CA2294549A1 - Heterocyclic substituted piperidines and uses thereof - Google Patents
Heterocyclic substituted piperidines and uses thereof Download PDFInfo
- Publication number
- CA2294549A1 CA2294549A1 CA002294549A CA2294549A CA2294549A1 CA 2294549 A1 CA2294549 A1 CA 2294549A1 CA 002294549 A CA002294549 A CA 002294549A CA 2294549 A CA2294549 A CA 2294549A CA 2294549 A1 CA2294549 A1 CA 2294549A1
- Authority
- CA
- Canada
- Prior art keywords
- branched
- straight chained
- alkyl
- compound
- aryl
- 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.)
- Abandoned
Links
- 150000003053 piperidines Chemical class 0.000 title description 3
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims abstract description 39
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims abstract description 39
- 210000001635 urinary tract Anatomy 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 27
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 26
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 26
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 201000010099 disease Diseases 0.000 claims abstract description 16
- 230000002040 relaxant effect Effects 0.000 claims abstract description 13
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 12
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 12
- 230000004410 intraocular pressure Effects 0.000 claims abstract description 12
- 230000008485 antagonism Effects 0.000 claims abstract description 11
- 239000003937 drug carrier Substances 0.000 claims abstract description 10
- 125000003118 aryl group Chemical group 0.000 claims description 122
- 125000001072 heteroaryl group Chemical group 0.000 claims description 116
- 125000003342 alkenyl group Chemical group 0.000 claims description 111
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 100
- 125000000217 alkyl group Chemical group 0.000 claims description 97
- 125000000304 alkynyl group Chemical group 0.000 claims description 97
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 96
- 239000007787 solid Substances 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 82
- -1 C1-C7 Chemical group 0.000 claims description 69
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 69
- 238000000034 method Methods 0.000 claims description 63
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 54
- 210000001519 tissue Anatomy 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 239000007788 liquid Substances 0.000 claims description 16
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 claims description 14
- 229960004039 finasteride Drugs 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 210000002460 smooth muscle Anatomy 0.000 claims description 14
- 230000036772 blood pressure Effects 0.000 claims description 10
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 229940113178 5 Alpha reductase inhibitor Drugs 0.000 claims description 6
- 239000002677 5-alpha reductase inhibitor Substances 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 5
- 230000036407 pain Effects 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 claims description 3
- 230000002508 compound effect Effects 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 abstract description 16
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 abstract description 14
- 230000002401 inhibitory effect Effects 0.000 abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 441
- 239000000243 solution Substances 0.000 description 373
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 353
- 239000002904 solvent Substances 0.000 description 174
- 235000019439 ethyl acetate Nutrition 0.000 description 152
