ZA200206581B - Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor XA activity and pharmaceutical compositions containing them. - Google Patents
Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor XA activity and pharmaceutical compositions containing them. Download PDFInfo
- Publication number
- ZA200206581B ZA200206581B ZA200206581A ZA200206581A ZA200206581B ZA 200206581 B ZA200206581 B ZA 200206581B ZA 200206581 A ZA200206581 A ZA 200206581A ZA 200206581 A ZA200206581 A ZA 200206581A ZA 200206581 B ZA200206581 B ZA 200206581B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- formula
- hydrogen
- benzyl
- phenyl
- Prior art date
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- 108010074860 Factor Xa Proteins 0.000 title claims description 25
- 239000003112 inhibitor Substances 0.000 title claims description 11
- 238000000034 method Methods 0.000 title claims description 11
- 230000008569 process Effects 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 230000000694 effects Effects 0.000 title description 10
- 150000002690 malonic acid derivatives Chemical class 0.000 title description 3
- -1 4-carbamimidoyl-benzyl Chemical group 0.000 claims description 101
- 150000001875 compounds Chemical class 0.000 claims description 96
- 229910052739 hydrogen Inorganic materials 0.000 claims description 94
- 239000001257 hydrogen Substances 0.000 claims description 94
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 84
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 150000001450 anions Chemical class 0.000 claims description 13
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 11
- 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 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 230000023555 blood coagulation Effects 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 9
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 7
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 7
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 7
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 6
- 208000007536 Thrombosis Diseases 0.000 claims description 6
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- 206010047249 Venous thrombosis Diseases 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 229910014585 C2-Ce Inorganic materials 0.000 claims description 4
- 206010053567 Coagulopathies Diseases 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 208000001435 Thromboembolism Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- WUEPMEXUMQVEGN-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;2,2,2-trifluoro-n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethylamino]ethyl]acetamide Chemical compound OC(=O)C(F)(F)F.FC(F)(F)C(=O)NCCNCCNC(=O)C(F)(F)F WUEPMEXUMQVEGN-UHFFFAOYSA-N 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- YMLXAUTYQKKZJN-LSDRXPFUSA-N methyl (2s)-2-[[2-[[3-[benzyl(methyl)amino]-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CCCCC1C(C(=O)N[C@@H](CCCNC(N)=N)C(=O)OC)NC(=O)C(C(=O)N(C)CC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 YMLXAUTYQKKZJN-LSDRXPFUSA-N 0.000 claims description 2
- SYBMAVPFCGYHCI-HGDDKUDHSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 SYBMAVPFCGYHCI-HGDDKUDHSA-N 0.000 claims description 2
- FVPDKVVUQVGXCM-RWVUOVKPSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(N)=O)NC(=O)[C@H](CCCC)NC(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 FVPDKVVUQVGXCM-RWVUOVKPSA-N 0.000 claims description 2
- JUOFXQJVVIEERS-HGDDKUDHSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 JUOFXQJVVIEERS-HGDDKUDHSA-N 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims 5
- 238000010168 coupling process Methods 0.000 claims 5
- 238000005859 coupling reaction Methods 0.000 claims 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
- 238000001356 surgical procedure Methods 0.000 claims 3
