NO328305B1 - Kinazolinonderivater, fremgangsmate for fremstilling og en farmasoytisk sammensetning omfattende disse - Google Patents

Kinazolinonderivater, fremgangsmate for fremstilling og en farmasoytisk sammensetning omfattende disse Download PDF

Info

Publication number: NO328305B1
Authority: NO; Norway
Prior art keywords: formula; compound; preparation; ethyl ester; solution
Prior art date: 2002-02-06

Application number

NO20043580A

Other languages

English (en)

Norwegian (no)

Other versions

NO20043580L (no

NO20043580D0 (no

Inventor

Christopher Thomas Brain

Edward Karol Dziadulewicz

Terance William Hart

Original Assignee

Novartis Ag

Priority date (The priority date 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 date listed.)

2002-02-06

Filing date

2004-08-27

Publication date

2010-01-25

2002-02-06 Priority claimed from GB0202755A external-priority patent/GB0202755D0/en

2002-06-10 Priority claimed from GB0213285A external-priority patent/GB0213285D0/en

2002-09-16 Priority claimed from GB0221460A external-priority patent/GB0221460D0/en

2002-09-16 Priority claimed from GB0221459A external-priority patent/GB0221459D0/en

2004-08-27 Application filed by Novartis Ag filed Critical Novartis Ag

2004-08-27 Publication of NO20043580D0 publication Critical patent/NO20043580D0/no

