CA2906134A1 - Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions - Google Patents

Info

Publication number

CA2906134A1

CA2906134A1 CA2906134A CA2906134A CA2906134A1 CA 2906134 A1 CA2906134 A1 CA 2906134A1 CA 2906134 A CA2906134 A CA 2906134A CA 2906134 A CA2906134 A CA 2906134A CA 2906134 A1 CA2906134 A1 CA 2906134A1

Authority

CA

Canada

Prior art keywords

oxopyrrolidin

hydroxy

methyl

thiophene

methylnon

Prior art date

2013-03-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• -1 Lactam compounds Chemical class 0.000 title claims description 109
• 239000000556 agonist Substances 0.000 title abstract description 17
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 16
• 101150109738 Ptger4 gene Proteins 0.000 title description 17
• 201000010099 disease Diseases 0.000 title description 9
• 230000001404 mediated effect Effects 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 231
• 238000000034 method Methods 0.000 claims abstract description 73
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
• 208000001132 Osteoporosis Diseases 0.000 claims abstract description 10
• 208000010412 Glaucoma Diseases 0.000 claims abstract description 8
• 208000004296 neuralgia Diseases 0.000 claims abstract description 6
• 208000021722 neuropathic pain Diseases 0.000 claims abstract description 6
• 208000010392 Bone Fractures Diseases 0.000 claims abstract description 5
• 201000004384 Alopecia Diseases 0.000 claims abstract description 4
• 231100000360 alopecia Toxicity 0.000 claims abstract description 4
• 230000000399 orthopedic effect Effects 0.000 claims abstract description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 194
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 183
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 75
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 70
• QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 claims description 68
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 63
• 125000000217 alkyl group Chemical group 0.000 claims description 57
• 150000003839 salts Chemical class 0.000 claims description 51
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 32
• 125000001424 substituent group Chemical group 0.000 claims description 31
• 125000001153 fluoro group Chemical group F* 0.000 claims description 29
• 239000001257 hydrogen Substances 0.000 claims description 28
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 229910052736 halogen Inorganic materials 0.000 claims description 24
• 150000002367 halogens Chemical group 0.000 claims description 24
• 229910052799 carbon Inorganic materials 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 13
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
• KPSZWAJWFMFMFF-UHFFFAOYSA-N hept-5-enoic acid Chemical compound CC=CCCCC(O)=O KPSZWAJWFMFMFF-UHFFFAOYSA-N 0.000 claims description 10
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
• 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 claims description 8
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 7
• 206010065687 Bone loss Diseases 0.000 claims description 6
• 125000005622 butynylene group Chemical group 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 238000002513 implantation Methods 0.000 claims description 4
• 208000028169 periodontal disease Diseases 0.000 claims description 4
• 230000004927 fusion Effects 0.000 claims description 3
• 229910052760 oxygen Inorganic materials 0.000 claims description 3
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 3
• 210000003781 tooth socket Anatomy 0.000 claims description 3
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 2
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 2
• LUMFGCXGZYQBGW-JFEFSJLHSA-N (5r)-1-(7-hydroxyheptyl)-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]pyrrolidin-2-one Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCCO LUMFGCXGZYQBGW-JFEFSJLHSA-N 0.000 claims 1
• QCXBTVSQVDPNAC-VIDOSBHOSA-N (5r)-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-1-[6-(2h-tetrazol-5-yl)hexyl]pyrrolidin-2-one Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC1=NNN=N1 QCXBTVSQVDPNAC-VIDOSBHOSA-N 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• HTRMTRTYTPSBDA-VFTDAYRLSA-N (z)-7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]hept-5-enoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)C\C=C/CCCC(O)=O)C#CC1=CC=CC=C1 HTRMTRTYTPSBDA-VFTDAYRLSA-N 0.000 claims 1
• VMFUAZWICRQOLZ-YEBWXDKISA-N (z)-7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]hept-5-enoic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/CCCC(O)=O VMFUAZWICRQOLZ-YEBWXDKISA-N 0.000 claims 1
• ULQPVMIAKPYEAV-HBCAMOHXSA-N (z)-7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]hept-5-enoic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/CCCC(O)=O ULQPVMIAKPYEAV-HBCAMOHXSA-N 0.000 claims 1
• LCDPIZFPSKLUFI-ULGUBMFYSA-N 3-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCC=1C=C(C=CC=1)C(O)=O)C#CC1=CC=CC=C1 LCDPIZFPSKLUFI-ULGUBMFYSA-N 0.000 claims 1
• PICAFVRDHQJMFP-BPZODPGYSA-N 3-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=CC(C(O)=O)=C1 PICAFVRDHQJMFP-BPZODPGYSA-N 0.000 claims 1
• SIZMDZRGLLGFNA-XZHPXJBXSA-N 3-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=CC(C(O)=O)=C1 SIZMDZRGLLGFNA-XZHPXJBXSA-N 0.000 claims 1
• VWVJGHUYPGVPLE-KNCLBMDMSA-N 3-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=CC(C(O)=O)=C1 VWVJGHUYPGVPLE-KNCLBMDMSA-N 0.000 claims 1
• WSWMPKRYVIPBSF-HZSMUKNUSA-N 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCC=1C=CC(=CC=1)C(O)=O)C#CC1=CC=CC=C1 WSWMPKRYVIPBSF-HZSMUKNUSA-N 0.000 claims 1
• ZEQRQASSBIVECC-FFKNSKTJSA-N 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCSCCCC(O)=O)C#CC1=CC=CC=C1 ZEQRQASSBIVECC-FFKNSKTJSA-N 0.000 claims 1
• SPQQXPMTGNWAOR-XZHPXJBXSA-N 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 SPQQXPMTGNWAOR-XZHPXJBXSA-N 0.000 claims 1
• NOYNLOFBPYBSKQ-KNCLBMDMSA-N 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 NOYNLOFBPYBSKQ-KNCLBMDMSA-N 0.000 claims 1
• IZOGAFRFLSBBAE-FTFFSTDUSA-N 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 IZOGAFRFLSBBAE-FTFFSTDUSA-N 0.000 claims 1
• BZUUPCIRSKSIFM-MMKZDMBBSA-N 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCSCCCC(O)=O BZUUPCIRSKSIFM-MMKZDMBBSA-N 0.000 claims 1
• GLZDLJYBUMTYIT-ASCRIOMFSA-N 5-[(z)-3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-enyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)C\C=C/C=1SC(=CC=1)C(O)=O)C#CC1=CC=CC=C1 GLZDLJYBUMTYIT-ASCRIOMFSA-N 0.000 claims 1
• CRRJJBDCQRPUNE-LIRTUGRKSA-N 5-[(z)-3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-enyl]thiophene-2-carboxylic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/C1=CC=C(C(O)=O)S1 CRRJJBDCQRPUNE-LIRTUGRKSA-N 0.000 claims 1
• WONXWFKEMIDHPY-BGCHRUAMSA-N 5-[(z)-3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-enyl]thiophene-2-carboxylic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/C1=CC=C(C(O)=O)S1 WONXWFKEMIDHPY-BGCHRUAMSA-N 0.000 claims 1
• BHQRIGSJGLSLIC-KGMQMRAYSA-N 5-[(z)-3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-enyl]thiophene-2-carboxylic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/C1=CC=C(C(O)=O)S1 BHQRIGSJGLSLIC-KGMQMRAYSA-N 0.000 claims 1
• DTMCXOOEGYTRCO-URCWZONMSA-N 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCC=1SC(=CC=1)C(O)=O)C#CC1=CC=CC=C1 DTMCXOOEGYTRCO-URCWZONMSA-N 0.000 claims 1
• JGLDKMIERUTTPB-KXGHQGSMSA-N 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 JGLDKMIERUTTPB-KXGHQGSMSA-N 0.000 claims 1
• YITXTUJDWOPLOM-KSHJQNSNSA-N 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 YITXTUJDWOPLOM-KSHJQNSNSA-N 0.000 claims 1
• XHBRELWGKCRMMH-GDXRVXTNSA-N 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 XHBRELWGKCRMMH-GDXRVXTNSA-N 0.000 claims 1
• MQIMWQHNKWBEEY-KVVBJZIMSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CC#CC=1SC(=CC=1)C(O)=O)C#CC1=CC=CC=C1 MQIMWQHNKWBEEY-KVVBJZIMSA-N 0.000 claims 1
• DTMCXOOEGYTRCO-KVVBJZIMSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCC=1SC(=CC=1)C(O)=O)C#CC1=CC=CC=C1 DTMCXOOEGYTRCO-KVVBJZIMSA-N 0.000 claims 1
• WNDUHSMPILKRAT-NIHFNGFISA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(O)=O)S1 WNDUHSMPILKRAT-NIHFNGFISA-N 0.000 claims 1
• JGLDKMIERUTTPB-NIHFNGFISA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 JGLDKMIERUTTPB-NIHFNGFISA-N 0.000 claims 1
• LJBQBOYAUOOSLH-UXJZIFKLSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(O)=O)S1 LJBQBOYAUOOSLH-UXJZIFKLSA-N 0.000 claims 1
• YITXTUJDWOPLOM-UXJZIFKLSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 YITXTUJDWOPLOM-UXJZIFKLSA-N 0.000 claims 1
• FSMKYAOTVQGMPD-OWJQIPJGSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(O)=O)S1 FSMKYAOTVQGMPD-OWJQIPJGSA-N 0.000 claims 1
• XHBRELWGKCRMMH-OWJQIPJGSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 XHBRELWGKCRMMH-OWJQIPJGSA-N 0.000 claims 1
• LSHMGTXEUMQTLQ-DMBFJYOSSA-N 7-[(2r)-2-[(e,3r)-3-hydroxy-3-(1-pent-2-ynylcyclobutyl)prop-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CCC1([C@H](O)\C=C\[C@@H]2N(C(=O)CC2)CCCCCCC(O)=O)CCC1 LSHMGTXEUMQTLQ-DMBFJYOSSA-N 0.000 claims 1
