3D Mol Similar

Erlotinib hydrochloride

Iupac Name：N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine;hydrochloride

CAS No.: 183319-69-9

Molecular Weight：429.901

Modify Date.: 2022-11-25 02:18

Introduction: Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. Antineoplastic View more+

Request For Quotation

1. Names and Identifiers

1.1 Name: Erlotinib hydrochloride
1.2 Synonyms: [6,7-Bis-(2-methoxy-ethoxy)-quinazolin-4yl]-(3-ethynyl-phenyl)-amine 4-Quinazolinamine, N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-, hydrochloride (1:1) CP-358774-01 Erlotinib (Hydrochloride) ERLOTINIB HCL ERLOTINIB HCL SALT ERLOTINIB HCL SALT :TARCEVA Erlotinib Hydrochloride Salt Erlotinib, Hydrochloride Salt Erlotinib,OS-774 Erlotinib-d6 HCl Erlotonid HCl Hydrogen chloride - N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine (1:1:1) MFCD07781272 N-(3-Ethinylphenyl)-6,7-bis(2-methoxyethoxy)chinazolin-4-aminhydrochlorid N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, Hydrochloride Salt, OSI 774, Tarceva N-(3-Ethynylphenyl)-6,7-bis-(2-methoxyethoxy)-quinazolin-4-amine N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine hydrochloride N-(3-Ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine hydrochloride (1:1) OSI 774 Tarceva HydrochlorideSee E625000

1.3 CAS No.: 183319-69-9

1.4 CID: 176871

1.5 EINECS(EC#): 1308068-626-2

1.6 Molecular Formula: C22H24ClN3O4 (isomer)

1.7 Inchi: InChI=1S/C22H23N3O4.ClH/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);1H

1.8 InChkey: GTTBEUCJPZQMDZ-UHFFFAOYSA-N

1.9 Canonical Smiles: COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC.Cl

1.10 Isomers Smiles: COCCOC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC=CC(=C3)C#C)OCCOC.Cl

2. Properties

2.1 Melting point: 223-225°C

2.1 Boiling point: 553.6 °C at 760 mmHg

2.1 Flash Point: 288.6 °C

2.1 Precise Quality: 429.14600

2.1 PSA: 74.73000

2.1 logP: 4.28010

2.1 Appearance: White or off-white powder

2.2 Storage: -20°C Freezer

2.3 Chemical Properties: Off-White Solid

2.4 Color/Form: Powder

2.5 pKa: pKa (25°): 5.42

2.6 StorageTemp: Inert atmosphere,Store in freezer, under -20°C

3. Use and Manufacturing

3.1 Definition: ChEBI: A quinazoline hydrochloride compound having a (3-ethynylphenyl)amino group at the 4-position and two 2-methoxyethoxy groups at the 6- and 7-positions.

3.2 General Description: Erlotinib is available as 25-, 100-, and 150-mg tablets fororal administration and is used after failure of first-linetherapy in metastatic NSCLC and as first-line therapy incombination with gemcitabine in the treatment of metastaticpancreatic cancer, and in treating malignant gliomas.The structural similarity to gefitnib imparts similar pharmacokineticbehavior with bioavailability of 60% and proteinbinding of 93%. The agent is extensively metabolizedprimarily by CYP3A4. Three major metabolic pathwayshave been identified, involving oxidative-O-demethylationof the side chains followed by further oxidation to give thecarboxlic acids, oxidation of the acetylene functionalityto give a carboxylic acid, and aromatic hydroxylation ofthe phenyl ring para to the electron-donating nitrogen. Themetabolites are primarily eliminated in the feces, and theterminal half-life is 36 hours.The major toxicities seenwith the agent are dose-limiting skin rash and diarrhea.Other common adverse effects include shortness of breath,fatigue, and nausea.

