RU2346944C2 - ПРОИЗВОДНЫЕ БЕНЗИМИДАЗОЛА В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Ха - Google Patents

Info

Publication number

RU2346944C2

RU2346944C2 RU2005139555/04A RU2005139555A RU2346944C2 RU 2346944 C2 RU2346944 C2 RU 2346944C2 RU 2005139555/04 A RU2005139555/04 A RU 2005139555/04A RU 2005139555 A RU2005139555 A RU 2005139555A RU 2346944 C2 RU2346944 C2 RU 2346944C2

Authority

RU

Russia

Prior art keywords

alkyl

benzoimidazole

ylcarbamoyl

carboxylic acid

unsubstituted

Prior art date

2003-05-19

Links

• Espacenet
• Global Dossier
• Discuss

• 108010074860 Factor Xa Proteins 0.000 title claims abstract description 33
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical class C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title description 32
• 230000002401 inhibitory effect Effects 0.000 title description 8
• 150000001875 compounds Chemical class 0.000 claims abstract description 234
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 187
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 115
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 100
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 97
• 238000000034 method Methods 0.000 claims abstract description 83
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 70
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 69
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 59
• 125000003118 aryl group Chemical group 0.000 claims abstract description 57
• 125000004122 cyclic group Chemical group 0.000 claims abstract description 56
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 53
• 150000003839 salts Chemical class 0.000 claims abstract description 50
• 125000002950 monocyclic group Chemical group 0.000 claims abstract description 48
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 47
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 47
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 45
• 239000001257 hydrogen Substances 0.000 claims abstract description 41
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
• 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 38
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 36
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 36
• 239000011593 sulfur Substances 0.000 claims abstract description 36
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 31
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 31
• 239000001301 oxygen Substances 0.000 claims abstract description 31
• 108010054265 Factor VIIa Proteins 0.000 claims abstract description 30
• 229940012414 factor viia Drugs 0.000 claims abstract description 29
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 26
• 229920006395 saturated elastomer Polymers 0.000 claims abstract description 22
• 238000011282 treatment Methods 0.000 claims abstract description 21
• 230000023555 blood coagulation Effects 0.000 claims abstract description 15
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims abstract description 14
• 125000005843 halogen group Chemical group 0.000 claims abstract description 14
• 230000005764 inhibitory process Effects 0.000 claims abstract description 13
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract description 12
• 239000003112 inhibitor Substances 0.000 claims abstract description 10
• 230000002441 reversible effect Effects 0.000 claims abstract description 9
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 9
• -1 8-azabicyclo [3.2.1] oct-3-yl Chemical group 0.000 claims description 402
• 239000000203 mixture Substances 0.000 claims description 124
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 112
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 108
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 78
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 75
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 67
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 66
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 59
• 238000006243 chemical reaction Methods 0.000 claims description 51
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 44
• 150000002367 halogens Chemical class 0.000 claims description 44
• PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 43
• 125000001544 thienyl group Chemical group 0.000 claims description 43
• 239000002904 solvent Substances 0.000 claims description 40
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 37
• WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 37
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 36
• 150000001408 amides Chemical class 0.000 claims description 36
• 239000000460 chlorine Substances 0.000 claims description 35
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 34
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 34
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 33
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 33