• SUMIZVFPECLVCC-OEDVWLICSA-N 7-[(2r)-2-[(e,3r)-3-hydroxy-4,4-dimethylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CCC(C)(C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O SUMIZVFPECLVCC-OEDVWLICSA-N 0.000 claims 1
• CBIUADIJQPJQEZ-JQQKYQAWSA-N 7-[(2r)-2-[(e,3r,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@@H](C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O CBIUADIJQPJQEZ-JQQKYQAWSA-N 0.000 claims 1
• RSMQQBKBATUTMJ-XQMOWUBYSA-N 7-[(2r)-2-[(e,3r,4r)-3-hydroxy-4-propan-2-ylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@H](C(C)C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O RSMQQBKBATUTMJ-XQMOWUBYSA-N 0.000 claims 1
• CBIUADIJQPJQEZ-HUXPJRAUSA-N 7-[(2r)-2-[(e,3r,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@H](C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O CBIUADIJQPJQEZ-HUXPJRAUSA-N 0.000 claims 1
• DCDMUZOWXFURHT-GUPMMHBCSA-N 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)C#CC1=CC=CC=C1 DCDMUZOWXFURHT-GUPMMHBCSA-N 0.000 claims 1
• SXXNVIDTHFZRHW-XCFFXWDTSA-N 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-9-phenylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)C#CCCC1=CC=CC=C1 SXXNVIDTHFZRHW-XCFFXWDTSA-N 0.000 claims 1
• CVUPACBLKGWFGO-FQGAQASWSA-N 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O CVUPACBLKGWFGO-FQGAQASWSA-N 0.000 claims 1
• CBIUADIJQPJQEZ-PIDBWSNSSA-N 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O CBIUADIJQPJQEZ-PIDBWSNSSA-N 0.000 claims 1
• XLBCQUAHSNWMTQ-DUNUYGSXSA-N 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O XLBCQUAHSNWMTQ-DUNUYGSXSA-N 0.000 claims 1
• DCDMUZOWXFURHT-FXDNMFHBSA-N 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)C#CC1=CC=CC=C1 DCDMUZOWXFURHT-FXDNMFHBSA-N 0.000 claims 1
• CVUPACBLKGWFGO-JTXTVYCZSA-N 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O CVUPACBLKGWFGO-JTXTVYCZSA-N 0.000 claims 1
• MVWHXRWUAFNXPI-JTXTVYCZSA-N 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]-n-methylsulfonylheptanamide Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)NS(C)(=O)=O MVWHXRWUAFNXPI-JTXTVYCZSA-N 0.000 claims 1
• XLBCQUAHSNWMTQ-OLMSDWHISA-N 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O XLBCQUAHSNWMTQ-OLMSDWHISA-N 0.000 claims 1
• DFGVADBSESALEJ-JTXTVYCZSA-N 7-[(2r)-2-[(e,3s,4s)-4-ethyl-3-hydroxynon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@H](CC)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O DFGVADBSESALEJ-JTXTVYCZSA-N 0.000 claims 1
• IUDVWVHGCZEPLF-PCCBWWKXSA-N C(C)NC(CCCCCCN1[C@H](CCC1=O)C=C[C@H]([C@H](CC#CCC)C)O)=O Chemical compound C(C)NC(CCCCCCN1[C@H](CCC1=O)C=C[C@H]([C@H](CC#CCC)C)O)=O IUDVWVHGCZEPLF-PCCBWWKXSA-N 0.000 claims 1
• RCGFDUVRRPQMQW-QHLFFQLOSA-N FC([C@@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)O)(CC#CCC)F Chemical compound FC([C@@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)O)(CC#CCC)F RCGFDUVRRPQMQW-QHLFFQLOSA-N 0.000 claims 1
• BELCCQPCCQSSLD-QYZOEREBSA-N O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@@H](CC#CCC)C Chemical compound O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@@H](CC#CCC)C BELCCQPCCQSSLD-QYZOEREBSA-N 0.000 claims 1
• BELCCQPCCQSSLD-FHWLQOOXSA-N O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@H](CC#CCC)C Chemical compound O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@H](CC#CCC)C BELCCQPCCQSSLD-FHWLQOOXSA-N 0.000 claims 1
• JTLRKIGJTKOWSW-AABGKKOBSA-N O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCC)C Chemical compound O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCC)C JTLRKIGJTKOWSW-AABGKKOBSA-N 0.000 claims 1
• JTLRKIGJTKOWSW-UFYCRDLUSA-N O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@H](CC#CCC)C Chemical compound O[C@@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@H](CC#CCC)C JTLRKIGJTKOWSW-UFYCRDLUSA-N 0.000 claims 1
• WZDMNHOPMNOXBU-VIDOSBHOSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CC#CCCCC(=O)O)[C@H](CC#CCC)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CC#CCCCC(=O)O)[C@H](CC#CCC)C WZDMNHOPMNOXBU-VIDOSBHOSA-N 0.000 claims 1
• SYPIOLXEOHHQKC-JTXTVYCZSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CC#CCCCC(=O)OC)[C@H](CC#CCC)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CC#CCCCC(=O)OC)[C@H](CC#CCC)C SYPIOLXEOHHQKC-JTXTVYCZSA-N 0.000 claims 1
• QEJHJVIRIRFMER-REPNIFTOSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CC=C/C1=CC=C(S1)C(=O)OC)[C@H](CC#CC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CC=C/C1=CC=C(S1)C(=O)OC)[C@H](CC#CC1=CC=CC=C1)C QEJHJVIRIRFMER-REPNIFTOSA-N 0.000 claims 1
• VAAKHCNUQMLZDF-FWILWFKNSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CC#CCC1=CC=CC=C1)C VAAKHCNUQMLZDF-FWILWFKNSA-N 0.000 claims 1
• TZXYQPALCPDSDU-NXGKZXSYSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CC#CCCC1=CC=CC=C1)C TZXYQPALCPDSDU-NXGKZXSYSA-N 0.000 claims 1
• VAAKHCNUQMLZDF-IJTXGDDHSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@H](CC#CCC1=CC=CC=C1)C VAAKHCNUQMLZDF-IJTXGDDHSA-N 0.000 claims 1
• TZXYQPALCPDSDU-QKIYNVSWSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@H](CC#CCCC1=CC=CC=C1)C TZXYQPALCPDSDU-QKIYNVSWSA-N 0.000 claims 1
• WPCKZAYZKXZTCD-NXGKZXSYSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@@H](CC#CCC1=CC=CC=C1)C WPCKZAYZKXZTCD-NXGKZXSYSA-N 0.000 claims 1
• UCJIJXBQFALSPX-ISDDRNPQSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@@H](CC#CCCC1=CC=CC=C1)C UCJIJXBQFALSPX-ISDDRNPQSA-N 0.000 claims 1
• WPCKZAYZKXZTCD-QKIYNVSWSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@H](CC#CCC1=CC=CC=C1)C WPCKZAYZKXZTCD-QKIYNVSWSA-N 0.000 claims 1
• UCJIJXBQFALSPX-JIDCDXGMSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@H](CC#CCCC1=CC=CC=C1)C UCJIJXBQFALSPX-JIDCDXGMSA-N 0.000 claims 1
• HGVSLOWMTLREFL-UAIJGWENSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)CCC#CCC Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)CCC#CCC HGVSLOWMTLREFL-UAIJGWENSA-N 0.000 claims 1
• RJKRFVAOVSYLQT-JZFAANTHSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@@H](CC#CCC1=CC=CC=C1)C RJKRFVAOVSYLQT-JZFAANTHSA-N 0.000 claims 1
• RJKRFVAOVSYLQT-GJOKGENYSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@H](CC#CCC1=CC=CC=C1)C RJKRFVAOVSYLQT-GJOKGENYSA-N 0.000 claims 1
• SXXNVIDTHFZRHW-GJMCBJSESA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@H](CC#CCCC1=CC=CC=C1)C SXXNVIDTHFZRHW-GJMCBJSESA-N 0.000 claims 1
• MUNDZKSQNKNMAL-CPLSZTBBSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC(C)C)[C@H](CC#CCC)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC(C)C)[C@H](CC#CCC)C MUNDZKSQNKNMAL-CPLSZTBBSA-N 0.000 claims 1
• PEJVZVSUPDZEHD-XCFFXWDTSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCC1=CC=CC=C1)C PEJVZVSUPDZEHD-XCFFXWDTSA-N 0.000 claims 1
• VHIWASQNWJMBMR-QNZFJJFASA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCCC1=CC=CC=C1)C VHIWASQNWJMBMR-QNZFJJFASA-N 0.000 claims 1
• VHIWASQNWJMBMR-ILHYATBKSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@H](CC#CCCC1=CC=CC=C1)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@H](CC#CCCC1=CC=CC=C1)C VHIWASQNWJMBMR-ILHYATBKSA-N 0.000 claims 1
• LTTXNUICDINWEA-SGRRYWTJSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OCC)[C@H](CC#CCC)C Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OCC)[C@H](CC#CCC)C LTTXNUICDINWEA-SGRRYWTJSA-N 0.000 claims 1
• KDVOTHZTFMHXGL-ZIFCJYIRSA-N O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CC#CCC)C Chemical compound O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CC#CCC)C KDVOTHZTFMHXGL-ZIFCJYIRSA-N 0.000 claims 1
• KDVOTHZTFMHXGL-JENIJYKNSA-N O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@H](CC#CCC)C Chemical compound O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@H](CC#CCC)C KDVOTHZTFMHXGL-JENIJYKNSA-N 0.000 claims 1
• SGOIRJCLQJVAGA-WSTZPKSXSA-N O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@@H](CC#CCC)C Chemical compound O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@@H](CC#CCC)C SGOIRJCLQJVAGA-WSTZPKSXSA-N 0.000 claims 1
• SGOIRJCLQJVAGA-CMKODMSKSA-N O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@H](CC#CCC)C Chemical compound O[C@H](CC[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)OC)[C@H](CC#CCC)C SGOIRJCLQJVAGA-CMKODMSKSA-N 0.000 claims 1
• BELCCQPCCQSSLD-CEXWTWQISA-N O[C@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@@H](CC#CCC)C Chemical compound O[C@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)O)[C@@H](CC#CCC)C BELCCQPCCQSSLD-CEXWTWQISA-N 0.000 claims 1
• JTLRKIGJTKOWSW-HSALFYBXSA-N O[C@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCC)C Chemical compound O[C@H](CC[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)[C@@H](CC#CCC)C JTLRKIGJTKOWSW-HSALFYBXSA-N 0.000 claims 1
• RJXHUNBUTWZNFV-POKBBOPGSA-N methyl (z)-7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]hept-5-enoate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/CCCC(=O)OC RJXHUNBUTWZNFV-POKBBOPGSA-N 0.000 claims 1
