NO324314B1 - Indolin-2-on-derivater, deres fremstilling og anvendelser, og farmasoytiske preparater, medikamenter og produkter omfattende slike forbindelser - Google Patents
Indolin-2-on-derivater, deres fremstilling og anvendelser, og farmasoytiske preparater, medikamenter og produkter omfattende slike forbindelser Download PDFInfo
- Publication number
- NO324314B1 NO324314B1 NO20024749A NO20024749A NO324314B1 NO 324314 B1 NO324314 B1 NO 324314B1 NO 20024749 A NO20024749 A NO 20024749A NO 20024749 A NO20024749 A NO 20024749A NO 324314 B1 NO324314 B1 NO 324314B1
- Authority
- NO
- Norway
- Prior art keywords
- chloro
- group
- methyl
- dimethoxybenzyl
- oxoindolin
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 264
- 238000002360 preparation method Methods 0.000 title claims description 48
- 239000003814 drug Substances 0.000 title claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 11
- 229940079593 drug Drugs 0.000 title claims description 8
- 239000000047 product Substances 0.000 title description 66
- 125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 title 1
- 239000000203 mixture Substances 0.000 claims description 67
- 238000000034 method Methods 0.000 claims description 64
- -1 carboxyl- Chemical group 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 125000005936 piperidyl group Chemical group 0.000 claims description 24
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
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- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 16
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
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- 125000001424 substituent group Chemical group 0.000 claims description 8
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- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
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- HCXANYLBMVVQQP-TUDONDPESA-N ethyl (2r)-1-[4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]benzoyl]piperidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1CCCCN1C(=O)C1=CC=C(Cl)C(C2(C)C3=CC(Cl)=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 HCXANYLBMVVQQP-TUDONDPESA-N 0.000 claims description 5
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- SZIKRGHFZTYTIT-SSDOTTSWSA-N ethyl (2r)-piperidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1CCCCN1 SZIKRGHFZTYTIT-SSDOTTSWSA-N 0.000 description 1
- UTYDAXQIOGSULE-ZJVVMWKJSA-N ethyl (2r,4r)-1-[4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]benzoyl]-4-methylpiperidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1C[C@H](C)CCN1C(=O)C1=CC=C(Cl)C(C2(C)C3=CC(Cl)=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 UTYDAXQIOGSULE-ZJVVMWKJSA-N 0.000 description 1
