NO331351B1 - Forbindelser med veksthormonfrigjorende egenskaper - Google Patents
Forbindelser med veksthormonfrigjorende egenskaper Download PDFInfo
- Publication number
- NO331351B1 NO331351B1 NO20006699A NO20006699A NO331351B1 NO 331351 B1 NO331351 B1 NO 331351B1 NO 20006699 A NO20006699 A NO 20006699A NO 20006699 A NO20006699 A NO 20006699A NO 331351 B1 NO331351 B1 NO 331351B1
- Authority
- NO
- Norway
- Prior art keywords
- ethyl
- methylcarbamoyl
- naphthyl
- oxoethyl
- benzyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 98
- 108010051696 Growth Hormone Proteins 0.000 title claims abstract description 41
- 239000000122 growth hormone Substances 0.000 title claims abstract description 41
- 102000018997 Growth Hormone Human genes 0.000 title claims abstract 3
- 230000003578 releasing effect Effects 0.000 title description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
- -1 amino, phenyl Chemical group 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 206010062767 Hypophysitis Diseases 0.000 claims description 11
- 210000003635 pituitary gland Anatomy 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 230000004936 stimulating effect Effects 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- YQIUOHNQOJDCBZ-WJJVUGRUSA-N (e)-4-(1-aminocyclobutyl)-n-[(2r)-1-[[(2r)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-n-methylbut-2-enamide Chemical compound C([C@@H](N(C)C(=O)\C=C\CC1(N)CCC1)C(=O)N(C)[C@H](CC=1C=CC=CC=1)C(=O)N1CCC(O)CC1)C(C=C1)=CC=C1C1=CC=CC=C1 YQIUOHNQOJDCBZ-WJJVUGRUSA-N 0.000 claims description 3
- DZKZMXVJARCRLV-KPMWTHKRSA-N (e)-4-(1-aminocyclobutyl)-n-[(2r)-1-[[(2r)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]but-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=CC(=CC=1)C=1C=CC=CC=1)NC(=O)\C=C\CC1(N)CCC1)C(=O)N1CCC(O)CC1)C1=CC=CC=C1 DZKZMXVJARCRLV-KPMWTHKRSA-N 0.000 claims description 3
- LDGXDMBXCGXVAJ-CTNZJEHSSA-N (e)-4-(1-aminocyclobutyl)-n-[(2r)-1-[[(2r)-1-[(3s)-3-[(dimethylamino)methyl]piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n-methylbut-2-enamide Chemical compound C1[C@H](CN(C)C)CCCN1C(=O)[C@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC1(N)CCC1)CC1=CC=CC=C1 LDGXDMBXCGXVAJ-CTNZJEHSSA-N 0.000 claims description 3
- VQPXWMYSKOQPPG-IVQLKPQISA-N (e)-5-amino-n-[(2r)-1-[[(2r)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)C(=O)N1CCC(O)CC1)C1=CC=CC=C1 VQPXWMYSKOQPPG-IVQLKPQISA-N 0.000 claims description 3
- QUEJGZUHNORKEW-MKVXCEBYSA-N (e)-5-amino-n-[(2r)-1-[[(2r)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-thiophen-2-ylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-n,3,5-trimethylhex-2-enamide Chemical compound C([C@@H](N(C)C(=O)\C=C(/C)CC(C)(C)N)C(=O)N(C)[C@H](CC=1SC=CC=1)C(=O)N1CCC(O)CC1)C(C=C1)=CC=C1C1=CC=CC=C1 QUEJGZUHNORKEW-MKVXCEBYSA-N 0.000 claims description 3
- PXXCTYHKGMNEKB-DUDRCQOBSA-N (e)-5-amino-n-[(2r)-1-[[(2r)-1-[(2s)-2-[(dimethylamino)methyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound CN(C)C[C@@H]1CCCN1C(=O)[C@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)CC1=CC=CC=C1 PXXCTYHKGMNEKB-DUDRCQOBSA-N 0.000 claims description 3
- BRXWONQWOVVDSR-XSEBBUNHSA-N (e)-5-amino-n-[(2r)-1-[[(2r)-1-[(3s)-3-[(dimethylamino)methyl]piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound C1[C@H](CN(C)C)CCCN1C(=O)[C@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)CC1=CC=CC=C1 BRXWONQWOVVDSR-XSEBBUNHSA-N 0.000 claims description 3
- MQALRGDLNLJOEJ-IYBWFBNASA-N (e)-5-amino-n-[(2r)-1-[[(2r)-1-[4-[(dimethylamino)methyl]piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound C1CC(CN(C)C)CCN1C(=O)[C@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)CC1=CC=CC=C1 MQALRGDLNLJOEJ-IYBWFBNASA-N 0.000 claims description 3
