.

PubMed ID : 23098265

DOI : 10.1021/jm301085w

Year : 2012

Volume : 55

Issue : 24

First Page : 10797

Last Page : 10822

Authors : Musumeci F, Radi M, Brullo C, Schenone S.

Reference

Journal : J. Med. Chem.

Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.

PubMed ID : 23098265

DOI : 10.1021/jm301085w

Year : 2012

Volume : 55

Issue : 24

First Page : 10797

Last Page : 10822

Authors : Musumeci F, Radi M, Brullo C, Schenone S.

Reference

Journal : J. Med. Chem.

Title : Vascular endothelial growth factor (VEGF) receptors: drugs and new inhibitors.

PubMed ID : 23098265

DOI : 10.1021/jm301085w

Year : 2012

Volume : 55

Issue : 24

First Page : 10797

Last Page : 10822

Authors : Musumeci F, Radi M, Brullo C, Schenone S.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Abstract : A novel series of 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives targeting VEGFR-2, PDGFR-β and c-Kit kinases were designed and synthesized. The molecular design was based on the SAR features of indolin-2-ones as kinase inhibitors. SAR study of the series allowed us to identify compounds possessing more potent inhibitory activities against the three kinases than sunitinb with IC50 values in the low nanomolar range in vitro. Additionally, some compounds also showed favorable antiproliferative activities against a panel of cancer cell lines (BXPC-3, T24, BGC, HEPG2 and HT29).

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Design, synthesis, and biological evaluation of novel 3-pyrrolo[b]cyclohexylene-2-dihydroindolinone derivatives as potent receptor tyrosine kinase inhibitors.

PubMed ID : 23999040

DOI : 10.1016/j.bmcl.2013.08.037

Year : 2013

Volume : 23

Issue : 20

First Page : 5630

Last Page : 5633

Authors : Ding L, Tang F, Huang W, Jin Q, Shen H, Wei P.

Assay Description	Organism	Bioactivity
Inhibition of PDGFR	None	5.0 nM
Inhibition of RET	None	5.0 nM
Inhibition of FLT3	None	5.0 nM
Inhibition of c-Kit	None	5.0 nM
Inhibition of VEGFR2	None	5.0 nM
Inhibition of FLT-3 (unknown origin)	Homo sapiens	1.3 nM
Inhibition of RET (unknown origin)	Homo sapiens	1.3 nM
Inhibition of VEGFR3 (unknown origin)	Homo sapiens	1.3 nM
Inhibition of VEGFR1 (unknown origin)	Homo sapiens	1.3 nM
Antiproliferative activity against human BxPC3 cells after 72 hrs by MTT assay	Homo sapiens	520.0 nM
Inhibition of c-KIT (unknown origin)	Homo sapiens	2.4 nM
Inhibition of PDGFR-beta (unknown origin)	Homo sapiens	10.1 nM
Inhibition of VEGFR2 (unknown origin)	Homo sapiens	2.3 nM

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Cross References

Resources	Reference
ChEMBL	CHEMBL2180602
FDA SRS	H4X2M2NN5N
Guide to Pharmacology	9921
PubChem	56935577
SureChEMBL	SCHEMBL12056459
ZINC	ZINC000095575309

CONTENTS

Structure
Chemical and Physical Properties
Related Entries