CN105982894A - Application of isoindolinone compounds in preparing medicines for preventing and treating inflammatory bowel diseases and preparation for preventing and treating inflammatory bowel diseases - Google Patents
Application of isoindolinone compounds in preparing medicines for preventing and treating inflammatory bowel diseases and preparation for preventing and treating inflammatory bowel diseases Download PDFInfo
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Abstract
The invention discloses an application of at least one of isoindolinone compounds in preparing medicines for preventing and treating inflammatory bowel diseases; the isoindolinone compounds include a compound as shown in formula (1) and a compound as shown in formula (2), wherein in the formula (1) and the formula (2), R1 and R2 are same or different and independently represent H or R, and R is shown as Formula (referring to Description), wherein n is an integer ranging from 0 to 2 and X is either hydrogen or halogen. The invention also discloses a preparation for preventing and treating the inflammatory bowel diseases, wherein the preparation consists of an active ingredient and adjuvant materials; the active ingredient includes at least one of the isoindolinone compounds; and the isoindolinone compounds include the compound as shown in formula (1) and the compound as shown in formula (2). The medicines containing the isoindolinone compounds disclosed by the invention, when used for preventing and treating the inflammatory bowel diseases, can achieve good preventing and treating effects (referring to Description).
Description
Technical field
The present invention relates to field of medicaments, in particular it relates to a kind of indolinone compounds is in preparation prevention
With the application in the medicine for the treatment of inflammatory bowel and a kind of preparation for preventing and treat inflammatory bowel.
Background technology
Inflammatory bowel, is called for short IBD, is a kind of special chronic gut inflammation disease, mainly include gram
Sieve grace sick (CD) and colitis (especially, such as ulcerative colitis (UC)).Over nearly 30 years,
China's IBD sickness rate has the most soaring trend.Reporting according to domestic literature, the case load of nearly 5 years is
8 times of the same period nineties in last century, IBD has been increasingly becoming the commonly encountered diseases of Gastroenterology dept. of China.IBD's
The cause of disease and pathogenesis are not yet completely clearly, it is known that Intestinal Mucosal Immunization system exception reacts the inflammation caused
Disease reaction plays an important role in IBD falls ill, it is believed that this is by caused by multifactor interaction, mainly wraps
Include environment, heredity, infection and immune factor, the inheritance susceptible that wherein specific gene sudden change or disappearance cause
Property is a key factor.
Ulcerative colitis is one of principal mode of IBD, and typical characteristic is the chronic inflammation of colon and rectum
Disease.In recent years, UC sickness rate presents the trend gradually risen.There is mucus or non-mucus in patient UC
Property hemafecia, suffer from abdominal pain, generate heat and weight loss.UC mechanism of causing a disease occurs mainly due to inside large intestine
The abnormal immune reaction that circumstances not known factor causes.Research show inflammation cytokine, including IL-4,
IL-5, IL-6, IL-10 and TNF α etc. play a significant role in mediated immunity reacts.To its machine of falling ill
The further investigation of system has caused the discovery of the medicine of the multiple targeting inflammatory factor of UC.These targeting
Medicine is different from conventional medicament, will not suppress overall immune system, and mechanism of action is the most special.At this
In a little inflammatory factors, the research to TNF α is the most extensive.TNF α is drenched by the macrophage activated and T
Bar emiocytosis, and cause on activation, the vascular endothelial cell further of macrophage and T lymphocyte
The expression of adhesion molecule and the gathering of neutrophilic granulocyte, finally cause degree of inflammation constantly to strengthen.At UC
The colon of patient, serum, feces and urine can detect that, the level of TNF α is significantly raised.Cause
This, TNF α is the target spot had a great attraction of biological preparation.
U.S. FDA has been approved by three kinds of TNF α antagonist for treating UC and Crohn disease (CD).
Although the treatment of TNF α antagonist achieves certain effect, but still has some patients to need corticosteroids
There is primary or insecondary TNF α antagonist resistance in treatment.
The situation of failure in treatment is generally divided into two classes: constitutional lost efficacy and secondary failure.In primary inefficacy
In patient, first use medicine can not alleviate clinical symptoms.In secondary failure patient, just
Secondary treatment is effective, but the most gradually loses curative effect in successive treatment.Therefore, other Inflammatory Pathway key because of
Son is also developed to the target spot of medicine.These factors include the adhesion molecule participating in lymphocyte transmigration
(integrin, ICAM, VCAM etc.), other cytokines (such as IL-12, IL-23, IL-10)
And t lymphocyte receptor (CD28, CD25) etc..
