OA10752A - Substituted (sulfinic acid sulfonic acid sulfonylamino or sulfinylamino) n-Ä(aminoiminomethyl) phenylalkylÜ-azaheterocyclylamide compounds - Google Patents
Substituted (sulfinic acid sulfonic acid sulfonylamino or sulfinylamino) n-Ä(aminoiminomethyl) phenylalkylÜ-azaheterocyclylamide compounds Download PDFInfo
- Publication number
- OA10752A OA10752A OA70149A OA70149A OA10752A OA 10752 A OA10752 A OA 10752A OA 70149 A OA70149 A OA 70149A OA 70149 A OA70149 A OA 70149A OA 10752 A OA10752 A OA 10752A
- Authority
- OA
- OAPI
- Prior art keywords
- oxopyrrolidin
- trifluoroacetate
- benzyl
- aminoiminomethyl
- sulfonic acid
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 656
- -1 sulfinylamino Chemical group 0.000 title claims description 224
- 108010074860 Factor Xa Proteins 0.000 claims abstract description 13
- 230000000694 effects Effects 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 272
- 229910052739 hydrogen Inorganic materials 0.000 claims description 247
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 187
- 239000002253 acid Substances 0.000 claims description 134
- 150000001408 amides Chemical class 0.000 claims description 119
- 239000001257 hydrogen Substances 0.000 claims description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 56
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 53
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 47
- CKARHIGQRRNVFD-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OC)=CC=C21 CKARHIGQRRNVFD-UHFFFAOYSA-N 0.000 claims description 41
- 150000002431 hydrogen Chemical group 0.000 claims description 36
- 230000015572 biosynthetic process Effects 0.000 claims description 32
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 30
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 30
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- FOIKGWJGRNNGQP-UHFFFAOYSA-N 6-methoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(OC)=CC=C21 FOIKGWJGRNNGQP-UHFFFAOYSA-N 0.000 claims description 14
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- HPUKOXOQHIMLHG-MERQFXBCSA-N N[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O Chemical compound N[C@@H](CCN1CC2=CC(C=NN)=CC=C2)C1=O.OC(C(F)(F)F)=O HPUKOXOQHIMLHG-MERQFXBCSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- QSELGEUCFNFITD-UHFFFAOYSA-N thiophene-2-carboximidamide Chemical compound NC(=N)C1=CC=CS1 QSELGEUCFNFITD-UHFFFAOYSA-N 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- GJJURAXVGOIXKG-UHFFFAOYSA-N 5-chloro-6,7-dimethoxynaphthalene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2C(Cl)=C(OC)C(OC)=CC2=C1 GJJURAXVGOIXKG-UHFFFAOYSA-N 0.000 claims description 5
- OKAUOXITMZTUOJ-UHFFFAOYSA-N 7-aminonaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 OKAUOXITMZTUOJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000003146 anticoagulant agent Substances 0.000 claims description 5
- JWOCZCVIXWLBNG-UHFFFAOYSA-N benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CC=C1 JWOCZCVIXWLBNG-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical group COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 5
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 5
- SEDIJOBQZYCMRX-UHFFFAOYSA-N 4,5-dichlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC(Cl)=C(Cl)S1 SEDIJOBQZYCMRX-UHFFFAOYSA-N 0.000 claims description 4
