CN107892687A - A kind of 2 acetic acid esters glyoxaline compound and its application in medicine for treating osteoporosis is prevented and treated - Google Patents

A kind of 2 acetic acid esters glyoxaline compound and its application in medicine for treating osteoporosis is prevented and treated Download PDF

Info

Publication number
CN107892687A
CN107892687A CN201810056718.0A CN201810056718A CN107892687A CN 107892687 A CN107892687 A CN 107892687A CN 201810056718 A CN201810056718 A CN 201810056718A CN 107892687 A CN107892687 A CN 107892687A
Authority
CN
China
Prior art keywords
compound
bone
acetic acid
medicine
osteoporosis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201810056718.0A
Other languages
Chinese (zh)
Other versions
CN107892687B (en
Inventor
吕迎春
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangdong Lane Pharmaceutical Research Institute Co Ltd
Original Assignee
吕迎春
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 吕迎春 filed Critical 吕迎春
Priority to CN201810056718.0A priority Critical patent/CN107892687B/en
Priority to CN201810717633.2A priority patent/CN108912103A/en
Publication of CN107892687A publication Critical patent/CN107892687A/en
Application granted granted Critical
Publication of CN107892687B publication Critical patent/CN107892687B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis

Abstract

The invention discloses a kind of 2 acetic acid esters glyoxaline compounds, its structural formula is