• OJHIYHLAKHTNDB-YEBWXDKISA-N methyl (z)-7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]hept-5-enoate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/CCCC(=O)OC OJHIYHLAKHTNDB-YEBWXDKISA-N 0.000 claims 1
• VWCUTVHSUBDXGD-IVTWNUDLSA-N methyl (z)-7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]hept-5-enoate Chemical compound COC(=O)CCC\C=C/CN1[C@@H](\C=C\[C@@H](O)[C@@H](C)CC#CC)CCC1=O VWCUTVHSUBDXGD-IVTWNUDLSA-N 0.000 claims 1
• QQYRZJFQGHTUCC-UPWRLUOJSA-N methyl 3-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=CC(C(=O)OC)=C1 QQYRZJFQGHTUCC-UPWRLUOJSA-N 0.000 claims 1
• NYDWMGNGCZQBDL-XZHPXJBXSA-N methyl 3-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound COC(=O)C1=CC=CC(CCCN2C(CC[C@@H]2\C=C\[C@@H](O)[C@@H](C)CC#CC)=O)=C1 NYDWMGNGCZQBDL-XZHPXJBXSA-N 0.000 claims 1
• NFDFUUJOLDSWKN-BPZODPGYSA-N methyl 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 NFDFUUJOLDSWKN-BPZODPGYSA-N 0.000 claims 1
• LOEUJHGORNUWIK-LTBIPVRFSA-N methyl 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCSCCCC(=O)OC LOEUJHGORNUWIK-LTBIPVRFSA-N 0.000 claims 1
• LCGIMEDKPRRHLW-DTCDPSDVSA-N methyl 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCSCCCC(=O)OC LCGIMEDKPRRHLW-DTCDPSDVSA-N 0.000 claims 1
• MZHLLEHIMPZPSL-KNCLBMDMSA-N methyl 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CC[C@@H]1\C=C\[C@@H](O)[C@@H](C)CC#CC MZHLLEHIMPZPSL-KNCLBMDMSA-N 0.000 claims 1
• SAFNDZFMTWLUJT-FYFUGGRKSA-N methyl 4-[2-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethylsulfanyl]butanoate Chemical compound COC(=O)CCCSCCN1[C@@H](\C=C\[C@@H](O)[C@@H](C)CC#CC)CCC1=O SAFNDZFMTWLUJT-FYFUGGRKSA-N 0.000 claims 1
• ZCWFJOHTEPXVLA-HJTASCSMSA-N methyl 5-[(z)-3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-enyl]thiophene-2-carboxylate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1C\C=C/C1=CC=C(C(=O)OC)S1 ZCWFJOHTEPXVLA-HJTASCSMSA-N 0.000 claims 1
• LNNGCJLDXLEGPD-BGCHRUAMSA-N methyl 5-[(z)-3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-enyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1\C=C/CN1C(=O)CC[C@@H]1\C=C\[C@@H](O)[C@@H](C)CC#CC LNNGCJLDXLEGPD-BGCHRUAMSA-N 0.000 claims 1
• DBZHSWMGEOFAIJ-DZFXHCIASA-N methyl 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(=O)OC)S1 DBZHSWMGEOFAIJ-DZFXHCIASA-N 0.000 claims 1
• AVZCAQNCYODQHK-KXGHQGSMSA-N methyl 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(=O)OC)S1 AVZCAQNCYODQHK-KXGHQGSMSA-N 0.000 claims 1
• PXCRHKVONMQIAW-KSHJQNSNSA-N methyl 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1\C=C\[C@@H](O)[C@H](C)CC#CC PXCRHKVONMQIAW-KSHJQNSNSA-N 0.000 claims 1
• ZLJOXRCJHCHKDR-FSZKDDNASA-N methyl 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(=O)OC)S1 ZLJOXRCJHCHKDR-FSZKDDNASA-N 0.000 claims 1
• DBZHSWMGEOFAIJ-FSZKDDNASA-N methyl 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(=O)OC)S1 DBZHSWMGEOFAIJ-FSZKDDNASA-N 0.000 claims 1
• VMFROVKJYQMOJO-NIHFNGFISA-N methyl 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(=O)OC)S1 VMFROVKJYQMOJO-NIHFNGFISA-N 0.000 claims 1
• AVZCAQNCYODQHK-NIHFNGFISA-N methyl 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(=O)OC)S1 AVZCAQNCYODQHK-NIHFNGFISA-N 0.000 claims 1
• KEWBZDCBJCWQDM-UXJZIFKLSA-N methyl 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C#CCN1C(=O)CC[C@@H]1\C=C\[C@@H](O)[C@@H](C)CC#CC KEWBZDCBJCWQDM-UXJZIFKLSA-N 0.000 claims 1
• PXCRHKVONMQIAW-UXJZIFKLSA-N methyl 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1\C=C\[C@@H](O)[C@@H](C)CC#CC PXCRHKVONMQIAW-UXJZIFKLSA-N 0.000 claims 1
• XCTLMJDQKYIAQZ-RIYOGWEESA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-3-(1-pent-2-ynylcyclobutyl)prop-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CCC1([C@H](O)\C=C\[C@@H]2N(C(=O)CC2)CCCCCCC(=O)OC)CCC1 XCTLMJDQKYIAQZ-RIYOGWEESA-N 0.000 claims 1
• HOGLITIZSUJPFC-DMBFJYOSSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-3-(1-pent-2-ynylcyclopropyl)prop-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CCC1([C@H](O)\C=C\[C@@H]2N(C(=O)CC2)CCCCCCC(=O)OC)CC1 HOGLITIZSUJPFC-DMBFJYOSSA-N 0.000 claims 1
• LJJNCVIWNFPFTG-VIDFKJSCSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-4,4-dimethylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CCC(C)(C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC LJJNCVIWNFPFTG-VIDFKJSCSA-N 0.000 claims 1
• GWSXPSKJHVHHLX-SLKVGHROSA-N methyl 7-[(2r)-2-[(e,3r)-4,4-difluoro-3-hydroxynon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CCC(F)(F)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC GWSXPSKJHVHHLX-SLKVGHROSA-N 0.000 claims 1
• DNPJRUISCQSSCL-KJZDPDCVSA-N methyl 7-[(2r)-2-[(e,3r,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@@H](C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC DNPJRUISCQSSCL-KJZDPDCVSA-N 0.000 claims 1
• ACAZRBWYQJKXES-QRVHACKSSA-N methyl 7-[(2r)-2-[(e,3r,4r)-3-hydroxy-4-propan-2-ylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@H](C(C)C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC ACAZRBWYQJKXES-QRVHACKSSA-N 0.000 claims 1
• DNPJRUISCQSSCL-KSAIBFCDSA-N methyl 7-[(2r)-2-[(e,3r,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@H](C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC DNPJRUISCQSSCL-KSAIBFCDSA-N 0.000 claims 1
• CQUJJAHGLDDWHY-FZMWVVQVSA-N methyl 7-[(2r)-2-[(e,3s)-3-hydroxynon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CCC[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC CQUJJAHGLDDWHY-FZMWVVQVSA-N 0.000 claims 1
• WMZRIOLCANOJPR-JZFAANTHSA-N methyl 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)[C@H](C)CC#CC1=CC=CC=C1 WMZRIOLCANOJPR-JZFAANTHSA-N 0.000 claims 1
• OKMFLOJZWHARQU-BLLHCEQASA-N methyl 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC OKMFLOJZWHARQU-BLLHCEQASA-N 0.000 claims 1
• DNPJRUISCQSSCL-FQGAQASWSA-N methyl 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC DNPJRUISCQSSCL-FQGAQASWSA-N 0.000 claims 1
• FCFQGZGDLMMISZ-PIDBWSNSSA-N methyl 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@@H](O)[C@H](C)CC#CC)CCC1=O FCFQGZGDLMMISZ-PIDBWSNSSA-N 0.000 claims 1
• WMZRIOLCANOJPR-GJOKGENYSA-N methyl 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)[C@@H](C)CC#CC1=CC=CC=C1 WMZRIOLCANOJPR-GJOKGENYSA-N 0.000 claims 1
• PEJVZVSUPDZEHD-GJMCBJSESA-N methyl 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-8-phenyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)[C@@H](C)CC#CCC1=CC=CC=C1 PEJVZVSUPDZEHD-GJMCBJSESA-N 0.000 claims 1
• OKMFLOJZWHARQU-SGRRYWTJSA-N methyl 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC OKMFLOJZWHARQU-SGRRYWTJSA-N 0.000 claims 1
• DNPJRUISCQSSCL-JTXTVYCZSA-N methyl 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC DNPJRUISCQSSCL-JTXTVYCZSA-N 0.000 claims 1
• FCFQGZGDLMMISZ-VIDOSBHOSA-N methyl 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@@H](O)[C@@H](C)CC#CC)CCC1=O FCFQGZGDLMMISZ-VIDOSBHOSA-N 0.000 claims 1
• ZILMVSCRTKCUMI-SGRRYWTJSA-N methyl 7-[(2r)-2-[(e,3s,4s)-4-ethyl-3-hydroxynon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@H](CC)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC ZILMVSCRTKCUMI-SGRRYWTJSA-N 0.000 claims 1
• 208000035475 disorder Diseases 0.000 abstract description 7
• 239000007943 implant Substances 0.000 abstract description 3
• 208000002679 Alveolar Bone Loss Diseases 0.000 abstract 1
• 238000002360 preparation method Methods 0.000 description 132
• 239000000203 mixture Substances 0.000 description 123
• 239000002904 solvent Substances 0.000 description 123
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
• 238000004809 thin layer chromatography Methods 0.000 description 100
• 239000000543 intermediate Substances 0.000 description 93
• 239000003921 oil Substances 0.000 description 67
• 235000019198 oils Nutrition 0.000 description 67
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
• 101001117509 Homo sapiens Prostaglandin E2 receptor EP4 subtype Proteins 0.000 description 50
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
• 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 description 49
• 230000014759 maintenance of location Effects 0.000 description 43
• 239000011541 reaction mixture Substances 0.000 description 42
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 40
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 38
• 238000002953 preparative HPLC Methods 0.000 description 38
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 37
• 238000004128 high performance liquid chromatography Methods 0.000 description 36
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 34
• 210000004027 cell Anatomy 0.000 description 33
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 33
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 33
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 32
• 239000000243 solution Substances 0.000 description 31
• 235000019441 ethanol Nutrition 0.000 description 29
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 29
• 238000000926 separation method Methods 0.000 description 29
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
