CA2511349A1 - Nouveaux composes heterobicycliques azotes substitues, leurs preparations et leurs utilisations comme compositions pharmaceutiques - Google Patents
Nouveaux composes heterobicycliques azotes substitues, leurs preparations et leurs utilisations comme compositions pharmaceutiques Download PDFInfo
- Publication number
- CA2511349A1 CA2511349A1 CA002511349A CA2511349A CA2511349A1 CA 2511349 A1 CA2511349 A1 CA 2511349A1 CA 002511349 A CA002511349 A CA 002511349A CA 2511349 A CA2511349 A CA 2511349A CA 2511349 A1 CA2511349 A1 CA 2511349A1
- Authority
- CA
- Canada
- Prior art keywords
- chloro
- carbonyl
- alkyl
- group
- benzimidazol
- Prior art date
- 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.)
- Abandoned
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title abstract description 3
- 238000002360 preparation method Methods 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 83
- 239000000203 mixture Substances 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 23
- 108010074860 Factor Xa Proteins 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 6
- -1 phenylsulphonyl group Chemical group 0.000 claims description 699
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 275
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 236
- 229910052801 chlorine Inorganic materials 0.000 claims description 226
- 239000000460 chlorine Substances 0.000 claims description 220
- 125000006842 cycloalkyleneimino group Chemical group 0.000 claims description 214
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 195
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 140
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 135
- 229910052757 nitrogen Inorganic materials 0.000 claims description 102
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 100
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 86
- 125000001072 heteroaryl group Chemical group 0.000 claims description 75
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 72
- 239000001301 oxygen Substances 0.000 claims description 72
- 229910052760 oxygen Inorganic materials 0.000 claims description 72
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 69
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 67
- 125000004432 carbon atom Chemical group C* 0.000 claims description 59
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 57
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 52
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 51
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000001153 fluoro group Chemical group F* 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 27
- 239000011737 fluorine Substances 0.000 claims description 27
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 26
- 125000002950 monocyclic group Chemical group 0.000 claims description 25
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 24
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 23
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 238000006467 substitution reaction Methods 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 150000001721 carbon Chemical group 0.000 claims description 19
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 17
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 14
- 238000001727 in vivo Methods 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims description 13
- 125000006164 6-membered heteroaryl group Chemical group 0.000 claims description 13
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 12
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 11
- VZQWOZQUPVBAOL-QMMMGPOBSA-N 6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazoline-7-carboxylic acid Chemical compound ClC1=CC=C2NC([C@@H](NC=3C4=CC(Cl)=C(C(O)=O)C=C4N=CN=3)C)=NC2=C1 VZQWOZQUPVBAOL-QMMMGPOBSA-N 0.000 claims description 11
- RQHGXOYKVGDQRP-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 RQHGXOYKVGDQRP-IBGZPJMESA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 11
- XGBHUMKSNKSZNX-AWEZNQCLSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]-6-methylquinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)N1CCCC1 XGBHUMKSNKSZNX-AWEZNQCLSA-N 0.000 claims description 10
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 10
