240486-10-6

Upstream product

• 7677-24-9 trimethylsilyl cyanide 
• 29976-53-2 N-ethoxycarbonyl-4-piperidone 
• 615-36-1 2-bromoaniline 

Downstream Products

• 1050595-96-4 N-(2-{[(2S)-3-({spiro[indole-2-4'-piperidin]-3(1H)-one}-1'-yl)-2-hydroxypropyl]oxy}-4-hydroxyphenyl)acetamide 
• 240486-28-6 C₂₂H₂₄N₂O₃ 
• 84145-25-5 4-cyano-4-phenylamino-piperidine-1-carboxylic acid ethyl ester 
• 240486-16-2 ethyl 1,3-dihydro-3-imino-spiro[2H-indole-2,4'-piperidine]-1'-carboxylate 

Relevant academic research and scientific papers

NOVEL COMBINATION OF COMPOUNDS TO BE USED IN THE TREATMENT OF AIRWAY DISEASES, ESPECIALLY CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) AND ASTHMA

The present invention provides a pharmaceutical product comprising, in combination of, (a) a (therapeutically effective) dose of a first active ingredient, which is a compound of formula (I) or a pharmaceutically acceptable salt thereof; and (b) a (therapeutically effective) dose of a second active ingredient, which is a glucocorticoid receptor agonist; and optionally, (c) a (therapeutically effective) dose of a third active ingredient, which is a β2-agonist. The invention further relates to pharmaceutical compositions comprising said combination and to methods of treating treatment of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma in mammals by administrating said combination. The invention further relates to a kit comprising the combination and use of said kit in treatment of airway diseases such as COPD and asthma.

Conformational Switching and the Synthesis of Spiro[2H-indol]-3(1H)-ones by Radical Cyclization

Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]-3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4′-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexane-carbonitrile (3, X-R2 = CH2), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R2 = CH2). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2c and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.