2004-09-21 Publication of NO20043580L publication Critical patent/NO20043580L/no

2010-01-25 Publication of NO328305B1 publication Critical patent/NO328305B1/no

Links

238000002360 preparation method Methods 0.000 title claims description 41
238000000034 method Methods 0.000 title claims description 21
230000008569 process Effects 0.000 title claims description 5
239000008194 pharmaceutical composition Substances 0.000 title claims description 3
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 91
229910052739 hydrogen Inorganic materials 0.000 claims description 75
239000001257 hydrogen Substances 0.000 claims description 24
150000003839 salts Chemical group 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 10
239000012458 free base Substances 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
PMBUDILHPXTDNY-UHFFFAOYSA-N ethyl 2-(2-hydroxyethylcarbamoyloxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylate Chemical compound O=C1C2=C(C)C(C(=O)OCC)=C(C)C=C2N=C(COC(=O)NCCO)N1C1=CC=CC=C1S(=O)(=O)NC PMBUDILHPXTDNY-UHFFFAOYSA-N 0.000 claims description 3
UFXNCSRAJJJLJN-UHFFFAOYSA-N ethyl 2-(ethylcarbamoyloxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylate Chemical compound CCNC(=O)OCC1=NC2=CC(C)=C(C(=O)OCC)C(C)=C2C(=O)N1C1=CC=CC=C1S(=O)(=O)NC UFXNCSRAJJJLJN-UHFFFAOYSA-N 0.000 claims description 3
239000008024 pharmaceutical diluent Substances 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
239000000243 solution Substances 0.000 description 57
239000011541 reaction mixture Substances 0.000 description 46
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
239000012074 organic phase Substances 0.000 description 30
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
239000003795 chemical substances by application Substances 0.000 description 26
239000000725 suspension Substances 0.000 description 26
239000007787 solid Substances 0.000 description 23
239000008346 aqueous phase Substances 0.000 description 19
239000003921 oil Substances 0.000 description 16
235000019198 oils Nutrition 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 14
238000012360 testing method Methods 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
-1 2,3-dihydroxypropyl Chemical group 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
239000012267 brine Substances 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
239000002904 solvent Substances 0.000 description 12
239000007858 starting material Substances 0.000 description 12
238000003756 stirring Methods 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
238000001914 filtration Methods 0.000 description 10
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
241000700159 Rattus Species 0.000 description 9
230000004913 activation Effects 0.000 description 9
201000010099 disease Diseases 0.000 description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
239000012528 membrane Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
208000010412 Glaucoma Diseases 0.000 description 8
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000012071 phase Substances 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
208000002193 Pain Diseases 0.000 description 7
239000000872 buffer Substances 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
239000000203 mixture Substances 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
102000018208 Cannabinoid Receptor Human genes 0.000 description 6
108050007331 Cannabinoid receptor Proteins 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
239000011324 bead Substances 0.000 description 6
238000010828 elution Methods 0.000 description 6
239000010410 layer Substances 0.000 description 6
230000014759 maintenance of location Effects 0.000 description 6
239000000825 pharmaceutical preparation Substances 0.000 description 6
238000001525 receptor binding assay Methods 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000011734 sodium Substances 0.000 description 6
239000011343 solid material Substances 0.000 description 6
102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 5
108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 5
102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 5
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
QGWNDRXFNXRZMB-UUOKFMHZSA-K GDP(3-) Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-K 0.000 description 5
208000004454 Hyperalgesia Diseases 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
239000007832 Na2SO4 Substances 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
230000027455 binding Effects 0.000 description 5
238000001514 detection method Methods 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
210000001328 optic nerve Anatomy 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
238000002560 therapeutic procedure Methods 0.000 description 5
OFBXYQLWNDBECP-UHFFFAOYSA-N 1-o-ethyl 3-o-methyl 4-amino-2,6-dimethylbenzene-1,3-dicarboxylate Chemical compound CCOC(=O)C1=C(C)C=C(N)C(C(=O)OC)=C1C OFBXYQLWNDBECP-UHFFFAOYSA-N 0.000 description 4
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
SSEZSHJJNNLTQI-UHFFFAOYSA-N 2-amino-n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC=C1N SSEZSHJJNNLTQI-UHFFFAOYSA-N 0.000 description 4
IZIUWDBVKJOXMF-UHFFFAOYSA-N 3-ethoxycarbonyl-2,4-dimethyl-6-[(2-phenylmethoxyacetyl)amino]benzoic acid Chemical compound OC(=O)C1=C(C)C(C(=O)OCC)=C(C)C=C1NC(=O)COCC1=CC=CC=C1 IZIUWDBVKJOXMF-UHFFFAOYSA-N 0.000 description 4
