NO326692B1 - Tetrahydrokarbazolderivater som ligander for G-proteinkoplede reseptorer (GPCR), anvendelse derav samt farmasøytiske preparater inneholdende disse - Google Patents
Tetrahydrokarbazolderivater som ligander for G-proteinkoplede reseptorer (GPCR), anvendelse derav samt farmasøytiske preparater inneholdende disse Download PDFInfo
- Publication number
- NO326692B1 NO326692B1 NO20042198A NO20042198A NO326692B1 NO 326692 B1 NO326692 B1 NO 326692B1 NO 20042198 A NO20042198 A NO 20042198A NO 20042198 A NO20042198 A NO 20042198A NO 326692 B1 NO326692 B1 NO 326692B1
- Authority
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- Norway
- Prior art keywords
- amino
- carbonyl
- tetrahydro
- residue
- methylbutyl
- Prior art date
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- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 title claims description 30
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 title claims description 30
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 19
- XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical class N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 title description 28
- 239000003446 ligand Substances 0.000 title description 24
- 150000001875 compounds Chemical class 0.000 claims description 147
- -1 -COCH3 Chemical group 0.000 claims description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- 125000004432 carbon atom Chemical group C* 0.000 claims description 38
- 125000005842 heteroatom Chemical group 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims description 23
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims description 23
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims description 23
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 19
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 15
- 239000008177 pharmaceutical agent Substances 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 9
- 230000035558 fertility Effects 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 230000001575 pathological effect Effects 0.000 claims description 8
- 208000007984 Female Infertility Diseases 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 238000001794 hormone therapy Methods 0.000 claims description 6
- 230000036512 infertility Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- VJXYPKNWNLTBLH-UHFFFAOYSA-N methyl 3-acetamido-1,2,4,9-tetrahydrocarbazole-3-carboxylate Chemical compound N1C2=CC=CC=C2C2=C1CCC(NC(C)=O)(C(=O)OC)C2 VJXYPKNWNLTBLH-UHFFFAOYSA-N 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 231100000535 infertility Toxicity 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 229910052702 rhenium Inorganic materials 0.000 claims description 5
- HEWZVFOZKYOIAF-UHFFFAOYSA-N 3-amino-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound N1C2=CC=CC=C2C2=C1CCC(C(O)=O)(N)C2 HEWZVFOZKYOIAF-UHFFFAOYSA-N 0.000 claims description 4
- 230000037396 body weight Effects 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- CNMXMAIKKGUUIH-AVJYQCBHSA-N (2s)-3-methyl-2-[[3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazol-3-yl]methylamino]butan-1-ol Chemical compound C1CC=2NC3=CC=CC=C3C=2CC1(CN[C@H](CO)C(C)C)CCCC1=CC=CC=C1 CNMXMAIKKGUUIH-AVJYQCBHSA-N 0.000 claims description 3
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 3
- NPDBKFIVTUJBRZ-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound N1C2=CC=CC=C2C2=C1CCC(C(O)=O)(NC(=O)OC(C)(C)C)C2 NPDBKFIVTUJBRZ-UHFFFAOYSA-N 0.000 claims description 3
