CA2432008A1 - Carbazole derivatives and their use as neuropeptide y5 receptor ligands - Google Patents
Carbazole derivatives and their use as neuropeptide y5 receptor ligands Download PDFInfo
- Publication number
- CA2432008A1 CA2432008A1 CA002432008A CA2432008A CA2432008A1 CA 2432008 A1 CA2432008 A1 CA 2432008A1 CA 002432008 A CA002432008 A CA 002432008A CA 2432008 A CA2432008 A CA 2432008A CA 2432008 A1 CA2432008 A1 CA 2432008A1
- Authority
- CA
- Canada
- Prior art keywords
- 4alkyl
- formula
- compound
- optionally substituted
- carbamoyl
- 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.)
- Abandoned
Links
- 102000028582 Neuropeptide Y5 receptor Human genes 0.000 title description 20
- 108010046593 Neuropeptide Y5 receptor Proteins 0.000 title description 20
- 125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 title 1
- 239000003446 ligand Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 215
- 238000000034 method Methods 0.000 claims abstract description 165
- 230000008569 process Effects 0.000 claims abstract description 36
- -1 cyano, hydroxy Chemical group 0.000 claims description 565
- 229910052757 nitrogen Inorganic materials 0.000 claims description 112
- 125000000623 heterocyclic group Chemical group 0.000 claims description 79
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 55
- 229910052799 carbon Inorganic materials 0.000 claims description 55
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 45
- 239000000651 prodrug Substances 0.000 claims description 43
- 229940002612 prodrug Drugs 0.000 claims description 43
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 41
- 239000012453 solvate Substances 0.000 claims description 37
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 150000001412 amines Chemical class 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 19
- 241001465754 Metazoa Species 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 17
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 16
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 13
- 208000030814 Eating disease Diseases 0.000 claims description 12
- 235000014632 disordered eating Nutrition 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000005844 heterocyclyloxy group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 125000004468 heterocyclylthio group Chemical group 0.000 claims description 3
- VRBFOCCJIARKLA-UHFFFAOYSA-N n-(6-fluoro-4-methyl-9-propan-2-ylcarbazol-3-yl)-4-hydroxypiperidine-1-carboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=C(F)C=C3C2=C(C)C=1NC(=O)N1CCC(O)CC1 VRBFOCCJIARKLA-UHFFFAOYSA-N 0.000 claims description 3
- OWFBVZBGOIYECX-UHFFFAOYSA-N 1-n-(2,4-dimethyl-9-propan-2-ylcarbazol-3-yl)piperidine-1,3-dicarboxamide Chemical compound CC=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)N1CCCC(C(N)=O)C1 OWFBVZBGOIYECX-UHFFFAOYSA-N 0.000 claims description 2
- LVVQMWROURBWIV-UHFFFAOYSA-N 1-n-(4-methyl-9-propan-2-ylcarbazol-3-yl)piperidine-1,3-dicarboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)N1CCCC(C(N)=O)C1 LVVQMWROURBWIV-UHFFFAOYSA-N 0.000 claims description 2
- WZBUYBRFHLEIOK-UHFFFAOYSA-N 2-(1,1-dioxothiolan-3-yl)-n-(4-methyl-9-propan-2-ylcarbazol-3-yl)acetamide Chemical compound C=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)CC1CCS(=O)(=O)C1 WZBUYBRFHLEIOK-UHFFFAOYSA-N 0.000 claims description 2
- WCIANFVRUMSDGK-UHFFFAOYSA-N 4-n-(2,4-dimethyl-9-propan-2-ylcarbazol-3-yl)-1-n,1-n-dimethylpiperidine-1,4-dicarboxamide Chemical compound CC=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)C1CCN(C(=O)N(C)C)CC1 WCIANFVRUMSDGK-UHFFFAOYSA-N 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims description 2
- ZNFMHLDBJPAFEQ-UHFFFAOYSA-N n-(4-methyl-9-propan-2-ylcarbazol-3-yl)morpholine-4-carboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)N1CCOCC1 ZNFMHLDBJPAFEQ-UHFFFAOYSA-N 0.000 claims description 2
- CVCCDFPEKAUSBB-UHFFFAOYSA-N n-(6-fluoro-4-methyl-9-propan-2-ylcarbazol-3-yl)morpholine-4-carboxamide Chemical compound C=1C=C2N(C(C)C)C3=CC=C(F)C=C3C2=C(C)C=1NC(=O)N1CCOCC1 CVCCDFPEKAUSBB-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 15
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 13
- 125000001475 halogen functional group Chemical group 0.000 claims 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 3