- GHBNOCBWSUHAAA-HTQZYQBOSA-N ethyl (2r,4r)-4-methylpiperidine-2-carboxylate Chemical compound CCOC(=O)[C@H]1C[C@H](C)CCN1 GHBNOCBWSUHAAA-HTQZYQBOSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- UVECLJDRPFNRRQ-UHFFFAOYSA-N ethyl trifluoromethanesulfonate Chemical compound CCOS(=O)(=O)C(F)(F)F UVECLJDRPFNRRQ-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010575 fractional recrystallization Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000052321 human OXTR Human genes 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000036033 hyponatraemia Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 230000004130 lipolysis Effects 0.000 description 1
- 238000006138 lithiation reaction Methods 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- RRZVACRVTPZHPE-SYQKMTEESA-N methyl (2r)-1-[4-chloro-3-[5-chloro-1-[(4-chloro-2-methoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]benzoyl]piperidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCCCN1C(=O)C1=CC=C(Cl)C(C2(C)C3=CC(Cl)=CC=C3N(CC=3C(=CC(Cl)=CC=3)OC)C2=O)=C1 RRZVACRVTPZHPE-SYQKMTEESA-N 0.000 description 1
- OUUBZQSUTKYVFL-UHFFFAOYSA-N methyl 2-methoxy-4-propan-2-yloxybenzoate Chemical compound COC(=O)C1=CC=C(OC(C)C)C=C1OC OUUBZQSUTKYVFL-UHFFFAOYSA-N 0.000 description 1
- BGKONJNFYYPCAL-UHFFFAOYSA-N methyl 4-chloro-3-[1-[(2,4-dimethoxyphenyl)methyl]-3-hydroxy-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(O)C3=CC=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 BGKONJNFYYPCAL-UHFFFAOYSA-N 0.000 description 1
- ZDLAGEROUKYNFI-UHFFFAOYSA-N methyl 4-chloro-3-[1-[(2,4-dimethoxyphenyl)methyl]-5-fluoro-3-hydroxy-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(O)C3=CC(F)=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 ZDLAGEROUKYNFI-UHFFFAOYSA-N 0.000 description 1
- RNULAJZSIGQQRB-UHFFFAOYSA-N methyl 4-chloro-3-[3-chloro-1-[(2,4-dimethoxyphenyl)methyl]-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(Cl)C3=CC=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 RNULAJZSIGQQRB-UHFFFAOYSA-N 0.000 description 1
- FECZEHXJZTZKLU-UHFFFAOYSA-N methyl 4-chloro-3-[3-chloro-1-[(2,4-dimethoxyphenyl)methyl]-5-fluoro-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(Cl)C3=CC(F)=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 FECZEHXJZTZKLU-UHFFFAOYSA-N 0.000 description 1
- KRAOJYSCRKCHQD-UHFFFAOYSA-N methyl 4-chloro-3-[5,7-dichloro-1-[(2,4-dimethoxyphenyl)methyl]-3-hydroxy-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(O)C3=C(C(=CC(Cl)=C3)Cl)N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 KRAOJYSCRKCHQD-UHFFFAOYSA-N 0.000 description 1
- PXQCDTAUJQFSGX-UHFFFAOYSA-N methyl 4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-hydroxy-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(O)C3=CC(Cl)=CC=C3N(CC=3C(=CC(OC)=CC=3)OC)C2=O)=C1 PXQCDTAUJQFSGX-UHFFFAOYSA-N 0.000 description 1
- GYRRURDBPBXPKZ-UHFFFAOYSA-N methyl 4-chloro-3-[5-chloro-1-[(4-chloro-2-methoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]benzoate Chemical compound COC(=O)C1=CC=C(Cl)C(C2(C)C3=CC(Cl)=CC=C3N(CC=3C(=CC(Cl)=CC=3)OC)C2=O)=C1 GYRRURDBPBXPKZ-UHFFFAOYSA-N 0.000 description 1
- LWENYAHUBUWONE-UHFFFAOYSA-N methyl 4-chloro-3-iodobenzoate Chemical compound COC(=O)C1=CC=C(Cl)C(I)=C1 LWENYAHUBUWONE-UHFFFAOYSA-N 0.000 description 1
