ES2382486T3 - 7,8-Dihidro-1,6-naftiridin-5(6H)-onas y compuestos bicíclicos relacionados como inhibidores de la dipeptidil peptidasa IV y procedimientos - Google Patents
7,8-Dihidro-1,6-naftiridin-5(6H)-onas y compuestos bicíclicos relacionados como inhibidores de la dipeptidil peptidasa IV y procedimientosInfo
- Publication number
- ES2382486T3 ES2382486T3 ES07864519T ES07864519T ES2382486T3 ES 2382486 T3 ES2382486 T3 ES 2382486T3 ES 07864519 T ES07864519 T ES 07864519T ES 07864519 T ES07864519 T ES 07864519T ES 2382486 T3 ES2382486 T3 ES 2382486T3
- Authority
- ES
- Spain
- Prior art keywords
- group
- alkyl
- aryl
- compound according
- amino
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 61
- GYQAXMJLFPXZAU-UHFFFAOYSA-N 7,8-dihydro-6h-1,6-naphthyridin-5-one Chemical class C1=CC=C2C(=O)NCCC2=N1 GYQAXMJLFPXZAU-UHFFFAOYSA-N 0.000 title description 7
- 125000002619 bicyclic group Chemical group 0.000 title description 5
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 title description 3
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 239000003814 drug Substances 0.000 claims abstract description 24
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 15
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 239000012453 solvate Substances 0.000 claims abstract 2
- -1 amino, substituted amino Chemical group 0.000 claims description 124
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 238000011282 treatment Methods 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 125000000304 alkynyl group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 18
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 14
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 13
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- 125000005592 polycycloalkyl group Polymers 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 11
- 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims description 11
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 11
- 125000001769 aryl amino group Chemical group 0.000 claims description 11
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 11
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 11
- 125000006684 polyhaloalkyl group Polymers 0.000 claims description 11
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 11
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 10
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 10
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 10
- 125000005089 alkenylaminocarbonyl group Chemical group 0.000 claims description 9
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 9
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 101100097467 Arabidopsis thaliana SYD gene Proteins 0.000 claims description 6
- 101100495925 Schizosaccharomyces pombe (strain 972 / ATCC 24843) chr3 gene Proteins 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000005095 alkynylaminocarbonyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000004171 alkoxy aryl group Chemical group 0.000 claims description 2
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 2
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 6
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- 125000006223 tetrahydrofuranylmethyl group Chemical group 0.000 claims 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 abstract description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 19
- 201000010099 disease Diseases 0.000 abstract description 10
- 208000035475 disorder Diseases 0.000 abstract description 9
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 abstract description 7
- 229940002612 prodrug Drugs 0.000 abstract description 7
- 239000000651 prodrug Substances 0.000 abstract description 7
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 52
- 239000003112 inhibitor Substances 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 30
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 28
- 150000002148 esters Chemical class 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 22
- 238000010828 elution Methods 0.000 description 20
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- 238000003818 flash chromatography Methods 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 18
- 150000001299 aldehydes Chemical class 0.000 description 15
- 150000002081 enamines Chemical class 0.000 description 14
