UA126584C2 - Похідні гліцирретинової кислоти для лікування гіперкаліємії - Google Patents

Info

Publication number

UA126584C2

UA126584C2 UAA202001392A UAA202001392A UA126584C2 UA 126584 C2 UA126584 C2 UA 126584C2 UA A202001392 A UAA202001392 A UA A202001392A UA A202001392 A UAA202001392 A UA A202001392A UA 126584 C2 UA126584 C2 UA 126584C2

Authority

UA

Ukraine

Prior art keywords

ethoxy

dihydro

inden

oxy

dichloro

Prior art date

2017-08-04

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• 208000002682 Hyperkalemia Diseases 0.000 title claims abstract description 29
• 239000002253 acid Substances 0.000 title description 17
• 150000001875 compounds Chemical class 0.000 claims abstract description 187
• 150000003839 salts Chemical class 0.000 claims abstract description 40
• -1 alkoxyacyloxy Chemical group 0.000 claims description 255
• 125000000217 alkyl group Chemical group 0.000 claims description 112
• 125000000623 heterocyclic group Chemical group 0.000 claims description 94
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 90
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
• 125000001072 heteroaryl group Chemical group 0.000 claims description 47
• 229910052736 halogen Inorganic materials 0.000 claims description 41
• 150000002367 halogens Chemical group 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 39
• 229910052799 carbon Inorganic materials 0.000 claims description 35
• 125000002947 alkylene group Chemical group 0.000 claims description 33
• 125000004043 oxo group Chemical group O=* 0.000 claims description 30
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
• 125000001188 haloalkyl group Chemical group 0.000 claims description 10
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 125000004423 acyloxy group Chemical group 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
• 208000035475 disorder Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
• 150000003852 triazoles Chemical group 0.000 claims description 2
• 201000010099 disease Diseases 0.000 claims 1
• 239000003112 inhibitor Substances 0.000 abstract description 58
• 102000004277 11-beta-hydroxysteroid dehydrogenases Human genes 0.000 abstract description 2
• 108090000874 11-beta-hydroxysteroid dehydrogenases Proteins 0.000 abstract description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 457
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• 239000007787 solid Substances 0.000 description 183
• 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 174
• 238000003786 synthesis reaction Methods 0.000 description 135
• 230000015572 biosynthetic process Effects 0.000 description 133
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
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• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 80
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 74
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 62
• 229910052700 potassium Inorganic materials 0.000 description 62
• 239000011591 potassium Substances 0.000 description 62
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• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
• 239000012043 crude product Substances 0.000 description 57
• 229910052739 hydrogen Inorganic materials 0.000 description 57
• CNWSQCLBDWYLAN-UHFFFAOYSA-N butylurea Chemical compound CCCCNC(N)=O CNWSQCLBDWYLAN-UHFFFAOYSA-N 0.000 description 56
• 238000002953 preparative HPLC Methods 0.000 description 51
• 238000005160 1H NMR spectroscopy Methods 0.000 description 49
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
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• 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 43
• 150000003384 small molecules Chemical class 0.000 description 43
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 42
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 41
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• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 28
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• 239000012298 atmosphere Substances 0.000 description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
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• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 24
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• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 20
• 239000011780 sodium chloride Substances 0.000 description 20
• 125000005647 linker group Chemical group 0.000 description 19
• 239000012044 organic layer Substances 0.000 description 19
• 238000003756 stirring Methods 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• 239000007864 aqueous solution Substances 0.000 description 18
• MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 17
• 125000005842 heteroatom Chemical group 0.000 description 17
• 229910052757 nitrogen Inorganic materials 0.000 description 17
• 239000000047 product Substances 0.000 description 17
• MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 description 16
• 125000001424 substituent group Chemical group 0.000 description 16
• 239000000556 agonist Substances 0.000 description 15
• 229960000890 hydrocortisone Drugs 0.000 description 15
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• 230000029142 excretion Effects 0.000 description 14
• 125000003545 alkoxy group Chemical group 0.000 description 13
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
• 229910052760 oxygen Inorganic materials 0.000 description 13
• 238000006243 chemical reaction Methods 0.000 description 12
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• 235000019439 ethyl acetate Nutrition 0.000 description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
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• 239000003814 drug Substances 0.000 description 11
• 150000002431 hydrogen Chemical group 0.000 description 11
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• 101000964584 Homo sapiens Zinc finger protein 160 Proteins 0.000 description 10
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