Description

A kind of 2- acetic acid esters glyoxaline compound and its in medicine for treating osteoporosis is prevented and treated Using
Technical field
The invention belongs to drug design and synthesis field, is related to a kind of 2- acetic acid esters glyoxaline compound and its in preventing and treating bone Application in the loose medicine of matter.
Technical background
Osteoporosis is a health problem that is worldwide, increasingly attracting people's attention.The whole world about 2 at present Hundred million people suffer from osteoporosis, its incidence of disease leapt to common disease, the 7th of frequently-occurring disease.Osteoporosis is that the elderly is most common Disease.In the U.S. and western countries, at the age more than 55 years old in postclimacteric women, the people for having half suffers from the different bone of degree Matter osteoporosis, and suffer from osteoporosis person in the elderly of over-65s and be up to more than 95%.With the reach of science and the mankind Progressive, the average life span constantly extends, and elderly population increase sharply, and the incidence of disease of osteoporosis is also with appearance rapidly increase. It is expected that the elderly to the year two thousand fifty whole world over-65s will increase to 15.55 hundred million by current 3.23 hundred million, osteoporosis is led at that time Cause hip fracture that number occurs also will increase to 6,260,000, wherein Asia, Latin America, the Middle East and African state by current 1,660,000 The patient of family will account for more than 70%.Osteoporosis causes huge society and financial burden, constitute one it is serious global Problem, the very big concern of countries in the world is caused.The arrival of aging society makes the incidence of osteoporosis increase increasingly, sternly The quality of life of people is threatened again.
The osteoporosis epidemiology survey result in China Beijing, Shanghai and the city of Chengdu 3 shows, 60-69 year age bracket bone The loose incidence women of matter and male are respectively 60% and 30% or so.China human mortality radix is big, and sufferers of osteoporosis face has reached 60000000~80,000,000, this brings serious burden to family and society.According to another the people of statistics national over-65s in 2000 Have 1.3 hundred million, account for the 10.7% of national population, it has also become typical veteran form country.And the patient with osteoporosis is at these 90% is accounted in crowd, and the patient of hip fracture will have 12%~40% to die from various complication in 1 year.In survivor There is 50% human action inconvenience.This not only causes serious body and mind to patient and wrecked, while also adds to family and society huge Big manpower and financial resources burden.Therefore, it is anti-aging to prevent and treat osteoporosis, extends the life-span, ensures the one of the quality of life of the people Individual very urgent research topic.
Osteoclast is a kind of terminal differentiation multinuclear macrophage originating from candidate stem cell, is uniquely joined in Bone m etabolism With the cell of bone information, it is in bone tissue this microenvironment by portion perimeter blood (spleen) monocyte and monokaryon of derived from bone marrow The osteoclastic precursor fusion of macrophage forms.Key link in bone remodeling is the bone information of osteoclast, and it is stable normal It is very important in bone homeostasis process.Some medicines such as bisphosphonates, calcitonin surround in anti-bone information medicine Osteoclast deploys, and bone information is reduced to prevent or treat osteoporosis by suppressing the activity of osteoclast.
The content of the invention
An object of the present invention is to provide a kind of 2- acetic acid esters glyoxaline compound, and its structural formula is as follows：
。
Another object of the present invention is to provide a kind of application of compound in osteoclast increment medicine is suppressed.
Another object of the present invention is to provide a kind of compound to prepare prevention and/or treatment medicine for treating osteoporosis In application.
Another object of the present invention is to provide a kind of synthetic route of the compound to be：
。
Further, its specific synthesis step is：
1) 3- phenyl-1-propanols (compound 1) are with occurring sulfonylation generation methanesulfonic acid 3- benzene under paratoluensulfonyl chloride low temperature Base propyl ester (compound 2)；
2) heating response generates 1- (3- (3- to compound 2 in the presence of an inorganic base with 1- (3- hy droxy furan -2- bases) second -1- ketone again Phenyl-propoxy) furans -2- bases) second -1- ketone (compound 3)；
3) bromo-reaction generation 2- bromo- 1- (3- (the 3- phenyl third of carbonyl α-carbon occurs with pyrrolidones hydrobromate for compound 3 Epoxide) furans -2- bases) second -1- ketone (compound 4)；
