ID: ALA3633143

Max Phase: Preclinical

Molecular Formula: C29H31N7O3

Molecular Weight: 525.61

Molecule Type: Small molecule

Representations

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

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 525.61

Molecular Weight (Monoisotopic): 525.2488

AlogP: 3.72

#Rotatable Bonds: 7

Polar Surface Area: 104.62

Molecular Species: NEUTRAL

HBA: 9

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 13.83

CX Basic pKa: 7.84

CX LogP: 4.00

CX LogD: 3.42

Aromatic Rings: 4

Heavy Atoms: 39

QED Weighted: 0.35

Np 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.,  6  (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,  6  (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 EGFR^L858R/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]

Source

Source(1):

• Scientific Literature