CA2910398A1 - Methods, systems, and compositions for promoting bone growth - Google Patents

Info

Publication number

CA2910398A1

CA2910398A1 CA2910398A CA2910398A CA2910398A1 CA 2910398 A1 CA2910398 A1 CA 2910398A1 CA 2910398 A CA2910398 A CA 2910398A CA 2910398 A CA2910398 A CA 2910398A CA 2910398 A1 CA2910398 A1 CA 2910398A1

Authority

CA

Canada

Prior art keywords

oxopyrrolidin

hydroxy

methyl

difluoro

thiophene

Prior art date

2013-07-19

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000000203 mixture Substances 0.000 title claims abstract description 285
• 238000000034 method Methods 0.000 title claims description 92
• 230000008468 bone growth Effects 0.000 title description 9
• 230000001737 promoting effect Effects 0.000 title description 7
• 210000000988 bone and bone Anatomy 0.000 claims abstract description 225
• 239000003814 drug Substances 0.000 claims abstract description 198
• 239000001506 calcium phosphate Substances 0.000 claims abstract description 82
• 239000004568 cement Substances 0.000 claims abstract description 78
• 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 abstract description 54
• 210000002805 bone matrix Anatomy 0.000 claims abstract description 50
• 229910000389 calcium phosphate Inorganic materials 0.000 claims abstract description 50
• 235000011010 calcium phosphates Nutrition 0.000 claims abstract description 50
• 230000007547 defect Effects 0.000 claims abstract description 30
• 230000008439 repair process Effects 0.000 claims abstract description 25
• 208000002193 Pain Diseases 0.000 claims abstract description 19
• 239000000515 collagen sponge Substances 0.000 claims abstract description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 193
• 229940079593 drug Drugs 0.000 claims description 185
• 150000001875 compounds Chemical class 0.000 claims description 181
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 164
• -1 C1-C3haloalkyl Chemical group 0.000 claims description 155
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 118
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 94
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 86
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 77
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 76
• QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 claims description 57
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 52
• 125000003118 aryl group Chemical group 0.000 claims description 43
• 125000001424 substituent group Chemical group 0.000 claims description 43
• 239000000556 agonist Substances 0.000 claims description 42
• 239000007787 solid Substances 0.000 claims description 41
• 239000003112 inhibitor Substances 0.000 claims description 38
• 229910052736 halogen Inorganic materials 0.000 claims description 36
• 150000002367 halogens Chemical group 0.000 claims description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 35
• 125000001153 fluoro group Chemical group F* 0.000 claims description 35
• 239000005711 Benzoic acid Substances 0.000 claims description 33
• 235000010233 benzoic acid Nutrition 0.000 claims description 33
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 32
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 32
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
• 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 30
• 210000002997 osteoclast Anatomy 0.000 claims description 30
• 229910000391 tricalcium phosphate Inorganic materials 0.000 claims description 29
• 229940078499 tricalcium phosphate Drugs 0.000 claims description 29
• 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 claims description 28
• 150000003839 salts Chemical class 0.000 claims description 28
• 229910052799 carbon Inorganic materials 0.000 claims description 27
• 239000001257 hydrogen Substances 0.000 claims description 26
• 230000008569 process Effects 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 23
• 125000001072 heteroaryl group Chemical group 0.000 claims description 21
• 230000001965 increasing effect Effects 0.000 claims description 21
• 239000003937 drug carrier Substances 0.000 claims description 20
• 229910052588 hydroxylapatite Inorganic materials 0.000 claims description 20
• 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 20
• 210000000963 osteoblast Anatomy 0.000 claims description 19
• 239000000919 ceramic Substances 0.000 claims description 18
• 125000000623 heterocyclic group Chemical group 0.000 claims description 18
• 229940122361 Bisphosphonate Drugs 0.000 claims description 16
