ID: ALA2426277

Max Phase: Preclinical

Molecular Formula: C26H27ClN8O2

Molecular Weight: 519.01

Molecule Type: Small molecule

Representations

Canonical SMILES:  C=CC(=O)Nc1cc(Nc2ncc(Cl)c(-c3cnn4ccccc34)n2)c(OC)cc1N1CCN(C)CC1

Standard InChI:  InChI=1S/C26H27ClN8O2/c1-4-24(36)30-19-13-20(23(37-3)14-22(19)34-11-9-33(2)10-12-34)31-26-28-16-18(27)25(32-26)17-15-29-35-8-6-5-7-21(17)35/h4-8,13-16H,1,9-12H2,2-3H3,(H,30,36)(H,28,31,32)

Standard InChI Key:  SOSWXMRNLZWISK-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: 519.01

Molecular Weight (Monoisotopic): 518.1945

AlogP: 4.07

#Rotatable Bonds: 7

Polar Surface Area: 99.92

Molecular Species: NEUTRAL

HBA: 9

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 10

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 13.64

CX Basic pKa: 7.56

CX LogP: 4.13

CX LogD: 3.74

Aromatic Rings: 4

Heavy Atoms: 37

QED Weighted: 0.35

Np Likeness Score: -1.50

References

1. Ward RA, Anderton MJ, Ashton S, Bethel PA, Box M, Butterworth S, Colclough N, Chorley CG, Chuaqui C, Cross DA, Dakin LA, Debreczeni JÉ, Eberlein C, Finlay MR, Hill GB, Grist M, Klinowska TC, Lane C, Martin S, Orme JP, Smith P, Wang F, Waring MJ..  (2013)  Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR).,  56  (17): [PMID:23930994] [10.1021/jm400822z]

2. Finlay MR, Anderton M, Ashton S, Ballard P, Bethel PA, Box MR, Bradbury RH, Brown SJ, Butterworth S, Campbell A, Chorley C, Colclough N, Cross DA, Currie GS, Grist M, Hassall L, Hill GB, James D, James M, Kemmitt P, Klinowska T, Lamont G, Lamont SG, Martin N, McFarland HL, Mellor MJ, Orme JP, Perkins D, Perkins P, Richmond G, Smith P, Ward RA, Waring MJ, Whittaker D, Wells S, Wrigley GL..  (2014)  Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor.,  57  (20): [PMID:25271963] [10.1021/jm500973a]

Source

Source(1):

• Scientific Literature