- GXWGRQOMOLFZDN-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2C(C)=C(S(O)(=O)=O)SC2=C1 GXWGRQOMOLFZDN-UHFFFAOYSA-N 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- OEOCMBHDNUYLJG-UHFFFAOYSA-N 1-(1-oxidopyridin-1-ium-3-yl)cyclohexa-2,4-diene-1-sulfonic acid Chemical compound C=1C=C[N+]([O-])=CC=1C1(S(=O)(=O)O)CC=CC=C1 OEOCMBHDNUYLJG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- JLTUANWNGKWRQO-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonyl chloride Chemical group C1=C(Cl)C=C2C(C)=C(S(Cl)(=O)=O)SC2=C1 JLTUANWNGKWRQO-UHFFFAOYSA-N 0.000 claims description 3
- DLEXGQNBBCPGTH-UHFFFAOYSA-N 7-ethoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OCC)=CC=C21 DLEXGQNBBCPGTH-UHFFFAOYSA-N 0.000 claims description 3
- MODKMHXGCGKTLE-UHFFFAOYSA-N N-acetylphenylethylamine Chemical compound CC(=O)NCCC1=CC=CC=C1 MODKMHXGCGKTLE-UHFFFAOYSA-N 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- KNXKVYCVGXFLES-UHFFFAOYSA-N pyridine-2-carboximidamide Chemical compound NC(=N)C1=CC=CC=N1 KNXKVYCVGXFLES-UHFFFAOYSA-N 0.000 claims description 3
- 230000002792 vascular Effects 0.000 claims description 3
- 210000005166 vasculature Anatomy 0.000 claims description 3
- HZKJAZKMSIAJRR-UHFFFAOYSA-N 1-(6-methoxypyridin-2-yl)cyclohexa-2,4-diene-1-sulfonic acid Chemical compound COC1=CC=CC(C2(C=CC=CC2)S(O)(=O)=O)=N1 HZKJAZKMSIAJRR-UHFFFAOYSA-N 0.000 claims description 2
- XPYLLZDJKWAGNP-NTISSMGPSA-N 4-[[(3s)-3-[benzyl-(4,5-dichlorothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](N(CC=3C=CC=CC=3)S(=O)(=O)C=3SC(Cl)=C(Cl)C=3)CC2)=O)=C1 XPYLLZDJKWAGNP-NTISSMGPSA-N 0.000 claims description 2
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- GOSCQCGNFATPPM-FERBBOLQSA-N 5-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=C(C(N)=N)S1 GOSCQCGNFATPPM-FERBBOLQSA-N 0.000 claims description 2
- QWZZUZAIHNZLEN-UHFFFAOYSA-N 5-pyridin-2-ylthiophene-2-sulfonic acid Chemical compound S1C(S(=O)(=O)O)=CC=C1C1=CC=CC=N1 QWZZUZAIHNZLEN-UHFFFAOYSA-N 0.000 claims description 2
- IMSZMAMIAUKQMV-UHFFFAOYSA-N 6,7-dimethoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(OC)C(OC)=CC2=C1 IMSZMAMIAUKQMV-UHFFFAOYSA-N 0.000 claims description 2
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 208000005189 Embolism Diseases 0.000 claims description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 2
- 206010022562 Intermittent claudication Diseases 0.000 claims description 2
- UMQQZKPPZYVKBT-BDQAORGHSA-N N-[(3S)-1-[(3-methanehydrazonoylphenyl)methyl]-2-oxopyrrolidin-3-yl]quinoline-6-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NN=CC1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=CC=NC4=CC=3)CC2)=O)=C1 UMQQZKPPZYVKBT-BDQAORGHSA-N 0.000 claims description 2
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 208000001435 Thromboembolism Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- FWRPUWOMIWLQKH-UHFFFAOYSA-N benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=CC=CC=C1 FWRPUWOMIWLQKH-UHFFFAOYSA-N 0.000 claims description 2
- FUVVSNUVSKUJAS-UHFFFAOYSA-N furan-2-carboximidamide Chemical compound NC(=N)C1=CC=CO1 FUVVSNUVSKUJAS-UHFFFAOYSA-N 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
- 208000021156 intermittent vascular claudication Diseases 0.000 claims description 2
- 210000003127 knee Anatomy 0.000 claims description 2