- HMXROEBLPFGRRC-UHFFFAOYSA-N 4-hydroxy-n-(2-methyl-9-propan-2-ylcarbazol-3-yl)piperidine-1-carboxamide Chemical compound CC=1C=C2N(C(C)C)C3=CC=CC=C3C2=CC=1NC(=O)N1CCC(O)CC1 HMXROEBLPFGRRC-UHFFFAOYSA-N 0.000 claims 1
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 11
- 239000003112 inhibitor Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 80
- 238000005481 NMR spectroscopy Methods 0.000 description 76
- 235000019439 ethyl acetate Nutrition 0.000 description 66
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 59
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 53
- 239000000203 mixture Substances 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 239000002904 solvent Substances 0.000 description 31
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 29
- 239000007858 starting material Substances 0.000 description 29
- 101150041968 CDC13 gene Proteins 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 22
- 125000005843 halogen group Chemical group 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 18
- 239000003480 eluent Substances 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 150000002148 esters Chemical class 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 125000000217 alkyl group Chemical group 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 101710151321 Melanostatin Proteins 0.000 description 13
- 102400000064 Neuropeptide Y Human genes 0.000 description 13
- 239000004480 active ingredient Substances 0.000 description 13
- 125000002252 acyl group Chemical group 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 12
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 12
- 241000282414 Homo sapiens Species 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- 125000003386 piperidinyl group Chemical group 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- VRPPTWROMMUVEU-UHFFFAOYSA-N 2,4-dimethyl-9-propan-2-ylcarbazol-3-amine Chemical compound NC1=C(C)C=C2N(C(C)C)C3=CC=CC=C3C2=C1C VRPPTWROMMUVEU-UHFFFAOYSA-N 0.000 description 7
- 208000008589 Obesity Diseases 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 235000020824 obesity Nutrition 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- 125000001246 bromo group Chemical group Br* 0.000 description 6
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 230000001737 promoting effect Effects 0.000 description 6
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- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-p-benzoquinone Substances ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 5
- 241000238631 Hexapoda Species 0.000 description 5
- 101000983116 Homo sapiens Pancreatic prohormone Proteins 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 239000012148 binding buffer Substances 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000000796 flavoring agent Substances 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 125000003373 pyrazinyl group Chemical group 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 108090000189 Neuropeptides Proteins 0.000 description 4
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- LUKAUQQNVSQJJZ-UHFFFAOYSA-N tert-butyl 3-[(2,4-dimethyl-9-propan-2-ylcarbazol-3-yl)carbamoyl]pyrrolidine-1-carboxylate Chemical compound CC=1C=C2N(C(C)C)C3=CC=CC=C3C2=C(C)C=1NC(=O)C1CCN(C(=O)OC(C)(C)C)C1 LUKAUQQNVSQJJZ-UHFFFAOYSA-N 0.000 description 1
- VTDNLPYMRWHOHB-UHFFFAOYSA-N tert-butyl n-[3-methoxy-1-[(4-methyl-9-propan-2-ylcarbazol-3-yl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C1=CC=C2C3=C(C)C(NC(=O)C(NC(=O)OC(C)(C)C)COC)=CC=C3N(C(C)C)C2=C1 VTDNLPYMRWHOHB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- 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
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- 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
- A61P3/06—Antihyperlipidemics
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles 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 to carbon atoms of the ring system
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Obesity (AREA)
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- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0031382.5 | 2000-12-22 | ||
| GBGB0031382.5A GB0031382D0 (en) | 1998-06-10 | 2000-12-22 | Chemical compounds |
| GBGB0121919.5A GB0121919D0 (en) | 2001-09-11 | 2001-09-11 | Chemical compounds |
| GB0121919.5 | 2001-09-11 | ||
