AU2008228303B2 - Substituted pyrimidodiazepines useful as PLK1 inhibitors - Google Patents

Info

Publication number

AU2008228303B2

AU2008228303B2 AU2008228303A AU2008228303A AU2008228303B2 AU 2008228303 B2 AU2008228303 B2 AU 2008228303B2 AU 2008228303 A AU2008228303 A AU 2008228303A AU 2008228303 A AU2008228303 A AU 2008228303A AU 2008228303 B2 AU2008228303 B2 AU 2008228303B2

Authority

AU

Australia

Prior art keywords

methyl

mole

tetrahydro

pyrimido

diazepin

Prior art date

2007-03-22

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.)

Ceased

Links

• Espacenet
• Global Dossier
• Discuss

• 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 title abstract description 14
• 108010056274 polo-like kinase 1 Proteins 0.000 title abstract description 13
• 239000003112 inhibitor Substances 0.000 title abstract description 5
• OHXQYFCNXHGKPJ-UHFFFAOYSA-N 1h-pyrimido[5,4-c]diazepine Chemical class N1N=CC=CC2=NC=NC=C12 OHXQYFCNXHGKPJ-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 51
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
• 150000003839 salts Chemical class 0.000 claims description 15
• DQJHTCZROXSXEZ-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=NC=C(N(C)C(=O)C(F)(F)CN2C3CCCC3)C2=N1 DQJHTCZROXSXEZ-UHFFFAOYSA-N 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 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 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 239000000203 mixture Substances 0.000 abstract description 397
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
• 206010028980 Neoplasm Diseases 0.000 abstract description 6
• 230000000771 oncological effect Effects 0.000 abstract description 4
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 abstract description 3
• 210000000481 breast Anatomy 0.000 abstract description 3
• 210000001072 colon Anatomy 0.000 abstract description 3
• 201000010099 disease Diseases 0.000 abstract description 3
• 210000004072 lung Anatomy 0.000 abstract description 3
• 230000002062 proliferating effect Effects 0.000 abstract description 3
• 208000026310 Breast neoplasm Diseases 0.000 abstract description 2
• 208000029742 colonic neoplasm Diseases 0.000 abstract description 2
• 238000009472 formulation Methods 0.000 abstract description 2
• 208000037841 lung tumor Diseases 0.000 abstract description 2
• 208000023958 prostate neoplasm Diseases 0.000 abstract description 2
• XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 531
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 299
• 230000002829 reductive effect Effects 0.000 description 217
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 193
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 153
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 147
• 239000000243 solution Substances 0.000 description 146
• 239000007787 solid Substances 0.000 description 117
• -1 PLK1 Proteins 0.000 description 112
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 111
• 238000010898 silica gel chromatography Methods 0.000 description 107
• 239000010410 layer Substances 0.000 description 102
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 98
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 94
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 94
• 239000012267 brine Substances 0.000 description 82
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 82
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 81
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 74
• 238000000746 purification Methods 0.000 description 58
• 238000000034 method Methods 0.000 description 54
• 238000001914 filtration Methods 0.000 description 51
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
• 239000012044 organic layer Substances 0.000 description 43
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
• 239000002244 precipitate Substances 0.000 description 40
• KYSGSGFXDCAVQB-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-5,7-dimethyl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2N(C)C(=O)C(C)CN1C1CCCC1 KYSGSGFXDCAVQB-UHFFFAOYSA-N 0.000 description 39
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 239000001257 hydrogen Substances 0.000 description 38
• 229910052739 hydrogen Inorganic materials 0.000 description 38
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 37
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 35
• 239000012071 phase Substances 0.000 description 35
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 33
• ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 32
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 32
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 32
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 31
• 239000003921 oil Substances 0.000 description 31
• 235000019198 oils Nutrition 0.000 description 31
• INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 30
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
• 238000001816 cooling Methods 0.000 description 28
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 27
• 235000015497 potassium bicarbonate Nutrition 0.000 description 27
• 239000011736 potassium bicarbonate Substances 0.000 description 27
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 26
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
• 238000010992 reflux Methods 0.000 description 26
• 239000000284 extract Substances 0.000 description 25
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
• 239000012312 sodium hydride Substances 0.000 description 23
• 229910000104 sodium hydride Inorganic materials 0.000 description 23
• JNFGLYJROFAOQP-UHFFFAOYSA-N 4-amino-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1N JNFGLYJROFAOQP-UHFFFAOYSA-N 0.000 description 22
• 239000000706 filtrate Substances 0.000 description 22
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 22
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• GJJNFZOPTJVXID-UHFFFAOYSA-N 5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound N1C(=O)CCNC2=NC=NC=C21 GJJNFZOPTJVXID-UHFFFAOYSA-N 0.000 description 20
• 239000000843 powder Substances 0.000 description 20
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
• 235000017557 sodium bicarbonate Nutrition 0.000 description 20
