BG106040A - Интегрин - рецепторни антагонисти - Google Patents
Интегрин - рецепторни антагонисти Download PDFInfo
- Publication number
- BG106040A BG106040A BG106040A BG10604001A BG106040A BG 106040 A BG106040 A BG 106040A BG 106040 A BG106040 A BG 106040A BG 10604001 A BG10604001 A BG 10604001A BG 106040 A BG106040 A BG 106040A
- Authority
- BG
- Bulgaria
- Prior art keywords
- gly
- bala
- bhs
- phhs
- tolhs
- Prior art date
Links
- 229940127449 Integrin Receptor Antagonists Drugs 0.000 title abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 143
- 108010044426 integrins Proteins 0.000 claims abstract description 33
- 102000006495 integrins Human genes 0.000 claims abstract description 33
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 10
- -1 alkylaryl radical Chemical class 0.000 claims description 372
- 150000003254 radicals Chemical class 0.000 claims description 99
- 125000003118 aryl group Chemical group 0.000 claims description 62
- 229920006395 saturated elastomer Polymers 0.000 claims description 55
- 239000005557 antagonist Substances 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 125000005842 heteroatom Chemical group 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 34
- 239000003112 inhibitor Substances 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 230000015572 biosynthetic process Effects 0.000 claims description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 210000004027 cell Anatomy 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 11
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 208000001132 Osteoporosis Diseases 0.000 claims description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 8
- 239000002412 selectin antagonist Substances 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 208000006011 Stroke Diseases 0.000 claims description 7
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 7
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 229920000669 heparin Polymers 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 229940127215 low-molecular weight heparin Drugs 0.000 claims description 7
- 208000037803 restenosis Diseases 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 239000005541 ACE inhibitor Substances 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical class 0.000 claims description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 6
- 108090000190 Thrombin Proteins 0.000 claims description 6
- 230000002776 aggregation Effects 0.000 claims description 6
- 238000004220 aggregation Methods 0.000 claims description 6
- 229940127282 angiotensin receptor antagonist Drugs 0.000 claims description 6
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 229960002897 heparin Drugs 0.000 claims description 6
- 102000005962 receptors Human genes 0.000 claims description 6
- 108020003175 receptors Proteins 0.000 claims description 6
- 229960004072 thrombin Drugs 0.000 claims description 6
- 230000029663 wound healing Effects 0.000 claims description 6
- 102000055006 Calcitonin Human genes 0.000 claims description 5
- 108060001064 Calcitonin Proteins 0.000 claims description 5
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 5
- 102000002045 Endothelin Human genes 0.000 claims description 5
- 108050009340 Endothelin Proteins 0.000 claims description 5
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 5
- 201000002980 Hyperparathyroidism Diseases 0.000 claims description 5
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 claims description 5
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 claims description 5
- 206010053648 Vascular occlusion Diseases 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 5
- 230000033115 angiogenesis Effects 0.000 claims description 5
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 5
- 229960004015 calcitonin Drugs 0.000 claims description 5
- 239000000480 calcium channel blocker Substances 0.000 claims description 5
- 201000009101 diabetic angiopathy Diseases 0.000 claims description 5
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 239000002243 precursor Substances 0.000 claims description 5
- 239000000021 stimulant Substances 0.000 claims description 5
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 5
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 5
- 208000021331 vascular occlusion disease Diseases 0.000 claims description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims description 4
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 claims description 4
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 claims description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 4
- 208000024248 Vascular System injury Diseases 0.000 claims description 4
- 208000012339 Vascular injury Diseases 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 4
- 235000012000 cholesterol Nutrition 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 4
- 230000035755 proliferation Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 3
- 102100032912 CD44 antigen Human genes 0.000 claims description 3
- 229940123583 Factor Xa inhibitor Drugs 0.000 claims description 3
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 claims description 3
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 claims description 3
- 102000004890 Interleukin-8 Human genes 0.000 claims description 3
- 108090001007 Interleukin-8 Proteins 0.000 claims description 3
- 208000003076 Osteolysis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 229940122388 Thrombin inhibitor Drugs 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 238000002399 angioplasty Methods 0.000 claims description 3
- 238000011444 antiresorptive therapy Methods 0.000 claims description 3
- 238000002657 hormone replacement therapy Methods 0.000 claims description 3
- 208000017169 kidney disease Diseases 0.000 claims description 3
- 208000029791 lytic metastatic bone lesion Diseases 0.000 claims description 3
- 206010062198 microangiopathy Diseases 0.000 claims description 3
- 229940044551 receptor antagonist Drugs 0.000 claims description 3
- 239000002464 receptor antagonist Substances 0.000 claims description 3
- 239000003868 thrombin inhibitor Substances 0.000 claims description 3
- 229940122361 Bisphosphonate Drugs 0.000 claims description 2
- 102000029816 Collagenase Human genes 0.000 claims description 2
- 108060005980 Collagenase Proteins 0.000 claims description 2
- 101100289989 Drosophila melanogaster alpha-Man-Ia gene Proteins 0.000 claims description 2
- 229940123457 Free radical scavenger Drugs 0.000 claims description 2