Colitis is the most important risk factor that colon cancer occurs.There is colon in the patient of ulcerative colitis
The probability of cancer is higher than normal person, statistics display: the canceration rate of left hemicolon inflammation patient is the 2.8 of normal person
Times, the canceration rate of pancolitis patient is normal person 15 times, and the pancolitis patient of onset childhood
Canceration rate is 162 times of normal person.
Therefore, develop and a kind of new there is important meaning for preventing and treat the medicine of inflammatory bowel disease
Justice.
Summary of the invention
It is an object of the invention to provide a kind of indolinone compounds in preparation prevention and treatment inflammatory bowel
The sick application in medicine and a kind of preparation for preventing and treat inflammatory bowel.
To achieve these goals, on the one hand, the present invention provides in a kind of indolinone compounds extremely
Few a kind of application in the medicine of preparation prevention and treatment inflammatory bowel, described indolinone compounds
Including the compound shown in the compound shown in formula (1) and formula (2),
Wherein, in formula (1) and formula (2), R1And R2Identical or different, it is each independently H
Or R, and R isN is the integer of 0-2, and X is hydrogen or halogen.
On the other hand, the present invention provides a kind of preparation for preventing and treat inflammatory bowel, in said preparation
Containing active component and adjuvant, described active component includes at least one in indolinone compounds,
In terms of the gross weight of described preparation, the content of described indolinone compounds is 0.5-100 weight %,
Described indolinone compounds includes the compound shown in formula (1) and the compound shown in formula (2),
Wherein, in formula (1) and formula (2), R1And R2Identical or different, it is each independently H
Or R, and R isN is the integer of 0-2, and X is hydrogen or halogen.
It is used for preventing and treating inflammatory bowel by the medicine containing indolinone compounds of the present invention
Well prevention and therapeutic effect can be obtained time sick, and, of the present invention containing indoline ketone
The drug toxicity of compound is low, bioavailability is high.
Further, of the present invention for preventing and treating the preparation of inflammatory bowel in prevention and treatment
There is during inflammatory bowel well prevention and therapeutic effect, and, of the present invention for preventing and controlling
The preparation treating inflammatory bowel also has the advantage that toxicity is low and bioavailability is high.
Especially, from the result of embodiments of the invention it can be seen that indolinone compounds can be pre-
Anti-inflammatory bowel, and suppress Mouse Weight to decline, after giving DSS, take indoline ketone in advance
The disease index of the mice of compound is significantly lower than the mice taking indolinone compounds the most in advance
Disease index.And, indolinone compounds can suppress the mouse Colon length contracting that DSS causes
Short.Pathology detection finds to take the colon structure that indolinone compounds can suppress DSS to induce in advance
Destroy and cell infiltration.
Further, the result of embodiments of the invention also shows: indolinone compounds can be treated
Inflammatory bowel, and suppress Mouse Weight to decline, after giving DSS, the body weight of each group mice is universal
Reducing, disease index increases, and after being administered indolinone compounds, it is possible to substantially suppress mice
Body weight reduces, and reduces disease index, and presents dosage effect dependency.And, indoline ketone chemical combination
Thing can treat the mouse Colon contraction in length caused by DSS.Pathology detection finds indoline ketone
Compound can be treated the colon structure induced by DSS and be destroyed and cell infiltration.
Other features and advantages of the present invention will be described in detail in detailed description of the invention part subsequently.
Detailed description of the invention
Hereinafter the detailed description of the invention of the present invention is described in detail.It should be appreciated that this place is retouched
The detailed description of the invention stated is merely to illustrate and explains the present invention, is not limited to the present invention.
On the one hand, the invention provides at least one in a kind of indolinone compounds in preparation prevention
With the application in the medicine for the treatment of inflammatory bowel, described indolinone compounds includes shown in formula (1)
Compound and formula (2) shown in compound,
Wherein, in formula (1) and formula (2), R1And R2Identical or different, it is each independently H
Or R, and R isN is the integer of 0-2, and X is hydrogen or halogen.
In the present invention, described n can be the arbitrary integer in 0,1 and 2.
