6975-44-6

Usage

Uses

Used in Pharmaceutical Industry:
4, 6-DIHYDROXYNICOTINIC ACID ETHYL ESTER is used as a reactant for the synthesis of pyridazinopyrimidinone and pyridopyrimidinone derivatives, which serve as PDE5 inhibitors. These inhibitors play a crucial role in the treatment of erectile dysfunction and other related conditions by enhancing blood flow to the genital area.
Additionally, 4, 6-DIHYDROXYNICOTINIC ACID ETHYL ESTER is used as a reactant in the synthesis of pyridone diaryl ether non-nucleoside inhibitors of HIV-1 reverse transcriptase. These inhibitors are essential in the development of antiretroviral drugs, which help in the treatment and management of HIV/AIDS by preventing the replication of the virus in the body.
Used in Chemical Industry:
4, 6-DIHYDROXYNICOTINIC ACID ETHYL ESTER, due to its unique chemical properties, can also be employed in various chemical reactions and processes. Its versatility as a white solid compound allows it to be used as an intermediate or building block in the synthesis of other complex molecules, contributing to the development of new materials and products in the chemical industry.

InChI:InChI=1/C8H9NO4/c1-2-13-8(12)5-4-9-7(11)3-6(5)10/h3-4H,2H2,1H3,(H2,9,10,11)

Upstream product

• 570-08-1 diethyl acetylmalonate 
• 64-19-7 acetic acid 
• 122-51-0 orthoformic acid triethyl ester 
• 105-50-0 diethyl 1,3-acetonedicarboxylate 
• 149-73-5 trimethyl orthoformate 
• 108-24-7 acetic anhydride 
• 1336-21-6 ammonium hydroxide 

Downstream Products

• 5466-62-6 4,6-dihydroxy-nicotinic acid 
• 40296-46-6 ethyl 4,6-dichloronicotinate 
• 846541-71-7 ethyl 5-chloro-4,6-dihydroxynicotinate 
• 6317-97-1 ethyl 2,4-dihydroxy-3-nitropyridine-5-carboxylate 
• 847608-28-0 4,5,6-trichloronicotinic acid 
• 847373-09-5 methyl 4-(4-bromo-2-chlorophenylamino)-5,6-dichloronicotinate 
• 874353-11-4 methyl 4-(4-bromo-2-chlorophenylamino)-5-chloro-6-methoxynicotinate 
• 847373-08-4 4-(4-bromo-2-chlorophenylamino)-5,6-dichloronicotinic acid 
• 874353-12-5 4-(4-bromo-2-chlorophenylamino)-5-chloro-6-methoxynicotinic acid 
• 181261-73-4 ethyl 4,5,6-trichloronicotinate 
• 143834-60-0 2,4-dihydroxy-5-hydroxymethyl-pyridine 
• 143834-61-1 Thiocarbonic acid O-(4,6-dihydroxy-pyridin-3-ylmethyl) ester O-p-tolyl ester 
• 143834-62-2 3-deaza-4-O-triisopropylphenylsulfonyl-thymidine 
• 143834-63-3 β-cyanoethyl-3-deaza-5'-O-dimethoxytrityl-thymidine-3'-O-N,N-diisopropylaminophosphoramidite 

Relevant academic research and scientific papers

Quinolone amides as antitrypanosomal lead compounds with In Vivo activity

Human African trypanosomiasis (HAT) is a major tropical disease for which few drugs for treatment are available, driving the need for novel active compounds. Recently, morpholino-substituted benzyl amides of the fluoroquinolone-type antibiotics were identified to be compounds highly active against Trypanosoma brucei brucei. Since the lead compound GHQ168 was challenged by poor water solubility in previous trials, the aim of this study was to introduce structural variations to GHQ168 as well as to formulate GHQ168 with the ultimate goal to increase its aqueous solubility while maintaining its in vitro antitrypanosomal activity. The pharmacokinetic parameters of spray-dried GHQ168 and the newly synthesized compounds GHQ242 and GHQ243 in mice were characterized by elimination half-lives ranging from 1.5 to 3.5 h after intraperitoneal administration (4 mice/compound), moderate to strong human serum albumin binding for GHQ168 (80%) and GHQ243 (45%), and very high human serum albumin binding (>99%) for GHQ242. For the lead compound, GHQ168, the apparent clearance was 112 ml/h and the apparent volume of distribution was 14 liters/kg of body weight (BW). Mice infected with T. b. rhodesiense (STIB900) were treated in a stringent study scheme (2 daily applications between days 3 and 6 postinfection). Exposure to spray-dried GHQ168 in contrast to the control treatment resulted in mean survival durations of 17 versus 9 days, respectively, a difference that was statistically significant. Results that were statistically insignificantly different were obtained between the control and the GHQ242 and GHQ243 treatments. Therefore, GHQ168 was further profiled in an early-treatment scheme (2 daily applications at days 1 to 4 postinfection), and the results were compared with those obtained with a control treatment. The result was statistically significant mean survival times exceeding 32 days (end of the observation period) versus 7 days for the GHQ168 and control treatments, respectively. Spray-dried GHQ168 demonstrated exciting antitrypanosomal efficacy.

