ES2384967T3 - Derivados de la quinazolinona y su uso como agonistas de CB - Google Patents
Derivados de la quinazolinona y su uso como agonistas de CB Download PDFInfo
- Publication number
- ES2384967T3 ES2384967T3 ES03737316T ES03737316T ES2384967T3 ES 2384967 T3 ES2384967 T3 ES 2384967T3 ES 03737316 T ES03737316 T ES 03737316T ES 03737316 T ES03737316 T ES 03737316T ES 2384967 T3 ES2384967 T3 ES 2384967T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- formula
- compound
- alkylene
- alkoxy
- 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.)
- Expired - Lifetime
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- 239000000556 agonist Substances 0.000 title description 10
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 96
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 239000001257 hydrogen Substances 0.000 claims abstract description 39
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 31
- 239000002253 acid Substances 0.000 claims abstract description 29
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 25
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 24
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 15
- 125000006413 ring segment Chemical group 0.000 claims abstract description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 12
- 239000012458 free base Substances 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000001301 oxygen Chemical group 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 6
- 229910052717 sulfur Chemical group 0.000 claims abstract description 6
- 239000011593 sulfur Chemical group 0.000 claims abstract description 6
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims abstract description 5
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims abstract description 3
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 20
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
- 208000010412 Glaucoma Diseases 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- -1 2-hydroxyethylcarbamoyloxymethyl Chemical group 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 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 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 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 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 208000030533 eye disease Diseases 0.000 claims description 3
- 206010067013 Normal tension glaucoma Diseases 0.000 claims description 2
- 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 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 201000002978 low tension glaucoma Diseases 0.000 claims description 2
- 210000001328 optic nerve Anatomy 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 208000017442 Retinal disease Diseases 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 230000000626 neurodegenerative effect Effects 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
- 239000000243 solution Substances 0.000 description 75
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 239000011541 reaction mixture Substances 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000002585 base Substances 0.000 description 33
- 239000012074 organic phase Substances 0.000 description 32
- 239000007787 solid Substances 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000000725 suspension Substances 0.000 description 27
- 238000012360 testing method Methods 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- 239000007832 Na2SO4 Substances 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 239000008346 aqueous phase Substances 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 8
- 108050007331 Cannabinoid receptor Proteins 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 235000019502 Orange oil Nutrition 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 238000010828 elution Methods 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000010502 orange oil Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 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 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 208000002193 Pain Diseases 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 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 6
- 239000011343 solid material Substances 0.000 description 6
- 238000001665 trituration Methods 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
- 208000004454 Hyperalgesia Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 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 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000000460 chlorine Chemical group 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000003818 flash chromatography Methods 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
- 230000002757 inflammatory effect Effects 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 238000000746 purification 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
- 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
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- QGWNDRXFNXRZMB-UUOKFMHZSA-N GDP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-N 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
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000002051 biphasic effect Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 239000000463 material Substances 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
- 239000012044 organic layer Substances 0.000 description 4
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- 238000001525 receptor binding assay Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- 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 3
- FDECFGWFSOPULW-UHFFFAOYSA-N 5-amino-3-ethoxycarbonyl-2,4-dimethyl-6-(2-phenylmethoxyacetyl)benzoic acid Chemical compound C(C)OC(C1=C(C(C(=O)O)=C(C(=C1C)N)C(COCC1=CC=CC=C1)=O)C)=O FDECFGWFSOPULW-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- 241000282414 Homo sapiens 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
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- 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 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
