JP5579720B2 - ベータ−セクレターゼ調節物質としてのスピロ四環式化合物および使用法 - Google Patents

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Publication number

JP5579720B2

JP5579720B2 JP2011527012A JP2011527012A JP5579720B2 JP 5579720 B2 JP5579720 B2 JP 5579720B2 JP 2011527012 A JP2011527012 A JP 2011527012A JP 2011527012 A JP2011527012 A JP 2011527012A JP 5579720 B2 JP5579720 B2 JP 5579720B2

Authority

JP

Japan

Prior art keywords

spiro

oxazole

alkyl

amine

xanthene

Prior art date

2008-09-11

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.)

Expired - Fee Related

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• 150000001875 compounds Chemical class 0.000 title claims description 194
• 238000000034 method Methods 0.000 title claims description 121
• 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title description 13
• 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title description 12
• 125000003003 spiro group Chemical group 0.000 title description 8
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 336
• -1 C 1-6 -alkyl Chemical group 0.000 claims description 284
• 125000005843 halogen group Chemical group 0.000 claims description 94
• 125000001188 haloalkyl group Chemical group 0.000 claims description 90
• 125000001424 substituent group Chemical group 0.000 claims description 78
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 75
• 229920006395 saturated elastomer Polymers 0.000 claims description 73
• 229910052760 oxygen Inorganic materials 0.000 claims description 69
• 125000005842 heteroatom Chemical group 0.000 claims description 67
• 125000002950 monocyclic group Chemical group 0.000 claims description 60
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 59
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 56
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 55
• 125000002619 bicyclic group Chemical group 0.000 claims description 54
• 150000003839 salts Chemical class 0.000 claims description 53
• 229910052757 nitrogen Inorganic materials 0.000 claims description 52
• 229910052731 fluorine Inorganic materials 0.000 claims description 50
• 125000004432 carbon atom Chemical group C* 0.000 claims description 49
• 229910052739 hydrogen Inorganic materials 0.000 claims description 45
• 125000004122 cyclic group Chemical group 0.000 claims description 42
• 229910052801 chlorine Inorganic materials 0.000 claims description 40
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• 229910052717 sulfur Inorganic materials 0.000 claims description 35
• 125000003118 aryl group Chemical group 0.000 claims description 34
• 208000024827 Alzheimer disease Diseases 0.000 claims description 33
• 125000000217 alkyl group Chemical group 0.000 claims description 33
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 32
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 31
• 229910052794 bromium Inorganic materials 0.000 claims description 29
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 26
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
• 229910052740 iodine Inorganic materials 0.000 claims description 21
• 125000001072 heteroaryl group Chemical group 0.000 claims description 19
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 18
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
• 125000004076 pyridyl group Chemical group 0.000 claims description 18
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
• 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 17
• 125000000623 heterocyclic group Chemical group 0.000 claims description 17
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 17
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 17
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 17
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 17
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
• QMYGFTJCQFEDST-UHFFFAOYSA-N 3-methoxybutyl acetate Chemical group COC(C)CCOC(C)=O QMYGFTJCQFEDST-UHFFFAOYSA-N 0.000 claims description 16
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
• 210000004556 brain Anatomy 0.000 claims description 16
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 125000004043 oxo group Chemical group O=* 0.000 claims description 16
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 16
• 125000006546 (C4-C10) cycloalkyl group Chemical group 0.000 claims description 14
• DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=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](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 13
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 13
• 125000004306 triazinyl group Chemical group 0.000 claims description 13
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
• 125000001544 thienyl group Chemical group 0.000 claims description 12
• 239000003814 drug Substances 0.000 claims description 11
• 125000002755 pyrazolinyl group Chemical group 0.000 claims description 11
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
• 125000002883 imidazolyl group Chemical group 0.000 claims description 10
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 10
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
• 125000002757 morpholinyl group Chemical group 0.000 claims description 10
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 10
• 125000004193 piperazinyl group Chemical group 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 10
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 10
• 125000000335 thiazolyl group Chemical group 0.000 claims description 10
• 125000001425 triazolyl group Chemical group 0.000 claims description 10
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 9
• 125000002541 furyl group Chemical group 0.000 claims description 9
• 125000003971 isoxazolinyl group Chemical group 0.000 claims description 9
• 125000005968 oxazolinyl group Chemical group 0.000 claims description 9
• 125000002971 oxazolyl group Chemical group 0.000 claims description 9
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
• 238000011282 treatment Methods 0.000 claims description 9
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 7
• NFVPWQQNOBOLMK-UHFFFAOYSA-N spiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=NC21C1=CC=CC=C1OC1=CC=CC=C12 NFVPWQQNOBOLMK-UHFFFAOYSA-N 0.000 claims description 7
• 206010012289 Dementia Diseases 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 230000007505 plaque formation Effects 0.000 claims description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
• CHZHWZAKWGFQNL-UHFFFAOYSA-N 2'-(2,2-dimethylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)(C)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2C21COC(N)=N2 CHZHWZAKWGFQNL-UHFFFAOYSA-N 0.000 claims description 5
• GXLBLAWTCDBEDC-UHFFFAOYSA-N 2'-propoxy-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCCC)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2C21COC(N)=N2 GXLBLAWTCDBEDC-UHFFFAOYSA-N 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• KHZHMWVTRYYGRT-SANMLTNESA-N (4s)-2'-(2,2-dimethylmorpholin-4-yl)-7'-(2-fluoropyridin-3-yl)spiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1COC(C)(C)CN1C1=CC=C(OC=2C(=CC(=CC=2)C=2C(=NC=CC=2)F)[C@]23N=C(N)OC3)C2=C1 KHZHMWVTRYYGRT-SANMLTNESA-N 0.000 claims description 4
• FBJBTFVUBFBZJR-QHCPKHFHSA-N (4s)-2'-(2-fluoro-2-methylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)(F)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 FBJBTFVUBFBZJR-QHCPKHFHSA-N 0.000 claims description 4
• WEUXIWLHTBHAJR-VWLOTQADSA-N (4s)-3'-(3,3-dimethylbut-1-ynyl)-7'-pyridin-3-ylspiro[5h-1,3-oxazole-4,5'-chromeno[2,3-b]pyridine]-2-amine Chemical compound C12=CC(C#CC(C)(C)C)=CN=C2OC2=CC=C(C=3C=NC=CC=3)C=C2[C@]21COC(N)=N2 WEUXIWLHTBHAJR-VWLOTQADSA-N 0.000 claims description 4
• BUCRNQGNPSKQGY-DEOSSOPVSA-N (4s)-3'-(3,3-dimethylbut-1-ynyl)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,5'-chromeno[2,3-b]pyridine]-2-amine Chemical compound C12=CC(C#CC(C)(C)C)=CN=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 BUCRNQGNPSKQGY-DEOSSOPVSA-N 0.000 claims description 4
• PFKCYCIUJHGSHR-UHFFFAOYSA-N 2'-chloro-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=NC21C1=CC(C=3C=NC=NC=3)=CC=C1OC1=CC=C(Cl)C=C12 PFKCYCIUJHGSHR-UHFFFAOYSA-N 0.000 claims description 4
• 208000010877 cognitive disease Diseases 0.000 claims description 4
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
• HBGLVJABBICLQC-RUZDIDTESA-N (4r)-2'-(3,3-dimethylbut-1-ynyl)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(C#CC(C)(C)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 HBGLVJABBICLQC-RUZDIDTESA-N 0.000 claims description 3
• YMAYLOQHOWPQQV-AREMUKBSSA-N (4r)-2'-(6,6-dimethyl-2,3-dihydropyran-4-yl)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound CC1(C)OCCC(C=2C=C3[C@@]4(N=C(N)OC4)C4=CC(=CC=C4OC3=CC=2)C=2C=NC=NC=2)=C1 YMAYLOQHOWPQQV-AREMUKBSSA-N 0.000 claims description 3
