9-Cyclopentyl-N2-(4-(4-methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine

ID: ALA2178352

Chembl Id: CHEMBL2178352

PubChem CID: 54760383

Max Phase: Preclinical

Molecular Formula: C27H32N8

Molecular Weight: 468.61

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CN1CCN(c2ccc(Nc3ncc4nc(Nc5ccccc5)n(C5CCCC5)c4n3)cc2)CC1

Standard InChI:  InChI=1S/C27H32N8/c1-33-15-17-34(18-16-33)22-13-11-21(12-14-22)29-26-28-19-24-25(32-26)35(23-9-5-6-10-23)27(31-24)30-20-7-3-2-4-8-20/h2-4,7-8,11-14,19,23H,5-6,9-10,15-18H2,1H3,(H,30,31)(H,28,29,32)

Standard InChI Key:  QPOURHROVVCOHC-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA2178352

   9-cyclopentyl-N2-[4-(4-methylpiperazin-1-yl)phenyl]-N8-phenyl-purine-2,8-diamine

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

Calculated Properties

Molecular Weight: 468.61

Molecular Weight (Monoisotopic): 468.2750

AlogP: 5.18

#Rotatable Bonds: 6

Polar Surface Area: 74.14

Molecular Species: NEUTRAL

HBA: 8

HBD: 2

#RO5 Violations: 1

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 1

CX Acidic pKa: ┄

CX Basic pKa: 7.96

CX LogP: 5.48

CX LogD: 4.82

Aromatic Rings: 4

Heavy Atoms: 35

QED Weighted: 0.40

Np Likeness Score: -1.27

References

1. Yang J, Wang LJ, Liu JJ, Zhong L, Zheng RL, Xu Y, Ji P, Zhang CH, Wang WJ, Lin XD, Li LL, Wei YQ, Yang SY..  (2012)  Structural optimization and structure-activity relationships of N2-(4-(4-Methylpiperazin-1-yl)phenyl)-N8-phenyl-9H-purine-2,8-diamine derivatives, a new class of reversible kinase inhibitors targeting both EGFR-activating and resistance mutations.,  55  (23): [PMID:23116168] [10.1021/jm301365e]

2.  (2015)  Arylamino purine derivatives, preparation method and pharmaceutical use thereof, 

3. Hei YY, Shen Y, Wang J, Zhang H, Zhao HY, Xin M, Cao YX, Li Y, Zhang SQ..  (2018)  Synthesis and evaluation of 2,9-disubstituted 8-phenylthio/phenylsulfinyl-9H-purine as new EGFR inhibitors.,  26  (8): [PMID:29576272] [10.1016/j.bmc.2018.03.025]

4. Zhao HY,Yang XY,Lei H,Xi XX,Lu SM,Zhang JJ,Xin M,Zhang SQ.  (2020)  Discovery of potent small molecule PROTACs targeting mutant EGFR.,  208  [PMID:32883633] [10.1016/j.ejmech.2020.112781]

5. Zhao HY, Wang HP, Mao YZ, Zhang H, Xin M, Xi XX, Lei H, Mao S, Li DH, Zhang SQ..  (2022)  Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands.,  65  (6.0): [PMID:35254067] [10.1021/acs.jmedchem.1c01827]

Source

Source(2):

• Scientific Literature
• BindingDB Database