ES2300478T3 - Derivados de quinolina como ligandos para el receptor de neuropeptido y. - Google Patents
Derivados de quinolina como ligandos para el receptor de neuropeptido y. Download PDFInfo
- Publication number
- ES2300478T3 ES2300478T3 ES02771639T ES02771639T ES2300478T3 ES 2300478 T3 ES2300478 T3 ES 2300478T3 ES 02771639 T ES02771639 T ES 02771639T ES 02771639 T ES02771639 T ES 02771639T ES 2300478 T3 ES2300478 T3 ES 2300478T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- pyrrolidin
- quinolin
- alkyl
- quinoline
- 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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- 150000001875 compounds Chemical class 0.000 claims abstract description 121
- -1 diaryloamino Chemical group 0.000 claims abstract description 93
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 64
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 43
- 239000001257 hydrogen Substances 0.000 claims abstract description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 38
- 150000002367 halogens Chemical class 0.000 claims abstract description 38
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 21
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 19
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 19
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 19
- 125000001424 substituent group Chemical group 0.000 claims abstract description 19
- 150000002148 esters Chemical class 0.000 claims abstract description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 13
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 11
- 125000005241 heteroarylamino group Chemical group 0.000 claims abstract description 11
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 8
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims abstract description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims abstract description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 7
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims abstract description 7
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 7
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims abstract description 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims abstract description 4
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 claims abstract description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims abstract description 3
- 125000002541 furyl group Chemical group 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 157
- HTWNTQBDROIOEZ-UHFFFAOYSA-N 2-methyl-4-pyrrolidin-1-ylquinolin-7-ol Chemical compound C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCC1 HTWNTQBDROIOEZ-UHFFFAOYSA-N 0.000 claims description 46
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 208000008589 Obesity Diseases 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 235000020824 obesity Nutrition 0.000 claims description 13
- 239000000460 chlorine Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 11
- 238000011321 prophylaxis Methods 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 10
- 229960001243 orlistat Drugs 0.000 claims description 10
- 206010003246 arthritis Diseases 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- 208000030814 Eating disease Diseases 0.000 claims description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 7
- 235000014632 disordered eating Nutrition 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Chemical group 0.000 claims description 6
- 238000009833 condensation Methods 0.000 claims description 6
- 230000005494 condensation Effects 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 239000011737 fluorine Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 102000004882 Lipase Human genes 0.000 claims description 5
- 108090001060 Lipase Proteins 0.000 claims description 5
