CA2704222A1 - Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 - Google Patents
Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 Download PDFInfo
- Publication number
- CA2704222A1 CA2704222A1 CA2704222A CA2704222A CA2704222A1 CA 2704222 A1 CA2704222 A1 CA 2704222A1 CA 2704222 A CA2704222 A CA 2704222A CA 2704222 A CA2704222 A CA 2704222A CA 2704222 A1 CA2704222 A1 CA 2704222A1
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- CA
- Canada
- Prior art keywords
- halo
- alkyl
- alkoxy
- ethyl
- cycloalkyl
- 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
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- 239000003112 inhibitor Substances 0.000 title description 11
- 101710088194 Dehydrogenase Proteins 0.000 title description 4
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 226
- 238000000034 method Methods 0.000 claims abstract description 87
- 150000003839 salts Chemical class 0.000 claims abstract description 70
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 22
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 241000124008 Mammalia Species 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims description 672
- 125000000217 alkyl group Chemical group 0.000 claims description 346
- -1 hydroxy, carboxy Chemical group 0.000 claims description 320
- 125000003545 alkoxy group Chemical group 0.000 claims description 313
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 238
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 203
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 157
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 153
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 146
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 139
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 115
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 108
- 125000003282 alkyl amino group Chemical group 0.000 claims description 98
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 95
- 125000001072 heteroaryl group Chemical group 0.000 claims description 94
- 125000004043 oxo group Chemical group O=* 0.000 claims description 90
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 87
- 125000001424 substituent group Chemical group 0.000 claims description 74
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 71
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 70
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 70
- 125000005148 cycloalkylalkanesulfinyl group Chemical group 0.000 claims description 70
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 70
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 70
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 68
- 229910052731 fluorine Inorganic materials 0.000 claims description 64
- 239000011737 fluorine Substances 0.000 claims description 61
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 60
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 58
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 57
- 125000004414 alkyl thio group Chemical group 0.000 claims description 54
- 229910052736 halogen Inorganic materials 0.000 claims description 54
- 150000002367 halogens Chemical group 0.000 claims description 54
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 53
- 125000003368 amide group Chemical class 0.000 claims description 50
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 47
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 46
- 239000000460 chlorine Substances 0.000 claims description 46
- 229910052801 chlorine Inorganic materials 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 41
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 41
- 229910052794 bromium Inorganic materials 0.000 claims description 39
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 38
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 37
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 37
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 36
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 35
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 35
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 34
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 34
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 33
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
- 125000001188 haloalkyl group Chemical group 0.000 claims description 28
- 125000002947 alkylene group Chemical group 0.000 claims description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- NQPJDJVGBDHCAD-UHFFFAOYSA-N 1,3-diazinan-2-one Chemical compound OC1=NCCCN1 NQPJDJVGBDHCAD-UHFFFAOYSA-N 0.000 claims description 25
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 25
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 22
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 21
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 20
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 20
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001769 aryl amino group Chemical group 0.000 claims description 16
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 16
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
- 125000005145 cycloalkylaminosulfonyl group Chemical group 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 230000014509 gene expression Effects 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 7
