라파티닙

라파티닙 · Tykerb · Tyverb · CS-220 · GW-2016 · CS-1860 · GW 57201 · Rapatini

https://huagongshe.com/ko/chemical/208908

식별자 및 물리적 특성

CAS No.	231277-92-2
분자식	C29H26ClFN4O4S
평균 분자량	581.1 g/mol
단동위원소 질량	580.13473221 g/mol
SMILES	CS(=O)(=O)CCNCc1ccc(-c2ccc3ncnc(Nc4ccc(OCc5cccc(F)c5)c(Cl)c4)c3c2)o1
InChIKey	BCFGMOOMADDAQU-UHFFFAOYSA-N
PubChem CID	208908
ChEMBL	CHEMBL554
ChEBI	CHEBI:49603
EC No.	878-720-7
DTXSID	DTXSID7046675
현지명	라파티닙

화학 및 물리적 성질

XLogP	5.1
극성 표면적	115
수소 결합 공여자 수	2
수소 결합 수용자 수	9
회전 가능 결합 수	11
무거운 원자 수	40
형식 전하	0
복잡도	898
의약품	PharmaceuticalsPharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antineoplastic and immunomodulating agents -> Antineoplastic agents
LogP(분배 계수)	5.4
용해도	Yellow solid. Solubility at 25 eg C (mg/mL): 0.007 in water0.001 in 0.1 N HCl /Lapatinib ditoluenesulfonate monohydrate/2.23e-02 g/LDMSO에 용해됨(최대 200mg/ml)
Human Drugs	Breast FeedingLactationAntineoplastic AgentsEnzyme InhibitorsProtein Kinase InhibitorsSignal Transduction InhibitorsTyrosine Kinase InhibitorsEMA approved medicines: Human medicine
Decomposition	Thermal decomposition may produce toxic gases such as carbon monoxide, carbon dioxide, and nitrogen oxides.
Physical Description	Solid
Stability/Shelf Life	Stable if stored as directedavoid strong oxidizing agents.
Dissociation Constants	pKa1 = 3.80 (amine)pKa2 = 7.20 (amine)
녹는점	144-146oC
끓는 점	750.7±60.0 °C(Predicted)
밀도	1.381±0.06 g/cm3(Predicted)
저장 조건	2-8°C(protect from light)
pKa(산도 계수)	6.34±0.19(Predicted)
물리적 상태	고체
색상	노란색
안정성	제공된 대로 구매일로부터 2년 동안 안정적입니다. DMSO의 솔루션은 -20°C에서 최대 1개월 동안 보관할 수 있습니다.
InChIKey	BCFGMOOMADDAQU-UHFFFAOYSA-N
SMILES	N1=C2C(C=C(C3=CC=C(CNCCS(C)(=O)=O)O3)C=C2)=C(NC2=CC=C(OCC3=CC=CC(F)=C3)C(Cl)=C2)N=C1

안전 및 규제

GHS 분류	WarningH319 (50%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]P203, P260, P263, P264, P264+P265, P270, P273, P280, P305+P351+P338, P318, P337+P317, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
FDA 요건	The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including lapatinib ditosylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Lapatinib ditosylate/
Toxic Combustion Products	Emits toxic fumes such as carbon monoxide, etc.
Hazard Classes and Categories	Eye Irrit. 2 (50%)
소화 절차	Suitable extinguishing agents: water spray, carbon dioxide, dry chemical powder or foam. Protective equipment: wear self-contained breathing apparatus and protective clothing to prevent contact with skin and eyes.
보관 조건	Store at 25 °C (77 °F)excursions permitted to 15 deg to 30 °C (59 deg to 86 °F).
정리 방법	Accidental release measures: After Inhalation: cordon off area of spillwear self-contained breathing apparatus, protective clothing and heavy rubber gloves Measures for cleaning/collecting absorb solutions with finely-powdered liquid-binding material (diatomite, universal binders)decontaminate surfaces and equipment by scrubbing with alcoholdispose of contaminated material /in accordance with prevailing country, fedreal, state and local regulations/.
처리 방법	SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

용도

개요

Lapatinib, a new member of the 4-anilinoquinazoline class of RTK inhibitors (RTKIs), was launched as an oral treatment for breast cancer. Lapatinib has dual affinity for EGFR and HER2 tyrosine kinases. It is indicated in combination with capecitabine for treating patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Previously marketed drugs from the 4-anilinoquinazoline class include erlotinib (Tarceva) and gefitinib (IressaTM), both of which are indicated for treating non-small-cell lung cancer (NSCLC). As with erlotinib and gefitinib, To Market, To Market 2007 475 lapatinib is an ATP-competitive kinase inhibitor. It inhibits the tyrosine kinase activity EGFR and HER-2 with apparent Ki values of 3 and 13 nM, respectively, and has slow off-rate kinetics (t1/2X300 min). In addition, dividing the daily dose of lapatinib results in approximately 2-fold higher exposure at steady state compared to the same total dose administered once daily.The chemical synthesis of lapatinib entails the condensation of 4-chloro-6-iodoquinazoline and 3-chloro-4-(3-fluorobenzyloxy)aniline to produce a diaryl amine intermediate followed by Stille coupling of the iodo group with 5-dioxolanyl-2-(tributylstannyl)furan and subsequent acid hydrolysis of the cyclic ketal to the corresponding aldehyde. Finally, reductive amination of the aldehyde intermediate with 2-(methanesulfonyl) ethylamine in the presence of sodium triacetoxyborohydride produces lapatinib. .

일반 설명

Class: receptor tyrosine kinaseTreatment: HER2-positive breast cancer Elimination half-life = 24 hProtein binding = 99%