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Medicinal Chemistry (AREA)
- Public Health (AREA)
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- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Anesthesiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0202755A GB0202755D0 (en) | 2002-02-06 | 2002-02-06 | Organic compounds |
| GB0202755 | 2002-02-06 | ||
| GB0213285 | 2002-06-10 | ||
| GB0213285A GB0213285D0 (en) | 2002-06-10 | 2002-06-10 | Organic compound |
| GB0221459 | 2002-09-16 | ||
| GB0221460A GB0221460D0 (en) | 2002-09-16 | 2002-09-16 | Organic compound |
| GB0221460 | 2002-09-16 | ||
| 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 (1)
| Publication Number | Publication Date |
|---|---|
| ES2384967T3 true ES2384967T3 (es) | 2012-07-16 |
Family
ID=27739227
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03737316T Expired - Lifetime ES2384967T3 (es) | 2002-02-06 | 2003-02-05 | Derivados de la quinazolinona y su uso como agonistas de CB |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US20050085493A1 (enExample) |
| EP (2) | EP1472234B1 (enExample) |
| JP (2) | JP4428479B2 (enExample) |
| KR (1) | KR100954626B1 (enExample) |
| CN (1) | CN100579968C (enExample) |
| AR (1) | AR038483A1 (enExample) |
| AT (1) | ATE551329T1 (enExample) |
| AU (1) | AU2003210212A1 (enExample) |
| BR (1) | BR0307461A (enExample) |
| CA (1) | CA2471974C (enExample) |
| CO (1) | CO5601021A2 (enExample) |
| EC (1) | ECSP045219A (enExample) |
| ES (1) | ES2384967T3 (enExample) |
| MX (1) | MXPA04007641A (enExample) |
| MY (1) | MY143958A (enExample) |
| NO (1) | NO328305B1 (enExample) |
| NZ (1) | NZ571615A (enExample) |
| PE (1) | PE20030867A1 (enExample) |
| PL (1) | PL370657A1 (enExample) |
| TW (1) | TW200306839A (enExample) |
| WO (1) | WO2003066603A1 (enExample) |
Families Citing this family (21)
| 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 (en) * | 2005-07-11 | 2008-04-02 | N.V. Organon | Synergistic combination for the treatment of pain (cannabioid receptor agonist and opiod receptor 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. |
| EP2531510B1 (en) | 2010-02-01 | 2014-07-23 | Novartis AG | Pyrazolo[5,1b]oxazole derivatives as crf-1 receptor antagonists |
| AR080056A1 (es) | 2010-02-01 | 2012-03-07 | Novartis Ag | Derivados de ciclohexil-amida como antagonistas de los receptores de crf |
| ES2527849T3 (es) | 2010-02-02 | 2015-01-30 | Novartis Ag | Derivados de ciclohexilamida como antagonistas del receptor de CRF |
| US8546416B2 (en) | 2011-05-27 | 2013-10-01 | Novartis Ag | 3-spirocyclic piperidine derivatives as ghrelin receptor agonists |
| CN104271579A (zh) | 2012-05-03 | 2015-01-07 | 诺华股份有限公司 | 作为生长素释放肽受体激动剂的2,7-二氮杂-螺[4,5]癸烷-7-基衍生物的l-苹果酸盐及其结晶 |
| 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)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR6200M (enExample) | 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 |
| JPS57118570A (en) * | 1981-01-16 | 1982-07-23 | Masayuki Ishikawa | Novel 3-phenyl-4-quinazolone derivative |
| AU543928B2 (en) * | 1981-01-16 | 1985-05-09 | Masayuki Ishikawa | 4(311)-quinazolinone derivatives |
| EP0639986A1 (en) * | 1992-05-13 | 1995-03-01 | Alcon Laboratories, Inc. | Topical ophthalmic compositions comprising a combination of calcium antagonists with known antiglaucoma agents |
| US6017919A (en) | 1996-02-06 | 2000-01-25 | Japan Tobacco Inc. | 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 |
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2003
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- 2003-02-04 PE PE2003000129A patent/PE20030867A1/es not_active Application Discontinuation
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- 2003-02-05 PL PL03370657A patent/PL370657A1/xx unknown
- 2003-02-05 WO PCT/EP2003/001140 patent/WO2003066603A1/en not_active Ceased
- 2003-02-05 AT AT03737316T patent/ATE551329T1/de active
- 2003-02-05 JP JP2003565977A patent/JP4428479B2/ja not_active Expired - Fee Related
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- 2003-02-05 CA CA2471974A patent/CA2471974C/en not_active Expired - Fee Related
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- 2003-02-05 ES ES03737316T patent/ES2384967T3/es not_active Expired - Lifetime
- 2003-02-05 US US10/503,779 patent/US20050085493A1/en not_active Abandoned
- 2003-02-05 KR KR1020047012147A patent/KR100954626B1/ko not_active Expired - Fee Related
- 2003-02-05 AU AU2003210212A patent/AU2003210212A1/en not_active Abandoned
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2004
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- 2004-08-27 NO NO20043580A patent/NO328305B1/no not_active IP Right Cessation
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2007
- 2007-06-26 US US11/823,315 patent/US8552015B2/en not_active Expired - Fee Related
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2009
- 2009-01-22 JP JP2009012064A patent/JP2009149658A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US8552015B2 (en) | 2013-10-08 |
| NO20043580D0 (no) | 2004-08-27 |
| CN1628104A (zh) | 2005-06-15 |
| EP1472234B1 (en) | 2012-03-28 |
| JP2009149658A (ja) | 2009-07-09 |
| BR0307461A (pt) | 2004-11-09 |
| NO328305B1 (no) | 2010-01-25 |
| ATE551329T1 (de) | 2012-04-15 |
| AR038483A1 (es) | 2005-01-19 |
| EP2319839A1 (en) | 2011-05-11 |
| US20050085493A1 (en) | 2005-04-21 |
| JP4428479B2 (ja) | 2010-03-10 |
| US20070265285A1 (en) | 2007-11-15 |
| KR100954626B1 (ko) | 2010-04-27 |
| CO5601021A2 (es) | 2006-01-31 |
| WO2003066603A1 (en) | 2003-08-14 |
| NZ571615A (en) | 2010-01-29 |
| AU2003210212A1 (en) | 2003-09-02 |
| CN100579968C (zh) | 2010-01-13 |
| TW200306839A (en) | 2003-12-01 |
| NO20043580L (no) | 2004-09-21 |
| CA2471974A1 (en) | 2003-08-14 |
| ECSP045219A (es) | 2004-09-28 |
| EP1472234A1 (en) | 2004-11-03 |
| PL370657A1 (en) | 2005-05-30 |
| MY143958A (en) | 2011-07-29 |
| KR20040083501A (ko) | 2004-10-02 |
| PE20030867A1 (es) | 2003-12-04 |
| HK1079518A1 (zh) | 2006-04-07 |
| CA2471974C (en) | 2011-11-22 |
| MXPA04007641A (es) | 2004-11-10 |
| JP2005522439A (ja) | 2005-07-28 |
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