4) substitution reaction generation 1- (3- (3- phenyl-propoxies) furans -2- bases) -2- (pyridine -2- base ammonia of amine occurs for compound 4 Base) ethane -1- ketone (compound 5)；
5) the acylation reaction generation acetic acid (2- oxos -2- (3- (oxygen of 3- phenyl third of amine occurs with acetic acid chloromethane acid anhydrides for compound 5 Base) furans -2- bases) ethyl) (pyridine -2- bases) carbamic acid acid anhydride (compound 6)；
6) compound 6 occur again cyclization generation (4- (3- (3- phenyl-propoxies) furans -2- bases) -1- (pyridine -2- bases) - 1H- imidazoles -2- bases) acetic acid esters (compound 7).
Further, synthesis step 1) in low temperature range be 0 ~ 10 DEG C, preferably 0 DEG C.
Further, synthesis step 2) in the inorganic base used can be sodium carbonate, potassium carbonate, cesium carbonate, saleratus, It is preferred that potassium carbonate.
Further, synthesis step 2) in heating-up temperature be 50 DEG C -100 DEG C, preferably 85 DEG C.
Obviously, according to the above of the present invention, according to the ordinary technical knowledge and means of this area, this hair is not being departed from Under the premise of bright above-mentioned basic fundamental thought, the modification, replacement or change of other diversified forms can also be made.
Embodiment
Embodiment：
The synthesis of 1-1 methanesulfonic acid 3- phenylpropyl acrylates：
3- phenyl-1-propanols (compound 1) (2.72g, 20mmol) are dissolved in dichloromethane (DCM) (25mL), add three second Amine (TEA) (4.05g, 40mmol) obtains mixture, and mixture then is cooled into 0 DEG C.Under agitation, delay into the mixture It is slow to add paratoluensulfonyl chloride (MsCl) (5.72g, 30mmol), and reactant mixture is stirred 1 hour at 0 DEG C, Ran Hou It is stirred at room temperature 1 hour (being completed until detecting reaction by HPLC).After removing solvent, it is molten to add saturated sodium bicarbonate water Liquid.Product is extracted with EtOAc (3 × 30mL) and washed with sodium bicarbonate solution and water, then removes solvent in a vacuum After obtain methanesulfonic acid 3- phenylpropyl acrylates (compound 2), 3.86g, yield 90.0%.1H-NMR (400 MHz, CDCl3) δ: 1.82(m, 2H), 2.77(t, 2H), 3.16(s, 3H), 4.02(t, 2H), 7.15-7.26(m, 5H). 13C-NMR (125 MHz, CDCl3) δ: 29.65, 34.34, 37.81, 67.65, 126.17, 128.33, 129.22, 142.31.LC-MS(ESI, pos, ion) m/z: 215[M+1]。
The synthesis of 1-2 1- (3- (3- phenyl-propoxies) furans -2- bases) second -1- ketone：
The compound 2 (3.86g, 18.01mmol) that above-mentioned synthesis step 1-1 is obtained is dissolved in anhydrous DMF (DMF) in (25mL), 1- (3- hy droxy furan -2- bases) second -1- ketone (2.27g, 18.01mmol) and potassium carbonate are then added (7.47g, 54.03mmol).Mixture is heated into 18 hours (being completed until detecting reaction by HPLC) at 85 DEG C, then will It is cooled to room temperature.Saturated sodium bicarbonate aqueous solution is added in mixture, is extracted with ethyl acetate and uses sodium bicarbonate solution Washed with water, after removing solvent in a vacuum, residue is obtained into off-white powder 1- (3- by purification by flash chromatography (3- phenyl-propoxies) furans -2- bases) second -1- ketone (compound 3) 3.91g, yield 88.9%.1H-NMR (400 MHz, CDCl3) δ: 2.05(m, 2H), 2.66(s, 3H), 2.77(t, 2H), 4.16(t, 2H), 6.28(d, 1H), 6.88(d, 1H), 7.15-7.26(m, 5H). 13C-NMR (125 MHz, CDCl3) δ: 24.66, 29.95, 34.34, 70.26, 111.03, 126.17, 128.33, 129.22, 137.15, 142.31, 146.41, 152.18, 193.54. LC-MS(ESI, pos, ion) m/z: 245[M+1]。
The synthesis of the bromo- 1- of 1-3 2- (3- (3- phenyl-propoxies) furans -2- bases) second -1- ketone：
At 0 DEG C, the compound 3 (3.91g, 16.00mmol) that synthesis step 1-2 is obtained is dissolved in anhydrous MeOH (30mL), Then pyrrolidones hydrobromate (6.26g, 19.2mmol) is added into this solution.Then by reactant mixture in nitrogen atmosphere Under stirred 4 hours at 0 DEG C, and be allowed to warm to room temperature and continue stirring until reaction is completed (to detect by TLC or HPLC aobvious Show).Then solvent is removed in a vacuum, the flash column chromatography isolated bromo- 1- of the 4.48g yellow 2- (3- (oxygen of 3- phenyl third Base) furans -2- bases) second -1- ketone (compound 4) powder, yield 86.7%.1H-NMR (400 MHz, CDCl3) δ: 2.05(m, 2H), 2.77(t, 2H), 4.16(t, 2H), 4.58(s, 2H), 6.25(d, 1H), 6.88(d, 1H), 7.15- 7.26(m, 5H). 13C-NMR (125 MHz, CDCl3) δ: 29.95, 32.52, 34.34, 70.26, 111.03, 126.17, 128.33, 129.22, 134.87, 142.31, 146.41, 150.86, 191.83. LC-MS(ESI, pos, ion) m/z: 323[M+1]。
The synthesis of 1-4 1- (3- (3- phenyl-propoxies) furans -2- bases) -2- (pyridine -2- bases amino) ethane -1- ketone：