- PNPPWLHLOSWOSY-MHTYAFTESA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-n'-benzyl-2-[(4-carbamimidoylphenyl)methyl]propanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 PNPPWLHLOSWOSY-MHTYAFTESA-N 0.000 claims 2
- AGTWMPCGSYNEBL-NZZIGVLWSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(N)=O)NC(=O)[C@H](CCCC)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 AGTWMPCGSYNEBL-NZZIGVLWSA-N 0.000 claims 2
- 208000037803 restenosis Diseases 0.000 claims 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 1
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims 1
- 208000005189 Embolism Diseases 0.000 claims 1
- 206010061216 Infarction Diseases 0.000 claims 1
- 208000034486 Multi-organ failure Diseases 0.000 claims 1
- 206010038563 Reocclusion Diseases 0.000 claims 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 1
- 230000002152 alkylating effect Effects 0.000 claims 1
- 238000002399 angioplasty Methods 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 230000002526 effect on cardiovascular system Effects 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 230000007574 infarction Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims 1
- WHBHOTQKYDCLBX-WBLNWVLRSA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 WHBHOTQKYDCLBX-WBLNWVLRSA-N 0.000 claims 1
- REUSIQPVMNGXFE-GCUDBOHNSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylmethoxypropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](COCC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 REUSIQPVMNGXFE-GCUDBOHNSA-N 0.000 claims 1
- AYOIHMIBZZSKMZ-HGDDKUDHSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-(4-aminophenyl)-1-oxopropan-2-yl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@@H](CC=1C=CC(N)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 AYOIHMIBZZSKMZ-HGDDKUDHSA-N 0.000 claims 1
- DFDPCBIXGZMIFX-VEXWSWROSA-N n-benzyl-n'-[2-[[(2s)-1-[benzyl(methyl)amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-2-[(4-carbamimidoylphenyl)methyl]-n-methylpropanediamide Chemical compound O=C([C@H](CCCN=C(N)N)NC(=O)C(NC(=O)C(CC=1C=CC(=CC=1)C(N)=N)C(=O)N(C)CC=1C=CC=CC=1)C1CCCCC1)N(C)CC1=CC=CC=C1 DFDPCBIXGZMIFX-VEXWSWROSA-N 0.000 claims 1
- 239000011347 resin Substances 0.000 claims 1
- 229920005989 resin Polymers 0.000 claims 1
- 238000007127 saponification reaction Methods 0.000 claims 1
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- 210000003462 vein Anatomy 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 description 32
- 108090000190 Thrombin Proteins 0.000 description 13
- 229960004072 thrombin Drugs 0.000 description 13
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 12
- 239000011575 calcium Substances 0.000 description 11
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- 108010000499 Thromboplastin Proteins 0.000 description 9
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- 125000003545 alkoxy group Chemical group 0.000 description 9
- 208000032843 Hemorrhage Diseases 0.000 description 8
- 101710163968 Antistasin Proteins 0.000 description 7
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- 230000015572 biosynthetic process Effects 0.000 description 6
- 208000034158 bleeding Diseases 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 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 description 5
- 239000003146 anticoagulant agent Substances 0.000 description 5
- 229940127219 anticoagulant drug Drugs 0.000 description 5
- 239000003130 blood coagulation factor inhibitor Substances 0.000 description 5
- 230000015271 coagulation Effects 0.000 description 5
- 238000005345 coagulation Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 206010051055 Deep vein thrombosis Diseases 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 4
- 230000035602 clotting Effects 0.000 description 4
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- 229940127215 low-molecular weight heparin Drugs 0.000 description 4
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
