ES2640800T3 - Imidazolcarboxamidas y su uso como inhibidores de la FAAH - Google Patents
Imidazolcarboxamidas y su uso como inhibidores de la FAAH Download PDFInfo
- Publication number
- ES2640800T3 ES2640800T3 ES14752676.8T ES14752676T ES2640800T3 ES 2640800 T3 ES2640800 T3 ES 2640800T3 ES 14752676 T ES14752676 T ES 14752676T ES 2640800 T3 ES2640800 T3 ES 2640800T3
- Authority
- ES
- Spain
- Prior art keywords
- salt
- compound
- disease
- mmol
- imidazol
- 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
- 239000003940 fatty acid amidase inhibitor Substances 0.000 title description 8
- NMIZONYLXCOHEF-UHFFFAOYSA-N 1h-imidazole-2-carboxamide Chemical class NC(=O)C1=NC=CN1 NMIZONYLXCOHEF-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims description 32
- -1 salt (2R, 3R) -2 , 3- dihydroxysuccinate Chemical class 0.000 claims description 28
- 102100029111 Fatty-acid amide hydrolase 1 Human genes 0.000 claims description 26
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 150000001200 N-acyl ethanolamides Chemical class 0.000 claims description 10
- 239000002621 endocannabinoid Substances 0.000 claims description 10
- 239000000758 substrate Substances 0.000 claims description 10
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 238000011161 development Methods 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- 208000012661 Dyskinesia Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- BOWVQLFMWHZBEF-KTKRTIGZSA-N oleoyl ethanolamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCO BOWVQLFMWHZBEF-KTKRTIGZSA-N 0.000 claims description 5
- HXYVTAGFYLMHSO-UHFFFAOYSA-N palmitoyl ethanolamide Chemical compound CCCCCCCCCCCCCCCC(=O)NCCO HXYVTAGFYLMHSO-UHFFFAOYSA-N 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010028813 Nausea Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 208000016620 Tourette disease Diseases 0.000 claims description 4
- 206010047700 Vomiting Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 206010015037 epilepsy Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 230000008693 nausea Effects 0.000 claims description 4
- 230000036407 pain Effects 0.000 claims description 4
- 208000030090 Acute Disease Diseases 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 206010006895 Cachexia Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 3
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 3
- 208000022531 anorexia Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 230000005796 circulatory shock Effects 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 206010061428 decreased appetite Diseases 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 108010046094 fatty-acid amide hydrolase Proteins 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 206010022437 insomnia Diseases 0.000 claims description 3
- 229960004502 levodopa Drugs 0.000 claims description 3
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 229950007031 palmidrol Drugs 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000007201 Myocardial reperfusion injury Diseases 0.000 claims description 2
- 206010029350 Neurotoxicity Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 206010030043 Ocular hypertension Diseases 0.000 claims description 2
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 claims description 2
- 159000000021 acetate salts Chemical class 0.000 claims description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 2
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 claims description 2
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 claims description 2
- 230000007135 neurotoxicity Effects 0.000 claims description 2
- 231100000228 neurotoxicity Toxicity 0.000 claims description 2