- 239000000556 agonist Substances 0.000 description 13
- 150000002825 nitriles Chemical class 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 11
- NGJOFQZEYQGZMB-KTKZVXAJSA-N (4S)-5-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[2-[[(1S)-4-carbamimidamido-1-carboxybutyl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-5-oxopentanoic acid Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NGJOFQZEYQGZMB-KTKZVXAJSA-N 0.000 description 10
- 101800004295 Glucagon-like peptide 1(7-36) Proteins 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 10
- 239000003524 antilipemic agent Substances 0.000 description 10
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 10
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 102000004190 Enzymes Human genes 0.000 description 9
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- 239000000758 substrate Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
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- 150000003573 thiols Chemical class 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
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- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- 150000008064 anhydrides Chemical class 0.000 description 7
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- 125000004432 carbon atom Chemical group C* 0.000 description 7
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- OLORIYWQMHWOID-UHFFFAOYSA-N 2-(aminomethyl)-8h-1,6-naphthyridine-5,7-dione Chemical class O=C1NC(=O)CC2=NC(CN)=CC=C21 OLORIYWQMHWOID-UHFFFAOYSA-N 0.000 description 4
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- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 4
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical class N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 description 1
- DATJETPTDKFEEF-UHFFFAOYSA-N pyrrolidine-3-carbonitrile Chemical class N#CC1CCNC1 DATJETPTDKFEEF-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
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- 239000011347 resin Substances 0.000 description 1
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- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
- 229960004937 saxagliptin Drugs 0.000 description 1
- 108010033693 saxagliptin Proteins 0.000 description 1
- IMNTVVOUWFPRSB-JWQCQUIFSA-N sch-48461 Chemical compound C1=CC(OC)=CC=C1[C@H]1N(C=2C=CC(OC)=CC=2)C(=O)[C@@H]1CCCC1=CC=CC=C1 IMNTVVOUWFPRSB-JWQCQUIFSA-N 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
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- 238000013207 serial dilution Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960002073 sertraline Drugs 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 1
- 229960002578 sitaxentan Drugs 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 229960004813 trichlormethiazide Drugs 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- ACWBQPMHZXGDFX-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
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- 239000003981 vehicle Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- 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
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Child & Adolescent Psychology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86020206P | 2006-11-20 | 2006-11-20 | |
| US860202P | 2006-11-20 | ||
| PCT/US2007/084927 WO2008064107A2 (en) | 2006-11-20 | 2007-11-16 | 7,8-dihydro-1,6-naphthyridin-5(6h)-ones and related bicyclic compounds as inhibitors of dipeptidyl peptidase iv and methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2382486T3 true ES2382486T3 (es) | 2012-06-08 |
Family
ID=39283892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07864519T Active ES2382486T3 (es) | 2006-11-20 | 2007-11-16 | 7,8-Dihidro-1,6-naftiridin-5(6H)-onas y compuestos bicíclicos relacionados como inhibidores de la dipeptidil peptidasa IV y procedimientos |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7723355B2 (OSRAM) |
| EP (1) | EP2086975B1 (OSRAM) |
| JP (1) | JP2010510317A (OSRAM) |
| CN (1) | CN101595109B (OSRAM) |
| AT (1) | ATE549334T1 (OSRAM) |
| ES (1) | ES2382486T3 (OSRAM) |
| NO (1) | NO20091938L (OSRAM) |
| WO (1) | WO2008064107A2 (OSRAM) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2426654C (en) * | 2000-10-23 | 2010-12-21 | Smithkline Beecham Corporation | 2,4,8-trisubstituted-8h-pyrido[2,3-d}pyrimidin-7-one compounds |