• GXLBLAWTCDBEDC-JOCHJYFZSA-N (4r)-2'-propoxy-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCCC)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@@]21COC(N)=N2 GXLBLAWTCDBEDC-JOCHJYFZSA-N 0.000 claims description 3
• CHZHWZAKWGFQNL-DEOSSOPVSA-N (4s)-2'-(2,2-dimethylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)(C)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 CHZHWZAKWGFQNL-DEOSSOPVSA-N 0.000 claims description 3
• GXLBLAWTCDBEDC-QFIPXVFZSA-N (4s)-2'-propoxy-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCCC)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 GXLBLAWTCDBEDC-QFIPXVFZSA-N 0.000 claims description 3
• BNXYWTJNPPCGPW-QHCPKHFHSA-N (4s)-4'-fluoro-2'-(2-fluoro-2-methylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)(F)C)=CC(F)=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 BNXYWTJNPPCGPW-QHCPKHFHSA-N 0.000 claims description 3
• JWSHQJYDXNPIKG-UHFFFAOYSA-N 2'-(2-methylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2C21COC(N)=N2 JWSHQJYDXNPIKG-UHFFFAOYSA-N 0.000 claims description 3
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 3
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
• MSMLICOHMGLKMX-RUZDIDTESA-N (4r)-2'-(3,3-dimethylbutyl)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(CCC(C)(C)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 MSMLICOHMGLKMX-RUZDIDTESA-N 0.000 claims description 2
• NZVBDKMMLGEBPO-XMMPIXPASA-N (4r)-2'-(3,6-dihydro-2h-pyran-4-yl)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=N[C@@]21C1=CC(C=3C=NC=NC=3)=CC=C1OC1=CC=C(C=3CCOCC=3)C=C12 NZVBDKMMLGEBPO-XMMPIXPASA-N 0.000 claims description 2
• RUIBVXOIMNQJGF-RUZDIDTESA-N (4r)-2'-(3-methoxy-3-methylbut-1-ynyl)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical class C12=CC(C#CC(C)(C)OC)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 RUIBVXOIMNQJGF-RUZDIDTESA-N 0.000 claims description 2
• CKZJFGZKBRWCEQ-SANMLTNESA-N (4s)-2'-(2,2-dimethylmorpholin-4-yl)-7'-pyridin-3-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1COC(C)(C)CN1C1=CC=C(OC=2C(=CC(=CC=2)C=2C=NC=CC=2)[C@]23N=C(N)OC3)C2=C1 CKZJFGZKBRWCEQ-SANMLTNESA-N 0.000 claims description 2
• MXXGFJVHXFOCJW-DEOSSOPVSA-N (4s)-2'-(2-fluoropyridin-3-yl)-7'-(3-methyl-1,2-oxazol-5-yl)spiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound O1N=C(C)C=C1C1=CC=C(OC=2C(=CC(=CC=2)C=2C(=NC=CC=2)F)[C@]23N=C(N)OC3)C2=C1 MXXGFJVHXFOCJW-DEOSSOPVSA-N 0.000 claims description 2
• VFGNVRBYPSZBJP-DEOSSOPVSA-N (4s)-2'-(2-fluoropyridin-3-yl)-7'-morpholin-4-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=N[C@@]21C1=CC(C=3C(=NC=CC=3)F)=CC=C1OC1=CC=C(N3CCOCC3)C=C12 VFGNVRBYPSZBJP-DEOSSOPVSA-N 0.000 claims description 2
• YCSZGOYPORRCOH-DEOSSOPVSA-N (4s)-2'-(2-methoxy-2-methylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)(C)OC)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 YCSZGOYPORRCOH-DEOSSOPVSA-N 0.000 claims description 2
• JWSHQJYDXNPIKG-QHCPKHFHSA-N (4s)-2'-(2-methylpropoxy)-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C12=CC(OCC(C)C)=CC=C2OC2=CC=C(C=3C=NC=NC=3)C=C2[C@]21COC(N)=N2 JWSHQJYDXNPIKG-QHCPKHFHSA-N 0.000 claims description 2
• OHUFLPUYJCMJNV-QHCPKHFHSA-N (4s)-2'-(3,3-difluoroazetidin-1-yl)-7'-pyridin-3-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=N[C@@]21C1=CC(C=3C=NC=CC=3)=CC=C1OC1=CC=C(N3CC(F)(F)C3)C=C12 OHUFLPUYJCMJNV-QHCPKHFHSA-N 0.000 claims description 2
• QTYGIEOEIDRQAB-DEOSSOPVSA-N (4s)-2'-(3,6-dihydro-2h-pyran-4-yl)-3'-fluoro-7'-pyrimidin-5-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=N[C@]21C1=CC(C=3CCOCC=3)=C(F)C=C1OC1=CC=C(C=3C=NC=NC=3)C=C12 QTYGIEOEIDRQAB-DEOSSOPVSA-N 0.000 claims description 2
• UBJVRJGPVXTXQB-VWLOTQADSA-N (4s)-2'-(3,6-dihydro-2h-pyran-4-yl)-4'-fluoro-7'-(2-fluoropyridin-3-yl)spiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=N[C@]21C1=CC(C=3CCOCC=3)=CC(F)=C1OC1=CC=C(C=3C(=NC=CC=3)F)C=C12 UBJVRJGPVXTXQB-VWLOTQADSA-N 0.000 claims description 2
• PZROFGPRPCCYLH-VWLOTQADSA-N (4s)-2'-(3,6-dihydro-2h-pyran-4-yl)-4'-fluoro-7'-pyridin-3-ylspiro[5h-1,3-oxazole-4,9'-xanthene]-2-amine Chemical compound C1OC(N)=N[C@]21C1=CC(C=3CCOCC=3)=CC(F)=C1OC1=CC=C(C=3C=NC=CC=3)C=C12 PZROFGPRPCCYLH-VWLOTQADSA-N 0.000 claims description 2
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