953780-78-4

Basic information

• Product Name: (R)-3-Methylmorpholine hydrochloride
• Synonyms: (R)-3-Methylmorpholine hydrochloride;(R)-3-MethylMorpholine HCl;(R)-3-Methylmorpholine Hydrochloride;Morpholine, 3-methyl-, hydrochloride (1:1), (3R)-;(3R)-3-Methylmorpholine hydrochloride
• CAS NO: 953780-78-4
• Molecular Formula: C₅H₁₁NO*ClH
• Molecular Weight: 138
• EINECS: 200-258-5
• Mol File: 953780-78-4.mol

Chemical Properties

• Melting Point: 123.0 to 127.0 °C
• Appearance: /
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• CAS DataBase Reference: (R)-3-Methylmorpholine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-Methylmorpholine hydrochloride(953780-78-4)
• EPA Substance Registry System: (R)-3-Methylmorpholine hydrochloride(953780-78-4)

Safety Data

• Hazardous Substances Data: 953780-78-4(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(R)-3-Methylmorpholine hydrochloride is used as a key intermediate in the synthesis of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones. These compounds are being studied as orally active GSK-3β inhibitors for the treatment of Alzheimer's disease. The R-configuration of (R)-3-Methylmorpholine hydrochloride plays a significant role in the development of these enantiomerically pure compounds, ensuring the desired biological activity and selectivity.
In the discovery studies of Alzheimer's disease treatments, (R)-3-Methylmorpholine hydrochloride is used as a building block for the development of new GSK-3β inhibitors. These inhibitors target the glycogen synthase kinase-3 beta (GSK-3β) enzyme, which is implicated in the pathogenesis of Alzheimer's disease. By inhibiting GSK-3β, these compounds have the potential to modulate the underlying disease processes and provide therapeutic benefits to patients suffering from Alzheimer's disease.
Furthermore, (R)-3-Methylmorpholine hydrochloride can also be used in other applications within the pharmaceutical industry, such as the synthesis of other chiral compounds, enantioselective catalysts, and chiral ligands for asymmetric reactions. Its unique R-configuration and reactivity make it a valuable component in the development of new drugs and chemical processes that require stereoselectivity.

InChI:InChI=1S/C5H11NO.ClH/c1-5-4-7-3-2-6-5;/h5-6H,2-4H2,1H3;1H/t5-;/m1./s1

Upstream product

• 954133-47-2 (R)-4-(4-methoxybenzyl)-3-methylmorpholine 
• 74571-98-5 (3R)-3-methyl-4-(phenylmethyl)morpholine 
• 120800-86-4 (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone 
• 570398-22-0 (R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one 

Downstream Products

• 1373489-53-2 2-chloro-N-(4-fluorobenzyl)-4-methyl-6-[(3R)-3-methylmorpholino]pyridine-3-carboxylic acid amide 
• 1355003-93-8 (3R)-3-methyl-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine 
• 1355003-95-0 (3R)-3-methyl-4-({1-[4-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine 
• 1445593-55-4 ((1R,2S)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)cyclopropyl)((R)-3-methylmorpholino)methanone 
• 1445593-53-2 ((1S,2R)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)cyclopropyl)((R)-3-methylmorpholino)methanone 
• 1445590-82-8 ((7R,8R)-8-(5-(4-bromophenyl)-1H-imidazol-2-yl)-1,4-dioxaspiro[4.4]nonan-7-yl)((R)-3-methylmorpholino)methanone 
• 1445590-34-0 ((1,2-trans)-2-(5-(4-bromophenyl)-1H-imidazol-2-yl)cyclobutyl)((R)-3-methylmorpholino)methanone 

Relevant articles and documents

Discovery of novel 2-(alkylmorpholin-4-yl)-6-(3-fluoropyridin-4-yl)-pyrimidin-4(3H)-ones as orally-active GSK-3β inhibitors for Alzheimer's disease

We herein describe the results of further evolution of GSK-3β inhibitors for Alzheimer's disease from our promising compounds with in vivo tau phosphorylation inhibitory activity by oral administration. Introduction of a low alkyl group instead of the phenyl group at the 3-position of the morpholine moiety aiming to improve pharmacokinetic profiles resulted in potent low molecular weight GSK-3β inhibitors with good in vitro pharmacokinetic profiles, which also showed in vivo tau phosphorylation inhibitory activity by oral administration. Effect of the stereochemistry of the alkyl moiety is also discussed using docking models.

Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors

Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

CHEMICAL COMPOUNDS

The invention is directed to 6-(4-pyι?midinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

CHEMICAL COMPOUNDS

The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

2-(CYCLIC AMINO)-PYRIMIDONE DERIVATIVES AS TPK1 INHIBITORS

A compound represented by the formula (I), an optically active isomer thereof, or a pharmaceutical acceptable salt thereof (I) wherein R2 represents a hydrogen or the like; R3 represents methyl group or the like; R20 represents a halogen atom or the like; q represents an integer of 0 to 3; Z represent nitrogen atom, CH, or the like; R4 represents hydrogen or the like; R5 represents hydrogen or the like; R6 represents a substituted alkyloxy and the like; p represents an integer of 0 to 3; X represents bond, CH2, oxygen atom, NH, or the like; any one or more of R5 and R6, R5 and R4, R6 and R4, X and R5, X and R4, X and R6, and R6 and R6 may combine to each other to form a ring, which is used for preventive and/or therapeutic treatment of a disease caused by tau protein kinase 1 hyperactivity such as a neurodegenerative diseases (e.g. Alzheimer disease).