NZ589671A - Macrocyclic urea and sulfamide derivatives as inhibitors of tafia - Google Patents

Info

Publication number

NZ589671A

NZ589671A NZ589671A NZ58967109A NZ589671A NZ 589671 A NZ589671 A NZ 589671A NZ 589671 A NZ589671 A NZ 589671A NZ 58967109 A NZ58967109 A NZ 58967109A NZ 589671 A NZ589671 A NZ 589671A

Authority

NZ

New Zealand

Prior art keywords

alkylene

formula

compound

twice

alkyl

Prior art date

2008-06-06

Links

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• Global Dossier
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• 239000003112 inhibitor Substances 0.000 title description 17
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title description 9
• 239000004202 carbamide Substances 0.000 title description 5
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 204
• 239000000203 mixture Substances 0.000 claims abstract description 74
• 150000003839 salts Chemical class 0.000 claims abstract description 21
• 208000007536 Thrombosis Diseases 0.000 claims abstract description 13
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
• 208000005189 Embolism Diseases 0.000 claims abstract description 6
• 230000003176 fibrotic effect Effects 0.000 claims abstract description 6
• 238000011321 prophylaxis Methods 0.000 claims abstract description 4
• 230000009863 secondary prevention Effects 0.000 claims abstract description 4
• 201000005665 thrombophilia Diseases 0.000 claims abstract description 4
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
• -1 benzimidazalinyl Chemical group 0.000 claims description 114
• 238000000034 method Methods 0.000 claims description 112
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 73
• 125000006239 protecting group Chemical group 0.000 claims description 66
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
• 229910052736 halogen Inorganic materials 0.000 claims description 44
• 150000002367 halogens Chemical class 0.000 claims description 44
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 44
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 38
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 32
• 125000002947 alkylene group Chemical group 0.000 claims description 30
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 230000008569 process Effects 0.000 claims description 25
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
• 125000003118 aryl group Chemical group 0.000 claims description 22
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 235000019260 propionic acid Nutrition 0.000 claims description 19
• 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 19
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 18
• 239000002253 acid Substances 0.000 claims description 16
• 150000001413 amino acids Chemical class 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 230000015572 biosynthetic process Effects 0.000 claims description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
• 125000004122 cyclic group Chemical group 0.000 claims description 12
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 11
• 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 claims description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
• 239000011593 sulfur Substances 0.000 claims description 10
• 125000004434 sulfur atom Chemical group 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 238000004587 chromatography analysis Methods 0.000 claims description 9
• 230000008030 elimination Effects 0.000 claims description 9
• 238000003379 elimination reaction Methods 0.000 claims description 9
• 150000002148 esters Chemical class 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 9
• 125000006413 ring segment Chemical group 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
• 102000009123 Fibrin Human genes 0.000 claims description 7
• 108010073385 Fibrin Proteins 0.000 claims description 7
• BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 7
• 230000005526 G1 to G0 transition Effects 0.000 claims description 7
• 150000007513 acids Chemical class 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
• 229950003499 fibrin Drugs 0.000 claims description 7
• 238000005984 hydrogenation reaction Methods 0.000 claims description 7
• 238000000926 separation method Methods 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 238000011282 treatment Methods 0.000 claims description 7
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 6
• 239000004480 active ingredient Substances 0.000 claims description 6
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
• 208000035475 disorder Diseases 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000000160 oxazolidinyl group Chemical group 0.000 claims description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• 230000002378 acidificating effect Effects 0.000 claims description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 229910052794 bromium Inorganic materials 0.000 claims description 5