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 compound 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 description 4
RTKLEOHYDUERAO-UHFFFAOYSA-N 4-ethoxycarbonyl-2-methoxycarbonyl-3,5-dimethylbenzoic acid Chemical compound CCOC(=O)C1=C(C)C=C(C(O)=O)C(C(=O)OC)=C1C RTKLEOHYDUERAO-UHFFFAOYSA-N 0.000 description 4
GNGNMHQUAACNST-UHFFFAOYSA-N 6-amino-3-ethoxycarbonyl-2,4-dimethylbenzoic acid Chemical compound CCOC(=O)C1=C(C)C=C(N)C(C(O)=O)=C1C GNGNMHQUAACNST-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 4
208000035154 Hyperesthesia Diseases 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000008186 active pharmaceutical agent Substances 0.000 description 4
239000000556 agonist Substances 0.000 description 4
239000012131 assay buffer Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
229930003827 cannabinoid Natural products 0.000 description 4
239000003557 cannabinoid Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
229940088679 drug related substance Drugs 0.000 description 4
230000000694 effects Effects 0.000 description 4
KHPXDOBGSHNKDM-UHFFFAOYSA-N ethyl 2-(hydroxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylate Chemical compound O=C1C2=C(C)C(C(=O)OCC)=C(C)C=C2N=C(CO)N1C1=CC=CC=C1S(=O)(=O)NC KHPXDOBGSHNKDM-UHFFFAOYSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
230000002757 inflammatory effect Effects 0.000 description 4
150000002500 ions Chemical class 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
DLJPYODODWSDBI-UHFFFAOYSA-N n-methyl-2-nitrobenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC=C1[N+]([O-])=O DLJPYODODWSDBI-UHFFFAOYSA-N 0.000 description 4
208000004296 neuralgia Diseases 0.000 description 4
208000021722 neuropathic pain Diseases 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
230000002265 prevention Effects 0.000 description 4
238000000746 purification Methods 0.000 description 4
238000001665 trituration Methods 0.000 description 4
WUFSMRKPYVAIFZ-UHFFFAOYSA-N 2-(hydroxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylic acid Chemical compound CNS(=O)(=O)C1=CC=CC=C1N1C(=O)C2=C(C)C(C(O)=O)=C(C)C=C2N=C1CO WUFSMRKPYVAIFZ-UHFFFAOYSA-N 0.000 description 3
FHUSFHDCSMXIBP-UHFFFAOYSA-N 4-o-ethyl 1-o,2-o-dimethyl 3,5-dimethylbenzene-1,2,4-tricarboxylate Chemical compound CCOC(=O)C1=C(C)C=C(C(=O)OC)C(C(=O)OC)=C1C FHUSFHDCSMXIBP-UHFFFAOYSA-N 0.000 description 3
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
108091006027 G proteins Proteins 0.000 description 3
102000030782 GTP binding Human genes 0.000 description 3
108091000058 GTP-Binding Proteins 0.000 description 3
XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
206010065390 Inflammatory pain Diseases 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
241000283973 Oryctolagus cuniculus Species 0.000 description 3
241000276498 Pollachius virens Species 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000003110 anti-inflammatory effect Effects 0.000 description 3
238000003556 assay Methods 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
230000001684 chronic effect Effects 0.000 description 3
239000006071 cream Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
XSGIMQYPEVHEGE-UHFFFAOYSA-N ethyl 5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxo-2-(phenylmethoxymethyl)quinazoline-6-carboxylate Chemical compound C=1C=CC=C(S(=O)(=O)NC)C=1N1C(=O)C2=C(C)C(C(=O)OCC)=C(C)C=C2N=C1COCC1=CC=CC=C1 XSGIMQYPEVHEGE-UHFFFAOYSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000006260 foam Substances 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
239000003446 ligand Substances 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000002821 scintillation proximity assay Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 2
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 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
WPHUUIODWRNJLO-UHFFFAOYSA-N 2-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1S(Cl)(=O)=O WPHUUIODWRNJLO-UHFFFAOYSA-N 0.000 description 2
QISAUDWTBBNJIR-UHFFFAOYSA-N 2-phenylmethoxyacetyl chloride Chemical compound ClC(=O)COCC1=CC=CC=C1 QISAUDWTBBNJIR-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
208000020925 Bipolar disease Diseases 0.000 description 2
238000006418 Brown reaction Methods 0.000 description 2
101710187010 Cannabinoid receptor 1 Proteins 0.000 description 2
102100033868 Cannabinoid receptor 1 Human genes 0.000 description 2
208000000094 Chronic Pain Diseases 0.000 description 2
102000010907 Cyclooxygenase 2 Human genes 0.000 description 2
108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
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 2
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
101000710899 Homo sapiens Cannabinoid receptor 1 Proteins 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical group C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 2
208000022873 Ocular disease Diseases 0.000 description 2
BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
206010033645 Pancreatitis Diseases 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
HQVHOQAKMCMIIM-HXUWFJFHSA-N WIN 55212-2 Chemical compound C([C@@H]1COC=2C=CC=C3C(C(=O)C=4C5=CC=CC=C5C=CC=4)=C(N1C3=2)C)N1CCOCC1 HQVHOQAKMCMIIM-HXUWFJFHSA-N 0.000 description 2