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 143
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 117
- 239000000725 suspension Substances 0.000 description 110
- 239000000047 product Substances 0.000 description 107
- 238000004440 column chromatography Methods 0.000 description 104
- 239000003921 oil Substances 0.000 description 98
- 235000019198 oils Nutrition 0.000 description 98
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 97
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
- 239000000741 silica gel Substances 0.000 description 85
- 229910002027 silica gel Inorganic materials 0.000 description 85
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
- 239000011541 reaction mixture Substances 0.000 description 73
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 60
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- 239000012044 organic layer Substances 0.000 description 53
- 238000000746 purification Methods 0.000 description 52
- 229940093499 ethyl acetate Drugs 0.000 description 49
- CCPHAMSKHBDMDS-UHFFFAOYSA-N Chetoseminudin B Natural products C=1NC2=CC=CC=C2C=1CC1(SC)NC(=O)C(CO)(SC)N(C)C1=O CCPHAMSKHBDMDS-UHFFFAOYSA-N 0.000 description 43
- 108020003175 receptors Proteins 0.000 description 41
- 102000005962 receptors Human genes 0.000 description 40
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 39
- 239000012267 brine Substances 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 36
- 229910000104 sodium hydride Inorganic materials 0.000 description 36
- 238000010992 reflux Methods 0.000 description 35
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
- 238000003756 stirring Methods 0.000 description 33
- 239000012300 argon atmosphere Substances 0.000 description 31
- 239000006188 syrup Substances 0.000 description 31
- 235000020357 syrup Nutrition 0.000 description 31
- 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 description 30
- 238000006243 chemical reaction Methods 0.000 description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- YTZZPWUZLNBVTH-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-2-oxo-1,3-oxazolidine-3-carboxylic acid Chemical compound C1OC(=O)N(C(=O)O)C1C1=CC=C(F)C(F)=C1 YTZZPWUZLNBVTH-UHFFFAOYSA-N 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- 229910052786 argon Inorganic materials 0.000 description 18
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 239000003814 drug Substances 0.000 description 15
- 239000012230 colorless oil Substances 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 150000001408 amides Chemical class 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- 239000012280 lithium aluminium hydride Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- BMZAHYNIZYKXCQ-UHFFFAOYSA-N (4-nitrophenyl) 4-(3,4-difluorophenyl)-2-oxo-1,3-oxazolidine-3-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC(=O)N1C(=O)OCC1C1=CC=C(F)C(F)=C1 BMZAHYNIZYKXCQ-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 229910021529 ammonia Inorganic materials 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 239000011521 glass Substances 0.000 description 10
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 239000012455 biphasic mixture Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 238000003818 flash chromatography Methods 0.000 description 8
- 239000012458 free base Substances 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical compound C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 7
