CN106389419A - Application of arylhydrazide compound in treatment of acute myocardial ischemic coronary heart disease - Google Patents
Application of arylhydrazide compound in treatment of acute myocardial ischemic coronary heart disease Download PDFInfo
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- CN106389419A CN106389419A CN201610792149.7A CN201610792149A CN106389419A CN 106389419 A CN106389419 A CN 106389419A CN 201610792149 A CN201610792149 A CN 201610792149A CN 106389419 A CN106389419 A CN 106389419A
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- heart disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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Abstract
The invention belongs to the technical field of medicine, and discloses an application of an arylhydrazide compound in the treatment of acute myocardial ischemic coronary heart disease. The arylhydrazide compound is N-(2-(1H-indole-3-yl)acetyl)phenyl acetic hydrazide. The provided arylhydrazide compound can increase the content of NO in serum of patients of acute myocardial ischemic coronary heart disease, and prolongs the hypoxia tolerance time to prevent the acute myocardial ischemic coronary heart disease. A novel drug for treating the disease is provided.
Description
Technical field
The invention belongs to pharmaceutical technology field, in particular to a kind of aromatic hydrazide kind compound in treatment Acute myocardial
Application in ischemic coronary heart disease.
Background technology
Coronary atherosclerotic heart disease is that coronary artery occurs atherosclerotic lesion to cause blood vessel
Chamber stenosis or occlusion, the heart disease causing myocardial ischemia, anoxia or necrosis and leading to, commonly referred to as " coronary heart disease ".Coronary heart disease
Type a lot, including acute myocardial ischemia coronary heart disease, its basic pathology is coronary insufficiency, and cardiac muscle is drastically
, temporary transient ischemia and anoxia.In recent years research shows that NO has stronger vasodilator, suppression vascular smooth muscle cell increases
Grow, antiplatelet aggregation, adhesion and release active substance effect, vasospasm and thrombosiss can be prevented.Vascular endothelial cell
Sustained release NO, regulating blood pressure and arteria coronaria basal tension, maintain the constant diastole state of cardiovascular system, keep myocardial blood flow
Perfusion, the contracting vascular effect of also scalable ET simultaneously.Vascular endothelial cell is impaired to lead to the synthesis of NO and release to reduce, and shows as
The relaxing factor Developmental and Metabolic Disorder of endothelium-dependent relaxation, easily promotes vasospasm, thrombosiss and atherosclerosiss, with coronary heart disease
Being related of acute ischemic event is close.Therefore, emphasize to protect vascular endothelial cell in coronary heart disease treatment, promote NO to release
Put, adjust the important channel that content in its blood is treatment coronary heart disease.
CN105732468A discloses a kind of N '-(2- (1H- indol-3-yl) acetyl group) aromatic hydrazide kind compound, and drapes over one's shoulders
Reveal such compound and there is to HCV virus obvious inhibitory action, preparation method has comprised the steps：Comprise the following steps：
(1) heteroauxing and C1-C5 alcohol occur esterification to obtain ethychlozate ester；(2) ethychlozate ester shown in Formula II and hydrazine hydrate
Reaction obtains indole acethydrazide；(3) aromatic carboxylic acids shown in formula IV are reacted with chlorination reagent and prepare aryl-acyl chlorides；(4) by
Indole acethydrazide shown in formula III and aryl-acyl chlorides shown in Formula V react and obtain N '-(2- (1H- indol-3-yl) acetyl group) virtue hydrazides
Class compound.At present, in terms of the treatment of coronary heart disease, not yet there is document report with N- (2- (1H- indol-3-yl) acetyl group) benzene
Acethydrazide is as the medicine of main active.
Content of the invention
It is an object of the invention to provide a kind of aromatic hydrazide kind compound is in treatment acute myocardial ischemia coronary heart disease
Application.
In order to realize the purpose of the present invention, inventor is by substantial amounts of test cell line and animal experiment study and persistent exploration
After find, N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine can protect vascular endothelial cell, promote its discharge NO, show
Write the serum NO levels improving Acute Myocardial Ischemia Rats it is also possible to extend the hypoxia endurance time of acute myocardial ischemia mice, from
And confirm that this compound has the biological activity of anti-acute myocardial ischemia coronary heart disease.
Therefore, the technical scheme overview of present invention offer is：N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine exists
Application in the medicine of preparation treatment acute myocardial ischemia coronary heart disease, described N- (2- (1H- indol-3-yl) acetyl group) benzene
The structural formula of acethydrazide is as follows：
The medicine of the anti-acute myocardial ischemia coronary heart disease prepared by the present invention is preferably injection.It is further preferred that
Described injection is selected from injection, lyophilized injectable powder.
