CN107382976A - A kind of compound and preparation method and application for treating pelvic infecton - Google Patents
A kind of compound and preparation method and application for treating pelvic infecton Download PDFInfo
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- CN107382976A CN107382976A CN201710539416.4A CN201710539416A CN107382976A CN 107382976 A CN107382976 A CN 107382976A CN 201710539416 A CN201710539416 A CN 201710539416A CN 107382976 A CN107382976 A CN 107382976A
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- 0 CC(C)(C)OC(*c1c(C(C(F)(F)F)=O)c(C=C(C)c(c(C)c2C)c(C)c(C(*3CC(NC)=C)=O)c2NC*3O)c(C)[n]1)=O Chemical compound CC(C)(C)OC(*c1c(C(C(F)(F)F)=O)c(C=C(C)c(c(C)c2C)c(C)c(C(*3CC(NC)=C)=O)c2NC*3O)c(C)[n]1)=O 0.000 description 2
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the compound and its pharmaceutically acceptable salt or hydrate and its preparation method and application of the treatment pelvic infecton shown in a kind of formula (I), its structure are as follows：
Description
Technical field
The present invention relates to field of medicaments, the more precisely a kind of compound for treating pelvic infecton and preparation method and should
With.
Background technology
The connective tissue of female pelvic cavity reproductive organs and its surrounding, when pelvic peritoneum is inflamed, referred to as pelvic infecton, including
Hysteritis, salpingo-oothecitis, connective tissue inflammation of pelvic cavity and pelvic peritonitis, can at one or a few places fall ill simultaneously, be that women is normal
See one of disease.Due to fallopian tubal, ovary is referred to as annex, and fallopian tubal inflammation involves the ovary of neighbour often.Therefore, there is annex again
The title of inflammation.
The symptom feature of acute pelvitis of pelvic cavity is：Its disease is anxious, state of an illness weight, may occur in which hypogastralgia, has a fever, and shivers with cold, and has a headache, food
It is intended to depressed, finds that patient is in face of acute ill during inspection, fever, heart rate is fast, and lower abdomen has muscle tonue, tenderness and Blumberg's sign, basin
Chamber inspection：Vagina has substantial amounts of purulent secretion, and fornix has obvious tenderness, and uterus and double accessory have tenderness, Blumberg's sign, or side
Annex thickens.The symptom feature of chronic pelvic inflammatory disease is：Its disease is slow, course of disease length, the more unobvious of constitutional symptom, can there is low-heat, susceptible
It is tired, found with lower abdomen pendant pain in the back etc., during inspection, uterus is in often that rear position, limitation of activity, or adhesion are fixed.
The content of the invention
It is an object of the invention to provide a kind of compound and preparation method and application for treating pelvic infecton.
The present invention uses following technical scheme：
The compound and its pharmaceutically acceptable salt or hydrate of a kind for the treatment of pelvic infecton shown in formula (I), its structure
It is as follows：
Described pharmaceutically acceptable salt is the compound and propionic acid, oxalic acid, malonic acid, butanedioic acid, richness that formula (I) represents
The salt that horse acid, maleic acid, lactic acid, malic acid, tartaric acid, the organic acid described in citric acid are formed；Or with hydrochloric acid, phosphoric acid, sulfuric acid,
Inorganic acid forming salt described in hydrofluoric acid, hydrobromic acid；Or the quaternary ammonium salt formed with alkyl halide, the alkyl halide are fluorine, chlorine, bromine or iodine generation
Alkane.
Compound (I) is prepared by the following method to obtain：
Compound 3 is prepared by the following method to obtain：
Compound 2 is prepared by the following method to obtain：
Application of the compound in pelvic infecton medicine is treated a kind of shown in formula (I).
It is an advantage of the invention that：The compound of the present invention can be developed for causing the pathogen significant effect of pelvic infecton
Into clinically effective new pharmaceutical composition.
Embodiment
The embodiment of the present invention is further elucidated below：
The compound and its pharmaceutically acceptable salt or hydrate of a kind for the treatment of pelvic infecton shown in formula (I), its feature
It is, its structure is as follows：
Described pharmaceutically acceptable salt is the compound and propionic acid, oxalic acid, malonic acid, butanedioic acid, richness that formula (I) represents
The salt that horse acid, maleic acid, lactic acid, malic acid, tartaric acid, the organic acid described in citric acid are formed；Or with hydrochloric acid, phosphoric acid, sulfuric acid,
Inorganic acid forming salt described in hydrofluoric acid, hydrobromic acid；Or the quaternary ammonium salt formed with alkyl halide, the alkyl halide are fluorine, chlorine, bromine or iodine generation
Alkane.