108010046516 Wheat Germ Agglutinins Proteins 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
230000000202 analgesic effect Effects 0.000 description 2
239000000730 antalgic agent Substances 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
239000002585 base Substances 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
239000003537 cannabinoid receptor agonist Substances 0.000 description 2
229940121376 cannabinoid receptor agonist Drugs 0.000 description 2
201000003146 cystitis Diseases 0.000 description 2
230000006378 damage Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 2
208000027866 inflammatory disease Diseases 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
208000014674 injury Diseases 0.000 description 2
230000004410 intraocular pressure Effects 0.000 description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
230000004770 neurodegeneration Effects 0.000 description 2
208000015122 neurodegenerative disease Diseases 0.000 description 2
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
239000006186 oral dosage form Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 2
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000002287 radioligand Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
238000011160 research Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
210000003497 sciatic nerve Anatomy 0.000 description 2
208000017520 skin disease Diseases 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 2
MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
MOUDFOLIRVUWKC-UHFFFAOYSA-N 3,3-dichloropentane Chemical compound CCC(Cl)(Cl)CC MOUDFOLIRVUWKC-UHFFFAOYSA-N 0.000 description 1
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
HVKHPNRUJWGELU-UHFFFAOYSA-N 3-o-ethyl 1-o-methyl 2,4-dimethyl-6-[(2-methylpropan-2-yl)oxycarbonylamino]benzene-1,3-dicarboxylate Chemical compound CCOC(=O)C1=C(C)C=C(NC(=O)OC(C)(C)C)C(C(=O)OC)=C1C HVKHPNRUJWGELU-UHFFFAOYSA-N 0.000 description 1
239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
208000008811 Agoraphobia Diseases 0.000 description 1
101100219283 Amycolatopsis orientalis cyp165C4 gene Proteins 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
208000006820 Arthralgia Diseases 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
208000008035 Back Pain Diseases 0.000 description 1
206010006002 Bone pain Diseases 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
206010058019 Cancer Pain Diseases 0.000 description 1
230000010737 Cannabinoid Receptor Interactions Effects 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
CPODOCVRVHEAAA-UHFFFAOYSA-N ClC(=O)OC1=CC=CC=C1.[N] Chemical compound ClC(=O)OC1=CC=CC=C1.[N] CPODOCVRVHEAAA-UHFFFAOYSA-N 0.000 description 1
GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
238000011767 DBA/2J (JAX™ mouse strain) Methods 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
208000032131 Diabetic Neuropathies Diseases 0.000 description 1
102100033902 Endothelin-1 Human genes 0.000 description 1
101800004490 Endothelin-1 Proteins 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
208000001640 Fibromyalgia Diseases 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
101000875075 Homo sapiens Cannabinoid receptor 2 Proteins 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
208000034693 Laceration Diseases 0.000 description 1
208000008930 Low Back Pain Diseases 0.000 description 1
206010026749 Mania Diseases 0.000 description 1
206010027951 Mood swings Diseases 0.000 description 1
208000007101 Muscle Cramp Diseases 0.000 description 1
208000008238 Muscle Spasticity Diseases 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
206010067013 Normal tension glaucoma Diseases 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
208000004983 Phantom Limb Diseases 0.000 description 1
206010056238 Phantom pain Diseases 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
208000025747 Rheumatic disease Diseases 0.000 description 1
206010041243 Social avoidant behaviour Diseases 0.000 description 1
208000005392 Spasm Diseases 0.000 description 1
101710137302 Surface antigen S Proteins 0.000 description 1
208000004760 Tenosynovitis Diseases 0.000 description 1
206010044565 Tremor Diseases 0.000 description 1
229940123445 Tricyclic antidepressant Drugs 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
206010046851 Uveitis Diseases 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
108010027597 alpha-chymotrypsin Proteins 0.000 description 1
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 description 1
239000003708 ampul Substances 0.000 description 1
229940025141 anafranil Drugs 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
238000010171 animal model Methods 0.000 description 1
210000002159 anterior chamber Anatomy 0.000 description 1
239000000604 anti-edema agent Substances 0.000 description 1
230000003501 anti-edematous effect Effects 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
239000006067 antibiotic powder Substances 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 description 1
210000001742 aqueous humor Anatomy 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
208000028683 bipolar I disease Diseases 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
