54221-95-3

Basic information

• Product Name: 2-ACETYLAMINO-ISONICOTINIC ACID
• Synonyms: 2-ACETYLAMINO-ISONICOTINIC ACID;2-AECTAMIDO-4-PYRIDINECARBOXYLIC ACID;2-ACETAMIDOISONICOTINIC ACID;2-(Acetylamino)isonicotinic acid 97%;2-Acetamido-4-pyridinecarboxylic acid;Zinc02559887;2-acetaMidopyridine-4-carboxylic acid;2-(Acetylamino)pyridine-4-carboxylic acid
• CAS NO: 54221-95-3
• Molecular Formula: C₈H₈N₂O₃
• Molecular Weight: 180.16
• Product Categories: Amines;blocks;Carboxes;Pyridines
• Mol File: 54221-95-3.mol

Chemical Properties

• Melting Point: 286-290
• Boiling Point: 585.3 °C at 760 mmHg
• Flash Point: 307.8 °C
• Appearance: /
• Density: 1.404 g/cm³
• Vapor Pressure: 1.52E-14mmHg at 25°C
• Refractive Index: 1.628
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 1.74±0.10(Predicted)
• CAS DataBase Reference: 2-ACETYLAMINO-ISONICOTINIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 2-ACETYLAMINO-ISONICOTINIC ACID(54221-95-3)
• EPA Substance Registry System: 2-ACETYLAMINO-ISONICOTINIC ACID(54221-95-3)

Safety Data

• Hazard Codes: Xi
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 54221-95-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-Acetylaminoisonicotinic Acid is used as a reactant for the preparation of nicotinic acid analogues, which are potent hypoxia-inducible factor (HIF)-1α inhibitors. These analogues play a crucial role in the development of drugs targeting various diseases, including anemia, cancer, and other conditions related to the HIF-1α pathway. By inhibiting HIF-1α, these analogues can help regulate cellular responses to hypoxia and potentially improve treatment outcomes for patients suffering from these diseases.

InChI:InChI=1/C8H8N2O3/c1-5(11)10-7-4-6(8(12)13)2-3-9-7/h2-4H,1H3,(H,12,13)(H,9,10,11)

Upstream product

• 6937-03-7 methyl 2-aminoisonicotinate 
• 75-36-5 acetyl chloride 
• 695-34-1 2-Amino-4-methylpyridine 
• 108-24-7 acetic anhydride 
• 13362-28-2 2-aminoisonicotinic acid 
• 5327-32-2 2-acetylamino-4-methylpyridine 

Downstream Products

• 6937-03-7 methyl 2-aminoisonicotinate 
• 13362-30-6 2-amino-4-ethoxycarbonyl-pyridine 
• 13362-28-2 2-aminoisonicotinic acid 
• 908380-97-2 N-{4-[5-(4-fluoro-phenyl)-3-methyl-2-methylsulfinyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide 
• 452056-88-1 C₁₇H₁₅FN₄OS 
• 105250-17-7 2-amino-4-hydroxymethylpyridine 
• 918955-30-3 methanesulfonic acid 2-(4-fluoro-phenyl)-3-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyridin-7-ylmethyl ester 
• 918955-31-4 methanesulfonic acid 2-(4-fluoro-phenyl)-3-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyridin-7-ylmethyl ester 
• 918955-32-5 methanesulfonic acid 3-[2-(benzyl-methyl-amino)-pyrimidin-4-yl]-2-(4-fluoro-phenyl)-imidazo[1,2-a]pyridin-7-ylmethyl ester 
• 918955-27-8 methanesulfonic acid 3-(2-benzylamino-pyrimidin-4-yl)-2-(4-fluoro-phenyl)-imidazo[1,2-a]pyridin-7-ylmethyl ester 
• 918955-33-6 methanesulfonic acid 3-(2-benzyloxy-pyrimidin-4-yl)-2-(4-fluoro-phenyl)-imidazo[1,2-a]pyridin-7-ylmethyl ester 
• 480453-80-3 {2-(4-fluoro-phenyl)-3-[2-(1-phenyl-ethylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyridin-7-yl}-methanol 

Relevant articles and documents

Discovery of 2-(cyclopropanecarboxamido)-N-(5-((1-(4-fluorobenzyl)piperidin-4-yl)methoxy)pyridin-3-yl)isonicotinamide as a potent dual AChE/GSK3β inhibitor for the treatment of Alzheimer's disease: Significantly increasing the level of acetylcholine in the brain without affecting that in intestine

Acetylcholinesterase (AChE) inhibitors are currently the first-line drugs approved by the FDA for the treatment of Alzheimer's disease (AD). However, a short effective-window limits their therapeutic benefits. Clinical studies have confirmed that the combination of AChE inhibitors and neuroprotective agents exhibits better anti-AD effects. We have previously reported that the dual AChE/GSK3β (Glycogen synthase kinase 3β) modulators have both neuroprotective effects and cognitive impairment-improvement effects. In this study, we characterized a new backbone of the AChE/GSK3β inhibitor 11c. It was identified as a highly potent AChE inhibitor and was found superior to donepezil, the first-line drug for the treatment of AD. In vivo studies confirmed that 11c significantly inhibited the activity of AChE in the brain but had little effect on the activity of AChE in the intestine. This advantage of 11c was expected to reduce the peripheral side effects caused by donepezil. Furthermore, biomarker studies have shown that 11c also improved the levels of acetylcholine and synaptophysin in the brain and exhibited neuroprotective effects. Preliminary in vivo and in vitro research results underline the exciting potential of compound 11c in the treatment of AD.

Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.

Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a Dual p38α MAPK/PDE-4 Inhibitor with Activity against TNFα-Related Diseases

The anti-inflammatory potential of p38 mitogen-activated protein kinase (MAPK) inhibitors was coincidentally expanded to a dual inhibition of p38α MAPK and phosphodiesterase 4 (PDE4), and the potential benefits arising from the blockage of both inflammation-related enzymes were thoroughly investigated. The most promising compound, CBS-3595 (1), was successively evaluated in in vitro experiments as well as in ex vivo and in vivo preclinical studies after administration of 1 to rodents, dogs, and monkeys. The resulting data clearly indicated a potent suppression of tumor necrosis factor alpha release. For reconfirming the findings of the animal studies when administering 1 to healthy human volunteers, a phase I clinical trial was conducted. Apart from further information regarding the pharmacokinetic and pharmacodynamic characteristics of 1, it was demonstrated that dual inhibition of p38α MAPK and PDE4 is able to synergistically attenuate the excessive anti-inflammatory response.

Development of first lead structures for phosphoinositide 3-kinase-c2γ inhibitors

The importance of complete elucidation of the biological functions of phosphoinositide 3-kinases (PI3K) was realized years ago. They generate 3-phosphoinositides, which are known to function as important second messengers in many inter- and intracellular signaling pathways. However, the functional role of class II PI3Ks is still unclear. Herein, we describe the synthesis of a panel of compounds that were tested against all eight mammalian PI3K-isoforms. We found inhibitors with some selectivity for class II PI3K-C2γ and also compounds with preferred inhibition of class II PI3K-C2β, providing structural leads to develop selective tool compounds.

DEUTERIUM-ENRICHED HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS

The present invention provides deuterium-enriched heteroaryl-containing urea compounds (I) and use of the same for treating conditions mediated by protein kinase such as

Characterization of nicotinamidases: Steady state kinetic parameters, classwide inhibition by nicotinaldehydes, and catalytic mechanism

Nicotinamidases are metabolic enzymes that hydrolyze nicotinamide to nicotinic acid. These enzymes are widely distributed across biology, with examples found encoded in the genomes of Mycobacteria, Archaea, Eubacteria, Protozoa, yeast, and invertebrates, but there are none found in mammals. Although recent structural work has improved our understanding of these enzymes, their catalytic mechanism is still not well understood. Recent data show that nicotinamidases are required for the growth and virulence of several pathogenic microbes. The enzymes of Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans regulate life span in their respective organisms, consistent with proposed roles in the regulation of NAD+ metabolism and organismal aging. In this work, the steady state kinetic parameters of nicotinamidase enzymes from C. elegans, Sa. cerevisiae, Streptococcus pneumoniae (a pathogen responsible for human pneumonia), Borrelia burgdorferi (the pathogen that causes Lyme disease), and Plasmodium falciparum (responsible for most human malaria) are reported. Nicotinamidases are generally efficient catalysts with steady state kcat values typically exceeding 1 s -1. The Km values for nicotinamide are low and in the range of 2 -110 μM. Nicotinaldehyde was determined to be a potent competitive inhibitor of these enzymes, binding in the low micromolar to low nanomolar range for all nicotinamidases tested. A variety of nicotinaldehyde derivatives were synthesized and evaluated as inhibitors in kinetic assays. Inhibitions are consistent with reaction of the universally conserved catalytic Cys on each enzyme with the aldehyde carbonyl carbon to form a thiohemiacetal complex that is stabilized by a conserved oxyanion hole. The S. pneumoniae nicotinamidase can catalyze exchange of 18O into the carboxy oxygens of nicotinic acid with H218O. The collected data, along with kinetic analysis of several mutants, allowed us to propose a catalytic mechanism that explains nicotinamidase and nicotinic acid 18O exchange chemistry for the S. pneumoniae enzyme involving key catalytic residues, a catalytic transition metal ion, and the intermediacy of a thioester intermediate.

Imidazole compounds having an antiinflammatory effect

The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the i

Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1α inhibitors

We report a new series of HIF-1α inhibitors which were obtained through structural modifications of previously reported lead 1. The in vitro inhibitory potencies of newly synthesized compounds were evaluated against hypoxia-induced HIF-1 activation using

2-SULFINYL- AND 2-SULFONYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS

The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula (I) in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the

MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 5: Carbon-substituted analogues at the C-2 position

A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with carbon-linked substituents, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas β-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Palladium-catalyzed cross-coupling methods were applied for the incorporation of aliphatic and aromatic substituents.