- FAKIZCQRTPAOSH-UHFFFAOYSA-N methyl 5-aminopentanoate;hydrochloride Chemical compound Cl.COC(=O)CCCCN FAKIZCQRTPAOSH-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 150000005172 methylbenzenes Chemical class 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000000754 myometrium Anatomy 0.000 description 1
- XNVDYEHMNIUSNW-UHFFFAOYSA-N n',n'-dimethyl-n-(2,2,2-trifluoroethyl)ethane-1,2-diamine Chemical compound CN(C)CCNCC(F)(F)F XNVDYEHMNIUSNW-UHFFFAOYSA-N 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- 229940078490 n,n-dimethylglycine Drugs 0.000 description 1
- XGSWMLWJRXPBDL-UHFFFAOYSA-N n-(4-chlorophenyl)-2-(2,5-dimethoxyphenyl)-2-hydroxypropanamide Chemical compound COC1=CC=C(OC)C(C(C)(O)C(=O)NC=2C=CC(Cl)=CC=2)=C1 XGSWMLWJRXPBDL-UHFFFAOYSA-N 0.000 description 1
- NXVUOSCKVKOPDF-UHFFFAOYSA-N n-(4-chlorophenyl)-2-oxopropanamide Chemical compound CC(=O)C(=O)NC1=CC=C(Cl)C=C1 NXVUOSCKVKOPDF-UHFFFAOYSA-N 0.000 description 1
- SGROJTFSHJVVSF-UHFFFAOYSA-N n-(pyridin-3-ylmethyl)ethanamine Chemical compound CCNCC1=CC=CN=C1 SGROJTFSHJVVSF-UHFFFAOYSA-N 0.000 description 1
- SHXZHUMBDNUFCU-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-2,2,2-trifluoroacetamide Chemical compound CN(C)CCNC(=O)C(F)(F)F SHXZHUMBDNUFCU-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- ARMIGUIPOZHVQO-UHFFFAOYSA-N n-[4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]phenyl]-n-methylbenzenesulfonamide Chemical compound COC1=CC(OC)=CC=C1CN1C2=CC=C(Cl)C=C2C(C)(C=2C(=CC=C(C=2)N(C)S(=O)(=O)C=2C=CC=CC=2)Cl)C1=O ARMIGUIPOZHVQO-UHFFFAOYSA-N 0.000 description 1
- MQVMICDETVWDTB-UHFFFAOYSA-N n-[4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]phenyl]formamide Chemical compound COC1=CC(OC)=CC=C1CN1C2=CC=C(Cl)C=C2C(C)(C=2C(=CC=C(NC=O)C=2)Cl)C1=O MQVMICDETVWDTB-UHFFFAOYSA-N 0.000 description 1
- RKGMINAMZKJALX-UHFFFAOYSA-N n-[4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]phenyl]methanesulfonamide Chemical compound COC1=CC(OC)=CC=C1CN1C2=CC=C(Cl)C=C2C(C)(C=2C(=CC=C(NS(C)(=O)=O)C=2)Cl)C1=O RKGMINAMZKJALX-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GFQKFGQPVBTZOV-UHFFFAOYSA-N n-ethyl-2,2,2-trifluoroethanamine Chemical compound CCNCC(F)(F)F GFQKFGQPVBTZOV-UHFFFAOYSA-N 0.000 description 1
- XUHUOUMBXWRQQH-UHFFFAOYSA-N n-ethyl-2-piperidin-1-ylethanamine Chemical compound CCNCCN1CCCCC1 XUHUOUMBXWRQQH-UHFFFAOYSA-N 0.000 description 1
- IFZVQNMIQKLTKI-UHFFFAOYSA-N n-ethyl-2-pyridin-2-ylethanamine Chemical compound CCNCCC1=CC=CC=N1 IFZVQNMIQKLTKI-UHFFFAOYSA-N 0.000 description 1
- CLCYLOJYUMTESR-UHFFFAOYSA-N n-ethyl-2-pyridin-4-ylethanamine Chemical compound CCNCCC1=CC=NC=C1 CLCYLOJYUMTESR-UHFFFAOYSA-N 0.000 description 1
- FBYCSNRISIMKFX-UHFFFAOYSA-N n-ethyl-2-pyrrolidin-1-ylethanamine Chemical compound CCNCCN1CCCC1 FBYCSNRISIMKFX-UHFFFAOYSA-N 0.000 description 1
- PQLZOJVOVZMIAE-UHFFFAOYSA-N n-ethyl-3-pyridin-4-ylpropan-1-amine Chemical compound CCNCCCC1=CC=NC=C1 PQLZOJVOVZMIAE-UHFFFAOYSA-N 0.000 description 1
- WLNSKTSWPYTNLY-UHFFFAOYSA-N n-ethyl-n',n'-dimethylethane-1,2-diamine Chemical compound CCNCCN(C)C WLNSKTSWPYTNLY-UHFFFAOYSA-N 0.000 description 1
