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Novel compounds for use in cognition improvement

A technology of compounds and groups, applied in the direction of active ingredients of heterocyclic compounds, organic chemistry, drug combination, etc.

Inactive Publication Date: 2017-09-01
FUNDACION PARA LA INVESTIGACION MEDICA APLICADA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] The search for effective AD management is largely based on the amyloid (Aβ) hypothesis, which has focused on reducing the number of senile plaques, although so far with little success

Method used

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  • Novel compounds for use in cognition improvement
  • Novel compounds for use in cognition improvement
  • Novel compounds for use in cognition improvement

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0238] The general procedure of the preparative HPLC purification method:

[0239] HPLC measurements were performed using a Gilson 281 from a 233 pump (binary), autosampler and UV detector. Fractions were detected by LC-MS. The MS detector was configured with an electrospray ionization source. The source temperature was maintained at 300°C to 350°C.

[0240] HPLC method (purification method):

[0241] method 1 : reverse phase HPLC on luna (100 x 30 mm; 5 μm). Solvent A: water with 0.075% TFA; solvent B: acetonitrile. Gradient: 28% B to 58% B in 10.5 minutes at 25°C; then hold 58% B for 4 minutes, PDA.

[0242] Method 2 : reverse phase HPLC on luna C8 (100 x 30 mm; 5 μm). Solvent A: NH 4 HCO 3 10 mM aqueous solution; solvent B: acetonitrile. Gradient: at 25°C, from 45% B to 65% B in 12 minutes, hold 65% B for 2 minutes; then from 65% B to 95% B in 0.2 minutes, hold 95% for 2 minutes B; then reach 45% B in 0.2 minutes, hold 45% B for 1.4 minutes. Flow rate: 20mL / ...

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Abstract

Novel compounds for use in cognition improvement. It relates to certain compounds having a polycyclic structure and a -(C=O)NRaRb moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and / or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases.

Description

[0001] The present invention relates to compounds as dual inhibitors of PDE and HDAC and methods for their preparation. The present invention also relates to pharmaceutical compositions containing said compounds, and their use in medicine, especially in the treatment and / or prevention of neurological disorders or neurodegenerative diseases accompanied by cognitive deficits or impairments. Background technique [0002] Mild cognitive impairment is characterized by deficits in memory, language, and / or other basic cognitive functions that do not interfere with an individual's daily life. The condition often progresses to dementia, which is characterized by an overall deterioration of cognitive abilities to the extent that it interferes with daily life. Alzheimer's disease (AD), the most common form of dementia in older adults, refers to dementia without a precursory cause (such as stroke, traumatic brain injury, or alcohol); characterized by the presence of extracellular amyloid ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04C07D471/14A61K31/519A61K31/53A61K31/506A61K31/4985A61P25/28A61P25/16A61P25/14A61P25/18A61P25/24
CPCC07D471/14C07D487/04A61P25/14A61P25/16A61P25/18A61P25/24A61P25/28
Inventor M·D·M·夸德拉多·特赫多尔A·M·加西亚·奥斯塔J·奥亚扎巴尔·圣玛丽娜M·O·拉巴尔·格雷西亚J·A·桑切斯·阿里亚斯A·乌加特·巴斯坦
Owner FUNDACION PARA LA INVESTIGACION MEDICA APLICADA
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