Category: 158078-04-7

A chemical probe for the methyl transferase PRMT5 with a novel binding mode was written by Pande, Vineet;Sun, Weimei;Beke, Lijs;Berthelot, Didier;Brehmer, Dirk;Brown, David;Corbera, Jordi;Irving, Steve;Meerpoel, Lieven;Nys, Thomas;Parade, Marc;Robinson, Colin;Sommen, Cois;Viellevoye, Marcel;Wu, Tongfei;Thuring, Jan Willem. And the article was included in ACS Medicinal Chemistry Letters in 2020.Related Products of 158078-04-7 The following contents are mentioned in the article:

Protein arginine methyltransferase 5 (PRMT5) is an enzyme that can sym. dimethylate arginine residues in histones and nonhistone proteins by using S-adenosyl methionine (SAM) as the Me donating cofactor. We have designed a library of SAM analogs and discovered potent, cell-active, and selective spiro diamines as inhibitors of the enzymic function of PRMT5. Crystallog. studies confirmed a very interesting binding mode, involving protein flexibility, where both the cofactor pocket and part of substrate binding site are occupied by these inhibitors. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7Related Products of 158078-04-7).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. Dioxole functionalized metal-organic frameworks have also been recently reported.Related Products of 158078-04-7

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem

6-Alkyl-, 6-aryl- or 6-hetaryl-7-deazapurine ribonucleosides as inhibitors of human or MTB adenosine kinase and potential antimycobacterial agents was written by Perlikova, Pavla;Konecny, Petr;Naus, Petr;Snasel, Jan;Votruba, Ivan;Dzubak, Petr;Pichova, Iva;Hajduch, Marian;Hocek, Michal. And the article was included in MedChemComm in 2013.Synthetic Route of C14H16ClN3O4 The following contents are mentioned in the article:

Title 6-alkyl-, 6-aryl- and 6-hetaryl-7-deazapurine ribonucleosides previously known as nanomolar cytostatics were found to be potent inhibitors of either human or mycobacterial (MTB) adenosine kinase (ADK). Several new derivatives bearing bulky substituents at position 6 were non-cytotoxic but selectively inhibited MTB ADK. However, most of the nucleosides (ADK inhibitors) as well as their octadecylphosphate prodrugs were inactive in the whole cell assay of inhibition of Mycobacterium bovis growth. 6-Methyl-7-deazapurine ribonucleoside was found to be a potent antimycobacterial agent. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7Synthetic Route of C14H16ClN3O4).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. Although benzodioxole is not particularly important, many related compounds containing the methylenedioxyphenyl group are bioactive, and thus are found in pesticides and pharmaceuticals.Synthetic Route of C14H16ClN3O4

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem

Hetaryl derivatives of 7-deazapurine ribonucleosides: potent cytostatic agents was written by Perlikova, Pavla;Naus, Petr;Bourderioux, Aurelie;Hocek, Michal. And the article was included in Collection Symposium Series in 2011.Application In Synthesis of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol The following contents are mentioned in the article:

A symposium. A series of novel 7-deazapurine ribonucleosides substituted with aryl and hetaryl groups has been prepared Suzuki or Stille cross-coupling reactions with 6-chloro-7-deazapurine ribonucleosides substituted with H, F of Cl atom in position 7 were used in the key step of the synthesis. Either cross-coupling of protected ribonucleoside with appropriate (het)aryl-boronic acid or stannane followed by deprotection, or single-step aqueous-phase Suzuki cross-coupling reaction of unprotected 7-deazapurine ribonucleoside with boronic acid provided target (het)aryl-7-deazapurine ribonucleosides. 6-Furyl- and 6-thienyl-7-deazapurine ribonucleosides showed cytostatic effect in multiple cancer cell lines in nano-molar range. Application of cyclosaligenyl and alanyl-ester phosphoramidate prodrugs did not improved cytostatic activity of parent nucleosides. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7Application In Synthesis of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. 1,3-Benzodioxole can be synthesized from catechol with disubstituted halomethanes.Application In Synthesis of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem

CycloSal-phosphate Pronucleotides of Cytostatic 6-(Het)aryl-7-deazapurine Ribonucleosides: Synthesis, Cytostatic Activity, and Inhibition of Adenosine Kinases was written by Spacilova, Pavla;Naus, Petr;Pohl, Radek;Votruba, Ivan;Snasel, Jan;Zabranska, Helena;Pichova, Iva;Ameral, Ria;Birkus, Gabriel;Cihlar, Tomas;Hocek, Michal. And the article was included in ChemMedChem in 2010.Recommanded Product: 158078-04-7 The following contents are mentioned in the article:

A series of cycloSal-phosphate prodrugs of a recently described new class of nucleoside cytostatics (6-hetaryl-7-deazapurine ribonucleosides) was prepared The corresponding 2′,3′-isopropylidene 6-chloro-7-deazapurine nucleosides were converted into 5-O’-cycloSal-phosphates. These underwent a series of Stille or Suzuki cross-couplings with diverse (het)arylstannanes or -boronic acids to yield the protected 6-(het)aryl-7-deazapurine pronucleotides that were subsequently deprotected to give 12 derivatives of free pronucleotides. The in vitro cytostatic effect of the pronucleotides was compared with parent nucleoside analogs. In most cases, the activity of the pronucleotide was similar to or somewhat lower than that of the corresponding parent nucleosides, with the exception of 7-fluoro pronucleotides 13a, 13b, and 13d, which had exhibited GIC₅₀ values that were improved by one order of magnitude (to the low nanomolar range). The presence of a cycloSal-phosphate group also influenced selectivity toward various cell lines. Several pronucleotides were found which strongly inhibit human adenosine kinase but only weakly inhibit the MTB adenosine kinase. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7Recommanded Product: 158078-04-7).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. Although benzodioxole is not particularly important, many related compounds containing the methylenedioxyphenyl group are bioactive, and thus are found in pesticides and pharmaceuticals.Recommanded Product: 158078-04-7

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem

LLY-283, a Potent and Selective Inhibitor of Arginine Methyltransferase 5, PRMT5, with Antitumor Activity was written by Bonday, Zahid Q.;Cortez, Guillermo S.;Grogan, Michael J.;Antonysamy, Stephen;Weichert, Ken;Bocchinfuso, Wayne P.;Li, Fengling;Kennedy, Steven;Li, Binghui;Mader, Mary M.;Arrowsmith, Cheryl H.;Brown, Peter J.;Eram, Mohammad S.;Szewczyk, Magdalena M.;Barsyte-Lovejoy, Dalia;Vedadi, Masoud;Guccione, Ernesto;Campbell, Robert M.. And the article was included in ACS Medicinal Chemistry Letters in 2018.Safety of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol The following contents are mentioned in the article:

Protein arginine methyltransferase 5 (PRMT5) is a type II arginine methyltransferase that catalyzes the formation of sym. dimethylarginine in a number of nuclear and cytoplasmic proteins. Although the cellular functions of PRMT5 have not been fully unraveled, it has been implicated in a number of cellular processes like RNA processing, signal transduction and transcriptional regulation. PRMT5 is ubiquitously expressed in most tissues and its expression has been shown to be elevated in several cancers including breast cancer, gastric cancer, glioblastoma and lymphoma. Here we describe the identification and characterization of a novel and selective PRMT5 inhibitor with potent in vitro and in vivo activity. Compound 1 (also called LLY-283) inhibited PRMT5 enzymic activity in vitro and in cells with IC₅₀ of 22 ± 3 nM and 25 ± 1 nM, resp. while its diastereomer, compound 2 (also called LLY-284) was much less active. Compound 1 also showed antitumor activity in mouse xenografts when dosed orally and can serve as an excellent probe mol. for understanding the biol. function of PRMT5 in normal and cancer cells. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7Safety of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. 1,3-Benzodioxole can be synthesized from catechol with disubstituted halomethanes.Safety of ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem

Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors was written by Yu, Wenyu;Chory, Emma J.;Wernimont, Amy K.;Tempel, Wolfram;Scopton, Alex;Federation, Alexander;Marineau, Jason J.;Qi, Jun;Barsyte-Lovejoy, Dalia;Yi, Joanna;Marcellus, Richard;Iacob, Roxana E.;Engen, John R.;Griffin, Carly;Aman, Ahmed;Wienholds, Erno;Li, Fengling;Pineda, Javier;Estiu, Guillermina;Shatseva, Tatiana;Hajian, Taraneh;Al-awar, Rima;Dick, John E.;Vedadi, Masoud;Brown, Peter J.;Arrowsmith, Cheryl H.;Bradner, James E.;Schapira, Matthieu. And the article was included in Nature Communications in 2012.SDS of cas: 158078-04-7 The following contents are mentioned in the article:

Selective inhibition of protein methyltransferases is a promising new approach to drug discovery. An attractive strategy towards this goal is the development of compounds that selectively inhibit binding of the cofactor, S-adenosylmethionine, within specific protein methyltransferases. Here we report the three-dimensional structure of the protein methyltransferase DOT1L bound to EPZ004777, the first S-adenosylmethionine-competitive inhibitor of a protein methyltransferase with in vivo efficacy. This structure and those of four new analogs reveal remodelling of the catalytic site. EPZ004777 and a brominated analog, SGC0946, inhibit DOT1L in vitro and selectively kill mixed lineage leukemia cells, in which DOT1L is aberrantly localized via interaction with an oncogenic MLL fusion protein. These data provide important new insight into mechanisms of cell-active S-adenosylmethionine-competitive protein methyltransferase inhibitors, and establish a foundation for the further development of drug-like inhibitors of DOT1L for cancer therapy. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7SDS of cas: 158078-04-7).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. Dioxole functionalized metal-organic frameworks have also been recently reported.SDS of cas: 158078-04-7

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem

Phosphoramidate pronucleotides of cytostatic 6-aryl-7-deazapurine ribonucleosides was written by Perlikova, Pavla;Pohl, Radek;Votruba, Ivan;Shih, Robert;Birkus, Gabriel;Cihlar, Tomas;Hocek, Michal. And the article was included in Bioorganic & Medicinal Chemistry in 2011.HPLC of Formula: 158078-04-7 The following contents are mentioned in the article:

A series of O-Ph methyl-, ethyl- and benzylalanyl phosphoramidate pronucleotides, e.g. I, derived from cytostatic 6-aryl-7-deazapurine ribonucleosides were prepared by the cross-coupling reactions of the 2′,3′-isopropylidene protected 6-chloro-7-deazapurine ribonucleoside phosphoramidates with (het)arylboronic acids or -stannanes followed by deprotection. Most of the prepared prodrugs exerted in vitro cytostatic effects against both solid tumor and lymphoid cancer cells within low micromolar range of concentrations These activities were in general weaker or comparable to the activities of the parent nucleosides. Addnl. testing of selected prodrugs suggests that the lack of activity improvement over parent nucleosides is not due to the lack of permeability or inefficient catabolism of alanyl-ester by intracellular hydrolases. More likely, active efflux of prodrugs may play a role in their weak cytotoxic activity. This study involved multiple reactions and reactants, such as ((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7HPLC of Formula: 158078-04-7).

((3aR,4R,6R,6aR)-6-(4-Chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (cas: 158078-04-7) belongs to dioxole derivatives. Dioxoles, particularly fluorinated dioxoles, are used as co-monomers to make polymers that find use in forming protective coatings for chemical resistance. Although benzodioxole is not particularly important, many related compounds containing the methylenedioxyphenyl group are bioactive, and thus are found in pesticides and pharmaceuticals.HPLC of Formula: 158078-04-7

Referemce:
1,3-Benzodioxole – Wikipedia,
Dioxole | C3H4O2 – PubChem