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- SIIPMODOOMLRBR-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-5-methyl-1,3-oxazolidin-2-one Chemical compound CC1OC(=O)NC1C1=CC=C(F)C(F)=C1 SIIPMODOOMLRBR-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 102000042567 non-coding RNA Human genes 0.000 description 6
- 108091027963 non-coding RNA Proteins 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 235000009518 sodium iodide Nutrition 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- ONJNHFPGJRBNQM-UHFFFAOYSA-N 2-amino-2-(3,4-difluorophenyl)ethanol Chemical compound OCC(N)C1=CC=C(F)C(F)=C1 ONJNHFPGJRBNQM-UHFFFAOYSA-N 0.000 description 5
- JPHKMYXKNKLNDF-UHFFFAOYSA-N 3,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1F JPHKMYXKNKLNDF-UHFFFAOYSA-N 0.000 description 5
- VRGZFSZAAYVZFS-UHFFFAOYSA-N 3-(4-pyridin-2-yl-3,6-dihydro-2h-pyridin-1-yl)propan-1-amine Chemical compound C1N(CCCN)CCC(C=2N=CC=CC=2)=C1 VRGZFSZAAYVZFS-UHFFFAOYSA-N 0.000 description 5
- WYJZKSPZJQCMII-UHFFFAOYSA-N 3-(4-pyridin-2-ylpiperidin-1-yl)propan-1-amine Chemical compound C1CN(CCCN)CCC1C1=CC=CC=N1 WYJZKSPZJQCMII-UHFFFAOYSA-N 0.000 description 5
- AIWCAYRHYGGWKF-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-1,3-oxazolidin-2-one Chemical compound C1=C(F)C(F)=CC=C1C1NC(=O)OC1 AIWCAYRHYGGWKF-UHFFFAOYSA-N 0.000 description 5
- AMNCOTKBKHXNLP-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-5-methyl-2-oxo-1,3-oxazolidine-3-carboxylic acid Chemical compound CC1OC(=O)N(C(O)=O)C1C1=CC=C(F)C(F)=C1 AMNCOTKBKHXNLP-UHFFFAOYSA-N 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 5
- 108060003345 Adrenergic Receptor Proteins 0.000 description 5
- 102000017910 Adrenergic receptor Human genes 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 5
- IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 5
- IZVVLUSOFWGLKN-UHFFFAOYSA-N 1-(3,4-difluorophenyl)-2-hydroxypropan-1-one Chemical compound CC(O)C(=O)C1=CC=C(F)C(F)=C1 IZVVLUSOFWGLKN-UHFFFAOYSA-N 0.000 description 4
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 4
- ZGIGPLHROHZCPO-UHFFFAOYSA-N 2-amino-2-(3,4-difluorophenyl)acetonitrile Chemical compound N#CC(N)C1=CC=C(F)C(F)=C1 ZGIGPLHROHZCPO-UHFFFAOYSA-N 0.000 description 4
- KVNQCSIGNRPHHM-UHFFFAOYSA-N 2-piperidin-4-ylpyridine Chemical compound C1CNCCC1C1=CC=CC=N1 KVNQCSIGNRPHHM-UHFFFAOYSA-N 0.000 description 4
- RMHQDKYZXJVCME-UHFFFAOYSA-N 2-pyridin-4-ylpyridine Chemical group N1=CC=CC=C1C1=CC=NC=C1 RMHQDKYZXJVCME-UHFFFAOYSA-N 0.000 description 4
- OQABVYWGBWMSIM-UHFFFAOYSA-N 5-cyclopropyl-4-(3,4-difluorophenyl)-1,3-oxazolidin-2-one Chemical compound C1=C(F)C(F)=CC=C1C1C(C2CC2)OC(=O)N1 OQABVYWGBWMSIM-UHFFFAOYSA-N 0.000 description 4
- NMAYRMNAGSPUHB-UHFFFAOYSA-N 5-cyclopropyl-4-(3,4-difluorophenyl)-2-oxo-1,3-oxazolidine-3-carboxylic acid Chemical compound O1C(=O)N(C(=O)O)C(C=2C=C(F)C(F)=CC=2)C1C1CC1 NMAYRMNAGSPUHB-UHFFFAOYSA-N 0.000 description 4
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- KBJXDTIYSSQJAI-UHFFFAOYSA-N propylcarbamic acid Chemical compound CCCNC(O)=O KBJXDTIYSSQJAI-UHFFFAOYSA-N 0.000 description 1
- 238000011471 prostatectomy Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- BBFCIBZLAVOLCF-UHFFFAOYSA-N pyridin-1-ium;bromide Chemical compound Br.C1=CC=NC=C1 BBFCIBZLAVOLCF-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- BLGXFZZNTVWLAY-DIRVCLHFSA-N rauwolscine Chemical compound C1=CC=C2C(CCN3C[C@H]4CC[C@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-DIRVCLHFSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 210000002265 sensory receptor cell Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000000526 short-path distillation Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
- 229960001693 terazosin Drugs 0.000 description 1