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 8
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 8
- YIXULUKTIICPNC-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 YIXULUKTIICPNC-IBGZPJMESA-N 0.000 claims description 8
- LAXOLIIYLHMPTH-VWLOTQADSA-N benzyl n-[(3s)-3-(6-chloro-1h-benzimidazol-2-yl)-3-[[6-chloro-7-(2,5-dihydropyrrole-1-carbonyl)quinazolin-4-yl]amino]propyl]carbamate Chemical compound C([C@@H](C=1NC2=CC=C(C=C2N=1)Cl)NC=1C2=CC(Cl)=C(C(=O)N3CC=CC3)C=C2N=CN=1)CNC(=O)OCC1=CC=CC=C1 LAXOLIIYLHMPTH-VWLOTQADSA-N 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 150000003413 spiro compounds Chemical class 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- QNFRWFBDOZLXTM-UHFFFAOYSA-N 2-[[4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoyl]-methylamino]acetic acid Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(CC(O)=O)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 QNFRWFBDOZLXTM-UHFFFAOYSA-N 0.000 claims description 7
- XLIRHZUKQOEEKW-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-1-(1-oxo-1,4-thiazinan-4-yl)butan-1-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)N1CCS(=O)CC1 XLIRHZUKQOEEKW-UHFFFAOYSA-N 0.000 claims description 7
- KPCJCGWQNRDYHS-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(2,2,2-trifluoroethyl)butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCC(F)(F)F)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 KPCJCGWQNRDYHS-UHFFFAOYSA-N 0.000 claims description 7
- HGWPBTGFBUCYDA-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(2-hydroxyethyl)butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCO)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 HGWPBTGFBUCYDA-UHFFFAOYSA-N 0.000 claims description 7
- IYKBEOXZYPPJCM-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(piperidin-4-ylmethyl)butanamide Chemical compound N1C2=CC(Cl)=CC=C2N=C1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NCC1CCNCC1 IYKBEOXZYPPJCM-UHFFFAOYSA-N 0.000 claims description 7
- GZERKQHTAMDCGI-UHFFFAOYSA-N 4-[4-[[1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methylquinoline-7-carbonyl]piperazin-2-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCSC)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCNC(=O)C1 GZERKQHTAMDCGI-UHFFFAOYSA-N 0.000 claims description 7
- ZZBSAXFWOZVWOG-OMOCHNIRSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]-6-methylquinolin-7-yl]methanone Chemical compound N=1C2=CC=C(Cl)C=C2NC=1C(C)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCC[C@@H]1CN ZZBSAXFWOZVWOG-OMOCHNIRSA-N 0.000 claims description 7
- XAHSRTFNRQVPDW-QRWLVFNGSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN XAHSRTFNRQVPDW-QRWLVFNGSA-N 0.000 claims description 7
- HPHBHDUSVYOGTD-QRWLVFNGSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN HPHBHDUSVYOGTD-QRWLVFNGSA-N 0.000 claims description 7
- RFWYAAZYBLYSRF-LJQANCHMSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](CO)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 RFWYAAZYBLYSRF-LJQANCHMSA-N 0.000 claims description 7
- CGVLJASAIJQWHX-NRFANRHFSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-(1,1-dioxo-1,2-thiazolidin-2-yl)propyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound C([C@@H](C=1NC2=CC=C(C=C2N=1)Cl)NC=1C2=CC(Cl)=C(C(=O)N3CC=CC3)C=C2N=CN=1)CN1CCCS1(=O)=O CGVLJASAIJQWHX-NRFANRHFSA-N 0.000 claims description 7
- UGIZUYOZZYUSLI-WMZOPIPTSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-[(2s)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]methanone Chemical compound C([C@@H]1CCCN1C(=O)C=1C=C2N=CN=C(C2=CC=1Cl)N[C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)N1CCCC1 UGIZUYOZZYUSLI-WMZOPIPTSA-N 0.000 claims description 7
- TVRYMMKZRZBXBH-VWLOTQADSA-N benzyl (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound C([C@@H](C=1NC2=CC=C(C=C2N=1)Cl)NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CC(=O)OCC1=CC=CC=C1 TVRYMMKZRZBXBH-VWLOTQADSA-N 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- VXLJQDPUTFXYCN-FQEVSTJZSA-N ethyl (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound N([C@@H](CCC(=O)OCC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 VXLJQDPUTFXYCN-FQEVSTJZSA-N 0.000 claims description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 7