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 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 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 229920002554 vinyl polymer Chemical group 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 4
- 229910003600 H2NS Inorganic materials 0.000 claims description 4
- 125000004633 N-oxo-pyridyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 3
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 3
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- LSLJKAPWUHORLT-GOSISDBHSA-N (4r)-4-methyl-1-(3-methylphenyl)-4-phenyl-1,3-diazinan-2-one Chemical compound CC1=CC=CC(N2C(N[C@](C)(CC2)C=2C=CC=CC=2)=O)=C1 LSLJKAPWUHORLT-GOSISDBHSA-N 0.000 claims description 2
- YUJAXGHCMAHYOR-CISYCMJJSA-N 1-[(1s)-1-(4-bromophenyl)ethyl]-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-3-methyl-1,3-diazinan-2-one Chemical compound CN1C(=O)N([C@@H](C)C=2C=CC(Br)=CC=2)CCC1(CCCO)C1=CC=C(F)C=C1 YUJAXGHCMAHYOR-CISYCMJJSA-N 0.000 claims description 2
- QCIZUNWRIKSICP-ZDGMYTEDSA-N 1-[(1s)-1-(4-chlorophenyl)ethyl]-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(Cl)=CC=2)CCC1(CCCO)C1=CC=C(F)C=C1 QCIZUNWRIKSICP-ZDGMYTEDSA-N 0.000 claims description 2
- CYOLONMWNWCSEK-WFFHQLTOSA-N 1-[(1s)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-4-(4-fluorophenyl)-4-(2-hydroxyethyl)-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C(=CC(F)=CC=2)F)CCC1(CCO)C1=CC=C(F)C=C1 CYOLONMWNWCSEK-WFFHQLTOSA-N 0.000 claims description 2
- HHDVTFNGTOKZQI-HSYKDVHTSA-N 1-[(1s)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C(=CC(F)=CC=2)F)CCC1(CCCO)C1=CC=C(F)C=C1 HHDVTFNGTOKZQI-HSYKDVHTSA-N 0.000 claims description 2
- BWCWPIIVYWOSFR-SVQMELKDSA-N 1-[(1s)-1-[4-(4-fluorophenyl)phenyl]ethyl]-4-(3-hydroxypropyl)-4-phenyl-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)CCC1(CCCO)C1=CC=CC=C1 BWCWPIIVYWOSFR-SVQMELKDSA-N 0.000 claims description 2
- LMFAJHPVXLIPOV-MSRYYJCKSA-N 4-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1-[(1s)-1-[4-(4-fluorophenyl)phenyl]ethyl]-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)CCC1(CC(O)CO)C1=CC=C(F)C=C1 LMFAJHPVXLIPOV-MSRYYJCKSA-N 0.000 claims description 2
- JKMBHCXGQGTPTQ-JDEXWRGDSA-N 4-(4-fluorophenyl)-1-[(1s)-1-[4-(4-fluorophenyl)phenyl]ethyl]-4-(3-hydroxypropyl)-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C=CC(F)=CC=2)CCC1(CCCO)C1=CC=C(F)C=C1 JKMBHCXGQGTPTQ-JDEXWRGDSA-N 0.000 claims description 2
- LSLJKAPWUHORLT-UHFFFAOYSA-N 4-methyl-1-(3-methylphenyl)-4-phenyl-1,3-diazinan-2-one Chemical compound CC1=CC=CC(N2C(NC(C)(CC2)C=2C=CC=CC=2)=O)=C1 LSLJKAPWUHORLT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 2
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000006262 isopropyl amino sulfonyl group Chemical group 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 61
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 2
- RLMGQOJHSREDKL-UHFFFAOYSA-N 3-[1-[1-[4-(4-fluorophenyl)phenyl]ethyl]-2-oxo-4-phenyl-1,3-diazinan-4-yl]propanamide Chemical compound C=1C=C(C=2C=CC(F)=CC=2)C=CC=1C(C)N(C(N1)=O)CCC1(CCC(N)=O)C1=CC=CC=C1 RLMGQOJHSREDKL-UHFFFAOYSA-N 0.000 claims 2
- LFBLXBZNMMITTO-UHFFFAOYSA-N 4-(4-fluorophenyl)-4-(2-hydroxyethyl)-1-[1-(4-methoxyphenyl)ethyl]-1,3-diazinan-2-one Chemical compound C1=CC(OC)=CC=C1C(C)N1C(=O)NC(CCO)(C=2C=CC(F)=CC=2)CC1 LFBLXBZNMMITTO-UHFFFAOYSA-N 0.000 claims 2
- TYIWTXBFSKFPKX-UHFFFAOYSA-N 1-(1-cyclohexylethyl)-4-(3-hydroxypropyl)-4-phenyl-1,3-diazinan-2-one Chemical compound C1CC(CCCO)(C=2C=CC=CC=2)NC(=O)N1C(C)C1CCCCC1 TYIWTXBFSKFPKX-UHFFFAOYSA-N 0.000 claims 1
- RDXLZJXIVYZKNT-UHFFFAOYSA-N 1-(1-cyclohexylethyl)-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-1,3-diazinan-2-one Chemical compound C1CC(CCCO)(C=2C=CC(F)=CC=2)NC(=O)N1C(C)C1CCCCC1 RDXLZJXIVYZKNT-UHFFFAOYSA-N 0.000 claims 1
- QLCKOLMCGHMETH-PVCZSOGJSA-N 1-[(1s)-1-(4-chlorophenyl)ethyl]-4-(4-fluorophenyl)-4-(2-hydroxyethyl)-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(Cl)=CC=2)CCC1(CCO)C1=CC=C(F)C=C1 QLCKOLMCGHMETH-PVCZSOGJSA-N 0.000 claims 1
- MMRCQVRXFLWAQD-IPOUSNRNSA-N 1-[(1s)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-4-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1,3-diazinan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C(=CC(F)=CC=2)F)CCC1(CC(O)CO)C1=CC=C(F)C=C1 MMRCQVRXFLWAQD-IPOUSNRNSA-N 0.000 claims 1
- TYIWTXBFSKFPKX-PBVYKCSPSA-N 1-[(1s)-1-cyclohexylethyl]-4-(3-hydroxypropyl)-4-phenyl-1,3-diazinan-2-one Chemical compound C1([C@H](C)N2C(NC(CCCO)(CC2)C=2C=CC=CC=2)=O)CCCCC1 TYIWTXBFSKFPKX-PBVYKCSPSA-N 0.000 claims 1
- YUJAXGHCMAHYOR-UHFFFAOYSA-N 1-[1-(4-bromophenyl)ethyl]-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-3-methyl-1,3-diazinan-2-one Chemical compound C=1C=C(Br)C=CC=1C(C)N(C(N1C)=O)CCC1(CCCO)C1=CC=C(F)C=C1 YUJAXGHCMAHYOR-UHFFFAOYSA-N 0.000 claims 1
- LKKJPODTAZOLGK-UHFFFAOYSA-N 1-[1-(4-bromophenyl)propyl]-4-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1,3-diazinan-2-one Chemical compound C=1C=C(Br)C=CC=1C(CC)N(C(N1)=O)CCC1(CC(O)CO)C1=CC=C(F)C=C1 LKKJPODTAZOLGK-UHFFFAOYSA-N 0.000 claims 1
- ODBJJXYRVIJKMP-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)ethyl]-4-(2,3-dihydroxypropyl)-4-propan-2-yl-1,3-diazinan-2-one Chemical compound O=C1NC(C(C)C)(CC(O)CO)CCN1C(C)C1=CC=C(Cl)C=C1 ODBJJXYRVIJKMP-UHFFFAOYSA-N 0.000 claims 1
- QLCKOLMCGHMETH-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)ethyl]-4-(4-fluorophenyl)-4-(2-hydroxyethyl)-1,3-diazinan-2-one Chemical compound C=1C=C(Cl)C=CC=1C(C)N(C(N1)=O)CCC1(CCO)C1=CC=C(F)C=C1 QLCKOLMCGHMETH-UHFFFAOYSA-N 0.000 claims 1