- UZMFROVMHGFRMC-UHFFFAOYSA-N 3-acetamido-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound N1C2=CC=CC=C2C2=C1CCC(C(O)=O)(NC(=O)C)C2 UZMFROVMHGFRMC-UHFFFAOYSA-N 0.000 claims description 3
- ODKCHFSJHGFUGC-UHFFFAOYSA-N 3-amino-6-methoxy-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound C1CC(N)(C(O)=O)CC2=C1NC1=CC=C(OC)C=C12 ODKCHFSJHGFUGC-UHFFFAOYSA-N 0.000 claims description 3
- MWDDESMQKUUEFL-UHFFFAOYSA-N 3-amino-6-phenylmethoxy-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound C1=C2C=3CC(N)(C(O)=O)CCC=3NC2=CC=C1OCC1=CC=CC=C1 MWDDESMQKUUEFL-UHFFFAOYSA-N 0.000 claims description 3
- ALWROAXCTQYWHE-UHFFFAOYSA-N 6,8-dichloro-3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound C1CC=2NC3=C(Cl)C=C(Cl)C=C3C=2CC1(C(=O)O)CCCC1=CC=CC=C1 ALWROAXCTQYWHE-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- XFUHUNHLQAJREJ-UHFFFAOYSA-N ethyl 6,8-dichloro-3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazole-3-carboxylate Chemical compound C1CC=2NC3=C(Cl)C=C(Cl)C=C3C=2CC1(C(=O)OCC)CCCC1=CC=CC=C1 XFUHUNHLQAJREJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001165 hydrophobic group Chemical group 0.000 claims description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
- KHKUFFZUSONXTD-CSMDKSQMSA-N n-[(2s)-1-hydroxy-3-methylbutan-2-yl]-3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound C1CC=2NC3=CC=CC=C3C=2CC1(C(=O)N[C@H](CO)C(C)C)CCCC1=CC=CC=C1 KHKUFFZUSONXTD-CSMDKSQMSA-N 0.000 claims description 3
- VUJGKDVZMCDYDE-ZCFIWIBFSA-N (2s)-3-methyl-2-(methylamino)butan-1-ol Chemical group CN[C@H](CO)C(C)C VUJGKDVZMCDYDE-ZCFIWIBFSA-N 0.000 claims description 2
- KCSZYNKOBASMGQ-BFHCPIPYSA-N (3r)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-(2,3-dihydro-1h-indene-1-carbonylamino)-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound C1CC2=CC=CC=C2C1C(=O)N[C@@]1(C(=O)N[C@@H](C(C)C)C(N)=O)CC(C2=CC=CC=C2N2)=C2CC1 KCSZYNKOBASMGQ-BFHCPIPYSA-N 0.000 claims description 2
- JQUQAJFCECXAJI-BHBYDHKZSA-N (3r)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-(6-phenylhexylamino)-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound N([C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)N[C@@H](C(C)C)C(N)=O)CCCCCCC1=CC=CC=C1 JQUQAJFCECXAJI-BHBYDHKZSA-N 0.000 claims description 2
- UFTUXTQRNULGOF-JYFHCDHNSA-N (3r)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-[[2-(3-bromophenyl)acetyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound N([C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)N[C@@H](C(C)C)C(N)=O)C(=O)CC1=CC=CC(Br)=C1 UFTUXTQRNULGOF-JYFHCDHNSA-N 0.000 claims description 2
- PIQVLOVWAXKFMP-JYFHCDHNSA-N (3r)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-[[2-(4-chlorophenyl)acetyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound N([C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)N[C@@H](C(C)C)C(N)=O)C(=O)CC1=CC=C(Cl)C=C1 PIQVLOVWAXKFMP-JYFHCDHNSA-N 0.000 claims description 2
- QCHLUGIRBJINMY-LSYYVWMOSA-N (3s)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-[[2-(1h-indol-3-yl)acetyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound C1=CC=C2C(CC(=O)N[C@@]3(CC=4C5=CC=CC=C5NC=4CC3)C(=O)N[C@@H](C(C)C)C(N)=O)=CNC2=C1 QCHLUGIRBJINMY-LSYYVWMOSA-N 0.000 claims description 2
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical group NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 claims description 2
- LSAOILNZYPXHRP-UHFFFAOYSA-N 3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazole-3-carboxylic acid Chemical compound C1CC=2NC3=CC=CC=C3C=2CC1(C(=O)O)CCCC1=CC=CC=C1 LSAOILNZYPXHRP-UHFFFAOYSA-N 0.000 claims description 2