• 150000001299 aldehydes Chemical class 0.000 description 28
• 238000006243 chemical reaction Methods 0.000 description 28
• 239000007787 solid Substances 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• 238000005481 NMR spectroscopy Methods 0.000 description 23
• XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 23
• 239000012071 phase Substances 0.000 description 23
• 150000002148 esters Chemical class 0.000 description 22
• 229960002986 dinoprostone Drugs 0.000 description 21
• XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 21
• 102000005962 receptors Human genes 0.000 description 21
• 108020003175 receptors Proteins 0.000 description 21
• 239000002585 base Substances 0.000 description 20
• 230000027455 binding Effects 0.000 description 19
• 239000003814 drug Substances 0.000 description 19
• 238000002825 functional assay Methods 0.000 description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 19
• 238000010898 silica gel chromatography Methods 0.000 description 19
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
• 238000005160 1H NMR spectroscopy Methods 0.000 description 18
• 239000005711 Benzoic acid Substances 0.000 description 18
• 235000010233 benzoic acid Nutrition 0.000 description 18
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
• 239000012267 brine Substances 0.000 description 17
• 150000001733 carboxylic acid esters Chemical class 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 230000000694 effects Effects 0.000 description 16
• 239000000377 silicon dioxide Substances 0.000 description 16
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• ZCLSQRQRWNDNLV-UHFFFAOYSA-N acetic acid;dichloromethane;methanol Chemical compound OC.ClCCl.CC(O)=O ZCLSQRQRWNDNLV-UHFFFAOYSA-N 0.000 description 15
• RWFPXJAUVOBOLJ-UHFFFAOYSA-N acetic acid;ethyl acetate;heptane Chemical compound CC(O)=O.CCOC(C)=O.CCCCCCC RWFPXJAUVOBOLJ-UHFFFAOYSA-N 0.000 description 15
• 239000002253 acid Substances 0.000 description 15
• 239000012230 colorless oil Substances 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• 230000007547 defect Effects 0.000 description 14
• 229940079593 drug Drugs 0.000 description 14
• 239000012453 solvate Substances 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 13
• 239000004568 cement Substances 0.000 description 13
• 239000012074 organic phase Substances 0.000 description 13
• 230000008569 process Effects 0.000 description 13
• 239000000126 substance Substances 0.000 description 13
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• 210000000988 bone and bone Anatomy 0.000 description 12
• 229910052938 sodium sulfate Inorganic materials 0.000 description 12
• 235000011152 sodium sulphate Nutrition 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
• 239000002168 alkylating agent Substances 0.000 description 11
• 229940100198 alkylating agent Drugs 0.000 description 11
• 239000001506 calcium phosphate Substances 0.000 description 11
• 150000001721 carbon Chemical group 0.000 description 11
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 11
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 10
• 150000007513 acids Chemical class 0.000 description 10
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
• UMYZHWLYICNGRQ-UHFFFAOYSA-N ethanol;heptane Chemical compound CCO.CCCCCCC UMYZHWLYICNGRQ-UHFFFAOYSA-N 0.000 description 10
• 238000006460 hydrolysis reaction Methods 0.000 description 10
• 238000009434 installation Methods 0.000 description 10
• 238000002844 melting Methods 0.000 description 10
• 230000008018 melting Effects 0.000 description 10
• 239000000843 powder Substances 0.000 description 10
• 230000002829 reductive effect Effects 0.000 description 10
• 239000007858 starting material Substances 0.000 description 10
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 9
• 125000005842 heteroatom Chemical group 0.000 description 9
• 230000007062 hydrolysis Effects 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000003112 inhibitor Substances 0.000 description 9
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 9
• 150000003180 prostaglandins Chemical class 0.000 description 9
• 230000009467 reduction Effects 0.000 description 9
• 238000006722 reduction reaction Methods 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 8
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 8
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 239000012279 sodium borohydride Substances 0.000 description 8
• 229910000033 sodium borohydride Inorganic materials 0.000 description 8
• LNNXOEHOXSYWLD-UHFFFAOYSA-N 1-bromobut-2-yne Chemical compound CC#CCBr LNNXOEHOXSYWLD-UHFFFAOYSA-N 0.000 description 7
• PQRJMMHOQSJORL-UHFFFAOYSA-N 1-dimethoxyphosphorylhept-5-yn-2-one Chemical compound COP(=O)(OC)CC(=O)CCC#CC PQRJMMHOQSJORL-UHFFFAOYSA-N 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 210000002805 bone matrix Anatomy 0.000 description 7
• 229910000389 calcium phosphate Inorganic materials 0.000 description 7
• 235000011010 calcium phosphates Nutrition 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 7
• NTUGPDFKMVHCCJ-SECBINFHSA-N ditert-butyl (2r)-2-aminopentanedioate Chemical compound CC(C)(C)OC(=O)CC[C@@H](N)C(=O)OC(C)(C)C NTUGPDFKMVHCCJ-SECBINFHSA-N 0.000 description 7
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 239000002502 liposome Substances 0.000 description 7
• 125000002950 monocyclic group Chemical group 0.000 description 7
• 239000011368 organic material Substances 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• 229940044601 receptor agonist Drugs 0.000 description 7
• 239000000018 receptor agonist Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 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 7
• BWTVLNGTVPSZFS-GFCCVEGCSA-N (2r)-1-[2-(4-methoxycarbonylphenyl)ethyl]-5-oxopyrrolidine-2-carboxylic acid Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CC[C@@H]1C(O)=O BWTVLNGTVPSZFS-GFCCVEGCSA-N 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 6
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 6
• OJOFMLDBXPDXLQ-UHFFFAOYSA-N 4-benzyl-1,3-oxazolidin-2-one Chemical class C1OC(=O)NC1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 238000005804 alkylation reaction Methods 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 6
• 230000001684 chronic effect Effects 0.000 description 6
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 6
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 6
• 229910052757 nitrogen Inorganic materials 0.000 description 6
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• XLEQAFNZWZDIPJ-UHFFFAOYSA-N 1-dimethoxyphosphoryl-6-phenylhex-5-yn-2-one Chemical compound COP(=O)(OC)CC(=O)CCC#CC1=CC=CC=C1 XLEQAFNZWZDIPJ-UHFFFAOYSA-N 0.000 description 5
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 5
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 5
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 5
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 5
• 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 5
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
• 238000010521 absorption reaction Methods 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 238000010511 deprotection reaction Methods 0.000 description 5
• IUNNATUFXICVNU-GOSISDBHSA-N ditert-butyl (2R)-2-[[4-(2-methoxy-2-oxoethyl)phenyl]methylamino]pentanedioate Chemical compound COC(CC1=CC=C(CN[C@@H](C(=O)OC(C)(C)C)CCC(=O)OC(C)(C)C)C=C1)=O IUNNATUFXICVNU-GOSISDBHSA-N 0.000 description 5
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
• 230000006870 function Effects 0.000 description 5
• 239000001963 growth medium Substances 0.000 description 5
• 230000004410 intraocular pressure Effects 0.000 description 5
• 150000003951 lactams Chemical group 0.000 description 5
• 150000002632 lipids Chemical class 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 239000011159 matrix material Substances 0.000 description 5
• IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 5
• HQGPKMSGXAUKHT-SCSAIBSYSA-N methyl (2r)-5-oxopyrrolidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCC(=O)N1 HQGPKMSGXAUKHT-SCSAIBSYSA-N 0.000 description 5
• HKTGGDULWDLYKQ-UHFFFAOYSA-N methyl 4-(2-oxoethyl)benzoate Chemical compound COC(=O)C1=CC=C(CC=O)C=C1 HKTGGDULWDLYKQ-UHFFFAOYSA-N 0.000 description 5
• XTHVSPVWRPWTCO-LLVKDONJSA-N methyl 7-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](CO)CCC1=O XTHVSPVWRPWTCO-LLVKDONJSA-N 0.000 description 5
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 238000006772 olefination reaction Methods 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
• ODHCTXKNWHHXJC-GSVOUGTGSA-N 5-oxo-D-proline Chemical compound OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 239000004215 Carbon black (E152) Substances 0.000 description 4
• 238000010485 C−C bond formation reaction Methods 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• NIWUMFULEUZEOT-UHFFFAOYSA-N O=P1OOO1 Chemical class O=P1OOO1 NIWUMFULEUZEOT-UHFFFAOYSA-N 0.000 description 4