3.3 GHS Classification: Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 9 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H301 (11.11%): Toxic if swallowed [Danger Acute toxicity, oral]
H302+H332 (11.11%): Harmful if swallowed or if inhaled [Warning Acute toxicity, oral; acute toxicity, inhalation]
H302 (88.89%): Harmful if swallowed [Warning Acute toxicity, oral]
H315 (22.22%): Causes skin irritation [Warning Skin corrosion/irritation]
H317 (33.33%): May cause an allergic skin reaction [Warning Sensitization, Skin]
H319 (22.22%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]
H332 (11.11%): Harmful if inhaled [Warning Acute toxicity, inhalation]
H335 (11.11%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]
H351 (33.33%): Suspected of causing cancer [Warning Carcinogenicity]
H360 (33.33%): May damage fertility or the unborn child [Danger Reproductive toxicity]
H361 (11.11%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]
H362 (11.11%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]
H372 (11.11%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]
H373 (11.11%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]
H411 (66.67%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]
H413 (11.11%): May cause long lasting harmful effects to aquatic life [Hazardous to the aquatic environment, long-term hazard]

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

Precautionary Statement Codes
P201, P202, P260, P261, P263, P264, P270, P271, P272, P273, P280, P281, P301+P310, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P391, P403+P233, P405, and P501

3.4 Usage: Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. Antineoplastic

4. Safety and Handling

4.1 Safety Statements: 24/25

4.1 Hazard Declaration: H301

4.1 Caution Statement: P201, P202, P260, P261, P263, P264, P270, P271, P272, P273, P280, P281, P301+P310, P301+P312, P302+P352, P304+P312, P304+P340, P305+P351+P338, P308+P313, P312, P314, P321, P330, P332+P313, P333+P313, P337+P313, P362, P363, P391, P403+P233, P405, P501

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Carcinogenicity, Category 2

Reproductive toxicity, Category 2

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 2

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H302 Harmful if swallowed H351 Suspected of causing cancer H361 Suspected of damaging fertility or the unborn child H411 Toxic to aquatic life with long lasting effects
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P201 Obtain special instructions before use. P202 Do not handle until all safety precautions have been read and understood. P280 Wear protective gloves/protective clothing/eye protection/face protection. P273 Avoid release to the environment.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth. P308+P313 IF exposed or concerned: Get medical advice/ attention. P391 Collect spillage.
Storage	P405 Store locked up.
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

View all

6. Synthesis Route

183319-69-9Total: 34 Synthesis Route

99-50-3 278 Suppliers

183319-69-9 429 Suppliers

Literatures:
Bulletin of the Korean Chemical Society, , vol. 32, # 3 p. 909 - 914
Yield: null

139-85-5 371 Suppliers

183319-69-9 429 Suppliers

Literatures:
Heterocycles, , vol. 71, # 1 p. 39 - 48
Yield: null

585-79-5 43 Suppliers

183319-69-9 429 Suppliers

Literatures:
EP2433931 A1, ;
Yield: null

View all

7. Precursor and Product

precursor:

591-19-5

585-79-5

958669-56-2

139-85-5

80407-68-7

183321-74-6

99-50-3

236750-65-5

80407-64-3

108-42-9

33432-52-9

183322-18-1

16064-15-6

183322-16-9

299912-59-7

4101-33-1

3943-89-3

69088-96-6

819813-71-3

179688-29-0

950596-59-5

54060-30-9

950596-58-4

179688-27-8

179688-26-7

View all

product :

183321-74-6

8. Other Information

8.0 Mesh: Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Agents that inhibit PROTEIN KINASES. (See all compounds classified as Protein Kinase Inhibitors.)

