CA2712500A1

CA2712500A1 - Cyclic carbazate and semicarbazide inhibitors of 11beta-hydroxysteroid dehydrogenase 1

Cyclic carbazate and semicarbazide inhibitors of 11beta-hydroxysteroid dehydrogenase 1 Download PDF

Info

Publication number: CA2712500A1
Authority: CA; Canada
Prior art keywords: halo; alkyl; alkoxy; bond; compound
Prior art date: 2008-01-24
Legal status : Abandoned

Application number

CA2712500A

Other languages

English (en)

French (fr)

Inventor

David A. Claremon

Linghang Zhuang

Yuanjie Ye

Suresh B. Singh

Colin M. Tice

Salvacion Cacatian

Current Assignee

Vitae Pharmaceuticals LLC

Original Assignee

Individual

Priority date

2008-01-24

Filing date

2009-01-21

Publication date

2009-07-30

2009-01-21 Application filed by Individual filed Critical Individual

2009-07-30 Publication of CA2712500A1 publication Critical patent/CA2712500A1/en

Status Abandoned legal-status Critical Current

Links

239000003112 inhibitor Substances 0.000 title description 22
102100036506 11-beta-hydroxysteroid dehydrogenase 1 Human genes 0.000 title description 4
125000004122 cyclic group Chemical group 0.000 title description 2
OWIUPIRUAQMTTK-UHFFFAOYSA-M n-aminocarbamate Chemical compound NNC([O-])=O OWIUPIRUAQMTTK-UHFFFAOYSA-M 0.000 title description 2
DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 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 180
150000003839 salts Chemical class 0.000 claims abstract description 46
238000000034 method Methods 0.000 claims abstract description 34
238000011282 treatment Methods 0.000 claims abstract description 27
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
201000010099 disease Diseases 0.000 claims abstract description 16
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
241000124008 Mammalia Species 0.000 claims abstract description 6
125000005843 halogen group Chemical group 0.000 claims description 397
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 208
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 184
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 134
-1 1H-benzimidazol-6-yl Chemical group 0.000 claims description 131
125000003545 alkoxy group Chemical group 0.000 claims description 110
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 97
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 84
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 77
125000000217 alkyl group Chemical group 0.000 claims description 74
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 62
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 56
125000001072 heteroaryl group Chemical group 0.000 claims description 51
125000004043 oxo group Chemical group O=* 0.000 claims description 48
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 42
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 42
125000000000 cycloalkoxy group Chemical group 0.000 claims description 42
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 42
125000005148 cycloalkylalkanesulfinyl group Chemical group 0.000 claims description 42
125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 42
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 38
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 36
125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 36
229910052731 fluorine Inorganic materials 0.000 claims description 36
239000011737 fluorine Substances 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 35
125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 34
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 34
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 30
125000003368 amide group Chemical class 0.000 claims description 28
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 28
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 27
229910052794 bromium Inorganic materials 0.000 claims description 27
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 26
239000000460 chlorine Substances 0.000 claims description 26
229910052801 chlorine Inorganic materials 0.000 claims description 26
125000004093 cyano group Chemical group *C#N 0.000 claims description 26
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 25
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 25
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
125000000623 heterocyclic group Chemical group 0.000 claims description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 21
230000000694 effects Effects 0.000 claims description 21
125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 21
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 18
125000004414 alkyl thio group Chemical group 0.000 claims description 18
125000003118 aryl group Chemical group 0.000 claims description 18
125000001188 haloalkyl group Chemical group 0.000 claims description 17
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 16
125000004076 pyridyl group Chemical group 0.000 claims description 16
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000004663 dialkyl amino group Chemical group 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical group 0.000 claims description 14
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
125000001544 thienyl group Chemical group 0.000 claims description 13
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 12
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 12
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 12
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 12
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 11
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
150000002431 hydrogen Chemical group 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
230000002401 inhibitory effect Effects 0.000 claims description 9
WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 claims description 8
LOZWAPSEEHRYPG-UHFFFAOYSA-N 1,4-dithiane Chemical compound C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 claims description 8
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 8
XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 8
