ZA200703311B - Pharmaceutical compounds - Google Patents
Pharmaceutical compounds Download PDFInfo
- Publication number
- ZA200703311B ZA200703311B ZA200703311A ZA200703311A ZA200703311B ZA 200703311 B ZA200703311 B ZA 200703311B ZA 200703311 A ZA200703311 A ZA 200703311A ZA 200703311 A ZA200703311 A ZA 200703311A ZA 200703311 B ZA200703311 B ZA 200703311B
- Authority
- ZA
- South Africa
- Prior art keywords
- ylmethyl
- morpholin
- thieno
- indazol
- pyrimidine
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 188
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 190
- 150000001412 amines Chemical class 0.000 claims description 108
- 239000000203 mixture Substances 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 28
- 229920006395 saturated elastomer Polymers 0.000 claims description 28
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 24
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 22
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 22
- 125000002947 alkylene group Chemical group 0.000 claims description 19
- 230000008569 process Effects 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000004060 metabolic process Effects 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 4
- 208000017701 Endocrine disease Diseases 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052792 caesium Inorganic materials 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 4
- AQNQGBUEVCAVML-UHFFFAOYSA-N oxazepane Chemical compound C1CCNOCC1 AQNQGBUEVCAVML-UHFFFAOYSA-N 0.000 claims description 4
- PGAZQSBUJDVGIX-UHFFFAOYSA-N thiazepane Chemical group C1CCNSCC1 PGAZQSBUJDVGIX-UHFFFAOYSA-N 0.000 claims description 4
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
- DBWYCBQJXDDKBO-UHFFFAOYSA-N 4-[2-(1-methylindazol-4-yl)-6-[(4-methylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C1CN(C)CCN1CC1=CC2=NC(C=3C=4C=NN(C)C=4C=CC=3)=NC(N3CCOCC3)=C2S1 DBWYCBQJXDDKBO-UHFFFAOYSA-N 0.000 claims description 3
- YMZLRXHMWNSCOL-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C=1C2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2SC=1CN(CC1)CCN1C1=NC=CC=N1 YMZLRXHMWNSCOL-UHFFFAOYSA-N 0.000 claims description 3
- QGLBMLUOLGHQCQ-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[[4-(2,2,2-trifluoroethyl)piperazin-1-yl]methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C1CN(CC(F)(F)F)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 QGLBMLUOLGHQCQ-UHFFFAOYSA-N 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 208000012902 Nervous system disease Diseases 0.000 claims description 3
- 208000025966 Neurological disease Diseases 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 230000010261 cell growth Effects 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- PVUAFOAHOPJEFX-UHFFFAOYSA-N 1-[4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-3-phenoxypropan-2-ol Chemical compound C1CN(CC=2SC3=C(N4CCOCC4)N=C(N=C3C=2)C=2C=3C=NNC=3C=CC=2)CCN1CC(O)COC1=CC=CC=C1 PVUAFOAHOPJEFX-UHFFFAOYSA-N 0.000 claims description 2
- HKNUXKSCUPDXOM-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-4-(pyridin-2-ylmethyl)piperidin-4-ol Chemical compound C1CN(CC=2SC3=C(N4CCOCC4)N=C(N=C3C=2)C=2C=3C=NNC=3C=CC=2)CCC1(O)CC1=CC=CC=N1 HKNUXKSCUPDXOM-UHFFFAOYSA-N 0.000 claims description 2
- HBCRHZPQEXEYFA-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-n-(2-methoxyethyl)-n-methylpiperidin-4-amine Chemical compound C1CC(N(C)CCOC)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 HBCRHZPQEXEYFA-UHFFFAOYSA-N 0.000 claims description 2
- FRXOVRUCCABHIB-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-n-(2-methoxyethyl)-n-methylpiperidine-4-carboxamide Chemical compound C1CC(C(=O)N(C)CCOC)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 FRXOVRUCCABHIB-UHFFFAOYSA-N 0.000 claims description 2
- PMOJDZSMXDOYCU-UHFFFAOYSA-N 3-[4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]sulfonyl-n,n-dimethylpropan-1-amine Chemical compound C1CN(S(=O)(=O)CCCN(C)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 PMOJDZSMXDOYCU-UHFFFAOYSA-N 0.000 claims description 2