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- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- 230000004913 activation Effects 0.000 description 3
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000005254 oxyacyl group Chemical group 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000006434 propyl cyclopropyl group Chemical group 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 108010065972 tick anticoagulant peptide Proteins 0.000 description 1
- 238000011541 total hip replacement Methods 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—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
- 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
-
- 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
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Crystallography & Structural Chemistry (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00104041A EP1127884A1 (en) | 2000-02-26 | 2000-02-26 | Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor XA activity and pharmaceutical compositions containing them |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200206581B true ZA200206581B (en) | 2003-07-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200206581A ZA200206581B (en) | 2000-02-26 | 2002-08-16 | Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor XA activity and pharmaceutical compositions containing them. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6794365B2 (enExample) |
| EP (2) | EP1127884A1 (enExample) |
| JP (1) | JP2003524001A (enExample) |
| KR (1) | KR20020079892A (enExample) |
| CN (1) | CN1406226A (enExample) |
| AR (1) | AR027533A1 (enExample) |
| AT (1) | ATE314350T1 (enExample) |
| AU (1) | AU2001235486A1 (enExample) |
| BR (1) | BR0108694A (enExample) |
| CA (1) | CA2400871C (enExample) |
| CZ (1) | CZ20022862A3 (enExample) |
| DE (1) | DE60116272T2 (enExample) |
| ES (1) | ES2254370T3 (enExample) |
| HK (1) | HK1052696A1 (enExample) |
| HU (1) | HUP0300080A3 (enExample) |
| IL (1) | IL151459A0 (enExample) |
| MX (1) | MXPA02007398A (enExample) |
| NO (1) | NO20024040L (enExample) |
| NZ (1) | NZ520982A (enExample) |
| PL (1) | PL357183A1 (enExample) |
| RU (1) | RU2002125671A (enExample) |
| WO (1) | WO2001062735A1 (enExample) |
| ZA (1) | ZA200206581B (enExample) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030224023A1 (en) * | 2002-05-29 | 2003-12-04 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Cosmetic compositions with hydroxy amine salts of malonic acid |
| US20040202689A1 (en) * | 2003-03-17 | 2004-10-14 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Terpenoid fragrance components stabilized with malonic acid salts |
| US20040185015A1 (en) * | 2003-03-17 | 2004-09-23 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Sunscreen cosmetic compositions storage stabilized with malonate salts |
| US20040185074A1 (en) * | 2003-03-17 | 2004-09-23 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Odor control in amine salt containing cosmetic compositions |
| US20040185073A1 (en) * | 2003-03-17 | 2004-09-23 | Unilever Home & Personal Care Usa, Division Of Conopco, Inc. | Cosmetic compositions containing salts of malonic acid |
| US20080194643A1 (en) * | 2005-03-24 | 2008-08-14 | Pfzer Inc | Factor Xa Inhibitor Crystalline Forms |
| US9249265B1 (en) | 2014-09-08 | 2016-02-02 | Sirrus, Inc. | Emulsion polymers including one or more 1,1-disubstituted alkene compounds, emulsion methods, and polymer compositions |
| EP2630191A4 (en) | 2010-10-20 | 2015-05-20 | Sirrus Inc | SYNTHESIS SUBSTANTIALLY CLEANING METHYLENE MALONATES |
| US9279022B1 (en) | 2014-09-08 | 2016-03-08 | Sirrus, Inc. | Solution polymers including one or more 1,1-disubstituted alkene compounds, solution polymerization methods, and polymer compositions |
| US9828324B2 (en) | 2010-10-20 | 2017-11-28 | Sirrus, Inc. | Methylene beta-diketone monomers, methods for making methylene beta-diketone monomers, polymerizable compositions and products formed therefrom |