• 102000008866 Prostaglandin E receptors Human genes 0.000 description 4
• 108010088540 Prostaglandin E receptors Proteins 0.000 description 4
• FAAKVWMYORXJKN-UHFFFAOYSA-N acetic acid;heptane;propan-2-one Chemical compound CC(C)=O.CC(O)=O.CCCCCCC FAAKVWMYORXJKN-UHFFFAOYSA-N 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 235000010443 alginic acid Nutrition 0.000 description 4
• 229920000615 alginic acid Polymers 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 238000000576 coating method Methods 0.000 description 4
• TZJSVFTWRHFSEN-MRXNPFEDSA-N ditert-butyl (2r)-2-[3-(5-methoxycarbonylthiophen-2-yl)prop-2-ynylamino]pentanedioate Chemical compound COC(=O)C1=CC=C(C#CCN[C@H](CCC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)S1 TZJSVFTWRHFSEN-MRXNPFEDSA-N 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 150000002430 hydrocarbons Chemical class 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• 238000011534 incubation Methods 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• 230000011164 ossification Effects 0.000 description 4
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
• 239000008177 pharmaceutical agent Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 229910000104 sodium hydride Inorganic materials 0.000 description 4
• 241000894007 species Species 0.000 description 4
• 230000000638 stimulation Effects 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
• HOBJEFOCIRXQKH-SCSAIBSYSA-N (5r)-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@H]1CCC(=O)N1 HOBJEFOCIRXQKH-SCSAIBSYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• HQNZZNBOVHKOPR-UHFFFAOYSA-N 1-dimethoxyphosphoryl-4-phenylbut-3-yn-2-one Chemical compound COP(=O)(OC)CC(=O)C#CC1=CC=CC=C1 HQNZZNBOVHKOPR-UHFFFAOYSA-N 0.000 description 3
• BGLHWTIZOGWJQR-UHFFFAOYSA-N 1-dimethoxyphosphorylnon-5-yn-2-one Chemical compound CCCC#CCCC(=O)CP(=O)(OC)OC BGLHWTIZOGWJQR-UHFFFAOYSA-N 0.000 description 3
• KREMNNSMJHRMMU-UHFFFAOYSA-N 1-dimethoxyphosphoryloct-5-yn-2-one Chemical compound CCC#CCCC(=O)CP(=O)(OC)OC KREMNNSMJHRMMU-UHFFFAOYSA-N 0.000 description 3
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
• 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 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 229920001817 Agar Polymers 0.000 description 3
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• 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 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 3
• 229910020667 PBr3 Inorganic materials 0.000 description 3
• 208000002193 Pain Diseases 0.000 description 3
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
• 102000015433 Prostaglandin Receptors Human genes 0.000 description 3
• 108010050183 Prostaglandin Receptors Proteins 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 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 3
• 229930006000 Sucrose Natural products 0.000 description 3
• UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 235000010419 agar Nutrition 0.000 description 3
• 125000003342 alkenyl group Chemical group 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 125000002947 alkylene group Chemical group 0.000 description 3
• 239000005557 antagonist Substances 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 3
• 238000006664 bond formation reaction Methods 0.000 description 3
• 150000001649 bromium compounds Chemical class 0.000 description 3
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000011248 coating agent Substances 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 239000007819 coupling partner Substances 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• YVMXASZMVGXHRQ-UHFFFAOYSA-N diethyl 2-but-2-ynylpropanedioate Chemical compound CCOC(=O)C(CC#CC)C(=O)OCC YVMXASZMVGXHRQ-UHFFFAOYSA-N 0.000 description 3
• CAMKJDNOGYICRO-UHFFFAOYSA-N diethyl 2-hex-2-ynylpropanedioate Chemical compound CCCC#CCC(C(=O)OCC)C(=O)OCC CAMKJDNOGYICRO-UHFFFAOYSA-N 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 239000003995 emulsifying agent Substances 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 230000032050 esterification Effects 0.000 description 3
• 238000005886 esterification reaction Methods 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• JFCQEDHGNNZCLN-UHFFFAOYSA-L glutarate(2-) Chemical compound [O-]C(=O)CCCC([O-])=O JFCQEDHGNNZCLN-UHFFFAOYSA-L 0.000 description 3
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 150000002690 malonic acid derivatives Chemical class 0.000 description 3
• APXOMRFLJBRHNX-UHFFFAOYSA-N methyl 2-[4-(bromomethyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CBr)C=C1 APXOMRFLJBRHNX-UHFFFAOYSA-N 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 150000003904 phospholipids Chemical class 0.000 description 3
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 3
• 230000035479 physiological effects, processes and functions Effects 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
• 229960004063 propylene glycol Drugs 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 230000008439 repair process Effects 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 125000006413 ring segment Chemical group 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 239000012047 saturated solution Substances 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 239000007909 solid dosage form Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 235000011149 sulphuric acid Nutrition 0.000 description 3
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 230000008733 trauma Effects 0.000 description 3
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
• 239000000080 wetting agent Substances 0.000 description 3
• 239000008096 xylene Substances 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• MJGBOFOZSAEULI-NRYLJRBGSA-N (2R)-5-oxopyrrolidine-2-carboxylic acid Chemical compound N1[C@H](CCC1=O)C(=O)O.O=C1CC[C@@H](N1)C(=O)O MJGBOFOZSAEULI-NRYLJRBGSA-N 0.000 description 2
• VWEMTNDGVRHRAJ-HIFRSBDPSA-N (2R)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylhept-4-ynamide Chemical compound OC[C@@H](C1=CC=CC=C1)NC([C@@H](CC#CCC)C)=O VWEMTNDGVRHRAJ-HIFRSBDPSA-N 0.000 description 2
• JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
• HOBJEFOCIRXQKH-BYPYZUCNSA-N (5s)-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@@H]1CCC(=O)N1 HOBJEFOCIRXQKH-BYPYZUCNSA-N 0.000 description 2
• GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 2
• PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 2
• VIXOOIRHFJMNBT-UHFFFAOYSA-N 1-bromohex-2-yne Chemical compound CCCC#CCBr VIXOOIRHFJMNBT-UHFFFAOYSA-N 0.000 description 2
• VDHGRVFJBGRHMD-UHFFFAOYSA-N 1-bromopent-2-yne Chemical compound CCC#CCBr VDHGRVFJBGRHMD-UHFFFAOYSA-N 0.000 description 2
• QZWVLYCFBGIJME-UHFFFAOYSA-N 1-dimethoxyphosphorylhex-3-yn-2-one Chemical compound CCC#CC(=O)CP(=O)(OC)OC QZWVLYCFBGIJME-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
• JRIIYTZWUDBBIA-UHFFFAOYSA-N 2-methylhept-4-ynoic acid Chemical compound CCC#CCC(C)C(O)=O JRIIYTZWUDBBIA-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
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• RRELDGDKULRRDM-UHFFFAOYSA-N 6-[2-chloro-4-nitro-5-(oxan-4-yloxy)anilino]-3,4-dihydro-1H-quinolin-2-one Chemical compound [O-][N+](=O)c1cc(Cl)c(Nc2ccc3NC(=O)CCc3c2)cc1OC1CCOCC1 RRELDGDKULRRDM-UHFFFAOYSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• 229940122361 Bisphosphonate Drugs 0.000 description 2
• 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 2
• 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-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
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 238000005750 Corey-Bakshi-Shibata reduction reaction Methods 0.000 description 2
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 238000012286 ELISA Assay Methods 0.000 description 2
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
• UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
• 241000206672 Gelidium 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
• 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 2
• 101710082112 Hematopoietic prostaglandin D synthase Proteins 0.000 description 2
• 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 2
• 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
• 208000029725 Metabolic bone disease Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 101100521345 Mus musculus Prop1 gene Proteins 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 108700017836 Prophet of Pit-1 Proteins 0.000 description 2
• 108090000748 Prostaglandin-E Synthases Proteins 0.000 description 2
• 102100033279 Prostaglandin-H2 D-isomerase Human genes 0.000 description 2
• 101710145576 Prostaglandin-H2 D-isomerase Proteins 0.000 description 2
• 208000008765 Sciatica Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 241001447056 Uristes Species 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 125000004450 alkenylene group Chemical group 0.000 description 2
