1056634-68-4

Basic information

• Product Name: Momelotinib
• Synonyms: momelotinib(JAK inhibitor)ORPHAN DRUG;CYT387, >=98%;Benzamide,N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-;CYT 11387;CYT 387;N-(Cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]benzamide;LM-1149;CYT 387(CYT 11387)
• CAS NO: 1056634-68-4
• Molecular Formula: C₂₃H₂₂N₆O₂
• Molecular Weight: 414.45978
• Product Categories: API;Inhibitors;Anti-cancer;Inhibitor
• Mol File: 1056634-68-4.mol

Chemical Properties

• Appearance: /
• Density: 1.292
• Solubility: insoluble in EtOH; insoluble in H2O; ≥20.7 mg/mL in DMSO
• PKA: 10.94±0.46(Predicted)
• CAS DataBase Reference: Momelotinib(CAS DataBase Reference)
• NIST Chemistry Reference: Momelotinib(1056634-68-4)
• EPA Substance Registry System: Momelotinib(1056634-68-4)

Safety Data

• Hazardous Substances Data: 1056634-68-4(Hazardous Substances Data)

Usage

Uses

Used in Hematology Applications:
Momelotinib is used as a therapeutic agent for hematological disorders, as dysregulation of the JAK-STAT pathway is often associated with these conditions. By inhibiting JAK1 and JAK2, Momelotinib can help regulate the pathway and potentially improve patient outcomes.
Used in Oncology Applications:
Momelotinib is used as an oncology treatment, targeting the JAK-STAT pathway, which is involved in the development and progression of various cancers. Inhibiting JAK1 and JAK2 with Momelotinib may help control tumor growth and improve treatment outcomes for cancer patients.
Used in Inflammatory Disease Applications:
Momelotinib is used as an anti-inflammatory agent, as the JAK-STAT pathway is also implicated in inflammatory diseases. By inhibiting the JAK1 and JAK2 kinases, Momelotinib may help reduce inflammation and alleviate symptoms associated with these conditions.

In vitro

CYT387 inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, CYT387 also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, CYT387 has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2μ-4 μM. A recent study shows that CYT387 inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, CYT387 induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells.

In vivo

In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines.

Biological Activity

cyt387, an aminopyrimidine derivative discovered by high-throughput enzyme and cell-based screening along with the optimization using structure-guided medicinal chemistry, is a potent and selective inhibitor of janus kinase 1 (jak1), janus kinase 2 (jak2) and tyrosine kinase 2 (tyk2) with values of 50% inhibition concentration ic50 of 11 nm, 18 nm, 155 nm and 17 nm respectively. recent studies have revealed that cyt387, at low nanomolar concentrations ranging between 500 and 1500 nm, is able to inhibit jak2 signaling pathway, suppress proliferation and induce apoptosis in jak2-dependent hematopoietic cell lines with non-hematopoietic cell lines intact.tyner jw, bumm tg, deininger j, wood l, aichberger kj, loriaux mm, druker bj, burns cj, fantino e, deininger mw. cyt387, a novel jak2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. blood. 2010;115(25):5232-5240.

Upstream product

• 701215-21-6 methyl 4-[3-(dimethylamino)-1-oxo-2-propen-1-yl]benzoate 
• 586-89-0 4-acetyl-benzoic acid 
• 247234-41-9 1-(4-morpholinophenyl)guanidine 
• 945749-71-3 4-(2-(4-(morpholinophenyl)amino)pyrimidin-4-yl)benzoic acid 
• 540-61-4 2-aminoacetonitrile 
• 499195-60-7 4-(4-carboethoxyphenyl)-2-chloropyrimidine 
• 4334-88-7 p-ethoxycarbonylphenylboronic acid 
• 1056634-62-8 ethyl 4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzoate 
• 114431-72-0 (E)-methyl 4-(3-(dimethylamino)acryloyl)benzoate 
• 3609-53-8 methyl 4-acetylbenzoate 
• 1026029-33-3 4-(2-chloropyrimidin-4-yl) methyl benzoate 
• 99768-12-4 4-methoxycarbonylphenylboronic acid 
• 100-00-5 4-chlorobenzonitrile 
• 2524-67-6 4-morpholino-4-yl-phenylamine 

Relevant articles and documents

New and Practical Synthesis of Momelotinib

New and practical synthetic route of momelotinib, a JAK inhibitor, is described on a decagram scale. A convergent synthetic process is adopted to prepare the methyl 4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl) benzoate intermediate, by cyclization of 1-(4-morpholinophenyl)guanidine and methyl 4-(3-(dimethylamino)acryloyl)benzoate in high yield and mild conditions. Momelotinib is obtained in 43.2% yield over five steps and 99.1% purity (HPLC).

