RU2502736C2 - МАКРОЦИКЛИЧЕСКИЕ ПРОИЗВОДНЫЕ МОЧЕВИНЫ И СУЛЬФАМИДА В КАЧЕСТВЕ ИНГИБИТОРОВ TAFIa - Google Patents

Info

Publication number

RU2502736C2

RU2502736C2 RU2010154089/04A RU2010154089A RU2502736C2 RU 2502736 C2 RU2502736 C2 RU 2502736C2 RU 2010154089/04 A RU2010154089/04 A RU 2010154089/04A RU 2010154089 A RU2010154089 A RU 2010154089A RU 2502736 C2 RU2502736 C2 RU 2502736C2

Authority

RU

Russia

Prior art keywords

ureido

alkylene

oxo

dioxa

trien

Prior art date

2008-06-06

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• 239000003112 inhibitor Substances 0.000 title claims abstract description 20
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• 239000004202 carbamide Substances 0.000 title description 6
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 title description 2
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• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 39
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 24
• 150000002367 halogens Chemical class 0.000 claims abstract description 24
• 150000003839 salts Chemical class 0.000 claims abstract description 21
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• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 13
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• 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
• 238000011282 treatment Methods 0.000 claims abstract description 9
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• -1 2-aminoethanesulfonyl Chemical group 0.000 claims description 123
• 238000000034 method Methods 0.000 claims description 104
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 83
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 52
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 49
• 125000006239 protecting group Chemical group 0.000 claims description 44
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 36
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 34
• 235000019260 propionic acid Nutrition 0.000 claims description 26
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 25
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
• 150000001413 amino acids Chemical class 0.000 claims description 16
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• 229910052757 nitrogen Inorganic materials 0.000 claims description 15
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
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• ZVEVQADHVAIPND-XPWALMASSA-N (2s)-3-(6-aminopyridin-3-yl)-2-[[(3r,6s)-4-oxo-6-propan-2-yl-8,13-dioxa-5-azabicyclo[12.2.2]octadeca-1(16),14,17-trien-3-yl]carbamoylamino]propanoic acid Chemical compound C([C@H](NC(=O)N[C@@H]1CC2=CC=C(C=C2)OCCCCOC[C@@H](NC1=O)C(C)C)C(O)=O)C1=CC=C(N)N=C1 ZVEVQADHVAIPND-XPWALMASSA-N 0.000 claims description 2
• IZDLTKHIFLHDDA-JQHSSLGASA-N (2s)-3-(6-aminopyridin-3-yl)-2-[[(3s,6r)-3-methyl-5-oxo-1-oxa-4-azacyclotetradec-6-yl]carbamoylamino]propanoic acid Chemical compound O=C1N[C@@H](C)COCCCCCCCC[C@H]1NC(=O)N[C@H](C(O)=O)CC1=CC=C(N)N=C1 IZDLTKHIFLHDDA-JQHSSLGASA-N 0.000 claims description 2
• OPTOXSVCVQEIKN-HSALFYBXSA-N (2s)-3-(6-aminopyridin-3-yl)-2-[[(3s,6r)-5-oxo-3-propan-2-yl-1-oxa-4-azacyclotetradec-6-yl]carbamoylamino]propanoic acid Chemical compound O=C1N[C@@H](C(C)C)COCCCCCCCC[C@H]1NC(=O)N[C@H](C(O)=O)CC1=CC=C(N)N=C1 OPTOXSVCVQEIKN-HSALFYBXSA-N 0.000 claims description 2
• LULOJIQVOUOYMX-BHDDXSALSA-N (2s)-6-amino-2-[[(3r,6s)-4-oxo-6-propan-2-yl-8,13-dioxa-5-azabicyclo[12.2.2]octadeca-1(16),14,17-trien-3-yl]carbamoylamino]hexanoic acid Chemical compound C1[C@@H](NC(=O)N[C@@H](CCCCN)C(O)=O)C(=O)N[C@@H](C(C)C)COCCCCOC2=CC=C1C=C2 LULOJIQVOUOYMX-BHDDXSALSA-N 0.000 claims description 2
• JSGVAFDSUVDMJG-CEXWTWQISA-N (2s)-6-amino-2-[[(3s,6r)-5-oxo-3-propan-2-yl-1-oxa-4-azacyclotetradec-6-yl]carbamoylamino]hexanoic acid Chemical compound CC(C)[C@H]1COCCCCCCCC[C@@H](NC(=O)N[C@@H](CCCCN)C(O)=O)C(=O)N1 JSGVAFDSUVDMJG-CEXWTWQISA-N 0.000 claims description 2
• 208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 2
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• FQONWTZXYFYCBR-ARFHVFGLSA-N (2s)-6-amino-2-[[(3s,6r)-5-oxo-3-propan-2-yl-1,8-dioxa-4-azacyclododec-6-yl]carbamoylamino]hexanoic acid Chemical compound CC(C)[C@H]1COCCCCOC[C@@H](NC(=O)N[C@@H](CCCCN)C(O)=O)C(=O)N1 FQONWTZXYFYCBR-ARFHVFGLSA-N 0.000 claims 1
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