CN104311622B - A kind of asiatic acid amide derivatives - Google Patents

A kind of asiatic acid amide derivatives Download PDF

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CN104311622B
CN104311622B CN201410524752.8A CN201410524752A CN104311622B CN 104311622 B CN104311622 B CN 104311622B CN 201410524752 A CN201410524752 A CN 201410524752A CN 104311622 B CN104311622 B CN 104311622B
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asiatic acid
compound
alkyl
butyl
group
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CN104311622A (en
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尹述凡
黎勇
袁明兴
宋长伟
袁丽
蒋丽娟
董林
李颖
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Sichuan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids

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Abstract

The invention provides a kind of amide derivatives carrying out based on asiatic acid structure and modifying.Pharmacologically active of the present invention experiment shows, the compounds of this invention (particularly 4c, 4d) has preferable fibrosis activity, and the fat-soluble relatively asiatic acid of compound increases, and provides new selection for clinical application.

Description

A kind of asiatic acid amide derivatives
Technical field
The present invention relates to the amide derivatives of asiatic acid.
Background technology
Herba Centellae is dicotyledon Umbelliferae Umbelliferae Herba Centellae Centella asiatica (L.) Urban Dry herb or whole herb with root.Heat-clearing and toxic substances removing, inducing diuresis and reducing edema, benefit brain is refreshed oneself, and is the long-lived medicine of Asians.Research shows have Nourishing, antiinflammatory, healing of wound, diuresis relieving constipation and calm effect.The most effective in cure, to blood purification and immunity to leprosy, ulcer Power has activation, because it can stimulate the replacement of deep skin cell.It is neural nourishing agent, can improve memory, alleviate essence Mental fatigue labor；Contribute to controlling blood pressure lowering, hepatopathy etc..
Research finds, asiatic acid is one of functional component of Herba Centellae, is also the ursane that in Herba Centellae, content is higher Type Pentacyclic triterpenic acid, research shows that asiatic acid and derivant thereof have treatment skin trauma, antidepressant, anti-alzheimer Sick, suppression hepatoma carcinoma cell hypertrophy isoreactivity.
Summary of the invention
It is an object of the invention to provide a kind of derivant carrying out based on asiatic acid structure and modifying.Another of the present invention Purpose is to provide the preparation method of this derivant and purposes.
Specifically, the invention provides compound or its pharmaceutically acceptable salt, hydrate, solvent conjunction shown in formula I Thing or crystal formation:
Wherein, R1Selected from amino, the alkyl of C1～C5.
Further, described R1Alkyl selected from C1～C4.
Further, described alkyl is selected from ethyl, propyl group or butyl.
Containing the introducing of the alkyl of different carbon numbers, change polarity and the fat water partition coefficients of primer, add it Fat-soluble, more conducively the compounds of this invention passes through blood fat barrier, reaches tissue and cell, is conducive to playing drug effect.But, this Bright research shows, owing to medicine absorption in vivo and metabolic demand medicine itself have a suitable fat water partition coefficients, institute Not being The more the better with the atomic number of alkyl carbon of introducing, it needs an adequate value.The present invention is the most right by compound The carbon atom number more suitable than have found, i.e. introduces propyl group and butyl.Therefore, alkyl of the present invention preferably is selected from propyl group or fourth Base.
In addition to pharmaceutically active is had an impact by atomic number of alkyl carbon, present invention research shows, the arrangement mode of alkyl is carried The change of the compound steric configuration come, there is also appreciable impact to the drug activity of compound, change prepared by the such as present invention Compound 4c, 4e, wherein, 4c contains n-pro-pyl, and 4e contains isopropyl, although carbon number is identical, but 4e compound possesses guarantor hardly Liver function is imitated.According to foregoing, in the present invention, described propyl group preferably is selected from n-pro-pyl；Described butyl preferably is selected from normal-butyl.
Present invention also offers the preparation method of above-claimed cpd, it includes following operating procedure:
(1)
Take asiatic acid 2, at K2CO3,Et3Adding bromoacetate in the presence of N, KI, reaction obtains asiatic acid derivant 3；
(2) take asiatic acid derivant 3, add NH2R1, alcohol solvent reacts production I；
Wherein, R1Selected from amino, the alkyl of C1～C5.
Present invention also offers above-claimed cpd or its pharmaceutically acceptable salt, hydrate, solvate or crystal formation exist Prepare the purposes in the medicine of anti-chemical damage, the liver protecting and ALT lowering.
Present invention also offers above-claimed cpd or its pharmaceutically acceptable salt, hydrate, solvate or crystal formation exist Prepare the purposes in the medicine of anti-hepatic fibrosis.
Medicine metabolism in vivo has a number of mechanisms, and the metabolic mechanism that asiatic acid and derivant thereof are in vivo the most not ten Clearly demarcated true, therefore the present invention changes molecule center of gravity and the dipole moment of primer by the introducing of alkyl, for studying accumulated snow further Oxalic acid and the molecular action of derivant and metabolic mechanism thereof provide certain theoretical basis.Meanwhile, pharmacologically active of the present invention is real Testing and show, the compounds of this invention (particularly 4c, 4d) has preferable fibrosis activity, and the fat-soluble relatively Herba Centellae of compound Acid increases, and provides new selection for clinical application.
Detailed description of the invention
The preparation of embodiment 1 the compounds of this invention
Asiaticoside 1 is initially charged sodium hydroxide, adds dilute hydrochloric acid afterwards, carries out saponification, generates free asiatic acid 2。
Asiatic acid 2 is at K2CO3,Et3Add bromoacetate in the presence of N, KI, react, obtain asiatic acid and derive Thing 3, finally with ethanol as solvent, adds NH2R1Reaction obtains corresponding compound of formula I.
The each compound structure appraising datum prepared is as follows:
4a:
θmp 62-63℃.1H NMR(400MHz,CDCl3)δ8.78(s,1H),8.36(s,1H),5.26(s,2H),4.93 (dd,J1=16.4Hz, J2=46.4Hz, 2H), 4.61 (dd, J1=15.2Hz, J2=20.8Hz, 1H), 3.73～3.79 (m, 2H), 3.67 (d, J=10.0Hz, 2H), 3.42 (t, J=8.0Hz, 3H), 2.29 (d, J=11.2Hz, 1H), 2.22 (d, J= 11.2Hz,1H),2.14(s,2H),1.98(s,3H),1.91(s,3H),1.81(s,6H),1.26(s,2H),1.09(s,3H), 1.03 (d, J=6.4Hz, 3H), 0.79 (s, 3H), 0.70 (s, 3H).
M/z:560.38 (100.0%), 561.39 (35.4%), 562.39 (7.3%), 563.39 (1.1%)
Elementary analysis: C, 68.54；H,9.35；N,5.00；O,17.12
4b:
θmp 62-65℃.1H NMR(400MHz,CDCl3) δ 6.19 (s, 1H), 5.26 (s, 1H), 4.68 (d, J= 15.6Hz, 1H), 4.29 (d, J=15.6Hz, 1H), 3.73～3.77 (m, 1H), 3.67 (d, J=10.4Hz, 1H), 3.42 (d, J=10.8Hz, 2H), 3.29～3.39 (m, 2H), 2.23 (d, J=11.2Hz, 1H), 1.93 (d, J=10.8Hz, 1H), 1.46 ～1.49 (m, 1H), 1.32～1.42 (m, 4H), 1.31 (s, 1H), 1.28 (s, 1H), 1.25 (s, 1H), 1.19 (t, J= 7.2Hz,3H),1.10(s,3H),1.01(s,3H),0.97(s,3H),0.96(s,1H),0.88(s,3H),0.87(s,3H), 0.69(s,3H).
M/z:573.40 (100.0%), 574.41 (37.6%), 575.41 (8.1%), 576.41 (1.3%)
Elementary analysis: C, 71.17；H,9.66；N,2.44；O,16.73
4c:
θmp68-70℃.1H NMR 400MHz,CDCl3) δ 6.20 (s, 1H), 5.26 (s, 1H), 4.66 (d, J= 15.6Hz, 1H), 4.32 (d, J=15.6Hz, 1H), 3.73～3.79 (m, 1H), 3.69 (d, J=10.0Hz, 1H), 3.42 (t, J=10.0Hz, 2H), 3.20～3.27 (m, 1H), 3.29～3.36 (m, 1H), 2.22 (d, J=11.2Hz, 1H), 1.94 (d, J =10.8Hz, 1H), 1.63 (d, J=4.8Hz, 1H), 1.61 (d, J=7.6Hz, 1H), 1.56 (t, J=7.2Hz, 2H), 1.52 (d, J=8.0Hz, 2H), 1.46～1.49 (m, 1H), 1.32～1.42 (m, 4H), 1.31 (s, 1H), 1.28 (s, 1H), 1.25 (s,1H),1.10(s,3H),1.02(s,1H),0.97(s,3H),0.96(s,3H),0.93(s,1H),0.90(s,3H),0.88 (d, J=6.4Hz, 3H), 0.70 (s, 3H).
