MXPA06001767A - Analogos de quinazolina como inhibidores de la tirosina quinasa receptora. - Google Patents

Info

Publication number

MXPA06001767A

MXPA06001767A MXPA06001767A MXPA06001767A MXPA06001767A MX PA06001767 A MXPA06001767 A MX PA06001767A MX PA06001767 A MXPA06001767 A MX PA06001767A MX PA06001767 A MXPA06001767 A MX PA06001767A MX PA06001767 A MXPA06001767 A MX PA06001767A

Authority

MX

Mexico

Prior art keywords

compound according

quinazolin

methyl

diamine

phenyl

Prior art date

2003-08-14

Links

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• 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 title abstract 2
• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 170
• 238000000034 method Methods 0.000 claims abstract description 48
• 125000002619 bicyclic group Chemical group 0.000 claims abstract description 35
• 201000010099 disease Diseases 0.000 claims abstract description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 34
• 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 21
• -1 resolved enantxomers Chemical class 0.000 claims description 168
• 125000000623 heterocyclic group Chemical group 0.000 claims description 117
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 92
• 125000003118 aryl group Chemical group 0.000 claims description 75
• 125000001072 heteroaryl group Chemical group 0.000 claims description 71
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 60
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 59
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 57
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 51
• 125000000217 alkyl group Chemical group 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 50
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 47
• 239000001257 hydrogen Substances 0.000 claims description 47
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
• 229910052736 halogen Inorganic materials 0.000 claims description 45
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 45
• 125000003342 alkenyl group Chemical group 0.000 claims description 44
• 241000124008 Mammalia Species 0.000 claims description 43
• 125000000304 alkynyl group Chemical group 0.000 claims description 42
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 42
• 150000002367 halogens Chemical group 0.000 claims description 41
• 229910052799 carbon Inorganic materials 0.000 claims description 38
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 36
• 125000004429 atom Chemical group 0.000 claims description 35
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 35
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 34
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 34
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 32
• 125000005842 heteroatom Chemical group 0.000 claims description 31
• OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 claims description 27
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 27
• 229910052760 oxygen Inorganic materials 0.000 claims description 25
• 229910052717 sulfur Inorganic materials 0.000 claims description 25
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 24
• 125000004434 sulfur atom Chemical group 0.000 claims description 20
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 17
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 15
• 125000004043 oxo group Chemical group O=* 0.000 claims description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
• 125000006413 ring segment Chemical group 0.000 claims description 8
