N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine

• ChemBase ID: 412
• Molecular Formular: C22H23N3O4
• Molecular Mass: 393.43572
• Monoisotopic Mass: 393.16885623
• SMILES: O(c1c(OCCOC)cc2ncnc(Nc3cc(ccc3)C#C)c2c1)CCOC
• Canonical SMILES: COCCOc1cc2c(ncnc2cc1OCCOC)Nc1cccc(c1)C#C
• InChI: InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25)
• InChIKey: AAKJLRGGTJKAMG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine
• IUPAC Traditional name: @erlotinib
• Brand Name: Tarceva
• Synonyms: OSI-774; erlotinib; Erlotinib

Database IDs

• CAS Number: 183321-74-6
• PubChem SID: 46508021; 160963875
• PubChem CID: 176870

CALCULATED PROPERTIES

JChem

• Acid pKa: 16.143808
• H Acceptors: 7
• H Donor: 1
• LogD (pH = 5.5): 3.1516304
• LogD (pH = 7.4): 3.2003288
• Log P: 3.2009876
• Molar Refractivity: 107.7859 cm^3
• Polarizability: 43.13458 Å^3
• Polar Surface Area: 74.73 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.13
• LOG S: -4.64
• Solubility (Water): 8.91e-03 g/l

PROPERTIES

Physical Property

• Solubility: Very slightly soluble (hydrochloride salt - maximal solubility of approximately 0.4 mg/mL occurs at a pH of approximately 2)
• Hydrophobicity(logP): 2.7

DETAILS

DrugBank - DB00530

• Drug Groups: approved; investigational
• Description: Erlotinib hydrochloride (trade name Tarceva, Genentech/OSIP, originally coded as OSI-774) is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer.; ; Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.
• Indication: For the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
• Pharmacology: Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/Epidermal Growth Factor Receptor (HER1/EGFR) tyrosine kinase inhibitor.
• Toxicity: Symptoms of overdose include diarrhea, rash, and liver transaminase elevation.
• Affected Organisms: Humans and other mammals
• Biotransformation: In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.
• Absorption: Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%.
• Half Life: Median half-life of 36.2 hours.
• Protein Binding: 93% protein bound to albumin and alpha-1 acid glycoprotein (AAG)
• References: Raymond E, Faivre S, Armand JP: Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000;60 Suppl 1:15-23; discussion 41-2. [Pubmed] ; Li Z, Xu M, Xing S, Ho WT, Ishii T, Li Q, Fu X, Zhao ZJ: Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. J Biol Chem. 2007 Feb 9;282(6):3428-32. Epub 2006 Dec 18. [Pubmed] ; Dudek AZ, Kmak KL, Koopmeiners J, Keshtgarpour M: Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. 2006 Jan;51(1):89-96. Epub 2005 Nov 14. [Pubmed] ; Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI: Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer. 2004 Dec;11(4):793-814. [Pubmed] ; Blum G, Gazit A, Levitzki A: Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry. 2000 Dec 26;39(51):15705-12. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Raymond E, Faivre S, Armand JP: Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000;60 Suppl 1:15-23; discussion 41-2. Pubmed
• Li Z, Xu M, Xing S, Ho WT, Ishii T, Li Q, Fu X, Zhao ZJ: Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. J Biol Chem. 2007 Feb 9;282(6):3428-32. Epub 2006 Dec 18. Pubmed
• Dudek AZ, Kmak KL, Koopmeiners J, Keshtgarpour M: Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. 2006 Jan;51(1):89-96. Epub 2005 Nov 14. Pubmed
• Jones HE, Goddard L, Gee JM, Hiscox S, Rubini M, Barrow D, Knowlden JM, Williams S, Wakeling AE, Nicholson RI: Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells. Endocr Relat Cancer. 2004 Dec;11(4):793-814. Pubmed
• Blum G, Gazit A, Levitzki A: Substrate competitive inhibitors of IGF-1 receptor kinase. Biochemistry. 2000 Dec 26;39(51):15705-12. Pubmed