CZ20014308A3 - Deriváty kyseliny nonanové - Google Patents

Info

Publication number

CZ20014308A3

CZ20014308A3 CZ20014308A CZ20014308A CZ20014308A3 CZ 20014308 A3 CZ20014308 A3 CZ 20014308A3 CZ 20014308 A CZ20014308 A CZ 20014308A CZ 20014308 A CZ20014308 A CZ 20014308A CZ 20014308 A3 CZ20014308 A3 CZ 20014308A3

Authority

CZ

Czechia

Prior art keywords

tetrahydro

oxo

naphthyridin

nonanoic acid

pyrimidin

Prior art date

1999-06-02

Links

• Espacenet
• Global Dossier
• Discuss

• FBUKVWPVBMHYJY-UHFFFAOYSA-N noncarboxylic acid Natural products CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 title claims description 154
• 150000001875 compounds Chemical class 0.000 claims abstract description 170
• 208000006386 Bone Resorption Diseases 0.000 claims abstract description 43
• 230000024279 bone resorption Effects 0.000 claims abstract description 43
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 31
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 28
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 26
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
• 201000010099 disease Diseases 0.000 claims abstract description 25
• 230000033115 angiogenesis Effects 0.000 claims abstract description 23
• 230000004614 tumor growth Effects 0.000 claims abstract description 23
• 201000011510 cancer Diseases 0.000 claims abstract description 20
• 206010061218 Inflammation Diseases 0.000 claims abstract description 18
• 230000004054 inflammatory process Effects 0.000 claims abstract description 18
• 239000005557 antagonist Substances 0.000 claims abstract description 17
• 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 16
• 208000002780 macular degeneration Diseases 0.000 claims abstract description 16
• 208000037803 restenosis Diseases 0.000 claims abstract description 16
• 206010061289 metastatic neoplasm Diseases 0.000 claims abstract description 15
• 230000003612 virological effect Effects 0.000 claims abstract description 14
• 206010003246 arthritis Diseases 0.000 claims abstract description 12
• 230000002757 inflammatory effect Effects 0.000 claims abstract description 9
• -1 aryl-C 1-6 -alkyl Chemical group 0.000 claims description 288
• 239000000203 mixture Substances 0.000 claims description 94
• 229910052739 hydrogen Inorganic materials 0.000 claims description 79
• 239000001257 hydrogen Substances 0.000 claims description 77
• 125000001424 substituent group Chemical group 0.000 claims description 70
• 125000003118 aryl group Chemical group 0.000 claims description 59
• 238000000034 method Methods 0.000 claims description 59
• 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 claims description 42
• 150000003839 salts Chemical class 0.000 claims description 42
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 39
• 241000124008 Mammalia Species 0.000 claims description 38
• 125000000217 alkyl group Chemical group 0.000 claims description 37
• 150000002431 hydrogen Chemical class 0.000 claims description 37
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 35
• 239000002253 acid Substances 0.000 claims description 32
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
• 210000002997 osteoclast Anatomy 0.000 claims description 29
• 229910052736 halogen Inorganic materials 0.000 claims description 28
• 150000002367 halogens Chemical class 0.000 claims description 28
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 26
• 230000000694 effects Effects 0.000 claims description 24
• 229920006395 saturated elastomer Polymers 0.000 claims description 24
• 125000004432 carbon atom Chemical group C* 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 22
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
• 125000005493 quinolyl group Chemical group 0.000 claims description 21
• 150000002148 esters Chemical class 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 19
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 19
• 125000004076 pyridyl group Chemical group 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
• 229940044551 receptor antagonist Drugs 0.000 claims description 16
• 239000002464 receptor antagonist Substances 0.000 claims description 16
• 102000005962 receptors Human genes 0.000 claims description 16
• 108020003175 receptors Proteins 0.000 claims description 16
• 108010041341 Integrin alpha1 Proteins 0.000 claims description 15
• 230000003042 antagnostic effect Effects 0.000 claims description 15
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 13
• 229940122361 Bisphosphonate Drugs 0.000 claims description 11
• 150000004663 bisphosphonates Chemical class 0.000 claims description 11
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 10
• 229910052760 oxygen Inorganic materials 0.000 claims description 10
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 9
• 239000004480 active ingredient Substances 0.000 claims description 9
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 9
• 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 9
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
• 125000003282 alkyl amino group Chemical group 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 230000009977 dual effect Effects 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
• FGXZHWSARJMWBB-NRFANRHFSA-N (2s)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 FGXZHWSARJMWBB-NRFANRHFSA-N 0.000 claims description 7
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 239000003112 inhibitor Substances 0.000 claims description 7
• VNNKGLKYUJUPHO-FQEVSTJZSA-N (2s)-2-(2-ethoxypyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 VNNKGLKYUJUPHO-FQEVSTJZSA-N 0.000 claims description 6
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 239000002834 estrogen receptor modulator Substances 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 239000000849 selective androgen receptor modulator Substances 0.000 claims description 6
• 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 6
• LLSWOFDIDNHBKI-UHFFFAOYSA-N 9-(6-amino-3,5-dimethylpyridin-2-yl)-3-(2-methoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=NC(N)=C(C)C=C1C LLSWOFDIDNHBKI-UHFFFAOYSA-N 0.000 claims description 5
• 229940121819 ATPase inhibitor Drugs 0.000 claims description 5
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 5
• 229940122156 Cathepsin K inhibitor Drugs 0.000 claims description 5
• 239000000362 adenosine triphosphatase inhibitor Substances 0.000 claims description 5
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
• 239000003324 growth hormone secretagogue Substances 0.000 claims description 5
• 230000001939 inductive effect Effects 0.000 claims description 5
• AYDDTLCITNWPKO-JOCHJYFZSA-N (2R)-2-(2,3-dihydro-1-benzofuran-6-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1ccc2CCOc2c1 AYDDTLCITNWPKO-JOCHJYFZSA-N 0.000 claims description 4
• DGUILINMWZCQNV-OAQYLSRUSA-N (2R)-2-(2-cyclopropylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1cnc(nc1)C1CC1 DGUILINMWZCQNV-OAQYLSRUSA-N 0.000 claims description 4
• GORJZZGBALVRQI-OAQYLSRUSA-N (2R)-2-(6-ethoxypyridin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CCOc1ccc(cn1)[C@@H](CCC(=O)CCCCc1ccc2CCCNc2n1)C(O)=O GORJZZGBALVRQI-OAQYLSRUSA-N 0.000 claims description 4
• HNGVWTANWOACNX-OAQYLSRUSA-N (2R)-7,7-dimethyl-2-(2-methylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound Cc1ncc(cn1)[C@@H](CCC(=O)CC(C)(C)CCc1ccc2CCCNc2n1)C(O)=O HNGVWTANWOACNX-OAQYLSRUSA-N 0.000 claims description 4
• OEJMPXAXGWKGQE-QFIPXVFZSA-N (2S)-2-(1-benzofuran-6-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1ccc2ccoc2c1 OEJMPXAXGWKGQE-QFIPXVFZSA-N 0.000 claims description 4
• DGUILINMWZCQNV-NRFANRHFSA-N (2S)-2-(2-cyclopropylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1cnc(nc1)C1CC1 DGUILINMWZCQNV-NRFANRHFSA-N 0.000 claims description 4
• CITGFEDLBWRGEJ-WCSIJFPASA-N (2S)-5-hydroxy-2-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N1=CC(=CC2=CC=CC=C12)[C@@H](C(=O)O)CCC(CCCCC1=NC=2NCCCC2C=C1)O CITGFEDLBWRGEJ-WCSIJFPASA-N 0.000 claims description 4
• YRKLRKQGAWLYDP-LJQANCHMSA-N (2r)-2-(2-methoxypyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OC)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 YRKLRKQGAWLYDP-LJQANCHMSA-N 0.000 claims description 4
• KYIUESBVXDONBH-HXUWFJFHSA-N (2r)-2-(2-methylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 KYIUESBVXDONBH-HXUWFJFHSA-N 0.000 claims description 4