- QCIZUNWRIKSICP-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)ethyl]-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-1,3-diazinan-2-one Chemical compound C=1C=C(Cl)C=CC=1C(C)N(C(N1)=O)CCC1(CCCO)C1=CC=C(F)C=C1 QCIZUNWRIKSICP-UHFFFAOYSA-N 0.000 claims 1
- MMRCQVRXFLWAQD-UHFFFAOYSA-N 1-[1-[4-(2,4-difluorophenyl)phenyl]ethyl]-4-(2,3-dihydroxypropyl)-4-(4-fluorophenyl)-1,3-diazinan-2-one Chemical compound C=1C=C(C=2C(=CC(F)=CC=2)F)C=CC=1C(C)N(C(N1)=O)CCC1(CC(O)CO)C1=CC=C(F)C=C1 MMRCQVRXFLWAQD-UHFFFAOYSA-N 0.000 claims 1
- QFPLXKGFPMGUQX-UHFFFAOYSA-N 1-[1-[4-(2,4-difluorophenyl)phenyl]ethyl]-4-(2-hydroxyethyl)-3-methyl-4-thiophen-2-yl-1,3-diazinan-2-one Chemical compound C=1C=C(C=2C(=CC(F)=CC=2)F)C=CC=1C(C)N(C(N1C)=O)CCC1(CCO)C1=CC=CS1 QFPLXKGFPMGUQX-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine 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 directly attached in position 2
- C07D239/10—Oxygen or sulfur atoms
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- 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
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- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D409/10—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 carbon chain containing aromatic rings
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Applications Claiming Priority (3)
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| US215707P | 2007-11-07 | 2007-11-07 | |
| US61/002,157 | 2007-11-07 | ||
| PCT/US2008/012618 WO2009061498A1 (en) | 2007-11-07 | 2008-11-07 | CYCLIC UREA INHIBITORS OF 11β -HYDROXYSTEROID DEHYDROGENASE 1 |
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| CA2704222A1 true CA2704222A1 (en) | 2009-05-14 |
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| CA2704222A Abandoned CA2704222A1 (en) | 2007-11-07 | 2008-11-07 | Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
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Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8835426B2 (en) | 2007-02-26 | 2014-09-16 | Vitae Pharmaceuticals, Inc. | Cyclic urea and carbamate inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| JP5451611B2 (ja) * | 2007-07-26 | 2014-03-26 | 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のサイクリックインヒビター |
| AR069207A1 (es) | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| US8859580B2 (en) | 2007-11-16 | 2014-10-14 | Boehringer Ingelheim International Gmbh | Aryl- and heteroarylcarbonyl derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| CA2708303A1 (en) | 2007-12-11 | 2009-06-18 | Vitae Pharmaceuticals, Inc. | Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
| TW200934490A (en) * | 2008-01-07 | 2009-08-16 | Vitae Pharmaceuticals Inc | Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1 |
| WO2009094169A1 (en) | 2008-01-24 | 2009-07-30 | Vitae Pharmaceuticals, Inc. | Cyclic carbazate and semicarbazide inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2714532A1 (en) * | 2008-02-11 | 2009-08-20 | Vitae Pharmaceuticals, Inc. | 1,3-oxazepan-2-one and 1,3-diazepan-2-one inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
| US8598160B2 (en) * | 2008-02-15 | 2013-12-03 | Vitae Pharmaceuticals, Inc. | Cycloalkyl lactame derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| KR20110002492A (ko) | 2008-05-01 | 2011-01-07 | 비타이 파마슈티컬즈, 인코포레이티드 | 11베타-하이드록시스테로이드 탈수소효소 1의 고리형 억제제 |
| TW201004945A (en) | 2008-05-01 | 2010-02-01 | Vitae Pharmaceuticals Inc | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2723032A1 (en) * | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2291370B1 (en) | 2008-05-01 | 2013-11-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| US8765780B2 (en) | 2008-05-13 | 2014-07-01 | Boehringer Ingelheim International Gmbh | Alicyclic carboxylic acid derivatives of benzomorphans and related scaffolds, medicaments containing such compounds and their use |
| US8846668B2 (en) | 2008-07-25 | 2014-09-30 | Vitae Pharmaceuticals, Inc. | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2729993A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Synthesis of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| WO2010011314A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Cyclic inhibitors of 11 beta-hydroxysteroid dehydrogenase 1 |
| CA2738453C (en) | 2008-10-23 | 2017-07-04 | Boehringer Ingelheim International Gmbh | Urea derivatives of substituted nortropanes, medicaments containing such compounds and their use |
| JP5679997B2 (ja) | 2009-02-04 | 2015-03-04 | 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の環状阻害剤 |
| UA109255C2 (ru) | 2009-04-30 | 2015-08-10 | Берінгер Інгельхайм Інтернешнл Гмбх | Циклические ингибиторы 11бета-гидроксистероиддегидрогеназы 1 |
| US8703765B2 (en) | 2009-06-02 | 2014-04-22 | Boehringer Ingelheim International Gmbh | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| WO2011011123A1 (en) | 2009-06-11 | 2011-01-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 based on the 1,3 -oxazinan- 2 -one structure |
| WO2011002910A1 (en) | 2009-07-01 | 2011-01-06 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2496589B1 (en) | 2009-11-05 | 2014-03-05 | Boehringer Ingelheim International GmbH | Novel chiral phosphorus ligands |