In the present invention, at least one during described halogen includes fluorine, chlorine, bromine and iodine.
In the present invention, it should be strongly noted that in R, the position of substitution of described X is not had
Particularly limit, can be any one in ortho position, meta and para-orientation.
In the present invention, to the amount ratio of various indolinone compounds, there is no particular limitation, ability
Field technique personnel can be according to the conventional amount used ratio in this area after having understood technical scheme
Example selects.
In the present invention, to the preparation method of described indolinone compounds, there is no particular limitation, this
Skilled person can prepare indoline ketone of the present invention according to the common knowledge in this area
Compound.In the case of Te Bieyouxuan, indolinone compounds of the present invention can basis
The method provided in CN101314584A prepares.
Under preferable case, in the present invention, described indolinone compounds can include formula (3) institute
Shown in compound, the compound shown in formula (5) and formula (6) shown in the compound that shows, formula (4)
Compound,
It is to say, at least one in the indolinone compounds of the present invention in preparation prevention and is controlled
Treating in the application in the medicine of inflammatory bowel, described indolinone compounds can include formula (3) institute
Shown in compound, the compound shown in formula (5) and formula (6) shown in the compound that shows, formula (4)
Compound at least one.
According to a kind of preferred embodiment of the present invention, in the present invention, described indoline ketone
Compound is shown in the compound shown in the compound shown in above-mentioned formula (3), formula (4), formula (5)
Compound and formula (6) shown in compound.In the present invention, when described indolinone compounds
For the compound shown in the compound shown in formula (3), formula (4), the compound shown in formula (5) and
During compound shown in formula (6), to the compound shown in the compound shown in formula (3), formula (4),
There is no particular limitation for the usage ratio of the compound shown in formula (5) and the compound shown in formula (6),
Those skilled in the art can select the amount ratio of above-mentioned four kinds of compounds, example in the most wide in range scope
As, embodiments of the invention exemplarily employ above-mentioned four kinds of compounds of identical mol ratio for making
The medicine of standby treatment inflammatory bowel, those skilled in the art should not be construed as the limit to the scope of the present invention
System.
According to the another kind of preferred embodiment of the present invention, in the present invention, described indolinone
Compounds is the compound shown in formula (3),
At least one in the indolinone compounds of the present invention is in preparation prevention and treatment inflammatory bowel
In the sick application in medicine, in described medicine, the content of described indolinone compounds can be
0.5-100 weight %, particularly preferably in the case of, the content of described indolinone compounds is 5-95 weight
Amount %.
At least one in indolinone compounds according to the present invention is at preparation prevention and treatment inflammatory
Application in the medicine of enteropathy, described medicine can be pill, unguentum, tablet, oral solutions, subcutaneous
At least one in injection and intravenous injection.
At least one in indolinone compounds according to the present invention is at preparation prevention and treatment inflammatory
Application in the medicine of enteropathy, the most described inflammatory bowel includes colitis.
On the other hand, the invention provides a kind of preparation for preventing and treat inflammatory bowel, said preparation
In containing active component and adjuvant, described active component includes at least in indolinone compounds
Kind, in terms of the gross weight of described preparation, the content of described indolinone compounds is 0.5-100 weight %,
Described indolinone compounds includes the compound shown in formula (1) and the compound shown in formula (2),
Wherein, in formula (1) and formula (2), R1And R2Identical or different, it is each independently H
Or R, and R isN is the integer of 0-2, and X is hydrogen or halogen.
According to the preparation for preventing and treat inflammatory bowel of the present invention, under preferable case, described
The content of indolinone compounds is 5-95 weight %.
According to the preparation for preventing and treat inflammatory bowel of the present invention, the most described indolinone
Compounds includes shown in the compound shown in the compound shown in formula (3), formula (4), formula (5)
Compound and formula (6) shown in compound,
In the case of Te Bieyouxuan, of the present invention for preventing and treating in the preparation of inflammatory bowel,
Described indolinone compounds is the compound shown in formula (3),
Of the present invention for preventing and treating in the preparation of inflammatory bowel, described preparation can include
At least one in pill, unguentum, tablet, oral solutions, subcutaneous injection agent and intravenous injection.
It is used for preventing and treating inflammatory bowel by the medicine containing indolinone compounds of the present invention
Well prevention and therapeutic effect can be obtained time sick, and, of the present invention containing indoline ketone
The drug toxicity of compound is low, bioavailability is high.