New and convergent synthesis of momelotinib dihydrochloride

A new and convergent synthesis of Momelotinib dihydrochloride, a new anticancer drug, is described in this article. The key step is cyclization of 1-(4-morpholinophenyl)guanidine (12) with N-(cyanomethyl)-4-(3-(dimethylamino)acryloyl)benzamide (17) to give Momelotinib under mild condition in 77% yield. The title product is obtained in 52.5% yield over 4 steps and 99.1% purity (HPLC).

A novel and efficient synthesis of momelotinib

An improved route for the synthesis of momelotinib has been developed. A nucleophilic addition reaction between the starting material, 4-morpholinoaniline, and cyanamide gave the 1-(4-morpholinophenyl)guanidine. Simultaneously, methyl 4-acetylbenzoate was converted into methyl (E)-4-[3-(dimethylamino)acryloyl]benzoate in the presence of N,N-dimethylformamide dimethylacetal. The enaminone intermediate was then condensed at elevated temperature in alcoholic alkali with the 1-(morpholinophenyl)guanidine to form the desired pyrimidine, which was hydrolysed to the corresponding acid. This procedure is simple in operation, without noble metal catalyst and suitable for industrial production. Finally, the desired compound momelotinib was acquired by an amidation reaction.

Synthesis of Imidazoles and Oxazoles via a Palladium-Catalyzed Decarboxylative Addition/Cyclization Reaction Sequence of Aromatic Carboxylic Acids with Functionalized Aliphatic Nitriles

We herein report an efficient approach for the assembly of multiply substituted imidazoles and oxazoles in a single-step manner. These transformations are based on a decarboxylation addition and annulation of readily accessible aromatic carboxylic acids a

Preparation method of JAK inhibitor momelotinib

The invention relates to a preparation method of a JAK inhibitor momelotinib. The preparation method provided by the invention has the advantages of simple preparation route, mild preparation conditions, cheap and easily available raw materials and relatively low synthesis cost.

Momelotinib preparation method

The invention relates to the field of organic synthesis and preparation of bulk drugs, in particular to an Momelotinib preparation method which comprises the following steps of (1) preparing 4-nitrochlorobenzene and morpholine to obtain 4-(4-nitrophenyl)morpholine, and performing reduction on 4-(4-nitrophenyl)morpholine to prepare 4-morpholinoaniline; (2) performing reaction on 4-morpholinoanilineand cyanamide to prepare 1-(4-morpholinyl phenyl)guanidine; (3) performing reaction on 4-acetylbenzoic acid and glycinonitrile hydrochloride to prepare 4-acetyl-N-(cyanomethyl)benzamide; (4) performing reaction on 4-acetyl-N-(cyanomethyl)benzamide and N,N-dimethylformamide dimethyl acetal to prepare N-(cyanomethyl)-4-(3-(dimethylamino)acryloyl)benzamide; and (5) performing reaction on N-(cyanomethyl)-4-(3-(dimethylamino)acryloyl)benzamide and 1-(4-morpholinyl phenyl)guanidine to prepare the Momelotinib. The method has the characteristics of availability in raw material, concision in technology, convenience in operation, high yield, low cost and the like.

A method for preparing Momelotinib JAK inhibitors (by machine translation)

The invention relates to a method for the synthesis of inhibitors JAK Momelotinib, chemical medicine, in the field of chemical engineering and technology. Comprises the following steps : (a) the 4 the aniline and morpholine- [...] 50% shan Jingan dissolve

DEUTERATED PHENYL AMINO PYRIMIDINE COMPOUND AND PHARMACEUTICAL COMPOSITION CONTAINING SAME

The present invention relates to a deuterated phenyl amino pyrimidine compound and pharmaceutical composition containing the same. Specifically provided are a deuterated phenyl amino pyrimidine compound as represented by formula (I), and pharmaceutical composition containing the compound, or polymorph, pharmaceutically acceptable salt, hydrate or solvate thereof. The compound of the present invention can treat and/or prevent JAK kinase-related diseases, such as bone marrow proliferative disease, cancer, immunologic diseases and the like.

PHENYL AMINO PYRIMIDINE COMPOUNDS AND USES THEREOF

The present invention relates to phenyl amino pyrimidine compounds which are inhibitors of protein kinases including JAK kinases. In particular the compounds are selective for JAK2 kinases. The kinase inhibitors can be used in the treatment of kinase associated diseases such as immunological and inflammatory diseases including organ transplants; hyperproliferative diseases including cancer and myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases.