CN112159373A - Compound and application thereof in preparation of PTL and/or NPC1L1 targeted inhibition drugs - Google Patents
Compound and application thereof in preparation of PTL and/or NPC1L1 targeted inhibition drugs Download PDFInfo
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- CN112159373A CN112159373A CN202011017004.2A CN202011017004A CN112159373A CN 112159373 A CN112159373 A CN 112159373A CN 202011017004 A CN202011017004 A CN 202011017004A CN 112159373 A CN112159373 A CN 112159373A
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Abstract
The invention provides a novel inhibitor targeting PTL and NPC1L1 simultaneously and application thereof. Namely, a compound having the structure shown in (I) and the use thereof in a medicament for inhibiting the absorption of intestinal triglycerides and cholesterol by simultaneously inhibiting PTL and NPC1L1, for the treatment and/or prevention of obesity, hypercholesterolemia and related cardiovascular and cerebrovascular diseases, for inhibiting PTL and/or NPC1L 1. The novel compound prepared by the invention shows good activity effect of inhibiting PTL and NPC1L1 simultaneously, and has application value in preparation of medicines for treating and/or preventing obesity, hypercholesterolemia and related cardiovascular and cerebrovascular diseases.
Description
Technical Field
The invention belongs to the field of targeted compounds, and particularly relates to a compound for inhibiting PTL/NPC1L1 and application thereof.
Background
Pancreatic Triglyceride Lipase (PTL) is a major component of pancreatic lipase, is secreted by pancreatic acinar cells, and functions to digest fat in the duodenum. PTL has the function of efficiently hydrolyzing fat, and in the presence of coenzyme and bile salt, triglyceride is hydrolyzed into diglyceride, and further hydrolyzed into monoglyceride and fatty acid, so that the diglyceride is absorbed by small intestine epithelial cells. The change of PTL expression has close relation with obesity and other metabolic diseases, and pancreatic lipase becomes a target for treating obesity and other metabolic diseases.
NPC1L1(Niemann-Pick-C1-Like 1, Niemann-Pick C1 type analogous protein 1) is a key protein for transmembrane cholesterol transport, is expressed in a large amount on human intestinal epidermal cell membranes and liver parenchymal cell membranes, and is one of key nodes of a human cholesterol metabolism regulation network. NPC1L1 interacts with the related cholesterol transporters Flotillin-1 and Flotillin-2 to transport cholesterol and other sterols across the brush border of intestinal epithelial cells into the intestinal epithelial cells. A large number of cell and animal experiments show that NPC1L1 can play an important role in the absorption and metabolism process of intestinal cholesterol, and becomes one of important new targets discovered in recent years and having a regulating effect on the absorption of cholesterol. It is the cholesterol lowering drug Ezetimibe that blocks the interaction of NPC1L1 with florillin-1 and florillin-2, thereby inhibiting cholesterol absorption. NPC1L1 can regulate and control genes such as SREBP1c, FAS and ABCT1 related to cholesterol metabolism by regulating the cholesterol level of cells, and further maintain the dynamic balance of cholesterol in vivo.
Hyperlipidemia and obesity are frequently accompanied, and the patient population is large. There is a need to develop new effective drugs.
Disclosure of Invention
In view of the above problems, the present invention provides a compound inhibiting PTL/NPC1L1 and its use.
A compound represented by the following formula (I),
wherein X is-O-, -S-or-NH-;
r can be a benzene ring, a benzene ring containing a substituent group, a five-membered heterocyclic ring or a six-membered heterocyclic ring;
when R is a benzene ring containing a substituent group, the substituent group is selected from the group consisting of: OH, CN, NO2、C1-C6Alkoxy, halogen (one or more of F, Cl, Br and I), C with 1 or more than 2 halogen (one or more of F, Cl, Br and I) substituent1-C61 to 5, preferably 1 to 3, of the alkoxy groups; the number of the substituent groups on the benzene ring is 1-5, preferably 1-3;
when R is a five-membered heterocyclic ring or a six-membered heterocyclic ring, the heteroatoms except C contained in the heterocyclic ring are any one or two of O, S, N, and the number of the heteroatoms in the heterocyclic ring is 1 or 2.
The application of one or more than two of the compounds or pharmaceutically acceptable salts thereof in preparing medicines for inhibiting the activity of PTL and/or NPC1L 1.
The use of one or more of said compounds or pharmaceutically acceptable salts thereof in the manufacture of a medicament for inhibiting intestinal triglyceride and/or cholesterol absorption.