- ZSXRNISZKBBQRN-UHFFFAOYSA-N 6-phenylhexan-1-amine Chemical group NCCCCCCC1=CC=CC=C1 ZSXRNISZKBBQRN-UHFFFAOYSA-N 0.000 claims description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical group CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims description 2
- HWASSKXXWRAEHO-JORHUTLDSA-N benzyl N-[(2S,3S)-1-[[(3R)-3-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]-6-chloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate Chemical compound C1(=CC=CC=C1)COC(N[C@@H]([C@H](CC)C)C(=O)N[C@@]1(CCC=2NC3=CC=C(C=C3C=2C1)Cl)C(=O)N[C@@H](C(C)C)C(=O)N)=O HWASSKXXWRAEHO-JORHUTLDSA-N 0.000 claims description 2
- OTAPEKJFBTZXDX-UHFFFAOYSA-N ethyl 3-[3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazol-3-yl]prop-2-enoate Chemical compound C1CC=2NC3=CC=CC=C3C=2CC1(C=CC(=O)OCC)CCCC1=CC=CC=C1 OTAPEKJFBTZXDX-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- WRURBELQCKTMFX-BXXZMZEQSA-N n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-[[2-(4-methoxyphenyl)acetyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1CC(=O)NC1(C(=O)N[C@@H](C(C)C)C(N)=O)CC(C2=CC=CC=C2N2)=C2CC1 WRURBELQCKTMFX-BXXZMZEQSA-N 0.000 claims description 2
- FLISZHCAWTUIGA-UHFFFAOYSA-N n-[[3-(3-phenylpropyl)-1,2,4,9-tetrahydrocarbazol-3-yl]methyl]-1-pyridin-2-ylmethanamine Chemical compound C1CC=2NC3=CC=CC=C3C=2CC1(CNCC=1N=CC=CC=1)CCCC1=CC=CC=C1 FLISZHCAWTUIGA-UHFFFAOYSA-N 0.000 claims description 2
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 2
- 206010021928 Infertility female Diseases 0.000 claims 2
- YUIYTRKYYPLVML-YFKPBYRVSA-N (2S)-2-isocyanato-3-methylbutanamide Chemical group CC(C)[C@H](N=C=O)C(N)=O YUIYTRKYYPLVML-YFKPBYRVSA-N 0.000 claims 1
- UKDPIVHHZNMZDT-DMTCNVIQSA-N (2S,3R)-3-hydroxy-2-isocyanatobutanamide Chemical group C[C@@H](O)[C@H](N=C=O)C(N)=O UKDPIVHHZNMZDT-DMTCNVIQSA-N 0.000 claims 1
- UITVZALBSDAAGO-ZCFIWIBFSA-N (2s)-2-isocyanato-3-methylbutan-1-ol Chemical group CC(C)[C@@H](CO)N=C=O UITVZALBSDAAGO-ZCFIWIBFSA-N 0.000 claims 1
- GDGZYYFUNCLBNJ-LXRQPLKBSA-N (2s,3s)-2-[[(3r)-6,8-dichloro-3-[[(2s,3s)-3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carbonyl]amino]-3-methylpentanoic acid Chemical compound N([C@H](C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O)[C@@H](C)CC)C(=O)OCC1=CC=CC=C1 GDGZYYFUNCLBNJ-LXRQPLKBSA-N 0.000 claims 1
- IORABLHFJVMQSR-JYFHCDHNSA-N (3r)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-[[2-(4-fluorophenyl)acetyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound N([C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)N[C@@H](C(C)C)C(N)=O)C(=O)CC1=CC=C(F)C=C1 IORABLHFJVMQSR-JYFHCDHNSA-N 0.000 claims 1
- BMCHBYKXFUQIFX-RPLLCQBOSA-N (3r)-n-[(2s)-1-amino-3-methyl-1-oxobutan-2-yl]-3-[[2-(4-methylphenyl)acetyl]amino]-1,2,4,9-tetrahydrocarbazole-3-carboxamide Chemical compound N([C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)N[C@@H](C(C)C)C(N)=O)C(=O)CC1=CC=C(C)C=C1 BMCHBYKXFUQIFX-RPLLCQBOSA-N 0.000 claims 1
- KREXIHWMIXFFMI-ZGEQFQDRSA-N C([C@H]1CCCC[C@@H]1C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H](C(C)CC)C(N)=O)NC(=O)OCC1=CC=CC=C1 Chemical compound C([C@H]1CCCC[C@@H]1C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H](C(C)CC)C(N)=O)NC(=O)OCC1=CC=CC=C1 KREXIHWMIXFFMI-ZGEQFQDRSA-N 0.000 claims 1
- OTPYPDRTOAWHLY-KDGVZHGYSA-N C1(=CC=CC=C1)COC(N[C@@H]([C@H](CC)C)C(=O)N[C@@]1(CCC=2NC3=CC=CC=C3C=2C1)C(=O)N[C@H](C(=O)N)CC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)COC(N[C@@H]([C@H](CC)C)C(=O)N[C@@]1(CCC=2NC3=CC=CC=C3C=2C1)C(=O)N[C@H](C(=O)N)CC1=CC=CC=C1)=O OTPYPDRTOAWHLY-KDGVZHGYSA-N 0.000 claims 1