- PRGNYYHZWGUONW-UHFFFAOYSA-N tert-butyl 4-cyano-4-(2,4-dichlorophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1(C#N)C1=CC=C(Cl)C=C1Cl PRGNYYHZWGUONW-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- FQZLNQAUUMSUHT-UHFFFAOYSA-N tert-butyl n,n-bis(2-chloroethyl)carbamate Chemical compound CC(C)(C)OC(=O)N(CCCl)CCCl FQZLNQAUUMSUHT-UHFFFAOYSA-N 0.000 description 1
- NHURGMJVQTWHPE-UHFFFAOYSA-N tert-butyl n-[1-(3,4-difluorophenyl)-2-hydroxyethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CO)C1=CC=C(F)C(F)=C1 NHURGMJVQTWHPE-UHFFFAOYSA-N 0.000 description 1
- RFQSCPGYIHARCZ-UHFFFAOYSA-N tert-butyl n-[2-(3,4-difluorophenyl)-2-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC(C)(O)C1=CC=C(F)C(F)=C1 RFQSCPGYIHARCZ-UHFFFAOYSA-N 0.000 description 1
- UETDOLUDTGQUJX-UHFFFAOYSA-N tert-butyl n-[3-[4-cyano-4-(2,4-dichlorophenyl)piperidin-1-yl]propyl]carbamate Chemical compound C1CN(CCCNC(=O)OC(C)(C)C)CCC1(C#N)C1=CC=C(Cl)C=C1Cl UETDOLUDTGQUJX-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- 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
- A61P9/06—Antiarrhythmics
-
- 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
-
- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87784697A | 1997-06-18 | 1997-06-18 | |
| US08/877,846 | 1997-06-18 | ||
| PCT/US1998/012668 WO1998057940A1 (en) | 1997-06-18 | 1998-06-17 | Heterocyclic substituted piperidines and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2294549A1 true CA2294549A1 (en) | 1998-12-23 |
Family
ID=25370847
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002294549A Abandoned CA2294549A1 (en) | 1997-06-18 | 1998-06-17 | Heterocyclic substituted piperidines and uses thereof |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0988295A4 (de) |
| JP (1) | JP2002505683A (de) |
| AU (1) | AU740064B2 (de) |
| CA (1) | CA2294549A1 (de) |
| WO (1) | WO1998057940A1 (de) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6319932B1 (en) | 1998-11-10 | 2001-11-20 | Merck & Co., Inc. | Oxazolidinones useful as alpha 1A adrenoceptor antagonists |
| US6228870B1 (en) | 1998-11-10 | 2001-05-08 | Merck & Co., Inc. | Oxazolidinones useful as alpha 1a adrenoceptor antagonists |
| US6046331A (en) * | 1998-12-17 | 2000-04-04 | Synaptic Pharmaceutical Corporation | Imidazolones and their use in treating benign prostatic hyperplasia and other disorders |
| GB2344821A (en) | 1998-12-17 | 2000-06-21 | Merck & Co Inc | Crystalline pharmaceutically acceptable salt of an oxazolidinone derivative |
| US6372911B1 (en) * | 1999-02-09 | 2002-04-16 | Merck & Co., Inc. | Process for preparing β-hydroxycarbamates and their conversion to oxazolidinones |
| US6645968B2 (en) | 1999-08-03 | 2003-11-11 | Abbott Laboratories | Potassium channel openers |
| GB2355456A (en) | 1999-09-30 | 2001-04-25 | Merck & Co Inc | Novel arylhydantoin derivatives useful as alpha 1a adrenoceptor antagonists |
| GB2355264A (en) | 1999-09-30 | 2001-04-18 | Merck & Co Inc | Spirohydantoin derivatives useful as alpha 1a adrenoceptor antagonists |
| GB2355263A (en) | 1999-09-30 | 2001-04-18 | Merck & Co Inc | Lactam and cyclic urea derivatives useful as alpha 1a adrenoceptor antagonists |
| GB2355457A (en) | 1999-09-30 | 2001-04-25 | Merck & Co Inc | Novel spirotricyclic substituted azacycloalkane derivatives useful as alpha 1a adrenoceptor antagonists |
| EP2125750B1 (de) | 2007-02-26 | 2014-05-21 | Vitae Pharmaceuticals, Inc. | Zyklische harnstoff- und carbamat-hemmer aus 11-beta-hydroxysteroid-dehydrogenase 1 |
| AR069207A1 (es) | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| JP5490014B2 (ja) | 2007-12-11 | 2014-05-14 | ヴァイティー ファーマシューティカルズ,インコーポレイテッド | 11β−ヒドロキシステロイドデヒドロゲナーゼ1型の環状尿素阻害剤 |