- 230000007774 longterm Effects 0.000 claims description 2
- 210000003141 lower extremity Anatomy 0.000 claims description 2
- 238000012423 maintenance Methods 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
- 229940080818 propionamide Drugs 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 230000009885 systemic effect Effects 0.000 claims description 2
- LDJAAPXNPMYLFA-UHFFFAOYSA-N thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CS1 LDJAAPXNPMYLFA-UHFFFAOYSA-N 0.000 claims description 2
- 230000002537 thrombolytic effect Effects 0.000 claims description 2
- 230000001052 transient effect Effects 0.000 claims description 2
- 210000003462 vein Anatomy 0.000 claims description 2
- 230000009385 viral infection Effects 0.000 claims description 2
- OYQYQSQKSQRLFR-YCBFMBTMSA-N 2-[[(3s)-1-[(5-carbamimidoylthiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]-n-(2-phenylethyl)acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C(N)=N)CC1)=O)CC(=O)NCCC1=CC=CC=C1 OYQYQSQKSQRLFR-YCBFMBTMSA-N 0.000 claims 2
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- PNQPQIIGGUWDPR-UHFFFAOYSA-N 1-(3-chloropyridin-2-yl)oxycyclohexa-2,4-diene-1-sulfonic acid Chemical compound N=1C=CC=C(Cl)C=1OC1(S(=O)(=O)O)CC=CC=C1 PNQPQIIGGUWDPR-UHFFFAOYSA-N 0.000 claims 1
- KQYGFKRYWDRQQV-BDQAORGHSA-N 2-[[(3s)-1-[(4-carbamimidoylthiophen-2-yl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]acetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)N(CC(N)=O)S(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(C(N)=N)=CS1 KQYGFKRYWDRQQV-BDQAORGHSA-N 0.000 claims 1
- KKPUHYNHYFSGJU-FERBBOLQSA-N 3-[[(3s)-2-oxo-3-(2-phenylethylsulfonylamino)pyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CC(CN2C([C@@H](NS(=O)(=O)CCC=3C=CC=CC=3)CC2)=O)=C1 KKPUHYNHYFSGJU-FERBBOLQSA-N 0.000 claims 1
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims 1
- ITSMLVBLBSCNPN-UHFFFAOYSA-N 4-(2-methoxyphenyl)benzenesulfonic acid Chemical compound COC1=CC=CC=C1C1=CC=C(S(O)(=O)=O)C=C1 ITSMLVBLBSCNPN-UHFFFAOYSA-N 0.000 claims 1
- ADAKMYBJTQFVMB-UHFFFAOYSA-N 4-(3-methylphenyl)benzenesulfonic acid Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)S(O)(=O)=O)=C1 ADAKMYBJTQFVMB-UHFFFAOYSA-N 0.000 claims 1
- YRDOJWMRCBPRCU-RMRYJAPISA-N 4-[[(3s)-3-[(6-aminonaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;dihydrochloride Chemical compound Cl.Cl.S1C(C(=N)N)=CC(CN2C([C@@H](NS(=O)(=O)C=3C=C4C=CC(N)=CC4=CC=3)CC2)=O)=C1 YRDOJWMRCBPRCU-RMRYJAPISA-N 0.000 claims 1
- NVHBZASBXMXHOU-ASMAMLKCSA-N 4-[[(3s)-3-[(7-aminonaphthalen-2-yl)sulfonyl-benzylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.S1C(C(=N)N)=CC(CN2C([C@@H](N(CC=3C=CC=CC=3)S(=O)(=O)C=3C=C4C=C(N)C=CC4=CC=3)CC2)=O)=C1 NVHBZASBXMXHOU-ASMAMLKCSA-N 0.000 claims 1
- BKODMNIABFWKMF-NRFANRHFSA-N 4-amino-3-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]benzenecarboximidamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(C(N)=N)=CC=C1N BKODMNIABFWKMF-NRFANRHFSA-N 0.000 claims 1
- CTEWUQNEQPLMMJ-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalene-2-sulfonic acid Chemical compound C1CCCC2=CC(S(=O)(=O)O)=CC=C21 CTEWUQNEQPLMMJ-UHFFFAOYSA-N 0.000 claims 1
- BLKOSTJSUMJMSR-UHFFFAOYSA-N 5-chlorothiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)S1 BLKOSTJSUMJMSR-UHFFFAOYSA-N 0.000 claims 1
