LU504076B1 - Application of compound in preparation of hdac2 gene activator - Google Patents
Application of compound in preparation of hdac2 gene activator Download PDFInfo
- Publication number
- LU504076B1 LU504076B1 LU504076A LU504076A LU504076B1 LU 504076 B1 LU504076 B1 LU 504076B1 LU 504076 A LU504076 A LU 504076A LU 504076 A LU504076 A LU 504076A LU 504076 B1 LU504076 B1 LU 504076B1
- Authority
- LU
- Luxembourg
- Prior art keywords
- hdac2
- gene activator
- methyl
- compound
- dihydropyrazol
- Prior art date
Links
- 239000012190 activator Substances 0.000 title claims abstract description 33
- 150000001875 compounds Chemical class 0.000 title claims description 21
- 108090000623 proteins and genes Proteins 0.000 title description 11
- 101150098261 Hdac2 gene Proteins 0.000 claims abstract description 31
- SPLSMCHCBCQKEV-UHFFFAOYSA-N [3-(3-methyl-5-oxo-4h-pyrazol-1-yl)phenyl]azanium;chloride Chemical compound Cl.O=C1CC(C)=NN1C1=CC=CC(N)=C1 SPLSMCHCBCQKEV-UHFFFAOYSA-N 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 7
- 239000007924 injection Substances 0.000 claims description 7
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000003995 emulsifying agent Substances 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 239000012669 liquid formulation Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 239000003381 stabilizer Substances 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 abstract description 21
- 101001035011 Homo sapiens Histone deacetylase 2 Proteins 0.000 abstract description 15
- 102100039999 Histone deacetylase 2 Human genes 0.000 abstract description 14
- -1 compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride Chemical class 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 102000003964 Histone deacetylase Human genes 0.000 description 18
- 108090000353 Histone deacetylase Proteins 0.000 description 18
- 206010052428 Wound Diseases 0.000 description 17
- 208000027418 Wounds and injury Diseases 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 241000700159 Rattus Species 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- 102100021455 Histone deacetylase 3 Human genes 0.000 description 5
- 101000899282 Homo sapiens Histone deacetylase 3 Proteins 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940099259 vaseline Drugs 0.000 description 4
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 102000011990 Sirtuin Human genes 0.000 description 2
- 108050002485 Sirtuin Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 101150028074 2 gene Proteins 0.000 description 1
- WHIXQFSPEDIMGL-UHFFFAOYSA-N 2-(4-chlorophenyl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(Cl)C=C1 WHIXQFSPEDIMGL-UHFFFAOYSA-N 0.000 description 1
- VJVFAPBCFDWAEX-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(F)C=C1 VJVFAPBCFDWAEX-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- RLFWWDJHLFCNIJ-UHFFFAOYSA-N Aminoantipyrine Natural products CN1C(C)=C(N)C(=O)N1C1=CC=CC=C1 RLFWWDJHLFCNIJ-UHFFFAOYSA-N 0.000 description 1
- RMMXTBMQSGEXHJ-UHFFFAOYSA-N Aminophenazone Chemical compound O=C1C(N(C)C)=C(C)N(C)N1C1=CC=CC=C1 RMMXTBMQSGEXHJ-UHFFFAOYSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 102100039996 Histone deacetylase 1 Human genes 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 108091005646 acetylated proteins Proteins 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000002555 anti-neurodegenerative effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- VEQOALNAAJBPNY-UHFFFAOYSA-N antipyrine Chemical compound CN1C(C)=CC(=O)N1C1=CC=CC=C1 VEQOALNAAJBPNY-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229960000362 metamizole sodium Drugs 0.000 description 1
- DJGAAPFSPWAYTJ-UHFFFAOYSA-M metamizole sodium Chemical compound [Na+].O=C1C(N(CS([O-])(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 DJGAAPFSPWAYTJ-UHFFFAOYSA-M 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 229960005222 phenazone Drugs 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Disclosed is the application of a compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride in the preparation of an HDAC2 gene activator. The present invention has revealed that the compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride is capable of up-regulating the HDAC2 gene expression, playing the role of HDAC2 gene activator, thereby providing a new option for the treatment of HDAC2-associated diseases.
Description
BL-5641
LU504076
APPLICATION OF COMPOUND IN PREPARATION OF HDAC2 GENE
ACTIVATOR
[01] The present invention relates to the technical field of gene activators, and particularly relates to the application of a compound in the preparation of an HDAC2 gene activator.
[02] Histone deacetylase (HAT) and histone deacetylase (HDAC) are a pair of functional antagonistic proteases that regulate the acetylation state of histones, and jointly regulate the normal physiological functions of human body. Misexpression or dysfunction, if any, may even lead to the occurrence of tumors.
[03] Mammalian cells express 18 HDAC enzymes, which are divided into two classes:
Class II NAD+-dependent HDACs or sirtuins (sirtuins 1 - 7) and typical zinc-dependent
HDACSs, including: Class I (HDACs 1, 2, 3 and 8), Class II (HDACs 4, 5, 7 and 9), Class IIb (HDACs 6 and 10) and Class IV (HDACI11), have become therapeutic targets a variety of diseases, and have very important scientific research value and clinical application prospects.
[04] The 2H-pyran and 4H-pyran ring heterocyclic backbone is a structural parent nucleus with a wide range of significant biological activities identified in natural compounds, such as anti-neurodegenerative diseases, anti-cancer, cytotoxicity, anti-HIV, anti-malaria, anti-bacteria, anti-hyperglycemia and anti-dyslipidemia, eg, Alzheimer's Disease,
Parkinson's Disease and Huntington's Disease. Among them, 1-phenyl-3-methyl-5-pyrazolone is used to synthesize pyrazolone antipyretic and analgesic drugs such as metamizole sodium, antipyrine and aminopyrine. However, neither report nor application of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride directly used in HDAC2 activators is available yet.
[05] The present invention provides for the first time the compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride as an active ingredient in an HDAC2 gene activator, providing a new option for the treatment of HDAC2-associated diseases.
[06] The technical scheme of the present invention: application of a compound in the preparation of an HDAC2 gene activator, where the compound is 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride, and the compound structure is as follows: 1
BL-5641
Co LU504076
ON
Mo
[07] Further, the dosage form of the HDAC2 gene activator is a solid formulation or a liquid formulation.
[08] Further, the HDAC2 gene activator is administered orally or by injection.
[09] Further, the HDAC2 gene activator also contains a pharmaceutically acceptable carrier or excipient.
[10] Further, the excipient includes one or some of a solvent, a binder, a filler, a stabilizer and an emulsifier.
[11] An HDAC2 gene activator, including 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride.
[12] The mass concentration of the 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride in the above HDAC2 gene activator is 10 - 300 ng/mL.
[13] Compared with the prior art, the present invention provides for the first time the application of a compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride in the preparation of an HDAC2 gene activator. The present invention has revealed that the compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride is capable of up-regulating the HDAC2 gene expression, playing the role of
HDAC2 gene activator, thereby providing a new option for the treatment of
HDAC2-associated diseases.
[14] FIG 1 is a schematic diagram of the structural formulae of three separate compounds numbered 50366, 01206 and 07509, respectively.
[15] FIG 2 shows the effect of three separate compounds on the expression of deacetylated proteins HDAC2 and HDACS3 in A375 cells.
[16] FIG 3 is a statistical diagram of the expression of deacetylated proteins HDAC2 and
HDAC3.
[17] FIG 4 shows the MRNA expression of HDAC in HUVEC cells after medication.
[18] FIG 5 shows the effect of the expression of proteins extracted from the skin at the wound site after external application.
[19] FIG 6 is a statistical diagram of the expression of HDAC1, HDAC2 and HDAC3 in the three groups of experiments.
[20] FIG 7 shows a comparison of the expression of deacetylated proteins HDAC2 and 2
BL-5641 . . Ce. LU504076
HDAC3 extracted from the skin at the wound site between the injection treatment group and the challenge group.
[21] FIG 8 is a statistical diagram of the expression of deacetylated proteins HDAC2 and
HDAC3 extracted from the skin at the wound site between the control group and the challenge group.
[22] The present invention will be further elaborated hereafter in conjunction with accompanying drawings and the embodiments, which, however, are not taken as a basis for limiting the present invention.
[23] Example: the application of a compound in the preparation of an HDAC2 gene activator, where the compound is 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride, and the compound structure is as follows:
MR pti
[24] Further, the dosage form of the HDAC2 gene activator is a solid formulation or a liquid formulation. The HDAC2 gene activator is administered orally or by injection. The
HDAC?2 gene activator also contains a pharmaceutically acceptable carrier or excipient. The excipient includes one or some of a solvent, a binder, a filler, a stabilizer and an emulsifier.
[25] Example 2: an HDAC2 gene activator, the HDAC2 gene activator includes 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride. Its dosage form is a solid formulation or a liquid formulation, it is administered orally or by injection, and it further contains a pharmaceutically acceptable carrier or excipient. The excipient includes one or some of a solvent, a binder, a filler, a stabilizer and an emulsifier.
[26] Example 3: effect of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride on A375 human melanoma cells.
[27] Three separate compounds were added to A375 human melanoma cells, the proteins were then extracted, and the inhibitory effect on acetylated proteins was verified by western blotting technique. The three separate compounds are numbered as 50366, 01206 and 07509, respectively, among which Compound No. 50366 is 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride, Compound No. 01206 is 1-(4-chlorophenyl )-3-methyl-2-pyrazoline-5-one, and Compound No. 07509 is 2-(4-fluorophenyl)-5-methyl-4H-pyrazol-3-one, with the structural formulae shown in FIG. 1. FIG 2 shows the effect of three separate compounds on the expression of deacetylated proteins in A375 cells. FIG 3 is a statistical diagram of the expression of each protein. The experimental results from FIG 2 and FIG 3 show that Compound No. 01206 and 07509 have 3
BL-5641 obvious inhibitory effect on acetylation, while Compound No. 50366 (namely, LUS04076 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride provided by the present invention) can promote acetylation.
[28] Example 4: effect of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride on stimulating HDAC in HUVEC.
[29] HUVEC cells refer to human umbilical vein endothelial cells in the human body, and an RT-PCR assay was used to detect whether HDAC2 gene activator containing 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride can promotes the increase of HDAC2 expression in HUVEC cells. FIG 4 shows the mRNA expression of
HDAC in HUVEC cells after medication. The results from FIG 2 show that, compared with the control group, the expression of HDAC2 and HDACS in the cells of the 50 ng/mL administration group was significantly increased.
[30] Example 5: effect of external application of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride on the expression of
HDAC protein at the wound site.
[31] After SD rats were shaved and disinfected, and two full-thickness wounds with a diameter of 20 mm were made on both sides of the back of the rats. The control group was treated by covering the wounds with a sterile transparent dressing for the first three days, the vaseline group was treated by covering the wounds with a sterile transparent dressing for the first three days and by reapplying the same once every two days after being covered with the vaseline, while the challenge group was treated by covering the wounds with a dressing containing 100 nmol/g of drug (containing 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride) once every two days, and the wound healing was observed and recorded for 21 days. After anesthesia, the rats were killed, the proteins were extracted from the skin at the wound site, and the expression of proteins was measured by the western blotting. FIG. 5 shows the effect of the expression of proteins extracted from the skin at the wound site; and FIG 6 is a statistical diagram of the expression of HDACI, HDAC2 and HDAC3 in the three groups of experiments. The experimental results from FIG 5 and FIG 6 show that HDAC 2/3 in the challenge group were up-regulated, indicating that external application of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride could have a stimulating effect on the activation of HDAC2 level at the wound site.
[32] Example 6: effect of the injection of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride on the expression of
HDAC proteins at the wound site.
[33] After SD rats were shaved and disinfected, and two full-thickness wounds with a diameter of 20mm were made on both sides of the back of the rats. The control group was treated by covering the wounds with a sterile transparent dressing for the first three days, the vaseline group was treated by covering the wounds with a sterile transparent dressing for the first three days and by reapplying the same once every two days after being covered with the vaseline, while the challenge group was treated by injecting the normal saline containing 100 nmol/g of drug (containing 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride) once every two days, and the control group was treated by injecting the normal saline. After anesthesia, the rats were killed, the proteins were extracted from the skin at the wound site, and the expression of proteins was measured by the western blotting.
The experimental results from FIG 7 and FIG 8 show that HDAC 2/3 in the challenge group 4
BL-5641 were up-regulated, indicating that injection of LUS04076 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride could have a stimulating effect on the activation of HDAC?2 level at the wound site.
[34] To sum up, the present invention provides for the first time the application of a compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride in the preparation of an HDAC2 gene activator. The present invention has revealed that the compound 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride is capable of up-regulating the HDAC2 gene expression, playing the role of HDAC2 gene activator, thereby providing a new option for the treatment of HDAC2-associated diseases.
Claims (7)
1. Application of a compound in the preparation of an HDAC2 gene activator, wherein the compound is 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride.
2. The application according to claim 1, wherein the dosage form of the HDAC2 gene activator is a solid formulation or a liquid formulation.
3. The application according to claim 1, wherein the HDAC2 gene activator 1s administered orally or by injection.
4. The application according to claim 1 or claim 2, wherein the HDAC2 gene activator also contains a pharmaceutically acceptable carrier or excipient.
5. The application according to claim 4, wherein the excipient comprises one or some of a solvent, a binder, a filler, a stabilizer and an emulsifier.
6. An HDAC2 gene activator, wherein the HDAC2 gene activator comprises 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride.
7. An HDAC2 gene activator according to claim 6, wherein the mass concentration of 2-(3-aminophenyl)-5-methyl-2,4-dihydropyrazol-3-one hydrochloride in the HDAC2 gene activator is 10 - 300 ng/mL. 6
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310169582.5A CN116211850A (en) | 2023-02-27 | 2023-02-27 | Application of compound in preparation of HDAC2 gene activator |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| LU504076B1 true LU504076B1 (en) | 2023-10-26 |
Family
ID=86580127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LU504076A LU504076B1 (en) | 2023-02-27 | 2023-04-26 | Application of compound in preparation of hdac2 gene activator |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN116211850A (en) |
| LU (1) | LU504076B1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116531369A (en) * | 2023-02-24 | 2023-08-04 | 杜娟娟 | Application of a compound in promoting wound healing medicine |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004115508A (en) * | 2002-09-06 | 2004-04-15 | Mitsubishi Pharma Corp | Drugs for improving the function of burned skin tissue |
| US20120022129A1 (en) * | 2008-08-18 | 2012-01-26 | Irfan Rahman | Targeting of Histone Deacetylase 2, Protein Kinase CK2, and Nuclear Factor NRF2 For Treatment of Inflammatory Diseases |
| US20160199463A1 (en) * | 2014-12-15 | 2016-07-14 | The Johns Hopkins University | Hdac2 defends vascular endothelium from injury |
| CN111346095B (en) * | 2020-03-14 | 2021-06-08 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | Pharmaceutical preparations for the treatment of post-neurosurgical headaches |
| CN111840261A (en) * | 2020-06-22 | 2020-10-30 | 广州中医药大学(广州中医药研究院) | A kind of agonist of deacetylase and its application |
| CN116531369A (en) * | 2023-02-24 | 2023-08-04 | 杜娟娟 | Application of a compound in promoting wound healing medicine |
-
2023
- 2023-02-27 CN CN202310169582.5A patent/CN116211850A/en active Pending
- 2023-04-26 LU LU504076A patent/LU504076B1/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| CN116211850A (en) | 2023-06-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11696890B2 (en) | Tumescent infiltration drug delivery of high subcutaneous drug concentrations with prolonged local and systemic effects and minimal local or systemic toxicity | |
| ES2620389T3 (en) | Topical formulations of co-enzyme Q10 and treatment of pain, fatigue and wounds | |
| US9107925B2 (en) | Sodium channel blocker for treatment of loss of superficial sensitivity | |
| US20120238623A1 (en) | Inflammation and Autoimmune Disorder Treatment using RARa Selective Agonists | |
| US20250268856A1 (en) | Pain Relieving Method | |
| ES2269404T3 (en) | EMPLOYMENT OF A MEK INHIBITOR IN THE PRODUCTION OF MEDICINES FOR THE TREATMENT OF INFECTIONS BY NEGATIVE CHAIN VIRUS RNA. | |
| Utz et al. | Amphotericin B toxicity: combined clinical staff conference at the National Institutes of Health | |
| LU504076B1 (en) | Application of compound in preparation of hdac2 gene activator | |
| US20200289466A1 (en) | Methods and uses of nampt activators for treatment of diabetes, cardiovascular diseases, and symptoms thereof | |
| EP1116487B1 (en) | Reduction of postoperative complications of cardiopulmonary bypass (CPB) surgery with Taurolidine or Taurultam | |
| Xu et al. | Use of remimazolam combined with alfentanil for plastic surgery anesthesia cases: a clinical trial | |
| US11278542B2 (en) | Use of nicotinamide composition in preparation of drug for treating hand-foot skin reaction induced by sorafenib | |
| CN118924766A (en) | Application of pentacyclic triterpenoid structure-modified compounds in the preparation of vitiligo drugs and new preparations | |
| BENNETT | Review of selected aspects of pharmacology | |
| Butler | Changes in renal function | |
| UTZ | General side effects | |
| Saxena et al. | Subgroup results from KARDIA-2: impact of demographic and baseline disease characteristics on zilebesiran response in patients with hypertension uncontrolled by a standard oral antihypertensive | |
| JP2001163783A (en) | External preparation for skin disease treatment | |
| Manna et al. | A review on potential drug delivery system as a treatment of intercellular bacterial infection | |
| CN116898830A (en) | Use of irismol in the preparation of medicines that promote skin wound healing | |
| MAGNER et al. | Successful treatment of pemphigus with heparin | |
| CN107814777A (en) | A kind of compound for treating liver fibrosis and its application | |
| CN116808045A (en) | Use of HDAC5 activator VLX600 in the preparation of drugs to promote skin wound healing | |
| RU2228742C2 (en) | Method for treating relapsing equine iridocyclochorioiditis | |
| JP3568881B2 (en) | External preparation for skin disease treatment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Patent granted |
Effective date: 20231026 |