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
• 125000005843 halogen group Chemical group 0.000 claims description 7
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 7
• 229910052721 tungsten Inorganic materials 0.000 claims description 6
• 229910052720 vanadium Inorganic materials 0.000 claims description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 4
• ZQUSYVORYNBGLG-FQEVSTJZSA-N (2s)-2-[[1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carbonyl]amino]-4-methylpentanoic acid Chemical compound COC1=CC=CC(OC)=C1C1=CC(C(=O)N[C@@H](CC(C)C)C(O)=O)=NN1C1=CC=NC2=CC(Cl)=CC=C12 ZQUSYVORYNBGLG-FQEVSTJZSA-N 0.000 claims description 3
• QCGMEWVZBGQOFN-UHFFFAOYSA-N 1,3-oxazole-5-carboxylic acid Chemical compound OC(=O)C1=CN=CO1 QCGMEWVZBGQOFN-UHFFFAOYSA-N 0.000 claims description 3
• CWZISLULKPYASC-UHFFFAOYSA-N 4-n-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-n-(1,8-dioxa-3-azaspiro[4.5]dec-2-en-2-yl)quinazoline-4,6-diamine Chemical compound C=1C=C(OCC=2SC=CN=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC(O1)=NCC21CCOCC2 CWZISLULKPYASC-UHFFFAOYSA-N 0.000 claims description 3
• FIZYYYJQZBMOCD-UHFFFAOYSA-N 6-n-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC(C1=C2)=NC=NC1=CC=C2NC1=NC(C)(C)CO1 FIZYYYJQZBMOCD-UHFFFAOYSA-N 0.000 claims description 3
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 claims description 3
• 239000012453 solvate Substances 0.000 claims description 3
• 229910052727 yttrium Inorganic materials 0.000 claims description 3
• QYTXQGUDLADZAW-UHFFFAOYSA-N 1-[2-[[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-6-yl]amino]-3a,4,6,6a-tetrahydropyrrolo[3,4-d][1,3]oxazol-5-yl]ethanone Chemical compound N=1C2CN(C(=O)C)CC2OC=1NC(C=C12)=CC=C1N=CN=C2NC(C=C1C)=CC=C1OC1=CC=C(C)N=C1 QYTXQGUDLADZAW-UHFFFAOYSA-N 0.000 claims description 2
• ORSVNYCYNDNVDZ-UHFFFAOYSA-N 2-methoxy-2-(methylideneamino)-N'-[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-6-yl]ethanimidamide Chemical compound COC(N=C)C(N)=Nc1ccc2ncnc(Nc3ccc(Oc4ccc(C)nc4)c(C)c3)c2c1 ORSVNYCYNDNVDZ-UHFFFAOYSA-N 0.000 claims description 2
• RUBJWKNIOKHRAC-HNNXBMFYSA-N 4-n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-6-n-[(5s)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine Chemical compound O1[C@@H](C)CN=C1NC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)C2=C1 RUBJWKNIOKHRAC-HNNXBMFYSA-N 0.000 claims description 2
• MUGQWAPKWHAXJL-UHFFFAOYSA-N 6-n-(3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]oxazol-2-yl)-4-n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]quinazoline-4,6-diamine Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(NC=5OC6COCC6N=5)=CC=C4N=CN=3)=CC=2)Cl)=C1 MUGQWAPKWHAXJL-UHFFFAOYSA-N 0.000 claims description 2
• LFKSHLJVZXWZBV-UHFFFAOYSA-N 6-n-(3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]oxazol-2-yl)-4-n-[3-methyl-4-(1,3-thiazol-2-ylmethoxy)phenyl]quinazoline-4,6-diamine Chemical compound CC1=CC(NC=2C3=CC(NC=4OC5COCC5N=4)=CC=C3N=CN=2)=CC=C1OCC1=NC=CS1 LFKSHLJVZXWZBV-UHFFFAOYSA-N 0.000 claims description 2
• KQDVDINVRJNBJA-UHFFFAOYSA-N 6-n-(4,5,6,6a-tetrahydro-3ah-pyrrolo[3,4-d][1,3]oxazol-2-yl)-4-n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]quinazoline-4,6-diamine Chemical compound ClC1=CC(NC=2C3=CC(NC=4OC5CNCC5N=4)=CC=C3N=CN=2)=CC=C1OCC1=CC=CC=N1 KQDVDINVRJNBJA-UHFFFAOYSA-N 0.000 claims description 2
• PUXXFLUZBJTRBM-UHFFFAOYSA-N 6-n-(5,5-dimethyl-4h-1,3-oxazol-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC(C1=C2)=NC=NC1=CC=C2NC1=NCC(C)(C)O1 PUXXFLUZBJTRBM-UHFFFAOYSA-N 0.000 claims description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
