1271022-90-2

Basic information

• Product Name: BMS-911543
• Synonyms: BMS-911543;N,N-Dicyclopropyl-4-[(1,5-dimethyl-1H-pyrazol-3-yl)amino]-6-ethyl-1,6-dihydro-1-methyl-imidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide;N,N-Dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[;N,N-Dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide
• CAS NO: 1271022-90-2
• Molecular Formula: C23H28N8O
• Molecular Weight: 432.52142
• EINECS: 1308068-626-2
• Mol File: 1271022-90-2.mol
• Article Data: 5

Chemical Properties

• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: ≥43.3 mg/mL in DMSO with gentle warming; insoluble in H2O; ≥9.8 mg/mL in EtOH with gentle warming and ultrasonic
• CAS DataBase Reference: BMS-911543(CAS DataBase Reference)
• NIST Chemistry Reference: BMS-911543(1271022-90-2)
• EPA Substance Registry System: BMS-911543(1271022-90-2)

Safety Data

• Hazardous Substances Data: 1271022-90-2(Hazardous Substances Data)

Usage

Uses

BMS 911543 is a functionally selective small molecule inhibitor of JAK2 and have been developed as a treatment for leukemia.

Biological Activity

bms-911543 is a selective small-molecule inhibitor of jak2 with ic50 value of 1.1nm [1].bms-911543 is a reversible pyrrolopyridine atp-competitive jak2 inhibitor with a high selectivity. in the in vitro assay using human recombinant jak enzyme, bms-911543 displays an ic50 value of 1.1nm against jak2 and the ki value is 0.48nm. the inhibition activity and affinity against jak2 are both much higher than those against jak1 and jak3. besides that, bms-911543 also has efficacy against other kinases, such as lyn and the c-fms receptor tyrosine kinase. in jak-dependent cells such as set2 or ba/f3, the treatment of bms-911543 causes an anti-proliferative effect with ic50 values of 60 and 70nm, respectively. the cell lines depending on other jak family members do not show significant anti-proliferative response to bms-911543. the colony growth assays prove that bms-911543 can suppress the growth of mpn patient-derived cells and is more potent in the jak2v617f pathway compared with the jak2wt pathway. bms-911543 is also found to be potent in vivo in both the jak2wt pathway and the jak2v617f pathway through suppressing pstat5 induction [1].

references

[1] purandare av, mcdevitt tm, wan h, you d, penhallow b, han x, vuppugalla r, zhang y, ruepp su, trainor gl, lombardo l, pedicord d, gottardis mm, ross-macdonald p, de silva h, hosbach j, emanuel sl, blat y, fitzpatrick e, taylor tl, mcintyre kw, michaud e, mulligan c, lee fy, woolfson a, lasho tl, pardanani a, tefferi a, lorenzi mv. characterization of bms-911543, a functionally selective small-molecule inhibitor of jak2. leukemia. 2012 feb;26(2):280-8.

Upstream product

• 1271024-67-9 4-amino-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide 
• 1271025-08-1 (Z)-N,N-dicyclopropyl-6-ethyl-1-methyl-4-(1-(methylthio)-3-oxobut-1-enylamino)-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide 
• 60-34-4 methylhydrazine 
• 1354706-38-9 3-iodo-1,5-dimethyl-1H-pyrazole 
• 35100-92-6 1,5-dimethyl-1H-pyrazol-3-ylamine 
• 66121-69-5 1-methyl-1H-imidazole-4-carbonitrile 
• 1356555-93-5 C₁₂H₁₈N₄ 
• 433267-55-1 4-bromo-1H-pyrrole-2-carboxylic acid ethyl ester 
• 246257-69-2 N-cyclopropylcyclopropanamine hydrochloride 
• 72652-32-5 1-(4-bromo-1H-pyrrol-2-yl)-2,2,2-trichloroethanone 
• 1480555-35-8 ethyl 4-bromo-1-ethyl-1H-pyrrole-2-carboxylate 
• 35302-72-8 pyrrol-2-yl trichloromethyl ketone 

Relevant articles and documents

Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C

C-H Arylation in the Formation of a Complex Pyrrolopyridine, the Commercial Synthesis of the Potent JAK2 Inhibitor, BMS-911543

The development of an improved short and efficient commercial synthesis of the JAK2 inhibitor, a complex pyrrolopyridine, BMS-911543, is described. During the discovery and development of this synthesis, a Pd-catalyzed C-H functionalization was invented which enabled the rapid union of the key pyrrole and imidazole fragments. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only six steps (longest linear sequence) from readily available materials.

JAK2 INHIBITORS AND THEIR USE FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND CANCER

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase activity of JAK2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.