• 239000008346 aqueous phase Substances 0.000 description 19
• 239000012074 organic phase Substances 0.000 description 19
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 18
• 239000012298 atmosphere Substances 0.000 description 17
• 239000003054 catalyst Substances 0.000 description 16
• 238000005406 washing Methods 0.000 description 16
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
• PDKXJKWLFFZPPF-UHFFFAOYSA-N [dimethylamino-(3-oxidotriazolo[4,5-b]pyridin-3-ium-1-yl)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(C(N(C)C)=[N+](C)C)N=[N+]([O-])C2=N1 PDKXJKWLFFZPPF-UHFFFAOYSA-N 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
• 229910000024 caesium carbonate Inorganic materials 0.000 description 11
• 238000004587 chromatography analysis Methods 0.000 description 11
• 150000002431 hydrogen Chemical class 0.000 description 11
• 229960004592 isopropanol Drugs 0.000 description 11
• 239000000741 silica gel Substances 0.000 description 11
• 229910002027 silica gel Inorganic materials 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• 239000005711 Benzoic acid Substances 0.000 description 10
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• 235000011114 ammonium hydroxide Nutrition 0.000 description 10
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
• VSMSBPFQRFQLGA-UHFFFAOYSA-N 4-[(9-cyclohexyl-6-oxo-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3N(C4CCCCC4)CCC(=O)NC3=CN=2)=C1 VSMSBPFQRFQLGA-UHFFFAOYSA-N 0.000 description 9
• GWRSATNRNFYMDI-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-fluoro-5-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound FC=1C=C(NC=2N=C3N(C4CCCC4)CC(F)(F)C(=O)N(C)C3=CN=2)C(OC)=CC=1C(=O)NC1CCN(C)CC1 GWRSATNRNFYMDI-UHFFFAOYSA-N 0.000 description 9
• XBYFLVPPIOYEJF-UHFFFAOYSA-N 4-amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamide Chemical compound C1=C(N)C(OC)=CC(C(=O)NC2CCN(C)CC2)=C1 XBYFLVPPIOYEJF-UHFFFAOYSA-N 0.000 description 9
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 9
• 239000000908 ammonium hydroxide Substances 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 9
• 150000002148 esters Chemical class 0.000 description 9
• XQSNXLDLKOJJOU-UHFFFAOYSA-N pyrimido[5,4-c]diazepin-3-one Chemical compound N1=NC(=O)C=CC2=NC=NC=C21 XQSNXLDLKOJJOU-UHFFFAOYSA-N 0.000 description 9
• 239000001632 sodium acetate Substances 0.000 description 9
• 235000017281 sodium acetate Nutrition 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 125000000217 alkyl group Chemical group 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
• 125000004494 ethyl ester group Chemical group 0.000 description 8
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 239000002671 adjuvant Substances 0.000 description 7
• 125000003118 aryl group Chemical group 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 239000012230 colorless oil Substances 0.000 description 7
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 7
• SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical class ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
• 239000004533 oil dispersion Substances 0.000 description 7
• 238000002360 preparation method Methods 0.000 description 7
• 238000001665 trituration Methods 0.000 description 7
• JXYPNRIYAMXJSE-UHFFFAOYSA-N 1,4-diazepin-6-one Chemical compound O=C1C=NC=CN=C1 JXYPNRIYAMXJSE-UHFFFAOYSA-N 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• 235000010233 benzoic acid Nutrition 0.000 description 6
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 239000012065 filter cake Substances 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• 235000019341 magnesium sulphate Nutrition 0.000 description 6
• 229910052757 nitrogen Chemical group 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 5
• VMCZIPPMGFWHDE-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-5,7,7-trimethyl-8h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C1C(C)(C)C(=O)N(C)C2=CN=C(Cl)N=C2N1C1CCCC1 VMCZIPPMGFWHDE-UHFFFAOYSA-N 0.000 description 5
• AWEBUXPVTLJUKN-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-5-methylspiro[8h-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropane]-6-one Chemical compound O=C1N(C)C2=CN=C(Cl)N=C2N(C2CCCC2)CC21CC2 AWEBUXPVTLJUKN-UHFFFAOYSA-N 0.000 description 5
• LRJURAIIMHELTD-UHFFFAOYSA-N 4-[(9-cyclopentyl-5,7,7-trimethyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=NC=C(N(C)C(=O)C(C)(C)CN2C3CCCC3)C2=N1 LRJURAIIMHELTD-UHFFFAOYSA-N 0.000 description 5
• OCAFBWCIHWDTKE-UHFFFAOYSA-N [dimethylamino-(3-oxidobenzotriazol-3-ium-1-yl)methylidene]-dimethylazanium Chemical compound C1=CC=C2[N+](=C(N(C)C)N(C)C)N=[N+]([O-])C2=C1 OCAFBWCIHWDTKE-UHFFFAOYSA-N 0.000 description 5
• 125000003545 alkoxy group Chemical group 0.000 description 5
• 125000001153 fluoro group Chemical group F* 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
• CAVNRDHSIUXHAV-UHFFFAOYSA-N methyl 2-[(5-amino-2-chloropyrimidin-4-yl)-cyclopentylamino]cyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1N(C=1C(=CN=C(Cl)N=1)N)C1CCCC1 CAVNRDHSIUXHAV-UHFFFAOYSA-N 0.000 description 5
• 229920006395 saturated elastomer Polymers 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• LUEAVCYZFCKHHU-UHFFFAOYSA-N 2-chloro-9-cyclohexyl-5,7-dimethyl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2N(C)C(=O)C(C)CN1C1CCCCC1 LUEAVCYZFCKHHU-UHFFFAOYSA-N 0.000 description 4
• ZDBVEKYYEGAKKY-UHFFFAOYSA-N 2-chloro-9-cyclohexyl-5-methyl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C1CC(=O)N(C)C2=CN=C(Cl)N=C2N1C1CCCCC1 ZDBVEKYYEGAKKY-UHFFFAOYSA-N 0.000 description 4
• SKDJWBCTSQLYAZ-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7,7-dimethyl-5,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)C(C)(C)CN1C1CCCC1 SKDJWBCTSQLYAZ-UHFFFAOYSA-N 0.000 description 4
• RSRPLYCCLBLNTJ-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)CCN1C1CCCC1 RSRPLYCCLBLNTJ-UHFFFAOYSA-N 0.000 description 4
• LIMGJPPDWITRHN-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7-methyl-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)C(C)CN1C1CCCC1 LIMGJPPDWITRHN-UHFFFAOYSA-N 0.000 description 4
• XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 description 4
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