10244-24-3

Usage

Uses

Used in Chemical Synthesis:
4,4'-(6-chloropyrimidine-2,4-diyl)dimorpholine is used as an intermediate in the synthesis of other complex chemicals or pharmaceutical substances. Its unique structure allows it to be a valuable component in the creation of various compounds.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 4,4'-(6-chloropyrimidine-2,4-diyl)dimorpholine is used as a building block for the development of new drugs. Its chemical properties make it a potential candidate for the synthesis of therapeutic agents.
Safety Measures:
As with all chemicals, 4,4'-(6-chloropyrimidine-2,4-diyl)dimorpholine must be handled with care to prevent harmful effects. More specific information regarding its physical and chemical properties, as well as safety measures, can be found in its Material Safety Data Sheet (MSDS). This ensures that proper precautions are taken during its use, storage, and disposal.

Upstream product

• 110-91-8 morpholine 
• 3764-01-0 2,4,6-trichloropyrimidine 
• 52127-83-0 4-(2,6-dichloropyrimidin-4-yl)morpholine 
• 10397-13-4 4,6-dichloro-2-(morpholine-4-yl)pyrimidine 

Downstream Products

• 1399879-64-1 (E)-4,4'-(6-(2-((1-(4-fluorobenzyl)-1H-indol-3-yl)methylene)hydrazinyl)pyrimidine-2,4-diyl)dimorpholine 
• 1399879-69-6 (E)-4,4'-(6-(2-((1-(3-(trifluoromethyl)benzyl)-1H-indol-3-yl)methylene)hydrazinyl)pyrimidine-2,4-diyl)dimorpholine 

Relevant academic research and scientific papers

Design, Synthesis, and Biological Evaluation of Substituted Pyrimidines as Potential Phosphatidylinositol 3-Kinase (PI3K) Inhibitors

Three series of substituted pyrimidines were designed and synthesized. All target compounds were screened for kinase inhibitory activities against PI3Kα, and most IC50 values were found within the nanomolar range. Compounds 5d and 5p displayed

Discovery of 1-(3-aryl-4-chlorophenyl)-3-(p-aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings

PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of PI3K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231.

Synthesis and bioevaluation of diaryl urea derivatives as potential antitumor agents for the treatment of human colorectal cancer

The development of inhibitors targeting the PI3K-Akt-mTOR signaling pathway has been greatly hindered by the on-target AEs, such as hyperglycemia and hepatotoxicities. In this study, a series of diaryl urea derivatives has been designed and synthesized based on clinical candidate gedatolisib (6aa), and most of the newly synthesized derivatives showed kinase inhibitory and antiproliferative activities within nanomolar and submicromolar level, respectively. The terminal l-prolineamide substituted derivative 6 ab showed 8.6-fold more potent PI3Kα inhibitory activity (0.7 nM) and 4.6-fold more potent antiproliferative effect against HCT116 cell lines (0.11 μM) compared with control 6aa. The potential antitumor mechanism and efficacy of 6 ab in HCT116 xenograft models have also been evaluated, and found 6 ab showed comparable in vivo antitumor activity with 6aa. The safety investigations revealed that compound 6 ab exhibited more safer profiles in the selectivity of liver cells (selectivity index: >6.6 vs 1.85) and blood glucose regulation than 6aa. In addition, the in vitro stability assays also indicated our developed compound 6 ab possessed good metabolic stabilities.

PI3Kalpha/mTOR bikinase inhibitor as well as pharmaceutical composition and application thereof

The invention discloses a PI3Kalpha/mTOR bikinase inhibitor as well as a pharmaceutical composition and application thereof. The PI3Kalpha/mTOR bikinase inhibitor is prepared from a compound shown ina general formula (I), or a stereoisomer, a geometric isomeride, a hydrate, a solvate, or pharmaceutically acceptable salt or a prodrug: (the formula (1) is shown in the description.) The invention provides the PI3Kalpha/mTOR bikinase inhibitor and the pharmaceutical composition thereof for inhibiting PI3Kalpha/mTOR bikinase and proliferation diseases having a PI3Kalpha/mTOR bikinase effect; moreover, a more effective and higher selectivity inhibitor can be provided for treating the proliferation diseases having the PI3Kalpha/mTOR bikinase effect.