Further, of the present invention for preventing and treating the preparation of inflammatory bowel in prevention and treatment
There is during inflammatory bowel well prevention and therapeutic effect, and, of the present invention for preventing and controlling
The preparation treating inflammatory bowel also has the advantage that toxicity is low and bioavailability is high.
Hereinafter will be described the present invention by embodiment.In following example, the most especially
In the case of explanation, the various reagent used and material are all from commercially available.
In the examples below, the indolinone compounds used carries according in CN101314584A
The method of confession prepares.
Mice inflammatory bowel (colitis) model that dextran sulfate sodium (DSS) is induced is at present should
Use most commonly used model, as the important tool in IBD and colon cancer research.The present invention with
The colitis model using DSS induction in lower embodiment evaluates indolinone compounds to IBD, spy
Not, the preventive and therapeutic action to colitis.
The mice used in the examples below is purchased from laboratory animal Technology Co., Ltd. of dimension tonneau China.?
In following example, the body weight of described mice is the Weight averages ± standard deviation (g) of each group of mice.
In the examples below, the evaluation methodology of disease index is as shown in table 1:
Table 1
| Score | Weight loss (%) | Stool hardness | Have blood in stool/occult blood |
| 0 | - | Normally | Normally |
| 1 | 1-5 | Nothing | Nothing |
| 2 | 5-10 | Loose | Occult blood |
| 3 | 11-15 | Loose | Occult blood |
| 4 | >15 | Watery stool | Hemorrhage |
Embodiment 1
The present embodiment is used for illustrating that the compound shown in formula of the present invention (3) is at preparation prevention inflammatory
Application in the medicine of enteropathy.
Select 50 mices, be randomly divided into 5 groups, be respectively designated as low dose group, middle dosage group, high agent
Amount group, matched group 1 and matched group 2.According to the dose requirements of each dosage group, take appropriate formula (3) respectively
Shown compound is dissolved in sodium carboxymethyl cellulose (CMC-Na) aqueous solution of 0.5 weight %, presses
Using gavage mode to be administered each mice according to the dosage in table 2, dosage period is 7 days, and once a day,
Meanwhile, matched group 1 and matched group 2 are given the 0.5 of same volume (200 microlitres, lower same) every time
The CMC-Na aqueous solution of weight % carries out gavage process, stops after being administered 7 days according to above-mentioned administering mode
It is administered, changes into all giving low dose group, middle dosage group, high dose group and matched group 1 mice to feed modeling
Water (containing the DSS of 3 weight % in this modeling water, lower same) 7 days, and matched group 2 is the most just giving
Often feed water (not containing DSS in this water, lower same) 7 days, and measure the body weight of each group of mice every day,
Weight averages ± the standard deviation (g) taking each group of mice is reported in Table 3 below, and after 7 days, disconnected neck puts to death each group
Mice, dissects and detects average length and the pathologic condition of each group of mouse Colon, be reported in Table 2 below.And
And evaluate the disease index (diarrhoea, the comprehensive evaluation index of fecal occult blood) putting to death front each group mice, note
Record in table 2.
Above-mentioned to the compound shown in formula (3) with in the DSS cycle, every day is given respectively by normal appetite
Organize mouse feeding and measurement and record the Weight averages ± standard deviation (g) of mice.
Table 2
Table 3
| 1st day | 2nd day | 3rd day | 4th day | 5th day | 6th day | 7th day | |
| Low dose group | 21.5±1.1 | 21.4±0.7 | 21.3±1.2 | 21.4±0.8 | 21.4±1.2 | 21.6±0.7 | 21.8±1.2 |
| Middle dosage group | 21.6±1.4 | 21.5±1.1 | 21.4±0.9 | 21.5±0.7 | 21.7±1.2 | 21.9±1.2 | 22.2±0.9 |
| High dose group | 21.5±0.9 | 21.4±1.1 | 21.5±0.8 | 21.7±1.2 | 22.1±0.8 | 22.5±0.7 | 22.8±1.2 |
| Matched group 1 | 21.6±0.9 | 21.5±1.3 | 21.1±1.1 | 20.8±0.9 | 20.3±1.2 | 19.8±0.8 | 19.2±0.7 |
| Matched group 2 | 21.5±1.2 | 21.7±1.1 | 21.9±0.7 | 22.2±1.2 | 22.7±0.7 | 23.5±0.9 | 24.1±1.2 |
Embodiment 2
The present embodiment is used for illustrating shown in the compound shown in formula of the present invention (3), formula (4)
The compositions that compound shown in compound, formula (5) and the compound shown in formula (6) are formed is in preparation
Application in the medicine of prophylaxis of inflammatory bowel disease, wherein, in the present embodiment, formula (3) institute used
Shown in compound, the compound shown in formula (5) and formula (6) shown in the compound that shows, formula (4)
The consumption mol ratio of compound be 1:1:1:1.
