JP2018507226A5 - - Google Patents

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Publication number

JP2018507226A5

JP2018507226A5 JP2017545908A JP2017545908A JP2018507226A5 JP 2018507226 A5 JP2018507226 A5 JP 2018507226A5 JP 2017545908 A JP2017545908 A JP 2017545908A JP 2017545908 A JP2017545908 A JP 2017545908A JP 2018507226 A5 JP2018507226 A5 JP 2018507226A5

Authority

JP

Japan

Prior art keywords

group

alkyl

ring

combination

hydrogen

Prior art date

2016-02-25

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.)

Granted

Links

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• 125000000217 alkyl group Chemical group 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 38
• 229940126013 glucocorticoid receptor antagonist Drugs 0.000 claims description 29
• 239000003850 glucocorticoid receptor antagonist Substances 0.000 claims description 29
• 239000001257 hydrogen Substances 0.000 claims description 28
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
• 229910052736 halogen Inorganic materials 0.000 claims description 22
• 150000002367 halogens Chemical class 0.000 claims description 22
• 239000000275 Adrenocorticotropic Hormone Substances 0.000 claims description 20
• 101800000414 Corticotropin Proteins 0.000 claims description 20
• 102100027467 Pro-opiomelanocortin Human genes 0.000 claims description 20
• IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 20
• 229960000258 corticotropin Drugs 0.000 claims description 20
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 19
• 125000003545 alkoxy group Chemical group 0.000 claims description 18
• 125000001072 heteroaryl group Chemical group 0.000 claims description 18
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 14
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 14
• 206010028980 Neoplasm Diseases 0.000 claims description 14
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 125000005842 heteroatom Chemical group 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 125000003118 aryl group Chemical group 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• -1 dimethylaminophenyl moiety Chemical group 0.000 claims description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 8
• 239000000203 mixture Substances 0.000 claims description 8
• 150000003839 salts Chemical class 0.000 claims description 8
• 230000003248 secreting effect Effects 0.000 claims description 8
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
• 150000003431 steroids Chemical group 0.000 claims description 6
• 102000005157 Somatostatin Human genes 0.000 claims description 5
• 108010056088 Somatostatin Proteins 0.000 claims description 5
• 229960000553 somatostatin Drugs 0.000 claims description 5
• PUDHBTGHUJUUFI-SCTWWAJVSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-p Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 PUDHBTGHUJUUFI-SCTWWAJVSA-N 0.000 claims description 4
• YJDDXMSIMBMMGY-UHFFFAOYSA-N 2-cyclohexylpyrimidine Chemical group C1CCCCC1C1=NC=CC=N1 YJDDXMSIMBMMGY-UHFFFAOYSA-N 0.000 claims description 4
• 150000001204 N-oxides Chemical class 0.000 claims description 4
• 229960002437 lanreotide Drugs 0.000 claims description 4
• 229960002700 octreotide Drugs 0.000 claims description 4
• 125000006413 ring segment Chemical group 0.000 claims description 4
• 230000028327 secretion Effects 0.000 claims description 4
• 230000001225 therapeutic effect Effects 0.000 claims description 4
• DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 claims description 3
• 238000009472 formulation Methods 0.000 claims description 3
• 108010021336 lanreotide Proteins 0.000 claims description 3
• 238000013268 sustained release Methods 0.000 claims description 3
• 239000012730 sustained-release form Substances 0.000 claims description 3
• ZCAUIZYRNPHJJO-CAMMJAKZSA-N (8s,10s,13s,14s)-10,13-dimethyl-1,2,6,7,8,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C([C@H]12)CC3=CC(=O)CC[C@]3(C)C1=CC[C@@]1(C)[C@H]2CCC1 ZCAUIZYRNPHJJO-CAMMJAKZSA-N 0.000 claims description 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• 208000007740 Ectopic ACTH Syndrome Diseases 0.000 claims description 2
• 102000003676 Glucocorticoid Receptors Human genes 0.000 claims description 2
• 108090000079 Glucocorticoid Receptors Proteins 0.000 claims description 2
• 206010052399 Neuroendocrine tumour Diseases 0.000 claims description 2
• 108010016076 Octreotide Proteins 0.000 claims description 2
• 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 claims description 2
• 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 claims description 2
• 229940124639 Selective inhibitor Drugs 0.000 claims description 2
• 125000002947 alkylene group Chemical group 0.000 claims description 2
• 208000011590 ectopic ACTH secretion syndrome Diseases 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
• VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical group C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 claims description 2
• 229960003248 mifepristone Drugs 0.000 claims description 2
• 208000016065 neuroendocrine neoplasm Diseases 0.000 claims description 2
• 201000011519 neuroendocrine tumor Diseases 0.000 claims description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
• CFODQUSMSYDHBS-UHFFFAOYSA-N octreotate Chemical compound O=C1NC(CC=2C=CC=CC=2)C(=O)NC(CC=2[C]3C=CC=CC3=NC=2)C(=O)NC(CCCCN)C(=O)NC(C(C)O)C(=O)NC(C(=O)NC(C(O)C)C(O)=O)CSSCC1NC(=O)C(N)CC1=CC=CC=C1 CFODQUSMSYDHBS-UHFFFAOYSA-N 0.000 claims description 2
• 125000004043 oxo group Chemical group O=* 0.000 claims description 2
• VMZMNAABQBOLAK-DBILLSOUSA-N pasireotide Chemical compound C([C@H]1C(=O)N2C[C@@H](C[C@H]2C(=O)N[C@H](C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](C(N[C@@H](CC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(=O)N1)=O)CCCCN)C=1C=CC=CC=1)OC(=O)NCCN)C1=CC=CC=C1 VMZMNAABQBOLAK-DBILLSOUSA-N 0.000 claims description 2
• 108700017947 pasireotide Proteins 0.000 claims description 2
• 229960005415 pasireotide Drugs 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 230000003637 steroidlike Effects 0.000 claims description 2
• 125000003944 tolyl group Chemical group 0.000 claims description 2
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
• 238000000034 method Methods 0.000 description 29
• 0 CCc1cc(C[C@](**)(CN(C)CC2)C2=C2)c2[n]1* Chemical compound CCc1cc(C[C@](**)(CN(C)CC2)C2=C2)c2[n]1* 0.000 description 2
• 150000001875 compounds Chemical class 0.000 description 1