The compounds of formula (I) reduce cholesterol absorption by inhibiting the activity of NPC1L 1.
The compounds of formula (I) reduce the rate of triglyceride hydrolysis by inhibiting the activity of PTL.
The compound shown in the formula (I) inhibits the absorption of triglyceride and cholesterol in intestinal tracts by simultaneously inhibiting PTL and NPC1L 1.
The application of one or more than two of the compounds or the pharmaceutically acceptable salts thereof in preparing medicines for treating and/or preventing obesity, hypercholesterolemia or related cardiovascular and cerebrovascular diseases.
The compound shown in the formula (I) inhibits the absorption of triglyceride and cholesterol in intestinal tracts by simultaneously inhibiting PTL and NPC1L 1.
The medicine comprises one or more than two of the compounds shown in the formula (I) and pharmaceutically acceptable salts thereof, and a medicinal carrier which is acceptable in medicine or pharmacology, and is prepared into powder, pills, capsules, tablets, microcapsules, soft capsules, films, suppositories, injections, paste, tinctures, powder or medicinal granules.
The compound can simultaneously act on Pancreatic Triglyceride Lipase (PTL) and a key protein NPC1L1 for transmembrane transport of cholesterol, has obvious effect and can better solve the absorption of triglyceride and cholesterol. The compound can be used as a PTL/NPC1L1 dual-target inhibitor, simultaneously acts on PTL and NPC1L1 which have important values on absorption of triglyceride and cholesterol by intestinal tracts, and shows double-effect characteristic advantages compared with the classical medicines orlistat and ezetimibe in the fields of weight loss and fat regulation.
The novel compound prepared by the invention shows good activity effect of inhibiting PTL and NPC1L1 simultaneously, and has application value in preparation of medicines for treating and/or preventing obesity, hypercholesterolemia and related cardiovascular and cerebrovascular diseases.
Additional features and advantages of the invention will be set forth in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in the written description and claims hereof as well as the appended drawings.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and those skilled in the art can also obtain other drawings according to the drawings without creative efforts.
FIG. 1 is a surface plasmon resonance method for evaluating the inhibitory effect of compounds 1-5 on NPC1L1, with Orlistat and Ezetime as controls.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
A substance inhibiting PTL/NPC1L1, which is a compound having a structure represented by formula (i):
wherein X is-O-, -S-or-NH-;
r can be a benzene ring or a benzene ring containing a substituent group, a five-membered heterocyclic ring or a six-membered heterocyclic ring;
when R is a benzene ring containing a substituent group, the substituent group is selected from the group consisting of: OH, CN, NO2、C1-C6Alkoxy, halogen (one or more of F, Cl, Br and I), C with 1 or more than 2 halogen (one or more of F, Cl, Br and I) substituent1-C61 to 5, preferably 1 to 3, of the alkoxy groups; the number of the substituent groups on the benzene ring is 1-5, preferably 1-3;
when R is a five-membered heterocyclic ring or a six-membered heterocyclic ring, the heteroatoms except C contained in the heterocyclic ring are any one or two of O, S, N, and the number of the heteroatoms in the heterocyclic ring is 1 or 2.
The preparation method of the compound with the structure shown as the formula (I) comprises the following steps: the compounds are synthesized using chemical synthesis methods and the compounds are synthesized using biosynthetic methods.
The use of a compound having the structure shown in formula (I) includes: acting on NPC1L1 alone, inhibiting intestinal cholesterol absorption, and preventing and treating hypercholesterolemia and related cardiovascular and cerebrovascular diseases;
simultaneously acts on PTL/NPC1L1, inhibits the absorption of triglyceride and cholesterol in intestinal tract, and is used for preventing and treating obesity, hypercholesterolemia and related cardiovascular and cerebrovascular diseases;
any single body or mixture of compounds having the structure shown in formula (I) and pharmaceutically acceptable salts, esters, ethers and other obvious chemical equivalents thereof can be used for preparing medical drugs for treating and/or preventing obesity and diseases related to hypermononeuremia.
The prepared medical drug for treating and/or preventing obesity and diseases related to high single-stranded sterolemia can act on NPC1L1 independently or act on PTL/NPC1L1 simultaneously.