TREATMENT OF SKIN LESIONS

The present invention is relates to a compound of formula (I), wherein X1, X2 and X3 are, independently of each other, N or CH; with the proviso that at least two of X1 X2 and X3 are N; Y is N or CH; W is H or F; with the proviso that when W is F, then X1, X2 and X3 are N; R1 and R2 are independently of each other (i) a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxy, C1alkoxyC1-C3alkyl, CN, or C(O)O-C1-C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (ii) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence C1-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1-C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue-R8R9- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-O-CH2- or -O-CH2CH2-O-; with the proviso that at least one of R1 and R2is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a skin lesion in a subject.

TREATMENT OF NEUROLOGICAL DISORDERS

The present invention is relates to a compound of formula (I), wherein X1, X2 andX3 are, independently of each other, N or CH; with the proviso that at least two of X1X2andX3 areN; Y is N or CH; R1 and R2 are independently of each other (iii)a morpholinyl of formula (II) wherein the arrow denotes the bond in formula (I); and wherein R3 and R4 are independently of each other H, C1-C3alkyl optionally substituted with one or two OH, C1-C2fhioroalkyl, C1-C2alkoxy, C1-C2alkoxyC1-C3alkyl, CN, or C(0)0-C1- C2alkyl; or R3 and R4 form together a bivalent residue -R5R6- selected from Ci-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2-, -CH2-NH-CH2-, or any of the structures wherein the arrows denote the bonds in formula (II); or (iv) a saturated 6-membered heterocyclic ring Z selected from thiomorpholinyl and piperazinyl, optionally substituted by 1 to 3 R7; wherein R7 is independently at each occurrence Ci-C3alkyl optionally substituted with one or two OH, C1-C2fluoroalkyl, C1- C2alkoxyC1-C3alkyl, C3-C6cycloalkyl; or two R7 substituents form together a bivalent residue -R8R9- selected from C1-C3alkylene optionally substituted with 1 to 4 F, -CH2-0-CH2- or -O- CH2CH2-0-; with the proviso that at least one of R1 and R2 is a morpholinyl of formula II; and prodrugs, metabolites, tautomers, solvates and pharmaceutically acceptable salts thereof, for use in the prevention or treatment of a neurological disorder in a subject.

DIFLUOROMETHYL-AMINOPYRIDINES AND DIFLUOROMETHYL-AMINOPYRIMIDINES

The invention relates to novel phosphoinositide 3-kinase (PI3K),mammalian target of rapamycin (mTOR)and PI3K-related kinase(PIKKs)inhibitor compounds of formula (I), wherein X1, X2 and X3 are N or CH, with the proviso that

And circular PI3K inhibitors (by machine translation)

The invention belongs to the field of medical technology, in particular to general formula (I) and of the everted shown in the PI3K inhibitor, or a pharmaceutically acceptable salt, ester, stereo isomers, solvates, wherein R 1, R 2, R 3 as defined in the specification. The invention also relates to methods of preparing such compounds, pharmaceutical formulations containing these compounds and pharmaceutical compositions, use of these compounds in the preparation and treatment and/or prevention of proliferative diseases of application of the medicament. (by machine translation)

multi-links class PI3K inhibitors (by machine translation)

The invention belongs to the field of medical technology, in particular of formula (I) shown in multi-links class of PI3K inhibitors, its stereoisomers or its pharmaceutically acceptable salt thereof, wherein the R 1, R 2, R 3, R 4 or R 5 as defined in the specification; the invention also relates to methods of preparing such compounds, pharmaceutical compositions of these compounds in the preparation and treatment and/or prevention of proliferative diseases of the use of the medicament. (by machine translation)

NEW PROCESS FOR PREPARING PI3K INHIBITOR BUPARSILIB

The present disclosure provides a new process for preparing PI3K inhibitor buparsilib. The whole reaction route of the present invention is simple and easy to control for the industrial production.