• CBEYPRXKRIRFIJ-HXUWFJFHSA-N (2r)-2-(2-methylpyrimidin-5-yl)-7-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1[C@H](C(O)=O)CCCCC(=O)CCC1=CC=C(CCCN2)C2=N1 CBEYPRXKRIRFIJ-HXUWFJFHSA-N 0.000 claims description 4
• FDHJJPVHTYVRIJ-OAQYLSRUSA-N (2r)-2-(5-methoxypyridin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound COC1=CN=CC([C@@H](CCC(=O)CCCCC=2N=C3NCCCC3=CC=2)C(O)=O)=C1 FDHJJPVHTYVRIJ-OAQYLSRUSA-N 0.000 claims description 4
• LUCRVWWAYGIHAB-LJQANCHMSA-N (2r)-2-(5-methylpyrazin-2-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=CN=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 LUCRVWWAYGIHAB-LJQANCHMSA-N 0.000 claims description 4
• ACNBIPIEGANMHS-HXUWFJFHSA-N (2r)-2-[2-(dimethylamino)pyrimidin-5-yl]-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(N(C)C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 ACNBIPIEGANMHS-HXUWFJFHSA-N 0.000 claims description 4
• QHDQGGPLXWADGC-LJQANCHMSA-N (2r)-2-[2-(methylamino)pyrimidin-5-yl]-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(NC)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 QHDQGGPLXWADGC-LJQANCHMSA-N 0.000 claims description 4
• UPNUQZLHTJMHSH-GOSISDBHSA-N (2r)-5-oxo-2-pyrazin-2-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1([C@@H](CCC(=O)CCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=CN=CC=N1 UPNUQZLHTJMHSH-GOSISDBHSA-N 0.000 claims description 4
• KCXMGCPGJGKFNN-HSZRJFAPSA-N (2r)-5-oxo-2-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC([C@@H](CCC(=O)CCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 KCXMGCPGJGKFNN-HSZRJFAPSA-N 0.000 claims description 4
• PXKRBNCCUNMPMJ-HXUWFJFHSA-N (2r)-5-oxo-2-quinoxalin-2-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=NC([C@@H](CCC(=O)CCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 PXKRBNCCUNMPMJ-HXUWFJFHSA-N 0.000 claims description 4
• IRXDEOIVUJASDE-GOSISDBHSA-N (2r)-9-(3-bromo-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)Br)=NC2=C1CCCN2 IRXDEOIVUJASDE-GOSISDBHSA-N 0.000 claims description 4
• LNBYIIKGGCJLKI-OAQYLSRUSA-N (2r)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-ethoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OCC)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 LNBYIIKGGCJLKI-OAQYLSRUSA-N 0.000 claims description 4
• WBNWAXSZYLDMNX-HXUWFJFHSA-N (2r)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 WBNWAXSZYLDMNX-HXUWFJFHSA-N 0.000 claims description 4
• MCVGEJRYKPRVRX-OAQYLSRUSA-N (2r)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(6-methoxypyridin-3-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=CC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 MCVGEJRYKPRVRX-OAQYLSRUSA-N 0.000 claims description 4
• AYDDTLCITNWPKO-QFIPXVFZSA-N (2s)-2-(2,3-dihydro-1-benzofuran-6-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2CCOC2=CC([C@H](CCC(=O)CCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=C1 AYDDTLCITNWPKO-QFIPXVFZSA-N 0.000 claims description 4
• YRKLRKQGAWLYDP-IBGZPJMESA-N (2s)-2-(2-methoxypyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 YRKLRKQGAWLYDP-IBGZPJMESA-N 0.000 claims description 4
• WFGOHYOLAUUXQA-FQEVSTJZSA-N (2s)-2-(2-methylpyrimidin-5-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 WFGOHYOLAUUXQA-FQEVSTJZSA-N 0.000 claims description 4
• ACNBIPIEGANMHS-FQEVSTJZSA-N (2s)-2-[2-(dimethylamino)pyrimidin-5-yl]-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(N(C)C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 ACNBIPIEGANMHS-FQEVSTJZSA-N 0.000 claims description 4
• QHDQGGPLXWADGC-IBGZPJMESA-N (2s)-2-[2-(methylamino)pyrimidin-5-yl]-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(NC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 QHDQGGPLXWADGC-IBGZPJMESA-N 0.000 claims description 4
• KCXMGCPGJGKFNN-QHCPKHFHSA-N (2s)-5-oxo-2-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC([C@H](CCC(=O)CCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 KCXMGCPGJGKFNN-QHCPKHFHSA-N 0.000 claims description 4
• OHUPCXOWIXFSDO-SFHVURJKSA-N (2s)-9-(3-chloro-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)Cl)=NC2=C1CCCN2 OHUPCXOWIXFSDO-SFHVURJKSA-N 0.000 claims description 4
• WBNWAXSZYLDMNX-FQEVSTJZSA-N (2s)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 WBNWAXSZYLDMNX-FQEVSTJZSA-N 0.000 claims description 4
• DMHGRCAGNKKTJL-QHCPKHFHSA-N (2s)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxo-2-quinolin-3-ylnonanoic acid Chemical compound C1=CC=CC2=CC([C@@H](C(O)=O)CCC(=O)CCCCC3=NC=4NCCCC=4C=C3C)=CN=C21 DMHGRCAGNKKTJL-QHCPKHFHSA-N 0.000 claims description 4
• OVPGZOBAJSOERO-AWEZNQCLSA-N (3s)-9-[6-(methylamino)pyridin-2-yl]-5-oxo-3-pyrimidin-5-ylnonanoic acid Chemical compound CNC1=CC=CC(CCCCC(=O)C[C@@H](CC(O)=O)C=2C=NC=NC=2)=N1 OVPGZOBAJSOERO-AWEZNQCLSA-N 0.000 claims description 4
• 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 4
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 4
• 102100033367 Appetite-regulating hormone Human genes 0.000 claims description 4
• 101710111255 Appetite-regulating hormone Proteins 0.000 claims description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
• 229940124226 Farnesyltransferase inhibitor Drugs 0.000 claims description 4
• 229940122091 Geranylgeranyltransferase inhibitor Drugs 0.000 claims description 4
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 4
• 239000012190 activator Substances 0.000 claims description 4
• 125000004442 acylamino group Chemical group 0.000 claims description 4
• 230000001028 anti-proliverative effect Effects 0.000 claims description 4
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
• 231100000433 cytotoxic Toxicity 0.000 claims description 4
• 230000001472 cytotoxic effect Effects 0.000 claims description 4
• 239000003102 growth factor Substances 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
• 125000002971 oxazolyl group Chemical group 0.000 claims description 4
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• 229960005356 urokinase Drugs 0.000 claims description 4
• HGMOQTQPWKYBJF-HXUWFJFHSA-N (2R)-2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1cnc2OCCOc2c1 HGMOQTQPWKYBJF-HXUWFJFHSA-N 0.000 claims description 3
• WFGOHYOLAUUXQA-HXUWFJFHSA-N (2R)-2-(2-methylpyrimidin-5-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound Cc1ncc(cn1)[C@@H](CCC(=O)CCCCc1nc2NCCCc2cc1C)C(O)=O WFGOHYOLAUUXQA-HXUWFJFHSA-N 0.000 claims description 3
• CAVMYLVDMTYJKW-GFOWMXPYSA-N (2R)-5-hydroxy-2-(2-methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CC1=NC=C(C=N1)[C@H](C(=O)O)CCC(CCCCC1=NC=2NCCCC2C=C1)O CAVMYLVDMTYJKW-GFOWMXPYSA-N 0.000 claims description 3
• CITGFEDLBWRGEJ-OZAIVSQSSA-N (2R)-5-hydroxy-2-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N1=CC(=CC2=CC=CC=C12)[C@H](C(=O)O)CCC(CCCCC1=NC=2NCCCC2C=C1)O CITGFEDLBWRGEJ-OZAIVSQSSA-N 0.000 claims description 3
• QVQCBDGBIZVTMM-OAQYLSRUSA-N (2R)-5-oxo-2-(2-propan-2-ylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CC(C)c1ncc(cn1)[C@@H](CCC(=O)CCCCc1ccc2CCCNc2n1)C(O)=O QVQCBDGBIZVTMM-OAQYLSRUSA-N 0.000 claims description 3
• LZQMLZXBYVIKNA-LJQANCHMSA-N (2R)-5-oxo-2-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1cncnc1 LZQMLZXBYVIKNA-LJQANCHMSA-N 0.000 claims description 3
• CBEYPRXKRIRFIJ-FQEVSTJZSA-N (2S)-2-(2-methylpyrimidin-5-yl)-7-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound Cc1ncc(cn1)[C@H](CCCCC(=O)CCc1ccc2CCCNc2n1)C(O)=O CBEYPRXKRIRFIJ-FQEVSTJZSA-N 0.000 claims description 3
• FDHJJPVHTYVRIJ-NRFANRHFSA-N (2S)-2-(5-methoxypyridin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound COc1cncc(c1)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)C(O)=O FDHJJPVHTYVRIJ-NRFANRHFSA-N 0.000 claims description 3
• CAVMYLVDMTYJKW-ANYOKISRSA-N (2S)-5-hydroxy-2-(2-methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CC1=NC=C(C=N1)[C@@H](C(=O)O)CCC(CCCCC1=NC=2NCCCC2C=C1)O CAVMYLVDMTYJKW-ANYOKISRSA-N 0.000 claims description 3
• QVQCBDGBIZVTMM-NRFANRHFSA-N (2S)-5-oxo-2-(2-propan-2-ylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CC(C)c1ncc(cn1)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)C(O)=O QVQCBDGBIZVTMM-NRFANRHFSA-N 0.000 claims description 3
• LZQMLZXBYVIKNA-IBGZPJMESA-N (2S)-5-oxo-2-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1cncnc1 LZQMLZXBYVIKNA-IBGZPJMESA-N 0.000 claims description 3
