AU2001235486A1 - 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

Info

Publication number: AU2001235486A1
Authority: AU; Australia
Prior art keywords: formula; alkyl; benzyl; hydrogen; methyl
Prior art date: 2000-02-26
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

Application number

AU2001235486A

Other languages

English (en)

Inventor

Fahad Al-Obeidi

Armin Walser

Peter Wildgoose

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Sanofi Aventis Deutschland GmbH

Original Assignee

Aventis Pharma Deutschland GmbH

Priority date (The priority date 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 date listed.)

2000-02-26

Filing date

2001-02-21

Publication date

2001-09-03

2001-02-21 Application filed by Aventis Pharma Deutschland GmbH filed Critical Aventis Pharma Deutschland GmbH

2001-09-03 Publication of AU2001235486A1 publication Critical patent/AU2001235486A1/en

Status Abandoned legal-status Critical Current

Links

108010074860 Factor Xa Proteins 0.000 title claims description 67
238000000034 method Methods 0.000 title claims description 48
239000008194 pharmaceutical composition Substances 0.000 title claims description 17
238000002360 preparation method Methods 0.000 title claims description 17
239000003112 inhibitor Substances 0.000 title claims description 14
230000008569 process Effects 0.000 title claims description 11
230000000694 effects Effects 0.000 title description 37
150000002690 malonic acid derivatives Chemical class 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims description 272
-1 4-carbamimidoyl-benzyl Chemical group 0.000 claims description 139
239000001257 hydrogen Substances 0.000 claims description 109
229910052739 hydrogen Inorganic materials 0.000 claims description 109
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 90
150000003839 salts Chemical class 0.000 claims description 62
239000000203 mixture Substances 0.000 claims description 50
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 35
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 32
125000003118 aryl group Chemical group 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
229920005989 resin Polymers 0.000 claims description 28
239000011347 resin Substances 0.000 claims description 28
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 20
125000000217 alkyl group Chemical group 0.000 claims description 20
230000008878 coupling Effects 0.000 claims description 20
238000010168 coupling process Methods 0.000 claims description 20
238000005859 coupling reaction Methods 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
239000000126 substance Substances 0.000 claims description 19
150000002431 hydrogen Chemical class 0.000 claims description 18
230000023555 blood coagulation Effects 0.000 claims description 17
150000001450 anions Chemical class 0.000 claims description 16
238000011282 treatment Methods 0.000 claims description 15
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 14
201000010099 disease Diseases 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
125000006239 protecting group Chemical group 0.000 claims description 13
230000009467 reduction Effects 0.000 claims description 13
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
208000007536 Thrombosis Diseases 0.000 claims description 12
125000003710 aryl alkyl group Chemical group 0.000 claims description 12
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 12
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 10
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 10
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 10
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
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 9
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
239000003937 drug carrier Substances 0.000 claims description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 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 9
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 8
206010053567 Coagulopathies Diseases 0.000 claims description 8
206010047249 Venous thrombosis Diseases 0.000 claims description 8
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
238000011321 prophylaxis Methods 0.000 claims description 8
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 8
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 8
YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 7
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 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
238000010511 deprotection reaction Methods 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 7
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
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 description 6
238000001356 surgical procedure Methods 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
208000024172 Cardiovascular disease Diseases 0.000 claims description 5
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 5
208000009190 disseminated intravascular coagulation Diseases 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
210000003462 vein Anatomy 0.000 claims description 5
208000001435 Thromboembolism Diseases 0.000 claims description 4
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 description 4
208000037803 restenosis Diseases 0.000 claims description 4
206010002383 Angina Pectoris Diseases 0.000 claims description 3
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
BUVZDJXWWZKNKM-UHFFFAOYSA-N n-[2-[[1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1CCCCC1C(C(=O)NC(CCCNC(N)=N)C(N)=O)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 BUVZDJXWWZKNKM-UHFFFAOYSA-N 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
238000007127 saponification reaction Methods 0.000 claims description 3
APCJUHZGIFNYHW-AKQSQHNNSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound N([C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 APCJUHZGIFNYHW-AKQSQHNNSA-N 0.000 claims description 2
XXUAYBLKRXHDJV-HGDDKUDHSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-3-cyclohexylpropanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid;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(O)=O)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 XXUAYBLKRXHDJV-HGDDKUDHSA-N 0.000 claims description 2
