CN1313853A - 作为生长激素释放剂的2-羟基吲哚衍生物 - Google Patents
作为生长激素释放剂的2-羟基吲哚衍生物 Download PDFInfo
- Publication number
- CN1313853A CN1313853A CN99809857A CN99809857A CN1313853A CN 1313853 A CN1313853 A CN 1313853A CN 99809857 A CN99809857 A CN 99809857A CN 99809857 A CN99809857 A CN 99809857A CN 1313853 A CN1313853 A CN 1313853A
- Authority
- CN
- China
- Prior art keywords
- diethyllaminoethyl
- replaces
- oxyindole
- optional
- hydroxyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000018997 Growth Hormone Human genes 0.000 title claims abstract description 21
- 108010051696 Growth Hormone Proteins 0.000 title claims abstract description 21
- 239000000122 growth hormone Substances 0.000 title claims abstract description 20
- 125000004095 oxindolyl group Chemical class N1(C(CC2=CC=CC=C12)=O)* 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 47
- 229940002612 prodrug Drugs 0.000 claims abstract description 47
- 239000000651 prodrug Substances 0.000 claims abstract description 47
- 239000001257 hydrogen Substances 0.000 claims abstract description 46
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 41
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims description 88
- -1 nitro, hydroxyl Chemical group 0.000 claims description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 18
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 16
- 230000003287 optical effect Effects 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
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- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
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- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
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- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
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- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 7
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- 239000000243 solution Substances 0.000 description 174
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 130
- 238000005160 1H NMR spectroscopy Methods 0.000 description 123
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- 238000005481 NMR spectroscopy Methods 0.000 description 64
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- 229920006395 saturated elastomer Polymers 0.000 description 36
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 33
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- 238000006243 chemical reaction Methods 0.000 description 32
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- 238000003810 ethyl acetate extraction Methods 0.000 description 26
- 229910052757 nitrogen Inorganic materials 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 238000005406 washing Methods 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000003513 alkali Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
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- 229910052740 iodine Inorganic materials 0.000 description 18
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- 238000004440 column chromatography Methods 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 238000000605 extraction Methods 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 13
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
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- 239000003480 eluent Substances 0.000 description 8
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- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
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- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 7
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
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- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- CBPYOHALYYGNOE-UHFFFAOYSA-M potassium;3,5-dinitrobenzoate Chemical compound [K+].[O-]C(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 CBPYOHALYYGNOE-UHFFFAOYSA-M 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 108010048734 sclerotin Proteins 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
