CA2715290A1 - Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 - Google Patents
Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 Download PDFInfo
- Publication number
- CA2715290A1 CA2715290A1 CA2715290A CA2715290A CA2715290A1 CA 2715290 A1 CA2715290 A1 CA 2715290A1 CA 2715290 A CA2715290 A CA 2715290A CA 2715290 A CA2715290 A CA 2715290A CA 2715290 A1 CA2715290 A1 CA 2715290A1
- Authority
- CA
- Canada
- Prior art keywords
- halo
- alkyl
- alkoxy
- compound
- bond
- 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
- 239000003112 inhibitor Substances 0.000 title description 23
- 102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title description 2
- 101710186107 11-beta-hydroxysteroid dehydrogenase 1 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 342
- 150000003839 salts Chemical class 0.000 claims abstract description 147
- 238000000034 method Methods 0.000 claims abstract description 44
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 125000005843 halogen group Chemical group 0.000 claims description 514
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 284
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 224
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 161
- 125000003545 alkoxy group Chemical group 0.000 claims description 151
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 122
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 113
- -1 cyano, carboxy Chemical group 0.000 claims description 109
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 101
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 90
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 63
- 125000001072 heteroaryl group Chemical group 0.000 claims description 62
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 56
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 54
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 54
- 125000004043 oxo group Chemical group O=* 0.000 claims description 54
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 53
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 52
- 125000005148 cycloalkylalkanesulfinyl group Chemical group 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 46
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 45
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 44
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 44
- 239000011737 fluorine Substances 0.000 claims description 43
- 229910052731 fluorine Inorganic materials 0.000 claims description 43
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 41
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 41
- 125000003282 alkyl amino group Chemical group 0.000 claims description 40
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 35
- 229910052794 bromium Inorganic materials 0.000 claims description 35
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 33
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 33
- 239000003862 glucocorticoid Substances 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 239000000460 chlorine Substances 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 29
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 26
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 24
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000001188 haloalkyl group Chemical group 0.000 claims description 22
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 20
- 125000003368 amide group Chemical class 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical group 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 206010020772 Hypertension Diseases 0.000 claims description 13
- 208000008589 Obesity Diseases 0.000 claims description 13
- 235000020824 obesity Nutrition 0.000 claims description 13
- 206010012601 diabetes mellitus Diseases 0.000 claims description 12
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 11
- 125000005145 cycloalkylaminosulfonyl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 10
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 208000010412 Glaucoma Diseases 0.000 claims description 9
- 230000014509 gene expression Effects 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 8
- 125000004633 N-oxo-pyridyl group Chemical group 0.000 claims description 8
- 208000001132 Osteoporosis Diseases 0.000 claims description 8
- 125000001769 aryl amino group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 206010022489 Insulin Resistance Diseases 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 208000014311 Cushing syndrome Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 6
- 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 5
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 5
- 206010024229 Leprosy Diseases 0.000 claims description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 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 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 208000024891 symptom Diseases 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 208000026872 Addison Disease Diseases 0.000 claims description 4
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 4
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 4
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 claims description 4
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 210000001596 intra-abdominal fat Anatomy 0.000 claims description 4
- 125000006262 isopropyl amino sulfonyl group Chemical group 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 201000008827 tuberculosis Diseases 0.000 claims description 4
- MYYQROWSYYOFPQ-INIZCTEOSA-N (6s)-3-(3-methylphenyl)-6-phenyl-1,3-oxazinan-2-one Chemical compound CC1=CC=CC(N2C(O[C@@H](CC2)C=2C=CC=CC=2)=O)=C1 MYYQROWSYYOFPQ-INIZCTEOSA-N 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- NLNCGJATPOBNNC-UHFFFAOYSA-N 3-(3-bromophenyl)-6-(2-chlorophenyl)-1,3-oxazinan-2-one Chemical compound ClC1=CC=CC=C1C1OC(=O)N(C=2C=C(Br)C=CC=2)CC1 NLNCGJATPOBNNC-UHFFFAOYSA-N 0.000 claims description 3
- JHZCLTDWJFCBMR-WHUIICBVSA-N 3-[(1s)-1-(4-bromophenyl)ethyl]-6-(4-fluorophenyl)-1,3-oxazinan-2-one Chemical compound O1C(=O)N([C@@H](C)C=2C=CC(Br)=CC=2)CCC1C1=CC=C(F)C=C1 JHZCLTDWJFCBMR-WHUIICBVSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 3
- 206010054834 Hypergonadism Diseases 0.000 claims description 3
- 206010049287 Lipodystrophy acquired Diseases 0.000 claims description 3
- 230000007000 age related cognitive decline Effects 0.000 claims description 3
- 230000006999 cognitive decline Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 208000000509 infertility Diseases 0.000 claims description 3
- 230000036512 infertility Effects 0.000 claims description 3
- 231100000535 infertility Toxicity 0.000 claims description 3
- 208000006132 lipodystrophy Diseases 0.000 claims description 3
- MYYQROWSYYOFPQ-MRXNPFEDSA-N (6r)-3-(3-methylphenyl)-6-phenyl-1,3-oxazinan-2-one Chemical compound CC1=CC=CC(N2C(O[C@H](CC2)C=2C=CC=CC=2)=O)=C1 MYYQROWSYYOFPQ-MRXNPFEDSA-N 0.000 claims description 2
- DQERNZFWFBSRPE-LJQANCHMSA-N (6r)-3-naphthalen-1-yl-6-phenyl-1,3-oxazinan-2-one Chemical compound C1([C@@H]2OC(N(CC2)C=2C3=CC=CC=C3C=CC=2)=O)=CC=CC=C1 DQERNZFWFBSRPE-LJQANCHMSA-N 0.000 claims description 2
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- JTEKTTBQNYWHKC-PBVYKCSPSA-N 1-[(1s)-1-[4-(2,4-difluorophenyl)phenyl]ethyl]-4-phenylpiperidin-2-one Chemical compound C1C(=O)N([C@@H](C)C=2C=CC(=CC=2)C=2C(=CC(F)=CC=2)F)CCC1C1=CC=CC=C1 JTEKTTBQNYWHKC-PBVYKCSPSA-N 0.000 claims description 2
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 2
- 125000004212 difluorophenyl group Chemical group 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 73
- 206010036049 Polycystic ovaries Diseases 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- QMCYJQJOFOLKJV-BUSXIPJBSA-N 4-phenyl-1-[(1s)-1-phenylethyl]-1,3-diazepan-2-one Chemical compound N1C(=O)N([C@@H](C)C=2C=CC=CC=2)CCCC1C1=CC=CC=C1 QMCYJQJOFOLKJV-BUSXIPJBSA-N 0.000 claims 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims 1
- 102200077464 rs398122966 Human genes 0.000 claims 1
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 abstract description 39
- 238000006243 chemical reaction Methods 0.000 abstract description 27
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- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 abstract description 10
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 abstract description 10
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 abstract description 7
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
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- 239000000243 solution Substances 0.000 description 31
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
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- 210000004027 cell Anatomy 0.000 description 15
- 239000007832 Na2SO4 Substances 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 229940037128 systemic glucocorticoids Drugs 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
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- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 10
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
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- 210000001519 tissue Anatomy 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
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- 229910000085 borane Inorganic materials 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 210000000229 preadipocyte Anatomy 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 6
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- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- DNGMYXZLJGHHOM-UHFFFAOYSA-N thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCCCN1 DNGMYXZLJGHHOM-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/06—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings
- C07D265/08—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D265/10—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen atoms directly attached to ring carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (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)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
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- Endocrinology (AREA)
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- Neurology (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Pregnancy & Childbirth (AREA)
- Pulmonology (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6589008P | 2008-02-15 | 2008-02-15 | |
| US61/065,890 | 2008-02-15 | ||
| PCT/US2009/000908 WO2009102460A2 (en) | 2008-02-15 | 2009-02-13 | Inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2715290A1 true CA2715290A1 (en) | 2009-08-20 |
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| CA (1) | CA2715290A1 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009102460A2 (cg-RX-API-DMAC7.html) |
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-
2009
- 2009-02-13 EP EP20090709458 patent/EP2254872A2/en not_active Withdrawn
- 2009-02-13 JP JP2010546784A patent/JP5730021B2/ja not_active Expired - Fee Related
- 2009-02-13 US US12/867,374 patent/US8598160B2/en not_active Expired - Fee Related
- 2009-02-13 CA CA2715290A patent/CA2715290A1/en not_active Abandoned
- 2009-02-13 WO PCT/US2009/000908 patent/WO2009102460A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US20110071139A1 (en) | 2011-03-24 |
| WO2009102460A2 (en) | 2009-08-20 |
| US8598160B2 (en) | 2013-12-03 |
| JP2011512352A (ja) | 2011-04-21 |
| EP2254872A2 (en) | 2010-12-01 |
| JP5730021B2 (ja) | 2015-06-03 |
| WO2009102460A3 (en) | 2009-11-05 |
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