| AR078887A1 (es) | 2009-11-06 | 2011-12-07 | Boehringer Ingelheim Int | Derivados arilo y heteroarilcarbonilo de hexahidroindenopiridina y octahidrobenzoquinolina y composiciones farmaceuticas que los contienen. |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2576570A1 (en) | 2010-05-26 | 2013-04-10 | Boehringer Ingelheim International GmbH | 2-oxo-1,2-dihydropyridin-4-ylboronic acid derivatives |
| EP2582698B1 (en) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| 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 |
| WO2011161128A1 (en) | 2010-06-25 | 2011-12-29 | Boehringer Ingelheim International Gmbh | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, 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 |
| CA2813671A1 (en) | 2010-11-02 | 2012-05-10 | Boehringer Ingelheim International Gmbh | Pharmaceutical combinations for the treatment of metabolic disorders |
| TWI537258B (zh) | 2010-11-05 | 2016-06-11 | 百靈佳殷格翰國際股份有限公司 | 六氫茚并吡啶及八氫苯并喹啉之芳基－及雜環芳基羰基衍生物 |
| US8735585B2 (en) | 2011-08-17 | 2014-05-27 | Boehringer Ingelheim International Gmbh | Indenopyridine derivatives |
| 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 |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP3235813A1 (en) | 2016-04-19 | 2017-10-25 | Cidqo 2012, S.L. | Aza-tetra-cyclo derivatives |
Family Cites Families (188)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3378587A (en) * | 1963-03-14 | 1968-04-16 | Du Pont | 3, 3'-diaminomethyl-1, 1'-biadamantane |
| NL127995C (enExample) | 1963-12-20 | Geigy Ag J R | ||
| US3341538A (en) * | 1965-06-18 | 1967-09-12 | Geigy Chem Corp | Certain 2, 6-methano-3-benzazocines |
| GB1304175A (enExample) * | 1969-03-31 | 1973-01-24 | ||
| US3681349A (en) * | 1970-03-05 | 1972-08-01 | Morton Norwich Products Inc | 1-(substituted benzyl) tetrahydro-2-(1h) pyrimidones |
| US4043927A (en) * | 1972-03-07 | 1977-08-23 | Sun Ventures, Inc. | Friction or tractive drive containing ethers of adamantanes |
| DE2338369A1 (de) * | 1973-07-26 | 1975-02-13 | Schering Ag | Mikrobiologische hydroxylierung von 2,6-methano-3-benzazocinen |
| US4009171A (en) * | 1974-02-21 | 1977-02-22 | Sterling Drug Inc. | N-acylated-11-oxygenated-2,6-methano-3-benzazocine intermediates |
| US4136162A (en) * | 1974-07-05 | 1979-01-23 | Schering Aktiengesellschaft | Medicament carriers in the form of film having active substance incorporated therein |
| US4136145A (en) * | 1974-07-05 | 1979-01-23 | Schering Aktiengesellschaft | Medicament carriers in the form of film having active substance incorporated therein |
| GB1513961A (en) * | 1975-02-25 | 1978-06-14 | Acf Chemiefarma Nv | 6,7-benzomorphans method for their preparation and intermediates |
| US4108857A (en) * | 1975-08-18 | 1978-08-22 | Sterling Drug Inc. | Imidazolylmethyl methanobenzazocines |
| US5393735A (en) * | 1990-08-09 | 1995-02-28 | Rohm And Haas Company | Herbicidal glutarimides |
| CA2023492A1 (en) | 1989-08-31 | 1991-03-01 | Barry Clifford Lange | Herbicidal glutarimides |
| US5098916A (en) * | 1990-03-29 | 1992-03-24 | G. D. Searle & Co. | Propanobicyclic amine derivatives for cns disorders |
| EP0454444A1 (en) | 1990-04-24 | 1991-10-30 | Nissan Chemical Industries Ltd. | Glutarimide derivatives and herbicides |
| US5215992A (en) * | 1990-04-30 | 1993-06-01 | G. D. Searle & Co. | Ethanobicyclic amine derivatives for CNS disorders |
| US5089506A (en) * | 1990-04-30 | 1992-02-18 | G. D. Searle & Co. | Ethanobicyclic amine derivatives for cns disorders |
| DK204291D0 (da) | 1991-12-20 | 1991-12-20 | Novo Nordisk As | Heterocykliske forbindelser deres fremstilling og anvendelse |
| CA2049244A1 (en) | 1990-08-16 | 1992-02-17 | Steven H. Christiansen | Process for absorption of sulfur compounds from fluids using heterocyclic compounds having at least one ring nitrogen atom |
| ATE122673T1 (de) * | 1990-10-10 | 1995-06-15 | Schering Corp | Pyridin- und pyridin-n-oxid-derivate von diarylmethyl- piperidinen oder piperazinen, deren zusammensetzungen und anwendung. |
| GB9023583D0 (en) | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
| US5610294A (en) * | 1991-10-11 | 1997-03-11 | The Du Pont Merck Pharmaceutical Company | Substituted cyclic carbonyls and derivatives thereof useful as retroviral protease inhibitors |
| KR100268694B1 (ko) | 1991-10-11 | 2000-10-16 | 미리암 디. 메코너헤이, 블레어큐. 퍼거슨 | 레트로바이러스 프로테아제 억제제로 유용한 시클릭 우레아 및 유사체 |
| HU220601B1 (hu) * | 1992-04-30 | 2002-03-28 | Taiho Pharmaceutical Co. Ltd. | Fenoxi-alkil-oxazolidin-származékok, eljárás előállításukra és ezeket tartalmazó gyógyszerkészítmények |
| GB9225377D0 (en) * | 1992-12-04 | 1993-01-27 | Ici Plc | Herbicides |
| TW280812B (enExample) * | 1993-07-02 | 1996-07-11 | Bayer Ag | |
| EP0640594A1 (en) | 1993-08-23 | 1995-03-01 | Fujirebio Inc. | Hydantoin derivative as metalloprotease inhibitor |
| DE19500118A1 (de) * | 1994-05-18 | 1995-11-23 | Bayer Ag | Substituierte Diazacyclohexandi(thi)one |
| US5780466A (en) * | 1995-01-30 | 1998-07-14 | Sanofi | Substituted heterocyclic compounds method of preparing them and pharmaceutical compositions in which they are present |
| FR2729954B1 (fr) * | 1995-01-30 | 1997-08-01 | Sanofi Sa | Composes heterocycliques substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
| GB9510459D0 (en) | 1995-05-24 | 1995-07-19 | Zeneca Ltd | Bicyclic amines |
| US5776959A (en) * | 1995-06-05 | 1998-07-07 | Washington University | Anticonvulsant and anxiolytic lactam and thiolactam derivatives |
| GB9517622D0 (en) * | 1995-08-29 | 1995-11-01 | Univ Edinburgh | Regulation of intracellular glucocorticoid concentrations |
