2499-96-9

Usage

InChI:InChI=1/C8H7N3O2/c1-4-2-3-5-6(9-4)7(12)11-8(13)10-5/h2-3H,1H3,(H2,10,11,12,13)

Upstream product

• 208708-54-7 3-amino-6-methyl-pyrrolo[3,4-c]pyridin-1-one 
• 53636-71-8 3-amino-6-methylpyridine-2-carboxylic acid 
• 57-13-6 urea 
• 123-73-9 trans-Crotonaldehyde 
• 932-52-5 5-Aminouracil 
• 123-73-9 crotonaldehyde 
• 932-52-5 5-amino-2,4-dihydroxy-pyrimidine 

Downstream Products

• 30212-52-3 2,4-dichloropyrido<3,2-d>pyrimidine 
• 1955-59-5 4-[(2,4-dioxo-1,2,3,4-tetrahydro-pyrido[3,2-d]pyrimidin-6-ylmethyl)-amino]-benzoic acid 
• 78711-29-2 6-methylpyrido<3,2-d>pyrimidin-4(3H)-one 
• 30265-87-3 4-Amino-2-chlor-6-methyl-1.3.5-triaza-naphtalin 
• 109506-86-7 6-methyl-2-phenoxy-pyrido[3,2-d]pyrimidin-4-ylamine 
• 1955-58-4 4-[(4-oxo-3,4-dihydro-pyrido[3,2-d]pyrimidin-6-ylmethyl)-amino]-benzoic acid 
• 1332075-56-5 (2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methanol 
• 1332076-39-7 1-(4-((2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methyl)piperidin-1-yl)ethanone 

Relevant academic research and scientific papers

Design, synthesis and biological activity of N5-substituted tetrahydropteroate analogs as non-classical antifolates against cobalamin-dependent methionine synthase and potential anticancer agents

Cobalamin-dependent methionine synthase (MetH) is involved in the process of tumor cell growth and survival. In this study, a novel series of N5-electrophilic substituted tetrahydropteroate analogs without glutamate residue were designed as non-classical antifolates and evaluated for their inhibitory activities against MetH. In addition, the cytotoxicity of target compounds was evaluated in human tumor cell lines. With N5-chloracetyl as the optimum group, further structure research on the benzene substituent and on the 2,4-diamino group was also performed. Compound 6c, with IC50 value of 12.1 μM against MetH and 0.16–6.12 μM against five cancer cells, acted as competitive inhibitor of MetH. Flow cytometry studies indicated that compound 6c arrested HL-60 cells in the G1-phase and then inducted late apoptosis. The molecular docking further explained the structure-activity relationship.

Synthesis and antiproliferative activity of a series of novel 6-substituted pyrido[3,2-d]pyrimidines as potential nonclassical lipophilic antifolates targeting dihydrofolate reductase

Dihydrofolate reductase (DHFR) has been a well-recognized target for the treatment of many diseases. Based on 8,10-dideazaminopterins, which are classical antifolates that potently inhibit DHFR, we have designed a series of novel 2,4-diamino-6-substituted pyrido[3,2-d]pyrimidines. By removing the glutamate moiety and introducing lipophilic groups, we hoped to improve passive diffuse through the cell membranes. The target compounds were efficiently synthesized using one-pot procedure and evaluated in?vitro for DHFR inhibition and antitumor activity. Compounds 5e, 5h, 5i and 5k were the most potent inhibitors of recombinant human DHFR (rhDHFR) with IC50values in the range 0.2–1.0?μM. Analysis using flow cytometric indicated that the effect of compound 5k on cell cycle progression was linked to induction of S phase arrest. Compounds 5g, 5h, 5i and 5k showed broad spectrum antitumor activity against four different tumor cell lines, with IC50values in the range 0.07–23?μM. Molecular docking investigations showed that the trimethoyphenyl ring of compound 5k occupied a position near the cofactor-binding site in the rhDHFR-inhibitor complex, with close intermolecular contacts with Asp21, Phe31, Ser59, Ile60 and Pro61.

Tetrahydrofurfuroxy folic acid analogue synthetic method

The invention relates to a novel method for synthesis of tetrahydrofolic acid analogues, and mainly solves the problems of uneasily controllable reaction conditions and many produced by products in a conventional synthesis method. A series of tetrahydrofolic acid analogues are prepared by employing 5-aminouracil or 2,4,5,6-tetraaminopyrimidine, 2,5,6-triamino-4-hydroxypyrimidine as an initial raw material and combining the steps of cyclization, oxidation, chlorination, ammonolysis, catalytic hydrogenation reduction, intramolecular cyclization, aziridine ring opening, nucleophilic substitution, ethoxycarbonyl hydrolysis, etc. Compared with a conventional synthesis method, the novel method provided by the invention has the characteristics of mild and stable reaction conditions, few by-products, wide application range, etc.

PYRIDO[3,2-d]PYRIMIDINE PI3K DELTA INHIBITOR COMPOUNDS AND METHODS OF USE

Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

8-SUBSTITUTED QUINOLINES AND RELATED ANALOGS AS SIRTUIN MODULATORS

Provided herein are 8-substituted quinolines and related analogues as sirtuin-modulating compounds of Structural Formula (I) and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

4-MORPHOLINO-PYRIDO[3,2-D]PYRIMIDINES

This invention relates to compounds of Formula (I) as Pi3k inhibitors for treating autoimmune deseases, inflammatory disorders, multiple sclerosis and other deseases like cancers.

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.

Pyrimidine derivatives and methods of making and using these 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.

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.

Derivatives of pyrido [2,3-d] and [3,2-d] pyrimidine and methods of using these derivatives

The invention discloses generic compound (2) and its analog (6) and pharmaceutically acceptable salts and methods of using these compounds for therapeutically and prophylactically treating a patient for an illness consisting of the group of Pneumocystis c