- 229960002715 nicotine Drugs 0.000 claims description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 229940127240 opiate Drugs 0.000 claims description 2
- 150000003891 oxalate salts Chemical class 0.000 claims description 2
- 239000003368 psychostimulant agent Substances 0.000 claims description 2
- 150000004728 pyruvic acid derivatives Chemical class 0.000 claims description 2
- 230000003893 regulation of appetite Effects 0.000 claims description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 230000008673 vomiting Effects 0.000 claims description 2
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000000725 suspension Substances 0.000 description 28
- 239000007787 solid Substances 0.000 description 25
- 239000000243 solution Substances 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- 235000002639 sodium chloride Nutrition 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- 210000004556 brain Anatomy 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 9
- 230000002093 peripheral effect Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229940125904 compound 1 Drugs 0.000 description 8
- 229940125782 compound 2 Drugs 0.000 description 8
- 229940126214 compound 3 Drugs 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 229940098773 bovine serum albumin Drugs 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- SRPCRBVBOIYYHS-UHFFFAOYSA-N 1-(4-methoxy-3-methylphenyl)ethanone Chemical compound COC1=CC=C(C(C)=O)C=C1C SRPCRBVBOIYYHS-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- VCTYBUSTAGLDKY-UHFFFAOYSA-N 2-bromo-1-(4-methoxy-3-methylphenyl)ethanone Chemical compound COC1=CC=C(C(=O)CBr)C=C1C VCTYBUSTAGLDKY-UHFFFAOYSA-N 0.000 description 3
- RVWRGTAOASDFAJ-UHFFFAOYSA-N 5-(4-methoxy-3-methylphenyl)-1h-imidazole Chemical compound C1=C(C)C(OC)=CC=C1C1=CN=CN1 RVWRGTAOASDFAJ-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 201000002661 Spondylitis Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 206010047115 Vasculitis Diseases 0.000 description 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate 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](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- NVPIRDDUWLQGHI-UHFFFAOYSA-N n-methyl-4-(3-nitrophenyl)-n-(oxan-4-yl)imidazole-1-carboxamide Chemical compound C1=NC(C=2C=C(C=CC=2)[N+]([O-])=O)=CN1C(=O)N(C)C1CCOCC1 NVPIRDDUWLQGHI-UHFFFAOYSA-N 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 239000002858 neurotransmitter agent Substances 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KKVLRRGKTDLJDF-UHFFFAOYSA-N 4-[carbonochloridoyl(methyl)amino]piperidine-1-carboxylic acid Chemical compound ClC(=O)N(C)C1CCN(C(O)=O)CC1 KKVLRRGKTDLJDF-UHFFFAOYSA-N 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- LIKVITVTZVDFGM-UHFFFAOYSA-N CN(C1CCOCC1)C(=O)n1cnc(c1)-c1cccc(N)c1 Chemical compound CN(C1CCOCC1)C(=O)n1cnc(c1)-c1cccc(N)c1 LIKVITVTZVDFGM-UHFFFAOYSA-N 0.000 description 2
- PCLQKVFWQVQSFT-UHFFFAOYSA-N COc1ccc(cc1C)-c1cn(cn1)C(=O)N(C)C1CCN(CC1)C(=O)C1CC1 Chemical compound COc1ccc(cc1C)-c1cn(cn1)C(=O)N(C)C1CCN(CC1)C(=O)C1CC1 PCLQKVFWQVQSFT-UHFFFAOYSA-N 0.000 description 2
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 2
- 108050007331 Cannabinoid receptor Proteins 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 201000005569 Gout Diseases 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
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 102000011040 TRPV Cation Channels Human genes 0.000 description 2
