HRP20040470A2 - Inhibitors of factor xa and other serine proteases involved in the coagulation cascade - Google Patents
Inhibitors of factor xa and other serine proteases involved in the coagulation cascade Download PDFInfo
- Publication number
- HRP20040470A2 HRP20040470A2 HR20040470A HRP20040470A HRP20040470A2 HR P20040470 A2 HRP20040470 A2 HR P20040470A2 HR 20040470 A HR20040470 A HR 20040470A HR P20040470 A HRP20040470 A HR P20040470A HR P20040470 A2 HRP20040470 A2 HR P20040470A2
- Authority
- HR
- Croatia
- Prior art keywords
- amide
- phenyl
- pyrrolidine
- chloro
- fluoro
- Prior art date
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- 108010074860 Factor Xa Proteins 0.000 title claims description 27
- 230000015271 coagulation Effects 0.000 title description 7
- 238000005345 coagulation Methods 0.000 title description 7
- 239000003112 inhibitor Substances 0.000 title description 5
- 108010022999 Serine Proteases Proteins 0.000 title description 3
- 102000012479 Serine Proteases Human genes 0.000 title description 3
- -1 O-(C1-C6) Chemical group 0.000 claims description 935
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 896
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 372
- 150000001875 compounds Chemical class 0.000 claims description 261
- QLEZWYHCXVFRKO-RFZPGFLSSA-N (2r,4r)-4-methoxypyrrolidine-1,2-dicarboxylic acid Chemical class CO[C@@H]1C[C@H](C(O)=O)N(C(O)=O)C1 QLEZWYHCXVFRKO-RFZPGFLSSA-N 0.000 claims description 184
- 125000005843 halogen group Chemical group 0.000 claims description 161
- OAWXZFGKDDFTGS-UHFFFAOYSA-N pyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCN1C(O)=O OAWXZFGKDDFTGS-UHFFFAOYSA-N 0.000 claims description 118
- 125000003118 aryl group Chemical group 0.000 claims description 96
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- HHDQVBSXYDRQGD-QWWZWVQMSA-N (2r,4r)-4-hydroxypyrrolidine-1,2-dicarboxylic acid Chemical class O[C@@H]1C[C@H](C(O)=O)N(C(O)=O)C1 HHDQVBSXYDRQGD-QWWZWVQMSA-N 0.000 claims description 68
- QLEZWYHCXVFRKO-UHFFFAOYSA-N 4-methoxypyrrolidine-1,2-dicarboxylic acid Chemical compound COC1CC(C(O)=O)N(C(O)=O)C1 QLEZWYHCXVFRKO-UHFFFAOYSA-N 0.000 claims description 68
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 59
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 50
- 229920006395 saturated elastomer Polymers 0.000 claims description 50
- 125000001072 heteroaryl group Chemical group 0.000 claims description 47
- 125000001475 halogen functional group Chemical group 0.000 claims description 46
- 125000001188 haloalkyl group Chemical group 0.000 claims description 42
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 35
- 229910052760 oxygen Inorganic materials 0.000 claims description 35
- HHDQVBSXYDRQGD-UHFFFAOYSA-N 4-hydroxypyrrolidine-1,2-dicarboxylic acid Chemical compound OC1CC(C(O)=O)N(C(O)=O)C1 HHDQVBSXYDRQGD-UHFFFAOYSA-N 0.000 claims description 32
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 25
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 25
- ZNNRVGZFHOROJG-PHDIDXHHSA-N (2r,4r)-4-ethoxypyrrolidine-1,2-dicarboxylic acid Chemical class CCO[C@@H]1C[C@H](C(O)=O)N(C(O)=O)C1 ZNNRVGZFHOROJG-PHDIDXHHSA-N 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 21
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 20
- 150000001408 amides Chemical class 0.000 claims description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 18
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 18
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 14
- GXFAYZBQUMULJS-UHFFFAOYSA-N 4-fluoropyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CC(F)CN1C(O)=O GXFAYZBQUMULJS-UHFFFAOYSA-N 0.000 claims description 14
- 208000007536 Thrombosis Diseases 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 13
- 125000003368 amide group Chemical group 0.000 claims description 13
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 13
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 10
- PSEFWMGUIGBSMX-UHFFFAOYSA-N 3,4-dihydropyrazole-2,3-dicarboxylic acid Chemical compound OC(=O)C1CC=NN1C(O)=O PSEFWMGUIGBSMX-UHFFFAOYSA-N 0.000 claims description 10
- 150000001413 amino acids Chemical class 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 150000004820 halides Chemical class 0.000 claims description 8
- 150000004702 methyl esters Chemical class 0.000 claims description 8