• VNNKGLKYUJUPHO-HXUWFJFHSA-N (2r)-2-(2-ethoxypyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 VNNKGLKYUJUPHO-HXUWFJFHSA-N 0.000 claims description 3
• MWPVEEPFXLFXMA-LJQANCHMSA-N (2r)-2-(2-methoxypyrimidin-5-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 MWPVEEPFXLFXMA-LJQANCHMSA-N 0.000 claims description 3
• IGYRCQAUOKNOCX-GOSISDBHSA-N (2r)-2-(6-methoxypyridazin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N1=NC(OC)=CC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 IGYRCQAUOKNOCX-GOSISDBHSA-N 0.000 claims description 3
• XAYSGSCETLFAQC-HXUWFJFHSA-N (2r)-2-(6-methoxypyridin-3-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=CC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 XAYSGSCETLFAQC-HXUWFJFHSA-N 0.000 claims description 3
• FGXZHWSARJMWBB-OAQYLSRUSA-N (2r)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 FGXZHWSARJMWBB-OAQYLSRUSA-N 0.000 claims description 3
• ROBTWMCHZFQAOU-OAQYLSRUSA-N (2r)-9-(3-ethenyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C=C)=NC2=C1CCCN2 ROBTWMCHZFQAOU-OAQYLSRUSA-N 0.000 claims description 3
• DMHGRCAGNKKTJL-HSZRJFAPSA-N (2r)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxo-2-quinolin-3-ylnonanoic acid Chemical compound C1=CC=CC2=CC([C@H](C(O)=O)CCC(=O)CCCCC3=NC=4NCCCC=4C=C3C)=CN=C21 DMHGRCAGNKKTJL-HSZRJFAPSA-N 0.000 claims description 3
• MWPVEEPFXLFXMA-IBGZPJMESA-N (2s)-2-(2-methoxypyrimidin-5-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 MWPVEEPFXLFXMA-IBGZPJMESA-N 0.000 claims description 3
• CKSPSTLZBJXIKM-FXMQYSIJSA-N (2s)-2-(2-methylpyrimidin-5-yl)-9-(6-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1([C@@H](C(O)=O)CCC(=O)CCCCC=2N=C3NCC(CC3=CC=2)C)=CN=C(C)N=C1 CKSPSTLZBJXIKM-FXMQYSIJSA-N 0.000 claims description 3
• RGRLZRNIQDXERL-NRFANRHFSA-N (2s)-2-(2-tert-butylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C(C)(C)C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 RGRLZRNIQDXERL-NRFANRHFSA-N 0.000 claims description 3
• IGYRCQAUOKNOCX-SFHVURJKSA-N (2s)-2-(6-methoxypyridazin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N1=NC(OC)=CC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 IGYRCQAUOKNOCX-SFHVURJKSA-N 0.000 claims description 3
• UPNUQZLHTJMHSH-SFHVURJKSA-N (2s)-5-oxo-2-pyrazin-2-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1([C@H](CCC(=O)CCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=CN=CC=N1 UPNUQZLHTJMHSH-SFHVURJKSA-N 0.000 claims description 3
• IRXDEOIVUJASDE-SFHVURJKSA-N (2s)-9-(3-bromo-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)Br)=NC2=C1CCCN2 IRXDEOIVUJASDE-SFHVURJKSA-N 0.000 claims description 3
• MCVGEJRYKPRVRX-NRFANRHFSA-N (2s)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(6-methoxypyridin-3-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=CC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 MCVGEJRYKPRVRX-NRFANRHFSA-N 0.000 claims description 3
• ROBTWMCHZFQAOU-NRFANRHFSA-N (2s)-9-(3-ethenyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C=C)=NC2=C1CCCN2 ROBTWMCHZFQAOU-NRFANRHFSA-N 0.000 claims description 3
• OVPGZOBAJSOERO-CQSZACIVSA-N (3r)-9-[6-(methylamino)pyridin-2-yl]-5-oxo-3-pyrimidin-5-ylnonanoic acid Chemical compound CNC1=CC=CC(CCCCC(=O)C[C@H](CC(O)=O)C=2C=NC=NC=2)=N1 OVPGZOBAJSOERO-CQSZACIVSA-N 0.000 claims description 3
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 3
• 102000000588 Interleukin-2 Human genes 0.000 claims description 3
• 108010002350 Interleukin-2 Proteins 0.000 claims description 3
• 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 3
• 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 3
• 229960004343 alendronic acid Drugs 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 125000002837 carbocyclic group Chemical group 0.000 claims description 3
• 108020001507 fusion proteins Proteins 0.000 claims description 3
• 102000037865 fusion proteins Human genes 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• 230000030991 negative regulation of bone resorption Effects 0.000 claims description 3
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 3
• 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 3
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 3
• GORJZZGBALVRQI-NRFANRHFSA-N (2S)-2-(6-ethoxypyridin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CCOc1ccc(cn1)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)C(O)=O GORJZZGBALVRQI-NRFANRHFSA-N 0.000 claims description 2
• HNGVWTANWOACNX-NRFANRHFSA-N (2S)-7,7-dimethyl-2-(2-methylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound Cc1ncc(cn1)[C@H](CCC(=O)CC(C)(C)CCc1ccc2CCCNc2n1)C(O)=O HNGVWTANWOACNX-NRFANRHFSA-N 0.000 claims description 2
• RGRLZRNIQDXERL-OAQYLSRUSA-N (2r)-2-(2-tert-butylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C(C)(C)C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 RGRLZRNIQDXERL-OAQYLSRUSA-N 0.000 claims description 2
• KYIUESBVXDONBH-FQEVSTJZSA-N (2s)-2-(2-methylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC1=CC=C(CCCN2)C2=N1 KYIUESBVXDONBH-FQEVSTJZSA-N 0.000 claims description 2
• PXKRBNCCUNMPMJ-FQEVSTJZSA-N (2s)-5-oxo-2-quinoxalin-2-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=NC([C@H](CCC(=O)CCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 PXKRBNCCUNMPMJ-FQEVSTJZSA-N 0.000 claims description 2
• QAHKIQBWURDABN-UHFFFAOYSA-N 3-(1-benzofuran-6-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2C=COC2=CC(C(CC(=O)CCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 QAHKIQBWURDABN-UHFFFAOYSA-N 0.000 claims description 2
• SCYLAETWALMUDS-UHFFFAOYSA-N 3-(2-cyclopropylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C=1C=C2CCCNC2=NC=1CCCCC(=O)CC(CC(=O)O)C(C=N1)=CN=C1C1CC1 SCYLAETWALMUDS-UHFFFAOYSA-N 0.000 claims description 2
• ISWGDMYFBALUTB-UHFFFAOYSA-N 3-(2-ethoxypyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 ISWGDMYFBALUTB-UHFFFAOYSA-N 0.000 claims description 2
• NMOYMTRZYRAJPD-UHFFFAOYSA-N 3-(2-ethoxypyrimidin-5-yl)-5-oxo-9-(6,7,8,9-tetrahydro-5h-pyrido[2,3-b]azepin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCCN2)C2=N1 NMOYMTRZYRAJPD-UHFFFAOYSA-N 0.000 claims description 2
• CQKYNXYYADIHTP-UHFFFAOYSA-N 3-(2-methoxypyrimidin-5-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 CQKYNXYYADIHTP-UHFFFAOYSA-N 0.000 claims description 2
• RWGYKDBFESDGHI-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)-9-(6-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C=1C=C2CC(C)CNC2=NC=1CCCCC(=O)CC(CC(O)=O)C1=CN=C(C)N=C1 RWGYKDBFESDGHI-UHFFFAOYSA-N 0.000 claims description 2
• GWHHCGJNCXNOFE-UHFFFAOYSA-N 3-(2-tert-butylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C(C)(C)C)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 GWHHCGJNCXNOFE-UHFFFAOYSA-N 0.000 claims description 2
• ZNBIHZSQJAURRN-UHFFFAOYSA-N 3-(5-methoxypyridin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound COC1=CN=CC(C(CC(O)=O)CC(=O)CCCCC=2N=C3NCCCC3=CC=2)=C1 ZNBIHZSQJAURRN-UHFFFAOYSA-N 0.000 claims description 2
• FIJQSMQSNSSYTC-UHFFFAOYSA-N 3-(6-methoxypyridazin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N1=NC(OC)=CC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 FIJQSMQSNSSYTC-UHFFFAOYSA-N 0.000 claims description 2
• LFOAWSUGJKSHHB-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=CC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 LFOAWSUGJKSHHB-UHFFFAOYSA-N 0.000 claims description 2
• JQZZSYZKNLEXOV-UHFFFAOYSA-N 3-[2-(dimethylamino)pyrimidin-5-yl]-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(N(C)C)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 JQZZSYZKNLEXOV-UHFFFAOYSA-N 0.000 claims description 2
• ZGXKNWNJVOZHCG-UHFFFAOYSA-N 5-hydroxy-3-(2-methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(O)CCCCC1=CC=C(CCCN2)C2=N1 ZGXKNWNJVOZHCG-UHFFFAOYSA-N 0.000 claims description 2
• ZYXRXQZAQSMRHD-UHFFFAOYSA-N 5-hydroxy-3-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC(C(CC(O)=O)CC(CCCCC=3N=C4NCCCC4=CC=3)O)=CN=C21 ZYXRXQZAQSMRHD-UHFFFAOYSA-N 0.000 claims description 2
• SEELZNMZMVOEBU-UHFFFAOYSA-N 5-oxo-3-(2-propan-2-ylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C(C)C)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 SEELZNMZMVOEBU-UHFFFAOYSA-N 0.000 claims description 2
• GKNVSRZWLDHKCU-UHFFFAOYSA-N 5-oxo-3-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C=1C=C2CCCNC2=NC=1CCCCC(=O)CC(CC(=O)O)C1=CN=CN=C1 GKNVSRZWLDHKCU-UHFFFAOYSA-N 0.000 claims description 2