PA (0.94g, 10mmol) is dissolved in dry DMF (20mL), then into solution add DIEA (3.88g, 30mmol), stirring one adds compound 4 (3.23g, 10mmol) after the meeting, by reactant mixture in a nitrogen atmosphere at room temperature Stirring is until reaction is completed and (completed by TLC or HPLC detection reactions).Then reactant mixture is diluted with cold water, uses acetic acid Ethyl ester extracts dilution, by the organic layer of merging salt water washing and dried over sodium sulfate.Obtained after solvent is evaporated in vacuo Required product 1- (3- (3- phenyl-propoxies) furans -2- bases) -2- (pyridine -2- bases amino) ethane -1- ketone (compounds 5), then crude product is purified by silica gel chromatography (2-4%MeOH/DCM), obtains purer compound 5,2.64g, production Rate 78.5%.1H-NMR (400 MHz, CDCl3) δ: 2.05(m, 2H), 2.77(t, 2H), 3.00(s, 1H),4.16 (t, 2H), 5.00(s, 2H), 6.22(d, 1H), 6.81(t, 1H),6.88(d, 1H), 7.13(d, 1H),7.15- 7.26(m, 5H). 13C-NMR (125 MHz, CDCl3) δ: 29.95, 34.34, 46.62, 70.26, 108.84, 110.44, 111.03, 126.17, 128.33, 129.22, 136.64, 138.85, 142.31, 146.41, 149.77, 156.49, 158.35, 182.94.LC-MS(ESI, pos, ion) m/z: 337[M+1]。
1-5 acetic acid (2- oxos -2- (3- (3- phenyl-propoxies) furans -2- bases) ethyl) (pyridine -2- bases) amino first The synthesis of acid anhydrides：
Compound 5 (1.68g, 5mmol) is dissolved in anhydrous DCM (20mL) at 0 DEG C, TEA is then added into solution (1.52g, 15mmol), it is slow added into acetic acid chloromethane acid anhydrides (1.84g, 15mmol).By reactant mixture in a nitrogen atmosphere Stirred 4 hours at 0 DEG C, be then allowed to warm to room temperature, continue stirring until reaction is completed (to detect by TLC or HPLC anti- It should complete).Then remove solvent under reduced pressure, obtain crude product acetic acid (2- oxos -2- (3- (3- phenyl-propoxies) furans -2- bases) second Base) (pyridine -2- bases) carbamic acid acid anhydride (compound 6), with acetone and ethyl alcohol recrystallization, obtain the compound after 1.90g is refined 6, yield 90.1%.1H-NMR (400 MHz, CDCl3) δ: 2.05(m, 2H), 2.24(s, 3H), 2.77(t, 2H), 4.16(t, 2H), 6.31(d, 1H), 6.44(s, 2H), 6.88(d,1H), 7.14-7.26(m, 5H), 7.49(t, 1H), 7.86(t, 1H), 8.49(d, 1H), 8.71(d, 1H). 13C-NMR (125 MHz, CDCl3) δ: 20.93, 29.95, 34.34, 47.17, 70.26, 111.03, 117.61, 122.24, 126.17, 128.33, 129.22, 137.21, 137.91, 142.31, 146.41, 149.46, 150.78, 152.20, 157.15, 169.27, 179.97. LC-MS(ESI, pos, ion) m/z: 423[M+1]。
1-6 (4- (3- (3- phenyl-propoxies) furans -2- bases) -1- (pyridine -2- bases) -1H- imidazoles -2- bases) acetic acid esters Synthesis：
Compound 6 (1.90g, 4.50mmol) obtained above is dissolved in acetic acid (20mL), it is then molten more than under agitation Ammonium acetate (6.94g, 90.00mmol) is added in liquid, reactant mixture is stirred overnight at 95 DEG C.Then by reactant mixture Room temperature is cooled to, and is neutralized with saturated sodium bicarbonate solution.Then after being extracted with EtOAc, then it is passed through into silica gel column chromatography (4- 6%MeOH/DCM elute) purifying, obtain product (4- (3- (3- phenyl-propoxies) furans -2- bases) -1- (pyridine -2- bases) - 1H- imidazoles -2- bases) acetic acid esters (compound 7) off-white powder 1.54g, yield 85%.1H-NMR (400 MHz, CDCl3) δ: 2.05(m, 2H), 2.09(s, 3H), 2.77(t, 2H), 4.16(t, 2H), 6.00(d, 1H),7.07(d, 1H), 7.15-7.26(m, 5H), 7.40(t, 1H), 7.90(d, 1H), 8.01(t, 1H), 8.51(d, 1H), 8.87(s, 1H). 13C-NMR (125 MHz, CDCl3) δ:20.67, 29.95, 34.34, 57.50, 70.26, 110.25, 123.60, 125.34, 126.17, 127.39, 128.33, 129.22, 133.51, 139.48, 142.30, 142.31, 142.68, 149.00, 149.03, 151.97, 152.25, 171.62. LC-MS(ESI, pos, ion) m/z: 404[M+1]。
Test example 1：Increment inhibitory action to osteoclast
First, experimental method
1st, osteoclast is separately cultured
Draw neck to put to death the Wistar rats in 24 h of birth, after distilled water cleans 1 min, 75% ethanol immersion 2min, separate stock Bone, shin bone and humerus, the soft tissue of bone surface is carefully removed, wipes out epiphysis, diaphyseal portion is washed 2 times with α-MEM nutrient solutions, is put into In cold α-MEM nutrient solutions, key stringer is cut off with microsurgical scissors, marrow inner cavity surface sclerotin gently scraped with scalpel Enter in nutrient solution, then sclerotin fragment 2min is gently blown and beaten with round end suction pipe, the osteoclast that will attach on bone cips pours training In nutrient solution, 15s is stood, draws upper cell suspension, it is about 10 that cell density, which is made,6Individual/ml cell suspension, it is inoculated in preset In 24 porocyte culture plates of cover glass, CO is put2Incubator（5% CO2, 37 DEG C）After cultivating 2h, the nutrient solution in culture hole is suctioned out Not adherent heteroproteose cell is removed, is gently rinsed 2 times with the α-MEM of pre-temperature, is grouped and continues to cultivate after being administered according to packet, Liquid 50% is changed per 48h.Above-mentioned α-MEM nutrient solutions are purchased from Hyclone companies.
2nd, packet and administration