- 239000004367 Lipase Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 235000019421 lipase Nutrition 0.000 claims description 5
- HFVCWXRIRISOEA-UHFFFAOYSA-N 2-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C(=CC=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 HFVCWXRIRISOEA-UHFFFAOYSA-N 0.000 claims description 4
- SRCYQRXUBMEAPQ-UHFFFAOYSA-N 3-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=C(C=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 SRCYQRXUBMEAPQ-UHFFFAOYSA-N 0.000 claims description 4
- DPMAQIWJJZJKLV-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methyl-7-(pyridin-4-ylmethoxy)quinoline Chemical compound C=12C=CC(OCC=3C=CN=CC=3)=CC2=NC(C)=CC=1N1CCCCCC1 DPMAQIWJJZJKLV-UHFFFAOYSA-N 0.000 claims description 4
- NHZYJKKSOGTTMR-UHFFFAOYSA-N 4-[(2-methyl-4-pyrrolidin-1-ylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCC1 NHZYJKKSOGTTMR-UHFFFAOYSA-N 0.000 claims description 4
- ZLJRLUWCTUDGGW-UHFFFAOYSA-N 4-[[4-(azepan-1-yl)-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C=12C=CC(OCC=3C=CC(=CC=3)C#N)=CC2=NC(C)=CC=1N1CCCCCC1 ZLJRLUWCTUDGGW-UHFFFAOYSA-N 0.000 claims description 4
- 101710151321 Melanostatin Proteins 0.000 claims description 4
- 102100028427 Pro-neuropeptide Y Human genes 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 4
- 238000006664 bond formation reaction Methods 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- DNCNFUQWEFNIKJ-NRFANRHFSA-N 4-[[4-[(3s)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-yl]oxymethyl]benzonitrile Chemical compound C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(OCC=3C=CC(=CC=3)C#N)=CC=C12 DNCNFUQWEFNIKJ-NRFANRHFSA-N 0.000 claims description 3
- NFLYDVKEEWHEKP-UHFFFAOYSA-N 7-[(3-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=C(Cl)C=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NFLYDVKEEWHEKP-UHFFFAOYSA-N 0.000 claims description 3
- AGTMGARQEGRFBT-UHFFFAOYSA-N 7-[(3-methoxyphenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound COC1=CC=CC(COC=2C=C3N=C(C)C=C(C3=CC=2)N2CCCC2)=C1 AGTMGARQEGRFBT-UHFFFAOYSA-N 0.000 claims description 3
- NUXDJOBRDWPOTK-UHFFFAOYSA-N 7-[(4-chlorophenyl)methoxy]-2-methyl-4-pyrrolidin-1-ylquinoline Chemical compound C=12C=CC(OCC=3C=CC(Cl)=CC=3)=CC2=NC(C)=CC=1N1CCCC1 NUXDJOBRDWPOTK-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003725 azepanyl group Chemical group 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 11
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 172
- 238000001819 mass spectrum Methods 0.000 description 158
- 239000000047 product Substances 0.000 description 120
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 44
- 239000000243 solution Substances 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- 239000000203 mixture Substances 0.000 description 31
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- VVVUSVRZYKHWCX-UHFFFAOYSA-N 4-[(4-chloro-2-methylquinolin-7-yl)oxymethyl]benzonitrile Chemical compound C=1C2=NC(C)=CC(Cl)=C2C=CC=1OCC1=CC=C(C#N)C=C1 VVVUSVRZYKHWCX-UHFFFAOYSA-N 0.000 description 24
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- 238000004587 chromatography analysis Methods 0.000 description 14
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 13
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
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- 239000002585 base Substances 0.000 description 10
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
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- 238000004458 analytical method Methods 0.000 description 9
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- SGSCTTZQIYSSSD-UHFFFAOYSA-N 4-(azepan-1-yl)-2-methylquinolin-7-ol hydrochloride Chemical compound Cl.C=12C=CC(O)=CC2=NC(C)=CC=1N1CCCCCC1 SGSCTTZQIYSSSD-UHFFFAOYSA-N 0.000 description 8