- 229940121672 Glycosylation inhibitor Drugs 0.000 claims description 2
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 2
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 2
- 239000000854 Human Growth Hormone Substances 0.000 claims description 2
- 108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 2
- 102000000589 Interleukin-1 Human genes 0.000 claims description 2
- 108010002352 Interleukin-1 Proteins 0.000 claims description 2
- 102000000743 Interleukin-5 Human genes 0.000 claims description 2
- 108010002616 Interleukin-5 Proteins 0.000 claims description 2
- 229940127448 Interleukin-6 Antagonists Drugs 0.000 claims description 2
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 claims description 2
- 101150021286 MAS1 gene Proteins 0.000 claims description 2
- 229940123313 MCP-1 antagonist Drugs 0.000 claims description 2
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 2
- 239000002876 beta blocker Substances 0.000 claims description 2
- 229940097320 beta blocking agent Drugs 0.000 claims description 2
- 150000004663 bisphosphonates Chemical class 0.000 claims description 2
- 230000003683 cardiac damage Effects 0.000 claims description 2
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 claims description 2
- 230000015271 coagulation Effects 0.000 claims description 2
- 238000005345 coagulation Methods 0.000 claims description 2
- 229960002424 collagenase Drugs 0.000 claims description 2
- 230000000295 complement effect Effects 0.000 claims description 2
- 239000004074 complement inhibitor Substances 0.000 claims description 2
- 239000000824 cytostatic agent Substances 0.000 claims description 2
- 230000001085 cytostatic effect Effects 0.000 claims description 2
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 claims description 2
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- 238000002513 implantation Methods 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims description 2
- 230000010118 platelet activation Effects 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 239000002516 radical scavenger Substances 0.000 claims description 2
- 239000003001 serine protease inhibitor Substances 0.000 claims description 2
- 230000019491 signal transduction Effects 0.000 claims description 2
- 102000009076 src-Family Kinases Human genes 0.000 claims description 2
- 108010087686 src-Family Kinases Proteins 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 102000008607 Integrin beta3 Human genes 0.000 claims 2
- 108010020950 Integrin beta3 Proteins 0.000 claims 2
- 229940124761 MMP inhibitor Drugs 0.000 claims 2
- 230000036755 cellular response Effects 0.000 claims 2
- 239000003055 low molecular weight heparin Substances 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 102100025390 Integrin beta-2 Human genes 0.000 claims 1
- 102000015696 Interleukins Human genes 0.000 claims 1
- 108010063738 Interleukins Proteins 0.000 claims 1
- 102000000853 LDL receptors Human genes 0.000 claims 1
- 108010001831 LDL receptors Proteins 0.000 claims 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims 1
- 208000030852 Parasitic disease Diseases 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 230000020764 fibrinolysis Effects 0.000 claims 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 claims 1
- 230000003071 parasitic effect Effects 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 132
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 113
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 84
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
- 239000000203 mixture Substances 0.000 description 38
- 239000011347 resin Substances 0.000 description 36
- 229920005989 resin Polymers 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 33
- 239000000243 solution Substances 0.000 description 30
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
- 125000006239 protecting group Chemical group 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 238000000034 method Methods 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 20
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 17
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
- 229960000583 acetic acid Drugs 0.000 description 16
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 14
- 229940000635 beta-alanine Drugs 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- 125000004093 cyano group Chemical group *C#N 0.000 description 11
- ZRMJQLUSQXZDCW-FQEVSTJZSA-N C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)CC(=O)NCC(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)CC(=O)NCC(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1 ZRMJQLUSQXZDCW-FQEVSTJZSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 230000007017 scission Effects 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 150000005840 aryl radicals Chemical class 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 239000012317 TBTU Substances 0.000 description 8
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 8
- 210000001772 blood platelet Anatomy 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 7
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 7
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- 102000003992 Peroxidases Human genes 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical group 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 238000010647 peptide synthesis reaction Methods 0.000 description 6
- 108040007629 peroxidase activity proteins Proteins 0.000 description 6
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 5
- 108010049003 Fibrinogen Proteins 0.000 description 5
- 102000008946 Fibrinogen Human genes 0.000 description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 5
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012131 assay buffer Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 229940012952 fibrinogen Drugs 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 4
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 4
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- 229920001213 Polysorbate 20 Polymers 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 108010031318 Vitronectin Proteins 0.000 description 4
- 102100035140 Vitronectin Human genes 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 235000004279 alanine Nutrition 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 150000001576 beta-amino acids Chemical class 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 235000013877 carbamide Nutrition 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 235000013336 milk Nutrition 0.000 description 4