The compound acting on NPC1L1 alone or simultaneously with PTL/NPC1L1 and its pharmaceutically acceptable salts, esters, ethers and other obvious chemical equivalents can be mixed with pharmaceutically acceptable pharmaceutical carriers to prepare powders, pills, capsules, tablets, microcapsules, soft capsules, films, suppositories, injections, ointments, tinctures, powders or granules.
Example 1
the synthetic route of compound (1) is shown below:
1 mol of Compound A-1 was added with 1.5 mol of m-methoxybenzoic acid, 20 ml of dried tetrahydrofuran (or dichloromethane) was added as a solvent, 1.2 mol of 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride was added as a condensing agent, and the reaction was carried out at room temperature for 12 hours. After concentration under reduced pressure, the mixture was purified by silica gel chromatography (volume ratio, petroleum ether: ethyl acetate: dichloromethane: 3:1:1) to obtain compound 1(366 mg of white solid, yield 75%).1H NMR(500MHz,Chloroform-d)7.62(d,J=7.6Hz,1H),7.55(s,1H),7.36(t,J=7.9Hz,1H),7.12(d,J=8.2Hz,1H),5.25–5.19(m,1H),4.39(q,J=5.9Hz,1H),3.86(s,3H),3.24(td,J=7.5,3.8Hz,1H),2.33(dt,J=14.7,7.3Hz,1H),2.11(dt,J=14.8,5.0Hz,1H),1.78(p,J=8.6,7.9Hz,2H),1.71(ddd,J=15.5,9.0,5.0Hz,2H),1.24(s,26H),0.86(dt,J=11.2,6.8Hz,6H).13C NMR(125MHz,cdcl3)171.06,165.93,159.60,131.35,129.46,121.89,119.41,114.26,74.68,71.83,56.90,55.44,38.68,34.20,31.89,31.41,29.59,29.51,29.43,29.34,29.31,28.93,27.66,26.66,25.28,22.67,22.45,14.10,13.99.HR-ESI-MS,calcd for C30H48O5[M+H]+:m/z 489.3575;found:m/z 489.3574.
Example 2
the synthetic route of compound (2) is shown below:
1 mol of the compound A-1 was added with 1.5 mol of 3-tert-butyldimethylsilyloxybenzoic acid, 20 ml of dried tetrahydrofuran (or dichloromethane) was added as a solvent, 1.2 mol of 1-ethyl- (3-dimethylaminopropyl) carbonyldiimine hydrochloride was added as a condensing agent, and the reaction was carried out at room temperature for 12 hours. After concentration under reduced pressure, the mixture was dissolved in 10 ml of tetrahydrofuran, and 2 mol of 4-butylammonium fluoride was added thereto to conduct a reaction at room temperature for 12 hours. Concentrating under reduced pressure, and purifying with silica gel chromatographic column (volume ratio, ethyl acetate: two)Methyl chloride ═ 1:3) to give compound 2(289 mg of white solid, yield 61%).1H NMR(500MHz,Chloroform-d)7.58(d,J=7.6Hz,1H),7.54(s,1H),7.31(t,J=7.8Hz,1H),7.07(d,J=7.9Hz,1H),6.08(s,1H),5.21(s,1H),4.40(q,J=5.8Hz,1H),3.25(q,J=7.1Hz,1H),2.32(dt,J=15.0,7.5Hz,1H),2.11(dt,J=14.9,4.9Hz,1H),1.81–1.64(m,4H),1.24(s,26H),0.86(dt,J=13.6,6.7Hz,6H).13C NMR(125MHz,cdcl3)171.58,166.10,155.99,131.34,129.73,121.78,120.44,116.32,75.00,72.09,56.84,38.62,34.20,31.89,31.39,29.59,29.52,29.44,29.36,29.32,28.91,27.62,26.66,25.25,22.67,22.45,14.11,13.99.HR-ESI-MS,calcd for C29H46O5[M+H]+:m/z 475.3418;found:m/z 475.3416.
Example 3
the synthesis of compound (3) is the same as in example 2, except that: the reaction material 3-tert-butyldimethylsilyloxybenzoic acid was replaced with 4-tert-butyldimethylsilyloxybenzoic acid, yield 67%.1H NMR(500MHz,Chloroform-d)7.94(d,J=8.1Hz,2H),6.87(d,J=8.2Hz,2H),5.19(s,1H),4.39(q,J=5.8Hz,1H),3.24(q,J=6.5,6.1Hz,1H),2.31(dt,J=14.8,7.4Hz,1H),2.10(dt,J=15.0,4.9Hz,1H),1.77(q,J=7.3Hz,2H),1.67(d,J=8.3Hz,2H),1.24(s,26H),0.86(dt,J=12.1,6.9Hz,6H).13C NMR(125MHz,cdcl3)171.38,165.83,160.12,131.91,122.44,115.27,74.88,71.37,56.85,38.73,34.28,31.89,31.40,29.69,29.59,29.51,29.44,29.36,29.32,28.92,27.64,26.64,25.29,22.67,22.45,14.11,14.00.HR-ESI-MS,calcd for C29H46O5[M+H]+:m/z 475.3418;found:m/z 475.3412.