8.1 Mesh Entry Terms: 11C erlotinib

8.2 Use Classification: Human drugs -> Tarceva -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

8.3 Target: Value

8.4 Description: Erlotinib, launched as once daily oral treatment for patients with non-small-cell lung cancer (NSCLC), is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, and it is the second small-molecule drug to be marketed with this mechanism of action. Both erlotinib and its predecessor, gefitinib, are members of the anilinoquinazoline class of tyrosine kinase inhibitors. They compete with the binding of ATP to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and blocking downstream signal transduction. Erlotinib is prepared by the condensation of 3-ethynylaniline with 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline, which is a key intermediate obtained in five synthetic steps starting from ethyl 3,4- dihydroxybenzoate. In vitro, Erlotinib inhibits purified human EGFR tyrosine kinase with an IC₅₀ of 2 nM and blocks EGFR autophosphorylation in cellular assays with an IC₅₀ of 20nM. Treatment of human colon cancer cells with erlotinib was associated with growth inhibition, G1 cell cycle arrest, and apoptosis. Oral administration of erlotinib in athymic mice produced potent antitumor effects with an ED₅₀ of 9.2 mg/kg/day for HN5 head and neck xenografts and 14 mg/ kg/day for A431 epidermoid xenografts. The absorption of Erlotinib following oral dosing is approximately 60%. Food greatly enhances the absorption allowing for almost 100% bioavailability of the dose. The time to reach peak plasma levels of the drug is about 4 hours, and the half-life is approximately 36 hours. Steady-state drug levels are reached in 7 to 8 days. Erlotinib has high protein binding (93%) and has an apparent volume of distribution of 232 L. It is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2 and CYP1A1. The drug is mainly excreted in the feces with less than 9% of the dose found in the urine. Erlotinib is labeled for the treatment of patients with locally advanced or metastatic NSCLC who have failed one or more previous chemotherapy regimens. The recommended dosage is 150 mg daily until disease progression is detected. In a randomized, double blind, placebo-controlled trial involving 731 patients, 150 mg/day oral dose of erlotinib resulted in a median overall survival of 6.7 months compared with 4.7 months in the placebo group (p＜0.001). Progression-free survival was 9.9 weeks and 7.9 weeks in the erlotinib and placebo groups, respectively (p＜0.001). Survival at one year was 31.2% in the erlotinib group versus 21.5% in the placebo group. The use of erlotinib showed greater benefit in patients with EGFR positive tumors and in those who never smoked. The most common adverse events reported in clinical trials were rash (9%) and diarrhea (6%). Elevations in liver function tests were also seen; however, these effects were mainly transient or associated with liver metastases. As previously noted for gefitinib, erlotinib is also shown to lack any clinical benefit in concurrent administration with platinum-based chemotherapy.

8.5 Originator: Pfizer (US)

8.6 Uses: Erlotinib HCl (OSI-744) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Phase 3.

8.7 Uses: Erlotinib hydrochloride (V), a quinazoline derived small molecule inhibitor of epidermal growth factor receptor (EDGFR) tyrosine kinase, was approved in November, 2004, for the treatment of advanced or metastatic non-smallcell lung cancer. It belongs to the same class as gefitinib,another quinazoline approved for treatment of advanced lung cancer, but with improved pharmacokinetic properties. The molecule was originated by Pfizer and development initiated in collaboration with OSI, which assumed full rights to the drug when Pfizer merged with Warner Lambert. Subsequently, Genentech/Roche went into licensing agreement with OSI to develop and market the drug in the US and Worldwide.

8.8 General Description: Erlotinib is available as 25-, 100-, and 150-mg tablets fororal administration and is used after failure of first-linetherapy in metastatic NSCLC and as first-line therapy incombination with gemcitabine in the treatment of metastaticpancreatic cancer, and in treating malignant gliomas.The structural similarity to gefitnib imparts similar pharmacokineticbehavior with bioavailability of 60% and proteinbinding of 93%. The agent is extensively metabolizedprimarily by CYP3A4. Three major metabolic pathwayshave been identified, involving oxidative-O-demethylationof the side chains followed by further oxidation to give thecarboxlic acids, oxidation of the acetylene functionalityto give a carboxylic acid, and aromatic hydroxylation ofthe phenyl ring para to the electron-donating nitrogen. Themetabolites are primarily eliminated in the feces, and theterminal half-life is 36 hours.The major toxicities seenwith the agent are dose-limiting skin rash and diarrhea.Other common adverse effects include shortness of breath,fatigue, and nausea.