The present embodiment uses method same as in Example 1 to carry out, except that, indoline ketone
The kind of compound is different, say, that the indolinone compounds used in embodiment 1 is only formula (3)
Shown compound, and in the present embodiment use indolinone compounds be mol ratio be 1:1:1:
Compound shown in the compound shown in formula (3) of 1, formula (4), the compound shown in formula (5) and
Compound shown in formula (6).Remaining is the most in the same manner as in Example 1.
In the present embodiment, the corresponding situation of each group mice is listed in table 4 and table 5.
Table 4
Table 5
| 1st day | 2nd day | 3rd day | 4th day | 5th day | 6th day | 7th day | |
| Low dose group | 20.5±0.8 | 20.4±0.6 | 20.4±1.4 | 20.4±0.7 | 20.5±1.1 | 20.6±0.9 | 20.9±1.5 |
| Middle dosage group | 20.4±0.5 | 20.3±1.2 | 20.4±1.4 | 20.6±1.2 | 20.8±1.4 | 21.1±1.3 | 21.4±1.7 |
| High dose group | 20.5±0.7 | 20.4±0.9 | 20.5±1.2 | 20.8±1.3 | 21.1±1.5 | 21.5±1.7 | 21.9±1.3 |
| Matched group 1 | 20.6±0.7 | 20.4±1.3 | 20.1±1.4 | 19.7±1.9 | 19.2±1.4 | 18.6±1.48 | 18.2±1.7 |
| Matched group 2 | 20.5±1.1 | 20.7±1.3 | 20.9±0.8 | 21.2±1.3 | 21.7±1.7 | 22.5±1.9 | 23.1±1.8 |
From the result of above-described embodiment 1 and embodiment 2 it can be seen that indolinone compounds can be pre-
Anti-colitis, and suppress Mouse Weight to decline, after giving DSS, take indoline ketone in advance
The disease index of the mice of compound is significantly lower than the disease of the mice taking indolinone compounds the most in advance
Sick index, and present dosage effect dependency.And, indolinone compounds can suppress DSS
The mouse Colon contraction in length caused.Pathology detection finds that taking indolinone compounds in advance can suppress
The colon structure of DSS induction destroys and cell infiltration.
Embodiment 3
The present embodiment is used for illustrating that the compound shown in formula of the present invention (3) is at preparation treatment inflammatory
Application in the medicine of enteropathy.
Selecting 50 mices, be randomly divided into 5 groups, take 1 group of named matched group 2, remaining 4 groups are mixed at random
Support and treat to be grouped further.Matched group 2 is given the most normal hello water, all gives to feed to remaining 4 groups to make
Mould water (containing the DSS of 3 weight %), continuous 7 days.After 7, above-mentioned 4 groups raised together with are re-started
Random packet, and it is respectively designated as low dose group, middle dosage group, high dose group and matched group 1.Press
Being administered each dosage group respectively according to the dose requirements in table 6, concrete medication is: take suitable respectively
Compound shown in amount formula (3) is dissolved in the CMC-Na aqueous solution of 0.5 weight %, according in table 6
Dosage use lumbar injection mode (injection volume is 200 microlitres) respectively to low dose group, middle dosage group
Being administered with high dose group mice, matched group 1 then gives 0.5 weight % of lumbar injection same volume
CMC-Na aqueous solution, dosage period is 7 days, is administered once a day, and matched group 2 is just still giving
Often feed water, measure the body weight ± standard deviation (g) of each group of mice, be reported in Table 7 below every day.
Stop experiment after 7 days, evaluate the disease index of each group of mice in table 6, and disconnected neck puts to death low dose
Amount group, middle dosage group, high dose group, matched group 1 and the mice of matched group 2, dissect and detect each group
The average length of mouse Colon and pathologic condition, be reported in Table 6 below.