Example 4
the synthesis of compound (4) is the same as in example 1, except that: the m-methoxybenzoic acid as the reaction raw material was changed to p-methoxybenzoic acid, with a yield of 83%.1H NMR(500MHz,Chloroform-d)7.98(d,J=8.2Hz,2H),6.93(d,J=8.4Hz,2H),5.19(dp,J=7.9,4.5Hz,1H),4.39(q,J=6.0Hz,1H),3.86(s,3H),3.24(td,J=7.5,3.8Hz,1H),2.31(dt,J=14.6,7.3Hz,1H),2.09(dt,J=14.7,5.1Hz,1H),1.76(tt,J=13.5,6.8Hz,2H),1.72–1.61(m,2H),1.24(d,J=8.3Hz,26H),0.86(dt,J=11.6,6.9Hz,6H).13C NMR(125MHz,cdcl3)171.18,165.77,163.50,131.61,122.40,113.67,74.73,71.26,56.85,55.45,38.70,34.26,31.89,31.41,29.60,29.51,29.50,29.44,29.36,29.32,28.94,27.65,26.64,25.30,22.67,22.46,14.12,14.01.HR-ESI-MS,calcd for C30H48O5[M+H]+:m/z 489.3575;found:m/z 489.3562.
Example 5
the synthesis of compound (5) is the same as in example 1, except that: the reaction material m-methoxybenzoic acid was changed to 3, 4-dimethoxybenzoic acid with a yield of 76%.1H NMR(500MHz,Chloroform-d)7.65(t,J=9.3Hz,1H),7.52(d,J=13.1Hz,1H),6.89(d,J=8.4Hz,1H),5.19(tt,J=7.9,4.6Hz,1H),4.39(q,J=6.0Hz,1H),3.96–3.90(m,6H),3.24(td,J=7.5,3.9Hz,1H),2.32(dt,J=14.8,7.5Hz,1H),2.10(dt,J=14.8,5.0Hz,1H),1.78(dt,J=14.3,7.0Hz,2H),1.70(ddd,J=14.0,9.7,4.8Hz,2H),1.24(d,J=9.0Hz,26H),0.86(dd,J=12.0,4.8Hz,6H).13C NMR(125MHz,cdcl3)171.13,165.87,153.14,148.69,123.52,122.51,111.98,110.22,74.80,71.55,56.87,56.04,56.01,38.75,34.30,31.89,31.48,31.42,29.69,29.60,29.55,29.52,29.50,29.44,29.36,29.32,28.94,27.65,26.65,25.29,22.67,22.46,14.11,14.01.HR-ESI-MS,calcd for C30H50O6[M+H]+:m/z 519.3680;found:m/z 519.3668.
Example 6
The inhibitory activity of compound 1, compound 2, compound 3, compound 4, compound 5 on PTL was examined.
The experimental process comprises the following steps:
PTL was dissolved in phosphate buffer solution (PH 7.4). Different concentrations (final concentrations in the mixed solution of 100. mu.M, 10. mu.M, 1. mu.M, 0.1. mu.M, 0.01. mu.M, respectively) of the compound to be tested or different concentrations of the positive control Orlistat (Orlistat) or Ezetimibe (Ezetimibe) (final concentrations in the mixed solution of 100. mu.M, 10. mu.M, 1. mu.M, 0.1. mu.M, 0.01. mu.M, respectively) were mixed with PTL (final concentration of 1. mu.g/mL of PTL), and the mixture was held at 37 ℃ for 30 minutes to obtain a mixed solution. The blank control group was an equal volume, equal concentration of PTL solution without the addition of test substance and positive control. P-nitrophenylacetate at a final concentration of 0.5mM in the mixed solution was added to the mixed solution and maintained at 37 ℃ for 60 minutes. The absorbance A at a wavelength of 405 nm was measured. Calculating IC by regression equation of the logarithm of the compound concentration to the inhibition ratio (i.e. the logarithm of the compound concentration is the abscissa and the inhibition ratio is the ordinate)50. The results of the inhibitory activity of the compounds on PTL are shown in Table 1.