• QTYNHONNXNWXBB-UHFFFAOYSA-N 5-oxo-3-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC(C(CC(=O)CCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 QTYNHONNXNWXBB-UHFFFAOYSA-N 0.000 claims description 2
• OGEHVFFGMRSQAU-UHFFFAOYSA-N 5-oxo-3-quinoxalin-2-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=NC(C(CC(=O)CCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 OGEHVFFGMRSQAU-UHFFFAOYSA-N 0.000 claims description 2
• UWTNKCIZAXFDTL-UHFFFAOYSA-N 9-(3-chloro-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)Cl)=NC2=C1CCCN2 UWTNKCIZAXFDTL-UHFFFAOYSA-N 0.000 claims description 2
• VJVOKCRUOUJQLZ-UHFFFAOYSA-N 9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(2-methoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 VJVOKCRUOUJQLZ-UHFFFAOYSA-N 0.000 claims description 2
• JPPRVOPOUMRIHF-UHFFFAOYSA-N 9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 JPPRVOPOUMRIHF-UHFFFAOYSA-N 0.000 claims description 2
• QBLMYYIXXTVYAY-UHFFFAOYSA-N 9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(6-methoxypyridin-3-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=CC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 QBLMYYIXXTVYAY-UHFFFAOYSA-N 0.000 claims description 2
• SMDKAGFIIKXBTI-UHFFFAOYSA-N 9-(3-ethenyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C=C)=NC2=C1CCCN2 SMDKAGFIIKXBTI-UHFFFAOYSA-N 0.000 claims description 2
• IIDYUNBWJDCHRZ-UHFFFAOYSA-N 9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxo-3-quinolin-3-ylnonanoic acid Chemical compound C1=CC=CC2=CC(C(CC(O)=O)CC(=O)CCCCC3=NC=4NCCCC=4C=C3C)=CN=C21 IIDYUNBWJDCHRZ-UHFFFAOYSA-N 0.000 claims description 2
• OVPGZOBAJSOERO-UHFFFAOYSA-N 9-[6-(methylamino)pyridin-2-yl]-5-oxo-3-pyrimidin-5-ylnonanoic acid Chemical compound CNC1=CC=CC(CCCCC(=O)CC(CC(O)=O)C=2C=NC=NC=2)=N1 OVPGZOBAJSOERO-UHFFFAOYSA-N 0.000 claims description 2
• 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 claims description 2
• 101100481404 Danio rerio tie1 gene Proteins 0.000 claims description 2
• 101100481408 Danio rerio tie2 gene Proteins 0.000 claims description 2
• 102000007317 Farnesyltranstransferase Human genes 0.000 claims description 2
• 108010007508 Farnesyltranstransferase Proteins 0.000 claims description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 claims description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 claims description 2
• 101100481410 Mus musculus Tek gene Proteins 0.000 claims description 2
• 101100481406 Mus musculus Tie1 gene Proteins 0.000 claims description 2
• 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 claims description 2
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 2
• 101100445392 Xenopus laevis ephb3 gene Proteins 0.000 claims description 2
• 230000008485 antagonism Effects 0.000 claims description 2
• 230000002942 anti-growth Effects 0.000 claims description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 210000001772 blood platelet Anatomy 0.000 claims description 2
• 210000002615 epidermis Anatomy 0.000 claims description 2
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 210000002950 fibroblast Anatomy 0.000 claims description 2
• 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 claims description 2
• 239000003771 matrix metalloproteinase inhibitor Substances 0.000 claims description 2
• 125000001624 naphthyl group Chemical group 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 238000001959 radiotherapy Methods 0.000 claims description 2
• 239000002525 vasculotropin inhibitor Substances 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
• ATKOUZSQSNFNTB-UHFFFAOYSA-N 2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1CCNC2=NC(C(C(O)=O)CCCCCCC)=CC=C21 ATKOUZSQSNFNTB-UHFFFAOYSA-N 0.000 claims 1
• LHXUSLZFFIODBJ-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-6-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2CCOC2=CC(C(CC(=O)CCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 LHXUSLZFFIODBJ-UHFFFAOYSA-N 0.000 claims 1
• GBWHLRNQBCQMDU-UHFFFAOYSA-N 3-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound O1CCOC2=CC(C(CC(=O)CCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 GBWHLRNQBCQMDU-UHFFFAOYSA-N 0.000 claims 1
• AXWCRKTXRMIKPF-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)-7-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CCCC(=O)CCC1=CC=C(CCCN2)C2=N1 AXWCRKTXRMIKPF-UHFFFAOYSA-N 0.000 claims 1
• DEUWUJFNKOTTIC-UHFFFAOYSA-N 3-(5-methylpyrazin-2-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=CN=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 DEUWUJFNKOTTIC-UHFFFAOYSA-N 0.000 claims 1
• DAUPDEKPSWOESJ-UHFFFAOYSA-N 3-(6-ethoxypyridin-3-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OCC)=CC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 DAUPDEKPSWOESJ-UHFFFAOYSA-N 0.000 claims 1
• CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 claims 1
• CLXOWWAVRFIKSW-UHFFFAOYSA-N 9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(2-ethoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OCC)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 CLXOWWAVRFIKSW-UHFFFAOYSA-N 0.000 claims 1
• 125000006574 non-aromatic ring group Chemical group 0.000 claims 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
• 108010044426 integrins Proteins 0.000 abstract description 29
• 102000006495 integrins Human genes 0.000 abstract description 29
• 229940127449 Integrin Receptor Antagonists Drugs 0.000 abstract description 13
• 201000001320 Atherosclerosis Diseases 0.000 abstract description 11
• 230000015572 biosynthetic process Effects 0.000 abstract description 11
• 238000003786 synthesis reaction Methods 0.000 abstract description 8
• 150000002842 nonanoic acids Chemical class 0.000 abstract description 6
• 230000002792 vascular Effects 0.000 abstract description 5
• 108010040765 Integrin alphaV Proteins 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
• 235000019439 ethyl acetate Nutrition 0.000 description 98
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
• 239000000243 solution Substances 0.000 description 47
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
• 210000000988 bone and bone Anatomy 0.000 description 37
• 235000002639 sodium chloride Nutrition 0.000 description 37
• 239000007787 solid Substances 0.000 description 37
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
• 239000000741 silica gel Substances 0.000 description 36
• 229910002027 silica gel Inorganic materials 0.000 description 36
• 229910001868 water Inorganic materials 0.000 description 36
• 210000004027 cell Anatomy 0.000 description 33
• 239000003921 oil Substances 0.000 description 31
• 238000004809 thin layer chromatography Methods 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 239000002904 solvent Substances 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 24
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• 238000002360 preparation method Methods 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• 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 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 20
• 238000012360 testing method Methods 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 17
• 239000000460 chlorine Substances 0.000 description 15
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• 239000011324 bead Substances 0.000 description 14
• 239000012148 binding buffer Substances 0.000 description 14
• 239000011734 sodium Substances 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
• 239000002609 medium Substances 0.000 description 12
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 239000000872 buffer Substances 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• 230000005764 inhibitory process Effects 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 239000000047 product Substances 0.000 description 11
• 238000000926 separation method Methods 0.000 description 11
• 238000009739 binding Methods 0.000 description 10
• 238000003821 enantio-separation Methods 0.000 description 10
• 125000000623 heterocyclic group Chemical group 0.000 description 10
• 238000001727 in vivo Methods 0.000 description 10
• 230000027455 binding Effects 0.000 description 9
• 238000001816 cooling Methods 0.000 description 9
• 238000001704 evaporation Methods 0.000 description 9