• 150000001350 alkyl halides Chemical class 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 125000004419 alkynylene group Chemical group 0.000 description 2
• 208000026935 allergic disease Diseases 0.000 description 2
• 229960000711 alprostadil Drugs 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
• 229920002988 biodegradable polymer Polymers 0.000 description 2
• 239000004621 biodegradable polymer Substances 0.000 description 2
• 230000036983 biotransformation Effects 0.000 description 2
• 150000004663 bisphosphonates Chemical class 0.000 description 2
• 230000008468 bone growth Effects 0.000 description 2
• 230000010072 bone remodeling Effects 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 238000013375 chromatographic separation Methods 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 235000012343 cottonseed oil Nutrition 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000002354 daily effect Effects 0.000 description 2
• 230000003111 delayed effect Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
• 229940038472 dicalcium phosphate Drugs 0.000 description 2
• FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 2
• UPQZOUHVTJNGFK-UHFFFAOYSA-N diethyl 2-methylpropanedioate Chemical compound CCOC(=O)C(C)C(=O)OCC UPQZOUHVTJNGFK-UHFFFAOYSA-N 0.000 description 2
• HOBAELRKJCKHQD-QNEBEIHSSA-N dihomo-γ-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCCCC(O)=O HOBAELRKJCKHQD-QNEBEIHSSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• KAKKHKRHCKCAGH-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate;hexahydrate Chemical compound O.O.O.O.O.O.[Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 KAKKHKRHCKCAGH-UHFFFAOYSA-L 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 230000004406 elevated intraocular pressure Effects 0.000 description 2
• 230000001804 emulsifying effect Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 2
• 229960001123 epoprostenol Drugs 0.000 description 2
• MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
• 229940093471 ethyl oleate Drugs 0.000 description 2
• 230000003203 everyday effect Effects 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• AEDIXYWIVPYNBI-UHFFFAOYSA-N heptanamide Chemical compound CCCCCCC(N)=O AEDIXYWIVPYNBI-UHFFFAOYSA-N 0.000 description 2
• 230000028993 immune response Effects 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 238000006317 isomerization reaction Methods 0.000 description 2
• 239000000787 lecithin Substances 0.000 description 2
• 235000010445 lecithin Nutrition 0.000 description 2
• 239000008297 liquid dosage form Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 238000004020 luminiscence type Methods 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 201000001119 neuropathy Diseases 0.000 description 2
• 230000007823 neuropathy Effects 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 230000000269 nucleophilic effect Effects 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 235000008390 olive oil Nutrition 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 238000006053 organic reaction Methods 0.000 description 2
• PFGVNLZDWRZPJW-OPAMFIHVSA-N otamixaban Chemical compound C([C@@H](C(=O)OC)[C@@H](C)NC(=O)C=1C=CC(=CC=1)C=1C=C[N+]([O-])=CC=1)C1=CC=CC(C(N)=N)=C1 PFGVNLZDWRZPJW-OPAMFIHVSA-N 0.000 description 2
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
• 101150032584 oxy-4 gene Proteins 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
• 239000002304 perfume Substances 0.000 description 2
• 208000033808 peripheral neuropathy Diseases 0.000 description 2
• 102000013415 peroxidase activity proteins Human genes 0.000 description 2
• 108040007629 peroxidase activity proteins Proteins 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000000047 product Substances 0.000 description 2
• BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 2
• GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 2
• SGUKUZOVHSFKPH-YNNPMVKQSA-N prostaglandin G2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](OO)CCCCC)[C@H]2C\C=C/CCCC(O)=O SGUKUZOVHSFKPH-YNNPMVKQSA-N 0.000 description 2
• BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 2
• 229940127293 prostanoid Drugs 0.000 description 2
• 150000003814 prostanoids Chemical class 0.000 description 2
• 230000004224 protection Effects 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 description 2
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
• 235000009518 sodium iodide Nutrition 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• 230000004797 therapeutic response Effects 0.000 description 2
• DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 229940078499 tricalcium phosphate Drugs 0.000 description 2
• 229910000391 tricalcium phosphate Inorganic materials 0.000 description 2
• 206010044652 trigeminal neuralgia Diseases 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• VWEMTNDGVRHRAJ-ZFWWWQNUSA-N (2s)-n-[(1r)-2-hydroxy-1-phenylethyl]-2-methylhept-4-ynamide Chemical compound CCC#CC[C@H](C)C(=O)N[C@@H](CO)C1=CC=CC=C1 VWEMTNDGVRHRAJ-ZFWWWQNUSA-N 0.000 description 1
• HOBAELRKJCKHQD-UHFFFAOYSA-N (8Z,11Z,14Z)-8,11,14-eicosatrienoic acid Natural products CCCCCC=CCC=CCC=CCCCCCCC(O)=O HOBAELRKJCKHQD-UHFFFAOYSA-N 0.000 description 1
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
• UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
• 229930182837 (R)-adrenaline Natural products 0.000 description 1
• NWIUTZDMDHAVTP-KRWDZBQOSA-N (S)-betaxolol Chemical compound C1=CC(OC[C@@H](O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-KRWDZBQOSA-N 0.000 description 1
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
• ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
• TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-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
• FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 229940058015 1,3-butylene glycol Drugs 0.000 description 1
• IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
• ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
• FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
• WOVLKKLXYZJMSN-UHFFFAOYSA-N 1-Hydroxy-2-pentanone Chemical group CCCC(=O)CO WOVLKKLXYZJMSN-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 1
• MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
• CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
• JPJOOTWNILDNAW-UHFFFAOYSA-N 1-cyclobutylethanone Chemical compound CC(=O)C1CCC1 JPJOOTWNILDNAW-UHFFFAOYSA-N 0.000 description 1
• LKENTYLPIUIMFG-UHFFFAOYSA-N 1-cyclopentylethanone Chemical compound CC(=O)C1CCCC1 LKENTYLPIUIMFG-UHFFFAOYSA-N 0.000 description 1
• HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 1
• PBHSTEUBJVZASU-UHFFFAOYSA-N 1-hydroxypyrrolidine-2,5-dione;2-methylhept-4-ynoic acid Chemical compound ON1C(=O)CCC1=O.CCC#CCC(C)C(O)=O PBHSTEUBJVZASU-UHFFFAOYSA-N 0.000 description 1
• WQHMXROXEJWWGS-UHFFFAOYSA-N 1-oxaspiro[3.4]octane Chemical compound O1CCC11CCCC1 WQHMXROXEJWWGS-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
• 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
• 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 1
• IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 description 1
• QLVGHFBUSGYCCG-UHFFFAOYSA-N 2-amino-n-(1-cyano-2-phenylethyl)acetamide Chemical compound NCC(=O)NC(C#N)CC1=CC=CC=C1 QLVGHFBUSGYCCG-UHFFFAOYSA-N 0.000 description 1
• UPSXAPQYNGXVBF-UHFFFAOYSA-N 2-bromobutane Chemical compound CCC(C)Br UPSXAPQYNGXVBF-UHFFFAOYSA-N 0.000 description 1
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• ZTTWQKYKGNLCCA-UHFFFAOYSA-N 2-methyl-10H-thieno[2,3-b][1,5]benzodiazepin-4-amine Chemical compound N1C2=CC=CC=C2N=C(N)C2=C1SC(C)=C2 ZTTWQKYKGNLCCA-UHFFFAOYSA-N 0.000 description 1
• 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• AVCRTLPJHCGTJM-UHFFFAOYSA-N 2-methylhept-4-ynoyl chloride Chemical compound CCC#CCC(C)C(Cl)=O AVCRTLPJHCGTJM-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 1
• 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• HOBJEFOCIRXQKH-UHFFFAOYSA-N 5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OCC1CCC(=O)N1 HOBJEFOCIRXQKH-UHFFFAOYSA-N 0.000 description 1
• COWZPSUDTMGBAT-UHFFFAOYSA-N 5-bromothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)S1 COWZPSUDTMGBAT-UHFFFAOYSA-N 0.000 description 1
• 125000006043 5-hexenyl group Chemical group 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• 108091006112 ATPases Proteins 0.000 description 1
• 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
• XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 235000003276 Apios tuberosa Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
• 229910015845 BBr3 Inorganic materials 0.000 description 1
• 108010049951 Bone Morphogenetic Protein 3 Proteins 0.000 description 1
• 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 1
• 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 1
• 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