The calculation mode of the inhibition rate is as follows: the inhibition rate is (experiment group A value-blank control group A value)/(control group A value-blank control group A value) × 100%
The experimental results are as follows: as shown in Table 1, each of the compounds 1 to 5 showed a good PTL inhibitory activity, and the inhibition rate was more than 50% at a concentration of 100. mu.M. Wherein the compound 1, the compound 3 and the compound 4The inhibitory activity against PTL is particularly prominent, IC50The values were 13.5. mu.M, 5.3. mu.M, and 15.8. mu.M, respectively.
Table 1 shows the inhibitory effect of compounds 1 to 5 according to the examples of the present invention on PTL. Wherein the structures of the compounds 1 to 5 are
TABLE 1. evaluation of the inhibitory activity of Compounds 1-5 on PTL (Orlistat and Ezetimibe as controls).
Example 7
The binding activity of compound 1, compound 2, compound 3, compound 4, compound 5 to NPC1L1 was examined.
The experimental process comprises the following steps:
the binding activity of the compounds to NPC1L1 was determined using Surface Plasmon Resonance (SPR). The CM5 series sensor chip, coupling reagents 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) were all purchased from GE.
Experimental groups: NPC1L1 (final concentration 50 μ g/ml) was dissolved in 10mM sodium acetate buffer (pH 4.56). Activation was performed for 7 minutes at a flow rate of 10. mu.L/min using a 1:1 volume ratio mixture of 100mM EDC and 100mM NHS, followed by coupling with NPC1L1 solution at a flow rate of 10. mu.L/min for 7 minutes. Excess reaction ester on the sensor chip surface was blocked with 1M ethanolamine (pH 8.5) at a flow rate of 10. mu.L/min for 7 min.
Control group: activation and blocking were performed as described above, but without the addition of NPC1L1 solution (no coupling).
On the chips of the experimental group and the control group, test compound 1-compound 5 (final concentration 100. mu.M, respectively), positive control Orlistat (final concentration 100. mu.M), and Ezetimibe (final concentration 100. mu.M) were injected at a flow rate of 10. mu.L/min for 4 minutes, respectively. Binding response values are reported in Response Units (RU), which are defined as the response of the flow cell containing the immobilized receptor (experimental chips) minus the response of the control flow cell (control chips).
The experimental results are as follows: compounds 1, 2, 3,4 all exhibited some NPC1L1 binding activity, with compound 2 and compound 3 binding best to NPC1L 1.
From the results of example 6 and example 7, it can be seen that: in the test of inhibitory activity against PTL, all tested compounds exhibited better inhibitory activity against PTL at a concentration of 100. mu.M, wherein the inhibitory activity IC of compounds 1, 3 and 4 against PTL50Respectively 13.5 mu M, 5.3 mu M and 15.8 mu M; in the inhibitory activity test on NPC1L1, compounds 1, 2, 3, and 4 all exhibited certain NPC1L1 binding activity, with compound 2 and compound 3 binding best to NPC1L 1. In summary, of the compounds tested, compounds 1, 2, 3,4 all exhibited simultaneous targeted inhibitory activity to PTL and NPC1L1 first.
The examples show that the compound with the structure shown in the general formula (I) and pharmaceutically acceptable salts, esters, ethers and other obvious chemical equivalents thereof can simultaneously act on Pancreatic Triglyceride Lipase (PTL) and a key protein NPC1L1 for transmembrane cholesterol transport, have obvious effect and can better solve the absorption problem of triglyceride and cholesterol.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (9)
1. A compound represented by the following formula (I),
wherein X is-O-, -S-or-NH-;
r can be a benzene ring, a benzene ring containing a substituent group, a five-membered heterocyclic ring or a six-membered heterocyclic ring;
when R is a benzene ring containing a substituent group, the substituent group is selected from the group consisting of: OH, CN, NO2、C1-C6Alkoxy, halogen (one or more of F, Cl, Br and I), C with 1 or more than 2 halogen (one or more of F, Cl, Br and I) substituent1-C61 to 5, preferably 1 to 3, of the alkoxy groups; the number of the substituent groups on the benzene ring is 1-5, preferably 1-3;
when R is a five-membered heterocyclic ring or a six-membered heterocyclic ring, the heteroatoms except C contained in the heterocyclic ring are any one or two of O, S, N, and the number of the heteroatoms in the heterocyclic ring is 1 or 2.
2. Use of a compound according to claim 1 or one or more of its pharmaceutically acceptable salts in the manufacture of a medicament for inhibiting the activity of PTL and/or NPC1L 1.
3. Use of a compound of claim 1 or one or more of its pharmaceutically acceptable salts in the manufacture of a medicament for inhibiting intestinal triglyceride and/or cholesterol absorption.
4. The use according to claim 3, wherein the compound of formula (I) reduces cholesterol absorption by inhibiting the activity of NPC1L 1.
5. Use according to claim 3, wherein the compound of formula (I) reduces the rate of triglyceride hydrolysis by inhibiting the activity of PTL.
6. The use as claimed in claim 4 or 5, wherein the compound of formula (I) inhibits intestinal triglyceride and cholesterol absorption by inhibiting both PTL and NPC1L 1.
7. Use of a compound of claim 1 or one or more of its pharmaceutically acceptable salts for the manufacture of a medicament for the treatment and/or prevention of obesity, hypercholesterolemia, or related cardiovascular and cerebrovascular diseases.
8. The use as claimed in claim 7, wherein the compound of formula (i) inhibits intestinal triglyceride and cholesterol absorption by inhibiting both PTL and NPC1L 1.
9. The use as claimed in any one of claims 2 to 8, wherein the medicament comprises one or more of the compounds represented by formula (I) and pharmaceutically acceptable salts thereof in the form of powder, pill, capsule, tablet, microcapsule, soft capsule, film, suppository, injection, ointment, tincture, powder or granule, in admixture with a pharmaceutically or pharmacologically acceptable carrier.
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CN202011017004.2A CN112159373B (en) | 2020-09-24 | 2020-09-24 | Compound and application thereof in preparation of targeted PTL and/or NPC1L1 inhibition drugs |
PCT/CN2021/119276 WO2022063071A1 (en) | 2020-09-24 | 2021-09-18 | Compound and use thereof in preparation of drug for targeted inhibition of ptl and/or npc1l1 |
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WO2022063071A1 (en) * | 2020-09-24 | 2022-03-31 | 青岛大学 | Compound and use thereof in preparation of drug for targeted inhibition of ptl and/or npc1l1 |
CN115813931A (en) * | 2022-10-31 | 2023-03-21 | 青岛艾科生物科技有限公司 | Application of GSK-J1 or pharmaceutically acceptable salt thereof in preparing medicines for reducing content of triglyceride and/or cholesterol |
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US20090124681A1 (en) * | 2007-10-31 | 2009-05-14 | Burnham Institute For Medical Research | Beta-lactone compounds |
CN109851592A (en) * | 2019-01-25 | 2019-06-07 | 中国人民解放军西部战区总医院 | Orlistat derivative |
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US5260310A (en) * | 1990-02-26 | 1993-11-09 | Hoffmann-La Roche Inc. | Oxetanone compounds and pharmaceutical compositions containing them |
CN112159373B (en) * | 2020-09-24 | 2023-10-20 | 青岛大学 | Compound and application thereof in preparation of targeted PTL and/or NPC1L1 inhibition drugs |
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US20090124681A1 (en) * | 2007-10-31 | 2009-05-14 | Burnham Institute For Medical Research | Beta-lactone compounds |
CN109851592A (en) * | 2019-01-25 | 2019-06-07 | 中国人民解放军西部战区总医院 | Orlistat derivative |
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SAEED ALQAHTANI等: "Orlistat limits cholesterol intestinal absorption by Niemann-pick C1-like 1 (NPC1L1) inhibition" * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022063071A1 (en) * | 2020-09-24 | 2022-03-31 | 青岛大学 | Compound and use thereof in preparation of drug for targeted inhibition of ptl and/or npc1l1 |
CN115813931A (en) * | 2022-10-31 | 2023-03-21 | 青岛艾科生物科技有限公司 | Application of GSK-J1 or pharmaceutically acceptable salt thereof in preparing medicines for reducing content of triglyceride and/or cholesterol |
CN115813931B (en) * | 2022-10-31 | 2023-09-08 | 青岛艾科生物科技有限公司 | Application of GSK-J1 or pharmaceutically acceptable salt thereof in preparation of medicines for reducing triglyceride and/or cholesterol content |
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