OBWKXZLNLCXWIH-UHFFFAOYSA-N butyl 2-(hydroxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylate Chemical compound O=C1C2=C(C)C(C(=O)OCCCC)=C(C)C=C2N=C(CO)N1C1=CC=CC=C1S(=O)(=O)NC OBWKXZLNLCXWIH-UHFFFAOYSA-N 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000003554 cannabinoid 1 receptor agonist Substances 0.000 description 1
239000003556 cannabinoid 2 receptor agonist Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
229960000590 celecoxib Drugs 0.000 description 1
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 1
CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
229960004475 chlortetracycline Drugs 0.000 description 1
235000019365 chlortetracycline Nutrition 0.000 description 1
238000011260 co-administration Methods 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
229940111134 coxibs Drugs 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 1
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
239000008298 dragée Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
229940011681 elavil Drugs 0.000 description 1
WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
239000003257 excitatory amino acid Substances 0.000 description 1
230000002461 excitatory amino acid Effects 0.000 description 1
230000003492 excitotoxic effect Effects 0.000 description 1
231100000063 excitotoxicity Toxicity 0.000 description 1
239000000284 extract Substances 0.000 description 1
230000004438 eyesight Effects 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
238000002825 functional assay Methods 0.000 description 1
229960002870 gabapentin Drugs 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
238000002682 general surgery Methods 0.000 description 1
208000037870 generalized anxiety Diseases 0.000 description 1
239000011521 glass Substances 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
229940029575 guanosine Drugs 0.000 description 1
230000004402 high myopia Effects 0.000 description 1
102000056693 human CNR2 Human genes 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
230000003447 ipsilateral effect Effects 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
230000003908 liver function Effects 0.000 description 1
201000002978 low tension glaucoma Diseases 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000005906 menstruation Effects 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
230000003387 muscular Effects 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
229940087480 norpramin Drugs 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
229940055692 pamelor Drugs 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
230000000649 photocoagulation Effects 0.000 description 1
239000000049 pigment Substances 0.000 description 1
210000002381 plasma Anatomy 0.000 description 1
230000002980 postoperative effect Effects 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
YPZMSENPJMICIF-UHFFFAOYSA-N propyl 2-(2-hydroxyethylcarbamoyloxymethyl)-5,7-dimethyl-3-[2-(methylsulfamoyl)phenyl]-4-oxoquinazoline-6-carboxylate Chemical compound O=C1C2=C(C)C(C(=O)OCCC)=C(C)C=C2N=C(COC(=O)NCCO)N1C1=CC=CC=C1S(=O)(=O)NC YPZMSENPJMICIF-UHFFFAOYSA-N 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
OGQDIIKRQRZXJH-UHFFFAOYSA-N protriptyline hydrochloride Chemical compound [Cl-].C1=CC2=CC=CC=C2C(CCC[NH2+]C)C2=CC=CC=C21 OGQDIIKRQRZXJH-UHFFFAOYSA-N 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
210000001525 retina Anatomy 0.000 description 1
208000032253 retinal ischemia Diseases 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
229960000371 rofecoxib Drugs 0.000 description 1
RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
239000004576 sand Substances 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000000050 smooth muscle relaxant Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
238000007655 standard test method Methods 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000007940 sugar coated tablet Substances 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000011477 surgical intervention Methods 0.000 description 1
229940118176 surmontil Drugs 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
229940041597 tofranil Drugs 0.000 description 1
229940035276 tofranil-pm Drugs 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
239000003029 tricyclic antidepressant agent Substances 0.000 description 1
YDGHCKHAXOUQOS-BTJKTKAUSA-N trimipramine maleate Chemical compound [O-]C(=O)\C=C/C([O-])=O.C1CC2=CC=CC=C2[NH+](CC(C[NH+](C)C)C)C2=CC=CC=C21 YDGHCKHAXOUQOS-BTJKTKAUSA-N 0.000 description 1
210000004291 uterus Anatomy 0.000 description 1
239000000085 vanilloid receptor antagonist Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229940045977 vivactil Drugs 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
- 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
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
- 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
- A61P11/02—Nasal agents, e.g. decongestants
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- 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
- A61P25/28—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
- A61P27/00—Drugs for disorders of the senses
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pulmonology (AREA)
Ophthalmology & Optometry (AREA)
Psychiatry (AREA)
Psychology (AREA)
Anesthesiology (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Otolaryngology (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