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 8
125000003107 substituted aryl group Chemical group 0.000 claims description 8
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 7
230000014509 gene expression Effects 0.000 claims description 7
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
229910003600 H2NS Inorganic materials 0.000 claims description 6
125000004633 N-oxo-pyridyl group Chemical group 0.000 claims description 6
125000001769 aryl amino group Chemical group 0.000 claims description 6
125000005241 heteroarylamino group Chemical group 0.000 claims description 6
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 6
125000003831 tetrazolyl group Chemical group 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
229920002554 vinyl polymer Chemical group 0.000 claims description 5
ADBZIZGMAVRJPN-UHFFFAOYSA-N 1,2,5-thiadiazolidine 1,1-dioxide Chemical compound O=S1(=O)NCCN1 ADBZIZGMAVRJPN-UHFFFAOYSA-N 0.000 claims description 4
CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims description 4
XGYCWCIGCYGQFU-UHFFFAOYSA-N 1,2-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCCN1 XGYCWCIGCYGQFU-UHFFFAOYSA-N 0.000 claims description 4
NQPJDJVGBDHCAD-UHFFFAOYSA-N 1,3-diazinan-2-one Chemical compound OC1=NCCCN1 NQPJDJVGBDHCAD-UHFFFAOYSA-N 0.000 claims description 4
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 claims description 4
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 4
IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 claims description 4
OYELEBBISJGNHJ-UHFFFAOYSA-N 1,3-oxazinan-2-one Chemical compound O=C1NCCCO1 OYELEBBISJGNHJ-UHFFFAOYSA-N 0.000 claims description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 4
GFPOCAYEKCWFPD-UHFFFAOYSA-N 1-(2,2,2-trifluoroethyl)piperazine Chemical compound FC(F)(F)CN1CCNCC1 GFPOCAYEKCWFPD-UHFFFAOYSA-N 0.000 claims description 4
DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 4
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 4
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
IHXNIOYEXQWUNI-UHFFFAOYSA-N 4,5-dihydro-1h-pyrimidin-6-one Chemical compound O=C1CCN=CN1 IHXNIOYEXQWUNI-UHFFFAOYSA-N 0.000 claims description 4
GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 claims description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 4
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 4
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 4
YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims description 4
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 4
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 4
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 4
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 4
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 4
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 4
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 4
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 4
DNGMYXZLJGHHOM-UHFFFAOYSA-N thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCCCN1 DNGMYXZLJGHHOM-UHFFFAOYSA-N 0.000 claims description 4
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 4
LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000005529 alkyleneoxy group Chemical group 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004212 difluorophenyl group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000006262 isopropyl amino sulfonyl group Chemical group 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
125000002757 morpholinyl group Chemical group 0.000 claims description 3
125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
125000003386 piperidinyl group Chemical group 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 2
GAJATKJMGCIIQL-UHFFFAOYSA-N 6-(4-fluorophenyl)-3-(n-methylanilino)-6-prop-2-enyl-1,3-oxazinan-2-one Chemical compound C=1C=CC=CC=1N(C)N(C(O1)=O)CCC1(CC=C)C1=CC=C(F)C=C1 GAJATKJMGCIIQL-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000001207 fluorophenyl group Chemical group 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
125000006531 (C2-C5) alkyl group Chemical group 0.000 claims 1
125000006532 (C3-C5) alkyl group Chemical group 0.000 claims 1
125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims 1
125000004966 cyanoalkyl group Chemical group 0.000 claims 1
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
229910052717 sulfur Inorganic materials 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 26
229960000890 hydrocortisone Drugs 0.000 abstract description 19
230000005764 inhibitory process Effects 0.000 abstract description 13
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
230000009467 reduction Effects 0.000 abstract description 9
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
229960004544 cortisone Drugs 0.000 abstract description 7
238000004519 manufacturing process Methods 0.000 abstract description 5
230000001225 therapeutic effect Effects 0.000 abstract description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 173
239000003862 glucocorticoid Substances 0.000 description 30
239000000203 mixture Substances 0.000 description 22
RDOXTESZEPMUJZ-UHFFFAOYSA-N methyl phenyl ether Natural products COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 21
125000003282 alkyl amino group Chemical group 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
239000000543 intermediate Substances 0.000 description 17
239000000243 solution Substances 0.000 description 14
229940037128 systemic glucocorticoids Drugs 0.000 description 14
210000004027 cell Anatomy 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
206010020772 Hypertension Diseases 0.000 description 11
239000004480 active ingredient Substances 0.000 description 11
239000003153 chemical reaction reagent Substances 0.000 description 11
229910052740 iodine Inorganic materials 0.000 description 11
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
125000001424 substituent group Chemical group 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
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