Table 6
Table 7
| 1st day | 2nd day | 3rd day | 4th day | 5th day | 6th day | 7th day | |
| Low dose group | 18.2±1.5 | 18.0±0.9 | 18.1±1.5 | 18.1±1.6 | 18.3±2.1 | 18.5±2.3 | 18.8±2.8 |
| Middle dosage group | 18.2±1.4 | 18.1±1.5 | 18.0±1.2 | 18.2±2.1 | 18.3±2.5 | 18.7±2.4 | 19.2±2.6 |
| High dose group | 18.2±1.5 | 18.1±1.3 | 18.3±1.9 | 18.5±2.2 | 18.8±2.1 | 19.2±2.5 | 19.7±2.2 |
| Matched group 1 | 18.2±1.6 | 17.9±1.2 | 17.6±1.5 | 17.2±1.3 | 16.7±1.9 | 16.2±2.1 | 15.6±2.3 |
| Matched group 2 | 22.8±1.3 | 23.1±1.5 | 23.5±1.6 | 23.9±1.7 | 24.3±2.1 | 24.8±1.6 | 25.3±2.6 |
Embodiment 4
The present embodiment is used for illustrating shown in the compound shown in formula of the present invention (3), formula (4)
The compositions that compound shown in compound, formula (5) and the compound shown in formula (6) are formed is in preparation
Application in the medicine for the treatment of inflammatory bowel, wherein, in the present embodiment, formula (3) institute used
Shown in compound, the compound shown in formula (5) and formula (6) shown in the compound that shows, formula (4)
The consumption mol ratio of compound be 1:1:1:1.
The present embodiment uses method same as in Example 3 to carry out, except that, indoline ketone
The kind of compound is different, say, that the indolinone compounds used in embodiment 3 is only formula (3)
Shown compound, and in the present embodiment use indolinone compounds be mol ratio be 1:1:1:
Compound shown in the compound shown in formula (3) of 1, formula (4), the compound shown in formula (5) and
Compound shown in formula (6).Remaining is the most in the same manner as in Example 3.
In the present embodiment, the corresponding situation of each group mice is listed in table 8 and table 9.That is, table 8 is each group little
Mus is to acquisition after the dosage of indolinone compounds, the disease index in experimental period and dissection
Colon average length and pathologic condition；Table 9 represents that each group of mice is in the week being administered indolinone compounds
Weight averages ± the standard deviation (g) of interim every day.
Table 8
Table 9
| 1st day | 2nd day | 3rd day | 4th day | 5th day | 6th day | 7th day | |
| Low dose group | 18.2±1.5 | 18.0±0.7 | 18.0±1.4 | 18.1±1.6 | 18.2±2.7 | 18.4±2.5 | 18.6±2.2 |
| Middle dosage group | 18.2±1.4 | 18.0±1.8 | 18.1±1.2 | 18.2±2.5 | 18.4±2.7 | 18.7±2.8 | 19.0±29 |
| High dose group | 18.2±1.4 | 18.1±1.7 | 18.2±2.1 | 18.4±2.4 | 18.7±2.5 | 19.2±2.45 | 19.8±2.2 |
| Matched group 1 | 18.2±1.6 | 17.9±1.3 | 17.7±1.4 | 17.4±1.7 | 17.0±1.6 | 16.7±2.2 | 16.3±2.3 |
| Matched group 2 | 22.5±1.2 | 22.8±1.5 | 23.2±1.7 | 23.6±1.9 | 23.9±2.2 | 24.1±1.8 | 23.4±2.7 |
From the result of above-described embodiment 3 and embodiment 4 it can be seen that indolinone compounds can be controlled
Treating colitis, and suppress Mouse Weight to decline, after giving DSS, the body weight of each group mice is universal
Reduce, and disease index is high, and after being administered indolinone compounds, it is possible to substantially suppress mice
Body weight reduce and can substantially make mice in the later stage in cycle being administered indolinone compounds
Body weight increase, and disease index substantially reduces, and presents dosage effect dependency.And, indoline
Ketone compounds can treat the mouse Colon contraction in length caused by DSS.Pathology detection finds indole
Quinoline ketone compounds can be treated the colon structure induced by DSS and be destroyed and cell infiltration.