- 239000008267 milk Substances 0.000 description 4
- 210000004080 milk Anatomy 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 4
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 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 4
- 208000019553 vascular disease Diseases 0.000 description 4
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 3
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 3
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 3
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 3
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 3
- KAUTWCRUPICGMP-UHFFFAOYSA-N 3-[[2-[[2-(benzylcarbamoylamino)-1,3-oxazole-5-carbonyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CN=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(O1)=CN=C1NC(=O)NCC1=CC=CC=C1 KAUTWCRUPICGMP-UHFFFAOYSA-N 0.000 description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 125000006050 3-methyl-2-pentenyl group Chemical group 0.000 description 3
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- WECZHQYTJHRMFV-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C WECZHQYTJHRMFV-UHFFFAOYSA-N 0.000 description 3
- CVRZBUMKXOKVGG-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N1)C(=O)NCC(=O)NC(CC(=O)O)C1=CC2=CC=CC=C2C=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N1)C(=O)NCC(=O)NC(CC(=O)O)C1=CC2=CC=CC=C2C=C1 CVRZBUMKXOKVGG-UHFFFAOYSA-N 0.000 description 3
- YIFVZCAGHMVGJN-UHFFFAOYSA-N CC([O-])=O.Cn1cc(NC(=O)NCc2ccccc2)cc1C(=O)NCC(=O)NC(CC(O)=O)c1ccc[nH+]c1 Chemical compound CC([O-])=O.Cn1cc(NC(=O)NCc2ccccc2)cc1C(=O)NCC(=O)NC(CC(O)=O)c1ccc[nH+]c1 YIFVZCAGHMVGJN-UHFFFAOYSA-N 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 3
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000001311 chemical methods and process Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 210000002997 osteoclast Anatomy 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 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 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 3
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- BVFMJXNUCPGEIP-FQEVSTJZSA-N (2s)-3-[3-[[5-(benzylcarbamoylamino)thiophene-2-carbonyl]amino]propanoylamino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)NC(=O)CCNC(=O)C(S1)=CC=C1NC(=O)NCC1=CC=CC=C1 BVFMJXNUCPGEIP-FQEVSTJZSA-N 0.000 description 2
- ZMVBGJMBSDZOLI-SFHVURJKSA-N (2s)-3-[[2-[[2-(benzylcarbamoylamino)-1,3-oxazole-5-carbonyl]amino]acetyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)NC(=O)CNC(=O)C(O1)=CN=C1NC(=O)NCC1=CC=CC=C1 ZMVBGJMBSDZOLI-SFHVURJKSA-N 0.000 description 2
- IVWXOXGKBZTJSX-SFHVURJKSA-N (2s)-3-[[2-[[2-(benzylcarbamoylamino)-1,3-thiazole-4-carbonyl]amino]acetyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)NC(=O)CNC(=O)C(N=1)=CSC=1NC(=O)NCC1=CC=CC=C1 IVWXOXGKBZTJSX-SFHVURJKSA-N 0.000 description 2
- LDIQFQWJORITBJ-QFIPXVFZSA-N (2s)-3-[[2-[[4-(benzylcarbamoylamino)-1-methylpyrrole-2-carbonyl]-methylamino]acetyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound N([C@@H](CNC(=O)CN(C)C(=O)C=1N(C=C(NC(=O)NCC=2C=CC=CC=2)C=1)C)C(O)=O)C(=O)OCC1=CC=CC=C1 LDIQFQWJORITBJ-QFIPXVFZSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000006079 1,1,2-trimethyl-2-propenyl group Chemical group 0.000 description 2
- 125000006059 1,1-dimethyl-2-butenyl group Chemical group 0.000 description 2
- 125000006033 1,1-dimethyl-2-propenyl group Chemical group 0.000 description 2
- 125000006060 1,1-dimethyl-3-butenyl group Chemical group 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- 125000006062 1,2-dimethyl-2-butenyl group Chemical group 0.000 description 2
- 125000006035 1,2-dimethyl-2-propenyl group Chemical group 0.000 description 2
- 125000006063 1,2-dimethyl-3-butenyl group Chemical group 0.000 description 2
- KATOLVAXCGIBLO-UHFFFAOYSA-N 1,3-dibenzylurea Chemical compound C=1C=CC=CC=1CNC(=O)NCC1=CC=CC=C1 KATOLVAXCGIBLO-UHFFFAOYSA-N 0.000 description 2
- 125000006065 1,3-dimethyl-2-butenyl group Chemical group 0.000 description 2
- 125000006066 1,3-dimethyl-3-butenyl group Chemical group 0.000 description 2
- 125000006080 1-ethyl-1-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000006074 1-ethyl-2-butenyl group Chemical group 0.000 description 2
- 125000006037 1-ethyl-2-propenyl group Chemical group 0.000 description 2
- 125000006075 1-ethyl-3-butenyl group Chemical group 0.000 description 2
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 2
- 125000006048 1-methyl-2-pentenyl group Chemical group 0.000 description 2
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000006030 1-methyl-3-butenyl group Chemical group 0.000 description 2
- 125000006055 1-methyl-4-pentenyl group Chemical group 0.000 description 2
- YSFQIJDACSFIOH-UHFFFAOYSA-N 2,2-diaminopropanoic acid Chemical class CC(N)(N)C(O)=O YSFQIJDACSFIOH-UHFFFAOYSA-N 0.000 description 2
- 125000006069 2,3-dimethyl-2-butenyl group Chemical group 0.000 description 2
- 125000006070 2,3-dimethyl-3-butenyl group Chemical group 0.000 description 2
- NDKDFTQNXLHCGO-UHFFFAOYSA-N 2-(9h-fluoren-9-ylmethoxycarbonylamino)acetic acid Chemical compound C1=CC=C2C(COC(=O)NCC(=O)O)C3=CC=CC=C3C2=C1 NDKDFTQNXLHCGO-UHFFFAOYSA-N 0.000 description 2
- OCZSTRUXDUIHAL-UHFFFAOYSA-N 2-(benzylcarbamoylamino)-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(NC(=O)NCC=2C=CC=CC=2)=N1 OCZSTRUXDUIHAL-UHFFFAOYSA-N 0.000 description 2
- TYRGLVWXHJRKMT-UHFFFAOYSA-N 2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound OC(=O)C(C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- GSYKNLXRWYWZAT-UHFFFAOYSA-N 2-[2-(benzylcarbamoylamino)-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(NC(=O)NCC=2C=CC=CC=2)=N1 GSYKNLXRWYWZAT-UHFFFAOYSA-N 0.000 description 2
- 125000006078 2-ethyl-3-butenyl group Chemical group 0.000 description 2
- 125000006040 2-hexenyl group Chemical group 0.000 description 2
- 125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 2
- 125000006049 2-methyl-2-pentenyl group Chemical group 0.000 description 2
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 2
- 125000006056 2-methyl-4-pentenyl group Chemical group 0.000 description 2
- JIZRGGUCOQKGQD-UHFFFAOYSA-N 2-nitrothiophene Chemical compound [O-][N+](=O)C1=CC=CS1 JIZRGGUCOQKGQD-UHFFFAOYSA-N 0.000 description 2
- 125000006024 2-pentenyl group Chemical group 0.000 description 2
- 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 description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- YSYYJJWVNKORRS-UHFFFAOYSA-N 3-[3-[[4-(benzylcarbamoylamino)-1-methylpyrrole-2-carbonyl]amino]propanoylamino]-3-pyridin-3-ylpropanoic acid Chemical compound C1=C(C(=O)NCCC(=O)NC(CC(O)=O)C=2C=NC=CC=2)N(C)C=C1NC(=O)NCC1=CC=CC=C1 YSYYJJWVNKORRS-UHFFFAOYSA-N 0.000 description 2