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 32
• 229910052731 fluorine Inorganic materials 0.000 claims description 32
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 32
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 30
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 30
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
• POXWDTQUDZUOGP-UHFFFAOYSA-N 1h-1,4-diazepine Chemical compound N1C=CC=NC=C1 POXWDTQUDZUOGP-UHFFFAOYSA-N 0.000 claims description 28
• 230000015572 biosynthetic process Effects 0.000 claims description 28
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 28
• JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 claims description 27
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 27
• 229910052801 chlorine Inorganic materials 0.000 claims description 27
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 27
• 125000002883 imidazolyl group Chemical group 0.000 claims description 27
• 125000000335 thiazolyl group Chemical group 0.000 claims description 27
• FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 claims description 26
• LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 claims description 26
• MSRJJSCOWHWGGX-UHFFFAOYSA-N 2h-1,3-diazepine Chemical compound C1N=CC=CC=N1 MSRJJSCOWHWGGX-UHFFFAOYSA-N 0.000 claims description 26
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 26
• 239000011737 fluorine Substances 0.000 claims description 26
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 26
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 26
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 26
• ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical compound C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims description 25
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 24
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 24
• 125000002971 oxazolyl group Chemical group 0.000 claims description 24
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 24
• FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 23
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 23
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 23
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 claims description 23
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 23
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims description 22
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 22
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 22
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 22
• 150000003536 tetrazoles Chemical class 0.000 claims description 22
• GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 claims description 21
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 21
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 21
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 21
• CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims description 20
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 20
• MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 20
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 20
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 18
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 18
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 18
• BWCDLEQTELFBAW-UHFFFAOYSA-N 3h-dioxazole Chemical compound N1OOC=C1 BWCDLEQTELFBAW-UHFFFAOYSA-N 0.000 claims description 17
• PPSZHCXTGRHULJ-UHFFFAOYSA-N dioxazine Chemical compound O1ON=CC=C1 PPSZHCXTGRHULJ-UHFFFAOYSA-N 0.000 claims description 17
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 17
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 17
• CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 claims description 17
• 229930192474 thiophene Natural products 0.000 claims description 17
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 16
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 16
• 125000002619 bicyclic group Chemical group 0.000 claims description 15
• 229910052794 bromium Inorganic materials 0.000 claims description 15
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
• 125000002053 thietanyl group Chemical group 0.000 claims description 15
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 14
• 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 14
• 208000007536 Thrombosis Diseases 0.000 claims description 13
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
• 229910052740 iodine Inorganic materials 0.000 claims description 13
• 125000002757 morpholinyl group Chemical group 0.000 claims description 13
• 239000003960 organic solvent Substances 0.000 claims description 13
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 13
• 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
• 239000002585 base Substances 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000004193 piperazinyl group Chemical group 0.000 claims description 12