The preferred embodiment of the present invention described in detail above, but, the present invention is not limited to above-mentioned reality
Execute the detail in mode, in the technology concept of the present invention, can be to the technical side of the present invention
Case carries out multiple simple variant, and these simple variant belong to protection scope of the present invention.
It is further to note that each the concrete technology described in above-mentioned detailed description of the invention is special
Levy, in the case of reconcilable, can be combined by any suitable means, in order to avoid need not
The repetition wanted, various possible compound modes are illustrated by the present invention the most separately.
Additionally, combination in any can also be carried out between the various different embodiment of the present invention, as long as its
Without prejudice to the thought of the present invention, it should be considered as content disclosed in this invention equally.
Claims (10)
1. at least one in indolinone compounds is at preparation prevention and the medicine for the treatment of inflammatory bowel
In application, described indolinone compounds includes shown in the compound shown in formula (1) and formula (2)
Compound,
Wherein, in formula (1) and formula (2), R1And R2Identical or different, it is each independently H
Or R, and R isN is the integer of 0-2, and X is hydrogen or halogen.
Application the most according to claim 1, wherein, described indolinone compounds includes formula
(3) compound shown in the compound shown in the compound shown in, formula (4), formula (5) and formula (6)
Shown compound,
Application the most according to claim 1, wherein, described indolinone compounds is formula (3)
Shown compound,
4. according to the application described in any one in claim 1-3, wherein, in described medicine,
The content of described indolinone compounds is 0.5-100 weight %.
5. according to the application described in any one in claim 1-4, wherein, described medicine be pill,
At least one in unguentum, tablet, oral solutions, subcutaneous injection agent and intravenous injection.
6. according to the application described in any one in claim 1-4, wherein, described inflammatory bowel bag
Include colitis.
7. for preventing and treat the preparation of inflammatory bowel, containing active component and auxiliary in said preparation
Material, it is characterised in that described active component includes at least one in indolinone compounds, with institute
Stating the gross weight meter of preparation, the content of described indolinone compounds is 0.5-100 weight %, described
Indolinone compounds includes the compound shown in formula (1) and the compound shown in formula (2),
Wherein, in formula (1) and formula (2), R1And R2Identical or different, it is each independently H
Or R, and R isN is the integer of 0-2, and X is hydrogen or halogen.
Preparation the most according to claim 7, wherein, the content of described indolinone compounds
For 5-95 weight %.
9. according to the preparation described in claim 7 or 8, wherein, described indolinone compounds bag
Include the compound shown in the compound shown in the compound shown in formula (3), formula (4), formula (5) and
Compound shown in formula (6),
The most described indolinone compounds is the compound shown in formula (3),
10. according to the preparation described in any one in claim 7-9, wherein, described preparation includes ball
At least one in agent, unguentum, tablet, oral solutions, subcutaneous injection agent and intravenous injection.
Priority Applications (1)
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107773559A (en) * | 2016-08-31 | 2018-03-09 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Application of the indoline ketone compounds in the medicine for preparing prophylactic treatment pulmonary fibrosis and the preparation for prophylactic treatment pulmonary fibrosis |
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| CN101314584A (en) * | 2007-05-28 | 2008-12-03 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | HGF/c-Met signalling channel restrainer, preparation method and application thereof |
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| CN101314584A (en) * | 2007-05-28 | 2008-12-03 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | HGF/c-Met signalling channel restrainer, preparation method and application thereof |
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| ANIKA E. WAGNERA等: "DSS-induced acute colitis in C57BL /6 mice is mitigated by sulforaphane pre-treatment", 《JOURNAL OF NUTRITIONAL BIOCHEMISTRY》 * |
| JIA-WEI YAO等: "Induction of activation of the antioxidant response element and stabilization of Nrf2 by 3-(3-pyridylmethylidene)-2-indolinone (PMID) confers protection against oxidative stress-induced cell death", 《TOXICOLOGY AND APPLIED PHARMACOLOGY》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107773559A (en) * | 2016-08-31 | 2018-03-09 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Application of the indoline ketone compounds in the medicine for preparing prophylactic treatment pulmonary fibrosis and the preparation for prophylactic treatment pulmonary fibrosis |
| CN107773559B (en) * | 2016-08-31 | 2021-06-15 | 中国人民解放军军事科学院军事医学研究院 | Application of indolinone compound in preparation of medicine for preventing and treating pulmonary fibrosis |
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