| PCT/GB2001/005577 WO2002051806A1 (en) | 2000-12-22 | 2001-12-17 | Carbazole derivatives and their use as neuropeptide y5 receptor ligands |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2432008A1 true CA2432008A1 (en) | 2002-07-04 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002432008A Abandoned CA2432008A1 (en) | 2000-12-22 | 2001-12-17 | Carbazole derivatives and their use as neuropeptide y5 receptor ligands |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20040067999A1 (https=) |
| EP (1) | EP1358157A1 (https=) |
| JP (1) | JP2004520324A (https=) |
| CN (1) | CN1531527A (https=) |
| BR (1) | BR0116388A (https=) |
| CA (1) | CA2432008A1 (https=) |
| IL (1) | IL156487A0 (https=) |
| MX (1) | MXPA03005648A (https=) |
| NO (1) | NO20032842L (https=) |
| NZ (1) | NZ526623A (https=) |
| WO (1) | WO2002051806A1 (https=) |
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| GB0121941D0 (en) | 2001-09-11 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| US6949564B2 (en) | 2002-12-18 | 2005-09-27 | Pfizer Inc. | NPY-5 antagonists |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2005090340A1 (ja) * | 2004-03-22 | 2005-09-29 | Banyu Pharmaceutical Co., Ltd. | ピペリジン－１－カルボキサミド誘導体 |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| ITMI20051523A1 (it) | 2005-08-03 | 2007-02-04 | Acraf | Composto del 3-ammino-carbazolo composizione farmaceutica che lo contiene e metodo per prepararlo |
| EP2520567A3 (en) | 2006-02-23 | 2012-12-12 | Shionogi & Co., Ltd. | Nitrogen-containing heterocycle derivatives substituted with cyclic group |
| US7601856B2 (en) | 2006-07-27 | 2009-10-13 | Wyeth | Benzofurans as potassium ion channel modulators |
| EP2081905B1 (en) * | 2006-07-28 | 2012-09-12 | Boehringer Ingelheim International GmbH | Sulfonyl compounds which modulate the cb2 receptor |
| CA2664310A1 (en) | 2006-09-25 | 2008-04-03 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| WO2008064054A2 (en) * | 2006-11-21 | 2008-05-29 | Boehringer Ingelheim International Gmbh | Compounds which modulate the cb2 receptor |
| EP2527360B1 (en) | 2007-06-04 | 2015-10-28 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4111850A (en) * | 1977-02-16 | 1978-09-05 | Amp Incorporated | Organic photoconductors and methods |
| FR2546163B1 (fr) * | 1983-05-16 | 1987-10-09 | Centre Nat Rech Scient | Nouveaux derives acyles hydrosolubles de peptides ou d'amino-acides, leur preparation et leur application |
| US5234942A (en) * | 1984-10-19 | 1993-08-10 | Ici Americas Inc. | Heterocyclic amides and leucotriene antagonistic use thereof |
| GB8524157D0 (en) * | 1984-10-19 | 1985-11-06 | Ici America Inc | Heterocyclic amides |
| US5254135A (en) * | 1989-10-20 | 1993-10-19 | L'oreal | Methods for dyeing keratinous fibres with aminoindoles, compositions and devices for use |
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| WO2000063171A1 (en) * | 1999-04-20 | 2000-10-26 | Meiji Seika Kaisha, Ltd. | Tricyclic compounds |
| AU6000900A (en) * | 1999-07-23 | 2001-02-13 | Astrazeneca Uk Limited | Carbazole derivatives and their use as neuropeptide y5 receptor ligands |
-
2001
- 2001-12-17 IL IL15648701A patent/IL156487A0/xx unknown
- 2001-12-17 BR BR0116388-4A patent/BR0116388A/pt not_active IP Right Cessation
- 2001-12-17 JP JP2002552903A patent/JP2004520324A/ja active Pending
- 2001-12-17 CA CA002432008A patent/CA2432008A1/en not_active Abandoned
- 2001-12-17 CN CNA018228259A patent/CN1531527A/zh active Pending
- 2001-12-17 EP EP01272068A patent/EP1358157A1/en not_active Withdrawn
- 2001-12-17 MX MXPA03005648A patent/MXPA03005648A/es unknown
- 2001-12-17 US US10/450,928 patent/US20040067999A1/en not_active Abandoned
- 2001-12-17 WO PCT/GB2001/005577 patent/WO2002051806A1/en not_active Ceased
- 2001-12-17 NZ NZ526623A patent/NZ526623A/en unknown
-
2003
- 2003-06-20 NO NO20032842A patent/NO20032842L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004520324A (ja) | 2004-07-08 |
| NO20032842D0 (no) | 2003-06-20 |
| WO2002051806A1 (en) | 2002-07-04 |
| US20040067999A1 (en) | 2004-04-08 |
| NO20032842L (no) | 2003-08-18 |
| IL156487A0 (en) | 2004-01-04 |
| MXPA03005648A (es) | 2003-10-06 |
| CN1531527A (zh) | 2004-09-22 |
| NZ526623A (en) | 2004-11-26 |
| EP1358157A1 (en) | 2003-11-05 |
| BR0116388A (pt) | 2003-09-30 |
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| Date | Code | Title | Description |
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