• 125000002950 monocyclic group Chemical group 0.000 claims description 2
• VTSUMCFFGMUODS-UHFFFAOYSA-N n'-[[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]methylideneamino]-2-methoxyethanimidamide Chemical compound C12=CC(C=NNC(=N)COC)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 VTSUMCFFGMUODS-UHFFFAOYSA-N 0.000 claims description 2
• QZGIWJNNXZVDII-UHFFFAOYSA-N 6-n-(4,5-dihydro-1,3-oxazol-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical group C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC(C1=C2)=NC=NC1=CC=C2NC1=NCCO1 QZGIWJNNXZVDII-UHFFFAOYSA-N 0.000 claims 2
• LWVKHUVLTCLRGM-YJYMSZOUSA-N (1r)-1-[(4s)-2-[[4-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)anilino]quinazolin-6-yl]amino]-4,5-dihydro-1,3-oxazol-4-yl]ethanol Chemical group C[C@@H](O)[C@@H]1COC(NC=2C=C3C(NC=4C=C(Cl)C(OCC=5SC=CN=5)=CC=4)=NC=NC3=CC=2)=N1 LWVKHUVLTCLRGM-YJYMSZOUSA-N 0.000 claims 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
• NOUZOQPYJWIZLS-UHFFFAOYSA-N 1-[2-[[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]quinazolin-6-yl]amino]-5-methyl-4h-1,3-oxazol-5-yl]ethanol Chemical compound O1C(C(O)C)(C)CN=C1NC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)C2=C1 NOUZOQPYJWIZLS-UHFFFAOYSA-N 0.000 claims 1
• KWAFQYBPDPQKQP-UHFFFAOYSA-N 1-[2-[[4-[3-methyl-4-(6-methylpyridin-3-yl)oxyanilino]quinazolin-6-yl]amino]-1-oxa-3,8-diazaspiro[4.5]dec-2-en-8-yl]ethanone Chemical compound C1CN(C(=O)C)CCC11OC(NC=2C=C3C(NC=4C=C(C)C(OC=5C=NC(C)=CC=5)=CC=4)=NC=NC3=CC=2)=NC1 KWAFQYBPDPQKQP-UHFFFAOYSA-N 0.000 claims 1
• UWXSAYUXVSFDBQ-CYBMUJFWSA-N 4-n-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-n-[(4r)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine Chemical compound C[C@@H]1COC(NC=2C=C3C(NC=4C=C(Cl)C(OCC=5SC=CN=5)=CC=4)=NC=NC3=CC=2)=N1 UWXSAYUXVSFDBQ-CYBMUJFWSA-N 0.000 claims 1
• UWXSAYUXVSFDBQ-ZDUSSCGKSA-N 4-n-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]-6-n-[(4s)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine Chemical compound C[C@H]1COC(NC=2C=C3C(NC=4C=C(Cl)C(OCC=5SC=CN=5)=CC=4)=NC=NC3=CC=2)=N1 UWXSAYUXVSFDBQ-ZDUSSCGKSA-N 0.000 claims 1
• TYCZDOZCSMTQMU-UHFFFAOYSA-N 4-n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-6-n-(1,8-dioxa-3-azaspiro[4.5]dec-2-en-2-yl)quinazoline-4,6-diamine Chemical compound C=1C=C(OCC=2N=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC(O1)=NCC21CCOCC2 TYCZDOZCSMTQMU-UHFFFAOYSA-N 0.000 claims 1
• FLAYOMMMHOCWGP-UHFFFAOYSA-N 4-n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-6-n-(1-oxa-3,8-diazaspiro[4.5]dec-2-en-2-yl)quinazoline-4,6-diamine Chemical compound C=1C=C(OCC=2N=CC=CC=2)C(Cl)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC(O1)=NCC21CCNCC2 FLAYOMMMHOCWGP-UHFFFAOYSA-N 0.000 claims 1
• RUBJWKNIOKHRAC-OAHLLOKOSA-N 4-n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-6-n-[(5r)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]quinazoline-4,6-diamine Chemical compound O1[C@H](C)CN=C1NC1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4N=CC=CC=4)=CC=3)C2=C1 RUBJWKNIOKHRAC-OAHLLOKOSA-N 0.000 claims 1
• GRURXRHVBDRMIL-UHFFFAOYSA-N 4-n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-n-(1,8-dioxa-3-azaspiro[4.5]dec-2-en-2-yl)quinazoline-4,6-diamine Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(NC=5OC6(CCOCC6)CN=5)=CC=C4N=CN=3)=CC=2)Cl)=C1 GRURXRHVBDRMIL-UHFFFAOYSA-N 0.000 claims 1