- AAQLVLMRJCRWNU-UHFFFAOYSA-N 6-chloro-6-(2-nitrophenoxy)cyclohexa-2,4-diene-1-sulfonic acid Chemical compound ClC1(C(C=CC=C1)S(=O)(=O)O)OC1=CC=CC=C1[N+](=O)[O-] AAQLVLMRJCRWNU-UHFFFAOYSA-N 0.000 claims 1
- LRYLPTQMSIXZGZ-UHFFFAOYSA-N 7-(methylamino)naphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(NC)=CC=C21 LRYLPTQMSIXZGZ-UHFFFAOYSA-N 0.000 claims 1
- AMTXWXZUNMMYFQ-UHFFFAOYSA-N 7-ethylnaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(CC)=CC=C21 AMTXWXZUNMMYFQ-UHFFFAOYSA-N 0.000 claims 1
- QLROFPQYNZPJHK-FYZYNONXSA-N FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC1=CC=C(S1)C(=N)N)=O Chemical compound FC(C(=O)O)(F)F.COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)CN[C@@H]1C(N(CC1)CC1=CC=C(S1)C(=N)N)=O QLROFPQYNZPJHK-FYZYNONXSA-N 0.000 claims 1
- MFBILERJKRDWIH-FGJQBABTSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)N)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC(=CC=C3C=C2)N)=O)C=CC1 MFBILERJKRDWIH-FGJQBABTSA-N 0.000 claims 1
- COGJBLGCWBGBOA-FJSYBICCSA-N FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC=C(C(=C3C=C2)Cl)N)=O)C=CC1 Chemical compound FC(C(=O)O)(F)F.FC(C(=O)O)(F)F.NN=CC=1C=C(CN2C([C@H](CC2)NS(=O)(=O)C2=CC3=CC=C(C(=C3C=C2)Cl)N)=O)C=CC1 COGJBLGCWBGBOA-FJSYBICCSA-N 0.000 claims 1
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- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- XMMFEKLHEGZKRS-UHFFFAOYSA-N butyl 5-methyl-1h-pyrazole-4-carboxylate Chemical compound CCCCOC(=O)C=1C=NNC=1C XMMFEKLHEGZKRS-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- YGHUUVGIRWMJGE-UHFFFAOYSA-N chlorodimethylsilane Chemical compound C[SiH](C)Cl YGHUUVGIRWMJGE-UHFFFAOYSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
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- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- ULCKEERECJMLHP-UHFFFAOYSA-N dibenzofuran-2-sulfonyl chloride Chemical compound C1=CC=C2C3=CC(S(=O)(=O)Cl)=CC=C3OC2=C1 ULCKEERECJMLHP-UHFFFAOYSA-N 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
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- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 229960004979 fampridine Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 125000006289 hydroxybenzyl group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-N iodic acid Chemical compound OI(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-N 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- JTNAXVPWJICRRJ-UHFFFAOYSA-N methyl 2-(4-cyano-2-methylphenoxy)acetate Chemical group COC(=O)COC1=CC=C(C#N)C=C1C JTNAXVPWJICRRJ-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- 125000006178 methyl benzyl group Chemical group 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- OYTYTAXVYNHHKD-IBGZPJMESA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-2-methoxyquinoline-7-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(N=C3C=2)OC)CN1CC1=CC=CC(C#N)=C1 OYTYTAXVYNHHKD-IBGZPJMESA-N 0.000 description 1
- TUSJYISYKKSYOT-DEOSSOPVSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-3-fluoro-n-methyl-4-phenylbenzenesulfonamide Chemical compound C([C@@H](C1=O)N(C)S(=O)(=O)C=2C=C(F)C(=CC=2)C=2C=CC=CC=2)CN1CC1=CC=CC(C#N)=C1 TUSJYISYKKSYOT-DEOSSOPVSA-N 0.000 description 1
- DQCTULKVFJUBNA-QHCPKHFHSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-4-phenylbenzenesulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC(=CC=2)C=2C=CC=CC=2)CN1CC1=CC=CC(C#N)=C1 DQCTULKVFJUBNA-QHCPKHFHSA-N 0.000 description 1