- XEVNETHTGZYGEY-UHFFFAOYSA-N 3-[[2-[[2-(benzylcarbamoylamino)-1,3-oxazole-4-carbonyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CN=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(N=1)=COC=1NC(=O)NCC1=CC=CC=C1 XEVNETHTGZYGEY-UHFFFAOYSA-N 0.000 description 2
- IHJDDZUSFQGHNY-UHFFFAOYSA-N 3-[[2-[[2-(benzylcarbamoylamino)-1,3-oxazole-5-carbonyl]amino]acetyl]amino]-3-(3,5-dichlorophenyl)propanoic acid Chemical compound C=1C(Cl)=CC(Cl)=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(O1)=CN=C1NC(=O)NCC1=CC=CC=C1 IHJDDZUSFQGHNY-UHFFFAOYSA-N 0.000 description 2
- FNQGLKRCVLOEOI-UHFFFAOYSA-N 3-[[2-[[4-(benzylcarbamoylamino)-1-methylpyrrole-2-carbonyl]amino]acetyl]amino]-3-naphthalen-2-ylpropanoic acid Chemical compound C1=C(C(=O)NCC(=O)NC(CC(O)=O)C=2C=C3C=CC=CC3=CC=2)N(C)C=C1NC(=O)NCC1=CC=CC=C1 FNQGLKRCVLOEOI-UHFFFAOYSA-N 0.000 description 2
- DCIXVMLLSRDBCL-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-2-carbonyl]amino]acetyl]amino]-3-(2,5-dimethoxyphenyl)propanoic acid Chemical compound COC1=CC=C(OC)C(C(CC(O)=O)NC(=O)CNC(=O)C=2SC(NC(=O)NCC=3C=CC=CC=3)=CC=2)=C1 DCIXVMLLSRDBCL-UHFFFAOYSA-N 0.000 description 2
- HNQGBAOSEITQQT-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-2-carbonyl]amino]acetyl]amino]-3-(3,4-dimethoxyphenyl)propanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(CC(O)=O)NC(=O)CNC(=O)C(S1)=CC=C1NC(=O)NCC1=CC=CC=C1 HNQGBAOSEITQQT-UHFFFAOYSA-N 0.000 description 2
- BLYATQCVCKGGPT-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-2-carbonyl]amino]acetyl]amino]-3-naphthalen-1-ylpropanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1C(CC(=O)O)NC(=O)CNC(=O)C(S1)=CC=C1NC(=O)NCC1=CC=CC=C1 BLYATQCVCKGGPT-UHFFFAOYSA-N 0.000 description 2
- WQEAUYPJMRZAST-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-3-carbonyl]amino]acetyl]amino]-3-(3,5-dichlorophenyl)propanoic acid Chemical compound C=1C(Cl)=CC(Cl)=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(C=1)=CSC=1NC(=O)NCC1=CC=CC=C1 WQEAUYPJMRZAST-UHFFFAOYSA-N 0.000 description 2
- LTAQWGJIAOYYEJ-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-3-carbonyl]amino]acetyl]amino]-3-(4-methylphenyl)propanoic acid Chemical compound C1=CC(C)=CC=C1C(CC(O)=O)NC(=O)CNC(=O)C1=CSC(NC(=O)NCC=2C=CC=CC=2)=C1 LTAQWGJIAOYYEJ-UHFFFAOYSA-N 0.000 description 2
- GITHMVUAHBUYNI-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-3-carbonyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CN=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(C=1)=CSC=1NC(=O)NCC1=CC=CC=C1 GITHMVUAHBUYNI-UHFFFAOYSA-N 0.000 description 2
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 2
- 125000006041 3-hexenyl group Chemical group 0.000 description 2
- 125000006032 3-methyl-3-butenyl group Chemical group 0.000 description 2
- 125000006054 3-methyl-3-pentenyl group Chemical group 0.000 description 2
- 125000006057 3-methyl-4-pentenyl group Chemical group 0.000 description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 125000006042 4-hexenyl group Chemical group 0.000 description 2
- 125000006051 4-methyl-2-pentenyl group Chemical group 0.000 description 2
- 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000006058 4-methyl-4-pentenyl group Chemical group 0.000 description 2
- 125000006043 5-hexenyl group Chemical group 0.000 description 2
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical group OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- NHXSXAWFKOWPGI-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C1=CC=CC=C1 NHXSXAWFKOWPGI-UHFFFAOYSA-N 0.000 description 2
- DPZDDBRERDSVMF-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NC(CC(=O)O)C1CCCCC1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NC(CC(=O)O)C1CCCCC1 DPZDDBRERDSVMF-UHFFFAOYSA-N 0.000 description 2
- MOJNHFGHMLRFJJ-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NC(CC(=O)O)C=1C=NC=CC1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NC(CC(=O)O)C=1C=NC=CC1 MOJNHFGHMLRFJJ-UHFFFAOYSA-N 0.000 description 2
- PJFPIEGKRHXYRZ-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)NCCC(=O)NC(CC(=O)O)C1CCCCC1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)NCCC(=O)NC(CC(=O)O)C1CCCCC1 PJFPIEGKRHXYRZ-UHFFFAOYSA-N 0.000 description 2
- VODWYCYDJAOEGL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)NCCC(=O)NC(CC(=O)O)C=1C=NC=CC=1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)NCCC(=O)NC(CC(=O)O)C=1C=NC=CC=1 VODWYCYDJAOEGL-UHFFFAOYSA-N 0.000 description 2
- DSFLVQKKKBGGIZ-ZZWBGTBQSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N[C@@H](C(=O)NC(CC(=O)O)C1=CC=C(C=C1)C(C)(C)C)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N[C@@H](C(=O)NC(CC(=O)O)C1=CC=C(C=C1)C(C)(C)C)C DSFLVQKKKBGGIZ-ZZWBGTBQSA-N 0.000 description 2
- DSFLVQKKKBGGIZ-HXBUSHRASA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N[C@H](C(=O)NC(CC(=O)O)C1=CC=C(C=C1)C(C)(C)C)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N[C@H](C(=O)NC(CC(=O)O)C1=CC=C(C=C1)C(C)(C)C)C DSFLVQKKKBGGIZ-HXBUSHRASA-N 0.000 description 2
- DUIXNWGIJUVLKZ-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC2=CC=CC=C2C=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC2=CC=CC=C2C=C1 DUIXNWGIJUVLKZ-UHFFFAOYSA-N 0.000 description 2
- ZOTXUVGEVRIEBL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C ZOTXUVGEVRIEBL-UHFFFAOYSA-N 0.000 description 2
- GJOOHTUKHNLNMU-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C1=CC=CC=C1 GJOOHTUKHNLNMU-UHFFFAOYSA-N 0.000 description 2
- GLIFBFFKWURDFZ-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=CC2=CC=CC=C12 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1=CC=CC2=CC=CC=C12 GLIFBFFKWURDFZ-UHFFFAOYSA-N 0.000 description 2
- XNOMNWRWDSVJGH-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C=1C=NC=CC1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C=1C=NC=CC1 XNOMNWRWDSVJGH-UHFFFAOYSA-N 0.000 description 2
- BAIQNBWCAKKOQA-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1CCCCC1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1CCCCC1 BAIQNBWCAKKOQA-UHFFFAOYSA-N 0.000 description 2
- PTNIAPRVCXSGTG-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCCC(=O)NC(CC(=O)O)C1=C(C=CC(=C1)OC)OC Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCCC(=O)NC(CC(=O)O)C1=C(C=CC(=C1)OC)OC PTNIAPRVCXSGTG-UHFFFAOYSA-N 0.000 description 2