- 108010062740 TRPV Cation Channels Proteins 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000007824 enzymatic assay Methods 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 210000001853 liver microsome Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000006241 metabolic reaction Methods 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- NAKDRLMQKGWRRQ-UHFFFAOYSA-N n-[1-(cyclopropanecarbonyl)piperidin-4-yl]-4-(4-hydroxy-3-methylphenyl)-n-methylimidazole-1-carboxamide Chemical compound C1=NC(C=2C=C(C)C(O)=CC=2)=CN1C(=O)N(C)C(CC1)CCN1C(=O)C1CC1 NAKDRLMQKGWRRQ-UHFFFAOYSA-N 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- SQEUAFKCEUYMBE-UHFFFAOYSA-N phenyl 4-(3-nitrophenyl)imidazole-1-carboxylate Chemical compound [O-][N+](=O)C1=CC=CC(C=2N=CN(C=2)C(=O)OC=2C=CC=CC=2)=C1 SQEUAFKCEUYMBE-UHFFFAOYSA-N 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 238000002731 protein assay Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- LXBHHIZIQVZGFN-UHFFFAOYSA-N 4-hydroxy-3-methylacetophenone Chemical compound CC(=O)C1=CC=C(O)C(C)=C1 LXBHHIZIQVZGFN-UHFFFAOYSA-N 0.000 description 1
- AMSITKGZVUXDQM-UHFFFAOYSA-N 5-(3-nitrophenyl)-1h-imidazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2NC=NC=2)=C1 AMSITKGZVUXDQM-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000027559 Appetite disease Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000030814 Eating disease Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 206010014967 Ependymoma Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 208000001718 Immediate Hypersensitivity Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000000172 Medulloblastoma Diseases 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 201000010133 Oligodendroglioma Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229920000388 Polyphosphate Polymers 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010063897 Renal ischaemia Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 206010045240 Type I hypersensitivity Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 208000010216 atopic IgE responsiveness Diseases 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 208000013355 benign neoplasm of brain Diseases 0.000 description 1
- 206010004398 benign neoplasm of skin Diseases 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229930003827 cannabinoid Natural products 0.000 description 1
- 239000003557 cannabinoid Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 210000004720 cerebrum Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 235000014632 disordered eating Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- CLIDMUTWHLMPMN-UHFFFAOYSA-N imidazole-1-carboxamide Chemical compound NC(=O)N1C=CN=C1 CLIDMUTWHLMPMN-UHFFFAOYSA-N 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 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
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- FPJBDHRFHAHNPA-UHFFFAOYSA-N n-methyl-n-(oxan-4-yl)-4-[3-(sulfamoylamino)phenyl]imidazole-1-carboxamide Chemical compound C1=NC(C=2C=C(NS(N)(=O)=O)C=CC=2)=CN1C(=O)N(C)C1CCOCC1 FPJBDHRFHAHNPA-UHFFFAOYSA-N 0.000 description 1
- WGYZZCUTSHNMET-UHFFFAOYSA-N n-methyloxan-4-amine Chemical compound CNC1CCOCC1 WGYZZCUTSHNMET-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000027831 neuroepithelial neoplasm Diseases 0.000 description 1
- 208000029986 neuroepithelioma Diseases 0.000 description 1
- 208000029974 neurofibrosarcoma Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000029340 primitive neuroectodermal tumor Diseases 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- 208000023958 prostate neoplasm Diseases 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000003774 sarcomatosis Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
- A61P25/34—Tobacco-abuse
-
- 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
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB201313204 | 2013-07-24 | ||
| GB201313202 | 2013-07-24 | ||
| GB201313204A GB201313204D0 (en) | 2013-07-24 | 2013-07-24 | Urea compound and its use as an enzyme inhibitor |
| GB201313203 | 2013-07-24 | ||
