200940-26-7

Usage

InChI:InChI=1/C11H9N3O3/c1-8-10(3-2-6-12-8)17-11-5-4-9(7-13-11)14(15)16/h2-7H,1H3

Upstream product

• 1121-25-1 2-methyl-3-pyridinol 
• 4548-45-2 2-chloro-5-nitropyridine 

Downstream Products

• 200940-22-3 5-methyl-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid [6-(2-methyl-pyridin-3-yloxy)-pyridin-3-yl]-amide 
• 181632-25-7 SB 242084 
• 200940-27-8 phenyl N-[[2-(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamate 
• 181633-42-1 [6-(2-methylpyridin-3-yloxy)pyridin-3-yl]amine 

Relevant academic research and scientific papers

Synthesis and Evaluation of Pyridyloxypyridyl Indole Carboxamides as Potential PET Imaging Agents for 5-HT2C Receptors

Nine pyridyloxypyridyl indole carboxamides were synthesized and displayed high affinities for 5-HT2C receptors and high selectivity over 5-HT2A and 5-HT2B. Among them, 6-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]1H-indole-3-carboxamide (8) exhibits the highest 5-HT2C binding affinity (Ki = 1.3 nM) and high selectivity over 5-HT2A (～1000 times) and 5-HT2B (～140 times). [11C]8 was synthesized by palladium-catalyzed coupling reaction between pinacolboranate 16 and [11C]CH3I with an average radiochemical yield of 27 ± 4% (n = 8, decay-corrected from end of [11C]CH3I synthesis). MicroPET imaging studies in rhesus monkeys showed regional uptake of [11C]8 in the choroid plexus, whereas the bindings in all other brain regions were low. The specific binding in the choroid plexus was confirmed by administration of a blocking dose of 0.1 mg/kg of the 5-HT2C antagonist SB-242084.

Preparation method of indoline compound

The invention discloses a preparation of indoline compound expressed by the following general formula 1; the method successfully passes through for step reactions by applying iodine monochloride, acetenyl trimethyl silane and other reaction reagents, and obtains 6-chlorine-5-methyl indoline. Relative to the prior art, the synthetic method of the indoline derivative reduces the reaction step while improves the reaction yield. Moreover, the reaction condition is gentle, and easy to control; the method is good for large-scale industrial production.

NOVEL INDOL CARBOXYLIC ACID BISPYRIDYL CARBOXAMIDE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD AND COMPOSITION CONTAINING THE SAME AS AN ACTIVE INGREDIENT

Disclosed herein are a new indole carboxylic acid bispyridyl carboxamide derivative, a preparation method thereof, and a composition for prevention or treatment of obesity, urinary disorders, and CNS disorders, containing the same as an active ingredient. Because the indole carboxylic acid bispyridyl carboxamide derivatives according to the present invention have high affinity for 5-HT2c receptors, act selectively on the 5-HT2c receptors, the derivatives rarely have adverse effects caused by other receptors. Because the derivatives effectively inhibit serotonin activity, they may be useful for treatment or prevention of obesity; urinary disorders such as urinary incontinence, premature ejaculation, erectile dysfunction, and prostatic hyperplasia; CNS disorders such as depression, anxiety, concern, panic disorder, epilepsy, obsessive-compulsive disorder, migraine, sleep disorder, withdrawal from drug abuse, Alzheimer's disease, and schizophrenia, associated with 5-HT2c receptors.

Novel indol carboxylic acid bispyridyl carboxamide derivatives as 5-HT2c receptor antagonists

Disclosed herein are a new indole carboxylic acid bispyridyl carboxamide derivative, a preparation method thereof, and a composition for prevention or treatment of obesity, urinary disorders, and CNS disorders, containing the same as an active ingredient. Because the indole carboxylic acid bispyridyl carboxamide derivatives according to the present invention have high affinity for 5-HT2c receptors, act selectively on the 5-HT2c receptors, the derivatives rarely have adverse effects caused by other receptors. Because the derivatives effectively inhibit serotonin activity, they may be useful for treatment or prevention of obesity; urinary disorders such as urinary incontinence, premature ejaculation, erectile dysfunction, and prostatic hyperplasia; CNS disorders such as depression, anxiety, concern, panic disorder, epilepsy, obsessive-compulsive disorder, migraine, sleep disorder, withdrawal from drug abuse, Alzheimer's disease, and schizophrenia, associated with 5-HT2c receptors.

NOVEL INDOL CARBOXYLIC ACID BISPYRIDYL CARBOXAMIDE DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD AND COMPOSITION CONTAINING THE SAME AS AN ACTIVE INGREDIENT

Disclosed herein are a new indole carboxylic acid bispyridyl carboxamide derivative, a preparation method thereof, and a composition for prevention or treatment of obesity, urinary disorders, and CNS disorders, containing the same as an active ingredient. Because the indole carboxylic acid bispyridyl carboxamide derivatives according to the present invention have high affinity for 5-HT2c receptors, act selectively on the 5-HT2c receptors, the derivatives rarely have adverse effects caused by other receptors. Because the derivatives effectively inhibit serotonin activity, they may be useful for treatment or prevention of obesity; urinary disorders such as urinary incontinence, premature ejaculation, erectile dysfunction, and prostatic hyperplasia; CNS disorders such as depression, anxiety, concern, panic disorder, epilepsy, obsessive-compulsive disorder, migraine, sleep disorder, withdrawal from drug abuse, Alzheimer's disease, and schizophrenia, associated with 5-HT2c receptors.

Synthesis and structure-activity relationship of 1H-indole-3-carboxylic acid pyridine-3-ylamides: A novel series of 5-HT2C receptor antagonists

A novel series of 1H-indole-3-carboxylic acid pyridine-3-ylamides were synthesized and identified to show high affinity and selectivity for 5-HT2C receptor. Among them, 1H-indole-3-carboxylic acid[6-(2-chloro-pyridin-3-yloxy)-pyridin-3-yl]-amide (15k) exhibits the highest affinity (IC50 = 0.5 nM) with an excellent selectivity (>2000 times) over other serotonin (5-HT1A, 5-HT2A, and 5-HT6) and dopamine (D2-D4) receptors.

Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: Identification of 5-methyl-1-[[2-[(2-methyl-3- pyridyl)oxy]5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent

The evolution, synthesis, and biological activity of a novel series of 5-HT(2C) receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT(2C) affinity and selectivity over 5- HT(2A) receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT(2B) receptor. Compounds from this series are inverse agonists at the human cloned 5-HT(2C) receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

1-[2-[(Heteroaryloxy)heteroaryl]carbamoyl]indolines: Novel and selective 5-HT(2C) receptor inverse agonists with potential as antidepressant/anxiolytic agents

Bisaryl ethers have been identified with excellent 5-HT(2C) affinity and selectivity over both 5-HT(2A) and 5-HT(2B) receptors. Compounds such as 11, 27 and 38 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT(2C) function and their potential as novel non-sedating anxiolytic and antidepressants is under investigation. (C) 2000 Elsevier Science Ltd. All rights reserved.