- DEJXXVQJMXTPLQ-SFHVURJKSA-N (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoic acid Chemical compound N([C@@H](CCC(=O)O)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 DEJXXVQJMXTPLQ-SFHVURJKSA-N 0.000 claims description 6
- MVGLQCNJKHVLGH-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-1-(4-methylpiperazin-1-yl)butan-1-one Chemical compound C1CN(C)CCN1C(=O)CCC(C=1NC2=CC(Cl)=CC=C2N=1)NC1=NC=NC2=CC(C(=O)N3CCCC3)=C(Cl)C=C12 MVGLQCNJKHVLGH-UHFFFAOYSA-N 0.000 claims description 6
- KZBRFLRQXMZOTJ-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-1-piperidin-1-ylbutan-1-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)N1CCCCC1 KZBRFLRQXMZOTJ-UHFFFAOYSA-N 0.000 claims description 6
- WKZLSULWHNTYQH-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[3-(dimethylamino)propyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCCN(C)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 WKZLSULWHNTYQH-UHFFFAOYSA-N 0.000 claims description 6
- SIJWTCYOPDQSDX-UHFFFAOYSA-N 4-[4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]-6-methylquinoline-7-carbonyl]piperazin-2-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCNC(=O)C1 SIJWTCYOPDQSDX-UHFFFAOYSA-N 0.000 claims description 6
- FFXMMUQJKCFJLO-GOSISDBHSA-N 4-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]amino]quinazoline-7-carbonyl]piperazin-2-one Chemical compound N([C@H](CO)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCNC(=O)C1 FFXMMUQJKCFJLO-GOSISDBHSA-N 0.000 claims description 6
- HGNBKXMAULMPKA-BEUBQONESA-N [(2r)-2-[amino(methylsulfonyl)methyl]pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1C(N)S(C)(=O)=O HGNBKXMAULMPKA-BEUBQONESA-N 0.000 claims description 6
- ULZQATHFDXQXMJ-JOCHJYFZSA-N [(2s)-2-(6-chloro-1h-benzimidazol-2-yl)-2-[[6-chloro-7-(2,5-dihydropyrrole-1-carbonyl)quinazolin-4-yl]amino]ethyl] 2-methylpropanoate Chemical compound N([C@H](COC(=O)C(C)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 ULZQATHFDXQXMJ-JOCHJYFZSA-N 0.000 claims description 6
- OWHUQAVYCBKEPD-SFHVURJKSA-N [4-[[(1s)-3-amino-1-(6-chloro-1h-benzimidazol-2-yl)propyl]amino]-6-chloroquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCN)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 OWHUQAVYCBKEPD-SFHVURJKSA-N 0.000 claims description 6
- WVBUFIWRIFMHHI-UHFFFAOYSA-N [4-[[1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methylquinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCSC)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCCC1 WVBUFIWRIFMHHI-UHFFFAOYSA-N 0.000 claims description 6
- RXMKXQLMQHESMK-UHFFFAOYSA-N [4-[[1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]-6-methylquinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound CC1=CC2=C(NC(CCS(C)(=O)=O)C=3NC4=CC=C(Cl)C=C4N=3)C=CN=C2C=C1C(=O)N1CCCC1 RXMKXQLMQHESMK-UHFFFAOYSA-N 0.000 claims description 6
- ZNQCCBMUUWWSSS-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methoxypropyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCOC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 ZNQCCBMUUWWSSS-IBGZPJMESA-N 0.000 claims description 6
- HAJMCTXDBRVESQ-WUTYVCDSSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfinylpropyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](CCS(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 HAJMCTXDBRVESQ-WUTYVCDSSA-N 0.000 claims description 6
- ZBLDZSBGMXPXNY-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfonylpropyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@@H](CCS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 ZBLDZSBGMXPXNY-IBGZPJMESA-N 0.000 claims description 6
- PULJCUHABQICCL-IBGZPJMESA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)butyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 PULJCUHABQICCL-IBGZPJMESA-N 0.000 claims description 6
- WQUXFWRNMWSHNO-NSHDSACASA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-(1,3-thiazolidin-3-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCSC1 WQUXFWRNMWSHNO-NSHDSACASA-N 0.000 claims description 6
- 125000005336 allyloxy group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 6
