ID: ALA3353341

Max Phase: Preclinical

Molecular Formula: C30H30N6O2

Molecular Weight: 506.61

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1ccc2c(c1)[C@]1(C[C@H]1c1ccc3c(/C=C/c4ccc(N5CCN(C)CC5)nc4)n[nH]c3c1)C(=O)N2

Standard InChI:  InChI=1S/C30H30N6O2/c1-35-11-13-36(14-12-35)28-10-4-19(18-31-28)3-8-25-22-7-5-20(15-27(22)34-33-25)24-17-30(24)23-16-21(38-2)6-9-26(23)32-29(30)37/h3-10,15-16,18,24H,11-14,17H2,1-2H3,(H,32,37)(H,33,34)/b8-3+/t24-,30-/m0/s1

Standard InChI Key:  XMHCFCMVNKTYOH-ZBVNWKHZSA-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: 506.61

Molecular Weight (Monoisotopic): 506.2430

AlogP: 4.27

#Rotatable Bonds: 5

Polar Surface Area: 86.38

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 13.44

CX Basic pKa: 7.53

CX LogP: 4.20

CX LogD: 3.83

Aromatic Rings: 4

Heavy Atoms: 38

QED Weighted: 0.42

Np Likeness Score: -0.44

References

1. Sampson PB, Liu Y, Patel NK, Feher M, Forrest B, Li SW, Edwards L, Laufer R, Lang Y, Ban F, Awrey DE, Mao G, Plotnikova O, Leung G, Hodgson R, Mason JM, Wei X, Kiarash R, Green E, Qiu W, Chirgadze NY, Mak TW, Pan G, Pauls HW..  (2015)  The discovery of Polo-like kinase 4 inhibitors: design and optimization of spiro[cyclopropane-1,3'[3H]indol]-2'(1'H).ones as orally bioavailable antitumor agents.,  58  (1): [PMID:24867403] [10.1021/jm5005336]

2. Sampson PB, Liu Y, Forrest B, Cumming G, Li SW, Patel NK, Edwards L, Laufer R, Feher M, Ban F, Awrey DE, Mao G, Plotnikova O, Hodgson R, Beletskaya I, Mason JM, Luo X, Nadeem V, Wei X, Kiarash R, Madeira B, Huang P, Mak TW, Pan G, Pauls HW..  (2015)  The discovery of Polo-like kinase 4 inhibitors: identification of (1R,2S).2-(3-((E).4-(((cis).2,6-dimethylmorpholino)methyl)styryl). 1H.indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one (CFI-400945) as a potent, orally active antitumor agent.,  58  (1): [PMID:25723005] [10.1021/jm5005336]

3. Li SW, Liu Y, Sampson PB, Patel NK, Forrest BT, Edwards L, Laufer R, Feher M, Ban F, Awrey DE, Hodgson R, Beletskaya I, Mao G, Mason JM, Wei X, Luo X, Kiarash R, Green E, Mak TW, Pan G, Pauls HW..  (2016)  Design and optimization of (3-aryl-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-ones as potent PLK4 inhibitors with oral antitumor efficacy.,  26  (19): [PMID:27592744] [10.1016/j.bmcl.2016.08.063]

Source

Source(1):

• Scientific Literature