- DZHCTHQUBIPMKS-UHFFFAOYSA-N n-ethyl-n',n'-dimethylpropane-1,3-diamine Chemical compound CCNCCCN(C)C DZHCTHQUBIPMKS-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000002130 sulfonic acid ester group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- HDJXKBNOXAOJKY-ZMLFZXNESA-N tert-butyl (2r)-1-[4-chloro-3-[5-chloro-1-[(2,4-dimethoxyphenyl)methyl]-3-methyl-2-oxoindol-3-yl]benzoyl]piperidine-2-carboxylate Chemical compound COC1=CC(OC)=CC=C1CN1C2=CC=C(Cl)C=C2C(C)(C=2C(=CC=C(C=2)C(=O)N2[C@H](CCCC2)C(=O)OC(C)(C)C)Cl)C1=O HDJXKBNOXAOJKY-ZMLFZXNESA-N 0.000 description 1
- DKTNVVSFJDPBNW-GFCCVEGCSA-N tert-butyl (2r)-2-(pyrrolidine-1-carbonyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC[C@@H]1C(=O)N1CCCC1 DKTNVVSFJDPBNW-GFCCVEGCSA-N 0.000 description 1
- MESKMUAFJDWOAR-MRVPVSSYSA-N tert-butyl (2r)-piperidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@H]1CCCCN1 MESKMUAFJDWOAR-MRVPVSSYSA-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
- 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
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940125712 tocolytic agent Drugs 0.000 description 1
- 239000003675 tocolytic agent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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FR0004193A FR2807038B1 (fr) | 2000-04-03 | 2000-04-03 | Nouveaux derives d'indolin-2-one, leur preparation et les compositions pharmaceutiques les contenant |
PCT/FR2001/000980 WO2001074775A1 (fr) | 2000-04-03 | 2001-04-02 | Derives d'indolin-2-one et leur utilisation en tant que ligands des recepteurs de l'ocytocine |
Publications (3)
Publication Number | Publication Date |
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NO20024749D0 NO20024749D0 (no) | 2002-10-02 |
NO20024749L NO20024749L (no) | 2002-12-03 |
NO324314B1 true NO324314B1 (no) | 2007-09-24 |
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Family Applications (1)
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NO20024749A NO324314B1 (no) | 2000-04-03 | 2002-10-02 | Indolin-2-on-derivater, deres fremstilling og anvendelser, og farmasoytiske preparater, medikamenter og produkter omfattende slike forbindelser |
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EP (1) | EP1272468B1 (es) |
JP (1) | JP2003529586A (es) |
KR (1) | KR100765028B1 (es) |
CN (1) | CN1224614C (es) |
AR (1) | AR034547A1 (es) |
AT (1) | ATE282593T1 (es) |
AU (2) | AU2001246671B2 (es) |
BR (1) | BR0109814A (es) |
CA (1) | CA2404592A1 (es) |
CZ (1) | CZ20023297A3 (es) |
DE (1) | DE60107221T2 (es) |
DK (1) | DK1272468T3 (es) |
EA (1) | EA005093B1 (es) |
EE (1) | EE05002B1 (es) |
ES (1) | ES2232610T3 (es) |
FR (1) | FR2807038B1 (es) |
HK (1) | HK1050004A1 (es) |
HU (1) | HUP0303109A3 (es) |
IL (1) | IL152085A0 (es) |
IS (1) | IS2458B (es) |
ME (1) | MEP24308A (es) |
MX (1) | MXPA02009773A (es) |
NO (1) | NO324314B1 (es) |
NZ (1) | NZ521617A (es) |
PL (1) | PL358222A1 (es) |
PT (1) | PT1272468E (es) |
SI (1) | SI1272468T1 (es) |
SK (1) | SK14272002A3 (es) |