| RU2539979C2 (ru) | 2008-07-25 | 2015-01-27 | Вайтаи Фармасьютиклз, Инк. | Циклические ингибиторы 11бета-гидроксистероид-дегидрогеназы 1 |
| JP5777030B2 (ja) | 2008-07-25 | 2015-09-09 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 11β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤 |
| WO2010089303A1 (en) | 2009-02-04 | 2010-08-12 | Boehringer Ingelheim International Gmbh | CYCLIC INHIBITORS OF 11 β-HYDROXYSTEROID DEHYDROGENASE 1 |
| MA33216B1 (fr) | 2009-04-30 | 2012-04-02 | Boehringer Ingelheim Int | Inhibiteurs cycliques de la 11béta-hydroxysteroïde déshydrogénase 1 |
| EP2440537A1 (de) | 2009-06-11 | 2012-04-18 | Vitae Pharmaceuticals, Inc. | Cyclische hemmer der 11beta-hydroxysteroiddehydrogenase 1 auf basis der 1,3 -oxazinan- 2 -on-struktur |
| WO2011002910A1 (en) | 2009-07-01 | 2011-01-06 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2582698B1 (de) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituierte 5-,6- und 7-gliedrige heterocyclen, medikamente mit derartigen verbindungen und ihre verwendung |
| JP5813106B2 (ja) | 2010-06-25 | 2015-11-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 代謝障害の処置のための11−β−HSD1のインヒビターとしてのアザスピロヘキサノン |
| BR112013010021A2 (pt) | 2010-11-02 | 2019-09-24 | Boehringer Ingelheim Int | combinações farmacêuticas para o tratamento de distúrbios metabólicos. |
| DK2906221T3 (da) | 2012-10-11 | 2019-07-22 | Southern Res Inst | Urinstof og amidderivater af aminoalkylpiperaziner og anvendelse deraf |
| SG11202105250TA (en) * | 2018-11-20 | 2021-06-29 | Sironax Ltd | Cyclic Ureas |
| CN116003380B (zh) * | 2023-01-31 | 2024-07-05 | 天津大学 | 指纹识别探针、显影剂和介质表面潜指纹荧光成像方法 |
| CN121554459B (zh) * | 2026-01-23 | 2026-05-08 | 成都天兴致远生物科技有限公司 | 一种佐米曲普坦的制备方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3334098A (en) * | 1964-05-07 | 1967-08-01 | American Cyanamid Co | 1-monocarbocyclic aryl-3-amino-alkanoyl-2-imidazolidinones |
| CH613205A5 (de) * | 1975-06-06 | 1979-09-14 | Hoffmann La Roche | |
| US4377578A (en) * | 1976-12-21 | 1983-03-22 | Janssen Pharmaceutica, N.V. | Piperazine derivatives |
| US4410540A (en) * | 1981-11-04 | 1983-10-18 | Merrell Dow Pharmaceuticals Inc. | Cardiotonic 4-aroylimidazolidin-2-ones |
| JPH0713017B2 (ja) * | 1986-06-18 | 1995-02-15 | 日本ケミファ株式会社 | 脳細胞保護作用を有する医薬組成物 |
| JPH0755937B2 (ja) * | 1986-07-29 | 1995-06-14 | 日本曹達株式会社 | オキサ(チア)ゾリジン誘導体その製造方法及び殺ダニ剤 |
| US5202345A (en) * | 1987-08-19 | 1993-04-13 | Shionogi & Co., Ltd. | Carbamoylpyrrolidone derivatives and drugs for senile dementia |
| FR2698359B1 (fr) * | 1992-11-25 | 1995-10-27 | Rhone Poulenc Agrochimie | Derives de 2-alkoxy 2-imidazoline-5-ones fongicides. |
| JPH09504272A (ja) * | 1993-09-15 | 1997-04-28 | メルク シヤープ エンド ドーム リミテツド | ドーパミンアンタゴニストとしてのイミダゾロン及びオキサゾロン誘導体 |
| JP3200070B2 (ja) * | 1994-11-16 | 2001-08-20 | シナプティック・ファーマスーティカル・コーポレーション | ジヒドロピリミジン類およびその使用 |
| WO1997017969A1 (en) * | 1995-11-16 | 1997-05-22 | Synaptic Pharmaceutical Corporation | Dihydropyrimidines and uses thereof |
-
1998
- 1998-06-17 JP JP50477899A patent/JP2002505683A/ja active Pending
- 1998-06-17 CA CA002294549A patent/CA2294549A1/en not_active Abandoned
- 1998-06-17 AU AU81498/98A patent/AU740064B2/en not_active Ceased
- 1998-06-17 EP EP98931350A patent/EP0988295A4/de not_active Withdrawn
- 1998-06-17 WO PCT/US1998/012668 patent/WO1998057940A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002505683A (ja) | 2002-02-19 |
| EP0988295A4 (de) | 2003-08-13 |
| EP0988295A1 (de) | 2000-03-29 |
| AU740064B2 (en) | 2001-10-25 |
| AU8149898A (en) | 1999-01-04 |
| WO1998057940A1 (en) | 1998-12-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Dead |