- BNCSGGPCCBXTGD-VMPYOYAXSA-N (e)-5-amino-n-[(2r)-1-[[(2r)-3-(4-fluorophenyl)-1-(4-hydroxypiperidin-1-yl)-1-oxopropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,3,5-trimethylhex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(/C)CC(C)(C)N)C(=O)N1CCC(O)CC1)C1=CC=C(F)C=C1 BNCSGGPCCBXTGD-VMPYOYAXSA-N 0.000 claims description 3
- GASZOSARLZFODU-YONGIPRNSA-N (e)-5-amino-n-[(2r)-1-[[(2r)-3-(4-fluorophenyl)-1-(4-hydroxypiperidin-1-yl)-1-oxopropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n,5-dimethylhex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)C(=O)N1CCC(O)CC1)C1=CC=C(F)C=C1 GASZOSARLZFODU-YONGIPRNSA-N 0.000 claims description 3
- QMHMDNQBFPHEHG-KKLWWLSJSA-N 3-(aminomethyl)-n-methyl-n-[(2r)-1-[methyl-[(2r)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]benzamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)C=1C=C(CN)C=CC=1)C(=O)N1CCN(C)CC1)C1=CC=CC=C1 QMHMDNQBFPHEHG-KKLWWLSJSA-N 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
- RDURIQJHVHWXMT-CCZICSFRSA-N (e)-5-amino-n,3,5-trimethyl-n-[(2r)-1-[methyl-[(2r)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C(/C)CC(C)(C)N)C(=O)N1CCN(C)CC1)C1=CC=CC=C1 RDURIQJHVHWXMT-CCZICSFRSA-N 0.000 claims description 2
- YELQOFRUOVMJKR-YWKCSOBASA-N (e)-5-amino-n,5-dimethyl-n-[(2r)-1-[methyl-[(2r)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylpropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hex-2-enamide Chemical compound C([C@@H](N(C)C(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)N(C)C(=O)\C=C\CC(C)(C)N)C(=O)N1CCN(C)CC1)C1=CC=CC=C1 YELQOFRUOVMJKR-YWKCSOBASA-N 0.000 claims description 2
- XXJWCXKFODRSHT-IYBWFBNASA-N (e)-n-[(2r)-1-[[(2r)-1-(4-hydroxypiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-methylamino]-1-oxo-3-(4-phenylphenyl)propan-2-yl]-n,5-dimethyl-5-(methylamino)hex-2-enamide Chemical compound C([C@@H](N(C)C(=O)/C=C/CC(C)(C)NC)C(=O)N(C)[C@H](CC=1C=CC=CC=1)C(=O)N1CCC(O)CC1)C(C=C1)=CC=C1C1=CC=CC=C1 XXJWCXKFODRSHT-IYBWFBNASA-N 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- GMVVFIATRLQYGY-HKIDPNTFSA-N n-[(2r)-1-[[(2r)-1-[(2s)-2-[(dimethylamino)methyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n-methyl-3-(methylaminomethyl)benzamide Chemical compound CNCC1=CC=CC(C(=O)N(C)[C@H](CC=2C=C3C=CC=CC3=CC=2)C(=O)N(C)[C@H](CC=2C=CC=CC=2)C(=O)N2[C@@H](CCC2)CN(C)C)=C1 GMVVFIATRLQYGY-HKIDPNTFSA-N 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 238000011282 treatment Methods 0.000 abstract description 42
- 239000000203 mixture Substances 0.000 abstract description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 267
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- 239000000243 solution Substances 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 78
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 71
- 239000002904 solvent Substances 0.000 description 62
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 60
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
- 238000005160 1H NMR spectroscopy Methods 0.000 description 42
- 102100038803 Somatotropin Human genes 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000007864 aqueous solution Substances 0.000 description 37
- 239000000377 silicon dioxide Substances 0.000 description 36
- 238000004128 high performance liquid chromatography Methods 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
- 239000012043 crude product Substances 0.000 description 33
- 238000000034 method Methods 0.000 description 31
- 238000003818 flash chromatography Methods 0.000 description 30
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 30
- 235000019341 magnesium sulphate Nutrition 0.000 description 30
- 239000003480 eluent Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 24
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 22
- 239000008346 aqueous phase Substances 0.000 description 22
- 235000017557 sodium bicarbonate Nutrition 0.000 description 21