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- HJMJEZOLJWXPCI-XJKSGUPXSA-N n-[[(2r)-1-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazoline-7-carbonyl]pyrrolidin-2-yl]methyl]acetamide Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CNC(C)=O HJMJEZOLJWXPCI-XJKSGUPXSA-N 0.000 claims description 6
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- GDIKJXXZRARNKX-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n,n-diethylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(CC)CC)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 GDIKJXXZRARNKX-UHFFFAOYSA-N 0.000 claims description 5
- FZMLWCDQELFMQZ-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(cyclopropylmethyl)-n-methylbutanamide Chemical compound N=1C=NC2=CC(C(=O)N3CCCC3)=C(Cl)C=C2C=1NC(C=1NC2=CC=C(Cl)C=C2N=1)CCC(=O)N(C)CC1CC1 FZMLWCDQELFMQZ-UHFFFAOYSA-N 0.000 claims description 5
- DWHYINQOWHPWPD-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[3-(2-oxopyrrolidin-1-yl)propyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NCCCN1CCCC1=O DWHYINQOWHPWPD-UHFFFAOYSA-N 0.000 claims description 5
- SRQBXGREFBIHPK-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-cyclopentylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NC1CCCC1 SRQBXGREFBIHPK-UHFFFAOYSA-N 0.000 claims description 5
- VKUSEKFRMNQHOK-ONMLUTBRSA-O C[C@@H](C1=NC2=CC(Cl)=CC=C2N1)NC(C1=C2)=NC=NC1=CC(C([S+]1C(CNC(C)=O)NCC1)=O)=C2Cl Chemical compound C[C@@H](C1=NC2=CC(Cl)=CC=C2N1)NC(C1=C2)=NC=NC1=CC(C([S+]1C(CNC(C)=O)NCC1)=O)=C2Cl VKUSEKFRMNQHOK-ONMLUTBRSA-O 0.000 claims description 5
- XANBDYJRXBRKPJ-ZUOKHONESA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxyethyl]amino]quinazolin-7-yl]methanone Chemical compound NC[C@H]1CCCN1C(=O)C1=CC2=NC=NC(N[C@H](CO)C=3NC4=CC=C(Cl)C=C4N=3)=C2C=C1Cl XANBDYJRXBRKPJ-ZUOKHONESA-N 0.000 claims description 5
- CPVNKLWRHQRGFJ-QBYSONFBSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfinylpropyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](CCS(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN CPVNKLWRHQRGFJ-QBYSONFBSA-N 0.000 claims description 5
- YLMSXNRSXYNMJV-GXTWGEPZSA-N [(2r)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@@H]1CN YLMSXNRSXYNMJV-GXTWGEPZSA-N 0.000 claims description 5
- GWIPBXROSQYNNI-UHFFFAOYSA-N [2-(aminomethyl)piperidin-1-yl]-[6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazolin-7-yl]methanone Chemical compound N=1C2=CC=C(Cl)C=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCCC1CN GWIPBXROSQYNNI-UHFFFAOYSA-N 0.000 claims description 5
- WVUUBWGNSHRFJO-HWYAHNCWSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-methylquinazolin-7-yl]-(1,3-thiazolidin-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)C1NCCS1 WVUUBWGNSHRFJO-HWYAHNCWSA-N 0.000 claims description 5
- QDEWTQJURKBCOQ-IBGZPJMESA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methoxyquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound COC1=CC2=C(N[C@@H](CCSC)C=3NC4=CC=C(Cl)C=C4N=3)N=CN=C2C=C1C(=O)N1CC=CC1 QDEWTQJURKBCOQ-IBGZPJMESA-N 0.000 claims description 5
- NXKZJYBXDNTGTI-FQEVSTJZSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-3-methylsulfanylpropyl]amino]-6-methylquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CCSC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)N1CC=CC1 NXKZJYBXDNTGTI-FQEVSTJZSA-N 0.000 claims description 5
- QHBCTTONRIWUBW-ZDUSSCGKSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]-6-methoxyquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound COC1=CC2=C(N[C@@H](C)C=3NC4=CC=C(Cl)C=C4N=3)N=CN=C2C=C1C(=O)N1CC=CC1 QHBCTTONRIWUBW-ZDUSSCGKSA-N 0.000 claims description 5
- YPHYCHLMZNDYID-HXUWFJFHSA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)N1CC=CC1 YPHYCHLMZNDYID-HXUWFJFHSA-N 0.000 claims description 5
- BCFWJMYQBDXGNR-HXUWFJFHSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 BCFWJMYQBDXGNR-HXUWFJFHSA-N 0.000 claims description 5
- ABXRNOGOFRLAFG-HXUWFJFHSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 ABXRNOGOFRLAFG-HXUWFJFHSA-N 0.000 claims description 5
- KDSFMIAZGVXFRR-UHFFFAOYSA-N [6-chloro-4-[[(6-chloro-1h-benzimidazol-2-yl)-thiophen-3-ylmethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C1=CSC=C1)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 KDSFMIAZGVXFRR-UHFFFAOYSA-N 0.000 claims description 5