PGIXMLLCCPHCCZ-NZZIGVLWSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCC)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 PGIXMLLCCPHCCZ-NZZIGVLWSA-N 0.000 claims description 2
DQVMQOOFTVHQGO-WBLNWVLRSA-N (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(methylamino)-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;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(O)=O)C(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 DQVMQOOFTVHQGO-WBLNWVLRSA-N 0.000 claims description 2
GQHZXDWTCGXGIB-MHTYAFTESA-N (2s)-2-[[(2s)-2-[[3-(benzylamino)-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;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(O)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 GQHZXDWTCGXGIB-MHTYAFTESA-N 0.000 claims description 2
LYJDLZMCPCKTKB-CTIJFNHYSA-N (3s)-4-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-4-oxobutanoic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)NCCC[C@@H](C(N)=O)N=C(O)[C@H](CC(O)=O)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 LYJDLZMCPCKTKB-CTIJFNHYSA-N 0.000 claims description 2
GLZOSBAYSOEXSG-BSOSBYQFSA-N (4s)-5-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-5-oxopentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 GLZOSBAYSOEXSG-BSOSBYQFSA-N 0.000 claims description 2
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
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
208000005189 Embolism Diseases 0.000 claims description 2
206010061216 Infarction Diseases 0.000 claims description 2
208000034486 Multi-organ failure Diseases 0.000 claims description 2
206010038563 Reocclusion Diseases 0.000 claims description 2
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
208000006011 Stroke Diseases 0.000 claims description 2
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
230000002152 alkylating effect Effects 0.000 claims description 2
238000002399 angioplasty Methods 0.000 claims description 2
230000000747 cardiac effect Effects 0.000 claims description 2
125000004185 ester group Chemical group 0.000 claims description 2
RQEROSMDTGDFBB-GCUDBOHNSA-N ethyl (2s)-2-[[(2s)-2-[[2-[(4-carbamimidoylphenyl)methyl]-3-(dimethylamino)-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoate;hydrochloride Chemical compound Cl.N([C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)OCC)C1CCCCC1)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 RQEROSMDTGDFBB-GCUDBOHNSA-N 0.000 claims description 2
230000007574 infarction Effects 0.000 claims description 2
208000015181 infectious disease Diseases 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
208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 2
XWODQEWOAFLMGW-MHTYAFTESA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-cyclohexyl-2-oxoethyl]-n'-benzyl-2-[[4-[(z)-n'-hydroxycarbamimidoyl]phenyl]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)NO)C=C1 XWODQEWOAFLMGW-MHTYAFTESA-N 0.000 claims description 2
PDJPAOGNYAKUPM-CORMSVGVSA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxo-1-phenylethyl]-2-[(4-carbamimidoylphenyl)methyl]-n',n'-dimethylpropanediamide;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)C=1C=CC=CC=1)C(=O)C(C(=O)N(C)C)CC1=CC=C(C(N)=N)C=C1 PDJPAOGNYAKUPM-CORMSVGVSA-N 0.000 claims description 2
XLGWGNOWMCFZJY-GCUDBOHNSA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-4-phenylbutan-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](CCC=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 XLGWGNOWMCFZJY-GCUDBOHNSA-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
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 description 2
AGHMAUIWCUHIOZ-MHTYAFTESA-N n-[(2s)-1-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-naphthalen-2-yl-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=C2C=CC=CC2=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 AGHMAUIWCUHIOZ-MHTYAFTESA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
BRAMBTDGZGHOES-MHTYAFTESA-N (2s)-2-[[(2s)-2-[[3-(benzylamino)-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;ethyl 2,2,2-trifluoroacetate Chemical compound CCOC(=O)C(F)(F)F.N([C@H](C(=O)N[C@@H](CCCNC(=N)N)C(O)=O)C1CCCCC1)C(=O)C(C(=O)NCC=1C=CC=CC=1)CC1=CC=C(C(N)=N)C=C1 BRAMBTDGZGHOES-MHTYAFTESA-N 0.000 claims 1
SHKDRBTXSLCNHH-YFGYHPHZSA-N (2s)-2-[[(2s)-2-[[3-[benzyl(methyl)amino]-2-[(4-carbamimidoylphenyl)methyl]-3-oxopropanoyl]amino]-2-cyclohexylacetyl]amino]-5-(diaminomethylideneamino)pentanoic acid;hydrochloride Chemical compound Cl.C=1C=C(C(N)=N)C=CC=1CC(C(=O)N[C@@H](C1CCCCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)N(C)CC1=CC=CC=C1 SHKDRBTXSLCNHH-YFGYHPHZSA-N 0.000 claims 1
HMLRTAJDZQXHMS-WBLNWVLRSA-N n-[(1s)-2-[[(2s)-1-amino-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-2-oxo-1-phenylethyl]-2-[(4-carbamimidoylphenyl)methyl]-n'-methylpropanediamide;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)C=1C=CC=CC=1)C(=O)C(C(=O)NC)CC1=CC=C(C(N)=N)C=C1 HMLRTAJDZQXHMS-WBLNWVLRSA-N 0.000 claims 1
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125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229960003766 thrombin (human) Drugs 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
238000011541 total hip replacement Methods 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000001131 transforming effect Effects 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
238000000825 ultraviolet detection Methods 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
239000003981 vehicle Substances 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
235000012431 wafers Nutrition 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
229960001600 xylazine Drugs 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- 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
- 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)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Biophysics (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Crystallography & Structural Chemistry (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Communicable Diseases (AREA)
Urology & Nephrology (AREA)
Diabetes (AREA)
Oncology (AREA)
Hematology (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)