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010129 solution processing Methods 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- XCAQIUOFDMREBA-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=O)OC(C)(C)C XCAQIUOFDMREBA-UHFFFAOYSA-N 0.000 description 1
- JAELLLITIZHOGQ-UHFFFAOYSA-N tert-butyl propanoate Chemical compound CCC(=O)OC(C)(C)C JAELLLITIZHOGQ-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000005313 thymus development Effects 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
-
- 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
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/40—Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims (19)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP23464398 | 1998-08-20 | ||
JP234643/1998 | 1998-08-20 |
Publications (2)
Publication Number | Publication Date |
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CN1313853A true CN1313853A (zh) | 2001-09-19 |
CN1161333C CN1161333C (zh) | 2004-08-11 |
Family
ID=16974248
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CNB998098574A Expired - Fee Related CN1161333C (zh) | 1998-08-20 | 1999-08-18 | 作为生长激素释放剂的2-羟基吲哚衍生物 |
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Country | Link |
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US (1) | US6576656B1 (zh) |
EP (1) | EP1105376B1 (zh) |
JP (1) | JP4445133B2 (zh) |
KR (1) | KR100680085B1 (zh) |
CN (1) | CN1161333C (zh) |
AT (1) | ATE288895T1 (zh) |
AU (1) | AU5301199A (zh) |
CA (1) | CA2340701C (zh) |
DE (1) | DE69923692T2 (zh) |
ES (1) | ES2237135T3 (zh) |
WO (1) | WO2000010975A1 (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102361865A (zh) * | 2009-02-12 | 2012-02-22 | 赛诺菲 | 在3位取代的3-苯并呋喃基-吲哚-2-酮衍生物,其制备及其治疗用途 |
CN103443076A (zh) * | 2007-08-16 | 2013-12-11 | 赛诺菲-安万特 | 在3位双取代的吲哚-2-酮衍生物、其制备和其治疗应用 |
CN102361864B (zh) * | 2009-02-12 | 2015-11-25 | 赛诺菲 | 取代的3-苯并呋喃基-吲哚-2-酮-3-乙酰氨基哌嗪衍生物、其制备及其治疗用途 |
Families Citing this family (24)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2004507456A (ja) | 2000-05-11 | 2004-03-11 | ブリストル−マイヤーズ スクイブ カンパニー | 成長ホルモン分泌促進薬として有用なテトラヒドロイソキノリン類縁体 |
EP1364945A4 (en) * | 2001-01-30 | 2005-08-31 | Sumitomo Pharma | BENZIMIDAZOLIDINONE DERIVATIVES |
US6649606B1 (en) | 2001-11-09 | 2003-11-18 | Bristol-Myers Squibb Co. | Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity |
SE0104340D0 (sv) | 2001-12-20 | 2001-12-20 | Astrazeneca Ab | New compounds |
SE0104341D0 (sv) * | 2001-12-20 | 2001-12-20 | Astrazeneca Ab | New use |
DE60221283T2 (de) * | 2001-12-21 | 2008-03-20 | Astrazeneca Ab | Verwendung von oxindolderivaten zur behandlung von mit demenz in zusammenhang stehenden krankheiten, alzheimer-krankheit und mit glycogensynthasekinase-3 assoziierten leiden |
TW200301123A (en) * | 2001-12-21 | 2003-07-01 | Astrazeneca Uk Ltd | New use |
SE0200979D0 (sv) | 2002-03-28 | 2002-03-28 | Astrazeneca Ab | New compounds |
ES2297200T3 (es) * | 2002-10-24 | 2008-05-01 | Pfizer Products Inc. | Derivados de acilo de 5-(2-(4-(1,2 bencisotiazol-3-il)-1-piperazinil)etil)-6-cloro-1,3-dihidro-2h-indol-2-ona que presentan actividad neuroleptica. |
US7476653B2 (en) | 2003-06-18 | 2009-01-13 | Tranzyme Pharma, Inc. | Macrocyclic modulators of the ghrelin receptor |
US6912165B2 (en) * | 2003-08-22 | 2005-06-28 | International Business Machines Corporation | Method for transparent updates of output driver impedance |
JPWO2005035498A1 (ja) * | 2003-10-08 | 2006-12-21 | 住友製薬株式会社 | 含窒素二環性化合物の摂食調節剤としての用途 |
AU2005277389A1 (en) | 2004-08-18 | 2006-03-02 | Elixir Pharmaceuticals, Inc. | Growth-hormone secretagogues |
WO2007032371A1 (ja) | 2005-09-14 | 2007-03-22 | Dainippon Sumitomo Pharma Co., Ltd. | 摂食調節剤としてのオキシインドール誘導体 |
CU23558A1 (es) | 2006-02-28 | 2010-07-20 | Ct Ingenieria Genetica Biotech | Compuestos análogos a los secretagogos peptidicos de la hormona de crecimiento |
EP2644618B1 (en) | 2007-02-09 | 2016-08-17 | Ocera Therapeutics, Inc. | tether intermediates for the synthesis of macrocyclic ghrelin receptor modulators |
CA2728767A1 (en) * | 2008-06-26 | 2009-12-30 | Amgen Inc. | Alkynyl alcohols as kinase inhibitors |
EP2246326A1 (de) * | 2009-05-02 | 2010-11-03 | Bayer CropScience AG | Verfahren zur Herstellung von Oxindolen und ortho-substituierten Anilinen und ihre Verwendung als Zwischenprodukte für Synthesen |
EP3153167B1 (en) | 2011-10-28 | 2019-10-02 | Vanderbilt University | Substituted 2-(4-heterocyclylbenzyl)isoindolin-1-one analogs as positive allosteric modulators of the muscarinic acetylcholine receptor m1 |
US9073935B2 (en) | 2011-11-11 | 2015-07-07 | Vanderbilt University | Substituted benzylspiroindolin-2-one analogs as positive allosteric modulators of the muscarinic acetylcholine receptor M1 |
US8697888B2 (en) * | 2012-01-06 | 2014-04-15 | Vanderbilt University | Substituted (1-(methylsulfonyl)azetidin-3-yl)(heterocycloalkyl)methanone analogs as antagonists of muscarinic acetylcholine M1 receptors |
US9029563B2 (en) | 2012-01-06 | 2015-05-12 | Vanderbilt University | Substituted 1-benzylindolin-2-one analogs as positive allosteric modulators of muscarinic acetylcholine M1 receptors |
WO2013106795A1 (en) | 2012-01-12 | 2013-07-18 | Vanderbilt University | Substituted 4-(1h~pyrazol-4.yl)benzyl analogues as positive allosteric modulators of machr m1 receptors |
JP6262661B2 (ja) | 2012-10-24 | 2018-01-17 | 第一三共株式会社 | 筋萎縮性側索硬化症治療剤 |
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GB125671A (en) | 1917-07-03 | 1919-05-01 | James Rossiter Hoyle | Improvements in or relating to Armour Piercing Projectiles. |
US3441570A (en) * | 1966-01-20 | 1969-04-29 | Parke Davis & Co | 3-tertiary aminoalkylamino-3-phenyl oxindole compounds |
US3891644A (en) * | 1971-01-11 | 1975-06-24 | Wyeth John & Brother Ltd | 10,10-Disubstituted-2,3,4,10-tetrahydro-and 1,2,3,4,10a-hexahydropyrimidol {8 1,2-a{9 indole derivatives |
GB1450137A (en) | 1973-12-20 | 1976-09-22 | Wyeth John & Brother Ltd | Indole derivatives |
US5283241A (en) * | 1992-08-28 | 1994-02-01 | Merck & Co., Inc. | Benzo-fused lactams promote release of growth hormone |
-
1999
- 1999-08-18 ES ES99938515T patent/ES2237135T3/es not_active Expired - Lifetime
- 1999-08-18 JP JP2000566249A patent/JP4445133B2/ja not_active Expired - Fee Related
- 1999-08-18 AU AU53011/99A patent/AU5301199A/en not_active Abandoned
- 1999-08-18 CN CNB998098574A patent/CN1161333C/zh not_active Expired - Fee Related
- 1999-08-18 KR KR1020017002123A patent/KR100680085B1/ko not_active IP Right Cessation
- 1999-08-18 AT AT99938515T patent/ATE288895T1/de not_active IP Right Cessation
- 1999-08-18 US US09/763,241 patent/US6576656B1/en not_active Expired - Fee Related
- 1999-08-18 WO PCT/JP1999/004443 patent/WO2000010975A1/en active IP Right Grant
- 1999-08-18 DE DE69923692T patent/DE69923692T2/de not_active Expired - Lifetime
- 1999-08-18 EP EP99938515A patent/EP1105376B1/en not_active Expired - Lifetime
- 1999-08-18 CA CA002340701A patent/CA2340701C/en not_active Expired - Fee Related
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103443076A (zh) * | 2007-08-16 | 2013-12-11 | 赛诺菲-安万特 | 在3位双取代的吲哚-2-酮衍生物、其制备和其治疗应用 |
CN103443076B (zh) * | 2007-08-16 | 2016-06-22 | 赛诺菲-安万特 | 在3位双取代的吲哚-2-酮衍生物、其制备和其治疗应用 |
CN102361865A (zh) * | 2009-02-12 | 2012-02-22 | 赛诺菲 | 在3位取代的3-苯并呋喃基-吲哚-2-酮衍生物,其制备及其治疗用途 |
CN102361864B (zh) * | 2009-02-12 | 2015-11-25 | 赛诺菲 | 取代的3-苯并呋喃基-吲哚-2-酮-3-乙酰氨基哌嗪衍生物、其制备及其治疗用途 |
CN102361865B (zh) * | 2009-02-12 | 2015-11-25 | 赛诺菲 | 在3位取代的3-苯并呋喃基-吲哚-2-酮衍生物,其制备及其治疗用途 |
Also Published As
Publication number | Publication date |
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CN1161333C (zh) | 2004-08-11 |
US6576656B1 (en) | 2003-06-10 |
AU5301199A (en) | 2000-03-14 |
KR20010085413A (ko) | 2001-09-07 |
CA2340701A1 (en) | 2000-03-02 |
ATE288895T1 (de) | 2005-02-15 |
ES2237135T3 (es) | 2005-07-16 |
DE69923692D1 (de) | 2005-03-17 |
JP2002523400A (ja) | 2002-07-30 |
EP1105376A1 (en) | 2001-06-13 |
JP4445133B2 (ja) | 2010-04-07 |
DE69923692T2 (de) | 2006-03-23 |
WO2000010975A1 (en) | 2000-03-02 |
EP1105376B1 (en) | 2005-02-09 |
KR100680085B1 (ko) | 2007-02-28 |
CA2340701C (en) | 2009-05-26 |
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