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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- C07D401/04—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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| TW (1) | TW200934495A (enExample) |
| WO (1) | WO2009061498A1 (enExample) |
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| EP2252601B1 (en) | 2008-01-24 | 2012-12-19 | 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 |
| JP5730021B2 (ja) * | 2008-02-15 | 2015-06-03 | 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の阻害剤としてのシクロアルキルラクタム誘導体 |
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| JP5390610B2 (ja) | 2008-07-25 | 2014-01-15 | 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型の阻害剤の合成 |
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| UA109255C2 (ru) | 2009-04-30 | 2015-08-10 | Берінгер Інгельхайм Інтернешнл Гмбх | Циклические ингибиторы 11бета-гидроксистероиддегидрогеназы 1 |
| JP5670440B2 (ja) * | 2009-06-02 | 2015-02-18 | 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 |
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-
2008
- 2008-11-06 AR ARP080104852A patent/AR069207A1/es unknown
- 2008-11-07 CL CL2008003339A patent/CL2008003339A1/es unknown
- 2008-11-07 US US12/745,663 patent/US9079861B2/en not_active Expired - Fee Related
- 2008-11-07 JP JP2010533113A patent/JP5695906B2/ja not_active Expired - Fee Related
- 2008-11-07 CA CA2704222A patent/CA2704222A1/en not_active Abandoned
- 2008-11-07 TW TW097143034A patent/TW200934495A/zh unknown
- 2008-11-07 WO PCT/US2008/012618 patent/WO2009061498A1/en not_active Ceased
- 2008-11-07 EP EP08846298.1A patent/EP2220052B1/en not_active Not-in-force
Also Published As
| Publication number | Publication date |
|---|---|
| EP2220052A1 (en) | 2010-08-25 |
| EP2220052B1 (en) | 2015-03-25 |
| CL2008003339A1 (es) | 2009-10-16 |
| JP5695906B2 (ja) | 2015-04-08 |
| US20100324045A1 (en) | 2010-12-23 |
| WO2009061498A1 (en) | 2009-05-14 |
| JP2011503068A (ja) | 2011-01-27 |
| TW200934495A (en) | 2009-08-16 |
| US9079861B2 (en) | 2015-07-14 |
| AR069207A1 (es) | 2010-01-06 |
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