NO20043580A 2002-02-06 2004-08-27 Kinazolinonderivater, fremgangsmate for fremstilling og en farmasoytisk sammensetning omfattende disse NO328305B1 (no)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB0202755A GB0202755D0 (en)	2002-02-06	2002-02-06	Organic compounds
GB0213285A GB0213285D0 (en)	2002-06-10	2002-06-10	Organic compound
GB0221460A GB0221460D0 (en)	2002-09-16	2002-09-16	Organic compound
GB0221459A GB0221459D0 (en)	2002-09-16	2002-09-16	Organic compound
PCT/EP2003/001140 WO2003066603A1 (en)	2002-02-06	2003-02-05	Quinazolinone derivatives and their use as cb agonists

Publications (3)

Publication Number	Publication Date
NO20043580D0 NO20043580D0 (no)	2004-08-27
NO20043580L NO20043580L (no)	2004-09-21
NO328305B1 true NO328305B1 (no)	2010-01-25

Family

ID=27739227

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20043580A NO328305B1 (no)	2002-02-06	2004-08-27	Kinazolinonderivater, fremgangsmate for fremstilling og en farmasoytisk sammensetning omfattende disse

Country Status (21)

Country	Link
US (2)	US20050085493A1 (de)
EP (2)	EP2319839A1 (de)
JP (2)	JP4428479B2 (de)
KR (1)	KR100954626B1 (de)
CN (1)	CN100579968C (de)
AR (1)	AR038483A1 (de)
AT (1)	ATE551329T1 (de)
AU (1)	AU2003210212A1 (de)
BR (1)	BR0307461A (de)
CA (1)	CA2471974C (de)
CO (1)	CO5601021A2 (de)
EC (1)	ECSP045219A (de)
ES (1)	ES2384967T3 (de)
MX (1)	MXPA04007641A (de)
MY (1)	MY143958A (de)
NO (1)	NO328305B1 (de)
NZ (1)	NZ571615A (de)
PE (1)	PE20030867A1 (de)
PL (1)	PL370657A1 (de)
TW (1)	TW200306839A (de)
WO (1)	WO2003066603A1 (de)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2000055153A1 (en)	1999-03-17	2000-09-21	Astrazeneca Ab	Amide derivatives
TW200306839A (en)	2002-02-06	2003-12-01	Novartis Ag	Quinazolinone derivatives and their use as CB agonists
GB0324790D0 (en) *	2003-10-24	2003-11-26	Astrazeneca Ab	Amide derivatives
JP2007510649A (ja)	2003-11-04	2007-04-26	メルク　エンド　カムパニー　インコーポレーテッド	置換ナフチリジノン誘導体
SE0303491D0 (sv) *	2003-12-19	2003-12-19	Astrazeneca Ab	New use VI
CN100506802C (zh) *	2004-06-04	2009-07-01	中国科学院上海药物研究所	一类甲酰肽样受体-1调节剂、其制备方法和用途
GB0413618D0 (en) *	2004-06-17	2004-07-21	Novartis Ag	Organic compounds
EP1904068A1 (de) *	2005-07-11	2008-04-02	N.V. Organon	Synergistische kombination zur behandlung von schmerzen (cannabinoid-rezeptor-agonist und opioid-rezeptor-agonist)
GB0525068D0 (en)	2005-12-08	2006-01-18	Novartis Ag	Organic compounds
US20090209536A1 (en) *	2007-06-17	2009-08-20	Kalypsys, Inc.	Aminoquinazoline cannabinoid receptor modulators for treatment of disease
US8349852B2 (en)	2009-01-13	2013-01-08	Novartis Ag	Quinazolinone derivatives useful as vanilloid antagonists
FR2944013B1 (fr) *	2009-04-07	2011-07-15	Sanofi Aventis	Derives de 1-alkyl-cinnolin-4(1h)-one substitues,leur preparation et leur application en therapeutique.
WO2011092293A2 (en)	2010-02-01	2011-08-04	Novartis Ag	Cyclohexyl amide derivatives as crf receptor antagonists
AR080055A1 (es)	2010-02-01	2012-03-07	Novartis Ag	Derivados de pirazolo-[5,1-b]-oxazol como antagonistas de los receptores de crf -1
ES2527849T3 (es)	2010-02-02	2015-01-30	Novartis Ag	Derivados de ciclohexilamida como antagonistas del receptor de CRF
AR086554A1 (es)	2011-05-27	2014-01-08	Novartis Ag	Derivados de la piperidina 3-espirociclica como agonistas de receptores de la ghrelina
JP2015525202A (ja)	2012-05-03	2015-09-03	ノバルティスアーゲー	グレリン受容体アゴニストとしての２，７−ジアザ−スピロ［４，５］デカ−７−イル誘導体のｌ−リンゴ酸塩およびその結晶形態
UY35675A (es)	2013-07-24	2015-02-27	Novartis Ag	Derivados sustituidos de quinazolin-4-ona
CN106146414A (zh) *	2016-07-07	2016-11-23	浙江大学	喹唑啉二酮类衍生物及其制备方法和用途
CN106831502A (zh) *	2017-03-13	2017-06-13	苏州市泽宸贸易有限公司	邻硝基苯磺酰氯、其合成方法及应用
CN109796360B (zh) *	2019-01-30	2022-03-18	上海阿拉丁生化科技股份有限公司	一种3-氨基-2-萘甲酸类化合物的制备工艺