• SYBWPILVBSAOAN-UHFFFAOYSA-N 4-n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-n-(3,8-dioxa-1-azaspiro[4.5]dec-1-en-2-yl)quinazoline-4,6-diamine Chemical compound FC1=CC=CC(COC=2C(=CC(NC=3C4=CC(NC=5OCC6(N=5)CCOCC6)=CC=C4N=CN=3)=CC=2)Cl)=C1 SYBWPILVBSAOAN-UHFFFAOYSA-N 0.000 claims 1
• YQXGRTPIASRQRG-UHFFFAOYSA-N 6-n-(1,8-dioxa-3-azaspiro[4.5]dec-2-en-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC(C1=C2)=NC=NC1=CC=C2NC(O1)=NCC11CCOCC1 YQXGRTPIASRQRG-UHFFFAOYSA-N 0.000 claims 1
• FPVNNVMHCPEEFS-UHFFFAOYSA-N 6-n-(3,8-dioxa-1-azaspiro[4.5]dec-1-en-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC(C1=C2)=NC=NC1=CC=C2NC(OC1)=NC21CCOCC2 FPVNNVMHCPEEFS-UHFFFAOYSA-N 0.000 claims 1
• PVFIWCZYIRQZSL-UHFFFAOYSA-N 6-n-(3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]oxazol-2-yl)-4-n-[3-chloro-4-(1,3-thiazol-2-ylmethoxy)phenyl]quinazoline-4,6-diamine Chemical group ClC1=CC(NC=2C3=CC(NC=4OC5COCC5N=4)=CC=C3N=CN=2)=CC=C1OCC1=NC=CS1 PVFIWCZYIRQZSL-UHFFFAOYSA-N 0.000 claims 1
• YQTHNULRNIAONX-UHFFFAOYSA-N 6-n-(3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]oxazol-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical compound C1=NC(C)=CC=C1OC(C(=C1)C)=CC=C1NC(C1=C2)=NC=NC1=CC=C2NC(O1)=NC2C1COC2 YQTHNULRNIAONX-UHFFFAOYSA-N 0.000 claims 1
• KYIRGUHXTKXFRE-UHFFFAOYSA-N 6-n-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-4-n-(3-methyl-4-pyridin-3-yloxyphenyl)quinazoline-4,6-diamine Chemical compound C=1C=C(OC=2C=NC=CC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC1=NC(C)(C)CO1 KYIRGUHXTKXFRE-UHFFFAOYSA-N 0.000 claims 1
• HUUUHRPGDGJSBF-UHFFFAOYSA-N 6-n-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-4-n-[4-(5-fluoropyridin-3-yl)oxy-3-methylphenyl]quinazoline-4,6-diamine Chemical compound C=1C=C(OC=2C=C(F)C=NC=2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC1=NC(C)(C)CO1 HUUUHRPGDGJSBF-UHFFFAOYSA-N 0.000 claims 1
• XZNJOPUUIBAHHG-UHFFFAOYSA-N 6-n-(4-methyl-4,5-dihydro-1,3-oxazol-2-yl)-4-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazoline-4,6-diamine Chemical compound CC1COC(NC=2C=C3C(NC=4C=C(C)C(OC=5C=NC(C)=CC=5)=CC=4)=NC=NC3=CC=2)=N1 XZNJOPUUIBAHHG-UHFFFAOYSA-N 0.000 claims 1
• OWNBNCHVWZNXTC-UHFFFAOYSA-N C1COC(=N1)NC2=CC3=C(C=C2)NC=NC3(C4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl)N Chemical compound C1COC(=N1)NC2=CC3=C(C=C2)NC=NC3(C4=CC(=C(C=C4)OCC5=CC(=CC=C5)F)Cl)N OWNBNCHVWZNXTC-UHFFFAOYSA-N 0.000 claims 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
• 150000001721 carbon Chemical group 0.000 claims 1
• 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 claims 1
• 238000011282 treatment Methods 0.000 abstract description 12
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• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 47
• 238000005481 NMR spectroscopy Methods 0.000 description 45
• 239000000460 chlorine Substances 0.000 description 29
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• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 22
• 238000006243 chemical reaction Methods 0.000 description 19
• 125000001424 substituent group Chemical group 0.000 description 19
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
• 238000002360 preparation method Methods 0.000 description 18
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• 229940002612 prodrug Drugs 0.000 description 16
• 150000003254 radicals Chemical class 0.000 description 16
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 16
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 15
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