- DBCQJALPCJPHFS-QFIPXVFZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-6-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3C=C2)OC)CN1CC1=CC=CC(C#N)=C1 DBCQJALPCJPHFS-QFIPXVFZSA-N 0.000 description 1
- OVGYUIMOPMHMJP-PMERELPUSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxy-n-[(3-methylphenyl)methyl]naphthalene-2-sulfonamide Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(C=CC=2)C#N)CC1)=O)CC1=CC=CC(C)=C1 OVGYUIMOPMHMJP-PMERELPUSA-N 0.000 description 1
- VZVDXIFQKAZFGJ-FQEVSTJZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]benzo[f][1,3]benzodioxole-6-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=C4OCOC4=CC3=CC=2)CN1CC1=CC=CC(C#N)=C1 VZVDXIFQKAZFGJ-FQEVSTJZSA-N 0.000 description 1
- MYHFINDNIJVRFK-ZDUSSCGKSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]ethenesulfonamide Chemical compound O=C1[C@@H](NS(=O)(=O)C=C)CCN1CC1=CC=CC(C#N)=C1 MYHFINDNIJVRFK-ZDUSSCGKSA-N 0.000 description 1
- TZRDBGOIVNEENX-FQEVSTJZSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]quinoline-6-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=C3C=CC=NC3=CC=2)CN1CC1=CC=CC(C#N)=C1 TZRDBGOIVNEENX-FQEVSTJZSA-N 0.000 description 1
- VGXAXDMAJHEEJI-NRFANRHFSA-N n-[(3s)-1-[(4-cyanothiophen-2-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxy-n-methylnaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)N(C)S(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC(C#N)=CS1 VGXAXDMAJHEEJI-NRFANRHFSA-N 0.000 description 1
- WGOOCXOJSBOEOY-FQEVSTJZSA-N n-[(3s)-1-[(5-cyanothiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CSC(C#N)=C1 WGOOCXOJSBOEOY-FQEVSTJZSA-N 0.000 description 1
- XEKKCLKOYUWYOE-FQEVSTJZSA-N n-[(3s)-1-[(5-cyanothiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-n-naphthalen-2-ylmethanesulfonamide Chemical compound C([C@@H](C1=O)N(S(=O)(=O)C)C=2C=C3C=CC=CC3=CC=2)CN1CC1=CSC(C#N)=C1 XEKKCLKOYUWYOE-FQEVSTJZSA-N 0.000 description 1
- NIYCWDHSWVJIKD-ZOWNYOTGSA-N n-[(3s)-pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N[C@H]1CCNC1 NIYCWDHSWVJIKD-ZOWNYOTGSA-N 0.000 description 1
- SGYAEZLTAXCMHM-UHFFFAOYSA-N n-[1-[(2-amino-5-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-3-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)C1=CC=CC(S(=O)(=O)NC2C(N(CC=3C(=CC=C(C=3)C#N)N)CC2)=O)=C1 SGYAEZLTAXCMHM-UHFFFAOYSA-N 0.000 description 1
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- FXNYECAOJHKOBG-IBGZPJMESA-N n-[[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]methyl]-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide Chemical compound C([C@@H](CNS(=O)(=O)C=1C=C2CNCCC2=CC=1)C1=O)CN1CC1=CC=CC(C#N)=C1 FXNYECAOJHKOBG-IBGZPJMESA-N 0.000 description 1
- IRHJKWHTARNEKT-QHCPKHFHSA-N n-benzyl-5-chloro-n-[(3s)-1-[(5-cyanothiophen-3-yl)methyl]-2-oxopyrrolidin-3-yl]-3-methyl-1-benzothiophene-2-sulfonamide Chemical compound S1C2=CC=C(Cl)C=C2C(C)=C1S(=O)(=O)N([C@@H]1C(N(CC=2C=C(SC=2)C#N)CC1)=O)CC1=CC=CC=C1 IRHJKWHTARNEKT-QHCPKHFHSA-N 0.000 description 1
- UZJLYRRDVFWSGA-UHFFFAOYSA-N n-benzylacetamide Chemical compound CC(=O)NCC1=CC=CC=C1 UZJLYRRDVFWSGA-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- JNHZPXFARRJZQR-UHFFFAOYSA-N n-ethylpyridin-3-amine Chemical compound CCNC1=CC=CN=C1 JNHZPXFARRJZQR-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- XELRMPRLCPFTBH-UHFFFAOYSA-N quinazoline-2,4-diamine Chemical compound C1=CC=CC2=NC(N)=NC(N)=C21 XELRMPRLCPFTBH-UHFFFAOYSA-N 0.000 description 1