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- AJGJINVEYVTDNH-GFCCVEGCSA-N (2r)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N(C)[C@@H](C(O)=O)CC1=CC=CC=C1 AJGJINVEYVTDNH-GFCCVEGCSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- 238000004949 mass spectrometry Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 14
- 238000010792 warming Methods 0.000 description 14
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- NRPOEGFAIJAQIE-VOTSOKGWSA-N (e)-5-methyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]hex-2-enoic acid Chemical compound CC(C)(C)OC(=O)NC(C)(C)C\C=C\C(O)=O NRPOEGFAIJAQIE-VOTSOKGWSA-N 0.000 description 10
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- 125000006239 protecting group Chemical group 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 7
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
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- 230000000694 effects Effects 0.000 description 7
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- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 7
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- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- DSCBERFCMRPLAS-VQHVLOKHSA-N (e)-3,5-dimethyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]hex-2-enoic acid Chemical compound OC(=O)\C=C(/C)CC(C)(C)NC(=O)OC(C)(C)C DSCBERFCMRPLAS-VQHVLOKHSA-N 0.000 description 5
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000005313 thymus development Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 230000006492 vascular dysfunction Effects 0.000 description 1
- 230000006815 ventricular dysfunction Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0207—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)4-C(=0), e.g. 'isosters', replacing two amino acids
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA199800857 | 1998-06-30 | ||
| DKPA199801440 | 1998-11-09 | ||
| PCT/DK1999/000368 WO2000001726A1 (en) | 1998-06-30 | 1999-06-29 | Compounds with growth hormone releasing properties |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20006699D0 NO20006699D0 (no) | 2000-12-29 |
| NO20006699L NO20006699L (no) | 2001-02-28 |
| NO331351B1 true NO331351B1 (no) | 2011-12-05 |
Family
ID=26064788
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20006699A NO331351B1 (no) | 1998-06-30 | 2000-12-29 | Forbindelser med veksthormonfrigjorende egenskaper |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1100824B1 (da) |
| JP (1) | JP4511040B2 (da) |
| KR (1) | KR100907638B1 (da) |
| CN (1) | CN1304424C (da) |
| AT (1) | ATE500269T1 (da) |
| AU (1) | AU771644B2 (da) |
| BR (1) | BRPI9911756B1 (da) |
| CA (1) | CA2334315C (da) |
| CY (1) | CY1111509T1 (da) |
| CZ (1) | CZ299648B6 (da) |
| DE (1) | DE69943239D1 (da) |
| DK (1) | DK1100824T3 (da) |
| HU (1) | HUP0102460A3 (da) |
| IL (1) | IL140044A0 (da) |
| NO (1) | NO331351B1 (da) |
| PL (1) | PL199853B1 (da) |
| PT (1) | PT1100824E (da) |
| RU (1) | RU2298547C2 (da) |
| TW (1) | TW593337B (da) |
| WO (1) | WO2000001726A1 (da) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2462200A1 (en) * | 2001-08-10 | 2003-02-20 | Palatin Technologies, Inc. | Peptidomimetics of biologically active metallopeptides |
| US7476653B2 (en) | 2003-06-18 | 2009-01-13 | Tranzyme Pharma, Inc. | Macrocyclic modulators of the ghrelin receptor |
| EP1735055A1 (en) * | 2004-03-30 | 2006-12-27 | Sapphire Therapeutics, Inc. | Method of reducing c-reactive protein using growth hormone secretagogues |
| ES2388501T3 (es) | 2004-08-12 | 2012-10-16 | Helsinn Healthcare S.A. | Uso de secretagogos de la hormona de crecimiento para estimular la motilidad del sistema gastrointestinal |
| JP4954983B2 (ja) | 2005-05-18 | 2012-06-20 | ファーマサイエンス・インコーポレイテッド | Ｂｉｒドメイン結合化合物 |