• OKUVXXZKJBEARR-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-4-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=C(C(O)=O)C=CC=C2N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 OKUVXXZKJBEARR-UHFFFAOYSA-N 0.000 claims description 11
• ZRQQXFMGYSOKDF-UHFFFAOYSA-N 1-propan-2-ylpiperidin-4-amine Chemical compound CC(C)N1CCC(N)CC1 ZRQQXFMGYSOKDF-UHFFFAOYSA-N 0.000 claims description 11
• 125000002947 alkylene group Chemical group 0.000 claims description 11
• 230000002792 vascular Effects 0.000 claims description 11
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• OTJKNFNMTJVBBI-UHFFFAOYSA-N 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-4-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=C(C(O)=O)C=CC=C2N1CC(=O)NC1=CC=C(Cl)C=N1 OTJKNFNMTJVBBI-UHFFFAOYSA-N 0.000 claims description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
• 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 9
• 125000002393 azetidinyl group Chemical group 0.000 claims description 9
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 9
• 125000002636 imidazolinyl group Chemical group 0.000 claims description 9
• 125000000160 oxazolidinyl group Chemical group 0.000 claims description 9
• 125000005968 oxazolinyl group Chemical group 0.000 claims description 9
• 150000003141 primary amines Chemical class 0.000 claims description 9
• 208000037803 restenosis Diseases 0.000 claims description 9
• 150000003335 secondary amines Chemical class 0.000 claims description 9
• 125000001984 thiazolidinyl group Chemical group 0.000 claims description 9
• 125000002769 thiazolinyl group Chemical group 0.000 claims description 9
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 9
• 125000001425 triazolyl group Chemical group 0.000 claims description 9
• 125000000183 1,4-thiazinyl group Chemical group S1C(C=NC=C1)* 0.000 claims description 8
• IMFFMUPJZJSIAL-UHFFFAOYSA-N 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC(C(O)=O)=CC=C2N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 IMFFMUPJZJSIAL-UHFFFAOYSA-N 0.000 claims description 8
• IEMAOEFPZAIMCN-UHFFFAOYSA-N 1H-pyrazole Chemical compound C=1C=NNC=1.C=1C=NNC=1 IEMAOEFPZAIMCN-UHFFFAOYSA-N 0.000 claims description 8
• 125000002785 azepinyl group Chemical group 0.000 claims description 8
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 8
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
• 125000003971 isoxazolinyl group Chemical group 0.000 claims description 8
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 8
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 7
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 7
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 7
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 7
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 7
• 125000000164 1,3-thiazinyl group Chemical group S1C(N=CC=C1)* 0.000 claims description 7
• OTHZUYXCXAQVKE-UHFFFAOYSA-N 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC(C(O)=O)=CC=C2N1CC(=O)NC1=CC=C(Cl)C=N1 OTHZUYXCXAQVKE-UHFFFAOYSA-N 0.000 claims description 7
• NVKJJNQVQGPXLK-UHFFFAOYSA-N 3-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC=C(C(O)=O)C=C2N1CC(=O)NC1=CC=C(Cl)C=N1 NVKJJNQVQGPXLK-UHFFFAOYSA-N 0.000 claims description 7
• 239000003146 anticoagulant agent Substances 0.000 claims description 7
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 7
• 238000002316 cosmetic surgery Methods 0.000 claims description 7
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 7
• 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 7
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
• 125000002755 pyrazolinyl group Chemical group 0.000 claims description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 claims description 7
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 claims description 6
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims description 6
• USHKKKQCKYHKPT-UHFFFAOYSA-N 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[[4-(3-oxomorpholin-4-yl)phenyl]carbamoyl]benzimidazole-4-carboxylic acid Chemical compound C=1C=C(N2C(COCC2)=O)C=CC=1NC(=O)C1=NC=2C(C(=O)O)=CC=CC=2N1CC(=O)NC1=CC=C(Cl)C=N1 USHKKKQCKYHKPT-UHFFFAOYSA-N 0.000 claims description 6
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• JWRBFKWKCPLVAN-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC=C(C(O)=O)C=C2N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 JWRBFKWKCPLVAN-UHFFFAOYSA-N 0.000 claims description 6
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 6
• 230000020764 fibrinolysis Effects 0.000 claims description 6
• NBTUSWGFIAOXSE-UHFFFAOYSA-N methyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C2=CC(C(=O)OC)=CC=C2N=C1C(=O)NC1CCN(C(C)C)CC1 NBTUSWGFIAOXSE-UHFFFAOYSA-N 0.000 claims description 6
• 150000004702 methyl esters Chemical class 0.000 claims description 6
• VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 claims description 6
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 6
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• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 5
• XFAGYLAXLABEPX-UHFFFAOYSA-N 1-[(3-methoxyphenyl)methyl]-2-[[4-(3-oxomorpholin-4-yl)phenyl]carbamoyl]benzimidazole-4-carboxylic acid Chemical compound COC1=CC=CC(CN2C3=CC=CC(=C3N=C2C(=O)NC=2C=CC(=CC=2)N2C(COCC2)=O)C(O)=O)=C1 XFAGYLAXLABEPX-UHFFFAOYSA-N 0.000 claims description 5
• DIMMCXSJHNXNGH-UHFFFAOYSA-N CC(C)N(CC1)CCC1N.OC(C1=NC2=CC=CN=C2N1CC1=NOC(C(S2)=CC=C2Cl)=C1)=O Chemical compound CC(C)N(CC1)CCC1N.OC(C1=NC2=CC=CN=C2N1CC1=NOC(C(S2)=CC=C2Cl)=C1)=O DIMMCXSJHNXNGH-UHFFFAOYSA-N 0.000 claims description 5
• VJZAULNSOFVHLR-UHFFFAOYSA-N CC(C)N(CC1)CCC1N.OCCS(C(C=C1)=CC2=C1N=C(C(O)=O)N2CC1=NOC(C(S2)=CC=C2Cl)=C1)(=O)=O Chemical compound CC(C)N(CC1)CCC1N.OCCS(C(C=C1)=CC2=C1N=C(C(O)=O)N2CC1=NOC(C(S2)=CC=C2Cl)=C1)(=O)=O VJZAULNSOFVHLR-UHFFFAOYSA-N 0.000 claims description 5
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• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
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• ZBZGBPFTYUQMBN-UHFFFAOYSA-N methyl 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC(C(=O)OC)=CC=C2N1CC(=O)NC1=CC=C(Cl)C=N1 ZBZGBPFTYUQMBN-UHFFFAOYSA-N 0.000 claims description 5
• CGDPDGHSZPKHCR-UHFFFAOYSA-N methyl 1-[[2-(5-chlorothiophen-2-yl)-1,3-thiazol-5-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC(C(=O)OC)=CC=C2N1CC(S1)=CN=C1C1=CC=C(Cl)S1 CGDPDGHSZPKHCR-UHFFFAOYSA-N 0.000 claims description 5
• WWAGMZQRSHCKNM-UHFFFAOYSA-N methyl 1-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-4-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC=2C(C(=O)OC)=CC=CC=2N1CC(=NO1)C=C1C1=CC=C(Cl)S1 WWAGMZQRSHCKNM-UHFFFAOYSA-N 0.000 claims description 5
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• SDNRWJHURGVZEU-UHFFFAOYSA-N methyl 3-[[2-(5-chlorothiophen-2-yl)-1,3-thiazol-5-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C=1N=C(C=2SC(Cl)=CC=2)SC=1CN1C2=CC(C(=O)OC)=CC=C2N=C1C(=O)NC1CCN(C(C)C)CC1 SDNRWJHURGVZEU-UHFFFAOYSA-N 0.000 claims description 5
• QUMVGVQEGRHYJL-UHFFFAOYSA-N methyl 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-4-carboxylate Chemical compound C1=C(C=2SC(Cl)=CC=2)ON=C1CN1C=2C(C(=O)OC)=CC=CC=2N=C1C(=O)NC1CCN(C(C)C)CC1 QUMVGVQEGRHYJL-UHFFFAOYSA-N 0.000 claims description 5
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• ULFLLWZVYQOGGX-UHFFFAOYSA-N 1-cyclohexyloxycarbonyloxyethyl 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-4-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=C(C(=O)OC(C)OC(=O)OC3CCCCC3)C=CC=C2N1CC(=O)NC1=CC=C(Cl)C=N1 ULFLLWZVYQOGGX-UHFFFAOYSA-N 0.000 claims description 4
• JECVXIDQIMIPQP-UHFFFAOYSA-N 1-cyclohexyloxycarbonyloxyethyl 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC(C(=O)OC(C)OC(=O)OC3CCCCC3)=CC=C2N1CC(=O)NC1=CC=C(Cl)C=N1 JECVXIDQIMIPQP-UHFFFAOYSA-N 0.000 claims description 4
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• OMERXXSQPSTCGL-UHFFFAOYSA-N 1-ethoxycarbonyloxyethyl 3-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C=1C=C(Cl)C=NC=1NC(=O)CN1C2=CC(C(=O)OC(C)OC(=O)OCC)=CC=C2N=C1C(=O)NC1CCN(C(C)C)CC1 OMERXXSQPSTCGL-UHFFFAOYSA-N 0.000 claims description 4
• KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 claims description 4
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• ZVQYJXQMUCYMIH-UHFFFAOYSA-N 3-[[5-(5-chlorothiophen-2-yl)-1,2-oxazol-3-yl]methyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-4-carboxylic acid Chemical compound C1CN(C(C)C)CCC1NC(=O)C1=NC2=CC=CC(C(O)=O)=C2N1CC1=NOC(C=2SC(Cl)=CC=2)=C1 ZVQYJXQMUCYMIH-UHFFFAOYSA-N 0.000 claims description 4
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• 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
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• CPGODECAMZKHGJ-UHFFFAOYSA-N NC(CC1)CCN1C1=NC=NC=C1.OC(C1=NC(C=CC=C2)=C2N1CC1=NOC(C(S2)=CC=C2Cl)=C1)=O Chemical compound NC(CC1)CCN1C1=NC=NC=C1.OC(C1=NC(C=CC=C2)=C2N1CC1=NOC(C(S2)=CC=C2Cl)=C1)=O CPGODECAMZKHGJ-UHFFFAOYSA-N 0.000 claims description 4
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• ZYDMMMUCMLISJM-UHFFFAOYSA-N methyl 1-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[[4-(3-oxomorpholin-4-yl)phenyl]carbamoyl]benzimidazole-4-carboxylate Chemical compound C=1C=C(N2C(COCC2)=O)C=CC=1NC(=O)C1=NC=2C(C(=O)OC)=CC=CC=2N1CC(=O)NC1=CC=C(Cl)C=N1 ZYDMMMUCMLISJM-UHFFFAOYSA-N 0.000 claims description 4
• XGKNSCVXIMCTPQ-UHFFFAOYSA-N methyl 3-[2-[(5-chloropyridin-2-yl)amino]-2-oxoethyl]-2-[(1-propan-2-ylpiperidin-4-yl)carbamoyl]benzimidazole-5-carboxylate Chemical compound C=1C=C(Cl)C=NC=1NC(=O)CN1C2=CC(C(=O)OC)=CC=C2N=C1C(=O)NC1CCN(C(C)C)CC1 XGKNSCVXIMCTPQ-UHFFFAOYSA-N 0.000 claims description 4
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