3D Mol Similar

Lapatinib ditosylate

: Iupac Name：N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine;4-methylbenzenesulfonic acid; CAS No.: 388082-78-8; Molecular Weight：925.46; Modify Date.: 2022-12-13 13:46; Introduction: Lapatinib is available in 250-mg tablets for oral administrationand is used in combination with cabecitabine in thetreatment of breast cancer for those patients that over expressthe type 2 EGF-R and who have previously receivedtaxane, anthracycline, and trastuzumab therapy. The type 2EGF-R is one subtype of this receptor and is also known asHER2 or ErbB-2. The agent is a receptor TK inhibitor targetingthe ErbB-1 and ErbB-2 subtypes. Binding occurs atthe ATP-binding site and thereby prevents phosphorylationand the subsequent activation of other kinase enzymes.ErbB-1 overexpression occurs in approximately27% to 30% of breast cancers, while ErbB-2 is over expressedin 20% to 25% of cases.The agent has demonstratedIC50 values of ＜0.2μM against ErbB-1 and 2 fromseveral different cancer cell lines and dissociates slowly(t1/2＝300 min) from these receptor TKs.The drug isboth a substrate and an inhibitor of the efflux transportersPgp and BCRP. It is also an inhibitor of the hepatic uptaketransporter OATP1B1, which is an organic anion transporter.The absorption of lapatinib is incomplete andvariable after oral administration. The agent is extensivelymetabolized by CYP3A4 and CYP3A5, with minor contributionsfrom CYP2C19 and CYP2C8. Lapatinib inhibitsCYP3A and CYP2C8 at clinically relevant concentrations.The agent is highly (99%) protein bound and eliminatedprimarily in the feces. The half-life of the agent increaseupon repeated dosing, taking 6 days to reach steady statethat gives an effective half-life of 24 hours. The most commonlyseen adverse effects of lapatinib therapy are skinrash and diarrhea. Skin rash is commonly seen with manyof the other TK inhibitors and agents that target ErbB-1.Lapatinib-induced diarrhea is usually mild to moderate.There have been reports of decreases in left ventricularejection fraction associated with the agent, although thisappears to occur only rarely and is reversible upon discontinuationof therapy. Lapatinib ditosylateSupplier View more+

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1. Names and Identifiers

: 1.1 Name; Lapatinib ditosylate; 1.2 Synonyms; 4-Quinazolinamine, N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furanyl]-, 4-methylbenzenesulfonate, hydrate (1:2:1) benzenesulfonic acid: N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6 -[5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine: h ydrate Lapatinib Ditosilate Lapatinib Ditosylate (GW-572016) Lapatinib ditosylate (USAN) Lapatinib ditosylate hydrate Lapatinib ditosylate monohydrate lapatinib(GW572016) Lapatinib, Tykerb, GW572016 N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2-(methylsulfonyl)ethyl)amino)methyl)-2-furanyl)-4-quinazolinamine bis(4-methylbenzenesulfonate) N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furanyl]-4-quinazolinamine, 4-methylbenzenesulfonate, hydrate (1:2:1) N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine 4-methylbenzenesulfonate hydrate (1:2:1) N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]quinazolin-4-amine bis(4-methylbenzenesulfonate) hydrate T66 BN DNJ EMR CG DO1R CF&& H- BT5OJ E1M2SW1 &&2 p-Tosoh H2O; View all

1.3 CAS No.: 388082-78-8

1.4 CID: 11557040

1.5 EINECS(EC#): 642-915-3

1.6 Molecular Formula: C41H40ClFN4O11S3 (isomer)

1.7 Inchi: InChI=1S/C29H26ClFN4O4S.2C7H8O3S.H2O/c1-40(36,37)12-11-32-16-22-9-10-27(39-22)24-14-21(35-29-23-7-2-3-8-26(23)33-18-34-29)15-25(30)28(24)38-17-19-5-4-6-20(31)13-19;2*1-6-2-4-7(5-3-6)11(8,9)10;/h2-10,13-15,18,32H,11-12,16-17H2,1H3,(H,33,34,35);2*2-5H,1H3,(H,8,9,10);1H2

1.8 InChIkey: UDGDJZMBLIHDBS-UHFFFAOYSA-N

1.9 Canonical Smiles: O.CC1=CC=C(C=C1)S(O)(=O)=O.CC1=CC=C(C=C1)S(O)(=O)=O.CS(=O)(=O)CCNCC1=CC=C(O1)C1=CC(NC2=NC=NC3=C2C=CC=C3)=CC(Cl)=C1OCC1=CC(F)=CC=C1

1.10 Isomers Smiles: CC1=CC=C(C=C1)S(=O)(=O)O.CC1=CC=C(C=C1)S(=O)(=O)O.CS(=O)(=O)CCNCC1=CC=C(O1)C2=CC3=C(C=C2)N=CN=C3NC4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl.O

2. Properties

2.1 Density: 1.381

2.1 Melting point: >200oC (dec.)

2.1 Boiling point: 750.7°C at 760 mmHg

2.1 Refractive index: n20/D 1.5520(lit.)

2.1 Flash Point: 407.8°C

2.1 Precise Quality: 924.17400

2.1 PSA: 240.23000

2.1 logP: 12.32880

2.1 Appearance: colourless to light-yellow crystal

2.2 StorageTemp: under inert gas (nitrogen or Argon) at 2-8°C

3. Use and Manufacturing

3.1 GHS Classification: Signal: Danger
GHS Hazard Statements
Aggregated GHS information provided by 4 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

H360 (50%): May damage fertility or the unborn child [Danger Reproductive toxicity]
H362 (25%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]
H372 (25%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]
H373 (25%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]
H413 (75%): 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, P263, P264, P270, P273, P281, P308+P313, P314, P405, and P501; View all

3.2 Usage: anticancer

4. Safety and Handling

4.1 Hazard Codes: Xi,N

4.1 Risk Statements: S24-S37-S61

4.1 Safety Statements: R43:May cause sensitization by skin contact. R51/53:Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment .

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 4

2.2 GHS label elements, including precautionary statements

Pictogram(s)	No symbol.
Signal word	No signal word.
Hazard statement(s)	H413 May cause long lasting harmful effects to aquatic life
Precautionary statement(s)
Prevention	P273 Avoid release to the environment.
Response	none
Storage	none
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

View all

6. NMR Spectrum

13C NMR : Predict

1H NMR : Predict

7. Synthesis Route

388082-78-8Total: 25 Synthesis Route

104-15-4 376 Suppliers

388082-78-8 215 Suppliers

Literatures:
WO2006/113649 A1, ; Page/Page column 48 ; WO 2006/113649 A1
Yield: null

3964-52-1 85 Suppliers

388082-78-8 215 Suppliers

Literatures:
WO2013/80218 A1, ;
Yield: null

1885-29-6 200 Suppliers

388082-78-8 215 Suppliers

Literatures:
WO2011/39759 A1, ;
Yield: null

View all

8. Precursor and Product

precursor:

27329-70-0

1885-29-6

16064-08-7

231278-20-9

908332-08-1

202197-26-0

1227853-05-5

231278-84-5

1227853-06-6

132131-24-9

903597-10-4

13529-27-6

1383531-70-1

1383531-71-2

98556-31-1

1440511-82-9

1440511-81-8

3964-52-1

104458-24-4

231277-92-2

104-15-4

1383531-68-7

1383531-69-8

1334953-74-0

49773-20-8

View all

product :

231277-92-2

9. Other Information

9.0 Uses: anticancer

9.1 Uses: binds to a(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors atypical antipsychotic agent

9.2 Target: Value

9.3 ErbB2 (Cell-free assay): 9.2 nM

9.4 EGFR (Cell-free assay): 10.8 nM

9.5 ErbB4 (Cell-free assay): 367 nM

9.6 Uses: Lapatinib ditosylate monohydrate is a form of Lapatinib I, an orally active drug for breast cancer as a dual EGFR and erbB-?2 inhibitor.

9.7 General Description: Lapatinib is available in 250-mg tablets for oral administrationand is used in combination with cabecitabine in thetreatment of breast cancer for those patients that over expressthe type 2 EGF-R and who have previously receivedtaxane, anthracycline, and trastuzumab therapy. The type 2EGF-R is one subtype of this receptor and is also known asHER2 or ErbB-2. The agent is a receptor TK inhibitor targetingthe ErbB-1 and ErbB-2 subtypes. Binding occurs atthe ATP-binding site and thereby prevents phosphorylationand the subsequent activation of other kinase enzymes.ErbB-1 overexpression occurs in approximately27% to 30% of breast cancers, while ErbB-2 is over expressedin 20% to 25% of cases.The agent has demonstratedIC50 values of ＜0.2μM against ErbB-1 and 2 fromseveral different cancer cell lines and dissociates slowly(t_1/2＝300 min) from these receptor TKs.The drug isboth a substrate and an inhibitor of the efflux transportersPgp and BCRP. It is also an inhibitor of the hepatic uptaketransporter OATP1B1, which is an organic anion transporter.The absorption of lapatinib is incomplete andvariable after oral administration. The agent is extensivelymetabolized by CYP3A4 and CYP3A5, with minor contributionsfrom CYP2C19 and CYP2C8. Lapatinib inhibitsCYP3A and CYP2C8 at clinically relevant concentrations.The agent is highly (99%) protein bound and eliminatedprimarily in the feces. The half-life of the agent increaseupon repeated dosing, taking 6 days to reach steady statethat gives an effective half-life of 24 hours. The most commonlyseen adverse effects of lapatinib therapy are skinrash and diarrhea. Skin rash is commonly seen with manyof the other TK inhibitors and agents that target ErbB-1.Lapatinib-induced diarrhea is usually mild to moderate.There have been reports of decreases in left ventricularejection fraction associated with the agent, although thisappears to occur only rarely and is reversible upon discontinuationof therapy.; View all

10. Computational chemical data

Molecular Weight: 925.46g/mol
Molecular Formula: C₄₁H₄₀ClFN₄O₁₁S₃
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 942.1841276
Monoisotopic Mass: 942.1841276
Complexity: 1100
Rotatable Bond Count: 13
Hydrogen Bond Donor Count: 5
Hydrogen Bond Acceptor Count: 16
Topological Polar Surface Area: 241
Heavy Atom Count: 63
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: 4
CACTVS Substructure Key Fingerprint: AAADcfB/vQBkAAAAAAAAAAAAAAAAASAAAAA8YMGDAAAAAACx/AAAHwYQCAAADA7l3i639/bIFMqoA6ZzZHDCiGk1J/AJ2Lm+b9iOLvPF//uHPSjs0BPY6ae42fOeGEACAAICCAAwgAQABAQQAAAAAAAAAA==

11. Question & Answer

What are the chemical properties of Lapatinib ditosylate and how is it used in medicine? Jul 08 2022
Lapatinib ditosylate is a commonly used chemical raw material in the pharmaceutical industry. Although its efficacy and function are powerful, the general public is not familiar with this name and may..

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