| WO1997036605A1 (en) | 1996-04-03 | 1997-10-09 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| CA2262502C (en) * | 1996-07-31 | 2002-11-26 | Nikken Chemicals Co., Ltd. | 6-phenyltetrahydro-1,3-oxazin-2-one derivatives and pharmaceutical composition containing the same |
| US6794390B2 (en) * | 1996-08-02 | 2004-09-21 | Cv Therapeutics, Inc. | Purine inhibitors of cyclin dependent kinase 2 & ikappabalpha |
| US5866702A (en) * | 1996-08-02 | 1999-02-02 | Cv Therapeutics, Incorporation | Purine inhibitors of cyclin dependent kinase 2 |
| GB9623944D0 (en) | 1996-11-15 | 1997-01-08 | Zeneca Ltd | Bicyclic amine derivatives |
| US6159990A (en) * | 1997-06-18 | 2000-12-12 | Synaptic Pharmaceutical Corporation | Oxazolidinones as α1A receptor antagonists |
| JP2002505683A (ja) | 1997-06-18 | 2002-02-19 | 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 | 複素環置換されたピペリジン類及びその使用 |
| GB9715892D0 (en) | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic compounds |
| US5936124A (en) * | 1998-06-22 | 1999-08-10 | Sepacor Inc. | Fluoxetine process from benzoylpropionic acid |
| US7410995B1 (en) | 1998-08-14 | 2008-08-12 | Gpi Nil Holdings Inc. | N-linked sulfonamide of heterocyclic thioesters for vision and memory disorders |
| US7256005B2 (en) * | 1999-08-10 | 2007-08-14 | The Chancellor, Masters And Scholars Of The University Of Oxford | Methods for identifying iminosugar derivatives that inhibit HCV p7 ion channel activity |
| WO2001013917A1 (en) | 1999-08-26 | 2001-03-01 | Bristol-Myers Squibb Company | Npy antagonists: spiroisoquinolinone derivatives |
| JP2003522739A (ja) | 1999-12-17 | 2003-07-29 | シェーリング コーポレイション | 選択的ニューロキニンアンタゴニスト |
| US6436928B1 (en) * | 1999-12-17 | 2002-08-20 | Schering Corporation | Selective neurokinin antagonists |
| WO2001055063A1 (en) | 2000-01-25 | 2001-08-02 | Idemitsu Petrochemical Co., Ltd. | Novel bisadamantane compounds, process for preparing the same, and novel biadamantane derivatives |
| GB0003397D0 (en) * | 2000-02-14 | 2000-04-05 | Merck Sharp & Dohme | Therapeutic agents |
| DE10035928A1 (de) * | 2000-07-21 | 2002-03-07 | Asta Medica Ag | Neue Heteroaryl-Derivate und deren Verwendung als Arzneimittel |
| DE10035908A1 (de) * | 2000-07-21 | 2002-03-07 | Asta Medica Ag | Neue Heteroaryl-Derivate und deren Verwendung als Arzneimittel |
| DE10035927A1 (de) * | 2000-07-21 | 2002-03-07 | Asta Medica Ag | Neue Heteroaryl-Derivate und deren Verwendung als Arzneimittel |
| US6559163B2 (en) * | 2000-08-16 | 2003-05-06 | Neurogen Corporation | 2,4-substituted quinoline derivatives |
| US7294637B2 (en) * | 2000-09-11 | 2007-11-13 | Sepracor, Inc. | Method of treating addiction or dependence using a ligand for a monamine receptor or transporter |
| EP1318988A2 (en) * | 2000-09-11 | 2003-06-18 | Sepracor, Inc. | Ligands for monoamine receptors and transporters, and methods of use thereof (neurotransmission) |
| US6841671B2 (en) * | 2000-10-26 | 2005-01-11 | Pfizer Inc. | Spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors |
| US20030143668A1 (en) | 2001-06-18 | 2003-07-31 | National Institute Of Advanced Industrial | Guanosine triphosphate-binding protein coupled receptors |
| JP4545437B2 (ja) * | 2001-10-15 | 2010-09-15 | シェーリング コーポレイション | アデノシンａ２ａ受容体アンタゴニストとしてのイミダゾ（４，３−ｅ）−１，２，４−トリアゾロ（１，５−ｃ）ピリミジン |
| JP2005527598A (ja) * | 2002-04-26 | 2005-09-15 | ファイザー・プロダクツ・インク | トリアリール−オキシ−アリール−スピロ−ピリミジン−２，４，６−トリオンメタロプロテイナーゼ阻害剤 |
| AU2003216660A1 (en) * | 2002-04-26 | 2003-11-10 | Pfizer Products Inc. | N-substituted-heteroaryloxy-aryl-spiro-pyrimidine-2,4,6-trione metalloproteinase inhibitors |
| DE60335359D1 (de) | 2002-04-30 | 2011-01-27 | Kudos Pharm Ltd | Phthalazinonderivate |
| WO2003097608A2 (en) | 2002-05-17 | 2003-11-27 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US7041682B2 (en) | 2002-07-03 | 2006-05-09 | Schering Corporation | NK1 antagonists |
| AU2003249812A1 (en) | 2002-07-18 | 2004-02-09 | Queen's University At Kingston | Dihydrouracil compounds as anti-ictogenic or anti-epileptogenic agents |
| GB0218630D0 (en) | 2002-08-10 | 2002-09-18 | Tanabe Seiyaku Co | Novel compounds |
| AR041198A1 (es) * | 2002-10-11 | 2005-05-04 | Otsuka Pharma Co Ltd | Compuesto 2,3-dihidro-6-nitroimidazo[2,1-b] oxaxol, y composiciones farmaceuticas que lo contienen |
| AU2003302027A1 (en) | 2002-11-21 | 2004-06-15 | Vicore Pharma Ab | New tricyclic angiotensin ii agonists |
| GB0228410D0 (en) * | 2002-12-05 | 2003-01-08 | Glaxo Group Ltd | Novel Compounds |
| WO2004055008A1 (en) * | 2002-12-13 | 2004-07-01 | Smithkline Beecham Corporation | Compounds, compositions and methods |
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| ATE474577T1 (de) * | 2003-03-26 | 2010-08-15 | Merck Sharp & Dohme | Bicyclische piperidin-derivate als melanocortin-4 rezeptor-agonisten |
| DE602004027171D1 (de) | 2003-04-11 | 2010-06-24 | High Point Pharmaceuticals Llc | Verbindungen mit Aktivität an der 11Beta-Hydroxasteroiddehydrogenase |
| US7700583B2 (en) * | 2003-04-11 | 2010-04-20 | High Point Pharmaceuticals, Llc | 11β-hydroxysteroid dehydrogenase type 1 active compounds |
| ITMI20031292A1 (it) | 2003-06-25 | 2004-12-26 | Nikem Research Srl | Derivati biciclici nk-2 antagonisti selettivi. |
| DE10358004A1 (de) * | 2003-12-11 | 2005-07-14 | Abbott Gmbh & Co. Kg | Ketolactam-Verbindungen und ihre Verwendung |
| US7186844B2 (en) * | 2004-01-13 | 2007-03-06 | Mitsubishi Gas Chemical Co., Inc. | Method for producing cyclic carbamate ester |
