JP2016527006A5 - - Google Patents
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- JP2016527006A5 JP2016527006A5 JP2016527117A JP2016527117A JP2016527006A5 JP 2016527006 A5 JP2016527006 A5 JP 2016527006A5 JP 2016527117 A JP2016527117 A JP 2016527117A JP 2016527117 A JP2016527117 A JP 2016527117A JP 2016527006 A5 JP2016527006 A5 JP 2016527006A5
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- bone
- methyl
- oxopyrrolidin
- difluoro
- Prior art date
- 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
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- 210000000988 bone and bone Anatomy 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 87
- 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 claims description 43
- 239000003795 chemical substances by application Substances 0.000 claims description 39
- 239000001506 calcium phosphate Substances 0.000 claims description 27
- 239000003814 drug Substances 0.000 claims description 25
- 229910000389 calcium phosphate Inorganic materials 0.000 claims description 23
- 235000011010 calcium phosphates Nutrition 0.000 claims description 23
- 239000004568 cement Substances 0.000 claims description 23
- 210000002805 bone matrix Anatomy 0.000 claims description 22
- 229940079593 drug Drugs 0.000 claims description 20
- 239000000556 agonist Substances 0.000 claims description 14
- 210000000963 osteoblast Anatomy 0.000 claims description 9
- 210000002997 osteoclast Anatomy 0.000 claims description 9
- 239000000919 ceramic Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims description 6
- 229940122361 Bisphosphonate Drugs 0.000 claims description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 5
- 102000003982 Parathyroid hormone Human genes 0.000 claims description 5
- 108090000445 Parathyroid hormone Proteins 0.000 claims description 5
- 150000004663 bisphosphonates Chemical class 0.000 claims description 5
- 230000037182 bone density Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000002834 estrogen receptor modulator Substances 0.000 claims description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 5
- 239000000199 parathyroid hormone Substances 0.000 claims description 5
- 229960001319 parathyroid hormone Drugs 0.000 claims description 5
- 239000000849 selective androgen receptor modulator Substances 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 229940079488 strontium ranelate Drugs 0.000 claims description 5
- 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 4
- 239000000515 collagen sponge Substances 0.000 claims description 4
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 claims description 4
- 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 4
- 229940038472 dicalcium phosphate Drugs 0.000 claims description 4
- 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 3
- 229940121819 ATPase inhibitor Drugs 0.000 claims description 3
- 102000015735 Beta-catenin Human genes 0.000 claims description 3
- 108060000903 Beta-catenin Proteins 0.000 claims description 3
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 claims description 3
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 claims description 3
- 229940122156 Cathepsin K inhibitor Drugs 0.000 claims description 3
- 108010047852 Integrin alphaVbeta3 Proteins 0.000 claims description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 3
- 102000014128 RANK Ligand Human genes 0.000 claims description 3
- 108010025832 RANK Ligand Proteins 0.000 claims description 3
- 229930003316 Vitamin D Natural products 0.000 claims description 3
- 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 claims description 3
- 239000012190 activator Substances 0.000 claims description 3
- 239000000362 adenosine triphosphatase inhibitor Substances 0.000 claims description 3
- 229960000711 alprostadil Drugs 0.000 claims description 3
- 239000003098 androgen Substances 0.000 claims description 3
- 210000002449 bone cell Anatomy 0.000 claims description 3
- 229940112869 bone morphogenetic protein Drugs 0.000 claims description 3
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 3
- 229960001467 bortezomib Drugs 0.000 claims description 3
- 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 claims description 3
- 229960002986 dinoprostone Drugs 0.000 claims description 3
- 229940125542 dual agonist Drugs 0.000 claims description 3
- 229940011871 estrogen Drugs 0.000 claims description 3