• 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
• 102100024504 Bone morphogenetic protein 3 Human genes 0.000 description 1
• 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 1
• 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
• 102000055006 Calcitonin Human genes 0.000 description 1
• 108060001064 Calcitonin Proteins 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 229940122156 Cathepsin K inhibitor Drugs 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
• GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 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
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
• 206010013774 Dry eye Diseases 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 239000004606 Fillers/Extenders Substances 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 241001539176 Hime Species 0.000 description 1
• 101000979284 Homo sapiens Protein kinase C-binding protein NELL1 Proteins 0.000 description 1
• 101000711796 Homo sapiens Sclerostin Proteins 0.000 description 1
• 241001546602 Horismenus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 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 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 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
• 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
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• 208000001344 Macular Edema Diseases 0.000 description 1
• 206010025415 Macular oedema Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• 238000007126 N-alkylation reaction Methods 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 206010030043 Ocular hypertension Diseases 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 241000906034 Orthops Species 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 238000003527 Peterson olefination reaction Methods 0.000 description 1
• 102000015439 Phospholipases Human genes 0.000 description 1
• 108010064785 Phospholipases Proteins 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920000954 Polyglycolide Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102100033076 Prostaglandin E synthase Human genes 0.000 description 1
• 102100023068 Protein kinase C-binding protein NELL1 Human genes 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• 102000014128 RANK Ligand Human genes 0.000 description 1
• 108010025832 RANK Ligand Proteins 0.000 description 1
• 235000004443 Ricinus communis Nutrition 0.000 description 1
• QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
• 235000019485 Safflower oil Nutrition 0.000 description 1
• 102100034201 Sclerostin Human genes 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• SSZBUIDZHHWXNJ-UHFFFAOYSA-N Stearinsaeure-hexadecylester Natural products CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 239000000150 Sympathomimetic Substances 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 229930003316 Vitamin D Natural products 0.000 description 1
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
• 238000007239 Wittig reaction Methods 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
• 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
• BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
• CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003655 absorption accelerator Substances 0.000 description 1
• 229960000571 acetazolamide Drugs 0.000 description 1
• BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• LWXXXTJCPXKWJU-UHFFFAOYSA-N acetic acid;ethanol;heptane Chemical compound CCO.CC(O)=O.CCCCCCC LWXXXTJCPXKWJU-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 239000000674 adrenergic antagonist Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 125000003158 alcohol group Chemical group 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• DCSBSVSZJRSITC-UHFFFAOYSA-M alendronate sodium trihydrate Chemical compound O.O.O.[Na+].NCCCC(O)(P(O)(O)=O)P(O)([O-])=O DCSBSVSZJRSITC-UHFFFAOYSA-M 0.000 description 1
• 229960004343 alendronic acid Drugs 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000001347 alkyl bromides Chemical class 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 150000001351 alkyl iodides Chemical class 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical group BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 239000003263 anabolic agent Substances 0.000 description 1
• 229940124325 anabolic agent Drugs 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 239000003098 androgen Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• IEJXVRYNEISIKR-UHFFFAOYSA-N apraclonidine Chemical compound ClC1=CC(N)=CC(Cl)=C1NC1=NCCN1 IEJXVRYNEISIKR-UHFFFAOYSA-N 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 229940114079 arachidonic acid Drugs 0.000 description 1
• 235000021342 arachidonic acid Nutrition 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• AXMNGEUJXLXFRY-UHFFFAOYSA-N azaspirodecane Chemical compound C1CCCC21CCNCC2 AXMNGEUJXLXFRY-UHFFFAOYSA-N 0.000 description 1
• 125000003725 azepanyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 125000004069 aziridinyl group Chemical group 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
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 229960002903 benzyl benzoate Drugs 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• NWIUTZDMDHAVTP-UHFFFAOYSA-N betaxolol Chemical compound C1=CC(OCC(O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-UHFFFAOYSA-N 0.000 description 1
• 229960004324 betaxolol Drugs 0.000 description 1
• BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 230000001851 biosynthetic effect Effects 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 230000037182 bone density Effects 0.000 description 1
• 230000010478 bone regeneration Effects 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• 208000029028 brain injury Diseases 0.000 description 1
• 229960003679 brimonidine Drugs 0.000 description 1
• HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 1
• 229960000722 brinzolamide Drugs 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• 235000019437 butane-1,3-diol Nutrition 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 238000013262 cAMP assay Methods 0.000 description 1
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
• 229960004015 calcitonin Drugs 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 238000004364 calculation method 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
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
• 229960001222 carteolol Drugs 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 239000006143 cell culture medium Substances 0.000 description 1
• 230000009134 cell regulation Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 239000004927 clay Substances 0.000 description 1
• 229960002896 clonidine Drugs 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000000515 collagen sponge Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 229940125796 compound 3d Drugs 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000013078 crystal Substances 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
• 230000001086 cytosolic effect Effects 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 125000002704 decyl group Chemical group [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])* 0.000 description 1
• 238000007257 deesterification reaction Methods 0.000 description 1
• 229960001251 denosumab Drugs 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 125000005959 diazepanyl group Chemical group 0.000 description 1
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• OFRFGNSZCYDFOH-UHFFFAOYSA-N diethyl 2-(2-methylpropyl)propanedioate Chemical compound CCOC(=O)C(CC(C)C)C(=O)OCC OFRFGNSZCYDFOH-UHFFFAOYSA-N 0.000 description 1
• MIIZSUOEOUHAIZ-UHFFFAOYSA-N diethyl 2-butan-2-ylpropanedioate Chemical compound CCOC(=O)C(C(C)CC)C(=O)OCC MIIZSUOEOUHAIZ-UHFFFAOYSA-N 0.000 description 1
• RPNFNBGRHCUORR-UHFFFAOYSA-N diethyl 2-butylpropanedioate Chemical compound CCCCC(C(=O)OCC)C(=O)OCC RPNFNBGRHCUORR-UHFFFAOYSA-N 0.000 description 1
• VQAZCUCWHIIFGE-UHFFFAOYSA-N diethyl 2-ethylpropanedioate Chemical compound CCOC(=O)C(CC)C(=O)OCC VQAZCUCWHIIFGE-UHFFFAOYSA-N 0.000 description 1
• BYQFBFWERHXONI-UHFFFAOYSA-N diethyl 2-propan-2-ylpropanedioate Chemical compound CCOC(=O)C(C(C)C)C(=O)OCC BYQFBFWERHXONI-UHFFFAOYSA-N 0.000 description 1
• GRRSDGHTSMJICM-UHFFFAOYSA-N diethyl 2-propylpropanedioate Chemical compound CCOC(=O)C(CCC)C(=O)OCC GRRSDGHTSMJICM-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 230000001079 digestive effect Effects 0.000 description 1
• 229940043279 diisopropylamine Drugs 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
• 230000003292 diminished effect Effects 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 125000003438 dodecyl group Chemical group [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])* 0.000 description 1
• IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 description 1