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR6200M (de)	1967-04-18	1968-07-22
DE1803210A1 (de)	1968-10-16	1970-05-14	Troponwerke Dinklage & Co	2-Methyl-3-(3-[4-phenylpiperazinyl-(1)]-2-hydroxypropyl)-chinazolinon-(4) und Verfahren zu seiner Herstellung
JPS5657768A (en) *	1979-10-18	1981-05-20	Masayuki Ishikawa	Novel 4-quinazolone derivative substituted by aromatic residue at 3-position
NZ192392A (en) *	1978-12-19	1983-02-15	M Ishikawa	3-(substituted (phenyl or pyridyl)) -3,4-dihydroquinazolin-4-ones
AU543928B2 (en) *	1981-01-16	1985-05-09	Masayuki Ishikawa	4(311)-quinazolinone derivatives
JPS57118570A (en) *	1981-01-16	1982-07-23	Masayuki Ishikawa	Novel 3-phenyl-4-quinazolone derivative
AU4246793A (en) *	1992-05-13	1993-12-13	Alcon Laboratories, Inc.	Topical ophthalmic compositions comprising a combination of calcium antagonists with known antiglaucoma agents
AU1618697A (en)	1996-02-06	1997-08-28	Japan Tobacco Inc.	Novel compounds and pharmaceutical use thereof
TW200306839A (en)	2002-02-06	2003-12-01	Novartis Ag	Quinazolinone derivatives and their use as CB agonists
SE0303491D0 (sv)	2003-12-19	2003-12-19	Astrazeneca Ab	New use VI
GB0413618D0 (en) *	2004-06-17	2004-07-21	Novartis Ag	Organic compounds

2003
- 2003-01-30 TW TW092102105A patent/TW200306839A/zh unknown
- 2003-02-04 PE PE2003000129A patent/PE20030867A1/es not_active Application Discontinuation
- 2003-02-04 AR ARP030100347A patent/AR038483A1/es unknown
- 2003-02-05 CA CA2471974A patent/CA2471974C/en not_active Expired - Fee Related
- 2003-02-05 CN CN03803448A patent/CN100579968C/zh not_active Expired - Fee Related
- 2003-02-05 ES ES03737316T patent/ES2384967T3/es not_active Expired - Lifetime
- 2003-02-05 MX MXPA04007641A patent/MXPA04007641A/es unknown
- 2003-02-05 EP EP10175740A patent/EP2319839A1/de not_active Withdrawn
- 2003-02-05 AU AU2003210212A patent/AU2003210212A1/en not_active Abandoned
- 2003-02-05 EP EP03737316A patent/EP1472234B1/de not_active Expired - Lifetime
- 2003-02-05 BR BR0307461-7A patent/BR0307461A/pt active Search and Examination
- 2003-02-05 KR KR1020047012147A patent/KR100954626B1/ko not_active Expired - Fee Related
- 2003-02-05 PL PL03370657A patent/PL370657A1/xx unknown
- 2003-02-05 AT AT03737316T patent/ATE551329T1/de active
- 2003-02-05 MY MYPI20030387A patent/MY143958A/en unknown
- 2003-02-05 NZ NZ571615A patent/NZ571615A/en not_active IP Right Cessation
- 2003-02-05 WO PCT/EP2003/001140 patent/WO2003066603A1/en not_active Ceased
- 2003-02-05 US US10/503,779 patent/US20050085493A1/en not_active Abandoned
- 2003-02-05 JP JP2003565977A patent/JP4428479B2/ja not_active Expired - Fee Related
2004
- 2004-08-04 EC EC2004005219A patent/ECSP045219A/es unknown
- 2004-08-25 CO CO04083224A patent/CO5601021A2/es not_active Application Discontinuation
- 2004-08-27 NO NO20043580A patent/NO328305B1/no not_active IP Right Cessation
2007
- 2007-06-26 US US11/823,315 patent/US8552015B2/en not_active Expired - Fee Related
2009
- 2009-01-22 JP JP2009012064A patent/JP2009149658A/ja active Pending

