RU2330853C2 - АЗАИНДОЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Xa - Google Patents

Info

Publication number

RU2330853C2

RU2330853C2 RU2005139557/04A RU2005139557A RU2330853C2 RU 2330853 C2 RU2330853 C2 RU 2330853C2 RU 2005139557/04 A RU2005139557/04 A RU 2005139557/04A RU 2005139557 A RU2005139557 A RU 2005139557A RU 2330853 C2 RU2330853 C2 RU 2330853C2

Authority

RU

Russia

Prior art keywords

alkyl

alkylene

group

hydrogen atom

unsubstituted

Prior art date

2003-05-19

Links

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• Global Dossier
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• 229940123583 Factor Xa inhibitor Drugs 0.000 title claims abstract description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 154
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 120
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 91
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 74
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 72
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 56
• 150000003839 salts Chemical class 0.000 claims abstract description 53
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 43
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 40
• 125000003118 aryl group Chemical group 0.000 claims abstract description 38
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 38
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 34
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 27
• 238000006243 chemical reaction Methods 0.000 claims abstract description 26
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 26
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims abstract description 23
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 19
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 18
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 18
• 239000011593 sulfur Substances 0.000 claims abstract description 18
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 17
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
• 239000001301 oxygen Substances 0.000 claims abstract description 17
• 239000003814 drug Substances 0.000 claims abstract description 13
• 125000004043 oxo group Chemical group O=* 0.000 claims abstract 8
• -1 2H-pyrrolyl Chemical group 0.000 claims description 280
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 54
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 53
• 239000000460 chlorine Chemical group 0.000 claims description 43
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 42
• 125000004122 cyclic group Chemical group 0.000 claims description 41
• 150000002367 halogens Chemical group 0.000 claims description 38
• 125000001544 thienyl group Chemical group 0.000 claims description 32
• 239000001257 hydrogen Substances 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• 125000002950 monocyclic group Chemical group 0.000 claims description 26
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 229910052801 chlorine Inorganic materials 0.000 claims description 22
• 239000002253 acid Substances 0.000 claims description 21
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 21
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 20
• 125000002883 imidazolyl group Chemical group 0.000 claims description 20
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 19
• 125000002971 oxazolyl group Chemical group 0.000 claims description 18
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 17
• 229910052794 bromium Chemical group 0.000 claims description 16
• 125000002541 furyl group Chemical group 0.000 claims description 14
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 14
• 150000002148 esters Chemical class 0.000 claims description 13
• 125000000524 functional group Chemical group 0.000 claims description 13
• VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims description 12
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
• 239000011737 fluorine Substances 0.000 claims description 12
• 229910052740 iodine Inorganic materials 0.000 claims description 11
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 10
• 125000002619 bicyclic group Chemical group 0.000 claims description 10
• 125000006239 protecting group Chemical group 0.000 claims description 10
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
• 238000004519 manufacturing process Methods 0.000 claims description 8
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
• 150000001408 amides Chemical class 0.000 claims description 7
• 125000002843 carboxylic acid group Chemical group 0.000 claims description 7
• 150000004702 methyl esters Chemical class 0.000 claims description 7
• 125000003386 piperidinyl group Chemical group 0.000 claims description 7
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
• ZRQQXFMGYSOKDF-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine Chemical compound CC(C)N1CCC(N)CC1 ZRQQXFMGYSOKDF-UHFFFAOYSA-N 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 229940079593 drug Drugs 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 6
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 6
• 125000002636 imidazolinyl group Chemical group 0.000 claims description 5
• 125000002755 pyrazolinyl group Chemical group 0.000 claims description 5
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 5
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
• 239000005977 Ethylene Substances 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 3
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims description 2
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims description 2
• KCNKJCHARANTIP-SNAWJCMRSA-N allyl-{4-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-but-2-enyl}-methyl-amine Chemical compound C=1OC2=CC(OC/C=C/CN(CC=C)C)=CC=C2C=1C1=CC=C(Br)C=C1 KCNKJCHARANTIP-SNAWJCMRSA-N 0.000 claims 6
• PFXRYXPRYTZFLP-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]pyrrolo[2,3-b]pyridine-5-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=CC2=CC(C(O)=O)=CN=C2N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 PFXRYXPRYTZFLP-UHFFFAOYSA-N 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
