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

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

Used in Pharmaceutical Industry:
BMS-911543 is used as an anticancer agent for the treatment of leukemia. It targets the JAK2 protein, which is often overactive in leukemia cells, leading to uncontrolled cell growth and proliferation. By inhibiting JAK2, BMS-911543 can effectively suppress the growth and survival of leukemia cells, offering a potential therapeutic option for patients with this type of cancer.
Additionally, BMS-911543 may be used as a research tool in the study of JAK2 signaling pathways and their role in cancer development. This can help researchers better understand the molecular mechanisms underlying leukemia and other related diseases, potentially leading to the discovery of new therapeutic targets and treatment strategies.

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

• 1271025-10-5 4-iodo-N,N-dicyclopropyl-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide 
• 35100-92-6 1,5-dimethyl-1H-pyrazol-3-ylamine 
• 35302-72-8 pyrrol-2-yl trichloromethyl ketone 
• 1480555-35-8 ethyl 4-bromo-1-ethyl-1H-pyrrole-2-carboxylate 
• 72652-32-5 1-(4-bromo-1H-pyrrol-2-yl)-2,2,2-trichloroethanone 
• 246257-69-2 N-cyclopropylcyclopropanamine hydrochloride 
• 433267-55-1 4-bromo-1H-pyrrole-2-carboxylic acid ethyl ester 
• 1356555-93-5 C₁₂H₁₈N₄ 
• 66121-69-5 1-methyl-1H-imidazole-4-carbonitrile 
• 1354706-38-9 3-iodo-1,5-dimethyl-1H-pyrazole 
• 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 
• 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 

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

Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543

BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.

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.

PROCESS FOR THE PREPARATION OF N,N-DICYCLOPROPYL-4-(1,5-DIMETHYL-1H-PYRAZOL-3-YLAMINO)-6-ETHYL-1-METHYL-1,6-DIHYDROIMIDAZO[4,5-d]PYRROLO[2,3-b]PYRIDINE-7-CARBOXAMIDE

The invention relates to an improved process for synthesizing N,N-dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide of the formula: (I) Compound (I) is currently in clinical trials for the treatment of myeloproliferative disorders, such as polycythaemia vera, thrombocythaemia and primary myelofibrosis.

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.