- GIBRMZKZDBMCTB-ZOWNYOTGSA-N 4-[(3S)-3-ethoxypyrrolidin-1-yl]-2-methylquinolin-7-ol hydrochloride Chemical compound Cl.C1[C@@H](OCC)CCN1C1=CC(C)=NC2=CC(O)=CC=C12 GIBRMZKZDBMCTB-ZOWNYOTGSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
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- DOGYZJVTBGICNB-KRWDZBQOSA-N (3s)-1-(2-methyl-7-phenylmethoxyquinolin-4-yl)pyrrolidin-3-ol Chemical compound C=12C=CC(OCC=3C=CC=CC=3)=CC2=NC(C)=CC=1N1CC[C@H](O)C1 DOGYZJVTBGICNB-KRWDZBQOSA-N 0.000 description 7
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- KBZHAYBXUFJHNE-LBPRGKRZSA-N 4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound COC[C@@H]1CCCN1C1=CC(C)=NC2=CC(O)=CC=C12 KBZHAYBXUFJHNE-LBPRGKRZSA-N 0.000 description 5
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- 125000004429 atom Chemical group 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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- HHEOOKPSFHYFOD-JTQLQIEISA-N 6-fluoro-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylquinolin-7-ol Chemical compound C=12C=C(F)C(O)=CC2=NC(C)=CC=1N1CCC[C@H]1CO HHEOOKPSFHYFOD-JTQLQIEISA-N 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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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
-
- 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
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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
- 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
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01112370 | 2001-05-21 | ||
| EP01112370 | 2001-05-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2300478T3 true ES2300478T3 (es) | 2008-06-16 |
Family
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| ES02771639T Expired - Lifetime ES2300478T3 (es) | 2001-05-21 | 2002-05-08 | Derivados de quinolina como ligandos para el receptor de neuropeptido y. |
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| AU (1) | AU2002338896B2 (enExample) |
| BR (1) | BR0209957A (enExample) |
| CA (1) | CA2446324A1 (enExample) |
| DE (1) | DE60225274T2 (enExample) |
| ES (1) | ES2300478T3 (enExample) |
| GT (1) | GT200200090A (enExample) |
| MX (1) | MXPA03010565A (enExample) |
| PA (1) | PA8545301A1 (enExample) |
| PE (1) | PE20021155A1 (enExample) |
| UY (1) | UY27300A1 (enExample) |
| WO (1) | WO2002094789A1 (enExample) |
| ZA (1) | ZA200308783B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
| AU2002352878B2 (en) * | 2001-11-27 | 2007-11-22 | Merck Sharp & Dohme Corp. | 2-Aminoquinoline compounds |
| RU2298002C2 (ru) * | 2002-02-04 | 2007-04-27 | Ф. Хоффманн-Ля Рош Аг | Производные хинолина в качестве антагонистов npy |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| JP2005535648A (ja) | 2002-07-05 | 2005-11-24 | エフ．ホフマン−ラ ロシュ アーゲー | キナゾリン誘導体 |
| JP2006502131A (ja) | 2002-08-07 | 2006-01-19 | エフ．ホフマン−ラ ロシュ アーゲー | チアゾール誘導体 |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2004080463A1 (en) * | 2003-03-10 | 2004-09-23 | Schering Corporation | Heterocyclic kinase inhibitors: methods of use and synthesis |
| ATE547404T1 (de) | 2003-09-22 | 2012-03-15 | Msd Kk | Piperidinderivate |
| TWI344364B (en) | 2003-11-10 | 2011-07-01 | Synta Pharmaceuticals Corp | Fused heterocyclic compounds |
| US20080125403A1 (en) | 2004-04-02 | 2008-05-29 | Merck & Co., Inc. | Method of Treating Men with Metabolic and Anthropometric Disorders |
| US20060183763A1 (en) * | 2004-12-31 | 2006-08-17 | Pfizer Inc | Novel pyrrolidyl derivatives of heteroaromatic compounds |
| BRPI0610580B8 (pt) | 2005-05-30 | 2021-05-25 | Banyu Pharma Co Ltd | composto derivado de piperidina |
| US20100216758A1 (en) | 2005-08-10 | 2010-08-26 | Makoto Ando | Pyridone Compounds |
