10224-66-5

Upstream product

• 21353-79-7 N-(2',5'-dimethoxyphenyl)-N-methylacetamide 
• 131451-76-8 (2,5-Dimethoxy-phenyl)-carbamic acid methyl ester 
• 2100-42-7 2-chloro-1,4-dimethoxybenzene 
• 25370-97-2 O-(p-toluenesulfonyl)-N-methylhydroxylamine 
• 150-78-7 1,4-dimethoxybezene 
• 50-00-0 formaldehyd 
• 102-56-7 2,5-dimethoxyaniline 
• 1314901-86-4 C₉H₁₁NO₂ 
• 3467-59-2 2,5-dimethoxyacetanilide 
• 74-88-4 methyl iodide 
• 93027-26-0 Methyl-benzyl-(2,5-dimethoxy-phenyl)-amin 
• 77-78-1 dimethyl sulfate 
• 71862-01-6 N-(2,5-dimethoxyphenyl)formamide 

Downstream Products

• 131451-77-9 N-(2,5-dimethoxyphenyl)-N-methyl-3-oxobutanamide 
• 138777-91-0 N-(2',5'-dimethoxyphenyl)-2,2,2-trifluoro-N-methylacetamide 
• 195711-16-1 ethyl [N-(2,5-dimethoxyphenyl)-N-methyl]aminomethylene hydrogen malonate 
• 1436870-23-3 N,N′-{6-[(2,5-dimethoxyphenyl)(methyl)amino]pyrido[2,3-d]-pyrimidine-2,4-diyl}bis(2,2-dimethylpropanamide) 
• 1349239-92-4 C₁₆H₁₈N₆O₂ 
• 936837-21-7 N-(2,5-dimethoxyphenyl)-N-methylthieno[3,2-d]pyrimidin-4-amine 
• 197461-27-1 6-Bromo-5-{[(2,5-dimethoxy-phenyl)-methyl-amino]-methyl}-thieno[2,3-d]pyrimidine-2,4-diamine 
• 216167-60-1 3-nitro-6-(N-methyl-2',5'-dimethoxyanilino)pyridine-2-carbonitrile 
• 857949-17-8 chloro-acetic acid-(2,5-dimethoxy-N-methyl-anilide) 

Relevant academic research and scientific papers

Total synthesis of 4-Acetyloxymethyl-1,6,9-trimethyl-1,9-diazaanthracene-2,5,8,10-tetrao ne, a nybomycin acetate analogue

4-Acetyloxymethyl-1,6,9-trimethyl-1,9-diazaanthracene-2,5,8,10- tetraone 2 (a potential metabolite of nybomycin) was prepared in thirteen steps with a hetero Diels-Alder reaction as a key step.

Regioselectivity of the Diels-Alder Reactions of 2,5,8(1H)-Quinolinetriones

Diels-Alder reactions of 2,5,8(1H)-quinolinetriones were completely regioselective for all the unsymmetrical dienes tested, except in the case of isoprene.This corresponds to a level of regioselectivity higher than the one found by previous workers for 5,

Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control β-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H … π interactions with Trp105 and Phe178 residues compared to the control β-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation.

A Metal-Free Direct Arene C?H Amination

The synthesis of aryl amines via the formation of a C?N bond is an essential tool for the preparation of functional materials, active pharmaceutical ingredients and bioactive products. Usually, this chemical connection is only possible by transition metal-catalyzed reactions, photochemistry or electrochemistry. Here, we report a metal-free arene C?H amination using hydroxylamine derivatives under benign conditions. A charge transfer interaction between the aminating reagents TsONHR and the arene substrates enables the chemoselective amination of the arene, even in the presence of various functional groups. Oxygen was crucial for an effective conversion and its accelerating role for the electron transfer step was proven experimentally. In addition, this was rationalized by a theoretical study which indicated the involvement of a dioxygen-bridged complex with a “Sandwich-like” arrangement of the aromatic starting materials and the aminating agents at the dioxygen molecule. (Figure presented.).

Design, synthesis, and molecular modeling of novel pyrido[2,3-d]pyrimidine analogues as antifolates; Application of buchwald-hartwig aminations of heterocycles

Opportunistic infections caused by Pneumocystis jirovecii (P. jirovecii, pj), Toxoplasma gondii (T. gondii, tg), and Mycobacterium avium (M. avium, ma) are the principal causes of morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). The absence of any animal models for human Pneumocystis jirovecii pneumonia and the lack of crystal structures of pjDHFR and tgDHFR make the design of inhibitors challenging. A novel series of pyrido[2,3-d]pyrimidines as selective and potent DHFR inhibitors against these opportunistic infections are presented. Buchwald-Hartwig coupling reaction of substituted anilines with pivaloyl protected 2,4-diamino-6-bromo-pyrido[2,3-d] pyrimidine was successfully explored to synthesize these analogues. Compound 26 was the most selective inhibitor with excellent potency against pjDHFR. Molecular modeling studies with a pjDHFR homology model explained the potency and selectivity of 26. Structural data are also reported for 26 with pcDHFR and 16 and 22 with variants of pcDHFR.