8.9 Chemical Synthesis: The synthesis of this agent is based on the original patent and is shown in the Scheme. The 3,4-dihydroxy benzoate 31 was reacted with bromoethyl methyl ether in the presence of potassium carbonate and tetrabutyl ammonium iodide to give 32 in 93% yield. Nitration followed by hydrogenation provided 34 in 88% yield, which was then cyclized in formamide with ammonium formate to provide quinazolone 35. Subsequent reaction with oxalyl chloride gave quinazoline chloride 36, which was then reacted with 3-ethynyl aniline (37) in isopropanol in the presence of pyridine to give the desired product erlotinib, which was isolated as the HCl salt (V). An alternate synthesis, that used protected 3-trimethylsilyl ethynyl aniline to couple to the quinazoline chloride 36, has also been published.

8.10 Indications and Usage: Erlotinib hydrochlorate is a small molecule tyrosine kinase inhibitor which acts reversibly on epidermal growth factor receptors, a hydrochloride of erlotinib, a molecular-targeted drug. The US Food and Drug Administration (FDA) has approved erlotinib (Tarceva) combined with gemcitabine as a first-line treatment for locally advanced and metastatic pancreatic cancer.
It is mainly used as a second- or third-line treatment for locally advanced or metstatic non-small cell lung cancer (NSCLC) and as a treatment for pancreatic cancer. It is used as a tyrosine inhibitor for NSCLC treatment.

8.11 Mechanisms of Action: The small molecular compound erlotinib is a tyrosine kinase receptor inhibitor which inhibits the proliferation of tumor cells by inhibiting phosphorylation, binding to the intracellular catalytic domain of tyrosine kinase in competition with ATP, thus blocking downstream signal transduction and inhibiting activity of tumor cell ligand dependent HER-1/EGFR.

8.12 Clinical Research: Phase I clinical trials showed that the main toxicities and side effects of erlotinib were dose-dependent rashes and diarrhea. Other rare side effects included headaches, nausea, and vomiting. Phase II trials used erlotinib as a second-line anticancer drug, with efficacy matching second-line chemotherapy drug docetaxel. Phase III randomized control trials (BR21) mainly focused on NSCLC patients (locally advanced and distant metastasis) after the failure of first- or second-line chemotherapy. The treatment group, with 488 cases in total, took 150mg of erlotinib daily. The control group (243 cases) took a placebo. The study showed:
Median survival rate: 6.7 months for the treatment group, 4.7 months for the control (P<0.001, hazard ratio HR=0.73)
1 year survival rate: 31.2% for the treatment group, 21.5% for the control
Median time of no progression: 9.9 weeks for the treatment group, 7.9 weeks for the control
Meanwhile, symptomatic improvement in the treatment group was more pronounced.
Based on the results of the BR21 study, several further phase III clinical trials were conducted. The TRIBUTE trial combined erlotinib with chemotherapy. The treatment group used chemotherapy (carboplatin + paclitaxel) + erlotinib, while the control used the same chemotherapy alone, with a total of 1,059 late-stage NSCLC patients. The effectiveness of the treatment group was 21.5%, and the control group 19.3%; median survival times were 10.8 and 10.6 months, respectively, and the times of tumor progression (TTP) were 5.1 and 5.0 months. Meanwhile, TALENT trials, with 1,172 NSCLC patients, also investigated the effects of adding erlotinib to chemotherapy (gemcitabine + cisplatin), and also failed to show that erlotinib significantly increased its effects.

8.13 Chemical Properties: Off-White Solid

8.14 Uses: Selective epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor. Antineoplastic

8.15 Uses: Erlotinib HCl is an HER1/EGFR inhibitor with IC50 of 2 nM.

8.16 Uses: Erlotinib HCl (OSI-744) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Phase 3.

8.17 Definition: ChEBI: A quinazoline hydrochloride compound having a (3-ethynylphenyl)amino group at the 4-position and two 2-methoxyethoxy groups at the 6- and 7-positions.