- NYFXIFORCJEPCK-FQEVSTJZSA-N ethyl (4s)-4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(2,5-dihydropyrrole-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound N([C@@H](CCC(=O)OCC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 NYFXIFORCJEPCK-FQEVSTJZSA-N 0.000 claims description 5
- WNCGGHURWVEGHN-IBGZPJMESA-N n-[(3s)-3-(6-chloro-1h-benzimidazol-2-yl)-3-[[6-chloro-7-(2,5-dihydropyrrole-1-carbonyl)quinazolin-4-yl]amino]propyl]methanesulfonamide Chemical compound N([C@@H](CCNS(=O)(=O)C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 WNCGGHURWVEGHN-IBGZPJMESA-N 0.000 claims description 5
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- RYLCXPVFVLAVSE-UHFFFAOYSA-N 1-[4-[6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazoline-7-carbonyl]piperazin-1-yl]ethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCN(C(C)=O)CC1 RYLCXPVFVLAVSE-UHFFFAOYSA-N 0.000 claims description 4
- VVFFDNFORBOEJD-HXUWFJFHSA-N 2-[(2s)-2-(6-chloro-1h-benzimidazol-2-yl)-2-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]ethoxy]acetic acid Chemical compound N([C@H](COCC(=O)O)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 VVFFDNFORBOEJD-HXUWFJFHSA-N 0.000 claims description 4
- CFANNSCKHYMDMN-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-1-[4-(1,3-thiazol-2-yl)piperazin-1-yl]butan-1-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)N(CC1)CCN1C1=NC=CS1 CFANNSCKHYMDMN-UHFFFAOYSA-N 0.000 claims description 4
- KTOSDBDBNCWIKN-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-1-morpholin-4-ylbutan-1-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)N1CCOCC1 KTOSDBDBNCWIKN-UHFFFAOYSA-N 0.000 claims description 4
- LOWSCQHGSZHIIX-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[2-(dimethylamino)ethyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCN(C)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 LOWSCQHGSZHIIX-UHFFFAOYSA-N 0.000 claims description 4
- MAUOWUDOVCSFNL-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-cyclopropylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NC1CC1 MAUOWUDOVCSFNL-UHFFFAOYSA-N 0.000 claims description 4
- SGTBMMKDVSGGJE-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-piperidin-2-ylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NC1CCCCN1 SGTBMMKDVSGGJE-UHFFFAOYSA-N 0.000 claims description 4
- DEJXXVQJMXTPLQ-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoic acid Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)O)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 DEJXXVQJMXTPLQ-UHFFFAOYSA-N 0.000 claims description 4
- SYJZUAHDFZZUGI-JPYJTQIMSA-N 6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-4-oxo-4-pyrrolidin-1-ylbutyl]amino]-n-[[(2r)-pyrrolidin-2-yl]methyl]quinazoline-7-carboxamide Chemical compound C([C@@H](C=1NC2=CC=C(C=C2N=1)Cl)NC=1C2=CC(Cl)=C(C(=O)NC[C@@H]3NCCC3)C=C2N=CN=1)CC(=O)N1CCCC1 SYJZUAHDFZZUGI-JPYJTQIMSA-N 0.000 claims description 4
- GPUHJPCLUJUQCD-UHFFFAOYSA-N 8-[4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)N(CC1)CCC21CNC(=O)O2 GPUHJPCLUJUQCD-UHFFFAOYSA-N 0.000 claims description 4
- HJUQOBQELSOVIZ-WUJWULDRSA-N [(2s)-2-(2-aminoethyl)pyrrolidin-1-yl]-[6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazolin-7-yl]methanone Chemical compound N=1C2=CC=C(Cl)C=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@H]1CCN HJUQOBQELSOVIZ-WUJWULDRSA-N 0.000 claims description 4
- QIGJISJNAWXPSF-STQMWFEESA-N [(3s)-3-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC[C@@H](CN)C1 QIGJISJNAWXPSF-STQMWFEESA-N 0.000 claims description 4
- VRNWJBJSTGHAJY-UHFFFAOYSA-N [2-(2-aminoethyl)piperidin-1-yl]-[6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazolin-7-yl]methanone Chemical compound N=1C2=CC=C(Cl)C=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCCC1CCN VRNWJBJSTGHAJY-UHFFFAOYSA-N 0.000 claims description 4
- GWOSHEGHIBUWTR-UHFFFAOYSA-N [4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]-6-methylquinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2C)=CC=NC1=CC=2C(=O)N1CCCC1 GWOSHEGHIBUWTR-UHFFFAOYSA-N 0.000 claims description 4
- BJTZBQBIYFZVGU-UHFFFAOYSA-N [4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2)=CC=NC1=CC=2C(=O)N1CCCC1 BJTZBQBIYFZVGU-UHFFFAOYSA-N 0.000 claims description 4
