635712-40-2

Usage

Compound type

Heterocyclic compound, specifically an indazole derivative

Functional group

Aldehyde

Usage

Synthesis of pharmaceuticals and organic compounds, research and development in organic chemistry, key intermediate in the production of drugs and agrochemicals

Unique feature

7-methyl substitution on the indazole ring, which provides unique reactivity and properties for various chemical applications.

Upstream product

• 68-12-2 N,N-dimethyl-formamide 
• 156454-43-2 5-bromo-7-methyl-1H-indazole 
• 24596-19-8 4-bromo-2,6-dimethylphenylamine 
• 1424621-40-8 C₁₂H₁₇BrN₂ 

Downstream Products

• 1374219-98-3 C₂₈H₃₁N₅O₄ 
• 1374220-12-8 C₂₇H₂₉N₅O₄ 
• 1374220-24-2 C₃₇H₄₇N₇O₃ 
• 1374220-37-7 C₂₇H₃₅N₃O₄Si 
• 1374220-38-8 C₃₃H₄₅N₃O₆Si 
• 1414976-17-2 methyl 2-benzamido-3-(7-methyl-1H-indazol-5-yl)-acrylate 
• 1414976-16-1 4-((7-methyl-1H-indazol-5-yl)methylene)-2-phenyloxazol-5(4H)-one 
• 635712-41-3 C₂₀H₁₉N₃O₄ 
• 1374125-19-5 C₃₅H₃₄N₆O₃ 

Relevant academic research and scientific papers

The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 2

Various substituted indazole and benzoxazolone amino acids were investigated as d-tyrosine surrogates in highly potent CGRP receptor antagonists. Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1. When dosed at 0.03 mg/kg SC, compound 2 (a racemic mixture of 3 and its (S)-enantiomer) demonstrated robust inhibition of CGRP-induced increases in mamoset facial blood flow up to 105 min. The compound possesses a favorable predictive in vitro toxicology profile, and good aqueous solubility. When dosed as a nasal spray in rabbits, 3 was rapidly absorbed and showed good intranasal bioavailability (42%).

Selection of an enantioselective process for the preparation of a CGRP receptor inhibitor

(R)-N-(3-(7-Methyl-1H-indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl) piperazine-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl) piperidine-1-carboxamide (1) is a potent calcitonin gene-related peptide (CGRP) receptor antagonist. We have developed a convergent, stereoselective, and economical synthesis of the hydrochloride salt of 1 and demonstrated the synthesis on a multikilogram scale. Two different routes to the chiral indazolyl amino ester subunit were developed utilizing either a Rh-catalyzed asymmetric hydrogenation or a biocatalytic process to install the single chiral center. The advantages and disadvantages of each of these process routes are discussed, as are challenges addressed in the assembly of the final drug substance.

Regioselective protection at N-2 and derivatization at C-3 of indazoles

Indazoles are regioselectively protected at N-2 by a 2-(trimethylsilyl) ethoxymethyl (SEM) group using novel conditions. The SEM group can efficiently direct regioselective C-3 lithiation, and the resulting nucleophile can react with a wide range of electrophiles to generate novel indazole derivatives. The SEM group can be removed by treatment with TBAF in THF or aqueous HCl in EtOH.

SELECTED CGRP-ANTAGONISTS, METHOD FOR THE PRODUCTION AND USE THEREOF AS MEDICAMENTS

The invention relates to substituted piperidines of general formula (I), wherein A, B, D, E, X, R1 and R2 have the meaning cited in claim 1, and to the tautomers, diastereomers, enantiomers, hydrates, mixtures and salts thereof, in addition to the hydrate of the salts, in particular the physiologically compatible salts thereof having inorganic or organic acids. The invention also relates to medicaments containing said compounds, to the use thereof and method for the production thereof.

Selected CGRP-antagonists process for preparing them and their use as pharmaceutical compositions

The present invention relates to substituted piperidines of general formula wherein A, B, D, E, X, R1 and R2 are defined as in claim 1, the tautomers, the diastereomers, the enantiomers, the hydrates thereof, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof.

Novel therapeutic agents for the treatment of migraine

The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their u

Selected CGRP-antagonists, process for preparing them and their use as pharmaceutical compositions

The present invention relates to the CGRP antagonists of general formula wherein A, X, Q and R1 to R3 are defined as in claim 1, the tautomers, the isomers, the diastereomers, the enantiomers, the hydrates, mixtures and salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids, pharmaceutical compositions containing these compounds, their use and processes for preparing them.

SELECTED CGRP ANTAGONISTS, METHODS FOR THE PRODUCTION THEREOF, AND USE THEREOF AS MEDICAMENTS

The invention relates to CGRP antagonists of general formula (I), wherein A, X, Q, and R1 to R3 are defined as indicated in claim 1, the tautomers, isomers, diastereomers, enantiomers, hydrates, mixtures, and salts thereof, and the hydrates of the salts, especially the physiologically acceptable salts thereof with inorganic or organic acids, medicaments containing said compounds, the use thereof, and methods for the production thereof.

HETEROCYCLIC ANTI-MIGRAINE AGENTS

The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

Calcitonin gene related peptide receptor antagonists

The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.