M/z:587.42 (100.0%), 588.42 (39.1%), 589.43 (7.3%), 589.42 (1.4%), 590.43 (1.4%)
Elementary analysis: C, 71.51；H,9.77；N,2.38；O,16.33
4d:
θmp60-61℃.1H NMR(400MHz,CDCl3) δ 6.18 (s, 1H), 5.26 (s, 1H), 4.66 (d, J= 15.6Hz, 1H), 4.32 (d, J=15.6Hz, 1H), 3.73～3.79 (m, 1H), 3.69 (d, J=10.8Hz, 1H), 3.42 (t, J=11.2Hz, 2H), 3.32～3.38 (m, 1H), 3.24～3.31 (m, 1H), 2.22 (d, J=11.2Hz, 1H), 2.02 (t, J =5.6Hz, 1H), 1.99 (d, J=4.4Hz, 1H), 1.94 (dd, J1=2.0Hz, J2=3.2Hz, 1H), 1.74 (s, 1H), 1.60～1.67 (m, 2H), 1.54～1.56 (m, 1H), 1.52 (d, J=8.0Hz, 2H), 1.46～1.49 (m, 1H), 1.32 (d, J=3.6Hz, 1H), 1.28 (s, 1H), 1.26 (s, 1H), 1.10 (s, 3H), 1.02 (s, 3H), 0.97 (s, 3H), 0.95 (s, 3H), 0.93 (s, 1H), 0.92 (s, 3H), 0.88 (d, J=6.4Hz, 3H), 0.70 (s, 3H).
M/z:601.43 (100.0%), 602.44 (39.8%), 603.44 (9.0%), 604.44 (1.4%)
Elementary analysis: C, 71.84；H,9.88；N,2.33；O,15.95
4e:
θmp69-72℃.1H NMR(400MHz,CDCl3) δ 5.95 (d, J=7.6Hz, 1H), 5.26 (s, 1H), 4.57 (d, J=15.6Hz, 1H), 4.33 (d, J=15.6Hz, 1H), 4.10～4.19 (m, 1H), 3.76 (td, J1=4.4Hz, J2= 10.4Hz, 1H), 3.68 (d, J=10.4Hz, 1H), 3.42 (t, J=8.4Hz, 2H), 2.22 (s, 1H), 2.18 (d, J= 5.6Hz, 1H), 1.90～2.12 (m, 6H), 1.74 (d, J=9.2Hz, 3H), 1.60～1.68 (m, 3H), 1.46～1.57 (m, 3H), 1.28～1.39 (m, 6H), 1.25 (s, 2H), 1.20 (t, J=6.4Hz, 6H), 1.10 (s, 3H), 1.02 (s, 3H), 0.96 (d, J=6.4Hz, 3H), 0.90 (s, 3H), 0.88 (d, J=6.4Hz, 3H), 0.70 (s, 3H).
M/z:587.42 (100.0%), 588.42 (39.1%), 589.43 (7.3%), 589.42 (1.4%), 590.43 (1.4%)
Elementary analysis: C, 71.51；H,9.77；N,2.38；O,16.33
The derivant at comparative example asiatic acid different modifying position
Asiatic acid is condensed with aldehyde or ketone, generates ring-type acetal ketone, asiatic acid derivant 3 at DMF, HClO4In the presence of add R2COR3React.
5a:
θmp80-81℃.1H NMR(400MHz,CDCl3) δ 5.26 (t, J=3.2Hz, 1H), 4.57 (dd, J1=16Hz, J2 =38Hz, 2H), 4.19 (q, J=7.2Hz, 2H), 3.78 (td, J1=4.4Hz, J2=10.0Hz, 1H), 3.49 (dd, J1= 10.8Hz,J2=17.6Hz, 2H), 3.32 (d, J=9.6Hz, 1H), 2.26 (d, J=9.2Hz, 1H), 2.05 (t, J= 4.8Hz,1H),1.95(dd,J1=3.6Hz, J2=8.8Hz, 2H), 1.69～1.83 (m, 4H), 1.62 (t, J=8.8Hz, 1H), 1.45 (d, J=3.6Hz, 6H), 1.51 (td, J1=3.2Hz, J2=13.2Hz, 2H), 1.31～1.43 (m, 3H), 1.27 (t, J=7.2Hz, 3H), 1.10 (s, 3H), 1.07 (s, 3H), 1.03 (s, 3H), 0.95 (d, J=6.0Hz, 3H), 0.86 (d, J =6.4Hz, 3H), 0.72 (s, 3H).