- AUDKCUOUBLCZQR-UHFFFAOYSA-N quinoline-6-sulfonyl chloride Chemical compound N1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 AUDKCUOUBLCZQR-UHFFFAOYSA-N 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- OWKBOTVGPHTUKQ-UHFFFAOYSA-N tert-butyl n-[1-[(4-cyanothiophen-2-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1C(NC(=O)OC(C)(C)C)CCN1CC1=CC(C#N)=CS1 OWKBOTVGPHTUKQ-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- HBUBRNBOYWHGHQ-UHFFFAOYSA-N tert-butyl-dimethyl-(3-methylphenoxy)silane Chemical compound CC1=CC=CC(O[Si](C)(C)C(C)(C)C)=C1 HBUBRNBOYWHGHQ-UHFFFAOYSA-N 0.000 description 1
- NLJDBTZLVTWXRG-UHFFFAOYSA-N tert-butylazanium;iodide Chemical compound [I-].CC(C)(C)[NH3+] NLJDBTZLVTWXRG-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- VTHCULBLEKIUTL-UHFFFAOYSA-N thiophene-3-carbonitrile Chemical compound N#CC1=[C]SC=C1 VTHCULBLEKIUTL-UHFFFAOYSA-N 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- GJINSWLNWKLWCH-UHFFFAOYSA-N trimethyl(naphthalen-1-yl)stannane Chemical compound C1=CC=C2C([Sn](C)(C)C)=CC=CC2=C1 GJINSWLNWKLWCH-UHFFFAOYSA-N 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- 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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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
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- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
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- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
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Applications Claiming Priority (1)
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| US08/481,024 US5612353A (en) | 1995-06-07 | 1995-06-07 | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
Publications (1)
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| OA10752A true OA10752A (en) | 2001-07-04 |
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| OA70149A OA10752A (en) | 1995-06-07 | 1997-12-03 | Substituted (sulfinic acid sulfonic acid sulfonylamino or sulfinylamino) n-Ä(aminoiminomethyl) phenylalkylÜ-azaheterocyclylamide compounds |
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| SI (1) | SI9620093A (enExample) |
| SK (1) | SK160697A3 (enExample) |
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| US5731315A (en) * | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
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| US6602864B1 (en) * | 1996-12-13 | 2003-08-05 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
| DK0944386T3 (da) * | 1996-12-13 | 2003-01-27 | Aventis Pharma Inc | Sulfonsyre- eller sulfonylamino-N-(heteroaralkyl)-azaheterocyclylamid-forbindelser |
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| WO1999037304A1 (en) * | 1998-01-27 | 1999-07-29 | Aventis Pharmaceuticals Products Inc. | SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS |
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| US6747023B1 (en) * | 1998-08-11 | 2004-06-08 | Daiichi Pharmaceutical Co., Ltd. | Sulfonyl derivatives |
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| DE19909237A1 (de) * | 1999-03-03 | 2000-09-07 | Merck Patent Gmbh | Pyrazol-3-on-derivate |