| US10414839B2 (en) | 2010-10-20 | 2019-09-17 | Sirrus, Inc. | Polymers including a methylene beta-ketoester and products formed therefrom |
| EP3339301A3 (en) | 2011-10-19 | 2018-08-08 | Sirrus, Inc. | Methods for making methylene beta-diketone monomers |
| CA2869108A1 (en) | 2012-03-30 | 2013-10-03 | Bioformix Inc. | Methods for activating polymerizable compositions, polymerizable systems, and products formed thereby |
| EP3626784A1 (en) | 2012-03-30 | 2020-03-25 | Sirrus, Inc. | Ink and coating formulations and polymerizable systems for producing the same |
| US10913875B2 (en) | 2012-03-30 | 2021-02-09 | Sirrus, Inc. | Composite and laminate articles and polymerizable systems for producing the same |
| US10047192B2 (en) | 2012-06-01 | 2018-08-14 | Sirrus, Inc. | Optical material and articles formed therefrom |
| CN105008438B (zh) | 2012-11-16 | 2019-10-22 | 拜奥福米克斯公司 | 塑料粘结体系及方法 |
| CN105164797B (zh) | 2012-11-30 | 2019-04-19 | 瑟拉斯公司 | 用于电子应用的复合组合物 |
| WO2014110388A1 (en) | 2013-01-11 | 2014-07-17 | Bioformix Inc. | Method to obtain methylene malonate via bis(hydroxymethyl) malonate pathway |
| US9315597B2 (en) | 2014-09-08 | 2016-04-19 | Sirrus, Inc. | Compositions containing 1,1-disubstituted alkene compounds for preparing polymers having enhanced glass transition temperatures |
| US9416091B1 (en) | 2015-02-04 | 2016-08-16 | Sirrus, Inc. | Catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
| US10501400B2 (en) | 2015-02-04 | 2019-12-10 | Sirrus, Inc. | Heterogeneous catalytic transesterification of ester compounds with groups reactive under transesterification conditions |
| US9334430B1 (en) | 2015-05-29 | 2016-05-10 | Sirrus, Inc. | Encapsulated polymerization initiators, polymerization systems and methods using the same |
| US9217098B1 (en) | 2015-06-01 | 2015-12-22 | Sirrus, Inc. | Electroinitiated polymerization of compositions having a 1,1-disubstituted alkene compound |
| US9518001B1 (en) | 2016-05-13 | 2016-12-13 | Sirrus, Inc. | High purity 1,1-dicarbonyl substituted-1-alkenes and methods for their preparation |
| US9617377B1 (en) | 2016-06-03 | 2017-04-11 | Sirrus, Inc. | Polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
| US9567475B1 (en) | 2016-06-03 | 2017-02-14 | Sirrus, Inc. | Coatings containing polyester macromers containing 1,1-dicarbonyl-substituted 1 alkenes |
| US10196481B2 (en) | 2016-06-03 | 2019-02-05 | Sirrus, Inc. | Polymer and other compounds functionalized with terminal 1,1-disubstituted alkene monomer(s) and methods thereof |
| US10428177B2 (en) | 2016-06-03 | 2019-10-01 | Sirrus, Inc. | Water absorbing or water soluble polymers, intermediate compounds, and methods thereof |
| CN106501472A (zh) * | 2016-11-29 | 2017-03-15 | 昆明理工大学 | 一种基于抗凝血生化指数评价三七活血作用的方法 |
| CN111018734B (zh) * | 2019-12-13 | 2020-12-22 | 福建海西新药创制有限公司 | 一种盐酸西那卡塞中间体的合成方法 |
| IL316963A (en) * | 2022-05-20 | 2025-01-01 | Radius Health Inc | Process for preparing avalopretide |
| CN115299636B (zh) * | 2022-08-17 | 2025-02-14 | 中国烟草总公司郑州烟草研究院 | 一种卷烟滤嘴用功能吸附丸芯及其制备方法和烟支 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU8866882A (en) * | 1981-09-25 | 1983-03-31 | Wellcome Foundation Limited, The | 2-(n-hydroxycarbamoyl)phenylpropanoyl amino acids |
| WO1992008709A1 (de) * | 1990-11-15 | 1992-05-29 | Pentapharm Ag | Meta-substituierte phenylalanin-derivate |
| JPH07509731A (ja) * | 1993-02-10 | 1995-10-26 | ペンタファルム アクチェンゲゼルシャフト | トロンビン阻害剤としての置換されたフェニルアラニン誘導体のピペラジド |
| NZ284977A (en) * | 1994-04-26 | 1998-09-24 | Selectide Corp | Factor xa enzyme inhibitor |
| WO1996005189A1 (de) * | 1994-08-09 | 1996-02-22 | Pentapharm Ag | Neue inhibitoren vom benzamidintyp |
| UA48993C2 (uk) * | 1995-12-20 | 2002-09-16 | Авентіс Фармасьютікалз, Інк | СПОСІБ ОТРИМАННЯ N-АЦЕТИЛ-(L)-4-ЦІАНОФЕНІЛАЛАНІНУ Аc-(L)-Phe(4-CN)-OH І N-АЦЕТИЛ-(L)-П-АМІДИНФЕНІЛАЛАНІН-ЦИКЛОГЕКСИЛГЛІЦИН-<font face="Symbol">b</font>-(3-N-МЕТИЛПІРИДИН)-АЛАНІНУ Аc-(L)-pАph-Сhg-PalMe(3)-NH<sub>2</sub> |