• 150000004663 bisphosphonates Chemical class 0.000 claims description 16
• 229940079488 strontium ranelate Drugs 0.000 claims description 14
• 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 claims description 14
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
• 239000004599 antimicrobial Substances 0.000 claims description 13
• 239000002246 antineoplastic agent Substances 0.000 claims description 13
• 239000002834 estrogen receptor modulator Substances 0.000 claims description 13
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 12
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 12
• 230000000921 morphogenic effect Effects 0.000 claims description 12
• 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 12
• XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims description 12
• 229960004276 zoledronic acid Drugs 0.000 claims description 12
• 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims description 10
• 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 10
• 230000037182 bone density Effects 0.000 claims description 10
• 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 10
• 229960002986 dinoprostone Drugs 0.000 claims description 10
• 102000055006 Calcitonin Human genes 0.000 claims description 9
• 108060001064 Calcitonin Proteins 0.000 claims description 9
• 102000003982 Parathyroid hormone Human genes 0.000 claims description 9
• 108090000445 Parathyroid hormone Proteins 0.000 claims description 9
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 9
• 229960004015 calcitonin Drugs 0.000 claims description 9
• 229960001319 parathyroid hormone Drugs 0.000 claims description 9
• 239000000199 parathyroid hormone Substances 0.000 claims description 9
• 229940125542 dual agonist Drugs 0.000 claims description 8
• 239000000849 selective androgen receptor modulator Substances 0.000 claims description 8
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
• 108091006112 ATPases Proteins 0.000 claims description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 7
• 102000057290 Adenosine Triphosphatases Human genes 0.000 claims description 7
• OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 7
• 102000014128 RANK Ligand Human genes 0.000 claims description 7
• 108010025832 RANK Ligand Proteins 0.000 claims description 7
• FBQUXLIJKPWCAO-AZIFJQEOSA-N Rivenprost Chemical compound COCC1=CC=CC(C[C@H](O)\C=C\[C@@H]2[C@H](C(=O)C[C@H]2O)CCSCCCC(=O)OC)=C1 FBQUXLIJKPWCAO-AZIFJQEOSA-N 0.000 claims description 7
• 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 claims description 7
• 229960004343 alendronic acid Drugs 0.000 claims description 7
• 229940011871 estrogen Drugs 0.000 claims description 7
• 239000000262 estrogen Substances 0.000 claims description 7
• 229940009626 etidronate Drugs 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• 229940044551 receptor antagonist Drugs 0.000 claims description 7
• 239000002464 receptor antagonist Substances 0.000 claims description 7
• 229940122156 Cathepsin K inhibitor Drugs 0.000 claims description 6
• DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims description 6
• MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims description 6
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 6
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 6
• IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims description 6
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 6
• DKJJVAGXPKPDRL-UHFFFAOYSA-N Tiludronic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)SC1=CC=C(Cl)C=C1 DKJJVAGXPKPDRL-UHFFFAOYSA-N 0.000 claims description 6
• 229930003316 Vitamin D Natural products 0.000 claims description 6
• 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 6
• UGEPSJNLORCRBO-UHFFFAOYSA-N [3-(dimethylamino)-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound CN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O UGEPSJNLORCRBO-UHFFFAOYSA-N 0.000 claims description 6
• 239000003098 androgen Substances 0.000 claims description 6
• 229960000817 bazedoxifene Drugs 0.000 claims description 6
• UCJGJABZCDBEDK-UHFFFAOYSA-N bazedoxifene Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UCJGJABZCDBEDK-UHFFFAOYSA-N 0.000 claims description 6
• 229940015872 ibandronate Drugs 0.000 claims description 6
• GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 claims description 6
• 229960002367 lasofoxifene Drugs 0.000 claims description 6
• PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 claims description 6
• 229950010733 neridronic acid Drugs 0.000 claims description 6
• WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 6
• 229940046231 pamidronate Drugs 0.000 claims description 6
• 102000004169 proteins and genes Human genes 0.000 claims description 6
• 108090000623 proteins and genes Proteins 0.000 claims description 6
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 6
• 229960004622 raloxifene Drugs 0.000 claims description 6
• 229940089617 risedronate Drugs 0.000 claims description 6
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 6
• 229960002855 simvastatin Drugs 0.000 claims description 6
• 229940019375 tiludronate Drugs 0.000 claims description 6
• 235000019166 vitamin D Nutrition 0.000 claims description 6
• 239000011710 vitamin D Substances 0.000 claims description 6
• 150000003710 vitamin D derivatives Chemical class 0.000 claims description 6
• 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 6
• 229940046008 vitamin d Drugs 0.000 claims description 6
• 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 claims description 5
• WPTLQOYLIXWRNN-SLKVGHROSA-N (5r)-5-[(e,3r)-4,4-difluoro-3-hydroxy-4-phenylbut-1-enyl]-1-[6-(2h-tetrazol-5-yl)hexyl]pyrrolidin-2-one Chemical compound C([C@@H]1/C=C/[C@@H](O)C(F)(F)C=2C=CC=CC=2)CC(=O)N1CCCCCCC=1N=NNN=1 WPTLQOYLIXWRNN-SLKVGHROSA-N 0.000 claims description 5
• XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 5
• XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 5
• PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 5
• TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 5
• AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims description 5
• 239000012190 activator Substances 0.000 claims description 5
• 229960005370 atorvastatin Drugs 0.000 claims description 5
• 229960005110 cerivastatin Drugs 0.000 claims description 5
• SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 5
• 229960003765 fluvastatin Drugs 0.000 claims description 5
• 229960004844 lovastatin Drugs 0.000 claims description 5
• PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 5
• QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 5
• AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 5
• 229950009116 mevastatin Drugs 0.000 claims description 5
• BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 5
• 229960002965 pravastatin Drugs 0.000 claims description 5
• TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 5
• 229960000672 rosuvastatin Drugs 0.000 claims description 5
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 5
• 230000011664 signaling Effects 0.000 claims description 5
• FWIVDMJALNEADT-SFTDATJTSA-N (2s)-n-(1-cyanocyclopropyl)-4-fluoro-4-methyl-2-[[(1s)-2,2,2-trifluoro-1-[4-(4-methylsulfonylphenyl)phenyl]ethyl]amino]pentanamide Chemical compound C1=CC([C@H](N[C@@H](CC(C)(F)C)C(=O)NC2(CC2)C#N)C(F)(F)F)=CC=C1C1=CC=C(S(C)(=O)=O)C=C1 FWIVDMJALNEADT-SFTDATJTSA-N 0.000 claims description 4
• JYZXGURJKNAFPT-ZWKOTPCHSA-N 5-[3-[(2s)-2-[(3r)-3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@@H]1CC[C@@H](O)CC=2C=C(C=CC=2)C(F)(F)F)CC(=O)N1CCCC1=CC=C(C(O)=O)S1 JYZXGURJKNAFPT-ZWKOTPCHSA-N 0.000 claims description 4
• 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 4
• 229960001467 bortezomib Drugs 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
• 238000003780 insertion Methods 0.000 claims description 4
• 230000037431 insertion Effects 0.000 claims description 4
• 229950009755 odanacatib Drugs 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
• 235000019739 Dicalciumphosphate Nutrition 0.000 claims description 3
• 229960000711 alprostadil Drugs 0.000 claims description 3
• 229910000390 dicalcium phosphate Inorganic materials 0.000 claims description 3
• 229940038472 dicalcium phosphate Drugs 0.000 claims description 3
• 238000001556 precipitation Methods 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
• MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 claims 15
• WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 claims 13
• WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 claims 9
• 229910052760 oxygen Inorganic materials 0.000 claims 4
• 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims 4
• DTMCXOOEGYTRCO-WSGGTOGVSA-N 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-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)CC#CC1=CC=CC=C1 DTMCXOOEGYTRCO-WSGGTOGVSA-N 0.000 claims 3
• ZECQOPFVRSEFGC-QFVHRSDDSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CC1=CC=CC=C1 ZECQOPFVRSEFGC-QFVHRSDDSA-N 0.000 claims 3
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