• 239000000460 chlorine Substances 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
• 150000001408 amides Chemical class 0.000 claims description 4
• 125000002785 azepinyl group Chemical group 0.000 claims description 4
• 125000002393 azetidinyl group Chemical group 0.000 claims description 4
• 238000001212 derivatisation Methods 0.000 claims description 4
• 230000002439 hemostatic effect Effects 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000002757 morpholinyl group Chemical group 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 239000002243 precursor Substances 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
• 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 3
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims description 3
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
• 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims description 3
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 3
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 3
• 125000005955 1H-indazolyl group Chemical group 0.000 claims description 3
• JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims description 3
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 claims description 3
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
• 230000001154 acute effect Effects 0.000 claims description 3
• 239000000654 additive Substances 0.000 claims description 3
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 3
• 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
• 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 3
• 239000000010 aprotic solvent Substances 0.000 claims description 3
• 125000004069 aziridinyl group Chemical group 0.000 claims description 3
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000005512 benztetrazolyl group Chemical group 0.000 claims description 3
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 3
• 125000004623 carbolinyl group Chemical group 0.000 claims description 3
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 claims description 3
• 230000006735 deficit Effects 0.000 claims description 3
• 125000005509 dibenzothiophenyl group Chemical group 0.000 claims description 3
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 3
• 125000000532 dioxanyl group Chemical group 0.000 claims description 3
• 125000003838 furazanyl group Chemical group 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 3
• 125000002636 imidazolinyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 3
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000005438 isoindazolyl group Chemical group 0.000 claims description 3
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 3
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
• 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 claims description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 claims description 3
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 claims description 3
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 claims description 3
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 claims description 3
• 125000005954 phenoxathiinyl group Chemical group 0.000 claims description 3
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 claims description 3
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 3
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
• 125000002755 pyrazolinyl group Chemical group 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
• 125000001422 pyrrolinyl group Chemical group 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 3
• 238000006798 ring closing metathesis reaction Methods 0.000 claims description 3
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 3
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 claims description 3
• DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 claims description 3
• 229940125670 thienopyridine Drugs 0.000 claims description 3
• 239000002175 thienopyridine Substances 0.000 claims description 3
• 125000004306 triazinyl group Chemical group 0.000 claims description 3
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 claims description 3
• OIDOVTVIWNAVJY-NJYVYQBISA-N (2r)-3-(2-aminoethylsulfonyl)-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 C1[C@@H](NC(=O)N[C@@H](CS(=O)(=O)CCN)C(O)=O)C(=O)N[C@@H](C(C)C)COCCCCOC2=CC=C1C=C2 OIDOVTVIWNAVJY-NJYVYQBISA-N 0.000 claims description 2
• DHYQTBANMOAJLV-IXDOHACOSA-N (2s)-3-(6-aminopyridin-3-yl)-2-[[(3s,6r)-5,9-dioxo-3-propan-2-yl-1-oxa-4,10-diazacyclotridec-6-yl]carbamoylamino]propanoic acid Chemical compound O=C1N[C@@H](C(C)C)COCCCNC(=O)CC[C@H]1NC(=O)N[C@H](C(O)=O)CC1=CC=C(N)N=C1 DHYQTBANMOAJLV-IXDOHACOSA-N 0.000 claims description 2