| ES2218827T3 (es) * | 1997-05-02 | 2004-11-16 | Akzo Nobel N.V. | Inhibidores de la serina proteasa. |
| ATE344246T1 (de) * | 1997-11-26 | 2006-11-15 | Ortho Mcneil Pharm Inc | Heteroaryl aminoguanidin- und alkoxyguanidinderivate und ihre verwendung als proteasehemmer |
| PT1042287E (pt) | 1997-12-24 | 2005-08-31 | Aventis Pharma Gmbh | Derivados de indole como inibidores do factor xa |
| JP3283485B2 (ja) * | 1998-04-10 | 2002-05-20 | 日本たばこ産業株式会社 | アミジン化合物 |
| NZ512669A (en) | 1999-01-02 | 2003-11-28 | Aventis Pharma Gmbh | Arylalkanoyl derivatives, processes for their preparation, their use and pharmaceutical compositions containing them |
| CA2358578A1 (en) * | 1999-01-02 | 2000-07-13 | Aventis Pharma Deutschland Gmbh | Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor xa activity) |
| EP1016663A1 (en) * | 1999-01-02 | 2000-07-05 | Aventis Pharma Deutschland GmbH | Novel malonic acid derivatives, processes for their preparation, their use and pharmaceutical compositions containing them (inhibition of factor Xa activity) |
-
2000
- 2000-02-26 EP EP00104041A patent/EP1127884A1/en not_active Withdrawn
-
2001
- 2001-02-21 ES ES01907546T patent/ES2254370T3/es not_active Expired - Lifetime
- 2001-02-21 DE DE60116272T patent/DE60116272T2/de not_active Expired - Lifetime
- 2001-02-21 HU HU0300080A patent/HUP0300080A3/hu unknown
- 2001-02-21 RU RU2002125671/04A patent/RU2002125671A/ru not_active Application Discontinuation
- 2001-02-21 NZ NZ520982A patent/NZ520982A/en unknown
- 2001-02-21 HK HK03104942.8A patent/HK1052696A1/zh unknown
- 2001-02-21 WO PCT/EP2001/001928 patent/WO2001062735A1/en not_active Ceased
- 2001-02-21 KR KR1020027011004A patent/KR20020079892A/ko not_active Withdrawn
- 2001-02-21 EP EP01907546A patent/EP1265867B1/en not_active Expired - Lifetime
- 2001-02-21 JP JP2001562517A patent/JP2003524001A/ja active Pending
- 2001-02-21 PL PL01357183A patent/PL357183A1/xx not_active Application Discontinuation
- 2001-02-21 CN CN01805589A patent/CN1406226A/zh active Pending
- 2001-02-21 AT AT01907546T patent/ATE314350T1/de not_active IP Right Cessation
- 2001-02-21 CA CA2400871A patent/CA2400871C/en not_active Expired - Fee Related
- 2001-02-21 IL IL15145901A patent/IL151459A0/xx unknown
- 2001-02-21 MX MXPA02007398A patent/MXPA02007398A/es active IP Right Grant
- 2001-02-21 CZ CZ20022862A patent/CZ20022862A3/cs unknown
- 2001-02-21 AU AU2001235486A patent/AU2001235486A1/en not_active Abandoned
- 2001-02-21 BR BR0108694-4A patent/BR0108694A/pt not_active Application Discontinuation
- 2001-02-22 AR ARP010100806A patent/AR027533A1/es not_active Application Discontinuation
- 2001-02-23 US US09/790,641 patent/US6794365B2/en not_active Expired - Lifetime
-
2002
- 2002-08-16 ZA ZA200206581A patent/ZA200206581B/en unknown
- 2002-08-23 NO NO20024040A patent/NO20024040L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20024040D0 (no) | 2002-08-23 |
| NO20024040L (no) | 2002-09-24 |
| IL151459A0 (en) | 2003-04-10 |
| AR027533A1 (es) | 2003-04-02 |
| MXPA02007398A (es) | 2002-12-09 |
| CZ20022862A3 (cs) | 2002-11-13 |
| EP1265867B1 (en) | 2005-12-28 |
| AU2001235486A1 (en) | 2001-09-03 |
| KR20020079892A (ko) | 2002-10-19 |
| ES2254370T3 (es) | 2006-06-16 |
| HUP0300080A3 (en) | 2004-07-28 |
| ATE314350T1 (de) | 2006-01-15 |
| EP1265867A1 (en) | 2002-12-18 |
| PL357183A1 (en) | 2004-07-26 |
| RU2002125671A (ru) | 2004-01-10 |
| US20020022596A1 (en) | 2002-02-21 |
| US6794365B2 (en) | 2004-09-21 |
| CN1406226A (zh) | 2003-03-26 |
| BR0108694A (pt) | 2002-12-10 |
| HK1052696A1 (zh) | 2003-09-26 |
| CA2400871A1 (en) | 2001-08-30 |
| JP2003524001A (ja) | 2003-08-12 |
| DE60116272D1 (de) | 2006-02-02 |
| DE60116272T2 (de) | 2006-08-17 |
| HUP0300080A2 (hu) | 2003-06-28 |
| WO2001062735A1 (en) | 2001-08-30 |
| NZ520982A (en) | 2004-05-28 |
| CA2400871C (en) | 2011-04-26 |
| EP1127884A1 (en) | 2001-08-29 |
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