Experiment is divided into medicine group to be measured and control group, is used in medicine group to be measured and contains 1 μm of ol/L testing compound（Corresponding embodiment Middle different compounds）α-MEM nutrient solutions, with the α-MEM nutrient solutions for not containing 1 μm of ol/L testing compound in control group.
3rd, osteoclast morphologic observation
Carry out somatoscopy after 48h to cell under inverted microscope, while each glass creep plate takes 5 different 200 at random Times visual field, count apocyte（3 or more than 3）Sum it is osteoclastic as the time point on each slide（Sample）Cell is total Number.
4th, statistical disposition
As a result represented with mean ± S.D., all data are handled using SPSS16.0 softwares, multiple-group analysis one way ANOVA variance analyses, compare between group and examined with q；Two groups are compared and are examined with t.P <0.05 is that difference is statistically significant.
5th, experimental result
The counting of the osteoclast of table 1 (individual/piece,)
Packet Number
Control group 28.1±3.6
Compound 6 20.8±3.4*
Compound 7 14.6±2.8*
Note：Compared with control group, * P ＜ 0.05
Compared with control group, amount of osteoclast has prepared each compound in embodiment it can be seen from upper table result Different degrees of reduction, and somatoscopy is carried out to cell under inverted microscope and finds the visible cell space of control group osteoclast It is very big, it is clear-cut, in pan-fried oily egg shape, dumbbell shape, funnel type, chopper type etc., there are a large amount of pseudopodium to be stretched to surrounding, nucleus is very It is more, generally 8~15.And cell space diminution occurs in the osteoclast of compound 6 and compound 7 in experimental group, pseudopodium disappears Lose, the apoptosis phenomenon such as karyopycnosis.Illustrate that increment of each compound of experimental group to osteoclast is inhibited.
Embodiment 2：To the preventive and therapeutic effect of vitamin A acid modeling osteoporosis rat
First, medicine is prepared
1st, vitamin A acid solution, vitamin A acid 3.0g is accurately weighed, adds 0.5% CMC-Na solution to obtain 15mg/ml solution to 200ml, it is standby With；
2nd, Ipriflavone solution, Ipriflavone 6.0g is taken, adds DMSO 12ml, added 0.5% CMC-Na solution to 300ml, obtain 20mg/ml solution, it is standby；
3rd, testing compound solution, prepared by the compound in corresponding embodiment, accurately weigh 0.3g, add DMSO 4ml, then add Enter 0.5% CMC-Na solution to 100ml, obtain 3mg/ml solution, it is standby.
2nd, experimental method
Healthy female SD rats, 4 groups, respectively control group are randomly divided into by body weight（N=5）, model group（N=10）, it is positive right According to group（Ipriflavone 100mg/kg, n=10）, some medicine groups to be measured（15mg/kg, n=10）.After experiment starts, per in the sky Noon other each group gavages in addition to control group give vitamin A acid 75mg/kg（5ml/kg）, control group gives isometric 0.5% CMC- Na, afternoon positive controls and medicine group to be measured give relative medicine solution respectively, control group and model group are given in equal volume 0.5% CMC-Na, continuous 2 weeks.
The left femur of animal is taken to use toy bone strength analyzer（YLS-16A toy bone strength analyzers, Huaibei Zhenghua Biological Instrument Co., Ltd.）Determine the bone breaking force of femur, each sample be placed on position on instrument and Direction is consistent；Residual bone is collected after measure, the wet gauze soaked with physiological saline wraps up, and seals after -20 DEG C of preservations For measure bone calcium and bone phosphorus.
The grey method assay of bone calcium, bone phosphorus：Room temperature naturally to thaw, 120 DEG C of baking 12h in baking oven, claims key weight（W1）, Bone is placed in 600 DEG C of muffle furnace ashing 3h again, makes the white bulk of bone, and claim bone ash weight（W2）.The bone ash that will be fully ground again （0.1g）It is dissolved in excess（4ml）3% HNO3In, fully extraction（Place 2 days and shake up）, grey method measure calcium, phosphorus content.
3rd, experimental result
As a result represented with mean ± S.D., all data are handled using SPSS16.0 softwares, multiple-group analysis one way ANOVA variance analyses, compare between group and examined with q；Two groups are compared and are examined with t.P <0.05 is that difference is statistically significant.
The compounds of this invention of table 2 is to bone breaking force and bone calcium, the influence of bone phosphorus
Note：Compared with model group, * P ＜ 0.05
From upper table result, to the rat of vitamin A acid modeling, the compounds of this invention 6 and compound 7 can increase bone breaking force Size, and raise the content of bone calcium and bone phosphorus, illustrate that the compounds of this invention can have prevention and/or control to osteoporosis Treatment acts on, and osteoporosis new construction medicine can be used as to carry out more in-depth study and exploitation.