TR (1) | TR200202288T2 (es) |
TW (1) | TWI225860B (es) |
UA (1) | UA73163C2 (es) |
WO (1) | WO2001074775A1 (es) |
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ZA (1) | ZA200207802B (es) |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004030524A2 (en) * | 2002-10-03 | 2004-04-15 | Pr Pharmaceuticals | Treatment of autism and similar disorders |
TWI289141B (en) | 2003-03-11 | 2007-11-01 | Hoffmann La Roche F. Ag. | Quinolinone derivatives and uses thereof |
FR2875499B1 (fr) * | 2004-09-20 | 2006-10-27 | Sanofi Aventis Sa | Nouveaux derives pyridiniques d'indolin-2-one, leur preparation et leur application en therapeutique |
MY144968A (en) | 2005-04-11 | 2011-11-30 | Xenon Pharmaceuticals Inc | Spiro-oxindole compounds and their uses as therapeutic agents |
MY145694A (en) | 2005-04-11 | 2012-03-30 | Xenon Pharmaceuticals Inc | Spiroheterocyclic compounds and their uses as therapeutic agents |
AR056317A1 (es) * | 2005-04-20 | 2007-10-03 | Xenon Pharmaceuticals Inc | Compuestos de oxindol y composicion farmaceutica |
US20080318847A1 (en) * | 2005-05-10 | 2008-12-25 | Ferring International Center Sa | Use of Antagonist of Oxytocin and/or Vasopressin in Assisted Reproduction |
US8044079B2 (en) * | 2005-12-02 | 2011-10-25 | Abbott Gmbh & Co. Kg | Substituted oxindole derivatives, medicaments containing said derivatives and use thereof |
US7855194B2 (en) | 2006-03-27 | 2010-12-21 | Hoffmann-La Roche Inc. | Pyrimidine, quinazoline, pteridine and triazine derivatives |
WO2007120102A1 (en) * | 2006-04-19 | 2007-10-25 | Astrazeneca Ab | New substituted oxindole derivatives |
EP2073806B1 (en) | 2006-10-12 | 2012-02-15 | Xenon Pharmaceuticals Inc. | Use of spiro-oxindole compounds as therapeutic agents |
WO2008046083A2 (en) * | 2006-10-12 | 2008-04-17 | Xenon Pharmaceuticals Inc. | Use of oxindole compounds as therapeutic agents |
FR2909668B1 (fr) * | 2006-12-12 | 2009-01-23 | Sanofi Aventis Sa | Derives de 5-alkyloxy-indolin-2-one,leur preparation et leurs applications en therapeutique |
EP2350091B1 (en) | 2008-10-17 | 2015-06-03 | Xenon Pharmaceuticals Inc. | Spiro-oxindole compounds and their use as therapeutic agents |
CN106928247A (zh) | 2008-10-17 | 2017-07-07 | 泽农医药公司 | 螺羟吲哚化合物及其作为治疗剂的用途 |
AR077252A1 (es) | 2009-06-29 | 2011-08-10 | Xenon Pharmaceuticals Inc | Enantiomeros de compuestos de espirooxindol y sus usos como agentes terapeuticos |
PE20170202A1 (es) | 2009-10-14 | 2017-03-24 | Xenon Pharmaceuticals Inc | Metodos sinteticos para compuestos espiro-oxoindol |
MA34083B1 (fr) | 2010-02-26 | 2013-03-05 | Xenon Pharmaceuticals Inc | Compositions pharmaceutques de composé spiro-oxindole pour administration topique et leur utilisation en tant qu'agents thérapeutiques |
CN103623268B (zh) * | 2013-12-04 | 2015-07-15 | 张国显 | 神经康复再造丸及其制备方法 |
CN103830666B (zh) * | 2014-02-14 | 2016-02-10 | 孔祥英 | 一种治疗高血压的中药足浴组合物 |
CN104402886B (zh) * | 2014-09-18 | 2017-01-25 | 陕西科技大学 | 一种具有抗肿瘤活性的7‑氮杂靛红类双螺环化合物及其合成方法 |
CN104230786B (zh) * | 2014-09-26 | 2017-03-22 | 陕西科技大学 | 一种具有抗肿瘤活性的含吲哚结构的化合物及其合成方法 |