- SYBDXZQXHBFRMZ-LMRWHKIXSA-N benzyl N-[(2S)-1-[[(3R)-3-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]carbamoyl]-6,8-dichloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)C(=O)OCC1=CC=CC=C1 SYBDXZQXHBFRMZ-LMRWHKIXSA-N 0.000 claims 1
- FUILLSUOWJPUHM-ZTMGNVKNSA-N benzyl n-[(2s)-1-[[(3r)-3-[[(2s)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]-6,8-dichloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H](CC(C)C)C(N)=O)C(=O)OCC1=CC=CC=C1 FUILLSUOWJPUHM-ZTMGNVKNSA-N 0.000 claims 1
- CWIJOYIYWHOLFF-WELJJBAASA-N benzyl n-[(2s)-1-[[(3r)-3-[[(2s,3s)-1-amino-3-methyl-1-oxopentan-2-yl]carbamoyl]-6,8-dichloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 CWIJOYIYWHOLFF-WELJJBAASA-N 0.000 claims 1
- PBLGDYQSTKGIEN-WCVCVYPRSA-N benzyl n-[(2s)-1-[[(3r)-3-[[(2s,3s)-1-amino-3-methyl-1-oxopentan-2-yl]carbamoyl]-6,8-dichloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)NC(=O)OCC=1C=CC=CC=1)C1=CC=C(O)C=C1 PBLGDYQSTKGIEN-WCVCVYPRSA-N 0.000 claims 1
- SMDDUNAMGVRVGR-SXSCIQPBSA-N benzyl n-[(2s)-1-[[(3r)-3-[[(2s,3s)-1-amino-3-methyl-1-oxopentan-2-yl]carbamoyl]-6,8-dichloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-4-(4-hydroxyphenyl)-1-oxobutan-2-yl]carbamate Chemical compound C([C@@H](C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)NC(=O)OCC=1C=CC=CC=1)CC1=CC=C(O)C=C1 SMDDUNAMGVRVGR-SXSCIQPBSA-N 0.000 claims 1
- HHRGEEXZCXRFKN-LCFOGWNRSA-N benzyl n-[(2s,3s)-1-[[(3r)-3-[(4-carbamoylphenyl)carbamoyl]-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N[C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)NC=1C=CC(=CC=1)C(N)=O)C(=O)OCC1=CC=CC=C1 HHRGEEXZCXRFKN-LCFOGWNRSA-N 0.000 claims 1
- FGZONZAPEDGCKJ-UTLAPFKUSA-N benzyl n-[(2s,3s)-1-[[(3r)-3-[[(2s)-1-(4-carbamoylanilino)-3-methyl-1-oxobutan-2-yl]carbamoyl]-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N[C@]1(CC=2C3=CC=CC=C3NC=2CC1)C(=O)N[C@@H](C(C)C)C(=O)NC=1C=CC(=CC=1)C(N)=O)C(=O)OCC1=CC=CC=C1 FGZONZAPEDGCKJ-UTLAPFKUSA-N 0.000 claims 1
- FMIJDJHYQSIBLB-WELJJBAASA-N benzyl n-[(2s,3s)-1-[[(3r)-3-[[(2s)-1-amino-1-oxo-4-phenylbutan-2-yl]carbamoyl]-6,8-dichloro-1,2,4,9-tetrahydrocarbazol-3-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H]([C@@H](C)CC)C(=O)N[C@]1(CC=2C3=CC(Cl)=CC(Cl)=C3NC=2CC1)C(=O)N[C@@H](CCC=1C=CC=CC=1)C(N)=O)C(=O)OCC1=CC=CC=C1 FMIJDJHYQSIBLB-WELJJBAASA-N 0.000 claims 1
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- YYVAQBRMUPGCDE-UHFFFAOYSA-N spiro[1,2,4,9-tetrahydrocarbazole-3,2'-1,3-dioxolane] Chemical compound O1CCOC11CC(C2=CC=CC=C2N2)=C2CC1 YYVAQBRMUPGCDE-UHFFFAOYSA-N 0.000 description 1
- JHNCLKKKIPEOFP-UHFFFAOYSA-N spiro[1,2,4,9-tetrahydrocarbazole-3,5'-imidazolidine]-2',4'-dione Chemical compound N1C(=O)NC(=O)C11CC(C2=CC=CC=C2N2)=C2CC1 JHNCLKKKIPEOFP-UHFFFAOYSA-N 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 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
- 150000003511 tertiary amides Chemical group 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 229960001479 tosylchloramide sodium Drugs 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 201000007954 uterine fibroid Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
Classifications
-
- 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
- C07K5/0202—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-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
- C07D209/86—Carbazoles; Hydrogenated carbazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the ring system