- BCWNNSHKFZVIAL-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[[4-(pyridin-2-ylmethyl)piperazin-1-yl]methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C=1C2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2SC=1CN(CC1)CCN1CC1=CC=CC=N1 BCWNNSHKFZVIAL-UHFFFAOYSA-N 0.000 claims description 2
- FLXMHMGVRRNXKE-UHFFFAOYSA-N 4-[2-(6-fluoro-1h-indazol-4-yl)-6-[(4-methylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C1CN(C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=C(F)C=3)=NC(N3CCOCC3)=C2S1 FLXMHMGVRRNXKE-UHFFFAOYSA-N 0.000 claims description 2
- RMTJOQQEPJTKHD-UHFFFAOYSA-N 4-[3-[4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]sulfonylpropyl]morpholine Chemical compound C1CN(CC=2SC3=C(N4CCOCC4)N=C(N=C3C=2)C=2C=3C=NNC=3C=CC=2)CCN1S(=O)(=O)CCCN1CCOCC1 RMTJOQQEPJTKHD-UHFFFAOYSA-N 0.000 claims description 2
- PBGHDMALTDMPLT-UHFFFAOYSA-N 4-[6-[[4-(1h-imidazol-5-ylmethyl)piperazin-1-yl]methyl]-2-(1h-indazol-4-yl)thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C=1N=CNC=1CN(CC1)CCN1CC(SC1=2)=CC1=NC(C=1C=3C=NNC=3C=CC=1)=NC=2N1CCOCC1 PBGHDMALTDMPLT-UHFFFAOYSA-N 0.000 claims description 2
- VVAAKMMNRYPULC-UHFFFAOYSA-N 4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-n-(2-methoxyethyl)-n-methylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)N(C)CCOC)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 VVAAKMMNRYPULC-UHFFFAOYSA-N 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims description 2
- AGFAKYCPLSQLCR-UHFFFAOYSA-N [4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-morpholin-4-ylmethanone Chemical compound C1CN(CC=2SC3=C(N4CCOCC4)N=C(N=C3C=2)C=2C=3C=NNC=3C=CC=2)CCN1C(=O)N1CCOCC1 AGFAKYCPLSQLCR-UHFFFAOYSA-N 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 230000006399 behavior Effects 0.000 claims description 2
- 230000003915 cell function Effects 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- ANWYJPNULDNFLO-UHFFFAOYSA-N n-[[1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperidin-4-yl]methyl]-2-methoxy-n-methylethanamine Chemical compound C1CC(CN(C)CCOC)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 ANWYJPNULDNFLO-UHFFFAOYSA-N 0.000 claims description 2
- XFKPHTUFNPCFFE-UHFFFAOYSA-N 1-[4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-methylpropan-2-ol Chemical compound C1CN(CC(C)(O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 XFKPHTUFNPCFFE-UHFFFAOYSA-N 0.000 claims 1
- YGNSRWJWCRCEEI-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-4-(1,3-thiazol-2-yl)piperidin-4-ol Chemical compound C1CC(O)(C=2SC=CN=2)CCN1CC(SC1=2)=CC1=NC(C=1C=3C=NNC=3C=CC=1)=NC=2N1CCOCC1 YGNSRWJWCRCEEI-UHFFFAOYSA-N 0.000 claims 1
- CBRZFCXFNKEPQW-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-n-(2-methoxyethyl)-n-(2,2,2-trifluoroethyl)piperidin-4-amine Chemical compound C1CC(N(CC(F)(F)F)CCOC)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 CBRZFCXFNKEPQW-UHFFFAOYSA-N 0.000 claims 1
- CKPCDQMPUCCQAK-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]-n-methyl-n-(3-methylsulfonylpropyl)piperidin-4-amine Chemical compound C1CC(N(CCCS(C)(=O)=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 CKPCDQMPUCCQAK-UHFFFAOYSA-N 0.000 claims 1
- WPOMZWXIRUMDFK-UHFFFAOYSA-N 1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperidine-4-carboxamide Chemical compound C1CC(C(=O)N)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 WPOMZWXIRUMDFK-UHFFFAOYSA-N 0.000 claims 1
- PDRCNHPSTXCVLR-UHFFFAOYSA-N 2-[4-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-methylpropan-1-ol Chemical compound C1CN(C(C)(CO)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 PDRCNHPSTXCVLR-UHFFFAOYSA-N 0.000 claims 1
- OFEYVODQKAFMCD-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[(4-methylsulfonylpiperidin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C1CC(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 OFEYVODQKAFMCD-UHFFFAOYSA-N 0.000 claims 1