- ZZHRRQMWVFZPLU-UUSAFJCLSA-N [4-[[(1s)-1-(6-bromo-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-chloroquinazolin-7-yl]-(2,5-dihydro-1h-pyrrol-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC(Br)=CC=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCC=C1 ZZHRRQMWVFZPLU-UUSAFJCLSA-N 0.000 claims description 4
- IQKAOIBKAHJEBY-PIJUOJQZSA-N [4-[[(1s)-1-(6-bromo-1h-benzimidazol-2-yl)ethyl]amino]-6-chloroquinazolin-7-yl]-(2,5-dihydro-1h-pyrrol-2-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC(Br)=CC=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCC=C1 IQKAOIBKAHJEBY-PIJUOJQZSA-N 0.000 claims description 4
- OWFUOMYKGDFREB-HXUWFJFHSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-methoxyquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2OC)=NC=NC1=CC=2C(=O)N1CC=CC1 OWFUOMYKGDFREB-HXUWFJFHSA-N 0.000 claims description 4
- NZRCKCNDRZSXHM-ZZWBGTBQSA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(1,3-thiazolidin-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)C1NCCS1 NZRCKCNDRZSXHM-ZZWBGTBQSA-N 0.000 claims description 4
- IKMZDHWOYWYJTR-LBPRGKRZSA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)N1CC=CC1 IKMZDHWOYWYJTR-LBPRGKRZSA-N 0.000 claims description 4
- NKRPWOFHPWVMTA-UHFFFAOYSA-N [6-chloro-4-[(6-chloro-1h-benzimidazol-2-yl)methylamino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1CNC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 NKRPWOFHPWVMTA-UHFFFAOYSA-N 0.000 claims description 4
- KRFFCDITXHDYGG-ZZWBGTBQSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]quinazolin-7-yl]-(1,3-thiazolidin-2-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCCS1 KRFFCDITXHDYGG-ZZWBGTBQSA-N 0.000 claims description 4
- KRKQMWHVCXTIFN-LBPRGKRZSA-N [6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC=CC1 KRKQMWHVCXTIFN-LBPRGKRZSA-N 0.000 claims description 4
- IEKZNBMAMSXMQW-VHOQYMNQSA-N [6-chloro-4-[[(1s,2s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-hydroxypropyl]amino]quinazolin-7-yl]-(2,5-dihydro-1h-pyrrol-2-yl)methanone Chemical compound N([C@H]([C@@H](O)C)C=1NC2=CC(Cl)=CC=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)C1NCC=C1 IEKZNBMAMSXMQW-VHOQYMNQSA-N 0.000 claims description 4
- OOYYVSNGPKBBSS-UHFFFAOYSA-N [6-chloro-4-[[(6-chloro-1h-benzimidazol-2-yl)-(2-chlorophenyl)methyl]amino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C=1C(=CC=CC=1)Cl)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 OOYYVSNGPKBBSS-UHFFFAOYSA-N 0.000 claims description 4
- TVRYMMKZRZBXBH-UHFFFAOYSA-N benzyl 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]butanoate Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)OCC1=CC=CC=C1 TVRYMMKZRZBXBH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
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- 125000005843 halogen group Chemical group 0.000 claims description 4
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- OJQJNCONUOXCEZ-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(1-phenylethyl)butanamide Chemical compound C=1C=CC=CC=1C(C)NC(=O)CCC(C=1NC2=CC(Cl)=CC=C2N=1)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 OJQJNCONUOXCEZ-UHFFFAOYSA-N 0.000 claims description 3
- TUEGSDGZOVSICV-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-(2-methoxyethyl)butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)NCCOC)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 TUEGSDGZOVSICV-UHFFFAOYSA-N 0.000 claims description 3
- LBIQDBLFUCVHAM-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[2-(dimethylamino)-2-oxoethyl]-n-methylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(C)CC(=O)N(C)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 LBIQDBLFUCVHAM-UHFFFAOYSA-N 0.000 claims description 3
- KJAZZYOZBPUDLE-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-[2-(dimethylamino)ethyl]-n-methylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(C)CCN(C)C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 KJAZZYOZBPUDLE-UHFFFAOYSA-N 0.000 claims description 3
- ALKOINOBWCYBTA-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-methyl-n-[2-(methylamino)-2-oxoethyl]butanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(CCC(=O)N(C)CC(=O)NC)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 ALKOINOBWCYBTA-UHFFFAOYSA-N 0.000 claims description 3