-
- 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
- C07D401/02—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
-
- 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Biophysics (AREA)
- Pregnancy & Childbirth (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10164564A DE10164564B4 (de) | 2001-12-14 | 2001-12-14 | Tetrahydrocarbazolderivate als Liganden für G-Protein gekoppelte Rezeptoren (GPCR) |
| US34187801P | 2001-12-21 | 2001-12-21 | |
| PCT/EP2002/014344 WO2003051837A2 (de) | 2001-12-14 | 2002-12-16 | Tetrahydrocarbazolderivate als liganden für g-protein gekoppelte rezeptoren (gpcr) |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20042198L NO20042198L (no) | 2004-07-09 |
| NO326692B1 true NO326692B1 (no) | 2009-02-02 |
Family
ID=26010882
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20042198A NO326692B1 (no) | 2001-12-14 | 2004-05-26 | Tetrahydrokarbazolderivater som ligander for G-proteinkoplede reseptorer (GPCR), anvendelse derav samt farmasøytiske preparater inneholdende disse |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP1453803A2 (es) |
| JP (1) | JP2005518375A (es) |
| CN (1) | CN100500654C (es) |
| AR (1) | AR037863A1 (es) |
| AU (1) | AU2002361430B2 (es) |
| BR (1) | BR0214958A (es) |
| CA (1) | CA2468880A1 (es) |
| HR (1) | HRP20040609A2 (es) |
| HU (1) | HUP0500014A3 (es) |
| IL (2) | IL161626A0 (es) |
| MX (1) | MXPA04005768A (es) |
| NO (1) | NO326692B1 (es) |
| NZ (1) | NZ533430A (es) |
| PL (1) | PL373400A1 (es) |
| RU (1) | RU2319692C2 (es) |
| TW (1) | TWI246423B (es) |
| WO (1) | WO2003051837A2 (es) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0410454A (pt) * | 2003-05-19 | 2006-06-13 | Irm Llc | composições e compostos imunossupressores |
| ES2314446T3 (es) * | 2003-06-10 | 2009-03-16 | Smithkline Beecham Corporation | Derivados de tetrahidrocarbazol y su uso farmaceutico. |
| US20060074124A1 (en) * | 2003-09-12 | 2006-04-06 | Andrew Napper | Methods of treating a disorder |
| WO2005026112A2 (en) * | 2003-09-12 | 2005-03-24 | Elixir Pharmaceuticals, Inc. | Methods of treating a disorder |
| DE102004033902A1 (de) * | 2004-07-14 | 2006-02-16 | Zentaris Gmbh | Neue Tetrahydrocarbazolderivate mit verbesserter biologischer Wirkung und verbesserter Löslichkeit als Liganden für G-Protein gekoppelte Rezeptoren (GPCR's) |
| US8039474B2 (en) * | 2004-12-27 | 2011-10-18 | Actelion Pharmaceutical Ltd. | 2,3,4,9-tetrahydro-1H-carbazole derivatives as CRTH2 receptor antagonists |
| AU2006262283B2 (en) * | 2005-06-24 | 2011-10-13 | Eli Lilly And Company | Tetrahydrocarbazole derivatives useful as androgen receptor modulators (SARM) |
| EP2051962B1 (en) * | 2006-08-07 | 2011-10-26 | Actelion Pharmaceuticals Ltd. | (3-amino-1,2,3,4-tetrahydro-9h-carbazol-9-yl)-acetic acid derivatives |
| EP1967202A1 (en) * | 2007-03-05 | 2008-09-10 | AEterna Zentaris GmbH | Use of LHRH Antagonists for the Treatment of Lower Urinary Tract Symptoms, in particular Overactive Bladder and/or Detrusor Overactivity |
| EP1988098A1 (en) * | 2007-04-27 | 2008-11-05 | AEterna Zentaris GmbH | Novel Tetrahydrocarbazole Derivatives as Ligands of G-protein Coupled Receptors |
| EP2095818A1 (en) * | 2008-02-29 | 2009-09-02 | AEterna Zentaris GmbH | Use of LHRH antagonists at non-castrating doses |
| PL2558447T3 (pl) | 2010-03-22 | 2015-03-31 | Idorsia Pharmaceuticals Ltd | Pochodne 3-(heteroaryloamino)-1,2,3,4-tetrahydro-9h-karbazolu i ich zastosowanie jako modulatorów receptora prostaglandyny D2 |
