N-(3-(2-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

ID: ALA3633143

Chembl Id: CHEMBL3633143

PubChem CID: 72201501

Max Phase: Preclinical

Molecular Formula: C29H31N7O3

Molecular Weight: 525.61

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Canonical SMILES:  C=CC(=O)Nc1cccc(-n2c(=O)cc(C)c3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)c1

Standard InChI:  InChI=1S/C29H31N7O3/c1-5-26(37)31-20-7-6-8-22(16-20)36-27(38)15-19(2)23-18-30-29(33-28(23)36)32-24-10-9-21(17-25(24)39-4)35-13-11-34(3)12-14-35/h5-10,15-18H,1,11-14H2,2-4H3,(H,31,37)(H,30,32,33)

Standard InChI Key:  VJQPNQROUWVJQN-UHFFFAOYSA-N

Associated Targets(Human)

NCI-H1975 (4994 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A-431 (6446 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EGFR Tclin Epidermal growth factor receptor erbB1 (33727 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ERBB2 Tclin Epidermal growth factor receptor (487 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
NT5DC1 Tdark 5'-nucleotidase domain-containing protein 1 (12 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AKT1 Tchem Serine/threonine-protein kinase AKT (9192 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AKT2 Tchem Serine/threonine-protein kinase AKT2 (4301 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AKT3 Tchem Serine/threonine-protein kinase AKT3 (3157 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
JAK3 Tclin Tyrosine-protein kinase JAK3 (8349 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: 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: 525.61Molecular Weight (Monoisotopic): 525.2488AlogP: 3.72#Rotatable Bonds: 7
Polar Surface Area: 104.62Molecular Species: NEUTRALHBA: 9HBD: 2
#RO5 Violations: 1HBA (Lipinski): 10HBD (Lipinski): 2#RO5 Violations (Lipinski): 1
CX Acidic pKa: 13.83CX Basic pKa: 7.84CX LogP: 4.00CX LogD: 3.42
Aromatic Rings: 4Heavy Atoms: 39QED Weighted: 0.35Np Likeness Score: -1.40

References

1. Wurz RP, Pettus LH, Ashton K, Brown J, Chen JJ, Herberich B, Hong FT, Hu-Harrington E, Nguyen T, St Jean DJ, Tadesse S, Bauer D, Kubryk M, Zhan J, Cooke K, Mitchell P, Andrews KL, Hsieh F, Hickman D, Kalyanaraman N, Wu T, Reid DL, Lobenhofer EK, Andrews DA, Everds N, Guzman R, Parsons AT, Hedley SJ, Tedrow J, Thiel OR, Potter M, Radinsky R, Beltran PJ, Tasker AS..  (2015)  Oxopyrido[2,3-d]pyrimidines as Covalent L858R/T790M Mutant Selective Epidermal Growth Factor Receptor (EGFR) Inhibitors.,  (9): [PMID:26396685] [10.1021/acsmedchemlett.5b00193]
2. Xu T, Peng T, Ren X, Zhang L, Yu L, Luo J, Zhang Z, Tu Z, Tong L, Huang Z, Lu X, Geng M, Xie H, Ding J, Ding K.  (2015)  C5-substituted pyrido[2,3-d]pyrimidin-7-ones as highly specific kinase inhibitors targeting the clinical resistance-related EGFRT790Mmutant,  (9): [10.1039/C5MD00208G]
3. Yu L, Huang M, Xu T, Tong L, Yan XE, Zhang Z, Xu Y, Yun C, Xie H, Ding K, Lu X..  (2017)  A structure-guided optimization of pyrido[2,3-d]pyrimidin-7-ones as selective inhibitors of EGFRL858R/T790M mutant with improved pharmacokinetic properties.,  126  [PMID:28033579] [10.1016/j.ejmech.2016.12.006]
4. Zhang X,Xu F,Tong L,Zhang T,Xie H,Lu X,Ren X,Ding K.  (2020)  Design and synthesis of selective degraders of EGFR mutant.,  192  [PMID:32171162] [10.1016/j.ejmech.2020.112199]
5. Lyu P, Jiang K, Zhou Y, Hu J, Chang Y, Zhang Z, Huang M, Zhang ZM, Ding K, Hao P, Lin L, Li Z..  (2022)  Proteome-wide Identification of Off-Targets of a Potent EGFRL858R/T790M Mutant Inhibitor.,  13  (2.0): [PMID:35178185] [10.1021/acsmedchemlett.1c00651]
6. Xu F, Zhang X, Chen Z, He S, Guo J, Yu L, Wang Y, Hou C, Ai-Furas H, Zheng Z, Smaill JB, Patterson AV, Zhang ZM, Chen L, Ren X, Ding K..  (2022)  Discovery of Isoform-Selective Akt3 Degraders Overcoming Osimertinib-Induced Resistance in Non-Small Cell Lung Cancer Cells.,  65  (20.0): [PMID:36173763] [10.1021/acs.jmedchem.2c01246]
7. Su W, Chen Z, Liu M, He R, Liu C, Li R, Gao M, Zheng M, Tu Z, Zhang Z, Xu T..  (2022)  Design, synthesis and structure-activity relationship studies of pyrido[2,3-d]pyrimidin-7-ones as potent Janus Kinase 3 (JAK3) covalent inhibitors.,  64  [PMID:35306167] [10.1016/j.bmcl.2022.128680]

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