| EP1725535A4 (en) | 2004-03-09 | 2009-11-25 | Merck & Co Inc | HIV integrase |
| US8519158B2 (en) * | 2004-03-12 | 2013-08-27 | Ligand Pharmaceuticals Incorporated | Androgen receptor modulator compounds and methods |
| EP1747198B1 (en) | 2004-05-07 | 2008-06-04 | Janssen Pharmaceutica N.V. | Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| CA2565630C (en) | 2004-05-07 | 2013-05-28 | Janssen Pharmaceutica N.V. | Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| GB0411404D0 (en) | 2004-05-21 | 2004-06-23 | Glaxo Group Ltd | Novel compounds |
| AU2005247929B2 (en) | 2004-05-24 | 2010-03-11 | Amgen Inc. | Inhibitors of 11-beta-hydroxy steroid dehydrogenase type 1 |
| MXPA06014572A (es) | 2004-06-24 | 2007-03-12 | Incyte Corp | Compuestos amido y su uso como farmaceuticos. |
| GB0414438D0 (en) | 2004-06-28 | 2004-07-28 | Syngenta Participations Ag | Chemical compounds |
| DOP2005000123A (es) * | 2004-07-02 | 2011-07-15 | Merck Sharp & Dohme | Inhibidores de cetp |
| EP1621536A1 (en) * | 2004-07-27 | 2006-02-01 | Aventis Pharma S.A. | Amino cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors |
| EP1621539A1 (en) * | 2004-07-27 | 2006-02-01 | Aventis Pharma S.A. | Heterocycle -substituted cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors |
| EP1621535A1 (en) * | 2004-07-27 | 2006-02-01 | Aventis Pharma S.A. | Substituted cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors |
| MX2007001399A (es) | 2004-08-02 | 2007-04-18 | Osi Pharm Inc | Compuestos que inhiben pirrolopirimidina multi-cinasa aril-amino sustituidas. |
| US7544677B2 (en) * | 2004-08-23 | 2009-06-09 | Merck & Co., Inc. | Inhibitors of Akt activity |
| CN101300005B (zh) | 2004-08-30 | 2013-05-01 | 詹森药业有限公司 | 作为11-β羟类固醇脱氢酶抑制剂的N-2金刚烷基-2-苯氧基-乙酰胺衍生物 |
| CA2579514A1 (en) * | 2004-09-10 | 2006-03-23 | Janssen Pharmaceutica N.V. | Novel imidazolidin-2-one derivatives as selective androgen receptor modulators (sarms) |
| EP1802623A1 (en) | 2004-10-12 | 2007-07-04 | Novo Nordisk A/S | 11beta-hydroxysteroid dehydrogenase type 1 active spiro compounds |
| WO2006044174A2 (en) | 2004-10-13 | 2006-04-27 | Neurogen Corporation | Aryl substituted 8-azabicyclo[3.2.1]octane compounds as ligands of the melanin concentrating hormone receptor |
| SG161261A1 (en) * | 2004-11-10 | 2010-05-27 | Incyte Corp | Lactam compounds and their use as pharmaceuticals |
| US20060167044A1 (en) | 2004-12-20 | 2006-07-27 | Arnaiz Damian O | Piperidine derivatives and their use as anti-inflammatory agents |
| KR20070090915A (ko) | 2004-12-23 | 2007-09-06 | 키에시 파르마슈티시 엣스. 피. 에이. | 항 무스카린성 활성을 가진 아졸유도체 |
| AU2005322085B2 (en) * | 2004-12-28 | 2012-07-19 | Exelixis, Inc. | [1H-pyrazolo[3, 4-d]pyrimidin-4-yl]-piperidine or -piperazine compounds as serine-threonine kinase modulators (p70S6K, Atk1 and Atk2) for the treatment of immunological, inflammatory and proliferative diseases |
| EP1838703A2 (en) * | 2005-01-19 | 2007-10-03 | Neurogen Corporation | Heteroaryl substituted piperazinyl-pyridine analogues |
| AU2006214378A1 (en) * | 2005-02-16 | 2006-08-24 | Pharmacopeia, Inc. | Pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity |
| CA2598458A1 (en) * | 2005-02-16 | 2006-08-24 | Schering Corporation | Pyrazinyl substituted piperazine-piperidines with cxcr3 antagonist activity |
| CN101189238A (zh) * | 2005-02-16 | 2008-05-28 | 先灵公司 | 具有cxcr3拮抗剂活性的哌嗪-哌啶 |
| US7566718B2 (en) * | 2005-02-16 | 2009-07-28 | Schering Corporation | Amine-linked pyridyl and phenyl substituted piperazine-piperidines with CXCR3 antagonist activity |
| JP2008530216A (ja) * | 2005-02-16 | 2008-08-07 | シェーリング コーポレイション | Ｃｘｃｒ３アンタゴニスト活性を有する、複素環で置換された新規のピリジンまたはフェニル化合物 |
| CN101163692B (zh) * | 2005-02-16 | 2012-01-18 | 先灵公司 | 具有cxcr3拮抗活性的杂环取代的哌嗪 |
| EP1864971A4 (en) * | 2005-03-31 | 2010-02-10 | Takeda Pharmaceutical | PROPHYLACTIC / THERAPEUTIC AGENT AGAINST DIABETES |
| WO2006109056A1 (en) | 2005-04-12 | 2006-10-19 | Vicore Pharma Ab | New tricyclic angiotensin ii agonists |
| WO2007008529A2 (en) | 2005-07-08 | 2007-01-18 | Kalypsys, Inc | Celullar cholesterol absorption modifiers |
| JP2009504769A (ja) | 2005-08-16 | 2009-02-05 | ジェンザイム・コーポレーション | ケモカイン受容体結合化合物 |
| EP1937666B1 (en) * | 2005-10-11 | 2012-02-22 | Schering Corporation | Substituted heterocyclic compounds with cxcr3 antagonist activity |
| US7943605B2 (en) | 2005-10-27 | 2011-05-17 | Ucb Pharma S.A. | Compounds comprising a lactam or a lactam derivative moiety, processes for making them, and their uses |
| EA200801243A1 (ru) | 2005-11-01 | 2008-10-30 | Транстек Фарма | Фармацевтическое применение замещенных амидов |
| US8541592B2 (en) | 2005-11-22 | 2013-09-24 | Amgen Inc. | Inhibitors of 11-beta-hydroxysteroid dehydrogenase type 1 |
| EA200870019A1 (ru) * | 2005-12-05 | 2008-12-30 | Инсайт Корпорейшн | Лактамовые соединения и способы их применения |
| EP1801098A1 (en) | 2005-12-16 | 2007-06-27 | Merck Sante | 2-Adamantylurea derivatives as selective 11B-HSD1 inhibitors |
| WO2007076055A2 (en) | 2005-12-22 | 2007-07-05 | Entremed, Inc. | Compositions and methods comprising proteinase activated receptor antagonists |
| DE102005062990A1 (de) * | 2005-12-28 | 2007-07-05 | Grünenthal GmbH | Substituierte Thiazole und ihre Verwendung zur Herstellung von Arzneimitteln |
| JP5040036B2 (ja) | 2005-12-30 | 2012-10-03 | メルク・シャープ・エンド・ドーム・コーポレイション | Ｃｅｔｐ阻害剤として有用な１，３−オキサゾリジン−２−オン誘導体 |
| US8865707B2 (en) * | 2005-12-30 | 2014-10-21 | Merck Sharp & Dohme Corp. | Cholesteryl ester transfer protein inhibitors |
