43120-28-1

Usage

Uses

Used in Pharmaceutical Industry:
1H-INDAZOLE-3-CARBOXYLIC ACID METHYL ESTER is used as a precursor in the synthesis of N-benzoylindazole derivatives and analogues for their potential application as inhibitors of human neutrophil elastase. This makes it a valuable compound in the development of treatments for various inflammatory and respiratory conditions.
Additionally, 1H-INDAZOLE-3-CARBOXYLIC ACID METHYL ESTER is used in the preparation of indazole-pyridine based protein kinase/Akt inhibitors. These inhibitors have potential applications in the treatment of various cancers and other diseases where protein kinase/Akt signaling pathways play a crucial role in their progression.

InChI:InChI=1/C9H8N2O2/c1-13-9(12)8-6-4-2-3-5-7(6)10-11-8/h2-5H,1H3,(H,10,11)

Upstream product

• 67-56-1 methanol 
• 4498-67-3 1H-Indazole-3-carboxylic acid 
• 134810-89-2 methyl 3-(2-acetamidophenyl)propanoate 
• 67-64-1 acetone 
• 30095-98-8 methyl (2-nitrophenyl)acetate 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 6832-16-2 methyl diazoacetate 
• 88284-48-4 2-(trimethylsilyl)phenyl trifluoromethanesulfonate 
• 4498-67-3 2H-indazole-3-carboxylic acid 
• 201230-82-2 carbon monoxide 
• 66607-27-0 3-iodoindazole 
• 100-63-0 phenylhydrazine 
• 16917-42-3 4-bromobenzaldehyde phenylhydrazone 
• 1630015-70-1 4-bromobenzylideneaminoisatine 

Downstream Products

• 99055-81-9 1⁽²⁾H-indazole-3-carboxylic acid dimethylamide 
• 34252-44-3 2-Methylindazole-3-carboxylic acid 
• 109216-61-7 3-methoxycarbonyl-2-methylisoindazole 
• 64132-13-4 3-(hydroxymethyl)-1H-indazole 
• 173600-05-0 methyl 1-isopropyl-1H-indazol-3-ylcarboxylate 
• 173600-03-8 benzyl-1H-indazole-3-carboxylic acid methyl ester 
• 126861-68-5 2-benzyl-2H-indazole-3-carboxylic acid 
• 41354-03-4 AF 1311TS 
• 252025-50-6 methyl 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylate 
• 1079-47-6 methyl 5-iodo-1H-indazole-3-carboxylate 
• 441717-61-9 methyl 1-(4-methoxybenzyl)-1H-indazole-3-carboxylate 
• 932041-16-2 methyl 1-(4-(trifluoromethyl)phenyl)-1H-indazole-3-carboxylate 
• 1198054-28-2 C₁₇H₁₆N₂O₃ 
• 1190097-05-2 N-(benzo[d][1,3]dioxol-5-yl)-1-(4-(methylsulfonyl)benzyl)-1H-indazole-3-carboxamide 

Relevant academic research and scientific papers

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

The indazole scaffold represents a promising pharmacophore, commonly incorporated in a variety of therapeutic drugs. Although indazole-containing drugs are frequently marketed as the corresponding N-alkyl 1H- or 2H-indazole derivative, the efficient synthesis and isolation of the desired N-1 or N-2 alkylindazole regioisomer can often be challenging and adversely affect product yield. Thus, as part of a broader study focusing on the synthesis of bioactive indazole derivatives, we aimed to develop a regioselective protocol for the synthesis of N-1 alkylindazoles. Initial screening of various conditions revealed that the combination of sodium hydride (NaH) in tetrahydrofuran (THF) (in the presence of an alkyl bromide), represented a promising system for N-1 selective indazole alkylation. For example, among fourteen C-3 substituted indazoles examined, we observed > 99% N-1 regioselectivity for 3-carboxymethyl, 3-tert-butyl, 3-COMe, and 3-carboxamide indazoles. Further extension of this optimized (NaH in THF) protocol to various C-3, -4, -5, -6, and -7 substituted indazoles has highlighted the impact of steric and electronic effects on N-1/N-2 regioisomeric distribution. For example, employing C-7 NO2 or CO2Me substituted indazoles conferred excellent N-2 regioselectivity (≥ 96%). Importantly, we show that this optimized N-alkylation procedure tolerates a wide structural variety of alkylating reagents, including primary alkyl halide and secondary alkyl tosylate electrophiles, while maintaining a high degree of N-1 regioselectivity.

