Selumetinib Sulfate

Selumetinib Sulfate Property

storage temp. 

Store at -20°C

solubility 

DMSO: 50 mg/mL (89.97 mM); Water: < 0.1 mg/mL (insoluble)

form 

Solid

color 

Light yellow to yellow

InChIKey

GRKFGZYYYYISDX-UHFFFAOYSA-N

SMILES

S(O)(O)(=O)=O.N(C1C=CC(Br)=CC=1Cl)C1C(=C2N=CN(C)C2=CC=1C(=O)NOCCO)F

CAS DataBase Reference

943332-08-9

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H317May cause an allergic skin reaction

H318Causes serious eye damage

H361Suspected of damaging fertility or the unborn child

H373May cause damage to organs through prolonged or repeated exposure

H411Toxic to aquatic life with long lasting effects

Precautionary statements

P201Obtain special instructions before use.

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P272Contaminated work clothing should not be allowed out of the workplace.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P281Use personal protective equipment as required.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P308+P313IF exposed or concerned: Get medical advice/attention.

P310Immediately call a POISON CENTER or doctor/physician.

P314Get medical advice/attention if you feel unwell.

P321Specific treatment (see … on this label).

P333+P313IF SKIN irritation or rash occurs: Get medical advice/attention.

P363Wash contaminated clothing before reuse.

P405Store locked up.

P501Dispose of contents/container to..…

Selumetinib Sulfate Chemical Properties,Usage,Production

Uses

Selumetinib Sulfate (Koselugo) is a selective ATP-noncompetitive MEK1/2 inhibitor developed by Array BioPharma for the treatment of neurofibromatosis type 1 (NF1).

Trade name

Koselugo

Mechanism of action

As a MEK1/2 inhibitor, Selumetinib Sulfate inhibits the activity of mitogen-activated protein kinase (MEK), thereby affecting the RAS/RAF/MEK/ERK signaling pathway, which plays a key role in the occurrence and development of NF1-related tumors.

Synthesis

The synthesis started from 2,3,4-trifluorobenzoic acid (345). Nitration of 345 gave compound 346. SNAr amination of 346 gave compound 348. Esterification of 348 gave the carboxylic acid derivative 347. Final SNAr amination of 347. Reduction of the nitro group in 349 with Pd(OH)2 and in situ condensation with formic acid gave 1H-benzimidazole 350 in good yield. Sequential halogenation of 350 with NBS and NCS gave the 4-bromo-2-chloroaniline group 352. Methylation of the 1H-benzimidazole gave 353 in moderate yield. Saponification (hydrolysis) of the ester group in 353 gave compound 356. 356 was reacted with hydroxylamine 355 using an EDCI/HOBt-mediated amidation reaction to give amide 356. Acid hydrolysis of the vinyl ether in 356 gave the alcohol 357 quantitatively. Finally, selumetinib sulfate was obtained by salt formation with sulfuric acid H2SO4 in 2-butanone.