- WQZNLXOLFPLAMV-UHFFFAOYSA-N 4-(6-chloro-1h-benzimidazol-2-yl)-4-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]-n-piperidin-4-ylbutanamide Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(NC=1C2=CC(Cl)=C(C(=O)N3CCCC3)C=C2N=CN=1)CCC(=O)NC1CCNCC1 WQZNLXOLFPLAMV-UHFFFAOYSA-N 0.000 claims description 3
- SRZZLKYSYHWCOK-NSHDSACASA-N 4-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazoline-7-carbonyl]piperazin-2-one Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCNC(=O)C1 SRZZLKYSYHWCOK-NSHDSACASA-N 0.000 claims description 3
- YLMSXNRSXYNMJV-JSGCOSHPSA-N [(2s)-2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCC[C@H]1CN YLMSXNRSXYNMJV-JSGCOSHPSA-N 0.000 claims description 3
- QIGJISJNAWXPSF-QWHCGFSZSA-N [(3r)-3-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)ethyl]amino]quinazolin-7-yl]methanone Chemical compound N([C@@H](C)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CC[C@H](CN)C1 QIGJISJNAWXPSF-QWHCGFSZSA-N 0.000 claims description 3
- YLMSXNRSXYNMJV-UHFFFAOYSA-N [2-(aminomethyl)pyrrolidin-1-yl]-[6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazolin-7-yl]methanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1CN YLMSXNRSXYNMJV-UHFFFAOYSA-N 0.000 claims description 3
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- HFMBNEJAARQWNS-UHFFFAOYSA-N [4-[(6-chloro-1h-benzimidazol-2-yl)methylamino]quinazolin-7-yl]-pyrrolidin-1-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1CNC(C1=CC=2)=NC=NC1=CC=2C(=O)N1CCCC1 HFMBNEJAARQWNS-UHFFFAOYSA-N 0.000 claims description 3
- BYOCAOZUUVQFAV-OAQYLSRUSA-N [4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)-2-methoxyethyl]amino]-6-methylquinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@H](COC)C=1NC2=CC=C(Cl)C=C2N=1)C(C1=CC=2C)=NC=NC1=CC=2C(=O)N1CC=CC1 BYOCAOZUUVQFAV-OAQYLSRUSA-N 0.000 claims description 3
- KPGWWZPSBAJRIR-IBGZPJMESA-N [6-bromo-4-[[(1s)-1-(6-chloro-1h-benzimidazol-2-yl)but-3-ynyl]amino]quinazolin-7-yl]-(2,5-dihydropyrrol-1-yl)methanone Chemical compound N([C@@H](CC#C)C=1NC2=CC=C(C=C2N=1)Cl)C(C1=CC=2Br)=NC=NC1=CC=2C(=O)N1CC=CC1 KPGWWZPSBAJRIR-IBGZPJMESA-N 0.000 claims description 3
- YDOKOCGIOPTMDF-UHFFFAOYSA-N [6-chloro-4-[1-(6-chloro-1h-benzimidazol-2-yl)ethylamino]quinazolin-7-yl]-morpholin-4-ylmethanone Chemical compound N=1C2=CC(Cl)=CC=C2NC=1C(C)NC(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCOCC1 YDOKOCGIOPTMDF-UHFFFAOYSA-N 0.000 claims description 3
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- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- SXNAZHCABMIBSZ-QFIPXVFZSA-N tert-butyl (5s)-5-(6-chloro-1h-benzimidazol-2-yl)-5-[[6-chloro-7-(pyrrolidine-1-carbonyl)quinazolin-4-yl]amino]pentanoate Chemical compound N([C@@H](CCCC(=O)OC(C)(C)C)C=1NC2=CC(Cl)=CC=C2N=1)C(C1=CC=2Cl)=NC=NC1=CC=2C(=O)N1CCCC1 SXNAZHCABMIBSZ-QFIPXVFZSA-N 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 3
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- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 229950002267 roxifiban Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960000216 tenecteplase Drugs 0.000 description 1
- XUTLOCQNGLJNSA-RGVLZGJSSA-N terbogrel Chemical compound CC(C)(C)\N=C(/NC#N)NC1=CC=CC(C(=C/CCCC(O)=O)\C=2C=NC=CC=2)=C1 XUTLOCQNGLJNSA-RGVLZGJSSA-N 0.000 description 1
- 229950006665 terbogrel Drugs 0.000 description 1
- ZCJWDAYHBBKSCE-UHFFFAOYSA-N tert-butyl 2-(aminomethyl)-6-chloro-2,3-dihydrobenzimidazole-1-carboxylate Chemical compound C1=C(Cl)C=C2N(C(=O)OC(C)(C)C)C(CN)NC2=C1 ZCJWDAYHBBKSCE-UHFFFAOYSA-N 0.000 description 1
- MYKMOIQAHCMLIR-UHFFFAOYSA-N tert-butyl 2-(methylamino)acetate Chemical compound CNCC(=O)OC(C)(C)C MYKMOIQAHCMLIR-UHFFFAOYSA-N 0.000 description 1
- XDNKVSNTIKZEMC-UHFFFAOYSA-N tert-butyl 2-(methylamino)propanoate Chemical compound CNC(C)C(=O)OC(C)(C)C XDNKVSNTIKZEMC-UHFFFAOYSA-N 0.000 description 1
- GEHBIWVQKQLYNB-UHFFFAOYSA-N tert-butyl 2-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1N GEHBIWVQKQLYNB-UHFFFAOYSA-N 0.000 description 1
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 1
- 229960003425 tirofiban Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OKZLYNSHAULDAT-UHFFFAOYSA-N triphenyl(3-triphenylphosphaniumylpropyl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CCC[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 OKZLYNSHAULDAT-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