- JIVPNEROKWDAEG-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N1)C(=O)NCC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N1)C(=O)NCC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C JIVPNEROKWDAEG-UHFFFAOYSA-N 0.000 description 2
- CCKWYMHBRBKPLC-LPHOPBHVSA-N C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)C(=O)N[C@H](C(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)C(=O)N[C@H](C(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1)C CCKWYMHBRBKPLC-LPHOPBHVSA-N 0.000 description 2
- JAEUOEXFAUZZMD-UWJYYQICSA-N C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)CC(=O)N[C@H](C(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)CC(=O)N[C@H](C(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1)C JAEUOEXFAUZZMD-UWJYYQICSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- 102000016359 Fibronectins Human genes 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000242362 Kordia Species 0.000 description 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 208000034827 Neointima Diseases 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 208000010191 Osteitis Deformans Diseases 0.000 description 2
- 208000027868 Paget disease Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 108060008245 Thrombospondin Proteins 0.000 description 2
- 102000002938 Thrombospondin Human genes 0.000 description 2
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 2
- 239000003875 Wang resin Substances 0.000 description 2
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 2
- 238000011481 absorbance measurement Methods 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000002141 anti-parasite Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000003096 antiparasitic agent Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000002805 bone matrix Anatomy 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- CRPUJAZIXJMDBK-UHFFFAOYSA-N camphene Chemical compound C1CC2C(=C)C(C)(C)C1C2 CRPUJAZIXJMDBK-UHFFFAOYSA-N 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229950005499 carbon tetrachloride Drugs 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 208000027202 mammary Paget disease Diseases 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 2
- 230000008692 neointimal formation Effects 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical compound NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 1
- PDRJLZDUOULRHE-ZETCQYMHSA-N (2s)-2-amino-3-pyridin-2-ylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=N1 PDRJLZDUOULRHE-ZETCQYMHSA-N 0.000 description 1
- MZJMMZBHRMYGQE-NRFANRHFSA-N (2s)-3-[[2-[[4-(benzylcarbamoylamino)-1-methylpyrrole-2-carbonyl]amino]acetyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C1=C(C(=O)NCC(=O)NC[C@H](NC(=O)OCC=2C=CC=CC=2)C(O)=O)N(C)C=C1NC(=O)NCC1=CC=CC=C1 MZJMMZBHRMYGQE-NRFANRHFSA-N 0.000 description 1
- IEFPFWXCTNNSQN-FQEVSTJZSA-N (2s)-3-[[2-[[5-(benzylcarbamoylamino)furan-2-carbonyl]-methylamino]acetyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound N([C@@H](CNC(=O)CN(C)C(=O)C=1OC(NC(=O)NCC=2C=CC=CC=2)=CC=1)C(O)=O)C(=O)OCC1=CC=CC=C1 IEFPFWXCTNNSQN-FQEVSTJZSA-N 0.000 description 1
- QXXVTZTYGKZSOS-IBGZPJMESA-N (2s)-3-[[2-[[5-(benzylcarbamoylamino)thiophene-2-carbonyl]amino]acetyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)NC(=O)CNC(=O)C(S1)=CC=C1NC(=O)NCC1=CC=CC=C1 QXXVTZTYGKZSOS-IBGZPJMESA-N 0.000 description 1
- ZRVZOBGMZWVJOS-VMXHOPILSA-N (2s)-6-amino-2-[[(2s)-1-[(2s)-2-[[(2s)-2-[[2-[[(2s)-2-[(2-aminoacetyl)amino]-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]pyrrolidine-2-carbonyl]amino]hexanoic acid Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)CN ZRVZOBGMZWVJOS-VMXHOPILSA-N 0.000 description 1
- RHBJBHPMIXWECR-OAQYLSRUSA-N (3r)-4-[[2-[[5-(benzylcarbamoylamino)furan-2-carbonyl]-methylamino]acetyl]amino]-3-(phenylmethoxycarbonylamino)butanoic acid Chemical compound N([C@H](CC(O)=O)CNC(=O)CN(C)C(=O)C=1OC(NC(=O)NCC=2C=CC=CC=2)=CC=1)C(=O)OCC1=CC=CC=C1 RHBJBHPMIXWECR-OAQYLSRUSA-N 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- DHBXNPKRAUYBTH-UHFFFAOYSA-N 1,1-ethanedithiol Chemical compound CC(S)S DHBXNPKRAUYBTH-UHFFFAOYSA-N 0.000 description 1
- JFLSOKIMYBSASW-UHFFFAOYSA-N 1-chloro-2-[chloro(diphenyl)methyl]benzene Chemical compound ClC1=CC=CC=C1C(Cl)(C=1C=CC=CC=1)C1=CC=CC=C1 JFLSOKIMYBSASW-UHFFFAOYSA-N 0.000 description 1
- 125000006082 1-ethyl-2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000004790 1-fluoroethoxy group Chemical group FC(C)O* 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- LJVQHXICFCZRJN-UHFFFAOYSA-N 1h-1,2,4-triazole-5-carboxylic acid Chemical compound OC(=O)C1=NC=NN1 LJVQHXICFCZRJN-UHFFFAOYSA-N 0.000 description 1
- 125000006067 2,2-dimethyl-3-butenyl group Chemical group 0.000 description 1
- BPKYIPMIYKDNDX-UHFFFAOYSA-N 2-(benzylcarbamoylamino)-1,3-oxazole-4-carboxylic acid Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N=1)C(=O)O BPKYIPMIYKDNDX-UHFFFAOYSA-N 0.000 description 1
- SMMIXYLWADEUHD-UHFFFAOYSA-N 2-(benzylcarbamoylamino)-1,3-oxazole-5-carboxylic acid Chemical compound O1C(C(=O)O)=CN=C1NC(=O)NCC1=CC=CC=C1 SMMIXYLWADEUHD-UHFFFAOYSA-N 0.000 description 1
- CZIBABWRWDOXIT-UHFFFAOYSA-N 2-(benzylsulfonylamino)propanoic acid Chemical compound OC(=O)C(C)NS(=O)(=O)CC1=CC=CC=C1 CZIBABWRWDOXIT-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- WEDLPAQWIONWGX-UHFFFAOYSA-N 2-(naphthalen-1-ylsulfonylamino)propanoic acid Chemical compound C1=CC=C2C(S(=O)(=O)NC(C)C(O)=O)=CC=CC2=C1 WEDLPAQWIONWGX-UHFFFAOYSA-N 0.000 description 1
- WDEXFHHXWOSJRV-UHFFFAOYSA-N 2-(naphthalen-2-ylsulfonylamino)propanoic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)NC(C)C(O)=O)=CC=C21 WDEXFHHXWOSJRV-UHFFFAOYSA-N 0.000 description 1
- JJBCTCGUOQYZHK-UHFFFAOYSA-N 2-acetyloxybenzoate;(5-amino-1-carboxypentyl)azanium Chemical compound OC(=O)C(N)CCCC[NH3+].CC(=O)OC1=CC=CC=C1C([O-])=O JJBCTCGUOQYZHK-UHFFFAOYSA-N 0.000 description 1
- SXRKNKLAGDXHDA-UHFFFAOYSA-N 2-bromoethyl 2-oxopropanoate Chemical compound CC(=O)C(=O)OCCBr SXRKNKLAGDXHDA-UHFFFAOYSA-N 0.000 description 1
- 125000006077 2-ethyl-2-butenyl group Chemical group 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006031 2-methyl-3-butenyl group Chemical group 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- 125000006188 2-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- YKIPCMAQZHPCHW-UHFFFAOYSA-N 3-(benzylcarbamoylamino)-1H-1,2,4-triazole-5-carboxylic acid Chemical compound OC(=O)c1nc(NC(=O)NCc2ccccc2)n[nH]1 YKIPCMAQZHPCHW-UHFFFAOYSA-N 0.000 description 1
- KDSSSTJCIAYSLL-UHFFFAOYSA-N 3-[[2-[[2-(benzylcarbamoylamino)-1,3-thiazole-5-carbonyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CN=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(S1)=CN=C1NC(=O)NCC1=CC=CC=C1 KDSSSTJCIAYSLL-UHFFFAOYSA-N 0.000 description 1