Also Published As

Publication number	Publication date
MY143958A (en)	2011-07-29
JP2005522439A (ja)	2005-07-28
EP1472234A1 (de)	2004-11-03
KR20040083501A (ko)	2004-10-02
KR100954626B1 (ko)	2010-04-27
US20050085493A1 (en)	2005-04-21
CO5601021A2 (es)	2006-01-31
PL370657A1 (en)	2005-05-30
US8552015B2 (en)	2013-10-08
MXPA04007641A (es)	2004-11-10
CN1628104A (zh)	2005-06-15
CN100579968C (zh)	2010-01-13
CA2471974A1 (en)	2003-08-14
EP2319839A1 (de)	2011-05-11
NZ571615A (en)	2010-01-29
AR038483A1 (es)	2005-01-19
TW200306839A (en)	2003-12-01
JP2009149658A (ja)	2009-07-09
ATE551329T1 (de)	2012-04-15
ES2384967T3 (es)	2012-07-16
NO20043580L (no)	2004-09-21
HK1079518A1 (zh)	2006-04-07
PE20030867A1 (es)	2003-12-04
CA2471974C (en)	2011-11-22
WO2003066603A1 (en)	2003-08-14
NO20043580D0 (no)	2004-08-27
AU2003210212A1 (en)	2003-09-02
JP4428479B2 (ja)	2010-03-10
ECSP045219A (es)	2004-09-28
US20070265285A1 (en)	2007-11-15
EP1472234B1 (de)	2012-03-28
BR0307461A (pt)	2004-11-09

Legal Events

Date	Code	Title	Description
2012-10-01	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
US8552015B2 (en)	2013-10-08	Quinazolinone derivatives and their use as CB agonists
ES2786298T3 (es)	2020-10-09	Inhibidores de benzimidazol del canal de sodio
JP2023071709A (ja)	2023-05-23	Ｊａｋファミリーのキナーゼの低分子阻害物質
CN101360738A (zh)	2009-02-04	调节门控离子通道的组合物和方法
RU2396261C2 (ru)	2010-08-10	Производные хиназолинона, полезные в качестве ванилоидных антагонистов
TW200908983A (en)	2009-03-01	Heterocyclic compounds and uses thereof
HUP0000914A2 (hu)	2001-04-28	3-Aril-4 (3H)-kinazolinon-származékok atropizomerjei és ezeket a vegyületeket tartalmazó gyógyszerkészítmények
CA2883172A1 (en)	2014-03-06	Ddr2 inhibitors for the treatment of osteoarthritis
TW201326143A (zh)	2013-07-01	Ｇ蛋白偶合ｍａｓ受體之調節劑及與其相關病症之治療
ES2813108T3 (es)	2021-03-22	Antagonista de TRPV4
AU2020256301A1 (en)	2020-11-05	Fused bicyclic compounds for the treatment of disease
JP2008534597A (ja)	2008-08-28	ＰＫＣ−θのインヒビターとして有用なピリジン誘導体
Wu et al.	2020	The development of a novel transforming growth factor-β (TGF-β) inhibitor that disrupts ligand-receptor interactions
BR112019012920A2 (pt)	2019-12-31	amidas aromáticas de ácido carboxílico como antagonistas do receptor b1 de bradicinina
TW201244720A (en)	2012-11-16	Compounds
KR20030016222A (ko)	2003-02-26	수술후 스트레스 예방ㆍ치료제
KR20000052876A (ko)	2000-08-25	아미노산 수용체의 결합 부위에 친화력을 갖는 벤족사졸 유도체
TW200948804A (en)	2009-12-01	Inhibitors of JNK
JP2025540086A (ja)	2025-12-11	２－オキソキナゾリン結晶形態
AU2007202781B2 (en)	2010-09-09	Quinazolinone derivatives and their use as CB agonists
JP2011201776A (ja)	2011-10-13	ヘテロシクリデン−ｎ−（３，４−ジヒドロ−２（１ｈ）−キナゾリノン−５−イル）アセトアミド誘導体
ZA200404959B (en)	2006-12-27	Quinazolinone derivatives and their use as CB agonists
HK1079518B (en)	2010-09-30	Quinazolinone derivatives and their use as cb agonists
JP2024534282A (ja)	2024-09-19	治療剤として使用するための転写因子ｂｒｎ２阻害性化合物
BR112018073700B1 (pt)	2024-05-14	Composto antagonista de trpv4, composição farmacêutica que compreende dito composto, processo para preparar a composição farmacêutica e usos terapêuticos do composto