| MY145343A (en) * | 2005-03-25 | 2012-01-31 | Glaxo Group Ltd | Novel compounds |
| KR20080002865A (ko) * | 2005-03-25 | 2008-01-04 | 글락소 그룹 리미티드 | 피리도[２,３-ｄ]피리미딘-７-온 및３,４-디히드로피리미도[４,５-ｄ]피리미딘-２(１ｈ)-온유도체의 제조 방법 |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| EP2308847B1 (en) | 2009-10-09 | 2014-04-02 | EMC microcollections GmbH | Substituted pyridines as inhibitors of dipeptidyl peptidase IV and their application for the treatment of diabetes and related diseases |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| US8933024B2 (en) | 2010-06-18 | 2015-01-13 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| US8477028B2 (en) * | 2010-09-24 | 2013-07-02 | T-Mobile Usa, Inc. | Misplaced device recovery |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| RU2648247C2 (ru) * | 2012-08-24 | 2018-03-23 | Ф. Хоффманн-Ля Рош Аг | Бициклические производные пиридина, полезные в качестве ингибитора белков, связывающих жирные кислоты (FABP) 4 и/или 5 |
| US20150297573A1 (en) | 2012-10-24 | 2015-10-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | TPL2 KINASE INHIBITORS FOR PREVENTING OR TREATING DIABETES AND FOR PROMOTING Beta-CELL SURVIVAL |
| CN104548096B (zh) * | 2013-10-09 | 2019-09-10 | 深圳翰宇药业股份有限公司 | 一种含有glp-1类似物和dpp-4抑制剂的药物组合物及其制备方法 |
| US10426818B2 (en) | 2015-03-24 | 2019-10-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Method and pharmaceutical composition for use in the treatment of diabetes |
| US11691971B2 (en) | 2020-06-19 | 2023-07-04 | Incyte Corporation | Naphthyridinone compounds as JAK2 V617F inhibitors |
| US11753413B2 (en) | 2020-06-19 | 2023-09-12 | Incyte Corporation | Substituted pyrrolo[2,1-f][1,2,4]triazine compounds as JAK2 V617F inhibitors |
| US11767323B2 (en) | 2020-07-02 | 2023-09-26 | Incyte Corporation | Tricyclic pyridone compounds as JAK2 V617F inhibitors |
| SI4175719T1 (sl) | 2020-07-02 | 2025-07-31 | Incyte Corporation | Triciklične sečninske spojine kot zaviralci jak2 v617f |
| US11661422B2 (en) | 2020-08-27 | 2023-05-30 | Incyte Corporation | Tricyclic urea compounds as JAK2 V617F inhibitors |
| WO2022140231A1 (en) | 2020-12-21 | 2022-06-30 | Incyte Corporation | Deazaguaine compounds as jak2 v617f inhibitors |
| US11958861B2 (en) | 2021-02-25 | 2024-04-16 | Incyte Corporation | Spirocyclic lactams as JAK2 V617F inhibitors |
| US12084430B2 (en) | 2022-03-17 | 2024-09-10 | Incyte Corporation | Tricyclic urea compounds as JAK2 V617F inhibitors |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6900224B2 (en) * | 2002-07-31 | 2005-05-31 | The Procter & Gamble Company | Antimicrobial quinolones, their compositions and uses |
| WO2004014866A1 (en) * | 2002-08-13 | 2004-02-19 | Warner-Lambert Company Llc | Azaisoquinoline derivatives as matrix metalloproteinase inhibitors |
| GB0413389D0 (en) | 2004-06-16 | 2004-07-21 | Astrazeneca Ab | Chemical compounds |
| WO2006019965A2 (en) * | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| GB0420970D0 (en) * | 2004-09-21 | 2004-10-20 | Smithkline Beecham Corp | Novel triazoloquinoline compounds |
| WO2006065842A2 (en) * | 2004-12-13 | 2006-06-22 | Synta Pharmaceuticals Corp. | 5,6,7,8-tetrahydroquinolines and related compounds and uses thereof |
-
2007
- 2007-11-16 CN CN2007800501380A patent/CN101595109B/zh not_active Expired - Fee Related
- 2007-11-16 WO PCT/US2007/084927 patent/WO2008064107A2/en not_active Ceased
- 2007-11-16 ES ES07864519T patent/ES2382486T3/es active Active
- 2007-11-16 US US11/941,181 patent/US7723355B2/en active Active
- 2007-11-16 JP JP2009538461A patent/JP2010510317A/ja not_active Withdrawn
- 2007-11-16 AT AT07864519T patent/ATE549334T1/de active
- 2007-11-16 EP EP07864519A patent/EP2086975B1/en active Active
-
2009
- 2009-05-19 NO NO20091938A patent/NO20091938L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN101595109A (zh) | 2009-12-02 |
| WO2008064107A2 (en) | 2008-05-29 |
| US20090149492A1 (en) | 2009-06-11 |
| NO20091938L (no) | 2009-06-08 |
| JP2010510317A (ja) | 2010-04-02 |
| CN101595109B (zh) | 2012-09-05 |
| US7723355B2 (en) | 2010-05-25 |
| ATE549334T1 (de) | 2012-03-15 |
| WO2008064107A3 (en) | 2008-07-10 |
| EP2086975B1 (en) | 2012-03-14 |
| EP2086975A2 (en) | 2009-08-12 |
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