US9682033B2 (en) | 2015-02-05 | 2017-06-20 | Teva Pharmaceuticals International Gmbh | Methods of treating postherpetic neuralgia with a topical formulation of a spiro-oxindole compound |
MY197370A (en) | 2015-11-06 | 2023-06-14 | Hoffmann La Roche | Indolin-2-one derivatives |
NZ744468A (en) | 2016-01-20 | 2022-07-01 | Chemocentryx Inc | 2-oxindole compounds |
CN109232290A (zh) * | 2018-11-07 | 2019-01-18 | 陕西科技大学 | 一种含氟酰胺及其制备方法 |
CN109678781B (zh) * | 2018-12-20 | 2022-03-29 | 苏州麦迪耐斯医药科技有限公司 | 一种刺猬通路抑制剂 |
EP3912625A1 (en) | 2020-05-20 | 2021-11-24 | Kaerus Bioscience Limited | Novel maxi-k potassium channel openers for the treatment of fragile x associated disorders |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
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DE3529994A1 (de) * | 1985-08-22 | 1987-02-26 | Hoechst Ag | Indolinonderivate, verfahren zu ihrer herstellung, sie enthaltende arzneimittel und deren verwendung |
ES2110965T3 (es) * | 1989-07-25 | 1998-03-01 | Taiho Pharmaceutical Co Ltd | Derivado de oxoindol. |
US5686624A (en) * | 1992-01-30 | 1997-11-11 | Sanofi | 1-benzenesulfonyl-1,3-dihydro-indol-2-one derivatives, their preparation and pharmaceutical compositions in which they are present |
FR2708605A1 (fr) * | 1993-07-30 | 1995-02-10 | Sanofi Sa | Dérivés du N-sulfonylindol-2-one, leur préparation, les compositions pharmaceutiques en contenant. |
FR2714378B1 (fr) * | 1993-12-24 | 1996-03-15 | Sanofi Sa | Dérivés de l'indol-2-one substitués en 3 par un groupe azoté, leur préparation, les compositions pharmaceutiques en contenant. |
JPH10338672A (ja) * | 1996-07-16 | 1998-12-22 | Takeda Chem Ind Ltd | 排尿調節剤および2環性化合物 |
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- 2001-04-02 EE EEP200200573A patent/EE05002B1/xx not_active IP Right Cessation
- 2001-04-02 CZ CZ20023297A patent/CZ20023297A3/cs unknown
- 2001-04-02 WO PCT/FR2001/000980 patent/WO2001074775A1/fr active IP Right Grant
- 2001-04-02 AT AT01919610T patent/ATE282593T1/de active
- 2001-04-02 MX MXPA02009773A patent/MXPA02009773A/es active IP Right Grant
- 2001-04-02 SK SK1427-2002A patent/SK14272002A3/sk unknown
- 2001-04-02 PL PL01358222A patent/PL358222A1/xx not_active Application Discontinuation
- 2001-04-02 YU YU80902A patent/YU80902A/sh unknown
- 2001-04-02 IL IL15208501A patent/IL152085A0/xx not_active IP Right Cessation
- 2001-04-02 EA EA200200912A patent/EA005093B1/ru not_active IP Right Cessation
- 2001-04-03 TW TW090107916A patent/TWI225860B/zh not_active IP Right Cessation
-
2002
- 2002-09-24 IS IS6566A patent/IS2458B/is unknown
- 2002-09-27 ZA ZA200207802A patent/ZA200207802B/en unknown
- 2002-10-02 NO NO20024749A patent/NO324314B1/no not_active IP Right Cessation
-
2003
- 2003-03-26 HK HK03102206A patent/HK1050004A1/xx not_active IP Right Cessation
- 2003-09-03 US US10/654,060 patent/US20040059132A1/en not_active Abandoned
-
2007
- 2007-05-03 US US11/744,003 patent/US20070203184A1/en not_active Abandoned
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