• JHSBJRHKOOHXDT-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]pyrrolo[3,2-b]pyridine-5-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=CC2=NC(C(O)=O)=CC=C2N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 JHSBJRHKOOHXDT-UHFFFAOYSA-N 0.000 claims 1
• ASPGNCDILNOTCI-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]pyrrolo[3,2-b]pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC2=NC=CC=C2N1CC(=NO1)C=C1C1=CC=C(Cl)S1 ASPGNCDILNOTCI-UHFFFAOYSA-N 0.000 claims 1
• FUBSIDMUEJBTPN-UHFFFAOYSA-N CC(C)N(CC1)CCC1N.OC(C1=CC2=CC=CN=C2N1CC1=NOC(C(S2)=CC=C2Cl)=C1)=O Chemical compound CC(C)N(CC1)CCC1N.OC(C1=CC2=CC=CN=C2N1CC1=NOC(C(S2)=CC=C2Cl)=C1)=O FUBSIDMUEJBTPN-UHFFFAOYSA-N 0.000 claims 1
• LRVRZLYXEHHMOK-UHFFFAOYSA-N CC(C)N(CC1)CCC1N.OCCOC1=NC=C2N(CC(NC(C=C3)=NC=C3Cl)=O)C(C(O)=O)=CC2=C1 Chemical compound CC(C)N(CC1)CCC1N.OCCOC1=NC=C2N(CC(NC(C=C3)=NC=C3Cl)=O)C(C(O)=O)=CC2=C1 LRVRZLYXEHHMOK-UHFFFAOYSA-N 0.000 claims 1
• 150000002431 hydrogen Chemical class 0.000 claims 1
• IFFHYPWKJWLMRH-UHFFFAOYSA-N methyl 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]pyrrolo[2,3-b]pyridine-5-carboxylate Chemical class C1CN(C(C)C)CCC1NC(=O)C1=CC2=CC(C(=O)OC)=CN=C2N1CC(=NO1)C=C1C1=CC=C(Cl)S1 IFFHYPWKJWLMRH-UHFFFAOYSA-N 0.000 claims 1
• 150000003053 piperidines Chemical class 0.000 claims 1
• 150000003222 pyridines Chemical class 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 41
• 230000000694 effects Effects 0.000 abstract description 18
• 238000011282 treatment Methods 0.000 abstract description 14
• 230000023555 blood coagulation Effects 0.000 abstract description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
• 208000037803 restenosis Diseases 0.000 abstract description 6
• 208000001435 Thromboembolism Diseases 0.000 abstract description 5
• 230000020764 fibrinolysis Effects 0.000 abstract description 5
• 239000000126 substance Substances 0.000 abstract description 5
• 208000024172 Cardiovascular disease Diseases 0.000 abstract description 4
• 201000010099 disease Diseases 0.000 abstract description 4
• 125000005843 halogen group Chemical group 0.000 abstract description 2
• 206010061218 Inflammation Diseases 0.000 abstract 1
• 230000004054 inflammatory process Effects 0.000 abstract 1
• 230000000069 prophylactic effect Effects 0.000 abstract 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 75
• 239000000243 solution Substances 0.000 description 65
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
• 239000000203 mixture Substances 0.000 description 57
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 56
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 55
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 54
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 44
• 239000000047 product Substances 0.000 description 43
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 42
• 239000002904 solvent Substances 0.000 description 42
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 35
• 108010074860 Factor Xa Proteins 0.000 description 35
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 34
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 33
• 230000015572 biosynthetic process Effects 0.000 description 33
• 230000002829 reductive effect Effects 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
• 108010054265 Factor VIIa Proteins 0.000 description 30
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
• 229940012414 factor viia Drugs 0.000 description 30
• 239000000651 prodrug Substances 0.000 description 30
• 229940002612 prodrug Drugs 0.000 description 30
• 238000003786 synthesis reaction Methods 0.000 description 30
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 27
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 27
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 125000001309 chloro group Chemical group Cl* 0.000 description 24
• 125000004093 cyano group Chemical group *C#N 0.000 description 23
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 23
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 22
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 21
• LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 21
• POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 description 21
• MSRJJSCOWHWGGX-UHFFFAOYSA-N 2h-1,3-diazepine Chemical compound C1N=CC=CC=N1 MSRJJSCOWHWGGX-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 21
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 21
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 21
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 20
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 20
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 20
• JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 19
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 19
• 239000011541 reaction mixture Substances 0.000 description 19
• 150000003536 tetrazoles Chemical class 0.000 description 19
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 18
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 18
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 18
• GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 18
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 239000007787 solid Substances 0.000 description 18
• CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 17
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 17
• 125000000335 thiazolyl group Chemical group 0.000 description 17
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 16
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 16
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 16
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 16
• 230000005764 inhibitory process Effects 0.000 description 16
• 239000012071 phase Substances 0.000 description 16
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 description 15
• PPSZHCXTGRHULJ-UHFFFAOYSA-N dioxazine Chemical compound O1ON=CC=C1 PPSZHCXTGRHULJ-UHFFFAOYSA-N 0.000 description 15
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 15
• 238000005160 1H NMR spectroscopy Methods 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 14
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
• 125000004433 nitrogen atom Chemical group N* 0.000 description 14
• 238000002953 preparative HPLC Methods 0.000 description 14
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 14
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