Pyrrolo pyrimidine and furo pyrimidine derivatives

This invention discloses compounds, and pharmaceutically acceptable salts thereof, useful in therapeutically and/or prophylactically treating patients with an illness. Such illnesses include cancer, and secondary infections caused by Pneumocystis carinii and Toxoplasmosis gondii in immunocompromised patients. The compounds themselves, methods of making these compounds, and methods of using these compounds are all disclosed. More specifically, the compounds include pyrrolo?2,3-d!pyrimidines and furo?2,3-d!pyrimides and derivatives thereof.

Selective Pneumocystis carinii dihydrofolate reductase inhibitors: Design, synthesis, and biological evaluation of new 2,4-diamino-5- substituted-furo[2,3-d]pyrimidines

Nonclassical antifolates, 2,4-diamino-5-substituted-furo[2,3- d]pyrimidines 3-12 with bridge region variations of C8-S9, C8-N9, and C8-O9 and 1-naphthyl, 2-naphthyl, 2-phenoxyphenyl, 4-phenoxyphenyl, and 2-biphenyl side chains were synthesized as phenyl r

Nonclassical 2,4-diamino-8-deazafolate analogues as inhibitors of dihydrofolate reductases from rat liver, Pneumocystis carinii, and Toxoplasma gondii

The synthesis and biological activity of 42 6-substituted-2,4- diaminopyrido[3,2-d]pyrimidines (2,4-diamino-8-deazafolate analogues) are reported. The compounds were synthesized in improved yields compared to previous classical analogues using modifications of procedures reported previously by us. Specifically, the S-phenyl-; mono-, di-, and trimethoxyphenyl-; and mono-, di-, and trichlorophenyl-substituted analogues with H or CH3 at the N10 position and methyl and trifluoromethyl phenyl ketone analogues with H, C0H3, and CH2C≡CH at the N10 position were synthesized. The S10 and N10 α- and β-naphthyl analogues along with the N10 CH3 analogues were also synthesized. These compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii (pc) and Toxoplasma gondii (tg); selectivity ratios were determined against rat liver (rl) DHFR as the mammalian reference enzyme. Against pcDHFR the IC50 values ranged from 0.038 x 10-6 M for 2,4-diamino-6-[(N-methyl-2'- naphthylamino)methyl]pyrido[3,2-d]pyrimidine (28) to 5.5 x 10-6 M for 2,4- diamino-6-[(2',4'-dimethoxyanilino)methyl]pyrido[3,2-d]pyrimidine (15). N10 methylation in all instances increased potency. None of the analogues were selective for pcDHFR. Against tgDHFR the most potent analogue was 2,4- diamino-6-[(N-methylanilino)methyl]pyrido[3,2-d]pyrimidine (5) (IC50 0.0084 x 10-6 M) and the least potent was 2,4-diamino-6-[(2'- naphthylamino)methyl]-pyrido[3,2-d]pyrimidine (37) (IC50 0.16 x 10-6 M). N10 methylation afforded an increase in potency up to 10-fold. In contrast to pcDHFR, several of the 8-deaza analogues were significantly selective for tgDHFR, most notably 2,4-diamino-6-[(2'-chloro-N- methylanilino)methyl]pyrido[3,2-d]pyrimidine (13), 2,4-diamino-6-[(3',4',5'- trimethoxyanilino)methyl]pyrido-[3,2-d]pyrimidine (29), and 2,4-diamino-6- [(2',4',6'-trichloroanilino)methyl]pyrido[3,2-d]pyrimidine (32) which combined high potency at 10-8 M along with selectivities of 8.0, 5.0, and 12.4, respectively. The potency of these three analogues are comparable to the clinically used agent trimetrexate while their selectivities for tgDHFR are 17-43-fold better than trimetrexate.

Anodic Oxidation Products of 2',5'-Dimethoxyacetanilide Derivatives, and Their Application to the Synthesis of Aminoanthraquinones

Anodic oxidation of simple 2',5'-dimethoxyacetanilides proceeds under mildly basic conditions to afford either monomeric or dimeric quinone bisacetals, depending on the structure of the substrate.Similarly, the oxidation of linked derivatives of 2',5'-dimethoxyacetanilides is shown to exhibit a comparable sensitivity, with non-alkylated amides being efficiently converted into bis(quinone bisacetals).The regiospecificity of acetal hydrolysis for both simple and linked quinone bisacetals is shown to be dependent upon the nature of the N-acyl group.The annelation of these hydrolysis products with the anion of 3-cyanophthalide to yield (acylamino)anthraquinones is also reported.