Claims (4)

1. a kind of 2- acetic acid esters glyoxaline compound, its structural formula are as follows：
。
2. application of the compound as claimed in claim 1 in osteoclast increment medicine is suppressed.
3. application of the compound as claimed in claim 1 in prevention and/or treatment medicine for treating osteoporosis is prepared.
4. the synthetic route of compound as claimed in claim 1 is：
。
CN201810056718.0A 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in preventing medicine for treating osteoporosis Active CN107892687B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN201810056718.0A CN107892687B (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in preventing medicine for treating osteoporosis
CN201810717633.2A CN108912103A (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in prevention and treatment medicine for treating osteoporosis

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810056718.0A CN107892687B (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in preventing medicine for treating osteoporosis

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201810717633.2A Division CN108912103A (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in prevention and treatment medicine for treating osteoporosis

Publications (2)

Publication Number Publication Date
CN107892687A true CN107892687A (en) 2018-04-10
CN107892687B CN107892687B (en) 2018-08-24

Family

ID=61809003

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201810717633.2A Pending CN108912103A (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in prevention and treatment medicine for treating osteoporosis
CN201810056718.0A Active CN107892687B (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in preventing medicine for treating osteoporosis

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN201810717633.2A Pending CN108912103A (en) 2018-01-21 2018-01-21 A kind of 2- acetic acid esters glyoxaline compound and its application in prevention and treatment medicine for treating osteoporosis

Country Status (1)

Country Link
CN (2) CN108912103A (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3504678A1 (en) * 1985-02-12 1986-08-14 A. Nattermann & Cie GmbH, 5000 Köln Novel imidazolyl-oxyalkanoic acids and -thioalkanoic acids, derivatives thereof, and processes for their preparation
EP1602656A1 (en) * 2004-05-24 2005-12-07 NEUROSCIENZE PHARMANESS S.C. a R.L. Pyrazole derivatives having affinity for cb1 and/or cb2 receptors
CN106795139A (en) * 2014-10-07 2017-05-31 伊莱利利公司 Aminopyridine base epoxide pyrazole compound
CN106831735A (en) * 2017-01-23 2017-06-13 牡丹江医学院 It is a kind of to treat heterocyclic compound of osteoporosis and its production and use