The preparation method of compound shown in formula (I), it is characterised in that compound (I) is prepared by the following method to obtain：
Its Structural Identification data is as follows：
ESI-MS(m/z)：643[M-1]-；
1H NMR(CDCl3,300MHz)：δ7.4(m,2H)；δ7.2(m,1H)；δ5.7(m,1H)；δ
4.97-5.03(m,2H)；δ4.05(s,2H)；δ2.71(s,3H)；δ2.46(m,2H)δ2.35(s,9H)；δ1.420
(t,9H)。
Compound 3 is prepared by the following method to obtain：
Compound 2 (0.2g) is dissolved in dry ether (15mL) and added at 20 DEG C dissolved with 0.3mL TFAAs
Dry ether (10mL) in, TLC tracking, post-process, extract, washing, dry after, concentration, obtain solid crude product, recrystallize
To target product.
Its Structural Identification data is as follows：
ESI-MS(m/z)：601[M-1]-；
1H NMR(CDCl3,300MHz)：δ7.8(m,1H)；δ7.5(d,1H)；δ7.3(1,2H)；
δ4.05(s,2H)；δ2.71(s,3H)；δ2.35(s,9H)；δ1.40(m,9H).
Compound 3 is prepared by the following method to obtain：
Compound 1 (0.4mmol) is dissolved in 20mL DMF solutions, adds potassium carbonate (0.8mmol), 80 DEG C of reactions
30min, dichloro n-formyl sarcolysine yl acetamide (0.5mmol) is added, 80 DEG C of reactions are overnight.After reaction terminates, room temperature is cooled to, is added suitable
Water, ethyl acetate extraction are measured, organic layer is washed with saturated sodium-chloride again, and anhydrous magnesium sulfate is dried, and vacuum rotary steam removes organic molten
Agent, through silica gel column chromatography separating-purifying, obtain compound 2.Its Structural Identification data is as follows：
ESI-MS(m/z)：505[M-1]-；
1H NMR(CDCl3,300MHz)：δ7.8(m,1H)；δ7.5(m,1H)；δ7.3(m,1H)；δ6.4(m,1H)；δ
4.05(s,2H)；δ2.71(s,3H)；δ2.35(s,9H)；δ1.40(m,9H).
Embodiment 2
The pharmacodynamic study of formula (I) the treatment rat chronic pelvic infecton of the present invention
1.1 experimental method
SD female rats, 3% yellow Jackets 30mgkg-1After Intravenous Anesthesia, Ventral Midline hair is cut off, cotton ball soaked in alcohol disappears
Poison, in lower abdomen median incision 2cm, uterus is exposed, the syringe needle of 0.2ml syringes is matched somebody with somebody with 0.1ml syringes, in uterus turnoff
Inserting needle enters in uterine cavity, and uterine cavity slowly injects 25% Hydroxybenzene mucilage 0.06ml and makes chronic pelvic inflammatory disease (CPID) rat to the right
Model.
The successful SD rats of modeling are randomly divided into 3 groups (n=12), are respectively：
(1) compound (I) group；
(2) prednisone acetate group (0.0054g/kg/d, 2ml)；
(3) model control group (0.9% physiological saline, 2ml)；The rat (0.9% physiological saline, 2ml) of sham-operation processing.
Other blank control group (0.9% physiological saline, 2ml) does not make any processing.Modeling starts to be administered after 1 week, successive administration 14d.
In 15d, after 3% yellow Jackets intraperitoneal anesthesia rat, abdominal aorta blood sampling, blood routine, hemorheology detection are carried out；
Visually observe the change of rat uterus modeling side anatomic form；Left and right side uterus is won, claims quality respectively, calculates uterus swelling
Rate and swelling inhibiting rate；Right side modeling uterus is taken to be soaked in formalin, HE normal dyeings, optical microphotograph Microscopic observation rat
The pathological change degree in uterus.