L'invention concerne de nouveaux composés hétérocycliques azotés substitués de formule générale (I), dans laquelle B, X?1¿ à X?3¿ et R?1¿ à R?5¿ sont tels que définis dans la revendication n·1, ainsi que leurs tautomères, énantiomères, diastéréoisomères, mélanges et sels, en particulier leurs sels physiologiquement tolérables contenant des acides ou des bases inorganiques ou organiques, ces composés présentant des propriétés intéressantes. Les composés de formule générale (I) et leurs tautomères, énantiomères, diastéréoisomères, mélanges et sels, en particulier leurs sels physiologiquement tolérables contenant des acides ou des bases inorganiques ou organiques, ainsi que leurs stéréoisomères présentent des propriétés pharmacologiques intéressantes, notamment un effet antithrombotique et un effet d'inhibition du facteur Xa.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10260730A DE10260730A1 (de) | 2002-12-23 | 2002-12-23 | Neue substituierte stickstoffhaltige Heterobicyclen, deren Herstellung und deren Verwendung als Arzneimittel |
DE10260730.3 | 2002-12-23 | ||
PCT/EP2003/014378 WO2004058743A1 (fr) | 2002-12-23 | 2003-12-17 | Nouveaux composes heterobicycliques azotes substitues et leur utilisation en tant qu'inhibiteurs du facteur xa |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2511349A1 true CA2511349A1 (fr) | 2004-07-15 |
Family
ID=32404214
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002511349A Abandoned CA2511349A1 (fr) | 2002-12-23 | 2003-12-17 | Nouveaux composes heterobicycliques azotes substitues, leurs preparations et leurs utilisations comme compositions pharmaceutiques |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP1583757A1 (fr) |
JP (1) | JP2006515301A (fr) |
AR (1) | AR043685A1 (fr) |
AU (1) | AU2003298192A1 (fr) |
CA (1) | CA2511349A1 (fr) |
CL (1) | CL2003002697A1 (fr) |
DE (1) | DE10260730A1 (fr) |
PE (1) | PE20040806A1 (fr) |
TW (1) | TW200424194A (fr) |
UY (1) | UY28143A1 (fr) |
WO (1) | WO2004058743A1 (fr) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2005299693B2 (en) | 2004-10-26 | 2012-07-05 | Janssen Pharmaceutica, N.V. | Factor Xa compounds |
EP2220079A2 (fr) | 2007-11-15 | 2010-08-25 | Boehringer Ingelheim International GmbH | Amides substitués, leur fabrication et utilisation sous forme de médicaments |
CN103265524B (zh) * | 2013-05-15 | 2016-01-20 | 华东师范大学 | β-氨基-2,5-二氧六环内酯衍生物的制备方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9514265D0 (en) * | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
PE121699A1 (es) | 1997-02-18 | 1999-12-08 | Boehringer Ingelheim Pharma | Heterociclos biciclicos disustituidos como inhibidores de la trombina |
US20030114448A1 (en) * | 2001-05-31 | 2003-06-19 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
PE20040804A1 (es) * | 2002-12-19 | 2004-12-31 | Boehringer Ingelheim Pharma | DERIVADOS DE CARBOXAMIDAS COMO INHIBIDORES DEL FACTOR Xa |
-
2002
- 2002-12-23 DE DE10260730A patent/DE10260730A1/de not_active Withdrawn
-
2003
- 2003-12-12 PE PE2003001281A patent/PE20040806A1/es not_active Application Discontinuation
- 2003-12-17 CA CA002511349A patent/CA2511349A1/fr not_active Abandoned
- 2003-12-17 EP EP03795904A patent/EP1583757A1/fr not_active Withdrawn
- 2003-12-17 WO PCT/EP2003/014378 patent/WO2004058743A1/fr active Application Filing
- 2003-12-17 AU AU2003298192A patent/AU2003298192A1/en not_active Abandoned
- 2003-12-17 JP JP2004562769A patent/JP2006515301A/ja not_active Ceased
- 2003-12-19 CL CL200302697A patent/CL2003002697A1/es unknown
- 2003-12-22 UY UY28143A patent/UY28143A1/es not_active Application Discontinuation
- 2003-12-22 TW TW092136403A patent/TW200424194A/zh unknown
- 2003-12-23 AR ARP030104807A patent/AR043685A1/es not_active Suspension/Interruption
Also Published As
Publication number | Publication date |
---|---|
JP2006515301A (ja) | 2006-05-25 |
CL2003002697A1 (es) | 2005-01-14 |
AR043685A1 (es) | 2005-08-10 |
TW200424194A (en) | 2004-11-16 |
PE20040806A1 (es) | 2004-12-23 |
AU2003298192A1 (en) | 2004-07-22 |
EP1583757A1 (fr) | 2005-10-12 |
WO2004058743A1 (fr) | 2004-07-15 |
UY28143A1 (es) | 2004-07-30 |
DE10260730A1 (de) | 2004-07-01 |
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