- SPEGLASITQIUHE-UHFFFAOYSA-N 3-[[2-[[5-(benzylcarbamoylamino)thiophene-2-carbonyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid Chemical compound C=1C=CN=CC=1C(CC(=O)O)NC(=O)CNC(=O)C(S1)=CC=C1NC(=O)NCC1=CC=CC=C1 SPEGLASITQIUHE-UHFFFAOYSA-N 0.000 description 1
- XQIGCIKMXNANJT-UHFFFAOYSA-N 3-amino-1,2,4-triazole-3-carboxylic acid Chemical compound OC(=O)C1(N)N=CN=N1 XQIGCIKMXNANJT-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- APTHSBLGVMYQRL-UHFFFAOYSA-N 4-amino-1h-pyrrole-2-carboxylic acid Chemical compound NC1=CNC(C(O)=O)=C1 APTHSBLGVMYQRL-UHFFFAOYSA-N 0.000 description 1
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- QEDKLMLRTUCIOX-UHFFFAOYSA-N 5-(benzylcarbamoylamino)furan-2-carboxylic acid Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(O1)C(=O)O QEDKLMLRTUCIOX-UHFFFAOYSA-N 0.000 description 1
- URBZWDMDTMKBKW-UHFFFAOYSA-N 5-(benzylcarbamoylamino)thiophene-2-carboxylic acid Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)O URBZWDMDTMKBKW-UHFFFAOYSA-N 0.000 description 1
- UYTYLLQCQDBCDW-UHFFFAOYSA-N 5-amino-2-methylpyrazole-3-carboxylic acid Chemical compound CN1N=C(N)C=C1C(O)=O UYTYLLQCQDBCDW-UHFFFAOYSA-N 0.000 description 1
- PPKYDYFPGZQNFM-UHFFFAOYSA-N 5-amino-2h-1,3,4-thiadiazole-5-carboxylic acid Chemical compound OC(=O)C1(N)SCN=N1 PPKYDYFPGZQNFM-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
- UNEPVPOHGXLUIR-UHFFFAOYSA-N 6317-37-9 Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)S1 UNEPVPOHGXLUIR-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 102100021267 Anion exchange protein 4 Human genes 0.000 description 1
- 101710160272 Anion exchange protein 4 Proteins 0.000 description 1
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 1
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 239000004604 Blowing Agent Substances 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- 229940123861 Bone formation stimulant Drugs 0.000 description 1
- SVPLJYKBSNVDJK-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NCC(CC(=O)O)NC(=O)OCC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC1=CC=C(S1)C(=O)N(C)CC(=O)NCC(CC(=O)O)NC(=O)OCC1=CC=CC=C1 SVPLJYKBSNVDJK-UHFFFAOYSA-N 0.000 description 1
- GQJHVQYYEAKHBG-HSZRJFAPSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(C(=O)NCC(=O)NC[C@H](C(=O)O)NC(=O)OCC2=CC=CC=C2)C=CC=1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(C(=O)NCC(=O)NC[C@H](C(=O)O)NC(=O)OCC2=CC=CC=C2)C=CC=1 GQJHVQYYEAKHBG-HSZRJFAPSA-N 0.000 description 1
- SXTXSDYXGSKJMR-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1CCCCC1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)N(C)CC(=O)NC(CC(=O)O)C1CCCCC1 SXTXSDYXGSKJMR-UHFFFAOYSA-N 0.000 description 1
- DOEFWBQLZRHEEE-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC(=C(C=C1)OC)OC Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC(=C(C=C1)OC)OC DOEFWBQLZRHEEE-UHFFFAOYSA-N 0.000 description 1
- DPCPATWVJROOKV-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC(=CC(=C1)Cl)Cl Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC(=CC(=C1)Cl)Cl DPCPATWVJROOKV-UHFFFAOYSA-N 0.000 description 1
- AEOASSGYTFLRSS-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1C=C(N(C1)C)C(=O)NCC(=O)NC(CC(=O)O)C1=CC=C(C=C1)C1=CC=CC=C1 AEOASSGYTFLRSS-UHFFFAOYSA-N 0.000 description 1
- FZDMIEJRFDIKEW-SFHVURJKSA-N C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N1)C(=O)NCC(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1OC=C(N1)C(=O)NCC(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1 FZDMIEJRFDIKEW-SFHVURJKSA-N 0.000 description 1
- PEJVNSVPBNEUQV-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(=O)NC=1SC(=CN1)C(=O)NCC(=O)NC(CC(=O)O)C1=C(C=CC(=C1)OC)OC Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1SC(=CN1)C(=O)NCC(=O)NC(CC(=O)O)C1=C(C=CC(=C1)OC)OC PEJVNSVPBNEUQV-UHFFFAOYSA-N 0.000 description 1
- JAEUOEXFAUZZMD-UTKZUKDTSA-N C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)CC(=O)N[C@@H](C(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1)C Chemical compound C(C1=CC=CC=C1)NC(=O)NC=1SC=C(N=1)CC(=O)N[C@@H](C(=O)NC[C@@H](C(=O)O)NC(=O)OCC1=CC=CC=C1)C JAEUOEXFAUZZMD-UTKZUKDTSA-N 0.000 description 1
- UWESUJDQQBSNCA-NRFANRHFSA-N C1=CC=C(C=C1)CNC(=O)NC2=CC(=CS2)C(=O)NCCC(=O)NC[C@@H](C(=O)O)NC(=O)OCC3=CC=CC=C3 Chemical compound C1=CC=C(C=C1)CNC(=O)NC2=CC(=CS2)C(=O)NCCC(=O)NC[C@@H](C(=O)O)NC(=O)OCC3=CC=CC=C3 UWESUJDQQBSNCA-NRFANRHFSA-N 0.000 description 1
- TWIZANLIQUUSQX-FQEVSTJZSA-N C1=CC=C(C=C1)CNC(=O)NC2=CC(=CS2)C(=O)NCCC(=O)NC[C@@H](C(=O)O)NS(=O)(=O)C3=CC=CC=C3 Chemical compound C1=CC=C(C=C1)CNC(=O)NC2=CC(=CS2)C(=O)NCCC(=O)NC[C@@H](C(=O)O)NS(=O)(=O)C3=CC=CC=C3 TWIZANLIQUUSQX-FQEVSTJZSA-N 0.000 description 1
- UCMLYXQCGSSOQD-LJQANCHMSA-N C1=CC=C(C=C1)CNC(=O)NC2=NNC(=N2)C(=O)NCCC(=O)NC[C@@H](CC(=O)O)NC(=O)OCC3=CC=CC=C3 Chemical compound C1=CC=C(C=C1)CNC(=O)NC2=NNC(=N2)C(=O)NCCC(=O)NC[C@@H](CC(=O)O)NC(=O)OCC3=CC=CC=C3 UCMLYXQCGSSOQD-LJQANCHMSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical class 0.000 description 1
- ATCBRYAUAXPURN-SFHVURJKSA-N CCCCS(=O)(=O)N[C@@H](CNC(=O)CCNC(=O)C1=CSC(=C1)NC(=O)NCC2=CC=CC=C2)C(=O)O Chemical compound CCCCS(=O)(=O)N[C@@H](CNC(=O)CCNC(=O)C1=CSC(=C1)NC(=O)NCC2=CC=CC=C2)C(=O)O ATCBRYAUAXPURN-SFHVURJKSA-N 0.000 description 1
- HHDDXIAZUZWAMX-FQEVSTJZSA-N CN(CC(=O)NC[C@@H](C(=O)O)NS(=O)(=O)C1=CC=CC=C1)C(=O)CC2=CSC(=N2)NC(=O)NCC3=CC=CC=C3 Chemical compound CN(CC(=O)NC[C@@H](C(=O)O)NS(=O)(=O)C1=CC=CC=C1)C(=O)CC2=CSC(=N2)NC(=O)NCC3=CC=CC=C3 HHDDXIAZUZWAMX-FQEVSTJZSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108090000201 Carboxypeptidase B2 Proteins 0.000 description 1
- 102100035023 Carboxypeptidase B2 Human genes 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 241000070918 Cima Species 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 108700021041 Disintegrin Proteins 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000545744 Hirudinea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000803709 Homo sapiens Vitronectin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
- 102100022339 Integrin alpha-L Human genes 0.000 description 1
- 102100022337 Integrin alpha-V Human genes 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- DGYHPLMPMRKMPD-BYPYZUCNSA-N L-propargylglycine Chemical compound OC(=O)[C@@H](N)CC#C DGYHPLMPMRKMPD-BYPYZUCNSA-N 0.000 description 1
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- 241000208202 Linaceae Species 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- DTOBPZXGVBQKJD-UHFFFAOYSA-N NC1(OC=CN1)C(=O)O Chemical compound NC1(OC=CN1)C(=O)O DTOBPZXGVBQKJD-UHFFFAOYSA-N 0.000 description 1