| WO2007081569A2 (en) | 2005-12-30 | 2007-07-19 | Merck & Co., Inc. | Cetp inhibitors |
| US7781426B2 (en) | 2005-12-30 | 2010-08-24 | Merck Sharp & Dohme Corp. | CETP inhibitors |
| US7998959B2 (en) | 2006-01-12 | 2011-08-16 | Incyte Corporation | Modulators of 11-β hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| RU2455925C2 (ru) | 2006-02-27 | 2012-07-20 | БАЙЕР ХЕЛТКЭА ЭлЭлСи | Определение исследуемого вещества с поправкой на температуру для систем биодатчиков |
| WO2007101270A1 (en) | 2006-03-02 | 2007-09-07 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| US20070208001A1 (en) * | 2006-03-03 | 2007-09-06 | Jincong Zhuo | Modulators of 11- beta hydroxyl steroid dehydrogenase type 1, pharmaceutical compositions thereof, and methods of using the same |
| WO2007109456A2 (en) | 2006-03-16 | 2007-09-27 | Pharmacopeia, Inc. | Substituted biphenyl isoxazole sulfonamides as dual angiotensin endothelin receptor antagonists |
| US7435833B2 (en) | 2006-04-07 | 2008-10-14 | Abbott Laboratories | Inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 enzyme |
| BRPI0710380A2 (pt) | 2006-04-20 | 2011-08-09 | Du Pont | composto, composição, composição de controle de pragas, invertebradas, de pulverização, de isca, dispositivo de armadilha, métodos de controle, métodos de proteção, semente tratada e composição de proteção |
| NZ571175A (en) | 2006-04-21 | 2011-10-28 | Lilly Co Eli | Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US8088776B2 (en) | 2006-04-21 | 2012-01-03 | Eli Lilly And Company | Biphenyl amide lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US7968585B2 (en) | 2006-04-25 | 2011-06-28 | Eli Lilly And Company | Inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| US8178005B2 (en) * | 2006-06-20 | 2012-05-15 | Chemtura Corporation | Liquid phosphite compositions having different alkyl groups |
| TW200811170A (en) | 2006-06-27 | 2008-03-01 | Sanofi Aventis | Urea derivatives of tropane, their preparation and their therapeutic application |
| WO2008012622A2 (en) * | 2006-07-25 | 2008-01-31 | Pfizer Products Inc. | Azabenzimidazolyl compounds as potentiators of mglur2 subtype of glutamate receptor |
| WO2008012623A1 (en) * | 2006-07-25 | 2008-01-31 | Pfizer Products Inc. | Benzimidazolyl compounds as potentiators of mglur2 subtype of glutamate receptor |
| US7618989B2 (en) * | 2006-08-15 | 2009-11-17 | Wyeth | Tricyclic oxazolidone derivatives useful as PR modulators |
| WO2008021337A1 (en) * | 2006-08-15 | 2008-02-21 | Wyeth | Oxazinan-2-one derivatives useful as pr modulators |
| US7649007B2 (en) * | 2006-08-15 | 2010-01-19 | Wyeth Llc | Oxazolidine derivatives as PR modulators |
| EP2064187A2 (en) | 2006-08-25 | 2009-06-03 | Vitae Pharmaceuticals, Inc. | Inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| CA2663280A1 (en) | 2006-09-14 | 2008-03-20 | Neuromed Pharmaceuticals Ltd. | Diaryl piperidine compounds as calcium channel blockers |
| MX2009003080A (es) | 2006-09-22 | 2009-04-02 | Novartis Ag | Compuestos organicos heterociclicos. |
| TW200829171A (en) * | 2006-11-17 | 2008-07-16 | Nihon Nohyaku Co Ltd | Haloalkyl sulfonanilide derivatives or salts thereof, herbicide using it as effective constituent and use-method thereof |
| EP1935420A1 (en) | 2006-12-21 | 2008-06-25 | Merck Sante | 2-Adamantyl-butyramide derivatives as selective 11beta-HSD1 inhibitors |
| US8835426B2 (en) * | 2007-02-26 | 2014-09-16 | Vitae Pharmaceuticals, Inc. | Cyclic urea and carbamate inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| EP2139911A2 (en) | 2007-03-23 | 2010-01-06 | Schering Corporation | Hydrazido-peptides as inhibitors of hcv ns3-protease |
| BRPI0809646A2 (pt) * | 2007-03-29 | 2014-09-23 | Hoffmann La Roche | Compostod antivirais heterocíclicos |
| JP5451611B2 (ja) | 2007-07-26 | 2014-03-26 | 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のサイクリックインヒビター |
| AR069207A1 (es) | 2007-11-07 | 2010-01-06 | Vitae Pharmaceuticals Inc | Ureas ciclicas como inhibidores de la 11 beta - hidroxi-esteroide deshidrogenasa 1 |
| US8859580B2 (en) | 2007-11-16 | 2014-10-14 | Boehringer Ingelheim International Gmbh | Aryl- and heteroarylcarbonyl derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| CA2708303A1 (en) | 2007-12-11 | 2009-06-18 | Vitae Pharmaceuticals, Inc. | Cyclic urea inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
| KR101460359B1 (ko) | 2007-12-13 | 2014-11-10 | 삼성전자주식회사 | 이동통신 시스템에서의 핸드오버 방법 및 장치 |
| TW200934490A (en) | 2008-01-07 | 2009-08-16 | Vitae Pharmaceuticals Inc | Lactam inhibitors of 11 &abgr;-hydroxysteroid dehydrogenase 1 |
| WO2009094169A1 (en) | 2008-01-24 | 2009-07-30 | Vitae Pharmaceuticals, Inc. | Cyclic carbazate and semicarbazide inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2714532A1 (en) * | 2008-02-11 | 2009-08-20 | Vitae Pharmaceuticals, Inc. | 1,3-oxazepan-2-one and 1,3-diazepan-2-one inhibitors of 11.beta.-hydroxysteroid dehydrogenase 1 |
| CA2711757C (en) | 2008-02-12 | 2016-07-26 | Boehringer Ingelheim International Gmbh | Urea derivatives of benzomorphanes and related scaffolds, medicaments containing such compounds and their use |
| US8598160B2 (en) | 2008-02-15 | 2013-12-03 | Vitae Pharmaceuticals, Inc. | Cycloalkyl lactame derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
| EP2265588B1 (en) | 2008-02-27 | 2013-06-26 | Vitae Pharmaceuticals, Inc. | INHIBITORS OF 11ß -HYDROXYSTEROID DEHYDROGENASE TYPE 1 |