| EP2697223B1 (en) | 2011-04-14 | 2016-07-13 | Actelion Pharmaceuticals Ltd. | 7-(heteroaryl-amino)-6,7,8,9-tetrahydropyrido[1,2-a]indol acetic acid derivatives and their use as prostaglandin d2 receptor modulators |
| UA117780C2 (uk) | 2014-03-17 | 2018-09-25 | Ідорсія Фармасьютікалз Лтд | Похідні азаіндолоцтової кислоти та їх застосування як модуляторів рецепторів простагландину d2 |
| RU2016140708A (ru) | 2014-03-18 | 2018-04-18 | Идорсиа Фармасьютиклз Лтд | Производные азаиндол уксусной кислоты и их применение в качестве модуляторов рецептора простагландина d2 |
| US10351560B2 (en) | 2015-09-15 | 2019-07-16 | Idorsia Pharmaceuticals Ltd | Crystalline forms |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1418703A (en) * | 1973-06-02 | 1975-12-24 | Pfizer Ltd | 3-alkyl-9-substituted-1,2,3,4-tetrahydrocarbazoles |
| EP0239306B1 (en) * | 1986-03-27 | 1993-06-02 | Merck Frosst Canada Inc. | Tetrahydrocarbazole esters |
| US5607939A (en) * | 1994-04-28 | 1997-03-04 | Takeda Chemical Industries, Ltd. | Condensed heterocyclic compounds, their production and use |
| WO1998055116A1 (en) * | 1997-06-05 | 1998-12-10 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
-
2002
- 2002-12-16 IL IL16162602A patent/IL161626A0/xx unknown
- 2002-12-16 CN CNB028241487A patent/CN100500654C/zh not_active Expired - Fee Related
- 2002-12-16 BR BR0214958-3A patent/BR0214958A/pt not_active IP Right Cessation
- 2002-12-16 MX MXPA04005768A patent/MXPA04005768A/es active IP Right Grant
- 2002-12-16 AU AU2002361430A patent/AU2002361430B2/en not_active Ceased
- 2002-12-16 PL PL02373400A patent/PL373400A1/xx not_active Application Discontinuation
- 2002-12-16 JP JP2003552724A patent/JP2005518375A/ja active Pending
- 2002-12-16 HU HU0500014A patent/HUP0500014A3/hu unknown
- 2002-12-16 EP EP02796648A patent/EP1453803A2/de not_active Withdrawn
- 2002-12-16 NZ NZ533430A patent/NZ533430A/en unknown
- 2002-12-16 CA CA002468880A patent/CA2468880A1/en not_active Abandoned
- 2002-12-16 WO PCT/EP2002/014344 patent/WO2003051837A2/de active Application Filing
- 2002-12-16 TW TW091136440A patent/TWI246423B/zh not_active IP Right Cessation
- 2002-12-16 RU RU2004121776/04A patent/RU2319692C2/ru not_active IP Right Cessation
- 2002-12-17 AR ARP020104893A patent/AR037863A1/es unknown
-
2004
- 2004-05-26 NO NO20042198A patent/NO326692B1/no not_active IP Right Cessation
- 2004-07-05 HR HR20040609A patent/HRP20040609A2/hr not_active Application Discontinuation
-
2008
- 2008-07-23 IL IL192991A patent/IL192991A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR0214958A (pt) | 2004-12-28 |
| CN100500654C (zh) | 2009-06-17 |
| MXPA04005768A (es) | 2004-09-10 |
| HUP0500014A3 (en) | 2010-06-28 |
| NZ533430A (en) | 2005-12-23 |
| TWI246423B (en) | 2006-01-01 |
| WO2003051837A2 (de) | 2003-06-26 |
| AR037863A1 (es) | 2004-12-09 |
| IL192991A0 (en) | 2011-08-01 |
| CA2468880A1 (en) | 2003-06-26 |
| IL161626A0 (en) | 2004-09-27 |
| RU2319692C2 (ru) | 2008-03-20 |
| HUP0500014A2 (hu) | 2005-04-28 |
| NO20042198L (no) | 2004-07-09 |
| JP2005518375A (ja) | 2005-06-23 |
| EP1453803A2 (de) | 2004-09-08 |
| TW200305405A (en) | 2003-11-01 |
| PL373400A1 (en) | 2005-08-22 |
| WO2003051837A8 (de) | 2004-05-06 |
| RU2004121776A (ru) | 2005-05-10 |
| WO2003051837A3 (de) | 2004-02-26 |
| CN1599720A (zh) | 2005-03-23 |
| HRP20040609A2 (en) | 2005-06-30 |
| AU2002361430A1 (en) | 2003-06-30 |
| AU2002361430B2 (en) | 2007-09-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |