DE60225174T2 - Beta-3 adrenergische agonisten - Google Patents
Beta-3 adrenergische agonisten Download PDFInfo
- Publication number
- DE60225174T2 DE60225174T2 DE60225174T DE60225174T DE60225174T2 DE 60225174 T2 DE60225174 T2 DE 60225174T2 DE 60225174 T DE60225174 T DE 60225174T DE 60225174 T DE60225174 T DE 60225174T DE 60225174 T2 DE60225174 T2 DE 60225174T2
- Authority
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- Germany
- Prior art keywords
- mmol
- compound according
- alkyl
- formula
- independently
- 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.)
- Expired - Lifetime
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- 239000000048 adrenergic agonist Substances 0.000 title abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims description 87
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
- -1 cyano, methyl Chemical group 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 208000008589 Obesity Diseases 0.000 claims description 12
- 235000020824 obesity Nutrition 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 10
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229930192474 thiophene Natural products 0.000 claims description 5
- 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 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 3
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 3
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 claims description 3
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 150000003852 triazoles Chemical class 0.000 claims description 3
- RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 229940126157 adrenergic receptor agonist Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 143
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 103
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 79
- 150000001412 amines Chemical class 0.000 description 78
- 239000000203 mixture Substances 0.000 description 62
- 239000000243 solution Substances 0.000 description 54
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
- 238000000034 method Methods 0.000 description 38
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 150000002924 oxiranes Chemical class 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 229960001866 silicon dioxide Drugs 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 19
- 108020003175 receptors Proteins 0.000 description 19
- 102000005962 receptors Human genes 0.000 description 19
- 229910021529 ammonia Inorganic materials 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 238000001914 filtration Methods 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
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- 239000002904 solvent Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
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- 239000000556 agonist Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 8
- WTBVSHZWSAUKDD-UHFFFAOYSA-N 2-bromo-4-methyl-4-nitropentanal Chemical compound [O-][N+](=O)C(C)(C)CC(Br)C=O WTBVSHZWSAUKDD-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
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Classifications
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- 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
- C07D409/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US334031P | 2001-11-20 | ||
| PCT/US2002/033625 WO2003044017A1 (en) | 2001-11-20 | 2002-11-12 | Beta 3 adrenergic agonists |
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| US7208505B2 (en) * | 2001-08-14 | 2007-04-24 | Eli Lilly And Company | β3 adrenergic agonists |
| ATE297925T1 (de) * | 2001-11-20 | 2005-07-15 | Lilly Co Eli | 3-substituierte oxindol beta 3 agonisten |
| WO2003044017A1 (en) * | 2001-11-20 | 2003-05-30 | Eli Lilly And Company | Beta 3 adrenergic agonists |
| EP1697301A2 (en) * | 2003-12-23 | 2006-09-06 | Astellas Pharma Inc. | Aminoalcohol derivatives |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| DE102004050952A1 (de) * | 2004-10-18 | 2006-04-20 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmazeutische Zusammensetzung zur Behandlung von Beschwerden, die mit krankhaften Veränderungen oder Irritationen der Prostata verbunden sind |
| JP2008100916A (ja) * | 2005-01-24 | 2008-05-01 | Dainippon Sumitomo Pharma Co Ltd | インドール類およびそれを含む医薬組成物 |
| JP4864982B2 (ja) * | 2005-12-27 | 2012-02-01 | エフ．ホフマン−ラ ロシュ アーゲー | アリール−イソオキサゾール−４−イル−イミダゾ［１，５−ａ］ピリジン誘導体 |
| MX2008014796A (es) | 2006-05-31 | 2008-12-02 | Hoffmann La Roche | Derivados de aril-4-etinil-isoxazol. |
| JP5416103B2 (ja) | 2007-06-22 | 2014-02-12 | エフ．ホフマン−ラ ロシュ アーゲー | イソオキサゾール−イミダゾール誘導体 |
| WO2009071464A1 (en) | 2007-12-04 | 2009-06-11 | F. Hoffmann-La Roche Ag | Isoxazolo-pyrazine derivatives |
| US7943619B2 (en) | 2007-12-04 | 2011-05-17 | Hoffmann-La Roche Inc. | Isoxazolo-pyridazine derivatives |
| US7902201B2 (en) | 2007-12-04 | 2011-03-08 | Hoffmann-La Roche Inc. | Isoxazolo-pyrazine derivatives |
| TW201033201A (en) | 2009-02-19 | 2010-09-16 | Hoffmann La Roche | Isoxazole-isoxazole and isoxazole-isothiazole derivatives |
| US8389550B2 (en) | 2009-02-25 | 2013-03-05 | Hoffmann-La Roche Inc. | Isoxazoles / O-pyridines with ethyl and ethenyl linker |
| US8222246B2 (en) | 2009-04-02 | 2012-07-17 | Hoffmann-La Roche Inc. | Substituted isoxazoles |
| US8227461B2 (en) | 2009-04-30 | 2012-07-24 | Hoffmann-La Roche Inc. | Isoxazoles |
| WO2010127976A1 (en) | 2009-05-05 | 2010-11-11 | F. Hoffmann-La Roche Ag | Isoxazole-pyridine derivatives |
| EP2427458B1 (en) | 2009-05-05 | 2014-05-07 | F.Hoffmann-La Roche Ag | Isoxazole-pyridazine derivatives |
| AU2010244552A1 (en) | 2009-05-05 | 2011-09-29 | F. Hoffmann-La Roche Ag | Isoxazole-pyrazole derivatives |
| MX2011011490A (es) | 2009-05-05 | 2011-11-18 | Hoffmann La Roche | Derivados de isoxazol-tiazol como agonistas inversos del receptor de acido gamma-aminobutirico a (gaba a), para usarse en el tratamiento de trastornos cognitivos. |
| MX2011011484A (es) | 2009-05-07 | 2011-11-18 | Hoffmann La Roche | Derivados de isoxazol-piridina como moduladores del acido gamma-aminobutirico. |
| US8785435B2 (en) | 2011-10-20 | 2014-07-22 | Hoffmann-La Roche Inc. | Solid forms |
| RU2764243C2 (ru) | 2017-09-22 | 2022-01-14 | ДЖУБИЛАНТ ЭПИПЭД ЭлЭлСи | Гетероциклические соединения в качестве ингибиторов PAD |
| AU2018352142B2 (en) | 2017-10-18 | 2022-08-25 | Jubilant Epipad LLC | Imidazo-pyridine compounds as PAD inhibitors |
| US11629135B2 (en) | 2017-11-06 | 2023-04-18 | Jubilant Prodell Llc | Pyrimidine derivatives as inhibitors of PD1/PD-L1 activation |
| PT3704120T (pt) | 2017-11-24 | 2024-07-03 | Jubilant Episcribe Llc | Compostos heterocíclicos como inibidores de prmt5 |
| MX2020009517A (es) | 2018-03-13 | 2021-01-20 | Jubilant Prodel LLC | Compuestos biciclicos como inhibidores de la interaccion/activacio n de pdl/pd-l1. |
| WO2023114844A1 (en) * | 2021-12-15 | 2023-06-22 | Delix Therapeutics, Inc. | Imidazopyridine psychoplastogens and uses thereof |
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| CH624395A5 (https=) | 1976-01-08 | 1981-07-31 | Ciba Geigy Ag | |
| US4234595A (en) * | 1977-07-13 | 1980-11-18 | Mead Johnson & Company | 3-Indolyl-tertiary butylaminopropanols |
| US4314943A (en) | 1977-07-13 | 1982-02-09 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| CA1116598A (en) | 1977-07-13 | 1982-01-19 | William T. Comer | 3-indolyl-tertiary butylaminopropanols |
| JPS6010021B2 (ja) | 1979-01-31 | 1985-03-14 | 田辺製薬株式会社 | 新規ベンジルアルコ−ル誘導体及びその製法 |
| DE3423429A1 (de) | 1984-06-26 | 1986-01-02 | Beiersdorf Ag, 2000 Hamburg | Substituierte phenoxyalkylaminopropanole, verfahren zu ihrer herstellung und ihre verwendung sowie diese verbindungen enthaltende zubereitungen |
| DE3426419A1 (de) | 1984-07-18 | 1986-01-23 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue oxindol-derivate, verfahren zu ihrer herstellung, diese verbindungen enthaltende arzneimittel und zwischenprodukte |
| US4728651A (en) | 1985-10-24 | 1988-03-01 | Hoechst-Roussel Pharmaceuticals Inc. | Antihypertensive thieno-isoxazoles and -pyrazoles |
| GB8528633D0 (en) | 1985-11-21 | 1985-12-24 | Beecham Group Plc | Compounds |
| US5451677A (en) | 1993-02-09 | 1995-09-19 | Merck & Co., Inc. | Substituted phenyl sulfonamides as selective β 3 agonists for the treatment of diabetes and obesity |
| IL113084A (en) | 1994-03-23 | 1999-01-26 | Sankyo Co | Thiazolidine and oxazolidine derivatives processes for the preparation thereof and pharmaceutical compositions containing the same |
| IL113410A (en) | 1994-04-26 | 1999-11-30 | Merck & Co Inc | Substituted sulfonamides having an asymmetric center and pharmaceutical compositions containing them |
| US5705515A (en) | 1994-04-26 | 1998-01-06 | Merck & Co., Inc. | Substituted sulfonamides as selective β-3 agonists for the treatment of diabetes and obesity |
| ZA967892B (en) | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
| US6075040A (en) | 1996-09-05 | 2000-06-13 | Eli Lilly And Company | Selective β3 adrenergic agonists |
| WO1997046556A1 (en) | 1996-06-07 | 1997-12-11 | Merck & Co., Inc. | OXADIAZOLE BENZENESULFONAMIDES AS SELECTIVE β3 AGONISTS FOR THE TREATMENT OF DIABETES AND OBESITY |
| ES2171839T3 (es) | 1996-09-05 | 2002-09-16 | Lilly Co Eli | Analogos de carbazol como agonistas adrenergicos selectivos de beta3. |
| US6011048A (en) | 1997-01-28 | 2000-01-04 | Merck & Co., Inc. | Thiazole benzenesulfonamides as β3 agonists for treatment of diabetes and obesity |
| ID22273A (id) | 1997-01-28 | 1999-09-23 | Merck & Co Inc | TIAZOL BENZENASULFONAMIDA SEBAGAI AGONIS β UNTUK PENGOBATAN DIABETES DAN OBESITAS |
| AUPP796798A0 (en) | 1998-12-30 | 1999-01-28 | Fujisawa Pharmaceutical Co., Ltd. | New compound |
| JP2003055344A (ja) | 1999-01-29 | 2003-02-26 | Dainippon Pharmaceut Co Ltd | ３，７−ジ置換インドール誘導体及びそれを含有する医薬組成物 |
| WO2001007026A2 (en) | 1999-07-22 | 2001-02-01 | Eli Lilly And Company | Improved method of treating type ii diabetes and obesity |
| WO2001036412A1 (en) | 1999-11-15 | 2001-05-25 | Eli Lilly And Company | Process for the preparation of aryloxy propanolamines |
| AU1572701A (en) | 1999-11-15 | 2001-05-30 | Eli Lilly And Company | Treating wasting syndromes with aryloxy propanolamines |
| US6420365B1 (en) | 2000-01-18 | 2002-07-16 | Neurogen Corporation | Imidazopyridines and related derivatives as selective modulators of bradykinin B2 receptors |
| EP1303509B1 (en) | 2000-07-13 | 2012-11-28 | Eli Lilly And Company | Beta3 adrenergic agonists |
| WO2002038544A2 (en) | 2000-11-10 | 2002-05-16 | Eli Lilly And Company | 3-substituted oxindole beta 3 agonists |
| US7208505B2 (en) * | 2001-08-14 | 2007-04-24 | Eli Lilly And Company | β3 adrenergic agonists |
| AU2002318206A1 (en) | 2001-08-14 | 2003-03-03 | Jolie Anne Bastian | 3-substituted oxindole beta-3 agonists |
| ATE297925T1 (de) * | 2001-11-20 | 2005-07-15 | Lilly Co Eli | 3-substituierte oxindol beta 3 agonisten |
| WO2003044017A1 (en) * | 2001-11-20 | 2003-05-30 | Eli Lilly And Company | Beta 3 adrenergic agonists |
-
2002
- 2002-11-12 WO PCT/US2002/033625 patent/WO2003044017A1/en not_active Ceased
- 2002-11-12 ES ES02789238T patent/ES2299618T3/es not_active Expired - Lifetime
- 2002-11-12 US US10/495,133 patent/US7071208B2/en not_active Expired - Lifetime
- 2002-11-12 JP JP2003545654A patent/JP2005518357A/ja active Pending
- 2002-11-12 EP EP02789238A patent/EP1448561B1/en not_active Expired - Lifetime
- 2002-11-12 AT AT02789238T patent/ATE386740T1/de not_active IP Right Cessation
- 2002-11-12 DE DE60225174T patent/DE60225174T2/de not_active Expired - Lifetime
- 2002-11-12 AU AU2002353844A patent/AU2002353844A1/en not_active Abandoned
-
2006
- 2006-02-17 US US11/276,201 patent/US7241772B2/en not_active Expired - Lifetime
- 2006-02-17 US US11/276,192 patent/US7253181B2/en not_active Expired - Lifetime
- 2006-02-17 US US11/276,198 patent/US7265127B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003044017A1 (en) | 2003-05-30 |
| US7265127B2 (en) | 2007-09-04 |
| US20060142329A1 (en) | 2006-06-29 |
| EP1448561A1 (en) | 2004-08-25 |
| US7071208B2 (en) | 2006-07-04 |
| ATE386740T1 (de) | 2008-03-15 |
| ES2299618T3 (es) | 2008-06-01 |
| EP1448561B1 (en) | 2008-02-20 |
| US7241772B2 (en) | 2007-07-10 |
| US20050020618A1 (en) | 2005-01-27 |
| US20060142327A1 (en) | 2006-06-29 |
| US20060142328A1 (en) | 2006-06-29 |
| US7253181B2 (en) | 2007-08-07 |
| JP2005518357A (ja) | 2005-06-23 |
| AU2002353844A1 (en) | 2003-06-10 |
| DE60225174D1 (de) | 2008-04-03 |
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