8.18 Brand name: Tarceva (OSI).

9. Computational chemical data

Molecular Weight: 429.901g/mol
Molecular Formula: C₂₂H₂₄ClN₃O₄
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 429.1455339
Monoisotopic Mass: 429.1455339
Complexity: 525
Rotatable Bond Count: 11
Hydrogen Bond Donor Count: 2
Hydrogen Bond Acceptor Count: 7
Topological Polar Surface Area: 74.7
Heavy Atom Count: 30
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 2
CACTVS Substructure Key Fingerprint: AAADceB7OAAEAAAAAAAAAAAAAAAAAAAAAAA8YIAAAAAAAACx9AAAHgAQAAAADAyhngY39vbIFADgGyZjZAiCiCkxIqAJ2CA+7JiNLuLE+duGPCru0BvK6Cew0BMOIEABQgACQABAgAKEAASAAAAAAAAAAA==

10. Recommended Suppliers

Global421SuppliersView all >>

Hebei Crovell Biotech Co. Ltd Diamond member

3YRS

Products:Cosmetic Raw Materials,solvents,etc.
Tel:86-311-66562153
Email:breeduan@crovellbio.com

Factory Supply erlotinib hydrochloride CAS 183319-69-9

Purity:99%Packing: 200kg/bag FOB
Price: 1 USD/kilogram
Time: 2023/05/30

Inquire

Wuhan Pharmchem Co., LTD. Diamond member

2YRS

Products:Pharma &Food Intermediates Water Treatment Chemicals Industrial Specialties Fine Chemicals
Tel:86-27-85835203
Email:steven@cspharmchem.com

Erlotinib hydrochloride

Purity:99%Packing: 200kg/bag FOB
Price: 9.90 USD/kg
Time: 2023/05/30

Inquire

Hebei Zebo Biotechnology Co., LTD Diamond member

2YRS

Products:Organic intermediates, Organic solvents,Cosmetic raw materials ...
Tel:00-86-15176962104
Email:Alice@hbzebo.com

Erlotinib HCl (OSI-744) cas 183319-69-9

Purity:99%Packing: 200kg/bag FOB
Price: 10 USD/kg
Time: 2023/05/30

Inquire

Hebei Ruiyao Biotechnology Co., Ltd Diamond member

2YRS

Products:Cosmetic Grade Chemical Raw Materical,Chemicals Raw Materials,API,Pharmaceutical Intermediates,Organic Chemicals
Tel:0311-88180881-19932787653
Email:sale06@ruiyaobio.com

High quality High quality Erlotinib Hydrochloride CAS NO.183319-69-9 supplier in China

Purity:99%Packing: 200kg/bag FOB
Price: 20 USD/kg
Time: 2023/05/30

Inquire

Wuhan Xiju Biotechnology Co., Ltd. Diamond member

2YRS

Products:My whatsapp:+86 13043111536 cas no.1451-82-7,79099-07-3,5449-12-7,5337-93-9,49851-31-2,288573-56-8
Tel:86-311-13043111536
Email:Rachel@wh-xiju.com

High Quality Erlotinib HCl (OSI-744) Cas 183319-69-9

Purity:99%Packing: 200kg/bag FOB
Price: 20 USD/kg
Time: 2023/05/30

Inquire

11. Realated Product Infomation

183321-69-9 Erlotinib Hydrochloride

882420-22-6 Erlotinib Hydrochloride iMpurity

1266534-68-2 [2H8]-Erlotinib hydrochloride

183320-12-9 Didesmethyl Erlotinib Hydrochloride Salt

1346601-52-2 4-Methyl Erlotinib Hydrochloride

183321-74-6 Erlotinib

938185-06-9 Erlotinib

Recently Updated : 147405-49-0 147405-54-7 147405-42-3 147405-52-5 2551114-72-6 156937-00-7 1824482-48-5 1378828-01-3 1849331-98-1 127235-92-1