NovelN-transfer reagent for converting α-amino acid derivatives to α-diazo compounds

A novel universalN-transfer reagent for direct and effective transformation of α-amino ketones, acetamides, and esters to the corresponding α-diazo products under mild basic conditions has been developed. This one-step synthetic approach not only allows for generation of α-substituted-α-diazo carbonyl compounds from α-amino acid derivatives but also permits preparation of α-diazo dipeptides fromN-terminal dipeptides (32 examples, up to 91%).

Preparation methods of 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine

The invention relates to preparation methods of a 1H-indazol-3-carboxylic acid derivative, granisetron and lonidamine. The 1H-indazol-3-carboxylic acid derivative is a compound with a structure shown in a formula (1) and a formula (2), and is mainly structurally characterized by having a 1H-indazol-3-carboxylic acid amide skeleton and a 1H-indazol-3-carboxylic ester skeleton. The 1H-indazol-3-carboxylic acid derivative can be synthesized by taking simple o-aminophenylacetic acid amide or o-aminophenylacetic acid ester as an initial raw material. The 1H-indazol-3-carboxylic acid derivative is a key intermediate for synthesizing a plurality of medicines, such as granisetron, lonidamine and the like. The synthesis method of the 1H-indazol-3-carboxylic acid derivative and the drug molecules glassetron and lonidamine is simple, the reaction condition is mild, the reaction speed is high, the yield is high, and purification is easy.

NOVEL ARYLALKYL PYRAZOLE COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS

Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

Substituted 3-indazole Mcl-1 protein inhibitor as well as preparation method and application thereof

The invention discloses a substituted 3-indazole Mcl-1 protein inhibitor as well as a preparation method and application thereof. The compound has a structure represented by a general formula (I) which is described in the specification. The compound discl

EPHA4 CYCLIC PEPTIDE ANTAGONISTS AND METHODS OF USE THEREOF

Disclosed herein are compounds and methods of use thereof for the modulation of EphA4 receptor activity. In an aspect, is provided a method of treating or preventing a disease or disorder mediated by EphA4, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as described herein, including certain embodiments, or the structural Formula (I), (l-A), (II), (III), (IV), (IV-1), (V), (Vl-A), (Vl-B), (VII-1), (VII-2), (VIII-1), or (VIII-2), or an enantiomer, a mixture of enantiomers, a mixture of two or more diastereomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, or hydrate thereof.

Access to 1: H -indazoles, 1 H -benzoindazoles and 1 H -azaindazoles from (het)aryl azides: A one-pot Staudinger-aza-Wittig reaction leading to N-N bond formation?

The synthesis of various substituted 1H-indazoles is reported through N-N bond formation from an iminophosphorane derivative. Supported by control experiments, an original Staudinger-aza-Wittig tandem mechanism is proposed for this transformation.

Targeting Serotonin 2A and Adrenergic α1 Receptors for Ocular Antihypertensive Agents: Discovery of 3,4-Dihydropyrazino[1,2-b]indazol-1(2H)-one Derivatives

Glaucoma affects millions of people worldwide and causes optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and decreasing IOP is the key therapeutic target of current pharmacological treatments. As potential ocular hypotensive agents, we studied compounds that act on two receptors (serotonin 2A and adrenergic α1) linked to the regulation of aqueous humour dynamics. Herein we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic N2-alkyl-indazole-amide derivatives. This study identified a 3,4-dihydropyrazino[1,2-b]indazol-1(2H)-one derivative with potent serotonin 2A receptor antagonism, >100-fold selectivity over other serotonin subtype receptors, and high affinity for the α1 receptor. Moreover, upon local administration, this compound showed superior ocular hypotensive action in vivo relative to the clinically used reference compound timolol.

HETEROARYL-SUBSTITUTED TRIAZOLES AS APJ RECEPTOR AGONISTS

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII

A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a–g (amide derivatives) and 7 a–h (triazoles) act as “prodrugs”, and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets. Moreover, no inhibition of the off-target hCA I and II isoforms was observed. Compounds 8 a–f (another set of triazoles) exhibited nanomolar inhibition against hCA isoforms I, II, IX and XII, among which compounds 8 c, 8 d, and 8 f were found to inhibit the tumor-associated hypoxia-induced hCA isoform IX with Ki values of 1.8, 2.3, and 2.0 nm respectively. Further exploration of these compounds could be useful for the development of novel antitumor agents with selective mechanisms of CA inhibitory action.