• 230000008020 evaporation Effects 0.000 description 9
• 239000000543 intermediate Substances 0.000 description 9
• 238000001819 mass spectrum Methods 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 206010065687 Bone loss Diseases 0.000 description 7
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
• 241000282414 Homo sapiens Species 0.000 description 7
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
• 229910052786 argon Inorganic materials 0.000 description 7
• 238000006243 chemical reaction Methods 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 239000012091 fetal bovine serum Substances 0.000 description 7
• 238000000338 in vitro Methods 0.000 description 7
• 229960004592 isopropanol Drugs 0.000 description 7
• 239000003446 ligand Substances 0.000 description 7
• 230000002265 prevention Effects 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 6
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
• UIZZSZJHTBHBCS-UHFFFAOYSA-N 6-bromo-n-[(4-methoxyphenyl)methyl]pyridin-2-amine Chemical compound C1=CC(OC)=CC=C1CNC1=CC=CC(Br)=N1 UIZZSZJHTBHBCS-UHFFFAOYSA-N 0.000 description 6
• AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 6
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 6
• 206010027476 Metastases Diseases 0.000 description 6
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
• 239000003814 drug Substances 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 5
• YEBNWOPGANTVGX-UHFFFAOYSA-N 2,4-dichloro-3-methyl-1,8-naphthyridine Chemical compound N1=CC=CC2=C(Cl)C(C)=C(Cl)N=C21 YEBNWOPGANTVGX-UHFFFAOYSA-N 0.000 description 5
• MERUNNHMVZFFRE-UHFFFAOYSA-N 2-methoxypyrimidine-5-carbaldehyde Chemical compound COC1=NC=C(C=O)C=N1 MERUNNHMVZFFRE-UHFFFAOYSA-N 0.000 description 5
• 102100022337 Integrin alpha-V Human genes 0.000 description 5
• 108010048673 Vitronectin Receptors Proteins 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 239000011575 calcium Substances 0.000 description 5
• 229940079593 drug Drugs 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 230000009401 metastasis Effects 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 5
• HEGSGKPQLMEBJL-RQICVUQASA-N (2r,3s,4s,5r)-2-(hydroxymethyl)-6-octoxyoxane-3,4,5-triol Chemical compound CCCCCCCCOC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RQICVUQASA-N 0.000 description 4
• ILYVXUGGBVATGA-DKWTVANSSA-N (2s)-2-aminopropanoic acid;hydrochloride Chemical compound Cl.C[C@H](N)C(O)=O ILYVXUGGBVATGA-DKWTVANSSA-N 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• KLHVJOCHLMWJPW-UHFFFAOYSA-N 9-(2,6-diaminopyrimidin-4-yl)-3-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC(N)=NC(N)=N1 KLHVJOCHLMWJPW-UHFFFAOYSA-N 0.000 description 4
• IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical group NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 4
• 241000283690 Bos taurus Species 0.000 description 4
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
• 102000005600 Cathepsins Human genes 0.000 description 4
• 108010084457 Cathepsins Proteins 0.000 description 4
• 208000037147 Hypercalcaemia Diseases 0.000 description 4
• 208000029725 Metabolic bone disease Diseases 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 208000010191 Osteitis Deformans Diseases 0.000 description 4
• 206010049088 Osteopenia Diseases 0.000 description 4
• 108010016731 PPAR gamma Proteins 0.000 description 4
• 208000027868 Paget disease Diseases 0.000 description 4
• 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 125000001931 aliphatic group Chemical group 0.000 description 4
• 229910052791 calcium Inorganic materials 0.000 description 4
• GKGLLPQNHWNANY-UHFFFAOYSA-N ethyl 5-[6-[(4-methoxyphenyl)methylamino]pyridin-2-yl]pentanoate Chemical compound CCOC(=O)CCCCC1=CC=CC(NCC=2C=CC(OC)=CC=2)=N1 GKGLLPQNHWNANY-UHFFFAOYSA-N 0.000 description 4
• OBJLGHTZWMPFCZ-UHFFFAOYSA-N ethyl 9-(6-amino-3,5-dimethylpyridin-2-yl)-3-(2-methoxypyrimidin-5-yl)-5-oxononanoate Chemical compound C=1N=C(OC)N=CC=1C(CC(=O)OCC)CC(=O)CCCCC1=NC(N)=C(C)C=C1C OBJLGHTZWMPFCZ-UHFFFAOYSA-N 0.000 description 4
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
• 230000000148 hypercalcaemia Effects 0.000 description 4
• 208000027202 mammary Paget disease Diseases 0.000 description 4
• ANABHCSYKASRRW-UHFFFAOYSA-N n-(3-formylpyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=NC=CC=C1C=O ANABHCSYKASRRW-UHFFFAOYSA-N 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 238000002953 preparative HPLC Methods 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 235000018102 proteins Nutrition 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 239000000377 silicon dioxide Substances 0.000 description 4
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• LUCRVWWAYGIHAB-IBGZPJMESA-N (2S)-2-(5-methylpyrazin-2-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound Cc1cnc(cn1)[C@H](CCC(=O)CCCCc1ccc2CCCNc2n1)C(O)=O LUCRVWWAYGIHAB-IBGZPJMESA-N 0.000 description 3
• KBSWBUKMTSUCOP-UHFFFAOYSA-N 1-(2-methylpyrimidin-5-yl)hepta-1,6-dien-3-one Chemical compound CC1=NC=C(C=CC(=O)CCC=C)C=N1 KBSWBUKMTSUCOP-UHFFFAOYSA-N 0.000 description 3
• FEYDZHNIIMENOB-UHFFFAOYSA-N 2,6-dibromopyridine Chemical compound BrC1=CC=CC(Br)=N1 FEYDZHNIIMENOB-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
• ZDOLXCKKXHSEJG-UHFFFAOYSA-N 2-but-3-enylisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC=C)C(=O)C2=C1 ZDOLXCKKXHSEJG-UHFFFAOYSA-N 0.000 description 3
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
• NTFUYEQEVHVXLC-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)prop-2-enal Chemical compound CC1=NC=C(C=CC=O)C=N1 NTFUYEQEVHVXLC-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• PTVSRINJXWDIKP-UHFFFAOYSA-N Ethyl 4-pentenoate Chemical compound CCOC(=O)CCC=C PTVSRINJXWDIKP-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 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 3
• 229940123038 Integrin antagonist Drugs 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 3
• 241000283973 Oryctolagus cuniculus Species 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000003098 androgen Substances 0.000 description 3
• 229940030486 androgens Drugs 0.000 description 3
• 230000002917 arthritic effect Effects 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 125000002619 bicyclic group Chemical group 0.000 description 3
• 210000002805 bone matrix Anatomy 0.000 description 3
• AOIFYMSHUIGTBL-UHFFFAOYSA-N butyl pent-4-ynoate Chemical compound CCCCOC(=O)CCC#C AOIFYMSHUIGTBL-UHFFFAOYSA-N 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• FOCNMAZYSQWYSH-UHFFFAOYSA-N diethyl 2-[1-(2-methylpyrimidin-5-yl)-3-oxohept-6-enyl]propanedioate Chemical compound C=CCCC(=O)CC(C(C(=O)OCC)C(=O)OCC)C1=CN=C(C)N=C1 FOCNMAZYSQWYSH-UHFFFAOYSA-N 0.000 description 3
• QDBYLSLDKMFZCY-UHFFFAOYSA-N ethyl 5-(6-amino-3,5-dimethylpyridin-2-yl)pentanoate Chemical compound CCOC(=O)CCCCC1=NC(N)=C(C)C=C1C QDBYLSLDKMFZCY-UHFFFAOYSA-N 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000012737 fresh medium Substances 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 208000030915 hypercalcemia disease Diseases 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000006166 lysate Substances 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• BSBYQAYWPXHLPQ-UHFFFAOYSA-N methyl 6-oxoheptanoate Chemical compound COC(=O)CCCCC(C)=O BSBYQAYWPXHLPQ-UHFFFAOYSA-N 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• LFLZOWIFJOBEPN-UHFFFAOYSA-N nitrate, nitrate Chemical compound O[N+]([O-])=O.O[N+]([O-])=O LFLZOWIFJOBEPN-UHFFFAOYSA-N 0.000 description 3
• 230000009871 nonspecific binding Effects 0.000 description 3
• 125000004043 oxo group Chemical group O=* 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 238000010791 quenching Methods 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 235000015424 sodium Nutrition 0.000 description 3
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
• 238000001228 spectrum Methods 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• HGMOQTQPWKYBJF-FQEVSTJZSA-N (2S)-2-(2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-7-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCC(=O)CCCCc1ccc2CCCNc2n1)c1cnc2OCCOc2c1 HGMOQTQPWKYBJF-FQEVSTJZSA-N 0.000 description 2