- KHUFYCSOWBSHFA-UHFFFAOYSA-N NC1=C(OC=C1)C(=O)OC(=O)NCC1=CC=CC=C1 Chemical compound NC1=C(OC=C1)C(=O)OC(=O)NCC1=CC=CC=C1 KHUFYCSOWBSHFA-UHFFFAOYSA-N 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- BYNPVIFXZBYHTL-JOCHJYFZSA-N OC(C[C@H](CNC(CCNC(C1=CSC(NC(NCC2=CC=CC=C2)=O)=C1)=O)=O)NC(OCC1=CC=CC=C1)=O)=O Chemical compound OC(C[C@H](CNC(CCNC(C1=CSC(NC(NCC2=CC=CC=C2)=O)=C1)=O)=O)NC(OCC1=CC=CC=C1)=O)=O BYNPVIFXZBYHTL-JOCHJYFZSA-N 0.000 description 1
- HMPVRYMNSVIJDI-KRWDZBQOSA-N OC([C@H](CNC(CNC(C1=NNC(NC(NCC2=CC=CC=C2)=O)=N1)=O)=O)NC(OCC1=CC=CC=C1)=O)=O Chemical compound OC([C@H](CNC(CNC(C1=NNC(NC(NCC2=CC=CC=C2)=O)=N1)=O)=O)NC(OCC1=CC=CC=C1)=O)=O HMPVRYMNSVIJDI-KRWDZBQOSA-N 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 1
- 102100038124 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
- PXRCIOIWVGAZEP-UHFFFAOYSA-N Primaeres Camphenhydrat Natural products C1CC2C(O)(C)C(C)(C)C1C2 PXRCIOIWVGAZEP-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 229940123924 Protein kinase C inhibitor Drugs 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 244000191761 Sida cordifolia Species 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102000007000 Tenascin Human genes 0.000 description 1
- 108010008125 Tenascin Proteins 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 108010048673 Vitronectin Receptors Proteins 0.000 description 1
- BHIRTUJCQXDFRD-UHFFFAOYSA-N [Si].[P].[S] Chemical compound [Si].[P].[S] BHIRTUJCQXDFRD-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- XCPQUQHBVVXMRQ-UHFFFAOYSA-N alpha-Fenchene Natural products C1CC2C(=C)CC1C2(C)C XCPQUQHBVVXMRQ-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 230000000123 anti-resoprtive effect Effects 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000024279 bone resorption Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 229930006739 camphene Natural products 0.000 description 1
- ZYPYEBYNXWUCEA-UHFFFAOYSA-N camphenilone Natural products C1CC2C(=O)C(C)(C)C1C2 ZYPYEBYNXWUCEA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 125000004789 chlorodifluoromethoxy group Chemical group ClC(O*)(F)F 0.000 description 1
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000002425 crystallisation Methods 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 108010073977 decorsin Proteins 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 201000002249 diabetic peripheral angiopathy Diseases 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 229960002768 dipyridamole Drugs 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- AVMSETIQLSEUJA-UHFFFAOYSA-N ethyl 2-(benzylcarbamoylamino)-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(NC(=O)NCC=2C=CC=CC=2)=N1 AVMSETIQLSEUJA-UHFFFAOYSA-N 0.000 description 1
- NZWGCFLAGUIPBG-UHFFFAOYSA-N ethyl 2-(benzylcarbamoylamino)-1,3-oxazole-5-carboxylate Chemical compound C(C)OC(=O)C1=CN=C(O1)NC(=O)NCC1=CC=CC=C1 NZWGCFLAGUIPBG-UHFFFAOYSA-N 0.000 description 1
- NBABLVASYFPOEV-UHFFFAOYSA-N ethyl 2-amino-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(N)=N1 NBABLVASYFPOEV-UHFFFAOYSA-N 0.000 description 1
- UHUDJKCNXFBBHU-UHFFFAOYSA-N ethyl 2-amino-1,3-oxazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)O1 UHUDJKCNXFBBHU-UHFFFAOYSA-N 0.000 description 1
- VNZXERIGKZNEKB-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(N)S1 VNZXERIGKZNEKB-UHFFFAOYSA-N 0.000 description 1
- DWXKSCKBUSAOKS-UHFFFAOYSA-N ethyl 2-chloro-3-oxopropanoate Chemical compound CCOC(=O)C(Cl)C=O DWXKSCKBUSAOKS-UHFFFAOYSA-N 0.000 description 1
- IZCSREAMZDZVFW-UHFFFAOYSA-N ethyl 5-amino-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC=C(N)S1 IZCSREAMZDZVFW-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 108010064365 glycyl- arginyl-glycyl-aspartyl-seryl-prolyl-lysine Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000002607 heparin antagonist Substances 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- SVWWNEYBEFASMP-UHFFFAOYSA-N methyl 2-aminopyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(N)=C1 SVWWNEYBEFASMP-UHFFFAOYSA-N 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- FZXQUCUWEZQIHL-UHFFFAOYSA-N methyl 2h-triazole-4-carboxylate Chemical compound COC(=O)C=1C=NNN=1 FZXQUCUWEZQIHL-UHFFFAOYSA-N 0.000 description 1
- XQNRXJWIFJQYPP-UHFFFAOYSA-N methyl 4-(aminomethyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC(CN)=CS1 XQNRXJWIFJQYPP-UHFFFAOYSA-N 0.000 description 1
- DXQCQLJXMICOKQ-UHFFFAOYSA-N methyl 4-amino-1-methylpyrrole-2-carboxylate Chemical compound COC(=O)C1=CC(N)=CN1C DXQCQLJXMICOKQ-UHFFFAOYSA-N 0.000 description 1
- YHOVYZINCVIRGK-UHFFFAOYSA-N methyl 4-aminopyridine-2-carboxylate Chemical compound COC(=O)C1=CC(N)=CC=N1 YHOVYZINCVIRGK-UHFFFAOYSA-N 0.000 description 1
- PYQRUDYLXHRTQU-UHFFFAOYSA-N methyl 4-aminopyrimidine-2-carboxylate Chemical compound COC(=O)C1=NC=CC(N)=N1 PYQRUDYLXHRTQU-UHFFFAOYSA-N 0.000 description 1
- KLKQGSISBRVCTK-UHFFFAOYSA-N methyl 5-aminofuran-2-carboxylate Chemical compound COC(=O)C1=CC=C(N)O1 KLKQGSISBRVCTK-UHFFFAOYSA-N 0.000 description 1
- LJYSUEZSIXOJFK-UHFFFAOYSA-N methyl 5-aminopyridine-2-carboxylate Chemical compound COC(=O)C1=CC=C(N)C=N1 LJYSUEZSIXOJFK-UHFFFAOYSA-N 0.000 description 1
- ROZWUNOYMSUTKS-UHFFFAOYSA-N methyl 5-nitrothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C([N+]([O-])=O)S1 ROZWUNOYMSUTKS-UHFFFAOYSA-N 0.000 description 1
- URSUGGQRGURMAM-UHFFFAOYSA-N methyl 6-aminopyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(N)=NC=N1 URSUGGQRGURMAM-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical class [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960004526 piracetam Drugs 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000044 progesterone antagonist Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003881 protein kinase C inhibitor Substances 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 239000000719 purinergic P2Y receptor antagonist Substances 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229940107685 reopro Drugs 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 230000015590 smooth muscle cell migration Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 229940055764 triaz Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D409/02—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
- C07D409/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Biophysics (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Hospice & Palliative Care (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1999119218 DE19919218A1 (de) | 1999-04-28 | 1999-04-28 | Neue Integrinrezeptorantagonisten |