• 229960003933 dorzolamide Drugs 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 229960002866 duloxetine Drugs 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 150000002066 eicosanoids Chemical class 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 230000007071 enzymatic hydrolysis Effects 0.000 description 1
• 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
• 229960005139 epinephrine Drugs 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 239000002834 estrogen receptor modulator Substances 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• ACJOYTKWHPEIHW-UHFFFAOYSA-N ethyl 3-phenylprop-2-ynoate Chemical compound CCOC(=O)C#CC1=CC=CC=C1 ACJOYTKWHPEIHW-UHFFFAOYSA-N 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• XDPRPKSTFBPPHU-UHFFFAOYSA-N ethyl pent-2-ynoate Chemical compound CCOC(=O)C#CCC XDPRPKSTFBPPHU-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 239000003885 eye ointment Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 230000035558 fertility Effects 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229960002870 gabapentin Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000000262 haloalkenyl group Chemical group 0.000 description 1
• 125000000232 haloalkynyl group Chemical group 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• MHGHBWVIEFLKBM-UHFFFAOYSA-N hept-5-ynoic acid Chemical compound CC#CCCCC(O)=O MHGHBWVIEFLKBM-UHFFFAOYSA-N 0.000 description 1
• YSZJHIGBFXADDH-UHFFFAOYSA-N heptane;propan-1-ol Chemical compound CCCO.CCCCCCC YSZJHIGBFXADDH-UHFFFAOYSA-N 0.000 description 1
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000003018 immunoassay Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 229940095437 iopidine Drugs 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000005969 isothiazolinyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 125000003971 isoxazolinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 229960001848 lamotrigine Drugs 0.000 description 1
• PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
• GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
• 229960001160 latanoprost Drugs 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229960004771 levobetaxolol Drugs 0.000 description 1
• IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
• 229960000831 levobunolol Drugs 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 239000004973 liquid crystal related substance Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 201000010230 macular retinal edema Diseases 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
• 239000000347 magnesium hydroxide Substances 0.000 description 1
• 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 1
• 229960004083 methazolamide Drugs 0.000 description 1
• FEIOASZZURHTHB-UHFFFAOYSA-N methyl 4-formylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 1
• DEOQEDOOGBWQOS-IHWYPQMZSA-N methyl 5-[(z)-3-hydroxyprop-1-enyl]thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(\C=C/CO)S1 DEOQEDOOGBWQOS-IHWYPQMZSA-N 0.000 description 1
• QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-UHFFFAOYSA-N 0.000 description 1
• ADZJUEIWBIXMNS-YSSOQSIOSA-N methyl 7-[(2r)-2-(1-ethoxyethoxymethyl)-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCOC(C)OC[C@H]1CCC(=O)N1CCCCCCC(=O)OC ADZJUEIWBIXMNS-YSSOQSIOSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 239000004570 mortar (masonry) Substances 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• APBBAQCENVXUHL-UHFFFAOYSA-N n,n-diethylethanamine;2,2,2-trifluoroacetic acid Chemical compound CCN(CC)CC.OC(=O)C(F)(F)F APBBAQCENVXUHL-UHFFFAOYSA-N 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000004007 neuromodulation Effects 0.000 description 1
• 230000004112 neuroprotection Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 229940078552 o-xylene Drugs 0.000 description 1
• OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
• 229940041678 oral spray Drugs 0.000 description 1
• 239000000668 oral spray Substances 0.000 description 1
• 150000002895 organic esters Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 238000010883 osseointegration Methods 0.000 description 1
• 210000002997 osteoclast Anatomy 0.000 description 1
• 125000005963 oxadiazolidinyl group Chemical group 0.000 description 1
• 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000005968 oxazolinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• SEVSMVUOKAMPDO-UHFFFAOYSA-N para-Acetoxybenzaldehyde Natural products CC(=O)OC1=CC=C(C=O)C=C1 SEVSMVUOKAMPDO-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 239000000734 parasympathomimetic agent Substances 0.000 description 1
• 239000004031 partial agonist Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 150000002978 peroxides Chemical group 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 150000008105 phosphatidylcholines Chemical class 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 229960001416 pilocarpine Drugs 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• GECKOGCXJZVPTI-UHFFFAOYSA-L potassium sodium hydrogen sulfate chloride hydrate Chemical compound O.[Na+].[Cl-].[K+].OS([O-])(=O)=O GECKOGCXJZVPTI-UHFFFAOYSA-L 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
• 229960001233 pregabalin Drugs 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 108010014374 puros Proteins 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 150000004040 pyrrolidinones Chemical class 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• 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 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 238000003653 radioligand binding assay Methods 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000004648 relaxation of smooth muscle Effects 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 230000008327 renal blood flow Effects 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 239000003340 retarding agent Substances 0.000 description 1
• 238000007142 ring opening reaction Methods 0.000 description 1
• 235000005713 safflower oil Nutrition 0.000 description 1
• 239000003813 safflower oil Substances 0.000 description 1
• 150000003333 secondary alcohols Chemical class 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 239000000849 selective androgen receptor modulator Substances 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000011343 solid material Substances 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 238000013223 sprague-dawley female rat Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 238000011916 stereoselective reduction Methods 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 230000002483 superagonistic effect Effects 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 229940127230 sympathomimetic drug Drugs 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 238000003419 tautomerization reaction Methods 0.000 description 1
• JTSBKTDXCWCPCK-OAHLLOKOSA-N tert-butyl (2r)-1-[2-(4-methoxycarbonylphenyl)ethyl]-5-oxopyrrolidine-2-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CC[C@@H]1C(=O)OC(C)(C)C JTSBKTDXCWCPCK-OAHLLOKOSA-N 0.000 description 1
• MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 description 1
• MLGCXEBRWGEOQX-UHFFFAOYSA-N tetradifon Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl MLGCXEBRWGEOQX-UHFFFAOYSA-N 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
• 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 150000003595 thromboxanes Chemical class 0.000 description 1
• 229960004605 timolol Drugs 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000001890 transfection Methods 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000001052 transient effect Effects 0.000 description 1
• MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 1
• 229960002368 travoprost Drugs 0.000 description 1
• 125000005270 trialkylamine group Chemical group 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 235000019731 tricalcium phosphate Nutrition 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• KPZSTOVTJYRDIO-UHFFFAOYSA-K trichlorocerium;heptahydrate Chemical compound O.O.O.O.O.O.O.Cl[Ce](Cl)Cl KPZSTOVTJYRDIO-UHFFFAOYSA-K 0.000 description 1
• BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005455 trithianyl group Chemical group 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• TVHAZVBUYQMHBC-SNHXEXRGSA-N unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O TVHAZVBUYQMHBC-SNHXEXRGSA-N 0.000 description 1
• 229960004317 unoprostone Drugs 0.000 description 1
• 230000001457 vasomotor Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 235000019166 vitamin D Nutrition 0.000 description 1
• 239000011710 vitamin D Substances 0.000 description 1
• 150000003710 vitamin D derivatives Chemical class 0.000 description 1
• MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
• 229940046008 vitamin d Drugs 0.000 description 1
• 239000011800 void material Substances 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1