• LNBYIIKGGCJLKI-NRFANRHFSA-N (2s)-9-(3-cyclopropyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-ethoxypyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(OCC)=NC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C2CC2)=NC2=C1CCCN2 LNBYIIKGGCJLKI-NRFANRHFSA-N 0.000 description 2
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 2
• ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 description 2
• GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 2
• DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical group N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 2
• HLSNQZQSNWFXET-UHFFFAOYSA-N 1-benzofuran-6-carbaldehyde Chemical compound O=CC1=CC=C2C=COC2=C1 HLSNQZQSNWFXET-UHFFFAOYSA-N 0.000 description 2
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 2
• XLBBKEHLEPNMMF-SSUNCQRMSA-N 129038-42-2 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(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](CS)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)[C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCC(O)=O)C1=CC=CC=C1 XLBBKEHLEPNMMF-SSUNCQRMSA-N 0.000 description 2
• NXMFJCRMSDRXLD-UHFFFAOYSA-N 2-aminopyridine-3-carbaldehyde Chemical compound NC1=NC=CC=C1C=O NXMFJCRMSDRXLD-UHFFFAOYSA-N 0.000 description 2
• NBVADWRNQAZAOK-UHFFFAOYSA-N 2-ethoxypyrimidine-5-carbaldehyde Chemical compound CCOC1=NC=C(C=O)C=N1 NBVADWRNQAZAOK-UHFFFAOYSA-N 0.000 description 2
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
• UDARCABNXUWGGP-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)prop-2-en-1-ol Chemical compound CC1=NC=C(C=CCO)C=N1 UDARCABNXUWGGP-UHFFFAOYSA-N 0.000 description 2
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
• 108091006112 ATPases Proteins 0.000 description 2
• 102000057290 Adenosine Triphosphatases Human genes 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• 208000010392 Bone Fractures Diseases 0.000 description 2
• 208000020084 Bone disease Diseases 0.000 description 2
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 108010022452 Collagen Type I Proteins 0.000 description 2
• 102000012422 Collagen Type I Human genes 0.000 description 2
• 102000005927 Cysteine Proteases Human genes 0.000 description 2
• 108010005843 Cysteine Proteases Proteins 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
• 206010017076 Fracture Diseases 0.000 description 2
• 241000287828 Gallus gallus Species 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• SCCPDJAQCXWPTF-VKHMYHEASA-N Gly-Asp Chemical compound NCC(=O)N[C@H](C(O)=O)CC(O)=O SCCPDJAQCXWPTF-VKHMYHEASA-N 0.000 description 2
• 201000002980 Hyperparathyroidism Diseases 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 101150003085 Pdcl gene Proteins 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• 229920000954 Polyglycolide Polymers 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• 229940123464 Thiazolidinedione Drugs 0.000 description 2
• 208000007536 Thrombosis Diseases 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 229940062527 alendronate Drugs 0.000 description 2
• 150000001335 aliphatic alkanes Chemical class 0.000 description 2
• 125000002877 alkyl aryl group Chemical group 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 125000003710 aryl alkyl group Chemical group 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• 239000002617 bone density conservation agent Substances 0.000 description 2
• 210000001185 bone marrow Anatomy 0.000 description 2
• 210000002798 bone marrow cell Anatomy 0.000 description 2
• GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
• WFXZDAJYVOGDEP-UHFFFAOYSA-N butyl 5-[6-[(4-methoxyphenyl)methylamino]pyridin-2-yl]pent-4-ynoate Chemical compound CCCCOC(=O)CCC#CC1=CC=CC(NCC=2C=CC(OC)=CC=2)=N1 WFXZDAJYVOGDEP-UHFFFAOYSA-N 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 230000021164 cell adhesion Effects 0.000 description 2
• 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 description 2
• 229940096422 collagen type i Drugs 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 238000006114 decarboxylation reaction Methods 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 108010025752 echistatin Proteins 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 230000003628 erosive effect Effects 0.000 description 2
• 210000003743 erythrocyte Anatomy 0.000 description 2
• HQGQCRJBCGODPW-UHFFFAOYSA-N ethyl 3-(2-methylpyrimidin-5-yl)pent-4-enoate Chemical compound CCOC(=O)CC(C=C)C1=CN=C(C)N=C1 HQGQCRJBCGODPW-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 201000003617 glucocorticoid-induced osteoporosis Diseases 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 230000023597 hemostasis Effects 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 125000000468 ketone group Chemical group 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000012139 lysis buffer Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000036210 malignancy Effects 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 230000001617 migratory effect Effects 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 229910052754 neon Inorganic materials 0.000 description 2
• GKAOGPIIYCISHV-UHFFFAOYSA-N neon atom Chemical compound [Ne] GKAOGPIIYCISHV-UHFFFAOYSA-N 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• HEGSGKPQLMEBJL-RKQHYHRCSA-N octyl beta-D-glucopyranoside Chemical compound CCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HEGSGKPQLMEBJL-RKQHYHRCSA-N 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 239000000816 peptidomimetic Substances 0.000 description 2
• 208000028169 periodontal disease Diseases 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000003285 pharmacodynamic effect Effects 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 239000011574 phosphorus Substances 0.000 description 2
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
• 229920000747 poly(lactic acid) Polymers 0.000 description 2
• 239000004633 polyglycolic acid Substances 0.000 description 2
• 239000004626 polylactic acid Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 235000019260 propionic acid Nutrition 0.000 description 2
• ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000007789 sealing Methods 0.000 description 2
• 230000003248 secreting effect Effects 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 150000001467 thiazolidinediones Chemical class 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 230000007306 turnover Effects 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• OEJMPXAXGWKGQE-JOCHJYFZSA-N (2r)-2-(1-benzofuran-6-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2C=COC2=CC([C@@H](CCC(=O)CCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=C1 OEJMPXAXGWKGQE-JOCHJYFZSA-N 0.000 description 1
• CKSPSTLZBJXIKM-MZVUKIKXSA-N (2r)-2-(2-methylpyrimidin-5-yl)-9-(6-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1([C@H](C(O)=O)CCC(=O)CCCCC=2N=C3NCC(CC3=CC=2)C)=CN=C(C)N=C1 CKSPSTLZBJXIKM-MZVUKIKXSA-N 0.000 description 1
• OHUPCXOWIXFSDO-GOSISDBHSA-N (2r)-9-(3-chloro-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-2-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1[C@H](C(O)=O)CCC(=O)CCCCC(C(=C1)Cl)=NC2=C1CCCN2 OHUPCXOWIXFSDO-GOSISDBHSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• XAYSGSCETLFAQC-FQEVSTJZSA-N (2s)-2-(6-methoxypyridin-3-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(OC)=CC=C1[C@@H](C(O)=O)CCC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 XAYSGSCETLFAQC-FQEVSTJZSA-N 0.000 description 1
• VMKAFJQFKBASMU-KRWDZBQOSA-N (3as)-1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C([C@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-KRWDZBQOSA-N 0.000 description 1
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
• JGFMNFBZRAISGQ-UHFFFAOYSA-N (propan-2-yloxy)phosphinic acid Chemical compound CC(C)OP(O)=O JGFMNFBZRAISGQ-UHFFFAOYSA-N 0.000 description 1
• VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical compound C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
• GWEATQMXNIFWCP-UHFFFAOYSA-N 1H-pyrazole-5-carboximidamide hydrochloride Chemical compound Cl.NC(=N)C=1C=CNN=1 GWEATQMXNIFWCP-UHFFFAOYSA-N 0.000 description 1
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
• SASMCBBEDSLPJR-UHFFFAOYSA-N 2,2,5,5-tetramethyl-4-oxohexanoyl chloride Chemical compound CC(C)(C)C(=O)CC(C)(C)C(Cl)=O SASMCBBEDSLPJR-UHFFFAOYSA-N 0.000 description 1
• ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 1
• HXGPBZKGPPZSGX-UHFFFAOYSA-N 2,7-bis[fluoro(dipyridin-2-yl)methyl]-1,8-naphthyridine Chemical compound C=1C=CC=NC=1C(C=1N=C2N=C(C=CC2=CC=1)C(F)(C=1N=CC=CC=1)C=1N=CC=CC=1)(F)C1=CC=CC=N1 HXGPBZKGPPZSGX-UHFFFAOYSA-N 0.000 description 1
• RFARBJJIUKDADJ-UHFFFAOYSA-N 2-(3-chloro-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound CCCCCCCC(C1=C(C=C2CCCNC2=N1)Cl)C(=O)O RFARBJJIUKDADJ-UHFFFAOYSA-N 0.000 description 1
• CQCAYWAIRTVXIY-UHFFFAOYSA-N 2-(triphenyl-$l^{5}-phosphanylidene)acetaldehyde Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC=O)C1=CC=CC=C1 CQCAYWAIRTVXIY-UHFFFAOYSA-N 0.000 description 1
• OIALIKXMLIAOSN-UHFFFAOYSA-N 2-Propylpyridine Chemical compound CCCC1=CC=CC=N1 OIALIKXMLIAOSN-UHFFFAOYSA-N 0.000 description 1
• ADSOSINJPNKUJK-UHFFFAOYSA-N 2-butylpyridine Chemical compound CCCCC1=CC=CC=N1 ADSOSINJPNKUJK-UHFFFAOYSA-N 0.000 description 1
• KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
• NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 1
• BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
• BXHGNAADUUXBKK-UHFFFAOYSA-N 2-methylpyrimidine-4-carbaldehyde Chemical compound CC1=NC=CC(C=O)=N1 BXHGNAADUUXBKK-UHFFFAOYSA-N 0.000 description 1
• IJBONYUNKRDIFC-UHFFFAOYSA-N 2-methylpyrimidine-5-carbaldehyde Chemical class CC1=NC=C(C=O)C=N1 IJBONYUNKRDIFC-UHFFFAOYSA-N 0.000 description 1
• FRWJCCYSBOOTSY-UHFFFAOYSA-N 3,5-dimethylpyrazole-3-carboximidamide;nitric acid Chemical compound O[N+]([O-])=O.CC1=CC(C)(C(N)=N)N=N1 FRWJCCYSBOOTSY-UHFFFAOYSA-N 0.000 description 1
• CKQPZIKYRFZYFW-UHFFFAOYSA-N 3-(2-methoxypyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OC)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 CKQPZIKYRFZYFW-UHFFFAOYSA-N 0.000 description 1
• MMIMNHFTOYWLHW-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 MMIMNHFTOYWLHW-UHFFFAOYSA-N 0.000 description 1
• HDRFULTXFCRTQX-UHFFFAOYSA-N 3-(2-methylpyrimidin-5-yl)-9-(3-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)C)=NC2=C1CCCN2 HDRFULTXFCRTQX-UHFFFAOYSA-N 0.000 description 1
• RCTLBKVHKHPTJY-UHFFFAOYSA-N 3-[2-(methylamino)pyrimidin-5-yl]-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(NC)=NC=C1C(CC(O)=O)CC(=O)CCCCC1=CC=C(CCCN2)C2=N1 RCTLBKVHKHPTJY-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
• ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
• GWCHTTSPSUWRBA-UHFFFAOYSA-N 3-chloro-1h-quinolin-4-one Chemical compound C1=CC=C2C(O)=C(Cl)C=NC2=C1 GWCHTTSPSUWRBA-UHFFFAOYSA-N 0.000 description 1
• FMNGYLNVEVDQQX-UHFFFAOYSA-N 3-cyclopropyl-1h-1,8-naphthyridin-2-one Chemical compound OC1=NC2=NC=CC=C2C=C1C1CC1 FMNGYLNVEVDQQX-UHFFFAOYSA-N 0.000 description 1
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
• SARKXLKWFKNUMR-UHFFFAOYSA-N 4-benzamido-5-chloro-2-methylbenzenediazonium;chloride Chemical compound [Cl-].C1=C([N+]#N)C(C)=CC(NC(=O)C=2C=CC=CC=2)=C1Cl SARKXLKWFKNUMR-UHFFFAOYSA-N 0.000 description 1
• DMAYBPBPEUFIHJ-UHFFFAOYSA-N 4-bromobut-1-ene Chemical compound BrCCC=C DMAYBPBPEUFIHJ-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• POXFXTSTVWDWIR-UHFFFAOYSA-N 4-iodobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(I)C=C1 POXFXTSTVWDWIR-UHFFFAOYSA-N 0.000 description 1
• CBMAMSBWMAVLPB-UHFFFAOYSA-N 5-oxo-3-pyrazin-2-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C=1C=C2CCCNC2=NC=1CCCCC(=O)CC(CC(=O)O)C1=CN=CC=N1 CBMAMSBWMAVLPB-UHFFFAOYSA-N 0.000 description 1
• HEOQXHNKRXRCTO-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulene Chemical compound C1CCCCC2=CC=CC=C21 HEOQXHNKRXRCTO-UHFFFAOYSA-N 0.000 description 1
• HUNFDTYSTHVENB-UHFFFAOYSA-N 7,7-dimethyl-3-(2-methylpyrimidin-5-yl)-5-oxo-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CC(C)(C)CCC1=CC=C(CCCN2)C2=N1 HUNFDTYSTHVENB-UHFFFAOYSA-N 0.000 description 1
• OXBOFCJANGRIBP-UHFFFAOYSA-N 9-(3-bromo-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)-3-(2-methylpyrimidin-5-yl)-5-oxononanoic acid Chemical compound C1=NC(C)=NC=C1C(CC(O)=O)CC(=O)CCCCC(C(=C1)Br)=NC2=C1CCCN2 OXBOFCJANGRIBP-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 229940078581 Bone resorption inhibitor Drugs 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 206010006811 Bursitis Diseases 0.000 description 1
• 206010007027 Calculus urinary Diseases 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
• 108010035532 Collagen Proteins 0.000 description 1
• 102000008186 Collagen Human genes 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
• 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 1
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
• 206010056438 Growth hormone deficiency Diseases 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 206010020100 Hip fracture Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 description 1
• 102000017347 Integrin beta-6 subunit Human genes 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 1
• 102000012750 Membrane Glycoproteins Human genes 0.000 description 1
• 108010090054 Membrane Glycoproteins Proteins 0.000 description 1
• 101710127721 Membrane protein Proteins 0.000 description 1
• 208000037848 Metastatic bone disease Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
• 102000016943 Muramidase Human genes 0.000 description 1
• 108010014251 Muramidase Proteins 0.000 description 1
• 208000010358 Myositis Ossificans Diseases 0.000 description 1
• 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
• LOJFGJZQOKTUBR-XAQOOIOESA-N NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O)C)CC1=CN=CN1 Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCC(O)=O)C)CC1=CN=CN1 LOJFGJZQOKTUBR-XAQOOIOESA-N 0.000 description 1
• 206010029240 Neuritis Diseases 0.000 description 1
• 239000004677 Nylon Substances 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 206010030247 Oestrogen deficiency Diseases 0.000 description 1
• 206010031240 Osteodystrophy Diseases 0.000 description 1
• 208000003076 Osteolysis Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 0.000 description 1
• 102000010752 Plasminogen Inactivators Human genes 0.000 description 1
• 108010077971 Plasminogen Inactivators Proteins 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920002873 Polyethylenimine Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 102100032709 Potassium-transporting ATPase alpha chain 2 Human genes 0.000 description 1
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 108010083204 Proton Pumps Proteins 0.000 description 1
• 241000700159 Rattus Species 0.000 description 1
• IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 206010039984 Senile osteoporosis Diseases 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• 102000007591 Tartrate-Resistant Acid Phosphatase Human genes 0.000 description 1
• 108010032050 Tartrate-Resistant Acid Phosphatase Proteins 0.000 description 1
• 208000003217 Tetany Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 206010064390 Tumour invasion Diseases 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 206010052428 Wound Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• 239000008351 acetate buffer Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• 102000001307 androgen receptors Human genes 0.000 description 1
• 108010080146 androgen receptors Proteins 0.000 description 1
• 230000001548 androgenic effect Effects 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 230000001772 anti-angiogenic effect Effects 0.000 description 1
• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 229960005370 atorvastatin Drugs 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• 235000012216 bentonite Nutrition 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• RVSGRNKUJJUAPV-UHFFFAOYSA-N benzo[d][1,2]benzoxazepine Chemical group O1N=CC2=CC=CC=C2C2=CC=CC=C12 RVSGRNKUJJUAPV-UHFFFAOYSA-N 0.000 description 1
• 229940049706 benzodiazepine Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 230000036770 blood supply Effects 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000002449 bone cell Anatomy 0.000 description 1
• 230000008468 bone growth Effects 0.000 description 1
• 230000037180 bone health Effects 0.000 description 1
• 230000010072 bone remodeling Effects 0.000 description 1
• 229910021538 borax Inorganic materials 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 235000011132 calcium sulphate Nutrition 0.000 description 1