| US6794412B1 (en) * | 1999-03-11 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Treatment of thrombosis by combined use of a factor Xa inhibitor and aspirin |
| JP2001026506A (ja) * | 1999-04-28 | 2001-01-30 | Takeda Chem Ind Ltd | スルホンアミド誘導体 |
| US6586617B1 (en) | 1999-04-28 | 2003-07-01 | Sumitomo Chemical Takeda Agro Company, Limited | Sulfonamide derivatives |
| ATE325114T1 (de) | 1999-06-22 | 2006-06-15 | Takeda Pharmaceutical | Acylhydrazinderivate, verfahren zu ihrer herstellung und ihre verwendung |
| CZ2002323A3 (cs) * | 1999-07-28 | 2002-05-15 | Aventis Pharmaceuticals Products Inc. | Substituované oxoazaheterocyklylové sloučeniny a farmaceutické prostředky, které je obsahují |
| US6544981B2 (en) * | 2000-06-09 | 2003-04-08 | Bristol-Myers Squibb Company | Lactam inhibitors of factor Xa and method |
| US6511973B2 (en) * | 2000-08-02 | 2003-01-28 | Bristol-Myers Squibb Co. | Lactam inhibitors of FXa and method |
| ATE338030T1 (de) | 2000-09-11 | 2006-09-15 | Genentech Inc | Amidine-inhibitoren der serine-proteasen |
| EP1340753B1 (en) * | 2000-11-08 | 2006-01-11 | Takeda Pharmaceutical Company Limited | Carbamate derivatives, process for producing the same and use thereof |
| US6982251B2 (en) | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| AR032230A1 (es) * | 2001-01-16 | 2003-10-29 | Sumitomo Chem Takeda Agro Co | Derivado sulfonamida conteniendo una composicion agricola y horticola |
| US7071181B2 (en) | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
| RS20100015A (sr) * | 2001-01-26 | 2010-12-31 | Schering Corporation | Kombinacija aktivatora receptora aktiviranog peroksizom- proliferatorom (ppar) fenofibrata sa inhibitorom apsorpcije sterola ezetimibom za vaskularne indikacije |
| HU230435B1 (hu) | 2001-01-26 | 2016-06-28 | Merck Sharp & Dohme Corp | Szubsztituált azetidinon vegyületek alkalmazása szitoszterinémia kezelésére |
| US20060287254A1 (en) * | 2001-01-26 | 2006-12-21 | Schering Corporation | Use of substituted azetidinone compounds for the treatment of sitosterolemia |
| JP2004518688A (ja) * | 2001-01-30 | 2004-06-24 | ブリストル−マイヤーズ スクイブ カンパニー | ファクターXa阻害剤のスルホンアミドラクタムおよびその方法 |
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| CA2460340C (en) | 2001-09-21 | 2011-02-15 | Schering Corporation | Methods and therapeutic combinations for the treatment of xanthoma using sterol absorption inhibitors |
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| US7459442B2 (en) * | 2003-03-07 | 2008-12-02 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
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| RU2364587C2 (ru) * | 2003-10-29 | 2009-08-20 | Элан Фармасьютикалз, Инк. | N-замещенные бензолсульфонамиды |
| EP1533298A1 (en) | 2003-11-21 | 2005-05-25 | Newron Pharmaceuticals S.p.A. | 3-aminopyrrolidone derivatives |
| TWI396686B (zh) | 2004-05-21 | 2013-05-21 | Takeda Pharmaceutical | 環狀醯胺衍生物、以及其製品和用法 |
| US8524715B2 (en) * | 2004-11-23 | 2013-09-03 | Astrazeneca Ab | Phenoxyacetic acid derivatives useful for treating respiratory diseases |
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|---|---|---|---|---|
| DE4121947A1 (de) * | 1991-07-03 | 1993-01-07 | Basf Ag | 2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung |
| AU2869092A (en) * | 1991-10-11 | 1993-05-03 | Smithkline Beecham Corporation | Heterocyclic 3-phenylpyrrolidin-2-ones, their preparation and use for the manufacture of a medicament for inhibiting tumor necrosis factor production |
| JPH05201971A (ja) * | 1992-01-28 | 1993-08-10 | Hokuriku Seiyaku Co Ltd | 環状アミン含有ベンゼンスルホンアミド誘導体 |
| US5665754A (en) * | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| AU7665694A (en) * | 1993-09-21 | 1995-04-10 | Yamanouchi Pharmaceutical Co., Ltd. | N-(3-pyrrolidinyl)benzamide derivative |
| FR2714378B1 (fr) * | 1993-12-24 | 1996-03-15 | Sanofi Sa | Dérivés de l'indol-2-one substitués en 3 par un groupe azoté, leur préparation, les compositions pharmaceutiques en contenant. |
-
1995
- 1995-06-07 US US08/481,024 patent/US5612353A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 SK SK1606-97A patent/SK160697A3/sk unknown
- 1996-06-07 CN CN96194489A patent/CN1190395A/zh active Pending
- 1996-06-07 BR BR9608405A patent/BR9608405A/pt not_active Application Discontinuation
- 1996-06-07 JP JP50202997A patent/JP4312829B2/ja not_active Expired - Fee Related
- 1996-06-07 SI SI9620093A patent/SI9620093A/sl unknown
- 1996-06-07 AP APAP/P/1997/001144A patent/AP799A/en active
- 1996-06-07 HU HU9801882A patent/HUP9801882A3/hu unknown
- 1996-06-07 EA EA199800043A patent/EA000700B1/ru not_active IP Right Cessation
- 1996-06-07 EP EP96919298A patent/EP0853618B1/en not_active Expired - Lifetime
- 1996-06-07 CA CA002223403A patent/CA2223403C/en not_active Expired - Fee Related
- 1996-06-07 AT AT96919298T patent/ATE520655T1/de not_active IP Right Cessation
- 1996-06-07 KR KR1019970708866A patent/KR100291711B1/ko not_active Expired - Fee Related
- 1996-06-07 WO PCT/US1996/009816 patent/WO1996040679A1/en not_active Ceased
- 1996-06-07 AU AU61669/96A patent/AU714319B2/en not_active Ceased
- 1996-06-07 PL PL96323780A patent/PL323780A1/xx unknown
- 1996-06-07 CZ CZ973853A patent/CZ385397A3/cs unknown
-
1997
- 1997-12-03 OA OA70149A patent/OA10752A/en unknown
- 1997-12-08 MX MX9709977A patent/MX9709977A/es not_active IP Right Cessation
- 1997-12-08 NO NO19975762A patent/NO310457B1/no unknown
-
1998
- 1998-01-06 BG BG102162A patent/BG63628B1/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA000700B1 (ru) | 2000-02-28 |
| CZ385397A3 (cs) | 1999-05-12 |
| EP0853618B1 (en) | 2011-08-17 |
| SK160697A3 (en) | 1998-11-04 |
| AU6166996A (en) | 1996-12-30 |
| JPH11507368A (ja) | 1999-06-29 |
| BG63628B1 (bg) | 2002-07-31 |
| EA199800043A1 (ru) | 1998-08-27 |
| US5612353A (en) | 1997-03-18 |
| EP0853618A1 (en) | 1998-07-22 |
| CA2223403C (en) | 2002-04-23 |
| AP799A (en) | 2000-01-19 |
| CN1190395A (zh) | 1998-08-12 |
| HUP9801882A3 (en) | 1999-01-28 |
| EP0853618A4 (en) | 2000-03-15 |
| AU714319B2 (en) | 2000-01-06 |
| KR100291711B1 (ko) | 2001-09-17 |
| AP9701144A0 (en) | 1998-01-31 |
| JP4312829B2 (ja) | 2009-08-12 |
| NO975762L (no) | 1998-02-06 |
| NO975762D0 (no) | 1997-12-08 |
| SI9620093A (sl) | 1999-02-28 |
| MX9709977A (es) | 1998-07-31 |
| ATE520655T1 (de) | 2011-09-15 |
| HUP9801882A2 (hu) | 1998-12-28 |
| WO1996040679A1 (en) | 1996-12-19 |
| KR19990022386A (ko) | 1999-03-25 |
| NO310457B1 (no) | 2001-07-09 |
| BR9608405A (pt) | 1999-08-24 |
| CA2223403A1 (en) | 1996-12-19 |
| BG102162A (en) | 1998-09-30 |
| PL323780A1 (en) | 1998-04-27 |
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