| DE1999148269 DE19948269A1 (de) | 1999-10-06 | 1999-10-06 | Neue Integrinrezeptorantagonisten |
| PCT/EP2000/003469 WO2000066618A1 (de) | 1999-04-28 | 2000-04-17 | Integrinrezeptorantagonisten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG106040A true BG106040A (bg) | 2002-05-31 |
Family
ID=26053109
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG106040A BG106040A (bg) | 1999-04-28 | 2001-10-23 | Интегрин - рецепторни антагонисти |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1173468A1 (pl) |
| JP (1) | JP2003500339A (pl) |
| KR (1) | KR20020010618A (pl) |
| CN (1) | CN1355811A (pl) |
| AU (1) | AU4551500A (pl) |
| BG (1) | BG106040A (pl) |
| BR (1) | BR0010092A (pl) |
| CA (1) | CA2371604A1 (pl) |
| CZ (1) | CZ20013846A3 (pl) |
| HK (1) | HK1046692A1 (pl) |
| HU (1) | HUP0202898A2 (pl) |
| IL (1) | IL146146A0 (pl) |
| MX (1) | MXPA01010834A (pl) |
| NO (1) | NO20015237L (pl) |
| PL (1) | PL352777A1 (pl) |
| RU (1) | RU2001132141A (pl) |
| SK (1) | SK15342001A3 (pl) |
| TR (1) | TR200103090T2 (pl) |
| WO (1) | WO2000066618A1 (pl) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10204789A1 (de) * | 2002-02-06 | 2003-08-14 | Merck Patent Gmbh | Inhibitoren des Integrins alpha¶v¶beta6 |
| KR100759130B1 (ko) * | 2005-02-12 | 2007-09-19 | 휴메드 주식회사 | 항 인테그린 항체 코팅스텐트 및 그의 제조방법 |
| US8716320B2 (en) * | 2006-07-21 | 2014-05-06 | Replidyne, Inc. | Antibacteriall heterocyclic ureas |
| WO2009015193A1 (en) | 2007-07-23 | 2009-01-29 | Replidyne, Inc. | Antibacterial sulfone and sulfoxide substituted heterocyclic urea compounds |
| US8148380B2 (en) | 2007-07-23 | 2012-04-03 | Crestone, Inc. | Antibacterial amide and sulfonamide substituted heterocyclic urea compounds |
| EA019990B1 (ru) * | 2009-06-02 | 2014-07-30 | Бёрингер Ингельхайм Интернациональ Гмбх | ПРОИЗВОДНЫЕ АМИДОВ 6,7-ДИГИДРО-5H-ИМИДАЗО[1,2-a]ИМИДАЗОЛ-3-КАРБОНОВОЙ КИСЛОТЫ |
| BR112014016736A8 (pt) * | 2012-01-27 | 2017-07-04 | Hoffmann La Roche | composto, composição farmacêutica, método para tratamento, uso de um composto e invenção |
| RU2731807C1 (ru) * | 2020-05-05 | 2020-09-08 | Федеральное государственное бюджетное научное учреждение "Научно-исследовательский институт ревматологии имени В.А.Насоновой» (ФГБНУ НИИР им. В.А. Насоновой) | Способ определения показаний к началу приема генно-инженерных биологических препаратов при неэффективности базисных противовоспалительных препаратов при ранних формах псориатического артрита |
| CN121079081A (zh) * | 2023-04-21 | 2025-12-05 | 图宾根埃伯哈德卡尔斯大学 | 转录因子HilD抑制剂 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9610422A (pt) * | 1995-08-30 | 1999-07-13 | Searle & Co | Derivados de meta-guanidina uréia tiouréia ou ácido aminobenzóico azacíclico como antagonistas de integrina |
| GB2327609A (en) * | 1997-07-23 | 1999-02-03 | Merck & Co Inc | A method for eliciting an avß5 or dual avß3/avß5 antagonizing effect |
| EP0928790B1 (en) * | 1998-01-02 | 2003-03-05 | F. Hoffmann-La Roche Ag | Thiazole derivatives |
| CZ20003672A3 (cs) * | 1998-04-10 | 2001-08-15 | G. D. Searle & Co. | Heterocyklické glycyl-beta-alaninové deriváty jako agonisté vitronektinu |
-
2000
- 2000-04-17 HU HU0202898A patent/HUP0202898A2/hu unknown
- 2000-04-17 HK HK02107883.3A patent/HK1046692A1/zh unknown
- 2000-04-17 IL IL14614600A patent/IL146146A0/xx unknown
- 2000-04-17 EP EP00926971A patent/EP1173468A1/de not_active Withdrawn
- 2000-04-17 AU AU45515/00A patent/AU4551500A/en not_active Abandoned
- 2000-04-17 CN CN00808907A patent/CN1355811A/zh active Pending
- 2000-04-17 RU RU2001132141/04A patent/RU2001132141A/ru unknown
- 2000-04-17 CZ CZ20013846A patent/CZ20013846A3/cs unknown
- 2000-04-17 CA CA002371604A patent/CA2371604A1/en not_active Abandoned
- 2000-04-17 SK SK1534-2001A patent/SK15342001A3/sk unknown
- 2000-04-17 MX MXPA01010834A patent/MXPA01010834A/es unknown
- 2000-04-17 KR KR1020017013790A patent/KR20020010618A/ko not_active Ceased
- 2000-04-17 TR TR2001/03090T patent/TR200103090T2/xx unknown
- 2000-04-17 BR BR0010092-7A patent/BR0010092A/pt not_active IP Right Cessation
- 2000-04-17 JP JP2000615647A patent/JP2003500339A/ja active Pending
- 2000-04-17 PL PL00352777A patent/PL352777A1/pl not_active Application Discontinuation
- 2000-04-17 WO PCT/EP2000/003469 patent/WO2000066618A1/de not_active Ceased
-
2001
- 2001-10-23 BG BG106040A patent/BG106040A/bg unknown
- 2001-10-26 NO NO20015237A patent/NO20015237L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2001132141A (ru) | 2004-03-20 |
| KR20020010618A (ko) | 2002-02-04 |
| HK1046692A1 (zh) | 2003-01-24 |
| BR0010092A (pt) | 2002-06-11 |
| JP2003500339A (ja) | 2003-01-07 |
| SK15342001A3 (sk) | 2002-06-04 |
| WO2000066618A1 (de) | 2000-11-09 |
| CZ20013846A3 (cs) | 2002-06-12 |
| PL352777A1 (pl) | 2003-09-08 |
| AU4551500A (en) | 2000-11-17 |
| TR200103090T2 (tr) | 2002-05-21 |
| NO20015237D0 (no) | 2001-10-26 |
| IL146146A0 (en) | 2002-07-25 |
| CN1355811A (zh) | 2002-06-26 |
| NO20015237L (no) | 2001-12-21 |
| EP1173468A1 (de) | 2002-01-23 |
| MXPA01010834A (es) | 2002-04-24 |
| CA2371604A1 (en) | 2000-11-09 |
| HUP0202898A2 (hu) | 2002-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT889875E (pt) | Derivados de acidos ciclopropilalcanoicos | |
| JP2000510098A (ja) | 桂皮酸誘導体 | |
| US20100048536A1 (en) | Novel Substituted Diaryl Azepine Derivatives as Integrin Ligands | |
| CZ2002961A3 (cs) | Benzamidy a příbuzné sloučeniny pro inhibici faktoru Xa | |
| SK287116B6 (sk) | Substituované indoly, spôsob ich prípravy, liečivo, ktoré ich obsahuje, a ich použitie | |
| HRP20000574A2 (en) | Meta-azacyclic amino benzoic acid compounds and derivatives thereof being integrin antagonists | |
| US6960594B2 (en) | Thiophene and furan 2,5-dicarboxamides useful in the treatment of cancer | |
| BG106040A (bg) | Интегрин - рецепторни антагонисти | |
| US7105508B1 (en) | Integrin receptors antagonists | |
| JPH10512581A (ja) | 血小板凝集阻害剤 | |
| JP3936844B2 (ja) | インテグリンレセプターリガンド | |
| US5681820A (en) | Guanidinoalkyl glycine β-amino acids useful for inhibiting tumor metastasis | |
| JP2004522800A (ja) | インテグリン受容体のリガンドとしての置換されたピリミジノン誘導体 | |
| JP2004501120A (ja) | インテグリンレセプターのリガンド | |
| SK13732003A3 (sk) | Inhibítory integrínov 'alfa'v'beta'6 | |
| US20030171368A1 (en) | Pyrimidinonesulfamoylureas` | |
| EP1102587A2 (en) | Vitronectin receptor antagonists | |
| DE19948269A1 (de) | Neue Integrinrezeptorantagonisten | |
| JP2004506637A (ja) | インテグリンリガンドとしての新規の置換されたジアリールアゼピン誘導体 | |
| DE19919218A1 (de) | Neue Integrinrezeptorantagonisten |