| GB201313203A GB201313203D0 (en) | 2013-07-24 | 2013-07-24 | Urea compound and its use as an enzyme inhibitor |
| GB201313202A GB201313202D0 (en) | 2013-07-24 | 2013-07-24 | Urea Compound And Its Use As An Enzyme Inhibitor |
| PCT/PT2014/000049 WO2015012708A1 (en) | 2013-07-24 | 2014-07-24 | Imidazolecarboxamides and their use as faah inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2640800T3 true ES2640800T3 (es) | 2017-11-06 |
Family
ID=51358056
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14752676.8T Active ES2640800T3 (es) | 2013-07-24 | 2014-07-24 | Imidazolcarboxamidas y su uso como inhibidores de la FAAH |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US10501447B2 (enExample) |
| EP (1) | EP3024825B1 (enExample) |
| JP (1) | JP6449277B2 (enExample) |
| KR (1) | KR20160034359A (enExample) |
| CN (1) | CN105793247B (enExample) |
| AU (1) | AU2014293731B2 (enExample) |
| CA (1) | CA2918993C (enExample) |
| CY (1) | CY1119482T1 (enExample) |
| DK (1) | DK3024825T3 (enExample) |
| ES (1) | ES2640800T3 (enExample) |
| HR (1) | HRP20171378T1 (enExample) |
| HU (1) | HUE033615T2 (enExample) |
| LT (1) | LT3024825T (enExample) |
| MX (1) | MX362315B (enExample) |
| PL (1) | PL3024825T3 (enExample) |
| PT (1) | PT3024825T (enExample) |
| RS (1) | RS56297B1 (enExample) |
| RU (1) | RU2671404C2 (enExample) |
| SI (1) | SI3024825T1 (enExample) |
| WO (1) | WO2015012708A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG10201802129QA (en) | 2017-07-05 | 2019-02-27 | Frimline Private Ltd | A pharmaceutical composition for neuropathic pain |
| US10702487B2 (en) | 2017-08-19 | 2020-07-07 | Frimline Private Limited | Pharmaceutical composition for prevention of diet induced obesity |
| PH12018000227B1 (en) | 2017-09-05 | 2019-03-11 | Frimline Private Ltd | A pharmaceutical composition for improving or preventing progression of chronic kidney disease |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2458965C3 (de) | 1974-12-13 | 1979-10-11 | Bayer Ag, 5090 Leverkusen | 3-Amino-indazol-N-carbonsäure-Derivate, Verfahren zu ihrer Herstellung sowie sie enthaltende Arzneimittel |
| EP0014810A3 (en) | 1979-01-18 | 1980-11-26 | Fbc Limited | Pesticidal pyrazoles, their production, compositions and uses, as well as intermediates and their preparation |
| JPH01203366A (ja) | 1988-02-10 | 1989-08-16 | Mitsui Petrochem Ind Ltd | Ｎ−置換イミダゾール誘導体 |
| CA2146755A1 (en) | 1992-10-28 | 1994-05-11 | Kenji Takeda | Novel 1,2-benzoisoxazole derivative or its salt and brain-protecting agent comprising the same |
| DE102004005172A1 (de) | 2004-02-02 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Indazolderivate als Inhibitoren der Hormon Sensitiven Lipase |
| WO2006074025A1 (en) * | 2004-12-30 | 2006-07-13 | Janssen Pharmaceutica N.V. | Piperazinyl and piperidinyl ureas as modulators of fatty acid amide hydrolase |
| FI20075264A0 (fi) | 2007-04-18 | 2007-04-18 | Kuopion Yliopisto | Heterosykliset fenyylikarbamaatit uusina FAAH-inhibiittoreina |
| US8324241B2 (en) | 2008-04-11 | 2012-12-04 | Bristol-Myers Squibb Company | Triazolo compounds useful as DGAT1 inhibitors |
| AU2009330821B2 (en) | 2008-12-24 | 2015-06-11 | Bial - Portela & Ca, S.A. | Pharmaceutical compounds |
| WO2012015324A1 (en) | 2010-07-29 | 2012-02-02 | Bial - Portela & Ca, S.A. | Process for the synthesis of substituted urea compounds |
| FR2965262A1 (fr) | 2010-09-24 | 2012-03-30 | Sanofi Aventis | Derives de nicotinamide, leur preparation et leur application en therapeutique |
| CA2879726A1 (en) | 2012-07-24 | 2014-01-30 | Bial- Portela & Ca, S.A. | Urea compounds and their use as enzyme inhibitors |
-
2014
- 2014-07-24 WO PCT/PT2014/000049 patent/WO2015012708A1/en not_active Ceased
- 2014-07-24 JP JP2016529739A patent/JP6449277B2/ja not_active Expired - Fee Related