Novel 1,6-naphthyridin-2(1H)-ones as potential anticancer agents targeting Hsp90

Hsp90 is an ATP-dependent chaperone known to be overexpressed in many cancers. This way, Hsp90 is an important target for drug discovery. Novobiocin, an aminocoumarin antibiotic, was reported to inhibit Hsp90 targeting C-terminal domain, and showed anti-proliferative properties, leading to the development of new and more active compounds. Consequently, a new set of novobiocin analogs derived from 1,6-naphthyridin-2(1H)-one scaffold was designed, synthesized and evaluated against two breast cancer cell lines. Subsequently, cell cycle progression and apoptosis were conducted on best candidates, finally Western Blot analysis was performed to measure their ability to induce degradation of Hsp90 client proteins.

Bicyclic heterocyclic anthranilic diamides as ryanodine receptor modulators with insecticidal activity

The diamide insecticides act on the ryanodine receptor (RyR). The synthesis of various bicyclic anthranilic derivatives is reported. Their activity against the insect ryanodine receptor (RyR) and their insecticidal activity in the greenhouse is presented,

Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer

A series of imidazo[4,5-c]pyridine-7-carboxamide derivatives as poly(ADP-ribose) polymerase (PARP) inhibitors have been developed. All target compounds were evaluated for their PARP-1 inhibitory activity and some were further assessed for cellular potency

COMPOUNDS FOR REGULATING FAK AND/OR SRC PATHWAYS

The present application provides novel optionally substituted fused pyridine and pyrimidine bicyclic compounds and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in co-regulating FAK and/or Src activity by administering a therapeutically effective amount of one or more of the compounds to a subject. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the FAK and/or Src pathway. Advantageously, these compounds perform as dual FAK and/or Src inhibitors. A variety of conditions can be treated using these compounds and include diseases which are characterized by inflammation or abnormal cellular proliferation. In one embodiment, the disease is cancer.

Differential Functionalization of 1,6-Naphthyridin-2(1H)-ones through Sequential One-Pot Suzuki-Miyaura Cross-Couplings

A practical synthesis of 7-chloro-3-iodo-1-methyl-1,6-naphthyridin-2(1H)-one is described that starts from 2-chloro-4-(methylamino)nicotinaldehyde. The dihalo compound then undergoes sequential, site-selective Suzuki-Miyaura cross-coupling reactions to afford highly functionalized 1,6-naphthyridones in good yields.

Design, synthesis and anti-HIV evaluation of novel diarylnicotinamide derivatives (DANAs) targeting the entrance channel of the NNRTI binding pocket through structure-guided molecular hybridization

Through a structure-based molecular hybridization approach, a novel series of diarylnicotinamide derivatives (DANAs) targeting the entrance channel of HIV-1 NNRTIs binding pocket (NNIBP) were rationally designed, synthesized and evaluated for their anti-H

Differential functionalization of 1,6-naphthyridin-2(1H)-ones through sequential one-pot Suzuki-Miyaura cross-couplings

A practical synthesis of 7-chloro-3-iodo-1-methyl-1,6-naphthyridin-2(1H)- one is described that starts from 2-chloro-4-(methylamino)nicotinaldehyde. The dihalo compound then undergoes sequential, site-selective Suzuki-Miyaura cross-coupling reactions to afford highly functionalized 1,6-naphthyridones in good yields. One-pot, sequential, site-selective Suzuki-Miyaura cross-coupling reactions of 7-chloro-3-iodo-1-methyl-1,6-naphthyridin-2(1H)-one afforded highly functionalized 1,6-naphthyridones in good yields. Copyright

MULTIPLE KINASE PATHWAY INHIBITORS

Kinase with inhibitory activity against kinases disposed in multiple signaling pathways and their therapeutic uses.

Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: Structure based design, synthesis, SAR and antimicrobial activity

The development of antibacterial drugs based on novel chemotypes is essential to the future management of serious drug resistant infections. We herein report the design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase. Consideration of structural aspects of the GyrB ATPase site has aided the development of this series resulting in derivatives that demonstrate excellent enzyme inhibitory activity coupled to potent Gram positive antibacterial efficacy.