• 238000011088 calibration curve Methods 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 230000009400 cancer invasion Effects 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000034196 cell chemotaxis Effects 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000036755 cellular response Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000003610 charcoal Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000004803 chlorobenzyl group Chemical group 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 210000003711 chorioallantoic membrane Anatomy 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 229940090805 clavulanate Drugs 0.000 description 1
• HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
• 239000003245 coal Substances 0.000 description 1
• 229920001436 collagen Polymers 0.000 description 1
• 108010049937 collagen type I trimeric cross-linked peptide Proteins 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 238000013267 controlled drug release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 210000004087 cornea Anatomy 0.000 description 1
• 125000006165 cyclic alkyl group Chemical group 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 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
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 125000000422 delta-lactone group Chemical group 0.000 description 1
• 239000005549 deoxyribonucleoside Substances 0.000 description 1
• 239000007933 dermal patch Substances 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 229910003460 diamond Inorganic materials 0.000 description 1
• 239000010432 diamond Substances 0.000 description 1
• PJQCANLCUDUPRF-UHFFFAOYSA-N dibenzocycloheptene Chemical compound C1CC2=CC=CC=C2CC2=CC=CC=C12 PJQCANLCUDUPRF-UHFFFAOYSA-N 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
• VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 1
• OGGXGZAMXPVRFZ-UHFFFAOYSA-M dimethylarsinate Chemical compound C[As](C)([O-])=O OGGXGZAMXPVRFZ-UHFFFAOYSA-M 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 229950004203 droloxifene Drugs 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 229940009662 edetate Drugs 0.000 description 1
• 229950005627 embonate Drugs 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 150000002085 enols Chemical group 0.000 description 1
• 229950000206 estolate Drugs 0.000 description 1
• 229930182833 estradiol Natural products 0.000 description 1
• 229960005309 estradiol Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
• JCEFWJJPNSIOLO-UHFFFAOYSA-N ethyl 4-[2-(6-aminopyridin-2-yl)ethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CCC1=CC=CC(N)=N1 JCEFWJJPNSIOLO-UHFFFAOYSA-N 0.000 description 1
• YXVCUBCOKSPXDN-UHFFFAOYSA-N ethyl 5-(5-bromopyridin-2-yl)pentanoate Chemical compound CCOC(=O)CCCCC1=CC=C(Br)C=N1 YXVCUBCOKSPXDN-UHFFFAOYSA-N 0.000 description 1
• RLRNJPRFFZKKRL-UHFFFAOYSA-N ethyl 5-(6-aminopyridin-2-yl)pentanoate Chemical compound CCOC(=O)CCCCC1=CC=CC(N)=N1 RLRNJPRFFZKKRL-UHFFFAOYSA-N 0.000 description 1
• MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 229940009626 etidronate Drugs 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000004175 fluorobenzyl group Chemical group 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 230000004153 glucose metabolism Effects 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• 239000003163 gonadal steroid hormone Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 210000003709 heart valve Anatomy 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• CATSNJVOTSVZJV-UHFFFAOYSA-N heptan-2-one Chemical compound CCCCCC(C)=O CATSNJVOTSVZJV-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 229940015872 ibandronate Drugs 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 230000003907 kidney function Effects 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-M 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000003908 liver function Effects 0.000 description 1
• 229960004844 lovastatin Drugs 0.000 description 1
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 208000029791 lytic metastatic bone lesion Diseases 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000001055 magnesium Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 230000009245 menopause Effects 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052987 metal hydride Inorganic materials 0.000 description 1
• 150000004681 metal hydrides Chemical class 0.000 description 1
• NZZDEODTCXHCRS-UHFFFAOYSA-N methyl 2-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1N NZZDEODTCXHCRS-UHFFFAOYSA-N 0.000 description 1
• 229940102396 methyl bromide Drugs 0.000 description 1
• LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
• 229940017219 methyl propionate Drugs 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
• 230000005012 migration Effects 0.000 description 1
• 238000013508 migration Methods 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 210000005088 multinucleated cell Anatomy 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000000474 nursing effect Effects 0.000 description 1
• 235000015097 nutrients Nutrition 0.000 description 1
• 229920001778 nylon Polymers 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 239000007935 oral tablet Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 239000013110 organic ligand Substances 0.000 description 1
• 230000011164 ossification Effects 0.000 description 1
• LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([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
• WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
• 229940046231 pamidronate Drugs 0.000 description 1
• 229940014662 pantothenate Drugs 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• MLBYLEUJXUBIJJ-UHFFFAOYSA-N pent-4-ynoic acid Chemical compound OC(=O)CCC#C MLBYLEUJXUBIJJ-UHFFFAOYSA-N 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005095 pioglitazone Drugs 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 230000033885 plasminogen activation Effects 0.000 description 1
• 239000002797 plasminogen activator inhibitor Substances 0.000 description 1
• 229920001610 polycaprolactone Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 230000008092 positive effect Effects 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 229960002965 pravastatin Drugs 0.000 description 1
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000013823 prenylation Effects 0.000 description 1
• 238000000327 preparative centrifugation Methods 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• UJEHWLFUEQHEEZ-UHFFFAOYSA-N quinoxaline-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=CN=C21 UJEHWLFUEQHEEZ-UHFFFAOYSA-N 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 239000002287 radioligand Substances 0.000 description 1
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 229940089617 risedronate Drugs 0.000 description 1
• 239000011435 rock Substances 0.000 description 1
• 229960004586 rosiglitazone Drugs 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 239000001433 sodium tartrate Substances 0.000 description 1
• 229960002167 sodium tartrate Drugs 0.000 description 1
• 235000011004 sodium tartrates Nutrition 0.000 description 1
• 239000004328 sodium tetraborate Substances 0.000 description 1
• 235000010339 sodium tetraborate Nutrition 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 206010041569 spinal fracture Diseases 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 238000005728 strengthening Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
• 210000002303 tibia Anatomy 0.000 description 1
• 239000003104 tissue culture media Substances 0.000 description 1
• 229950003937 tolonium Drugs 0.000 description 1
• HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 102000027257 transmembrane receptors Human genes 0.000 description 1
• 108091008578 transmembrane receptors Proteins 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
• 229960001641 troglitazone Drugs 0.000 description 1
• GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
• 230000005747 tumor angiogenesis Effects 0.000 description 1
• 210000000689 upper leg Anatomy 0.000 description 1
• 208000008281 urolithiasis Diseases 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 239000011534 wash buffer Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1