- GTTHXOLXOFAUPD-CALCHBBNSA-N 4-[2-(1h-indazol-4-yl)-6-[[(2r,6s)-2,4,6-trimethylpiperazin-1-yl]methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C[C@H]1CN(C)C[C@@H](C)N1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 GTTHXOLXOFAUPD-CALCHBBNSA-N 0.000 claims 1
- DNMZJEONAKYIJZ-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[[4-(1,3-thiazol-2-yl)piperazin-1-yl]methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C=1C2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2SC=1CN(CC1)CCN1C1=NC=CS1 DNMZJEONAKYIJZ-UHFFFAOYSA-N 0.000 claims 1
- VTOMTDBYFIVUNJ-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C1CN(CCOC)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 VTOMTDBYFIVUNJ-UHFFFAOYSA-N 0.000 claims 1
- TXWOQUYQDYHSPT-UHFFFAOYSA-N 4-[2-(1h-indazol-4-yl)-6-[[4-(pyridin-2-ylmethyl)piperidin-1-yl]methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C=1C=CC=NC=1CC(CC1)CCN1CC(SC1=2)=CC1=NC(C=1C=3C=NNC=3C=CC=1)=NC=2N1CCOCC1 TXWOQUYQDYHSPT-UHFFFAOYSA-N 0.000 claims 1
- BALSJHHKLXBRQR-UHFFFAOYSA-N 4-[6-[[4-(cyclopropylmethyl)piperazin-1-yl]methyl]-2-(1h-indazol-4-yl)thieno[3,2-d]pyrimidin-4-yl]morpholine Chemical compound C1CN(CC=2SC3=C(N4CCOCC4)N=C(N=C3C=2)C=2C=3C=NNC=3C=CC=2)CCN1CC1CC1 BALSJHHKLXBRQR-UHFFFAOYSA-N 0.000 claims 1
- JEAFDZZBPCFQGC-UHFFFAOYSA-N [1-[[2-(1h-indazol-4-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperidin-4-yl]methanol Chemical compound C1CC(CO)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 JEAFDZZBPCFQGC-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 description 102
- 238000005481 NMR spectroscopy Methods 0.000 description 94
- 239000000243 solution Substances 0.000 description 91
- 239000002904 solvent Substances 0.000 description 84
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 83
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- 238000002360 preparation method Methods 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- -1 pentylene, hexylene, heptylene, octylene Chemical group 0.000 description 54
- 239000012267 brine Substances 0.000 description 53
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
- 238000003818 flash chromatography Methods 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- 238000003756 stirring Methods 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 34
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- 108091007960 PI3Ks Proteins 0.000 description 18
- 102000038030 PI3Ks Human genes 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- UKRUSUPRQFIBBZ-UHFFFAOYSA-N tert-butyl 2-(methoxymethyl)piperidine-1-carboxylate Chemical compound COCC1CCCCN1C(=O)OC(C)(C)C UKRUSUPRQFIBBZ-UHFFFAOYSA-N 0.000 description 1
- OJCLHERKFHHUTB-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CO)C1 OJCLHERKFHHUTB-UHFFFAOYSA-N 0.000 description 1
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- FZOFMKCQDCVJKS-UHFFFAOYSA-N tert-butyl 3-(methoxymethyl)piperidine-1-carboxylate Chemical compound COCC1CCCN(C(=O)OC(C)(C)C)C1 FZOFMKCQDCVJKS-UHFFFAOYSA-N 0.000 description 1
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- LZNDQDBMBDHOBL-UHFFFAOYSA-N tert-butyl 4-(3-methoxypropylsulfanyl)piperidine-1-carboxylate Chemical compound COCCCSC1CCN(C(=O)OC(C)(C)C)CC1 LZNDQDBMBDHOBL-UHFFFAOYSA-N 0.000 description 1
- FKYRISKJPQMJRI-UHFFFAOYSA-N tert-butyl 4-(3-methoxypropylsulfonyl)piperidine-1-carboxylate Chemical compound COCCCS(=O)(=O)C1CCN(C(=O)OC(C)(C)C)CC1 FKYRISKJPQMJRI-UHFFFAOYSA-N 0.000 description 1
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- VRVUOIHXJJWKIY-UHFFFAOYSA-N tert-butyl 4-(dimethylcarbamoyl)piperidine-1-carboxylate Chemical compound CN(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1 VRVUOIHXJJWKIY-UHFFFAOYSA-N 0.000 description 1
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- BFPYLKMLSYLUJO-UHFFFAOYSA-N tert-butyl 4-(morpholine-4-carbonyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C(=O)N1CCOCC1 BFPYLKMLSYLUJO-UHFFFAOYSA-N 0.000 description 1