• YUFHUHQAWMPSLE-GVDBMIGSSA-N (2s)-3-(6-aminopyridin-3-yl)-2-[[(3s,6r)-5-oxo-3-propan-2-yl-1,8-dioxa-4-azacyclododec-6-yl]carbamoylamino]propanoic acid Chemical compound O=C1N[C@@H](C(C)C)COCCCCOC[C@H]1NC(=O)N[C@H](C(O)=O)CC1=CC=C(N)N=C1 YUFHUHQAWMPSLE-GVDBMIGSSA-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
• 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 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
• ALMMBDDTZHEVOE-TYRYEOGQSA-N (2s)-6-amino-2-[[(3s,6s)-4-oxo-6-propan-2-yl-8,13-dioxa-5-azabicyclo[12.2.2]octadecan-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)COCCCCOC2CCC1CC2 ALMMBDDTZHEVOE-TYRYEOGQSA-N 0.000 claims description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
• 206010002383 Angina Pectoris Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 229910014585 C2-Ce Inorganic materials 0.000 claims description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
• 206010051055 Deep vein thrombosis Diseases 0.000 claims description 2
• 206010061218 Inflammation Diseases 0.000 claims description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
• 206010027476 Metastases Diseases 0.000 claims description 2
• 206010028980 Neoplasm Diseases 0.000 claims description 2
• 208000010378 Pulmonary Embolism Diseases 0.000 claims description 2
• 206010040047 Sepsis Diseases 0.000 claims description 2
• 206010047249 Venous thrombosis Diseases 0.000 claims description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 2
• 230000000996 additive effect Effects 0.000 claims description 2
• 238000002399 angioplasty Methods 0.000 claims description 2
• 206010003119 arrhythmia Diseases 0.000 claims description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
• 230000007211 cardiovascular event Effects 0.000 claims description 2
• 230000008878 coupling Effects 0.000 claims description 2
• 238000010168 coupling process Methods 0.000 claims description 2
• 238000005859 coupling reaction Methods 0.000 claims description 2
• 230000003412 degenerative effect Effects 0.000 claims description 2
• 206010012601 diabetes mellitus Diseases 0.000 claims description 2
• 230000003073 embolic effect Effects 0.000 claims description 2
• GZXMRXNUWAQHMP-BHIFYINESA-N ethyl (2s)-3-(6-aminopyridin-3-yl)-2-[[(3s,6r)-5-oxo-3-propan-2-yl-1-oxa-4-azacyclotetradec-6-yl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OCC)NC(=O)N[C@H]1C(N[C@H](COCCCCCCCC1)C(C)C)=O)C1=CC=C(N)N=C1 GZXMRXNUWAQHMP-BHIFYINESA-N 0.000 claims description 2
• 210000004394 hip joint Anatomy 0.000 claims description 2
• 238000002513 implantation Methods 0.000 claims description 2
• 230000002757 inflammatory effect Effects 0.000 claims description 2
• 230000004054 inflammatory process Effects 0.000 claims description 2
• 239000011630 iodine Substances 0.000 claims description 2
• 229910052740 iodine Inorganic materials 0.000 claims description 2
• 210000000629 knee joint Anatomy 0.000 claims description 2
• 210000004072 lung Anatomy 0.000 claims description 2
• 230000009401 metastasis Effects 0.000 claims description 2
• LCRYZTZMZVSBME-RCCFBDPRSA-N methyl (2s)-3-(6-aminopyridin-3-yl)-2-[[(3s,6r)-5-oxo-3-propan-2-yl-1,8-dioxa-4-azacyclododec-6-yl]carbamoylamino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)N[C@H]1C(N[C@H](COCCCCOC1)C(C)C)=O)C1=CC=C(N)N=C1 LCRYZTZMZVSBME-RCCFBDPRSA-N 0.000 claims description 2
• 208000010125 myocardial infarction Diseases 0.000 claims description 2
• 201000008482 osteoarthritis Diseases 0.000 claims description 2
• 230000002265 prevention Effects 0.000 claims description 2
• 208000037803 restenosis Diseases 0.000 claims description 2
• 230000000250 revascularization Effects 0.000 claims description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
• 230000037390 scarring Effects 0.000 claims description 2
• 238000001356 surgical procedure Methods 0.000 claims description 2
• 230000004614 tumor growth Effects 0.000 claims description 2
• 229910052720 vanadium Inorganic materials 0.000 claims description 2
• 208000019553 vascular disease Diseases 0.000 claims description 2
• 229910052727 yttrium Inorganic materials 0.000 claims description 2
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• XHVSCKNABCCCAC-UHFFFAOYSA-N trimethylsilyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound C[Si](C)(C)OC(=O)C(F)(F)S(F)(=O)=O XHVSCKNABCCCAC-UHFFFAOYSA-N 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
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• 229960000281 trometamol Drugs 0.000 description 1
• JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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• 238000005303 weighing Methods 0.000 description 1
• 230000036642 wellbeing Effects 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
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