KR20150124985A - 베타-세크레타제 억제제로서 퍼플루오르화된 사이클로프로필 융합된 1,3-옥사진-2-아민 화합물 및 그의 사용 방법 - Google Patents

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Publication number

KR20150124985A

KR20150124985A KR1020157026887A KR20157026887A KR20150124985A KR 20150124985 A KR20150124985 A KR 20150124985A KR 1020157026887 A KR1020157026887 A KR 1020157026887A KR 20157026887 A KR20157026887 A KR 20157026887A KR 20150124985 A KR20150124985 A KR 20150124985A

Authority

KR

South Korea

Prior art keywords

alkyl

independently

stereoisomer

acceptable salt

pharmaceutically acceptable

Prior art date

2013-03-08

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.)

Withdrawn

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• 238000000034 method Methods 0.000 title claims abstract description 70
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• RWRGWJAYHSYMIU-UHFFFAOYSA-N 2H-1,3-oxazin-2-amine Chemical class NC1OC=CC=N1 RWRGWJAYHSYMIU-UHFFFAOYSA-N 0.000 title 1
• 239000002439 beta secretase inhibitor Substances 0.000 title 1
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• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 38
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• 238000011282 treatment Methods 0.000 claims abstract description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
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• 208000010877 cognitive disease Diseases 0.000 claims abstract description 3
• -1 CH 2 OH Chemical group 0.000 claims description 644
• 229910052731 fluorine Inorganic materials 0.000 claims description 252
• 150000003839 salts Chemical class 0.000 claims description 187
• 229910052739 hydrogen Inorganic materials 0.000 claims description 184
• 229910052801 chlorine Inorganic materials 0.000 claims description 123
• 125000000217 alkyl group Chemical group 0.000 claims description 117
• 125000003545 alkoxy group Chemical group 0.000 claims description 71
• 125000001424 substituent group Chemical group 0.000 claims description 69
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 67
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 64
• 125000003342 alkenyl group Chemical group 0.000 claims description 63
• 125000000304 alkynyl group Chemical group 0.000 claims description 63
• 125000005842 heteroatom Chemical group 0.000 claims description 55
• 229910052757 nitrogen Inorganic materials 0.000 claims description 52
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 50
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 49
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 46
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 46
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 46
• 229910052760 oxygen Inorganic materials 0.000 claims description 45
• 229910052799 carbon Inorganic materials 0.000 claims description 42
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 42
• 125000002757 morpholinyl group Chemical group 0.000 claims description 42
• 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims description 41
• 125000002619 bicyclic group Chemical group 0.000 claims description 40
• 125000002950 monocyclic group Chemical group 0.000 claims description 39
• 125000005843 halogen group Chemical group 0.000 claims description 35
• 229910052717 sulfur Inorganic materials 0.000 claims description 34
• 125000001188 haloalkyl 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
• 125000000335 thiazolyl group Chemical group 0.000 claims description 30
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 29
• 229910052794 bromium Inorganic materials 0.000 claims description 27
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 25
• 125000004432 carbon atom Chemical group C* 0.000 claims description 24
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 24
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 24
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 24
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 23
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 23
• 125000004193 piperazinyl group Chemical group 0.000 claims description 23
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 21
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• 125000005309 thioalkoxy group Chemical group 0.000 claims description 21
• 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 20
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 19
• 239000012453 solvate Substances 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
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• 125000004076 pyridyl group Chemical group 0.000 claims description 15
• 210000004556 brain Anatomy 0.000 claims description 14
• 125000001153 fluoro group Chemical group F* 0.000 claims description 13
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• 125000003373 pyrazinyl group Chemical group 0.000 claims description 11
• 201000010099 disease Diseases 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000002971 oxazolyl group Chemical group 0.000 claims description 9
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
• IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 206010012289 Dementia Diseases 0.000 claims description 5
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
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• 229940079593 drug Drugs 0.000 claims description 4
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• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 3
• 125000004414 alkyl thio group Chemical group 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 208000012902 Nervous system disease Diseases 0.000 claims description 2
• 208000025966 Neurological disease Diseases 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• 230000007850 degeneration Effects 0.000 claims description 2
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 11
• 239000013043 chemical agent Substances 0.000 claims 6
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical group OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 4
• 229940125810 compound 20 Drugs 0.000 claims 2
• 208000027089 Parkinsonian disease Diseases 0.000 claims 1
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• 239000012190 activator Substances 0.000 claims 1
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