Compared with prior art, pharmaceutical composition according to the present invention can improve acute myocardial ischemia patients with coronary heart disease blood
Clear NO content, extends patient's hypoxia endurance time, thus reaching the purpose of anti-acute myocardial ischemia coronary heart disease, for the treatment of this disease
Provide a kind of new medication to select.
Specific embodiment
The following is the specific embodiment of the present invention, technical scheme is done and is described further, but the present invention
Protection domain be not limited to these embodiments.Every change without departing substantially from present inventive concept or equivalent substitute are included in this
Within bright protection domain.
Embodiment 1：The preparation of N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine
(1) heteroauxing 8.8g (50mmol), methanol (60mL), concentrated sulphuric acid are added in 500 milliliters of round-bottomed flasks
(3mL), 70 DEG C of reaction 1-3 hours, TLC detects after completion of the reaction, steams methanol, adds water (50mL), separates organic faciess, aqueous phase
With ethyl acetate (3 × 20mL) extraction, merge organic faciess, use saturated sodium bicarbonate solution and water washing, anhydrous sodium sulfate successively
It is dried, after concentrating under reduced pressure, obtain heteroauxing methyl ester crude product.
(2) addition heteroauxing methyl ester 9.46g (48mmol) in 500 milliliters of round-bottomed flasks, ethylene glycol monomethyl ether (40mL),
Hydrazine hydrate 5mL, 115 DEG C of heating reflux reactions about 20 hours, thin layer chromatography (TLC) detection raw material point disappears, stopped reaction, cooling
To room temperature, add water (50mL), standing separates out white solid, and sucking filtration obtains crude product, obtains indole acethydrazide with ethyl alcohol recrystallization
9.2 grams of white solid.
(3) aromatic carboxylic acids 1.6mmol, anhydrous tetrahydro furan 10mL, Deca one are added in 100 milliliters of round-bottomed flasks
DMF, adds 0.5mL thionyl chloride, oil bath, 70 DEG C of reacting by heating about 10 hours, TLC detects after completion of the reaction, steams solvent, obtains
Phenyllacetyl chloride crude product is directly used in next step reaction.
(4) 3- indole acethydrazide (300mg, 1.59mmol), anhydrous tetrahydro furan 10 are added in 100 milliliters of round-bottomed flasks
Milliliter, Et3N (3mL, 1.59mmol), the tetrahydrofuran solution of Deca phenyllacetyl chloride (1.59mmol), produce precipitation, continue room
Temperature (25 DEG C) stir 12 hours, TLC detect after completion of the reaction, removal of solvent under reduced pressure obtains orange/yellow solid, respectively use ethyl acetate,
Water washing, sucking filtration obtains faint yellow crude product, and solvent recrystallization obtains white solid sterling, yield：89.1%；mp：96.4-
197.4℃；1H-NMR (500MHz, DMSO-d6), δ (ppm)：3.58 (s, 2H, CH2), 3.73 (s, 2H, CH2), 7.23 (s,
1H, Ar-H), 7.31 (m, 2H, Ar-H), 7.32 (m, 1H, Ph-H), 7.33 (m, 2H, Ar-H), 7.35-7.36 (m, 4H, Ar-
H), 10.01 (2H, 2NH), 10.42 (1H, NH- indole)；m/z307.1[M+].
Embodiment 2：N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine contains to Acute Myocardial Ischemia Rats serum NO level
The impact experimental study of amount
Male and healthy Wistar rat 30, weight 220-250g, it is randomly divided into following 3 groups：Normal group, model
Matched group, compound test group, every group 10.On the basis of rat body weight, compound test group rat intravenous injection N- (2-
(1H- indol-3-yl) acetyl group) phenylacetyl hydrazine 20mg/kg, model control group and the life of Normal group equal intravenous injection equal-volume
Reason saline.Each group is all in the daily morning 9：00-10：Drug administration by injection 1 time between 00, continuous 7 days.In the 5th, 6,7 days drug administration by injection
10min afterwards, in addition to Normal group, remaining two groups of rats by intraperitoneal injection isoproterenol 2mg/kg, causes the rat acute heart
Myocardial ischemia model.Last to rat injection isoproterenol after 24h, start ventral aorta blood sampling 3ml be placed in test tube, through from
After scheming 3500r/min centrifugation 10min, extract supernatant, prepare serum sample.Then grasp in strict accordance with NO kit specification
Make, measure rat blood serum NO content's index.After test data statistics, it is shown in Table 1.