With blank control group ratio, uterus swelling significantly raises after model group rats injection of uterus Hydroxybenzene mucilage.With model
Control group compares, and compound (I) group can substantially reduce rat CPID models uterus swelling rate.
The influence of rat CPID models uterus swelling rate caused by the compound of table 1 (I) group Pyrogentisinic Acid's rubber cement
| Group | Dosage | Uterus swelling rate (%) |
| Blank control group | 0.09% physiological saline | 3.23±0.37 |
| Model control group | 0.09% physiological saline | 17.25±0.55 |
| Compound (I) | 5.4mg.kg-1 | 4.98±0.48 |
| Prednisone acetate group | 5.4mg.kg-1 | 14.32±0.60 |
As can be seen from the above table, the influence of rat CPID models uterus swelling rate caused by compound (I) Pyrogentisinic Acid's rubber cement with
Blank control group ratio, uterus swelling significantly raises after model group rats injection of uterus Hydroxybenzene mucilage.Compared with model control group,
Compound (I) can substantially reduce rat CPID models uterus swelling rate, therefore the compound of the present invention can be used for preparing treatment woman
Application in section's anti-inflammatory drugs.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all essences in the present invention
All any modification, equivalent and improvement made within refreshing and principle etc., should be included in the scope of the protection.
Claims (6)
1. the compound and its pharmaceutically acceptable salt or hydrate of the treatment pelvic infecton shown in a kind of formula (I), its feature exist
In its structure is as follows：
2. the compound and its pharmaceutically acceptable salt of the treatment pelvic infecton shown in formula (I) according to claim 1 or
Hydrate, it is characterised in that described pharmaceutically acceptable salt be formula (I) represent compound and propionic acid, oxalic acid, the third two
The salt that acid, butanedioic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, the organic acid described in citric acid are formed；Or and salt
Acid, phosphoric acid, sulfuric acid, hydrofluoric acid, the inorganic acid forming salt described in hydrobromic acid；Or the quaternary ammonium salt formed with alkyl halide, the alkyl halide are
Fluorine, chlorine, bromine or iodine are for alkane.
3. the preparation method of compound shown in a kind of formula (I), it is characterised in that compound (I) is prepared by the following method to obtain:
4. the preparation method of compound shown in formula (I) according to claim 3, it is characterised in that compound 3 is by following
Method is prepared：
5. the preparation method of compound shown in formula (I) according to claim 4, it is characterised in that compound 2 is by following
Method is prepared：
6. a kind of compound as claimed in claim 1 is preparing the application in treating pelvic infecton medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710539416.4A CN107382976A (en) | 2017-07-04 | 2017-07-04 | A kind of compound and preparation method and application for treating pelvic infecton |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710539416.4A CN107382976A (en) | 2017-07-04 | 2017-07-04 | A kind of compound and preparation method and application for treating pelvic infecton |
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| CN107382976A true CN107382976A (en) | 2017-11-24 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710539416.4A Pending CN107382976A (en) | 2017-07-04 | 2017-07-04 | A kind of compound and preparation method and application for treating pelvic infecton |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1498212A (en) * | 2001-03-21 | 2004-05-19 | ��������ʲ��������ι�˾ | New spirotricyclic derivatives and their use as phosphodiesterase-7-inhibitors |
| CN101743229A (en) * | 2007-07-13 | 2010-06-16 | 默克专利有限公司 | quinazolinamide derivatives |
| EP1836174B1 (en) * | 2004-10-01 | 2013-02-27 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and their use as kinase inhibitors |
| WO2016053771A1 (en) * | 2014-09-30 | 2016-04-07 | Merck Sharp & Dohme Corp. | Inhibitors of irak4 activity |
-
2017
- 2017-07-04 CN CN201710539416.4A patent/CN107382976A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1498212A (en) * | 2001-03-21 | 2004-05-19 | ��������ʲ��������ι�˾ | New spirotricyclic derivatives and their use as phosphodiesterase-7-inhibitors |
| EP1836174B1 (en) * | 2004-10-01 | 2013-02-27 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and their use as kinase inhibitors |
| CN101743229A (en) * | 2007-07-13 | 2010-06-16 | 默克专利有限公司 | quinazolinamide derivatives |
| WO2016053771A1 (en) * | 2014-09-30 | 2016-04-07 | Merck Sharp & Dohme Corp. | Inhibitors of irak4 activity |
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Application publication date: 20171124 |