ES2776628T3 - Amida seleccionada del ácido ?-hidroxibutírico y usos de la misma en el tratamiento del uso inapropiado del alcohol - Google Patents
Amida seleccionada del ácido ?-hidroxibutírico y usos de la misma en el tratamiento del uso inapropiado del alcohol Download PDFInfo
- Publication number
- ES2776628T3 ES2776628T3 ES16791313T ES16791313T ES2776628T3 ES 2776628 T3 ES2776628 T3 ES 2776628T3 ES 16791313 T ES16791313 T ES 16791313T ES 16791313 T ES16791313 T ES 16791313T ES 2776628 T3 ES2776628 T3 ES 2776628T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- alcohol
- formula
- treatment
- acget61
- 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.)
- Active
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims description 109
- 150000001408 amides Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 23
- 208000007848 Alcoholism Diseases 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 201000007930 alcohol dependence Diseases 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 206010013663 drug dependence Diseases 0.000 claims description 7
- 208000011117 substance-related disease Diseases 0.000 claims description 7
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 206010022437 insomnia Diseases 0.000 claims description 6
- VHDGWXQBVWAMJA-UHFFFAOYSA-N methyl 4-methoxybutanoate Chemical compound COCCCC(=O)OC VHDGWXQBVWAMJA-UHFFFAOYSA-N 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000009132 Catalepsy Diseases 0.000 claims description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 2
- 206010039897 Sedation Diseases 0.000 claims description 2
- 206010047853 Waxy flexibility Diseases 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 201000006517 essential tremor Diseases 0.000 claims description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 2
- 201000003631 narcolepsy Diseases 0.000 claims description 2
- 230000004112 neuroprotection Effects 0.000 claims description 2
- 208000001797 obstructive sleep apnea Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 230000036280 sedation Effects 0.000 claims description 2
- 201000002859 sleep apnea Diseases 0.000 claims description 2
- 208000025746 alcohol use disease Diseases 0.000 claims 1
- 229930188620 butyrolactone Natural products 0.000 claims 1
- YEJRWHAVMIAJKC-UHFFFAOYSA-N gamma-butyrolactone Natural products O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 description 28
- 239000000203 mixture Substances 0.000 description 27
- 241000700159 Rattus Species 0.000 description 22
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 15
- 229930195712 glutamate Natural products 0.000 description 15
- 230000000971 hippocampal effect Effects 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 12
- 239000003642 reactive oxygen metabolite Substances 0.000 description 12
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 11
- 229930006000 Sucrose Natural products 0.000 description 11
- 239000005720 sucrose Substances 0.000 description 11
- QLZOWJNFLXSDSH-UHFFFAOYSA-N 4-methoxy-n-[[4-(trifluoromethyl)phenyl]methyl]butanamide Chemical compound COCCCC(=O)NCC1=CC=C(C(F)(F)F)C=C1 QLZOWJNFLXSDSH-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000003833 cell viability Effects 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 230000009467 reduction Effects 0.000 description 7
- UNIDAFCQFPGYJJ-UHFFFAOYSA-N 2-amino-2-(2-chloro-5-hydroxyphenyl)acetic acid Chemical compound OC(=O)C(N)C1=CC(O)=CC=C1Cl UNIDAFCQFPGYJJ-UHFFFAOYSA-N 0.000 description 6
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 230000002075 anti-alcohol Effects 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 210000001320 hippocampus Anatomy 0.000 description 6
- 230000000324 neuroprotective effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 5
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
- 239000000314 lubricant Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 206010012335 Dependence Diseases 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- VWYANPOOORUCFJ-UHFFFAOYSA-N alpha-Fernenol Chemical compound CC1(C)C(O)CCC2(C)C3=CCC4(C)C5CCC(C(C)C)C5(C)CCC4(C)C3CCC21 VWYANPOOORUCFJ-UHFFFAOYSA-N 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000001603 reducing effect Effects 0.000 description 4
- 230000002787 reinforcement Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229960003928 sodium oxybate Drugs 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940099112 cornstarch Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 2
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001032845 Homo sapiens Metabotropic glutamate receptor 5 Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 2
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 2
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 208000029650 alcohol withdrawal Diseases 0.000 description 2