| BRPI0617751A2 (pt) | 2005-10-25 | 2011-08-02 | Aegera Therapeutics Inc | compostos de ligação do domìnio iap bir |
| CU23558A1 (es) | 2006-02-28 | 2010-07-20 | Ct Ingenieria Genetica Biotech | Compuestos análogos a los secretagogos peptidicos de la hormona de crecimiento |
| JP2010518090A (ja) | 2007-02-09 | 2010-05-27 | トランザイム・ファーマ，インコーポレイテッド | 大環状グレリン受容体修飾因子およびその使用方法 |
| CN107382827B (zh) * | 2017-04-14 | 2021-01-01 | 江苏普莱医药生物技术有限公司 | 氨基酸衍生物或其药学上可接受的盐及应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SK282166B6 (sk) * | 1992-12-11 | 2001-11-06 | Merck & Co., Inc. | Spiropiperidínové deriváty, spôsob ich výroby a farmaceutický prostriedok s ich obsahom |
| AU711104B2 (en) * | 1995-06-22 | 1999-10-07 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| EP0869974B1 (en) * | 1995-12-22 | 2009-03-04 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
| DE69734215T2 (de) * | 1996-07-22 | 2006-06-29 | Novo Nordisk A/S | Verbindungen mit Wachstumshormon-freisetzenden Eigenschaften |
| EP1005484A1 (en) * | 1997-06-20 | 2000-06-07 | Novo Nordisk A/S | Compounds with growth hormone releasing properties |
-
1999
- 1999-06-29 DK DK99929114.9T patent/DK1100824T3/da active
- 1999-06-29 PL PL345204A patent/PL199853B1/pl unknown
- 1999-06-29 EP EP99929114A patent/EP1100824B1/en not_active Expired - Lifetime
- 1999-06-29 CA CA2334315A patent/CA2334315C/en not_active Expired - Lifetime
- 1999-06-29 WO PCT/DK1999/000368 patent/WO2000001726A1/en active IP Right Grant
- 1999-06-29 HU HU0102460A patent/HUP0102460A3/hu unknown
- 1999-06-29 JP JP2000558127A patent/JP4511040B2/ja not_active Expired - Lifetime
- 1999-06-29 DE DE69943239T patent/DE69943239D1/de not_active Expired - Lifetime
- 1999-06-29 CZ CZ20004565A patent/CZ299648B6/cs not_active IP Right Cessation
- 1999-06-29 RU RU2001102617/04A patent/RU2298547C2/ru active
- 1999-06-29 AU AU46038/99A patent/AU771644B2/en not_active Ceased
- 1999-06-29 KR KR1020007015040A patent/KR100907638B1/ko not_active IP Right Cessation
- 1999-06-29 CN CNB998080861A patent/CN1304424C/zh not_active Expired - Fee Related
- 1999-06-29 AT AT99929114T patent/ATE500269T1/de active
- 1999-06-29 PT PT99929114T patent/PT1100824E/pt unknown
- 1999-06-29 BR BRPI9911756A patent/BRPI9911756B1/pt not_active IP Right Cessation
- 1999-06-29 IL IL14004499A patent/IL140044A0/xx not_active IP Right Cessation
- 1999-08-18 TW TW088114089A patent/TW593337B/zh not_active IP Right Cessation
-
2000
- 2000-12-29 NO NO20006699A patent/NO331351B1/no not_active IP Right Cessation
-
2011
- 2011-06-01 CY CY20111100528T patent/CY1111509T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1304424C (zh) | 2007-03-14 |
| EP1100824B1 (en) | 2011-03-02 |
| CY1111509T1 (el) | 2015-08-05 |
| CZ20004565A3 (en) | 2001-06-13 |
| JP4511040B2 (ja) | 2010-07-28 |
| PL199853B1 (pl) | 2008-11-28 |
| ATE500269T1 (de) | 2011-03-15 |
| HUP0102460A3 (en) | 2001-12-28 |
| CA2334315C (en) | 2011-07-26 |
| HUP0102460A2 (hu) | 2001-11-28 |
| PT1100824E (pt) | 2011-06-16 |
| CZ299648B6 (cs) | 2008-10-01 |
| BRPI9911756B1 (pt) | 2016-06-14 |
| DE69943239D1 (de) | 2011-04-14 |
| JP2002519436A (ja) | 2002-07-02 |
| PL345204A1 (en) | 2001-12-03 |
| CA2334315A1 (en) | 2000-01-13 |
| CN1307588A (zh) | 2001-08-08 |
| BR9911756A (pt) | 2001-04-03 |
| DK1100824T3 (da) | 2011-06-20 |
| NO20006699D0 (no) | 2000-12-29 |
| EP1100824A1 (en) | 2001-05-23 |
| KR20010053310A (ko) | 2001-06-25 |
| IL140044A0 (en) | 2002-02-10 |
| RU2298547C2 (ru) | 2007-05-10 |
| AU4603899A (en) | 2000-01-24 |
| WO2000001726A1 (en) | 2000-01-13 |
| AU771644B2 (en) | 2004-04-01 |
| NO20006699L (no) | 2001-02-28 |
| KR100907638B1 (ko) | 2009-07-14 |
| TW593337B (en) | 2004-06-21 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: HELSINN HEALTHCARE SA, CH |
|
| MM1K | Lapsed by not paying the annual fees |