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- VBSVOQDOXQGNFV-UHFFFAOYSA-N tert-butyl 4-(pyridin-4-ylmethyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC=NC=C1 VBSVOQDOXQGNFV-UHFFFAOYSA-N 0.000 description 1
- FTUGDRKBXMMROC-UHFFFAOYSA-N tert-butyl 4-[(2-chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl)methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC2=NC(Cl)=NC(N3CCOCC3)=C2S1 FTUGDRKBXMMROC-UHFFFAOYSA-N 0.000 description 1
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- CBJGTHZUHVNXFG-UHFFFAOYSA-N tert-butyl 4-[2-(dimethylamino)-2-oxoethyl]piperazine-1-carboxylate Chemical compound CN(C)C(=O)CN1CCN(C(=O)OC(C)(C)C)CC1 CBJGTHZUHVNXFG-UHFFFAOYSA-N 0.000 description 1
- LOKMEVPNFNZZBD-UHFFFAOYSA-N tert-butyl 4-[2-methoxyethyl(1,3-thiazol-2-ylmethyl)amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N(CCOC)CC1=NC=CS1 LOKMEVPNFNZZBD-UHFFFAOYSA-N 0.000 description 1
- KCQLRNNVATXXOV-UHFFFAOYSA-N tert-butyl 4-[2-methoxyethyl(methyl)amino]piperidine-1-carboxylate Chemical compound COCCN(C)C1CCN(C(=O)OC(C)(C)C)CC1 KCQLRNNVATXXOV-UHFFFAOYSA-N 0.000 description 1
- HDIQYMCOHWFMMJ-UHFFFAOYSA-N tert-butyl 4-[2-methoxyethyl(methyl)carbamoyl]piperazine-1-carboxylate Chemical compound COCCN(C)C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 HDIQYMCOHWFMMJ-UHFFFAOYSA-N 0.000 description 1
- RATHEUYXLKVECW-UHFFFAOYSA-N tert-butyl 4-[2-methoxyethyl(methylsulfonyl)amino]piperidine-1-carboxylate Chemical compound COCCN(S(C)(=O)=O)C1CCN(C(=O)OC(C)(C)C)CC1 RATHEUYXLKVECW-UHFFFAOYSA-N 0.000 description 1
- XGQXHWWZAYUGSC-UHFFFAOYSA-N tert-butyl 4-[2-methoxyethyl(propan-2-yl)amino]piperidine-1-carboxylate Chemical compound COCCN(C(C)C)C1CCN(C(=O)OC(C)(C)C)CC1 XGQXHWWZAYUGSC-UHFFFAOYSA-N 0.000 description 1
- COSNXNXVRPEJCB-UHFFFAOYSA-N tert-butyl 4-[cyclopropylmethyl(2-methoxyethyl)amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N(CCOC)CC1CC1 COSNXNXVRPEJCB-UHFFFAOYSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- IBDXIJWCSGQNAR-UHFFFAOYSA-N tert-butyl 4-methylsulfonylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(S(C)(=O)=O)CC1 IBDXIJWCSGQNAR-UHFFFAOYSA-N 0.000 description 1
- LYGIBBFCSCAULH-UHFFFAOYSA-N tert-butyl 4-pyridin-2-yloxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=CC=N1 LYGIBBFCSCAULH-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-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
- 229960003604 testosterone Drugs 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical class N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 229960003741 tranylcypromine Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- 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]
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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
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- A61P3/04—Anorexiants; Antiobesity agents
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- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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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
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0423653.5A GB0423653D0 (en) | 2004-10-25 | 2004-10-25 | Pharmaceutical compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200703311B true ZA200703311B (en) | 2008-06-25 |
Family
ID=33485146
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200703311A ZA200703311B (en) | 2004-10-25 | 2007-04-23 | Pharmaceutical compounds |
ZA200703312A ZA200703312B (en) | 2004-10-25 | 2007-04-23 | Pharmaceutical compounds |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200703312A ZA200703312B (en) | 2004-10-25 | 2007-04-23 | Pharmaceutical compounds |
Country Status (17)
Country | Link |
---|---|
US (8) | US7776856B2 (es) |
EP (3) | EP1812446B1 (es) |
JP (3) | JP5048504B2 (es) |
KR (3) | KR20070097422A (es) |
CN (2) | CN101087794B (es) |
AU (2) | AU2005298404B2 (es) |
BR (2) | BRPI0517019A (es) |
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NO (2) | NO20072116L (es) |
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