- 235000013334 alcoholic beverage Nutrition 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 210000004295 hippocampal neuron Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- NRBNGHCYDWUVLC-UHFFFAOYSA-N mtep Chemical compound S1C(C)=NC(C#CC=2C=NC=CC=2)=C1 NRBNGHCYDWUVLC-UHFFFAOYSA-N 0.000 description 2
- 229940126662 negative allosteric modulator Drugs 0.000 description 2
- 230000001722 neurochemical effect Effects 0.000 description 2
- 230000002887 neurotoxic effect Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000003014 reinforcing effect Effects 0.000 description 2
- MYFATKRONKHHQL-UHFFFAOYSA-N rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C2C=CC(=[NH2+])C=C2OC2=CC(N)=CC=C21 MYFATKRONKHHQL-UHFFFAOYSA-N 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- JEEVPUIUWRQPCU-ZBEIYLNJSA-N (1ar,2r,2's,3r,7bs)-2-hydroxy-2',3,3a-trimethyl-6-oxospiro[2,3,4,7b-tetrahydro-1ah-naphtho[1,2-b]oxirene-5,3'-oxirane]-2'-carbaldehyde Chemical compound C1([C@@H]2O[C@@H]2[C@H](O)[C@@H](C1(C1)C)C)=CC(=O)C21O[C@]2(C)C=O JEEVPUIUWRQPCU-ZBEIYLNJSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- 206010053164 Alcohol withdrawal syndrome Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 1
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 description 1
- 102100036834 Metabotropic glutamate receptor 1 Human genes 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 206010048010 Withdrawal syndrome Diseases 0.000 description 1
- INAPMGSXUVUWAF-GCVPSNMTSA-N [(2r,3s,5r,6r)-2,3,4,5,6-pentahydroxycyclohexyl] dihydrogen phosphate Chemical compound OC1[C@H](O)[C@@H](O)C(OP(O)(O)=O)[C@H](O)[C@@H]1O INAPMGSXUVUWAF-GCVPSNMTSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 230000008856 allosteric binding Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- APUPEJJSWDHEBO-UHFFFAOYSA-P ammonium molybdate Chemical compound [NH4+].[NH4+].[O-][Mo]([O-])(=O)=O APUPEJJSWDHEBO-UHFFFAOYSA-P 0.000 description 1
- 235000018660 ammonium molybdate Nutrition 0.000 description 1
- 239000011609 ammonium molybdate Substances 0.000 description 1
- 229940010552 ammonium molybdate Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 229960000794 baclofen Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical compound [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229940059082 douche Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 108010014719 metabotropic glutamate receptor type 1 Proteins 0.000 description 1
- 102000006239 metabotropic receptors Human genes 0.000 description 1
- 108020004083 metabotropic receptors Proteins 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
- 229960003086 naltrexone Drugs 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000001962 neuropharmacologic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000001009 nucleus accumben Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000000506 psychotropic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- -1 sticks Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000035899 viability Effects 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITUB2015A002860A ITUB20152860A1 (it) | 2015-08-04 | 2015-08-04 | Selezionata amide dell?acido ?-idrossibutirrico e suoi usi nel trattamento dell?abuso da alcool |
| PCT/EP2016/068517 WO2017021438A1 (en) | 2015-08-04 | 2016-08-03 | SELECTED AMIDE OF γ -HYDROXYBUTYRIC ACID AND USES THEREOF IN THE TREATMENT OF ALCOHOL MISUSE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2776628T3 true ES2776628T3 (es) | 2020-07-31 |
Family
ID=54542363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16791313T Active ES2776628T3 (es) | 2015-08-04 | 2016-08-03 | Amida seleccionada del ácido ?-hidroxibutírico y usos de la misma en el tratamiento del uso inapropiado del alcohol |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US10336687B2 (enExample) |
| EP (1) | EP3331853B1 (enExample) |
| JP (1) | JP6832336B2 (enExample) |
| KR (1) | KR102817897B1 (enExample) |
| CN (1) | CN108026029B (enExample) |
| AU (1) | AU2016302869B2 (enExample) |
| CA (1) | CA2994599C (enExample) |
| CL (1) | CL2018000282A1 (enExample) |
| CO (1) | CO2018002428A2 (enExample) |
| DK (1) | DK3331853T3 (enExample) |
| EA (1) | EA033769B9 (enExample) |
| ES (1) | ES2776628T3 (enExample) |
| GE (1) | GEP20207107B (enExample) |
| IL (1) | IL257314B (enExample) |
| IT (1) | ITUB20152860A1 (enExample) |
| MX (1) | MX2018001239A (enExample) |
| MY (1) | MY185942A (enExample) |
| PH (1) | PH12018550008A1 (enExample) |
| PL (1) | PL3331853T3 (enExample) |
| PT (1) | PT3331853T (enExample) |
| SM (1) | SMT202000337T1 (enExample) |
| UA (1) | UA121994C2 (enExample) |
| WO (1) | WO2017021438A1 (enExample) |
| ZA (1) | ZA201801402B (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA3066711A1 (en) | 2017-07-31 | 2019-02-07 | Novartis Ag | Use of mavoglurant in the reduction of cocaine use or in preventing relapse into cocaine use |
| US12201612B2 (en) | 2017-07-31 | 2025-01-21 | Novartis Ag | Use of mavoglurant in the reduction of alcohol use or in preventing relapse into alcohol use |
| CN113185403A (zh) * | 2021-07-02 | 2021-07-30 | 山东国邦药业有限公司 | 一种甲醚制备环丙胺中间体环丙甲酸甲酯的方法 |
| WO2023126076A1 (en) * | 2022-01-03 | 2023-07-06 | Laboratorio Farmaceutico C.T. S.R.L. | Medical use of an amide of y-hydroxybutyric acid in the treatment of fragile x syndrome |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1283782B1 (it) * | 1996-08-09 | 1998-04-30 | Ct Lab Farm Srl | Uso di ammidi dell'acido gamma-idrossibutirrico nel trattamento di tossicodipendenze,ed in particolare sell'alcolismo |
-
2015
- 2015-08-04 IT ITUB2015A002860A patent/ITUB20152860A1/it unknown
-
2016
- 2016-08-03 KR KR1020187006231A patent/KR102817897B1/ko active Active
- 2016-08-03 ES ES16791313T patent/ES2776628T3/es active Active
- 2016-08-03 GE GEAP201614717A patent/GEP20207107B/en unknown
- 2016-08-03 US US15/750,047 patent/US10336687B2/en active Active
- 2016-08-03 PT PT167913136T patent/PT3331853T/pt unknown
- 2016-08-03 DK DK16791313.6T patent/DK3331853T3/da active
- 2016-08-03 JP JP2018502356A patent/JP6832336B2/ja not_active Expired - Fee Related
- 2016-08-03 AU AU2016302869A patent/AU2016302869B2/en not_active Ceased
- 2016-08-03 UA UAA201801726A patent/UA121994C2/uk unknown
- 2016-08-03 MY MYPI2018700405A patent/MY185942A/en unknown
- 2016-08-03 CN CN201680045364.9A patent/CN108026029B/zh not_active Expired - Fee Related
- 2016-08-03 MX MX2018001239A patent/MX2018001239A/es active IP Right Grant
- 2016-08-03 WO PCT/EP2016/068517 patent/WO2017021438A1/en not_active Ceased
- 2016-08-03 EA EA201890419A patent/EA033769B9/ru not_active IP Right Cessation
- 2016-08-03 SM SM20200337T patent/SMT202000337T1/it unknown
- 2016-08-03 PL PL16791313T patent/PL3331853T3/pl unknown
- 2016-08-03 EP EP16791313.6A patent/EP3331853B1/en active Active
- 2016-08-03 CA CA2994599A patent/CA2994599C/en active Active
-
2018
- 2018-01-31 CL CL2018000282A patent/CL2018000282A1/es unknown
- 2018-02-01 IL IL257314A patent/IL257314B/en active IP Right Grant
- 2018-02-02 PH PH12018550008A patent/PH12018550008A1/en unknown
- 2018-02-28 ZA ZA2018/01402A patent/ZA201801402B/en unknown
- 2018-03-02 CO CONC2018/0002428A patent/CO2018002428A2/es unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240335418A1 (en) | Safer psychoactive compositions | |
| ES2587368T3 (es) | Derivados deuterados de catecolamina y medicamentos que comprenden dichos compuestos | |
| KR101991327B1 (ko) | 오피오이드 수용체 리간드와 그 용도 및 제조방법 | |
| ES2535466T3 (es) | Compuestos específicos de diariltiohidantoína | |
| ES2776628T3 (es) | Amida seleccionada del ácido ?-hidroxibutírico y usos de la misma en el tratamiento del uso inapropiado del alcohol | |
| CN103739553B (zh) | 含有醚侧链的n-取代咪唑羧酸酯手性化合物、制备方法和用途 | |
| ES2573315T3 (es) | Derivados de 5-metil-1-(naftalen-2-il)-1H-pirazol y su uso en potenciar el efecto de analgésicos opioides | |
| Jose et al. | Structure–activity relationships for ketamine esters as short-acting anaesthetics | |
| ES2802049T3 (es) | Derivados de ácido alfa- y gamma-truxílico y composiciones farmacéuticas de los mismos | |
| Zapata-Sudo et al. | Sedative–hypnotic profile of novel isatin ketals | |
| ES2881267T3 (es) | Antagonistas/agonistas parciales selectivos del receptor D3 de dopamina; método de preparación; y uso de los mismos | |
| US9023788B2 (en) | Methods compounds and pharmaceutical compositions for treating anxiety and mood disorders | |
| US6169094B1 (en) | Compositions of (S) (-)-amisulpride | |
| Dong et al. | Synthesis and pharmacological activity of vinpocetine derivatives | |
| ES2967976T3 (es) | Compuestos dirigidos a receptor de serotonina | |
| ES2819833T3 (es) | Compuestos orgánicos | |
| US10590167B2 (en) | NMDA receptor modulators and prodrugs, salts, and uses thereof | |
| KR102235994B1 (ko) | 환상 아민 유도체의 결정 및 그 의약 용도 | |
| ES2655646T3 (es) | Derivados de fentanilo como agonistas de receptores opioides dependientes del PH | |
| PT86776B (pt) | Processo para a preparacao de acido piperazinocarboxilico e de composicoes farmaceuticas que o contem | |
| ES2553891T3 (es) | Derivados de piridina como moduladores NET/SERT | |
| CN110878048B (zh) | 作为防治精神障碍疾病的苯胺类化合物 | |
| BR112018002245B1 (pt) | Composto amida selecionado do ácido ?-hidroxybutírico, processo para a preparação do referido composto, uso do referido composto e composição farmacêutica compreendendo o referido composto | |
| WO2024124050A1 (en) | Multicyclic compounds | |
| WO2025260159A1 (en) | Isoindoline and indoline derivative compounds, combinations, pharmaceutical compositions, medicaments, use of the compounds and method of treatment of pain |