| CA2619770A1 (en) | 2005-08-24 | 2007-03-01 | Banyu Pharmaceutical Co., Ltd. | Phenylpyridone derivative |
| CA2621470A1 (en) | 2005-09-07 | 2007-03-15 | Banyu Pharmaceutical Co., Ltd. | Bicyclic aromatic substituted pyridone derivative |
| WO2007049798A1 (ja) | 2005-10-27 | 2007-05-03 | Banyu Pharmaceutical Co., Ltd. | 新規ベンゾオキサチイン誘導体 |
| KR101318127B1 (ko) | 2005-11-10 | 2013-10-16 | 엠에스디 가부시키가이샤 | 아자 치환된 스피로 유도체 |
| WO2008020302A2 (en) * | 2006-08-17 | 2008-02-21 | Pfizer Products Inc. | Heteroaromatic quinoline-based compounds as phosphodiesterase (pde) inhibitors |
| WO2008038692A1 (en) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | Diaryl ketimine derivative |
| JP5319518B2 (ja) | 2007-04-02 | 2013-10-16 | Ｍｓｄ株式会社 | インドールジオン誘導体 |
| WO2008141077A1 (en) * | 2007-05-10 | 2008-11-20 | Janssen Pharmaceutica N.V. | Process for the preparation of tetrahydroquinolinyl, benzoxazine and benzothiazine derivatives |
| US8759348B2 (en) * | 2007-05-17 | 2014-06-24 | Helperby Therapeutics Limited | Use of 4-(pyrrolidin-1-yl)quinoline compounds to kill clinically latent microorganisms |
| JP5401449B2 (ja) * | 2007-06-01 | 2014-01-29 | イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニー | 緑色発光用途のためのクリセン類 |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| US8377960B2 (en) * | 2007-11-15 | 2013-02-19 | Gilead Sciences, Inc. | Inhibitors of human immunodeficiency virus replication |
| NZ585226A (en) | 2007-11-16 | 2012-08-31 | Gilead Sciences Inc | Inhibitors of human immunodeficiency virus replication |
| AU2009220605A1 (en) | 2008-03-06 | 2009-09-11 | Msd K.K. | Alkylaminopyridine derivative |
| AU2009229860A1 (en) | 2008-03-28 | 2009-10-01 | Msd K.K. | Diarylmethylamide derivative having antagonistic activity on melanin-concentrating hormone receptor |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| AU2009261248A1 (en) | 2008-06-19 | 2009-12-23 | Banyu Pharmaceutical Co., Ltd. | Spirodiamine-diarylketoxime derivative |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| EP2319841A1 (en) | 2008-07-30 | 2011-05-11 | Msd K.K. | (5-membered)-(5-membered) or (5-membered)-(6-membered) fused ring cycloalkylamine derivative |
| CA2741125A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| CN102271509A (zh) | 2008-10-31 | 2011-12-07 | 默沙东公司 | 用于抗糖尿病药的新型环苯并咪唑衍生物 |
| AU2011218830B2 (en) | 2010-02-25 | 2014-07-24 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| KR101668514B1 (ko) | 2011-02-25 | 2016-10-21 | 머크 샤프 앤드 돔 코포레이션 | 항당뇨병제로서 유용한 신규 시클릭 아자벤즈이미다졸 유도체 |
| EP2880028B1 (en) | 2012-08-02 | 2020-09-30 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| CN104994848A (zh) | 2013-02-22 | 2015-10-21 | 默沙东公司 | 抗糖尿病二环化合物 |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP3004138B1 (en) | 2013-06-05 | 2024-03-13 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| US11072602B2 (en) | 2016-12-06 | 2021-07-27 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
| EP3558298A4 (en) | 2016-12-20 | 2020-08-05 | Merck Sharp & Dohme Corp. | ANTIDIABETIC SPIROCHROMAN COMPOUNDS |
| WO2019014402A1 (en) | 2017-07-14 | 2019-01-17 | Innate Tumor Immunity, Inc. | MODULATORS OF NLRP3 |
Family Cites Families (16)
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| LU43730A1 (enExample) * | 1962-06-14 | 1963-07-13 | ||
| US3272824A (en) * | 1962-12-06 | 1966-09-13 | Norwich Pharma Co | 4-amino-6, 7-di(lower) alkoxyquinolines |
| US3812127A (en) * | 1966-10-31 | 1974-05-21 | Pfizer | 4-(quinolin-4-yl)piperazine-1-carboxylic acid esters |
| US4035367A (en) * | 1974-09-09 | 1977-07-12 | Sandoz, Inc. | Hydroxyalkyl-substituted-amino-quinolines |
| CA1247547A (en) | 1983-06-22 | 1988-12-28 | Paul Hadvary | Leucine derivatives |
| CA1328881C (en) | 1984-12-21 | 1994-04-26 | Pierre Barbier | Process for the manufacture of oxetanones |