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU1199600A (en) * 1998-10-02 2000-04-26 Board Of Trustees Of The University Of Illinois, The Estrogen receptor ligands
KR101149529B1 (en) * 2009-09-11 2012-05-25 한국화학연구원 Indenone derivatives and pharmaceutical composition comprising the same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3504678A1 (en) * 1985-02-12 1986-08-14 A. Nattermann & Cie GmbH, 5000 Köln Novel imidazolyl-oxyalkanoic acids and -thioalkanoic acids, derivatives thereof, and processes for their preparation
EP1602656A1 (en) * 2004-05-24 2005-12-07 NEUROSCIENZE PHARMANESS S.C. a R.L. Pyrazole derivatives having affinity for cb1 and/or cb2 receptors
CN106795139A (en) * 2014-10-07 2017-05-31 伊莱利利公司 Aminopyridine base epoxide pyrazole compound
CN106831735A (en) * 2017-01-23 2017-06-13 牡丹江医学院 It is a kind of to treat heterocyclic compound of osteoporosis and its production and use

Also Published As

Publication number Publication date
CN107892687B (en) 2018-08-24
CN108912103A (en) 2018-11-30

Similar Documents

Publication Publication Date Title
CN110818691A (en) Ketoamide compound and preparation method, pharmaceutical composition and application thereof
CN109563082A (en) Magnetic resonance imaging compound, wherein mesosome, magnetic resonance imaging agent and application and magnetic resonance imaging method employing
US7582767B2 (en) Substituted sulphonamide compound and uses thereof
CN107964009A (en) A kind of glyoxaline compound of 2- pyridine derivates substitution and its application in medicine for treating osteoporosis is prevented
CN107892687A (en) A kind of 2 acetic acid esters glyoxaline compound and its application in medicine for treating osteoporosis is prevented and treated
CN108129465A (en) A kind of glyoxaline compound of 2- pyrazines derivatives substitution and its application in medicine for treating osteoporosis is prevented
CN107936000A (en) A kind of glyoxaline compound of 2 trifluoromethyl substitution and its application in medicine for treating osteoporosis is prevented
CN108129466A (en) A kind of 2- butyl imidazoles class compound and its application in medicine for treating osteoporosis is prevented
CN104725372B (en) Tetracyclic indole alkaloid derivative as well as preparation method and application thereof
CN106389432B (en) Nitidine Chloride is preparing the application in anti-osteoporosis and bone loss diseases
CN112110864B (en) 4-amide substituted pyrimidine targeted DDR1 inhibitor, preparation method thereof and application of inhibitor in antitumor activity
CN105085391B (en) Cyclopropyl unsaturated quionoline compound and application as LTRA
CN102180941B (en) Derivatives of betulonic acid, method for preparing same and application thereof
CN105055381B (en) The pharmacy application of Lignanoids compounds and pharmaceutical composition
CN108840850A (en) A kind of flavone derivative that treating osteoporosis and its pharmaceutical composition and application
WO2011096642A2 (en) Pharmaceutical composition for preventing and treating inflammatory diseases
CN104814973B (en) Application in the drug of diseases associated with inflammation of the Cappariloside A in preparation for treating influenza and influenza virus mediation
CN102060875A (en) Novel quinazoline derivative, and preparation method and application thereof
CN112941027B (en) Human keratinocyte malignant transformation cell strain caused by dimethylarsinic acid and application thereof
CN103040813B (en) Application of p-chloroaniline substituted pyranone in preparation of fungal infection resisting drugs
CN103040811B (en) Application of p-methoxyphenylamino pyranone in preparation of fungal infection resisting drugs
CN110452231A (en) A kind of tryptophan class compound and its preparation method and application
CN102167720B (en) Betulonic acid derivant for restraining differentiation of osteoclast, preparation method thereof and application thereof
CN108743595A (en) A kind of NK cellular immunities checkpoint inhibitor and preparation method thereof
CN103040832B (en) Application of substituted cyanobenzene in preparation of fungal infection resisting drugs

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
TA01 Transfer of patent application right

Effective date of registration: 20180712

Address after: 510900 high tech Industrial Park, No. 18, A, 2, 3, 4, 5 building, high tech Industrial Park, Conghua Economic Development Zone, Guangzhou, Guangdong

Applicant after: Guangdong Lane Pharmaceutical Research Institute Co Ltd

Address before: 250355 No. 7 building, Renhe garden, north gate, Shandong University of Traditional Chinese Medicine, 4655 Changqing Road, Changqing, Shandong.

Applicant before: Lv Yingchun

TA01 Transfer of patent application right
GR01 Patent grant
GR01 Patent grant