M/z:614.42 (100.0%), 615.42 (41.0%), 616.42 (9.2%), 617.43 (1.6%)
Elementary analysis: C, 72.28；H,9.51；O,18.22
5b:
θmp25-30℃.1H NMR(400MHz,CDCl3) δ 8.13 (d, J=7.6Hz, 2H), 7.63 (t, J=7.6Hz, 1H), 7.49 (t, J=7.6Hz, 2H), 5.55 (s, 1H), 5.27 (s, 1H), 4.53 (dd, J1=15.6Hz, J2=38.8Hz, 2H),4.20(dd,J1=11.2Hz, J2=14.4Hz, 2H), 3.92 (d, J=10.4Hz, 2H), 3.49 (d, J=10.4Hz, 1H), 3.33 (d, J=9.6Hz, 1H), 2.27 (d, J=10.2Hz, 1H), 2.12 (dd, J1=4.4Hz, J2=12.8Hz, 1H), 2.02～2.06 (m, 1H), 1.97 (dd, J1=3.2Hz, J2=8.8Hz, 2H), 1.69～1.85 (m, 4H), 1.65 (t, J= 8.8Hz, 1H), 1.45～1.57 (m, 3H), 1.31～1.38 (m, 3H), 1.29 (s, 1H), 1.26 (d, J=6.8Hz, 3H), 1.22 (s, 3H), 1.11 (s, 3H), 1.08 (s, 3H), 0.99～1.05 (m, 2H), 0.96 (d, J=7.0Hz, 3H), 0.87 (d, J=6.4Hz, 3H), 0.75 (s, 3H).
M/z:662.42 (100.0%), 663.42 (45.3%), 664.42 (11.0%), 665.43 (2.1%)
Elementary analysis: C, 74.29；H,8.82；O,16.89
5c:
θmp61-63℃.1H NMR(400MHz,CDCl3) δ 5.26 (t, J=3.2Hz, 1H), 1.57 (d, J=15.6Hz, 1H), 1.52 (t, J=4.8Hz, 1H), 1.47 (d, J=16.0Hz, 1H), 1.19 (q, J=7.2Hz, 2H), 3.85 (td, J1= 4.4Hz,J2=10.0Hz, 1H), 3.75 (d, J=10.4Hz, 1H), 3.25 (d, J=10.4Hz, 1H), 3.06 (d, J= 9.6Hz, 1H), 2.26 (d, J=10.8Hz, 2H), 2.00～2.10 (m, 2H), 1.95 (dd, J1=3.2Hz, J2=8.8Hz, 2H), 1.75～1.82 (m, 3H), 1.63 (t, J=8.8Hz, 1H), 1.57 (s, 3H), 1.30～1.52 (m, 6H), 1.26 (t, J =7.2Hz, 3H), 1.14～1.20 (m, 1H), 1.09 (s, 3H), 1.08 (s, 3H), 1.04 (s, 3H), 0.98 (s, 1H), 0.96 (d, J=4.0Hz, 3H), 0.94 (d, J=2.4Hz, 3H), 0.86 (d, J=6.4Hz, 3H), 0.72 (s, 3H).
M/z:614.42 (100.0%), 615.42 (41.0%), 616.42 (9.2%), 617.43 (1.6%)
Elementary analysis: C, 72.28；H,9.51；O,18.22
5d:
1H NMR(400MHz,CDCl3) δ 7.26 (d, J=15.6Hz, 1H), 7.07 (d, J=8.0Hz, 1H), 7.01 (s, 1H),6.83(dd,J1=2.0Hz, J2=7.2Hz, 1H), 5.50 (s, 1H), 5.27 (s, 1H), 4.53 (dd, J1=16.0Hz, J2=38.8Hz, 2H), 4.20 (q, J=7.2Hz, 2H), 3.91 (d, J=10.4Hz, 1H), 3.47 (d, J=10.0Hz, 1H), 3.30 (d, J=9.6Hz, 1H), 2.27 (d, J=11.2Hz, 1H), 2.11 (dd, J1=4.8Hz, J2=12.4Hz, 1H), 2.04 (dd,J1=7.0Hz, J2=12.4Hz, 1H), 1.97 (dd, J1=4.0Hz, J2=8.8Hz, 2H), 1.69～1.84 (m, 1H), 1.65 (t, J=8.8Hz, 3H), 1.41～1.55 (m, 1H), 1.31～1.37 (m, 3H), 1.27 (t, J=7.2Hz, 3H), 1.20 (s, 3H), 1.11 (s, 3H), 1.07 (s, 3H), 1.01～1.04 (m, 2H), 0.95 (d, J=7.0Hz, 3H), 0.91～ 0.93 (m, 1H), 0.87 (d, J=8.4Hz, 3H), 0.79～0.84 (m, 1H), 0.74 (s, 3H).
