4-Dimethylamino-but-2-enoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide

ID: ALA94061

Chembl Id: CHEMBL94061

PubChem CID: 5328969

Max Phase: Preclinical

Molecular Formula: C20H20BrN5O

Molecular Weight: 426.32

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CN(C)C/C=C/C(=O)Nc1ccc2ncnc(Nc3cccc(Br)c3)c2c1

Standard InChI:  InChI=1S/C20H20BrN5O/c1-26(2)10-4-7-19(27)24-16-8-9-18-17(12-16)20(23-13-22-18)25-15-6-3-5-14(21)11-15/h3-9,11-13H,10H2,1-2H3,(H,24,27)(H,22,23,25)/b7-4+

Standard InChI Key:  ZCIXBBSRVLSRJQ-QPJJXVBHSA-N

Alternative Forms

1. Parent:

   

   ALA94061

   (2e)-N-{4-[(3-Bromophenyl)amino]quinazolin-6-Yl}-4-(Dimethylamino)but-2-Enamide

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: 426.32

Molecular Weight (Monoisotopic): 425.0851

AlogP: 4.19

#Rotatable Bonds: 6

Polar Surface Area: 70.15

Molecular Species: BASE

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 8.81

CX LogP: 4.04

CX LogD: 2.62

Aromatic Rings: 3

Heavy Atoms: 27

QED Weighted: 0.58

Np Likeness Score: -1.36

References

1. Tsou HR, Mamuya N, Johnson BD, Reich MF, Gruber BC, Ye F, Nilakantan R, Shen R, Discafani C, DeBlanc R, Davis R, Koehn FE, Greenberger LM, Wang YF, Wissner A..  (2001)  6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity.,  44  (17): [PMID:11495584] [10.1021/jm0005555]

2. Wissner A, Overbeek E, Reich MF, Floyd MB, Johnson BD, Mamuya N, Rosfjord EC, Discafani C, Davis R, Shi X, Rabindran SK, Gruber BC, Ye F, Hallett WA, Nilakantan R, Shen R, Wang YF, Greenberger LM, Tsou HR..  (2003)  Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER-2).,  46  (1): [PMID:12502359] [10.1021/jm020241c]

3. Mishani E, Abourbeh G, Jacobson O, Dissoki S, Ben Daniel R, Rozen Y, Shaul M, Levitzki A..  (2005)  High-affinity epidermal growth factor receptor (EGFR) irreversible inhibitors with diminished chemical reactivities as positron emission tomography (PET)-imaging agent candidates of EGFR overexpressing tumors.,  48  (16): [PMID:16078851] [10.1021/jm0580196]

4. Michalczyk A, Klüter S, Rode HB, Simard JR, Grütter C, Rabiller M, Rauh D..  (2008)  Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR.,  16  (7): [PMID:18316192] [10.1016/j.bmc.2008.02.053]

5. Barf T, Kaptein A..  (2012)  Irreversible protein kinase inhibitors: balancing the benefits and risks.,  55  (14): [PMID:22621397] [10.1021/jm3003203]

6. Jackson PA, Widen JC, Harki DA, Brummond KM..  (2017)  Covalent Modifiers: A Chemical Perspective on the Reactivity of α,β-Unsaturated Carbonyls with Thiols via Hetero-Michael Addition Reactions.,  60  (3): [PMID:27996267] [10.1021/acs.jmedchem.6b00788]

7. Li Y, Xiao J, Zhang Q, Yu W, Liu M, Guo Y, He J, Liu Y..  (2019)  The association between anti-tumor potency and structure-activity of protein-kinases inhibitors based on quinazoline molecular skeleton.,  27  (3): [PMID:30600149] [10.1016/j.bmc.2018.12.032]

Source

Source(1):

• Scientific Literature