93683-65-9

Usage

Chemical Properties

Light yellow Cryst

InChI:InChI=1/C6H2ClN3O2/c7-6-2-1-5(10(11)12)4(3-8)9-6/h1-2H

Upstream product

• 16013-85-7 2,6-dicholoro-3-nitropyridine 
• 544-92-3 copper(I) cyanide 
• 950778-43-5 6-methoxy-3-nitropyridine-2-carbonitrile 
• 2402-78-0 2,6-dichloropyridine 
• 872-50-4 1-methyl-pyrrolidin-2-one 

Downstream Products

• 93683-77-3 2-Benzyl-5'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-carbonitrile 
• 95095-89-9 6-<<4-(Dimethylamino)phenyl>thio>-3-nitro-2-pyridinecarbonitrile 
• 95095-87-7 3-Nitro-6-(3-trifluoromethyl-phenylsulfanyl)-pyridine-2-carbonitrile 
• 93683-71-7 6-[(4-Chloro-benzyl)-propyl-amino]-3-nitro-pyridine-2-carbonitrile 
• 93683-75-1 6-[(3,4-Dichloro-benzyl)-methyl-amino]-3-nitro-pyridine-2-carbonitrile 
• 93683-72-8 6-[(4-Chloro-benzyl)-isopropyl-amino]-3-nitro-pyridine-2-carbonitrile 
• 93683-76-2 6-{[1-(3,4-Dichloro-phenyl)-ethyl]-methyl-amino}-3-nitro-pyridine-2-carbonitrile 
• 93683-68-2 6-[(3-Chloro-benzyl)-methyl-amino]-3-nitro-pyridine-2-carbonitrile 
• 93683-67-1 6-<<(3-bromophenyl)methyl>methylamino>-3-nitro-2-pyridinecarbonitrile 
• 93683-70-6 6-[(4-Chloro-benzyl)-ethyl-amino]-3-nitro-pyridine-2-carbonitrile 
• 93683-66-0 6-(Benzyl-ethyl-amino)-3-nitro-pyridine-2-carbonitrile 
• 93683-73-9 6-[Methyl-(4-trifluoromethyl-benzyl)-amino]-3-nitro-pyridine-2-carbonitrile 
• 93683-78-4 2-(4-Chloro-benzyl)-5'-nitro-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-6'-carbonitrile 
• 95095-84-4 3-amino-6-chloro-pyridine-2-carbonitrile 

Relevant academic research and scientific papers

Optimization of 4,6-Disubstituted Pyrido[3,2-d]pyrimidines as Dual MNK/PIM Inhibitors to Inhibit Leukemia Cell Growth

Mitogen-activated protein kinase-interacting kinases (MNKs) and provirus integration in maloney murine leukemia virus kinases (PIMs) are downstream enzymes of cell proliferation signaling pathways associated with the resistance of tyrosine kinase inhibitors. MNKs and PIMs have complementary effects to regulate cap-dependent translation of oncoproteins. Dual inhibitors of MNKs and PIMs have not been developed. We developed a novel 4,6-disubstituted pyrido[3,2-d]pyrimidine compound 21o with selective inhibition of MNKs and PIMs. The IC50’s of 21o to inhibit MNK1 and MNK2 are 1 and 7 nM and those to inhibit PIM1, PIM2, and PIM3 are 43, 232, and 774 nM, respectively. 21o inhibits the growth of myeloid leukemia K562 and MOLM-13 cells with GI50’s of 2.1 and 1.2 μM, respectively. 21o decreases the levels ofp-eIF4E andp-4EBP1, the downstream products of MNKs and PIMs, as well as cap-dependent proteins c-myc, cyclin D1, and Mcl-1. 21o inhibits the growth of MOLM-13 cell xenografts without causing evident toxicity. 21o represents an innovative dual MNK/PIM inhibitor with a good pharmacokinetic profile.

4, 6-disubstituted pyridine [3, 2-d] pyrimidine compound as well as preparation and application thereof

The invention belongs to the technical field of medicines. The invention relates to the field of pharmaceutical chemistry, in particular to a 4, 6-disubstituted pyridine [3, 2-d] pyrimidine compound and pharmaceutically acceptable salt thereof, a preparation method of the compound, a pharmaceutical composition taking the compound as an active ingredient, and application of the compound in preparation of an MNK inhibitor and drugs for treating and/or preventing various cancers and/or metabolic diseases. The present invention relates to compounds represented by formulas I, II, III or IV, and pharmaceutically acceptable salts, hydrates, solvates and metabolites thereof, wherein the variables are described in the claims and the description.

Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection

Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (pj) can lead to serious health consequences in patients with an immunocompromised system. Trimethoprim (TMP), used as first-line therapy in combination with sulfamethoxazole, is a selective but only moderately potent pj dihydrofolate reductase (pjDHFR) inhibitor, whereas non-clinical pjDHFR inhibitors, such as, piritrexim and trimetrexate are potent but non-selective pjDHFR inhibitors. To meet the clinical needs for a potent and selective pjDHFR inhibitor for PCP treatment, fourteen 6-substituted pyrido[3,2-d]pyrimidines were developed. Comparison of the amino acid residues in the active site of pjDHFR and human DHFR (hDHFR) revealed prominent amino acid differences which could be exploited to structurally design potent and selective pjDHFR inhibitors. Molecular modeling followed by enzyme assays of the compounds revealed 15 as the best compound of the series with an IC50 of 80 nM and 28-fold selectivity for inhibiting pjDHFR over hDHFR. Compound 15 serves as the lead analog for further structural variations to afford more potent and selective pjDHFR inhibitors.

Preparation method of novel substituted pyridine pyrimidine compound

The invention belongs to the field of pharmaceutical and chemical industry, and provides a preparation method of a novel substituted pyridine pyrimidine compound. The pyridine pyrimidine compound is of great significance to medical research and new drug development. The problem that an amide compound is easily destroyed by strong alkalis in a synthesis process under a high temperature condition issolved, and meanwhile the problem that a pyrimidine 4-amino group is difficult to react to synthesize amide due to poorer amino activity is solved. Moreover, a two-step reaction for reducing a nitrogroup into an amino group and hydrolyzing cyano group into the amide group is completed in a one-step reaction, thereby simplifying the reaction flow. The invention provides a preparation method of the compound. The compound provides important support for the application of the compound in the field of new drug development in the future in terms of synthesis conditions, methods and processes.

MONOCYCLIC, THIENO, PYRIDO, AND PYRROLO PYRIMIDINE COMPOUNDS AND METHODS OF USE AND MANUFACTURE OF THE SAME

The present invention provides monocyclic, thieno, pyrido and pyrrolo pyrimidine compounds. Pharmaceutical compositions comprising one or more of these compounds and optionally comprising a pharmaceutically acceptable salt or hydrate of one or more of the compounds are provided. Preferably, these pharmaceutical compositions further comprise at least one pharmaceutically acceptable carrier. Methods of treating a patient having cancer are provided wherein a therapeutically effective amount of one or more of these compounds or pharmaceutical compositions are administered to the patient.

QUINOLINES AND RELATED ANALOGS AS SIRTUIN MODULATORS

Provided herein are novel sirtuin-modulating compounds 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.

Design and synthesis of substituted pyrido[3,2-d]-1,2,3-triazines as potential Pim-1 inhibitors

A novel series of substituted pyrido[3,2-d]-1,2,3-triazines were designed and synthesized as Pim-1 inhibitors through scaffold hopping. Most of the derivatives showed potent in vitro Pim-1 inhibitory activities and anti-proliferative effects toward prosta

Cyclohexylpropionic polypyridine deriv.

A problem of the present invention is to provide a new compound which has NK 1 receptor antagonist activity ,whose CYP3A4 inhibitory activity is reduced compared to aprepitant, and which are useful for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting. That is, the present invention relates to cyclohexyl pyridine derivatives represented by the following formula (I) or a pharmaceutically acceptable salt thereof. wherein, ring A is 4-fluoro-2-methylphenyl or the like; X is a hydrogen atom or the like; R 1 is carboxymethyl or the like; R 2 is alkyl or the like; Y is 0-2 or the like; U is-N(CH 3 )COC(CH 3 ) 2 -3,5-bistrifluoromethylphenyl or the like.

Carboxymethyl piperidine derivative

The present invention provides a novel compound useful in the prevention or treatment of nausea and vomiting associated with the administration of antineoplastics, the compound having an NK1 receptor-antagonizing effect, and an inhibitory effect on CYP3A4 that is attenuated to a greater extent than in aprepitant. Specifically, the present invention relates to a carboxymethyl piperidine derivative represented by formula (I) or a pharmacologically acceptable salt thereof. In the formula, ring A is a benzene ring or the like, ring B is a pyridine ring or the like, R1 is a C1-6 alkyl or C1-6 alkoxy, R2 and R3 are hydrogen atoms or methyl, and n represents an integer of from 0 to 5.

CARBOXYMETHYL PIPERIDINE DERIVATIVE

The present invention provides a new compound which has NK1 receptor antagonist activity, whose CYP3A4 inhibitory activity is reduced compared to aprepitant, and which are useful for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting. That is, the present invention relates to carboxymethyl piperidine derivatives represented by the following formula (I) or a pharmaceutically acceptable salt thereof. Wherein, ring A is a benzene ring or the like; ring B is a pyridine ring or the like; R1 is C1-6 alkyl or C1-6 alkoxy; R2 and R3 are a hydrogen atom or methyl; and n is an integral number from 0 to 5.