Table 1 each group rat blood serum NO comparision contents
Note：Compare with model control group,#P ＜ 0.05,##P ＜ 0.01.
Can be seen that model control group by the result of the test of table 1 to compare with Normal group, under serum NO levels are obvious
Fall (P ＜ 0.01), this shows that success of the test replicates Model Rats with Acute Myocardial Ischemia；In addition, the serum of compound test group
NO content, apparently higher than model control group, is compared for two groups and is respectively provided with pole significant difference (P ＜ 0.01), this imply that N- (2-
(1H- indol-3-yl) acetyl group) phenylacetyl hydrazine has the biological activity of anti-acute myocardial ischemia coronary heart disease.
Embodiment 3：When N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine is to acute myocardial ischemia mice anoxia enduring
Between impact experimental study
The kunming mice 50 of health, weight 18-22g, male and female half and half, it is randomly divided into following 3 groups：Normal group,
Model control group, compound test group, every group 10.On the basis of Mouse Weight, compound test group mouse mainline N-
(2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine 32mg/kg, model control group and the equal intravenous injection of Normal group etc. are held
Long-pending normal saline.Each group is all in the daily morning 9：00-10：Drug administration by injection 1 time between 00, continuous 8 days.In the 8th day drug administration by injection
After 10min, in addition to Normal group, to each group mouse subcutaneous injection isoproterenol 2mg/kg, cause chmice acute cardiac muscle
Ischemia model.After each group injected in mice isoproterenol 15rnin, it is immediately placed in 250ml wide mouthed bottle, bottle cap beyond the Great Wall, bottle stopper
Apply vaseline, record mouse survival time (to the time of respiratory arrest), i.e. hypoxia endurance time.
Table 2 each group mice hypoxia endurance time compares
Note：Compare with model control group,#P ＜ 0.05,##P ＜ 0.01.
Be can be seen that by the result of the test of table 2 and compare with blank control group, Model of Acute Myocardial Ischemia matched group resistance to
Hypoxic exposure significantly shortens (P ＜ 0.01), and this shows that success of the test replicates chmice acute myocardial infarction and ischemia model；In addition, and mould
Type matched group compares, and the hypoxia endurance time of compound test group is all significantly extended, and has pole compared with model control group
Significant difference (P ＜ 0.01), this confirms that N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine has from another point of view
The biological activity of resisting myocardial ischemia property coronary heart disease.
Claims (3)
1.N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine is in the medicine of preparation treatment acute myocardial ischemia coronary heart disease
In application, the structural formula of described N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine is as follows：
2. N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine lacks in preparation treatment Acute myocardial according to claim 1
Application in the medicine of upright coronary heart disease it is characterised in that：Described pharmaceutical composition is injection.
3. N- (2- (1H- indol-3-yl) acetyl group) phenylacetyl hydrazine lacks in preparation treatment Acute myocardial according to claim 2
Application in the medicine of upright coronary heart disease it is characterised in that：Described injection is selected from injection, lyophilized injectable powder.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610792149.7A CN106389419A (en) | 2016-08-31 | 2016-08-31 | Application of arylhydrazide compound in treatment of acute myocardial ischemic coronary heart disease |
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| CN201610792149.7A CN106389419A (en) | 2016-08-31 | 2016-08-31 | Application of arylhydrazide compound in treatment of acute myocardial ischemic coronary heart disease |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602662A (en) * | 2017-08-17 | 2018-01-19 | 河南师范大学 | A kind of preparation method of fragrant hydrazides macrocyclic compounds |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104000809A (en) * | 2014-05-23 | 2014-08-27 | 纪村传 | Medicine composition for preventing and treating angina pectoris of coronary heart disease and application thereof |
| CN105732468A (en) * | 2016-04-07 | 2016-07-06 | 昆明理工大学 | N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound and preparation method and application thereof |
-
2016
- 2016-08-31 CN CN201610792149.7A patent/CN106389419A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104000809A (en) * | 2014-05-23 | 2014-08-27 | 纪村传 | Medicine composition for preventing and treating angina pectoris of coronary heart disease and application thereof |
| CN105732468A (en) * | 2016-04-07 | 2016-07-06 | 昆明理工大学 | N'-(2-(1H-indole-3-yl)acetyl)arylhydrazide compound and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 刘白璐: "《STN检索报告》", 26 March 2019 * |
| 安素红: "吲哚布芬治疗不稳定型心绞痛的疗效观察", 《临床合理用药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107602662A (en) * | 2017-08-17 | 2018-01-19 | 河南师范大学 | A kind of preparation method of fragrant hydrazides macrocyclic compounds |
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