AU2001235486A 2000-02-26 2001-02-21 Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor xa activity and pharmaceutical compositions containing them Abandoned AU2001235486A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP00104041		2000-02-26
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
PCT/EP2001/001928 WO2001062735A1 (en)	2000-02-26	2001-02-21	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
AU2001235486A1 true AU2001235486A1 (en)	2001-09-03

Family

ID=8167968

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU2001235486A Abandoned AU2001235486A1 (en)	2000-02-26	2001-02-21	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 (xx)
EP (2)	EP1127884A1 (xx)
JP (1)	JP2003524001A (xx)
KR (1)	KR20020079892A (xx)
CN (1)	CN1406226A (xx)
AR (1)	AR027533A1 (xx)
AT (1)	ATE314350T1 (xx)
AU (1)	AU2001235486A1 (xx)
BR (1)	BR0108694A (xx)
CA (1)	CA2400871C (xx)
CZ (1)	CZ20022862A3 (xx)
DE (1)	DE60116272T2 (xx)
ES (1)	ES2254370T3 (xx)
HK (1)	HK1052696A1 (xx)
HU (1)	HUP0300080A3 (xx)
IL (1)	IL151459A0 (xx)
MX (1)	MXPA02007398A (xx)
NO (1)	NO20024040L (xx)
NZ (1)	NZ520982A (xx)
PL (1)	PL357183A1 (xx)
RU (1)	RU2002125671A (xx)
WO (1)	WO2001062735A1 (xx)
ZA (1)	ZA200206581B (xx)

