| Identification | Back Directory | [Name]
LONAFARNIB | [CAS]
193275-84-2 | [Synonyms]
Sarasar
Sch66336
EOS-61911
Sch 66336
LONAFARNIB
SCH-066336
LonafarMib
Unii-iow153004f
Lonafarnib [usan]
LONAFARNIB USP/EP/BP
Lonafarnib (SCH66336)
SARASAR; SCH 66336; SCH66336; SCH-66336
1-PiperidinecarboxaMide, 4-[2-[4-[(11R)-3,10-dibroMo-8-chloro-6
4-[2-[4-[(11R)-3,10-DibroMo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-1-
4-(2-(4-((R)-3,10-dibroMo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)cyclohexyl)-2-oxoethyl)piperidine-1-carboxaMide
(R)-4-(2-(4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl)-2-oxoethyl)piperidine-1-carboxamide
( )4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo(5,6)cyclohepta (1,2-b)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)-1-piperidinecarboxami de
4-[2-[4-[(11R)-3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxamide
4-(2-(4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo-(5,6)-cyclohepta(1,2-B)-pyridin-11(R)-yl)-1-piperidinyl)-2-oxo-ethyl)-1-piperidinecarboxamide
1-Piperidinecarboxamide, 4-(2-(4-((11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo(5,6)cyclohepta(1,2-B)pyridin-11-yl)-1-piperidinyl)-2-oxoethyl)- | [Molecular Formula]
C27H31Br2ClN4O2 | [MDL Number]
MFCD06795138 | [MOL File]
193275-84-2.mol | [Molecular Weight]
638.82 |
| Chemical Properties | Back Directory | [Melting point ]
214.5-215.9° (monohydrate); mp 222-223° | [alpha ]
D25 = +49.1° (c = 0.21 in methanol) | [Boiling point ]
710.4±70.0 °C(Predicted) | [density ]
1.536 | [storage temp. ]
-20°C | [solubility ]
Chloroform (Slightly), Methanol (Slightly) | [form ]
powder | [pka]
15.76±0.40(Predicted) | [color ]
white to beige | [InChIKey]
DHMTURDWPRKSOA-RUZDIDTESA-N | [SMILES]
O=C(N)N(CC1)CCC1CC(N2CCC([C@H]3C(N=CC(Br)=C4)=C4CCC5=C3C(Br)=CC(Cl)=C5)CC2)=O |
| Safety Data | Back Directory | [WGK Germany ]
WGK 3 | [Storage Class]
11 - Combustible Solids | [Hazard Classifications]
Eye Irrit. 2
Skin Irrit. 2
STOT SE 3 |
| Hazard Information | Back Directory | [Uses]
Chemotherapeutic (farnesyl transfer ase inhibitor). | [Definition]
ChEBI: A 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide that has R configuration. It is used as oral farnesyltransferase
nhibitor. | [General Description]
Lonafarnib (SCH66336) is a farnesyl transferase inhibitor (FTI). K- and N-Ras are substrates of farnesyl transferase. | [Biological Activity]
lonafarnib (sch66336, sarasar) is an potent, selective, orally, bioavailable tricyclic nonpeptidyl nonsulfhydry inhibitor of farnesyltransferase (ftase).[1] it is a small molecular with the formula of c27h31br2cln4o2 and molecular weight of 638.82. farnesylated ras proteins was found to regulate signal transduction pathways which drive cell proliferation, growth and survival and be required for its membrane localization.[1, 2] lonafarnib inhibits the post-translational farnesylcation of ras proteins, therefore blocking translocation of ras to the plasma membrane.[3][1] eric w, malcolm j. m, kim n. c, d. scott e, et al. a multinomial phase ii study of lonafarnib (sch 66336) in patients with refractory urothelial cancer. urologic oncology: seminars and original investigations. 2005, 23. 143-149.[2] gongjie l, stacey a. t, cindy h. m, yunsheng h, w. robert b, et al. continuous and intermittent dosing of lonafarnib potentiates the therapeutic efficacy of docetaxel on preclinical human prostate cancer models. int. j. cancer. 2009, 125. 2711–2720.[3] vasiliki a. n, alexander j. s, keith t. f, hensin t, et al. melanoma: new insights and new therapies. j invest dermatol. 2012, 132. 854–863. | [Biochem/physiol Actions]
Lonafarnib prevents the post-translational lipid modification of H-Ras and other farnesylated proteins. Lonafarnib treatment results in microtubule bundling, increased microtubule acetylation and stabilization and suppression of microtubule dynamics. | [Mechanism of action]
Lonafarnib is a protein farnesyltransferase inhibitor (FTI) that reversibly binds to the farnesyltransferase CAAX binding site9, thereby inhibiting progerin farnesylation and subsequent intercalation into the nuclear membrane. | [Side effects]
- vomiting
- diarrhea
- nausea
- stomach pain
- constipation
- gas
- decreased appetite
- decreased weight
| [Synthesis]
The two benzylic protons of tricyclic compound 177 were removed in the presence of quinine and mesylate 180 to generate intermediate 181 with excellent conversion and 95% enantiomeric purity (ee). In situ removal of the Boc protecting group under acidic conditions allowed 181 to crystallize as N-acetyl-L-phenylalaninate 182, which was isolated from 177 in 80% yield, further increasing the yield to 99%. N-Boc piperidine acetic acid 183 was coupled to 182 under conventional amide bond formation conditions. Subsequent removal of the Boc protecting group and urea bond formation using N-methylpyrrolidone (NMP) and urea ultimately afforded lonafarnib (XXIV).
| [target]
FT | [storage]
Store at -20°C |
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