M/z:678.41 (100.0%), 679.42 (45.3%), 680.42 (11.7%), 681.42 (2.1%)
Elementary analysis: C, 72.54；H,8.61；O,18.85
5e:
θmp55-57℃
M/z:692.43 (100.0%), 693.43 (45.7%), 694.44 (10.5%), 695.44 (2.3%), 694.43 (1.6%)
Elementary analysis: C, 72.80；H,8.73；O,18.47
5f:
θmp63-65℃.1H NMR(400MHz,CDCl3) δ 8.24 (d, J=8.4Hz, 2H), 7.70 (d, J=8.8Hz, 2H), 5.63 (s, 1H), 5.27 (s, 1H), 4.58 (d, J=15.6Hz, 1H), 4.48 (d, J=15.6Hz, 1H), 4.20 (q, J =7.2Hz, 2H), 3.94 (d, J=10.4Hz, 2H), 3.51 (d, J=10.4Hz, 1H), 3.34 (d, J=0.96Hz, 1H), 2.27 (d, J=11.2Hz, 1H), 2.13 (dd, J1=4.8Hz, J2=12.8Hz, 1H), 2.02～2.10 (m, 1H), 1.97 (dd,J1=3.2Hz, J2=8.8Hz, 2H), 1.70～1.85 (m, 4H), 1.65 (t, J=8.8Hz, 1H), 1.43～1.55 (m, 6H), 1.26 (t, J=7.2Hz, 3H), 1.20～1.23 (m, 1H), 1.19 (s, 3H), 1.11 (s, 3H), 1.08 (s, 3H), 0.95 (d, J=6.4Hz, 3H), 0.87 (d, J=6.8Hz, 3H), 0.77～0.91 (m, 4H), 0.75 (s, 3H).
M/z:707.40 (100.0%), 708.41 (45.3%), 709.41 (11.9%), 710.41 (2.3%)
Elementary analysis: C, 69.56；H,8.12；N,1.98；O,20.34
Beneficial effects of the present invention is illustrated below by way of test example.
The impact on rat liver fibrosis of the test example 1 asiatic acid compounds
1 material and instrument
1.1 materials:
Asiatic acid compounds: white powder；
SD rat, male and female half and half, Sichuan University's Experimental Animal Center provide；
CMC: specification: 500g, product batch number: 20120320, manufacturer: Chengdu Ke Long chemical reagent factory；
CCl4: analytical pure, specification: 500ml, product batch number: 20110701, manufacturer: Chengdu section dragon chemical reagent Factory.
Cyprinus carpio board Oleum Brassicae campestris: specification: 900ml, manufacturer: Yi Haijiaquan food marketing company limited
1.2 instruments:
Sartorius electronic balance (0.0001g) BS210S: Beijing Sai Duolisi balance company limited；
Double outstanding (group) company limited of T-1000 type electronic balance (0.1g) made in CCCP 0000193: the U.S., the double outstanding test in Changshu Instrument plant；
Olympus AU400: Beijing Puri Sai Si Instrument Ltd..
2 are configured by test product
With analytical balance prepare weigh CMC5.0g add pure water 1000ml configure CMC solution, weigh respectively 4b, 5d, 4e, 5f, 4a, 4c, 5c, 5b, 4d, 5e, 5a, 0.3214g, 0.3208,0.3200g, 0.3173g, 0.3204g, 0.3198g, 0.3193g, 0.3223g, 0.3164g, 0.3184g, 0.3190g add CMC solution 200ml configure suspension:
Oleum Brassicae campestris and carbon tetrachloride configure 20% carbon tetrachloride oil solution by 1:4.
