Compound for treating cerebral infarction and preparation method thereof

A compound and alkyl technology, which is applied in the field of preparation of drugs for the treatment of cerebral infarction and compounds for the treatment of cerebral infarction, can solve the problems of stealing blood, small clinical curative effect, toxic and side effects, etc.

Inactive Publication Date: 2019-04-09
牡丹江医学院附属红旗医院
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The common characteristics of the above-mentioned drugs for the treatment of cerebral infarction are: strong pertinence, clear target, but single curative effect, can only provide partial protective effect, and the clinical curative effect is relatively small
And there are different degrees of toxic and side effects. For example, it is difficult for thrombolytic drugs to enter the damaged brain tissue through the blood-brain barrier to exert their effects, so the curative effect is uncertain, and there are side effects of causing reperfusion injury and bleeding; vasodilators can make normal The blood vessels in the area dilate, causing the blood in the lesion to flow to the normal brain tissue, resulting in the so-called "stealing blood" phenomenon

Method used

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  • Compound for treating cerebral infarction and preparation method thereof
  • Compound for treating cerebral infarction and preparation method thereof
  • Compound for treating cerebral infarction and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] 4-((5-(5-(1H-tetrazol-5-yl)pyrimidin-2-yl)-3-methyl-5,6,7,8-tetrahydro-1,5-naphthyridine -2-yl)methyl)morpholine

[0064]

[0065] Step 1: Dissolve morpholine (2.58 g, 30 mmol) and 60% NaOH (1.40 g, 35 mmol) in 150 mL of anhydrous THF, and stir at 50° C. for 30 min under nitrogen protection. Cool to room temperature, slowly add dropwise 100mL of anhydrous THF solution containing 6-bromomethyl-7-methyl-1,2,3,4-tetrahydro-1,5-naphthyridine (6.01g, 25mmol) Then heat and stir for 3h, pour the reaction solution into 150mL of ice water, extract three times with ethyl acetate, combine the organic phases, wash once with saturated brine, dry the organic phases with anhydrous magnesium sulfate, filter, and evaporate the solvent under reduced pressure. The resulting residue was subjected to column chromatography (eluent volume ratio: cyclohexane:ethyl acetate=6:1), and the solvent was distilled off under reduced pressure to obtain off-white solid 4-((3-methyl-5,6,7, 8-Tetrahy...

Embodiment 2

[0072] (2S,6R)-4-((5-(5-(1H-tetrazol-5-yl)pyrimidin-2-yl)-3-trifluoromethyl-5,6,7,8-tetrahydro- 1,5-naphthyridine-2-yl)methyl)-2,6-dimethylmorpholine

[0073]

[0074] According to the method of Example 1, (2S,6R)-2,6-dimethylmorpholine was used instead of morpholine, and 6-bromomethyl-7-trifluoromethyl-1,2,3,4-tetrafluoromethyl-1,2,3,4-tetra Hydrogen-1,5-naphthyridine replaced 6-bromomethyl-7-methyl-1,2,3,4-tetrahydro-1,5-naphthyridine, and the total yield of the three steps was 48.7%.

[0075] ESI-MS: 475.21[M+H] +

[0076] Elemental analysis: theoretical value / measured value, C(53.05 / 53.17), H(5.09 / 5.02), F(11.99 / 11.89), N(26.51 / 26.54), O(3.36 / 3.38)

[0077] 1 H NMR (400MHz, CDCl 3 )δ13.09(s,1H),9.06(s,2H),7.35(s,1H),3.94(s,2H),3.51(m,2H),3.08(t,2H),3.02(t,2H ), 2.48(d,4H), 1.92(m,2H), 1.18(d,6H).

Embodiment 3

[0079] 5-(5-(1H-tetrazol-5-yl)pyridin-2-yl)-2-((4-methylsulfonyl-piperazin-1-yl)methyl)-5,6,7, 8-tetrahydro-1,5-naphthyridine-4-ol

[0080]

[0081] According to the method of Example 1, morpholine was replaced with 1-methylsulfonyl-piperazine, and 2-bromomethyl-5,6,7,8-tetrahydro-1,5-naphthalene-4- Alcohol was used instead of 6-bromomethyl-7-methyl-1,2,3,4-tetrahydro-1,5-naphthyridine, and the total yield of the three steps was 45.5%.

[0082] ESI-MS: 472.18[M+H] +

[0083] Elemental analysis: theoretical value / measured value, C(50.94 / 50.82), H(5.34 / 5.42), N(26.73 / 26.64), O(10.18 / 10.27), S(6.80 / 6.85)

[0084] 1 H NMR (400MHz, CDCl 3 )δ13.09(s,1H),10.04(s,1H),8.35(d,1H),7.62(q,1H),6.74(d,1H),6.48(s,1H),3.94(s,2H ), 3.08(t,2H), 3.02(t,2H), 2.93(s,3H), 2.43(t,4H), 2.33(t,4H), 1.92(m,2H).

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Abstract

The invention relates to a compound for treating cerebral infarction. The invention further relates to a preparation method of the compound and an application of the compound for preparing a drug for treating the cerebral infarction. The compound can significantly reduce thrombosis generated after rat vein ligation, and can obviously reduce an area of the cerebral infarction of a rat with middle cerebral artery occlusion. Therefore, the compound can prevent the thrombosis, can facilitate thrombolysis, and can be used in prevention and treatment of the cerebral infarction such as cerebral thrombosis and cerebral embolism.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a compound for treating cerebral infarction, and also relates to a preparation method of the compound and its use for preparing a medicine for treating cerebral infarction. Background technique [0002] Cerebral infarction, also known as ischemic stroke or ischemic cerebral apoplexy, is a disorder of blood supply to the local brain tissue caused by various reasons, resulting in ischemic and hypoxic lesions and necrosis of the brain tissue, which in turn produces clinically corresponding neurological functions. missing performance. Cerebral infarction is divided into cerebral thrombosis, cerebral embolism, and lacunar infarction according to different pathogenesis. Among them, cerebral thrombosis is the most common type of cerebral infarction, accounting for 60% of all cerebral infarctions. [0003] At present, the clinical treatment of cerebral infarction mainly ad...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04A61K31/5377A61K31/506A61K31/496A61K31/444A61P7/02A61P9/10
CPCC07D471/04
Inventor 罗海龙李欣焦杨徐丹贾茜袁秀梅姜爱英
Owner 牡丹江医学院附属红旗医院
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