Small molecule inhibitor for preventing Alzheimer's disease Abeta polypeptide from fiberizing and its preparation method, pharmaceutical composition and application

A compound and pharmaceutical technology, applied in the field of medicinal chemistry, can solve the problems of protease degradation, impermeability of the blood-brain barrier, toxicity, etc.

Inactive Publication Date: 2008-01-09
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most other reported Aβ inhibitors have not entered clinical trials due to toxicity, easy degradation by proteases in vivo, and inability to pass through the blood-brain barrier, and further chemical structure modification and optimization are needed

Method used

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  • Small molecule inhibitor for preventing Alzheimer's disease Abeta polypeptide from fiberizing and its preparation method, pharmaceutical composition and application
  • Small molecule inhibitor for preventing Alzheimer's disease Abeta polypeptide from fiberizing and its preparation method, pharmaceutical composition and application
  • Small molecule inhibitor for preventing Alzheimer's disease Abeta polypeptide from fiberizing and its preparation method, pharmaceutical composition and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0097] Preparation of 2,2-bis[3,5-dibromo-4-(2-hydroxy)propoxyphenyl]propane

[0098]

[0099] 1.1.1 Preparation of 2,2-bis(4-hydroxyphenyl)propane (method 1)

[0100] Put 1.16 g (0.02 mol) of acetone and 5.64 g. (0.06 mol) of phenol in a 100 mL flask, stir, add 12 mL of concentrated hydrochloric acid, and pass through dry hydrogen chloride gas, stop the reaction after one week of reaction. Add water, crush the solid reactant, distill off excess phenol, and filter with suction to obtain an almost white solid, dry it, and then recrystallize it with 20 mL of ethanol to give 4.1 g of a white needle-like product (yield 90%), melting point 151-153 ℃ (reported in literature 151 ℃).

[0101] 1.1.2 Preparation of 2,2-bis(4-hydroxyphenyl)propane (method 2)

[0102] Put 0.02 mole of phenol and 0.02 mole of 2,2-diethylthiopropane in a 100mL flask, stir, feed hydrogen chloride gas, and continue the reaction at room temperature for 6.5 hours; then, stop the reaction, distill, and dry ...

Embodiment 2

[0109] Preparation of 2,2-bis[3,5-dibromo-4-furyl-2-formyloxyphenyl]propane

[0110]

[0111] The 1-chloro-2-propanol in Step 1.3 of Example 1 was replaced with furan-2-formyl chloride, and the rest of the required raw materials, reagents and preparation methods were the same as in Example 1 to obtain the product 2,2-bis[3,5 -Dibromo-4-furyl-2-formyloxyphenyl]propane.

[0112] 1 HNMR (CDCl 3 )ppm: δ1.68(s, 6H, CH 3 ), δ6.63(m, 2H, ArH), δ7.42(s, 4H, ArH), δ7.49(m, 2H, ArH), δ7.73(m, 2H, ArH).EI-MS m / s 732[M+].

Embodiment 3

[0114] Preparation of 2,2-bis[3,5-dibromo-4-(5-bromo-furyl)-2-formyloxyphenyl]propane

[0115]

[0116] The 1-chloro-2-propanol in Step 1.3 of Example 1 is replaced by 5-bromo-furan-2-formyl chloride, and the rest of the required raw materials, reagents and preparation methods are the same as in Example 1 to obtain the product 2,2-di [3,5-Dibromo-4-(5-bromo-furyl)-2-formyloxyphenyl]propane.

[0117] 1 HNMR (CDCl 3 )ppm: δ1.71(s, 6H, CH 3 ), δ6.55(m, 2H, ArH), δ7.12(s, 3H, ArH), δ7.31(m, 3H, ArH).EI-MS m / s 889[M+].

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Abstract

A compound for inhibiting beta-starch protein aggregation and fibrillation or its medicinal accepted slat, composition, its production and use in prevention and treatment of Alzheimer's disease are disclosed. The compound or medicinal accepted slat combines with Alpha-beta polypeptide and inhibits Alpha-beta polypeptide aggregation and fibrillation.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to an inhibitor of β-amyloid protein (Aβ) associated with Alzheimer's disease. More specifically, the present invention relates to a novel compound (general formula I) with a symmetrical structure capable of inhibiting the aggregation and fibrosis of β-amyloid protein, or a pharmaceutically acceptable salt thereof and a preparation method thereof; It also relates to a pharmaceutical composition comprising such a compound or a pharmaceutically acceptable salt thereof, and the use of the compound or a pharmaceutically acceptable salt and a pharmaceutical composition thereof in the preparation of a drug for preventing and treating Alzheimer's disease application. Background technique [0002] Among typical intractable dementia cases, 50%-70% are Alzheimer's disease (Alzheimer's Disease, AD). It is a degenerative disease of the brain, often with brain atrophy, especially the atrophy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C43/23C07D307/68C07D295/084C07D209/48C07C69/94A61K31/216A61K31/4035A61K31/5377A61K31/34A61P25/28
CPCC07D209/48C07D307/68C07C2101/14C07D295/088C07C43/23C07C69/92A61P25/28C07C2601/14
Inventor 刘东祥许叶春柳红周宇沈旭陈凯先蒋华良
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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