- 239000000262 estrogen Substances 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 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 claims description 3
- 229940044551 receptor antagonist Drugs 0.000 claims description 3
- 239000002464 receptor antagonist Substances 0.000 claims description 3
- 230000011664 signaling Effects 0.000 claims description 3
- 235000019166 vitamin D Nutrition 0.000 claims description 3
- 239000011710 vitamin D Substances 0.000 claims description 3
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 3
- 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 claims description 3
- 229940046008 vitamin d Drugs 0.000 claims description 3
- 230000007547 defect Effects 0.000 claims description 2
- XXUZFRDUEGQHOV-UHFFFAOYSA-J strontium ranelate Chemical compound [Sr+2].[Sr+2].[O-]C(=O)CN(CC([O-])=O)C=1SC(C([O-])=O)=C(CC([O-])=O)C=1C#N XXUZFRDUEGQHOV-UHFFFAOYSA-J 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 174
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 154
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 90
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 64
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 52
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 50
- 239000005711 Benzoic acid Substances 0.000 description 34
- 125000000217 alkyl group Chemical group 0.000 description 34
- 235000010233 benzoic acid Nutrition 0.000 description 34
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 32
- -1 2-((R) -3,3-difluoro-5-((S, E) -3-hydroxyoct-1-en-1-yl) -2-oxopyrrolidin-1-yl) ethyl Chemical group 0.000 description 24
- 229910052799 carbon Inorganic materials 0.000 description 20
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 20
- 229910052739 hydrogen Inorganic materials 0.000 description 18
- 125000003545 alkoxy group Chemical group 0.000 description 14
- 125000001188 haloalkyl group Chemical group 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 125000004438 haloalkoxy group Chemical group 0.000 description 10
- 229910052736 halogen Inorganic materials 0.000 description 10
- 150000002367 halogens Chemical class 0.000 description 10
- 239000002253 acid Substances 0.000 description 8
- 125000004450 alkenylene group Chemical group 0.000 description 8
- 125000002947 alkylene group Chemical group 0.000 description 8
- 125000004419 alkynylene group Chemical group 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000002260 anti-inflammatory agent Substances 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000000262 haloalkenyl group Chemical group 0.000 description 4
- 125000000232 haloalkynyl group Chemical group 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- KVJIIORUFXGTFN-UHFFFAOYSA-L strontium;5-[bis(carboxymethyl)amino]-3-(carboxymethyl)-4-cyanothiophene-2-carboxylate Chemical compound [Sr+2].OC(=O)CN(CC(O)=O)C=1SC(C([O-])=O)=C(CC(O)=O)C=1C#N.OC(=O)CN(CC(O)=O)C=1SC(C([O-])=O)=C(CC(O)=O)C=1C#N KVJIIORUFXGTFN-UHFFFAOYSA-L 0.000 description 4
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 4
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 4
- 229960004276 zoledronic acid Drugs 0.000 description 4
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
- HZIMMLOLVHSVMP-FYBNUODKSA-N (5R)-3,3-difluoro-1-heptyl-5-[(E,3R)-3-hydroxy-7-phenylhept-1-enyl]pyrrolidin-2-one Chemical compound FC1(C(N([C@H](C1)\C=C\[C@@H](CCCCC1=CC=CC=C1)O)CCCCCCC)=O)F HZIMMLOLVHSVMP-FYBNUODKSA-N 0.000 description 2
- HZIMMLOLVHSVMP-IRAQTCESSA-N (5R)-3,3-difluoro-1-heptyl-5-[(E,3S)-3-hydroxy-7-phenylhept-1-enyl]pyrrolidin-2-one Chemical compound FC1(C(N([C@H](C1)\C=C\[C@H](CCCCC1=CC=CC=C1)O)CCCCCCC)=O)F HZIMMLOLVHSVMP-IRAQTCESSA-N 0.000 description 2
- MVCFMJVPAKMEFL-WFJXPABVSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCC[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 MVCFMJVPAKMEFL-WFJXPABVSA-N 0.000 description 2
- BMBNIHYSJNFUPW-PNVKXUSSSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound C([C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCC=1C=CC(=CC=1)C(O)=O)CCCC1=CC=CC=C1 BMBNIHYSJNFUPW-PNVKXUSSSA-N 0.000 description 2
- MVCFMJVPAKMEFL-QTYXSNHHSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 MVCFMJVPAKMEFL-QTYXSNHHSA-N 0.000 description 2
- AWMIWDCKBUKDKJ-XGRPXUFSSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCC=1C=CC(=CC=1)C(O)=O)CCC1=CC=CC=C1 AWMIWDCKBUKDKJ-XGRPXUFSSA-N 0.000 description 2