| CA2718264A1 (en) | 2008-03-18 | 2009-09-24 | Vitae Pharmaceuticals, Inc. | Inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| TW200944526A (en) | 2008-04-22 | 2009-11-01 | Vitae Pharmaceuticals Inc | Carbamate and urea inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| KR20110002492A (ko) | 2008-05-01 | 2011-01-07 | 비타이 파마슈티컬즈, 인코포레이티드 | 11베타-하이드록시스테로이드 탈수소효소 1의 고리형 억제제 |
| CA2723032A1 (en) | 2008-05-01 | 2009-11-05 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| EP2291370B1 (en) | 2008-05-01 | 2013-11-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| TW201004945A (en) | 2008-05-01 | 2010-02-01 | Vitae Pharmaceuticals Inc | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| US8765780B2 (en) | 2008-05-13 | 2014-07-01 | Boehringer Ingelheim International Gmbh | Alicyclic carboxylic acid derivatives of benzomorphans and related scaffolds, medicaments containing such compounds and their use |
| WO2010010149A1 (en) | 2008-07-23 | 2010-01-28 | Bioalliance Pharma | Styrylquinolines, their process of preparation and their therapeutic uses |
| US20110224242A1 (en) | 2008-07-23 | 2011-09-15 | Bioalliance Pharma | Styrlyquinolines, their process of preparation and their therapeutic uses |
| CA2729993A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Synthesis of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| WO2010011314A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Cyclic inhibitors of 11 beta-hydroxysteroid dehydrogenase 1 |
| US8846668B2 (en) | 2008-07-25 | 2014-09-30 | Vitae Pharmaceuticals, Inc. | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| CA2730208C (en) | 2008-07-25 | 2016-10-25 | Boehringer Ingelheim International Gmbh | 1,1'-diadamantyl carboxylic acids, medicaments containing such compounds and their use |
| CA2735204C (en) | 2008-08-25 | 2017-06-20 | Boehringer Ingelheim International Gmbh | Aryl- and heteroarylcarbonyl derivatives of substituted nortropanes, medicaments containing such compounds and their use |
| CA2738453C (en) | 2008-10-23 | 2017-07-04 | Boehringer Ingelheim International Gmbh | Urea derivatives of substituted nortropanes, medicaments containing such compounds and their use |
| US8598163B2 (en) | 2009-02-04 | 2013-12-03 | Vitae Pharmaceuticals, Inc. | Derivatives of [1,3]Oxazin-2-one useful for the treatment of metabolic diseases such as lipid disorders |
| JP5679997B2 (ja) | 2009-02-04 | 2015-03-04 | 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の環状阻害剤 |
| US8563583B2 (en) | 2009-03-09 | 2013-10-22 | Bristol-Myers Squibb Company | Pyridone analogs useful as melanin concentrating hormone receptor-1 antagonists |
| UA109255C2 (ru) | 2009-04-30 | 2015-08-10 | Берінгер Інгельхайм Інтернешнл Гмбх | Циклические ингибиторы 11бета-гидроксистероиддегидрогеназы 1 |
| KR20120061771A (ko) | 2009-04-30 | 2012-06-13 | 비타이 파마슈티컬즈, 인코포레이티드 | 11베타-하이드록시스테로이드 탈수소효소 1의 고리형 억제제 |
| AR076936A1 (es) | 2009-06-02 | 2011-07-20 | Vitae Pharmaceuticals Inc | Inhibidores de carbamato y urea de la 11 beta hidroxiesteroide deshidrogenasa 1 |
| US8703765B2 (en) | 2009-06-02 | 2014-04-22 | Boehringer Ingelheim International Gmbh | Cyclic inhibitors of 11β-hydroxysteroid dehydrogenase 1 |
| WO2011011123A1 (en) | 2009-06-11 | 2011-01-27 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 based on the 1,3 -oxazinan- 2 -one structure |
| WO2011002910A1 (en) | 2009-07-01 | 2011-01-06 | Vitae Pharmaceuticals, Inc. | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
| MX2012002994A (es) | 2009-09-11 | 2012-07-17 | Cylene Pharmaceuticals Inc | Lactamas heterociclo-substituidas farmaceuticamente utiles. |
| EP2496589B1 (en) | 2009-11-05 | 2014-03-05 | Boehringer Ingelheim International GmbH | Novel chiral phosphorus ligands |
| AR078887A1 (es) | 2009-11-06 | 2011-12-07 | Boehringer Ingelheim Int | Derivados arilo y heteroarilcarbonilo de hexahidroindenopiridina y octahidrobenzoquinolina y composiciones farmaceuticas que los contienen. |
| EP2582698B1 (en) | 2010-06-16 | 2016-09-14 | Vitae Pharmaceuticals, Inc. | Substituted 5-,6- and 7-membered heterocycles, medicaments containing such compounds, and their use |
| WO2011161128A1 (en) | 2010-06-25 | 2011-12-29 | Boehringer Ingelheim International Gmbh | Azaspirohexanones as inhibitors of 11-beta-hsd1 for the treatment of metabolic disorders |
| CA2813671A1 (en) | 2010-11-02 | 2012-05-10 | Boehringer Ingelheim International Gmbh | Pharmaceutical combinations for the treatment of metabolic disorders |
-
2008
- 2008-11-06 AR ARP080104852A patent/AR069207A1/es unknown
- 2008-11-07 TW TW097143034A patent/TW200934495A/zh unknown
- 2008-11-07 CL CL2008003339A patent/CL2008003339A1/es unknown
- 2008-11-07 EP EP08846298.1A patent/EP2220052B1/en not_active Not-in-force
- 2008-11-07 CA CA2704222A patent/CA2704222A1/en not_active Abandoned
- 2008-11-07 US US12/745,663 patent/US9079861B2/en not_active Expired - Fee Related
- 2008-11-07 WO PCT/US2008/012618 patent/WO2009061498A1/en not_active Ceased
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|---|---|
| AR069207A1 (es) | 2010-01-06 |
| CL2008003339A1 (es) | 2009-10-16 |
| TW200934495A (en) | 2009-08-16 |
| EP2220052A1 (en) | 2010-08-25 |
| WO2009061498A1 (en) | 2009-05-14 |
| JP2011503068A (ja) | 2011-01-27 |
| US20100324045A1 (en) | 2010-12-23 |
| JP5695906B2 (ja) | 2015-04-08 |
| US9079861B2 (en) | 2015-07-14 |
| EP2220052B1 (en) | 2015-03-25 |
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