Novel imidazothiazoles and imidazoxazoles

An alkyl and compound technology, applied in the field of novel imidazothiazoles and imidazoxazoles, can solve the problems of excessive and uncontrolled expression of pro-inflammatory cytokines

Inactive Publication Date: 2009-10-07
ABBOTT LAB INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

While this response is part of the normal physiological response to cellular stress, acute or chronic cellular stress can lead to excessive or unregulated expression of pro-inflammatory cytokines

Method used

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  • Novel imidazothiazoles and imidazoxazoles
  • Novel imidazothiazoles and imidazoxazoles
  • Novel imidazothiazoles and imidazoxazoles

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0215] In the preparation of capsules, 10 parts by weight of the active compound and 240 parts by weight of lactose can be dispersed and blended. The mixture is then filled into hard gelatin capsules, each capsule containing a unit dose or part of a unit dose of the active compound.

[0216] b) Tablet

[0217] Tablets can be prepared from, for example, the following components.

[0218] Parts by weight

[0219] Active compound 10

[0220] Lactose 190

[0221] Corn starch 22

[0222] Polyvinylpyrrolidone 10

[0223] Magnesium stearate 3

[0224] The active compound, lactose and part of the starch are dispersed and blended, and the obtained mixture is granulated with an ethanol solution of polyvinylpyrrolidone. The dry granules are mixed with magnesium stearate and the remaining starch. The mixture is then compressed in a tablet press to obtain tablets each containing a unit dose or part of a unit dose of active compound.

[0225] c) Enteric-coated tablets

[0226] Tablets can be pr...

Embodiment

[0496] Example #I.1.1: 5-(3-Cyclobutyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-6-(2,4,5-tri Fluorophenyl)imidazo[2,1-b]oxazole

[0497]

[0498] Add 5-(6-hydrazinopyridin-3-yl)-6-(2,4,5-trifluorophenyl)imidazo[2,1-b]oxazole (0.30g, 0.87) to the round bottom flask mmol; start with preparation #O.1 and NIS with A, use 2-fluoropyridine-5-boronic acid [Asymchem] in C, prepare with hydrazine in D) and cyclobutanecarboxylic acid chloride (1.5mL, 13mmol) . The reaction mixture was heated to about 100°C for about 1 hour. The reaction mixture was diluted with heptane and filtered. The solid was dissolved in DCM (50mL) and washed with saturated aqueous NaHCO 3 (50mL) Wash the organic layer with MgSO 4 Dry, filter and concentrate under reduced pressure. The crude solid was purified by flash chromatography (silica gel; DCM / MeOH gradient from 1:0 to 19:1) to obtain the title compound (0.28 g, 78%): LC / MS (Table 1, Method a) R t = 2.26 minutes; MS m / z: 410.1 (M+H) + .

[0499] Table I.1.1: Using ...

Embodiment P11

[0651] Example P.1.1: 1-(3-(6-(6-(4-fluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazole And [4,3-a]pyridin-3-yl)pyrrolidin-1-yl)ethanone

[0652]

[0653] Containing 6-(4-fluorophenyl)-5-(3-(pyrrolidin-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)imidazole And [2,1-b]oxazole (0.100g, 0.26mmol; Example #M.1.1.3) in DCM suspension (5mL) was added TEA (0.04mL, 0.26mmol) and acetyl chloride (0.02mL , 0.26mmol). The reaction mixture was allowed to stir for approximately 16 hours at ambient temperature. The crude reaction mixture was purified by flash chromatography (silica gel; DCM / MeOH gradient from 99:1 to 90:10) to give the title compound (0.02 g, 17%). LC / MS (Table 1, Method a) R t = 1.79 minutes; MS m / z: 431.1 (M+H) + .

[0654] Table P.1: Using general method P from 6-(4-fluorophenyl)-5-(3-(pyrrolidin-3-yl)-[1,2,4]triazolo[4,3-a ]Pyridin-6-yl)imidazo[2,1-b]oxazole [Example#M1.1.3] Preparation example

[0655]

Acylating agent

Product

Example#...

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Abstract

The present invention is directed to novel compounds of formula (I) wherein the variables are as defined herein. The compounds of formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases and proliferative disorders and conditions, for example, cancers.

Description

[0001] Cross-references to related applications [0002] This application claims priority from U.S. Patent Application No. 60 / 849873 filed on October 6, 2006. Background of the invention [0003] Protein phosphorylation on specific amino acid residues is important for the regulation of various cellular processes including cell cycle progression and division, signal transduction, and apoptosis. Phosphorylation is usually a reaction that transfers terminal phosphate groups from ATP to a protein substrate. The specific structures where phosphate groups are transferred into the target substrate are tyrosine, serine and threonine residues. Since these amino acid residues are the target structures for phosphoryl transfer, these protein kinases are often referred to as tyrosine kinases or serine / threonine (S / T) kinases. The phosphorylation and dephosphorylation reactions that occur on tyrosine, serine and threonine residues are related to a variety of cellular processes. These processes...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/41C07D257/04
CPCC07D519/00C07D513/04C07D498/04A61P1/04A61P1/16A61P1/18A61P11/00A61P11/02A61P11/04A61P11/06A61P13/02A61P13/12A61P15/00A61P17/00A61P17/02A61P17/04A61P17/06A61P17/14A61P19/02A61P19/10A61P21/02A61P21/04A61P25/00A61P25/02A61P25/06A61P25/14A61P25/16A61P25/32A61P27/02A61P27/06A61P29/00A61P31/04A61P31/10A61P31/12A61P31/14A61P31/18A61P31/20A61P33/00A61P33/10A61P35/00A61P35/02A61P37/02A61P37/06A61P37/08A61P43/00A61P5/14A61P5/24A61P7/00A61P7/02A61P7/06A61P7/10A61P9/00A61P9/02A61P9/04A61P9/06A61P9/10A61P9/12A61P9/14A61P3/10
Inventor D·W·博尔哈尼D·J·考德伍德K·E·弗兰克H·M·戴维斯N·S·约瑟夫索恩B·S·斯金纳
Owner ABBOTT LAB INC
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