- PLPPXVWLEPOTQM-KNUMWTCJSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyloct-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 PLPPXVWLEPOTQM-KNUMWTCJSA-N 0.000 description 2
- UFEKCCMQUIWXBK-UXBVXSMZSA-N 5-[3-[(2R)-2-[(E,3R)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound O[C@@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)C(CCCC1=CC=CC=C1)C UFEKCCMQUIWXBK-UXBVXSMZSA-N 0.000 description 2
- ZXECFDRPIPRVFB-GWCPOKRPSA-N 5-[3-[(2r)-2-[(e,3r,4r)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-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)CC1=CC=CC=C1 ZXECFDRPIPRVFB-GWCPOKRPSA-N 0.000 description 2
- ATRZOBDJGRNPEF-YFZNZOHDSA-N 5-[3-[(2r)-2-[(e,3r,4r)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-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)CCCC1=CC=CC=C1 ATRZOBDJGRNPEF-YFZNZOHDSA-N 0.000 description 2
- ZXECFDRPIPRVFB-BLRXGEEQSA-N 5-[3-[(2r)-2-[(e,3r,4s)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-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)CC1=CC=CC=C1 ZXECFDRPIPRVFB-BLRXGEEQSA-N 0.000 description 2
- ATRZOBDJGRNPEF-JXKHCBOESA-N 5-[3-[(2r)-2-[(e,3r,4s)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-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)CCCC1=CC=CC=C1 ATRZOBDJGRNPEF-JXKHCBOESA-N 0.000 description 2
- CRUNFNWPSSJCFB-FPQZKKRFSA-N 5-[3-[(2r)-2-[(e,3r,4s)-3-hydroxy-4-methyl-9-phenylnon-1-enyl]-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)CCCCC1=CC=CC=C1 CRUNFNWPSSJCFB-FPQZKKRFSA-N 0.000 description 2
- ZCCXWUVQGLSWPS-WSGGTOGVSA-N 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound CC([C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CC#CC=1SC(=CC=1)C(O)=O)CCCC1=CC=CC=C1 ZCCXWUVQGLSWPS-WSGGTOGVSA-N 0.000 description 2
- UFEKCCMQUIWXBK-WSGGTOGVSA-N 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CC([C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCC=1SC(=CC=1)C(O)=O)CCCC1=CC=CC=C1 UFEKCCMQUIWXBK-WSGGTOGVSA-N 0.000 description 2
- UFEKCCMQUIWXBK-URCWZONMSA-N 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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)CCC1=CC=CC=C1 UFEKCCMQUIWXBK-URCWZONMSA-N 0.000 description 2
- ATRZOBDJGRNPEF-FWILWFKNSA-N 5-[3-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-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)CCCC1=CC=CC=C1 ATRZOBDJGRNPEF-FWILWFKNSA-N 0.000 description 2
- ZXECFDRPIPRVFB-DPLGJEHESA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-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)CC1=CC=CC=C1 ZXECFDRPIPRVFB-DPLGJEHESA-N 0.000 description 2
- UFEKCCMQUIWXBK-KVVBJZIMSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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)CCC1=CC=CC=C1 UFEKCCMQUIWXBK-KVVBJZIMSA-N 0.000 description 2
- ATRZOBDJGRNPEF-IJTXGDDHSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-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)CCCC1=CC=CC=C1 ATRZOBDJGRNPEF-IJTXGDDHSA-N 0.000 description 2
- CRUNFNWPSSJCFB-QKIYNVSWSA-N 5-[3-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-9-phenylnon-1-enyl]-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)CCCCC1=CC=CC=C1 CRUNFNWPSSJCFB-QKIYNVSWSA-N 0.000 description 2
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| US9657052B2 (en) | 2014-12-09 | 2017-05-23 | Warsaw Orthopedic, Inc. | Compounds and methods of making sterols using diols |
| WO2016196925A1 (en) * | 2015-06-04 | 2016-12-08 | The Regents Of The University Of California | Composition for bone and methods of making and using the same |
| CN105012995B (zh) * | 2015-06-04 | 2018-03-09 | 武汉维斯第医用科技股份有限公司 | 一种含促骨愈合药物的胶原蛋白海绵及其制备方法 |
| US10632230B2 (en) | 2015-07-10 | 2020-04-28 | Warsaw Orthopedic, Inc. | Implants having a high drug load of an oxysterol and methods of use |
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-
2014
- 2014-07-18 AU AU2014290512A patent/AU2014290512A1/en not_active Abandoned
- 2014-07-18 JP JP2016527117A patent/JP2016527006A/ja active Pending
- 2014-07-18 CN CN201480039423.2A patent/CN105392505A/zh active Pending
- 2014-07-18 WO PCT/US2014/047138 patent/WO2015009991A2/en not_active Ceased
- 2014-07-18 EP EP14750837.8A patent/EP3021879A2/en not_active Withdrawn
- 2014-07-18 US US14/905,663 patent/US10729810B2/en active Active
- 2014-07-18 KR KR1020167001059A patent/KR20160048054A/ko not_active Withdrawn
- 2014-07-18 CA CA2910398A patent/CA2910398A1/en not_active Abandoned
-
2015
- 2015-12-22 PH PH12015502854A patent/PH12015502854A1/en unknown
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