| CA1270837A (en) | 1984-12-21 | 1990-06-26 | Hoffmann-La Roche Limited | Oxetanones |
| AU641215B2 (en) | 1990-02-13 | 1993-09-16 | Merrell Dow Pharmaceuticals Inc. | Stabilized sulfonate, sulfate, phosphonate and phosphate derivatives of hirudin |
| US5274143A (en) | 1991-07-23 | 1993-12-28 | Hoffmann-La Roche Inc. | Process for the preparation of (R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-pyran-2-one and (R)-5,6-dihydro-6-undecyl-2H-pyran-2,4(3H)-dione |
| WO1998014431A1 (en) * | 1996-10-01 | 1998-04-09 | Kyowa Hakko Kogyo Co., Ltd. | Nitrogenous heterocyclic compounds |
| US6004996A (en) | 1997-02-05 | 1999-12-21 | Hoffman-La Roche Inc. | Tetrahydrolipstatin containing compositions |
| US6267952B1 (en) | 1998-01-09 | 2001-07-31 | Geltex Pharmaceuticals, Inc. | Lipase inhibiting polymers |
| ATE293970T1 (de) | 1998-08-14 | 2005-05-15 | Hoffmann La Roche | Lipasehemmer enthaltende pharmazeutische zusammensetzungen |
| PT1105123E (pt) | 1998-08-14 | 2004-08-31 | Hoffmann La Roche | Composicoes farmaceuticas contendo inibidores da lipase e quitosano |
| AU1047401A (en) * | 1999-11-08 | 2001-06-06 | Cytion Sa | Apparatus and methods for positioning and analyzing biological membranous objects |
| US6900226B2 (en) * | 2000-09-06 | 2005-05-31 | Hoffman-La Roche Inc. | Neuropeptide Y antagonists |
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2002
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- 2002-05-08 MX MXPA03010565A patent/MXPA03010565A/es active IP Right Grant
- 2002-05-08 AT AT02771639T patent/ATE387428T1/de not_active IP Right Cessation
- 2002-05-08 WO PCT/EP2002/005120 patent/WO2002094789A1/en not_active Ceased
- 2002-05-08 AU AU2002338896A patent/AU2002338896B2/en not_active Ceased
- 2002-05-08 CA CA002446324A patent/CA2446324A1/en not_active Abandoned
- 2002-05-08 BR BR0209957-8A patent/BR0209957A/pt not_active IP Right Cessation
- 2002-05-08 JP JP2002591462A patent/JP3715280B2/ja not_active Expired - Fee Related
- 2002-05-08 ES ES02771639T patent/ES2300478T3/es not_active Expired - Lifetime
- 2002-05-08 DE DE60225274T patent/DE60225274T2/de not_active Expired - Fee Related
- 2002-05-08 KR KR1020037015121A patent/KR100621287B1/ko not_active Expired - Fee Related
- 2002-05-08 EP EP02771639A patent/EP1395564B1/en not_active Expired - Lifetime
- 2002-05-16 PA PA20028545301A patent/PA8545301A1/es unknown
- 2002-05-17 PE PE2002000425A patent/PE20021155A1/es not_active Application Discontinuation
- 2002-05-17 AR ARP020101836A patent/AR035979A1/es not_active Application Discontinuation
- 2002-05-20 GT GT200200090A patent/GT200200090A/es unknown
- 2002-05-20 US US10/151,505 patent/US6818767B2/en not_active Expired - Fee Related
- 2002-05-21 UY UY27300A patent/UY27300A1/es not_active Application Discontinuation
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Also Published As
| Publication number | Publication date |
|---|---|
| ATE387428T1 (de) | 2008-03-15 |
| ZA200308783B (en) | 2005-02-11 |
| EP1395564B1 (en) | 2008-02-27 |
| DE60225274T2 (de) | 2009-03-26 |
| AU2002338896B2 (en) | 2006-04-27 |
| KR20030096416A (ko) | 2003-12-24 |
| PA8545301A1 (es) | 2003-01-24 |
| DE60225274D1 (de) | 2008-04-10 |
| AR035979A1 (es) | 2004-07-28 |
| PE20021155A1 (es) | 2002-12-17 |
| JP3715280B2 (ja) | 2005-11-09 |
| US20020198194A1 (en) | 2002-12-26 |
| CN1522249A (zh) | 2004-08-18 |
| JP2004536066A (ja) | 2004-12-02 |
| US20050049413A1 (en) | 2005-03-03 |
| CA2446324A1 (en) | 2002-11-28 |
| CN100376557C (zh) | 2008-03-26 |
| KR100621287B1 (ko) | 2006-09-13 |
| MXPA03010565A (es) | 2004-03-02 |
| GT200200090A (es) | 2003-06-19 |
| US6818767B2 (en) | 2004-11-16 |
| WO2002094789A1 (en) | 2002-11-28 |
| BR0209957A (pt) | 2004-03-30 |
| EP1395564A1 (en) | 2004-03-10 |
| UY27300A1 (es) | 2002-11-29 |
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