- 229940123583 Factor Xa inhibitor Drugs 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 239000012948 isocyanate Substances 0.000 claims description 7
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- 125000003831 tetrazolyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- OAWXZFGKDDFTGS-SCSAIBSYSA-N (2r)-pyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)[C@H]1CCCN1C(O)=O OAWXZFGKDDFTGS-SCSAIBSYSA-N 0.000 claims description 6
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 6
- 150000001721 carbon Chemical group 0.000 claims description 6
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
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- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 5
- 206010047249 Venous thrombosis Diseases 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- DMFOFFOEZAPORN-SCSAIBSYSA-N (2r)-4-oxopyrrolidine-1,2-dicarboxylic acid Chemical class OC(=O)[C@H]1CC(=O)CN1C(O)=O DMFOFFOEZAPORN-SCSAIBSYSA-N 0.000 claims description 4
- OAWXZFGKDDFTGS-BYPYZUCNSA-N (2s)-pyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(O)=O OAWXZFGKDDFTGS-BYPYZUCNSA-N 0.000 claims description 4
- STRUTHDFPCSAAP-DYESRHJHSA-N 1-[4-[[(2r,4r)-1-[(4-chlorophenyl)carbamoyl]-4-methoxypyrrolidine-2-carbonyl]amino]-3-fluorophenyl]-2-oxopyridine-3-carboxylic acid Chemical compound N1([C@H](C[C@H](C1)OC)C(=O)NC=1C(=CC(=CC=1)N1C(C(C(O)=O)=CC=C1)=O)F)C(=O)NC1=CC=C(Cl)C=C1 STRUTHDFPCSAAP-DYESRHJHSA-N 0.000 claims description 4
- UFMHTRMGVQGSMS-DNVCBOLYSA-N 1-[4-[[(2r,4r)-1-[(5-chloropyridin-2-yl)carbamoyl]-4-methoxypyrrolidine-2-carbonyl]amino]-3-fluorophenyl]-2-oxopyridine-3-carboxylic acid Chemical compound N1([C@H](C[C@H](C1)OC)C(=O)NC=1C(=CC(=CC=1)N1C(C(C(O)=O)=CC=C1)=O)F)C(=O)NC1=CC=C(Cl)C=N1 UFMHTRMGVQGSMS-DNVCBOLYSA-N 0.000 claims description 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
- LGLWSZNPYYMBRY-UHFFFAOYSA-N 3-[4-[[1-[(4-chlorophenyl)carbamoyl]-4-methoxypyrrolidine-2-carbonyl]amino]-3-fluorophenyl]-2-oxoimidazolidine-4-carboxylic acid Chemical compound C1C(OC)CC(C(=O)NC=2C(=CC(=CC=2)N2C(NCC2C(O)=O)=O)F)N1C(=O)NC1=CC=C(Cl)C=C1 LGLWSZNPYYMBRY-UHFFFAOYSA-N 0.000 claims description 4
- ZNNRVGZFHOROJG-UHFFFAOYSA-N 4-ethoxypyrrolidine-1,2-dicarboxylic acid Chemical compound CCOC1CC(C(O)=O)N(C(O)=O)C1 ZNNRVGZFHOROJG-UHFFFAOYSA-N 0.000 claims description 4
- DMFOFFOEZAPORN-UHFFFAOYSA-N 4-oxopyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CC(=O)CN1C(O)=O DMFOFFOEZAPORN-UHFFFAOYSA-N 0.000 claims description 4
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- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
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- GXFAYZBQUMULJS-IUYQGCFVSA-N (2r,4s)-4-fluoropyrrolidine-1,2-dicarboxylic acid Chemical class OC(=O)[C@H]1C[C@H](F)CN1C(O)=O GXFAYZBQUMULJS-IUYQGCFVSA-N 0.000 claims description 3
- JLMAPPKOALEWAR-OXQOHEQNSA-N 2-[4-[[(2r,4r)-1-[(4-chlorophenyl)carbamoyl]-4-methoxypyrrolidine-2-carbonyl]amino]-3-fluorophenyl]pyrazole-3-carboxylic acid Chemical compound N1([C@H](C[C@H](C1)OC)C(=O)NC=1C(=CC(=CC=1)N1C(=CC=N1)C(O)=O)F)C(=O)NC1=CC=C(Cl)C=C1 JLMAPPKOALEWAR-OXQOHEQNSA-N 0.000 claims description 3
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- XTCRVHGRTFHROD-CRAIPNDOSA-N 5-[4-[[(2r,4r)-1-[(4-chlorophenyl)carbamoyl]-4-methoxypyrrolidine-2-carbonyl]amino]-3-fluorophenyl]-1,3-oxazole-4-carboxylic acid Chemical compound N1([C@H](C[C@H](C1)OC)C(=O)NC=1C(=CC(=CC=1)C1=C(N=CO1)C(O)=O)F)C(=O)NC1=CC=C(Cl)C=C1 XTCRVHGRTFHROD-CRAIPNDOSA-N 0.000 claims description 3
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- KJPJLXBZWPQGKD-UHFFFAOYSA-N 1-[(4-chlorophenyl)carbamoyl]-5-[[2-fluoro-4-(2-methylsulfonylphenyl)phenyl]carbamoyl]pyrrolidine-3-carboxylic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(C=C1F)=CC=C1NC(=O)C1N(C(=O)NC=2C=CC(Cl)=CC=2)CC(C(O)=O)C1 KJPJLXBZWPQGKD-UHFFFAOYSA-N 0.000 claims description 2
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- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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US33416801P | 2001-11-29 | 2001-11-29 | |
US38489502P | 2002-05-31 | 2002-05-31 | |
PCT/IB2002/004757 WO2003045912A1 (en) | 2001-11-29 | 2002-11-14 | Inhibitors of factor xa and other serine proteases involved in the coagulation cascade |
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