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CN110204441A (zh)	2013-01-11	2019-09-06	瑟拉斯公司	经过双(羟甲基)丙二酸酯的途径获得亚甲基丙二酸酯的方法
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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
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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
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2000
- 2000-02-26 EP EP00104041A patent/EP1127884A1/en not_active Withdrawn
2001
- 2001-02-21 RU RU2002125671/04A patent/RU2002125671A/ru not_active Application Discontinuation
- 2001-02-21 AU AU2001235486A patent/AU2001235486A1/en not_active Abandoned
- 2001-02-21 NZ NZ520982A patent/NZ520982A/en unknown
- 2001-02-21 KR KR1020027011004A patent/KR20020079892A/ko not_active Application Discontinuation
- 2001-02-21 MX MXPA02007398A patent/MXPA02007398A/es active IP Right Grant
- 2001-02-21 EP EP01907546A patent/EP1265867B1/en not_active Expired - Lifetime
- 2001-02-21 PL PL01357183A patent/PL357183A1/xx not_active Application Discontinuation
- 2001-02-21 BR BR0108694-4A patent/BR0108694A/pt not_active Application Discontinuation
- 2001-02-21 DE DE60116272T patent/DE60116272T2/de not_active Expired - Lifetime
- 2001-02-21 JP JP2001562517A patent/JP2003524001A/ja active Pending
- 2001-02-21 AT AT01907546T patent/ATE314350T1/de not_active IP Right Cessation
- 2001-02-21 WO PCT/EP2001/001928 patent/WO2001062735A1/en active IP Right Grant
- 2001-02-21 CN CN01805589A patent/CN1406226A/zh active Pending
- 2001-02-21 ES ES01907546T patent/ES2254370T3/es not_active Expired - Lifetime
- 2001-02-21 CZ CZ20022862A patent/CZ20022862A3/cs unknown
- 2001-02-21 IL IL15145901A patent/IL151459A0/xx unknown
- 2001-02-21 HU HU0300080A patent/HUP0300080A3/hu unknown
- 2001-02-21 CA CA2400871A patent/CA2400871C/en not_active Expired - Fee Related
- 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
2003
- 2003-07-09 HK HK03104942.8A patent/HK1052696A1/zh unknown

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN115299636A (zh) *	2022-08-17	2022-11-08	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

Also Published As

Publication number	Publication date
MXPA02007398A (es)	2002-12-09
KR20020079892A (ko)	2002-10-19
NZ520982A (en)	2004-05-28
AR027533A1 (es)	2003-04-02
NO20024040L (no)	2002-09-24
DE60116272D1 (de)	2006-02-02
CN1406226A (zh)	2003-03-26
NO20024040D0 (no)	2002-08-23
US20020022596A1 (en)	2002-02-21
WO2001062735A1 (en)	2001-08-30
CA2400871A1 (en)	2001-08-30
CZ20022862A3 (cs)	2002-11-13
CA2400871C (en)	2011-04-26
ES2254370T3 (es)	2006-06-16
HUP0300080A3 (en)	2004-07-28
HK1052696A1 (zh)	2003-09-26
ATE314350T1 (de)	2006-01-15
EP1265867A1 (en)	2002-12-18
US6794365B2 (en)	2004-09-21
PL357183A1 (en)	2004-07-26
HUP0300080A2 (hu)	2003-06-28
JP2003524001A (ja)	2003-08-12
EP1127884A1 (en)	2001-08-29
RU2002125671A (ru)	2004-01-10
BR0108694A (pt)	2002-12-10
EP1265867B1 (en)	2005-12-28
ZA200206581B (en)	2003-07-28
DE60116272T2 (de)	2006-08-17
IL151459A0 (en)	2003-04-10

Publication	Publication Date	Title
US6794365B2 (en)	2004-09-21	Malonic acid derivatives, processes for their preparation their use and pharmaceutical compositions containing them
US6395737B1 (en)	2002-05-28	Malonic acid derivatives, processes for their preparation, for their use and pharmaceutical compositions containing them
CN102858744B (zh)	2015-03-04	胰蛋白酶样丝氨酸蛋白酶抑制剂及其制备方法和用途
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AU2001235486A1 - Novel malonic acid derivatives, processes for their preparation, their use as inhibitor of factor xa activity and pharmaceutical compositions containing them - Google Patents

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