| Identification | Back Directory | [Name]
4-[(3-BROMOPHENYL)AMINO]-6-ACRYLAMIDOQUINAZOLINE | [CAS]
194423-15-9 | [Synonyms]
CS-2316
PD 168393
PD168393 USP/EP/BP
PD-168393;PD 168393
PD168393;PD-168393;PD 168393
4-[(3-BROMOPHENYL)AMINO]-6-ACRYLAMIDOQUINAZOLINE
N-[4-(3-Bromoanilino)quinazolin-6-yl]prop-2-enamide
N-(4-((3-Bromophenyl)amino)quinazolin-6-yl)acrylamide
N-[4-[(3-Bromophenyl)amino]-6-quinazolinyl]-2-propenamide
2-Propenamide, N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]- | [Molecular Formula]
C17H13BrN4O | [MDL Number]
MFCD02179207 | [MOL File]
194423-15-9.mol | [Molecular Weight]
369.22 |
| Chemical Properties | Back Directory | [Melting point ]
279℃ | [Boiling point ]
571.1±50.0 °C(Predicted) | [density ]
1.558±0.06 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
insoluble in H2O; ≥1 mg/mL in EtOH with gentle warming and ultrasonic; ≥18.45 mg/mL in DMSO | [form ]
powder | [pka]
12.19±0.43(Predicted) | [color ]
white to beige | [InChI]
InChI=1S/C17H13BrN4O/c1-2-16(23)21-13-6-7-15-14(9-13)17(20-10-19-15)22-12-5-3-4-11(18)8-12/h2-10H,1H2,(H,21,23)(H,19,20,22) | [InChIKey]
HTUBKQUPEREOGA-UHFFFAOYSA-N | [SMILES]
C(NC1C=CC2C(C=1)=C(NC1=CC=CC(Br)=C1)N=CN=2)(=O)C=C |
| Hazard Information | Back Directory | [Uses]
Potent, cell permeable, irreversible, and selective inhibitor of EGF receptor (EGFR) tyrosine kinase activity (IC50=700pM). Antitumor agent in vivo. | [Definition]
ChEBI: A member of the class of quinazolines carrying bromoanilino and acrylamido substituents at positions 4 and 6 respectively. | [Biochem/physiol Actions]
PD168393 is a 6-acrylamido-4-anilinoquinazoline compound. It increases apoptosis in malignant peripheral nerve sheath tumor cells, stimulated by lysosomal dysfunction. | [Synthesis]
Acrylic acid (12.7 mmol, 0.87 mL) was added to an anhydrous N,N-dimethylformamide (DMF, 20 mL) solution of 6-amino-4-[(3-bromophenyl)amino]quinazoline (2.0 g, 6.35 mmol) under nitrogen protection. The reaction mixture was cooled to 0 °C, followed by the addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI-HCl, 7.62 mmol, 1.46 g). The reaction was stirred at 0 °C for 15 min and then gradually warmed up to room temperature and continued stirring for 2 h. The reaction was carried out at 0 °C for 1 h. The reaction was then stirred for 2 h. After that, acrylic acid (0.30 mL) and EDCI-HCl (0.30 g) were added supplementally. The reaction continued to stir for 2 h. After the reaction was continued, the completion of the reaction was confirmed by thin layer chromatography (TLC). The solvent was removed under reduced pressure and the residue was diluted with saturated sodium bicarbonate (NaHCO3) solution and extracted several times with ethyl acetate (EtOAc). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The crude product was purified by chromatography on a class III alumina column using ethyl acetate/methanol (95:5, v/v) as eluent, followed by recrystallization with ethyl acetate/hexane to give a spongy white solid. After drying in high vacuum for several hours, N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45% yield) was obtained as a cream-colored powder with a melting point of 258-261 °C. 1H NMR ((CD3)2SO, 200 MHz): δ 10.51 (s, 1H, CONH), 9.93 (s, 1H, NH), and 8.83 (br s, 1H, H-5), 8.59 (s, 1H, H-2), 8.18 (br s, 1H, H-2'), 7.94-7.78 (m, 3H, H-6', 8,5'), 7.40-7.27 (m, 2H, H-7,4'), 6.54 (dd, J = 9.8 Hz, J = 17.0 Hz, 1H CH2CHCO), 6.36 (dd, J = 2.1 Hz, J = 16.9 Hz, 1H, CH2CHCO), 5.85 (dd, J = 2.0 Hz, J = 9.7 Hz, 1H, CH2CHCO). Mass spectrum (CI): m/z 371 (95, 81BrMH+), 370 (53, 81BrM+), 369 (100, 79BrMH+), 368 (33, 79BrM+). Elemental analysis (C17H13BrN4O) Calculated values: C, 55.30; H, 3.55; N, 15.17%. Measured values: C, 55.19; H, 3.34; N, 14.88%. | [Enzyme inhibitor]
This photosensitive quinazoline (FW = 369.22 g/mol), also known as 4-[ (3-
bromophenyl) amino]-6-acrylamido-quinazoline, irreversibly inhibits
epidermal growth factor receptor (EGFR) protein-tyrosine kinase, IC50 = 0.7
nM. See also PD 174265 | [in vivo]
PD168393 (intraperitoneal injection; 58 mg/kg; once daily; days 10-14, 17-21, and 24-28) is effective?in vivo, and produces tumor growth inhibition of 115% after 15 days’ treatment in human epidermoid carcinoma xenografts in mice[1]. | Animal Model: | A431 human epidermoid carcinoma grown as a xenograft in nude mice[1] | | Dosage: | 58 mg/kg | | Administration: | Intraperitoneal injection; 58 mg/kg; once daily; days 10-14, 17-21, and 24-28 | | Result: | Suppressed the growth of human epidermoid carcinoma xenografts. |
| [target]
EGFR | [IC 50]
EGFR: 0.7 nM (IC50) | [References]
[1] Journal of Medicinal Chemistry, 1999, vol. 42, # 10, p. 1803 - 1815
[2] Patent: US6344459, 2002, B1. Location in patent: Page column 48 |
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