(E)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)propanamide

ID: ALA4439424

Chembl Id: CHEMBL4439424

PubChem CID: 138454771

Max Phase: Preclinical

Molecular Formula: C30H31F3N6OS

Molecular Weight: 580.68

Molecule Type: Unknown

Associated Items:

Names and Identifiers

Canonical SMILES:  CN1CCN(Cc2ccc(NC(=O)CCSc3ccc4c(/C=C/c5ccccn5)n[nH]c4c3)cc2C(F)(F)F)CC1

Standard InChI:  InChI=1S/C30H31F3N6OS/c1-38-13-15-39(16-14-38)20-21-5-6-23(18-26(21)30(31,32)33)35-29(40)11-17-41-24-8-9-25-27(36-37-28(25)19-24)10-7-22-4-2-3-12-34-22/h2-10,12,18-19H,11,13-17,20H2,1H3,(H,35,40)(H,36,37)/b10-7+

Standard InChI Key:  UDEAKWSKOGAXIJ-JXMROGBWSA-N

Alternative Forms

  1. Parent:

    ALA4439424

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Associated Targets(Human)

ABL1 Tclin Bcr/Abl fusion protein (1667 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ABL1 Tclin Tyrosine-protein kinase ABL (18331 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CSF1R Tclin Macrophage colony stimulating factor receptor (5179 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FLT1 Tclin Vascular endothelial growth factor receptor 1 (6262 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDGFRA Tclin Platelet-derived growth factor receptor alpha (5682 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDGFRB Tclin Platelet-derived growth factor receptor beta (5195 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIT Tclin Stem cell growth factor receptor (10667 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FLT3 Tclin Tyrosine-protein kinase receptor FLT3 (13481 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FGFR1 Tclin Fibroblast growth factor receptor 1 (9149 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FGFR2 Tclin Fibroblast growth factor receptor 2 (3405 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FGFR3 Tclin Fibroblast growth factor receptor 3 (7811 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FGFR4 Tclin Fibroblast growth factor receptor 4 (3668 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EPHA1 Tchem Ephrin type-A receptor 1 (1040 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EPHA2 Tclin Ephrin type-A receptor 2 (3499 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
RET Tclin Tyrosine-protein kinase receptor RET (6732 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SRC Tclin Tyrosine-protein kinase SRC (10310 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BMX Tchem Tyrosine-protein kinase BMX (1995 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
DDR1 Tchem Epithelial discoidin domain-containing receptor 1 (1050 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
DDR2 Tchem Discoidin domain-containing receptor 2 (2199 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
K562 (73714 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KU812 cell line (232 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MEG-01 (204 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MEC1 (72 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HL-60 (67320 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
OCI-AML2 (350 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
U-937 (7138 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NTRK1 Tclin Nerve growth factor receptor Trk-A (7922 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

BaF3 (4657 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CHO (4503 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: UnknownTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 580.68Molecular Weight (Monoisotopic): 580.2232AlogP: 6.02#Rotatable Bonds: 9
Polar Surface Area: 77.15Molecular Species: NEUTRALHBA: 6HBD: 2
#RO5 Violations: 2HBA (Lipinski): 7HBD (Lipinski): 2#RO5 Violations (Lipinski): 2
CX Acidic pKa: 13.40CX Basic pKa: 7.63CX LogP: 5.23CX LogD: 4.80
Aromatic Rings: 4Heavy Atoms: 41QED Weighted: 0.24Np Likeness Score: -1.81

References

1. Liu X, Wang B, Chen C, Jiang Z, Hu C, Wu H, Zhang Y, Liu X, Wang W, Wang J, Hu Z, Wang A, Huang T, Liu Q, Wang W, Wang L, Wang W, Ren T, Li L, Xia R, Ge J, Liu Q, Liu J..  (2018)  Discovery of (E)-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-((3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thio)propanamide (CHMFL-ABL-121) as a highly potent ABL kinase inhibitor capable of overcoming a variety of ABL mutants including T315I for chronic myeloid leukemia.,  160  [PMID:30317026] [10.1016/j.ejmech.2018.10.007]
2. Wang B,Zhang W,Liu X,Zou F,Wang J,Liu Q,Wang A,Hu Z,Chen Y,Qi S,Jiang Z,Chen C,Hu C,Wang L,Wang W,Liu Q,Liu J.  (2020)  Discovery of (E)-N-(4-methyl-5-(3-(2-(pyridin-2-yl)vinyl)-1H-indazol-6-yl)thiazol-2-yl)-2-(4-methylpiperazin-1-yl)acetamide (IHMT-TRK-284) as a novel orally available type II TRK kinase inhibitor capable of overcoming multiple resistant mutants.,  207  [PMID:32949955] [10.1016/j.ejmech.2020.112744]

Source