2 experimental techniques
Take body weight (150-190) g healthy SD rat 116, by body weight random packet, remaining every group in addition to model group 12 8, male and female half and half.It is divided into model control group, Normal group, asiatic acid compounds matched group.Herba Centellae acids chemical combination Thing matched group gives the CMC suspension of above-mentioned 12 kinds of compounds respectively according to dosage 0.5ml/100g gavage, every day 1 time, continuously Six weeks；Model control group, the CMC solution of Normal group gavage equivalent.Being administered twice for the first time, Normal group starts abdominal cavity Injection 0.2ml/100g20% Oleum Brassicae campestris, 2 times a week, continuous six weeks；Remaining respectively organizes rat equal lumbar injection equivalent 20% tetrachloro Change carbon oil solution, 2 times a week, continuous six weeks.Each group SD rat claims a body weight in every 7 days, and weigh fasted for one day prior 12h.Last After being administered 24h, rat stock arteriovenous takes blood, clip liver and weighs, rat blood, liver censorship.During experiment, model group is dead Die two, dead 1 of administration group 5a, dead 2 of dead 1 of dead 1 of dead 2 of 5b, 4e, 5e, 5c, long-pending dead 1 of 5f, just Chang Zuwei is dead.
3 statistical method
Administration group and Normal group often group is removed one or two exceptional values and is taken six values and add up, experimental data Representing with x ± s, result uses SPSS 17.0 software to carry out statistical procedures, one factor analysis of variance, and P ＜ 0.05 has statistics Meaning.
4 experimental results
Table 1 asiatic acid compounds is to ccl4Cause rat chronic hepatic fibrosis serum mesobilirubin, ALT, AST etc. Impact
Note: with Normal group ratio,△△<0.01,△<0.05；With model control group ratio,*P<0.05
5 results and analysis
5.1 clinical symptoms
During experiment, major part rat body weight increases, and indivedual rats have become thin, the more thin and weak rat mental status is the best, Defecate diluter, diet is less.After the last fortnight lumbar injection carbon tetrachloride oil solution, most of rats there will be lethargy, appetite Drinking-water reduces.4, within 5 weeks, it is adjusted to 1 times a week according to its mental status, death condition lumbar injection carbon tetrachloride oil solution, the 6th It is adjusted to one week 2 times week.
5.2 analyze and discuss
This experiment uses CC14Liver injury model, observes the protective effect to hepatic injury of the asiatic acid compounds.CC14Institute Cause hepatic injury and mainly activate generation free radical through cytochromes P450, attack phospholipid molecule on liver plasma membrane, damage Impairing the liver membrane structure and the integrity of function, so that during in endochylema, permeable enzyme such as AST, ALT etc. penetrate into blood, serum AST, ALT activity is significantly raised.
Model group AST in this research, ALT activity are significantly raised, and modeling success is described.5a in experiment, 5d, 5b, 4d, 4c, 5f group serum AST activity reduces, and has significant difference compared with model group；4d, 4a, 4c, 5f group serum ALT activities reduces, And have significant difference compared with model group, show that these asiatic acid compounds have certain function for protecting liver and reducing enzyme activity, To CC14Hepatic injury has good preventing/treating effect.
Meanwhile, the above results also indicates that, not arbitrarily asiatic acid is carried out structural modification, can ensure good guarantor Liver effect.

Claims (8)

  1. Compound or its pharmaceutically acceptable salt the most shown in formula I:
    Wherein, R1Selected from amino, the alkyl of C1～C5.
  2. Compound the most according to claim 1, it is characterised in that: described R1Selected from amino, the alkyl of C1～C4.
  3. Compound the most according to claim 2, it is characterised in that: described alkyl is selected from ethyl, propyl group or butyl.
  4. Compound the most according to claim 3, it is characterised in that: described alkyl is selected from propyl group or butyl.
  5. 5. according to the compound described in claim 3 or 4, it is characterised in that: described propyl group is selected from n-pro-pyl；Described butyl is selected from Normal-butyl.
  6. 6. the preparation method of compound described in claim 1, it is characterised in that: it includes following operating procedure:
    (1)
    Take asiatic acid 2, at K2CO3,Et3Adding bromoacetate in the presence of N, KI, reaction obtains asiatic acid derivant 3；
    (2) take asiatic acid derivant 3, add NH2R1, alcohol solvent reacts production I；
    Wherein, R1Selected from amino, the alkyl of C1～C5.
  7. 7. compound described in Claims 1 to 5 any one or its pharmaceutically acceptable salt prepare anti-chemical damage, Purposes in the medicine of the liver protecting and ALT lowering.
  8. 8. compound described in Claims 1 to 5 any one or its pharmaceutically acceptable salt are preparing the medicine of anti-hepatic fibrosis Purposes in thing.
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