- 2014-07-24 RU RU2016104221A patent/RU2671404C2/ru active
- 2014-07-24 MX MX2016000797A patent/MX362315B/es active IP Right Grant
- 2014-07-24 LT LTEP14752676.8T patent/LT3024825T/lt unknown
- 2014-07-24 PL PL14752676T patent/PL3024825T3/pl unknown
- 2014-07-24 EP EP14752676.8A patent/EP3024825B1/en active Active
- 2014-07-24 RS RS20170905A patent/RS56297B1/sr unknown
- 2014-07-24 KR KR1020167004236A patent/KR20160034359A/ko not_active Abandoned
- 2014-07-24 SI SI201430380T patent/SI3024825T1/sl unknown
- 2014-07-24 US US14/906,822 patent/US10501447B2/en not_active Expired - Fee Related
- 2014-07-24 AU AU2014293731A patent/AU2014293731B2/en not_active Ceased
- 2014-07-24 HR HRP20171378TT patent/HRP20171378T1/hr unknown
- 2014-07-24 CN CN201480041611.9A patent/CN105793247B/zh not_active Expired - Fee Related
- 2014-07-24 DK DK14752676.8T patent/DK3024825T3/en active
- 2014-07-24 PT PT147526768T patent/PT3024825T/pt unknown
- 2014-07-24 ES ES14752676.8T patent/ES2640800T3/es active Active
- 2014-07-24 HU HUE14752676A patent/HUE033615T2/hu unknown
- 2014-07-24 CA CA2918993A patent/CA2918993C/en not_active Expired - Fee Related
-
2017
- 2017-09-20 CY CY20171100984T patent/CY1119482T1/el unknown
-
2019
- 2019-12-06 US US16/705,277 patent/US20200255412A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP3024825B1 (en) | 2017-06-21 |
| HRP20171378T1 (hr) | 2017-12-15 |
| US20160176854A1 (en) | 2016-06-23 |
| PL3024825T3 (pl) | 2017-12-29 |
| SI3024825T1 (sl) | 2017-11-30 |
| CN105793247B (zh) | 2018-03-16 |
| RU2671404C2 (ru) | 2018-10-31 |
| JP2016525543A (ja) | 2016-08-25 |
| WO2015012708A1 (en) | 2015-01-29 |
| CA2918993A1 (en) | 2015-01-29 |
| US20200255412A1 (en) | 2020-08-13 |
| DK3024825T3 (en) | 2017-10-02 |
| CA2918993C (en) | 2021-08-24 |
| CN105793247A (zh) | 2016-07-20 |
| JP6449277B2 (ja) | 2019-01-09 |
| AU2014293731A1 (en) | 2016-02-11 |
| US10501447B2 (en) | 2019-12-10 |
| AU2014293731B2 (en) | 2018-03-08 |
| KR20160034359A (ko) | 2016-03-29 |
| PT3024825T (pt) | 2017-09-28 |
| MX362315B (es) | 2019-01-11 |
| MX2016000797A (es) | 2016-09-08 |
| CY1119482T1 (el) | 2018-03-07 |
| LT3024825T (lt) | 2017-12-11 |
| HUE033615T2 (hu) | 2017-12-28 |
| RU2016104221A (ru) | 2017-08-29 |
| EP3024825A1 (en) | 2016-06-01 |
| RS56297B1 (sr) | 2017-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2327760T3 (es) | Compuestos de aril-heteroaril-amida ortosustituidos. | |
| ES2623133T3 (es) | Compuestos de pirrolopirimidina y sus usos | |
| JP2019503385A (ja) | Ｒｏｒ−ガンマのモジュレータとしてのベンズイミダゾール誘導体 | |
| WO2009106980A2 (en) | Indazole derivatives | |
| CN102884052B (zh) | 氧-取代的3-杂芳酰基氨基-丙酸衍生物及其药物用途 | |
| CA2691776A1 (en) | Substituted imidazoheterocycles | |
| KR20100126706A (ko) | 인다졸 유도체 | |
| ES2667056T3 (es) | Compuestos de urea y su uso como inhibidores enzimáticos | |
| JP2007500700A (ja) | 化合物 | |
| US7329678B2 (en) | Chemical compounds | |
| CN104302289A (zh) | 具有激酶抑制活性的二苯基甲醇-吡唑衍生物及其用途 | |
| US20200255412A1 (en) | Imidazolecarboxamides and Their Use as FAAH Inhibitors | |
| US20060106058A1 (en) | Chemical compounds | |
| ES3030634T3 (en) | Substituted pyrrolo [2, 3-d]pyridazin-4-ones and pyrazolo [3, 4-d]pyridazin-4-ones as protein kinase inhibitors | |
| US20080194561A1 (en) | Compounds | |
| JP2025030528A (ja) | グルタミナーゼ１阻害剤 | |
| WO2025217141A1 (en) | Pharmaceutical compounds and compositions as modulators of mas-related g-protein receptor x2 | |
| JP2025521596A (ja) | Ｍａｓ関連ｇタンパク質受容体ｄのモジュレーターとしてのトリアゾール誘導体 | |
| HK1227036A1 (en) | Imidazolecarboxamides and their use as faah inhibitors | |
| HK1227036B (en) | Imidazolecarboxamides and their use as faah inhibitors | |
| OM et al. | SSSeS-ļO) GGGS | |
| WO2015016729A1 (en) | Urea compounds and their use as faah enzyme inhibitors |