• SPQQXPMTGNWAOR-MKRWDCGMSA-N 4-[2-[(2r)-2-[(e,3r)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC#CCC(C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 SPQQXPMTGNWAOR-MKRWDCGMSA-N 0.000 claims 2
• NOYNLOFBPYBSKQ-HWMFFEOQSA-N 4-[2-[(2r)-2-[(e,3r,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-HWMFFEOQSA-N 0.000 claims 2
• SPQQXPMTGNWAOR-MDLHZHKYSA-N 4-[2-[(2r)-2-[(e,3s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC#CCC(C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 SPQQXPMTGNWAOR-MDLHZHKYSA-N 0.000 claims 2
• 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 2
• NXJWISYZCAYZPY-YVVIOCEBSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 NXJWISYZCAYZPY-YVVIOCEBSA-N 0.000 claims 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 claims 2
• CQOSGTHOLIIXJE-PNVKXUSSSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxy-7-phenylhept-1-en-6-ynyl]-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)CC#CC1=CC=CC=C1 CQOSGTHOLIIXJE-PNVKXUSSSA-N 0.000 claims 2
• WYMVUOQRJZKZQA-DSJWGCTQSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxydec-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC#CCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 WYMVUOQRJZKZQA-DSJWGCTQSA-N 0.000 claims 2
• WMAIQOKKOVCLDZ-JUFISIKESA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxynon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCC#CCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 WMAIQOKKOVCLDZ-JUFISIKESA-N 0.000 claims 2
• ZVAZYAPXMXOPPN-QTYXSNHHSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CC#CCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 ZVAZYAPXMXOPPN-QTYXSNHHSA-N 0.000 claims 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 claims 2
• NXJWISYZCAYZPY-IUHIUDCESA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 NXJWISYZCAYZPY-IUHIUDCESA-N 0.000 claims 2
• DRSOGYFAOXZDJI-XGRPXUFSSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-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)C#CC1=CC=CC=C1 DRSOGYFAOXZDJI-XGRPXUFSSA-N 0.000 claims 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 claims 2
• QRQRHHPAUOQXPB-DIINUUSZSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 QRQRHHPAUOQXPB-DIINUUSZSA-N 0.000 claims 2
• NXJWISYZCAYZPY-XOWFKELMSA-N 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(O)=O)C=C1 NXJWISYZCAYZPY-XOWFKELMSA-N 0.000 claims 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 claims 2
• ZCCXWUVQGLSWPS-UXBVXSMZSA-N 5-[3-[(2R)-2-[(E,3R)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound O[C@@H](/C=C/[C@@H]1N(C(CC1)=O)CC#CC1=CC=C(S1)C(=O)O)C(CCCC1=CC=CC=C1)C ZCCXWUVQGLSWPS-UXBVXSMZSA-N 0.000 claims 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 claims 2
• DTMCXOOEGYTRCO-UXBVXSMZSA-N 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-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)CC#CC1=CC=CC=C1 DTMCXOOEGYTRCO-UXBVXSMZSA-N 0.000 claims 2
• YITXTUJDWOPLOM-ZNIBZUMBSA-N 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 YITXTUJDWOPLOM-ZNIBZUMBSA-N 0.000 claims 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 claims 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 claims 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 claims 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 claims 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 claims 2
• LJBQBOYAUOOSLH-CCJZRUHMSA-N 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound CCC#CCC(C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(O)=O)S1 LJBQBOYAUOOSLH-CCJZRUHMSA-N 0.000 claims 2
• YITXTUJDWOPLOM-CCJZRUHMSA-N 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CCC(C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(O)=O)S1 YITXTUJDWOPLOM-CCJZRUHMSA-N 0.000 claims 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 claims 2
• 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 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 claims 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 claims 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 claims 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 claims 2
• UMYXRXWDPHAKGZ-IRBBKKBFSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 UMYXRXWDPHAKGZ-IRBBKKBFSA-N 0.000 claims 2
• QCQZBSOBEKMLKJ-MATWNZDUSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCCCC[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 QCQZBSOBEKMLKJ-MATWNZDUSA-N 0.000 claims 2
• JMHMEEBPWHFLBX-AQLJEJBYSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-5-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)C1=CC=CC=C1 JMHMEEBPWHFLBX-AQLJEJBYSA-N 0.000 claims 2
• UXQWNSWYEJSWBM-DYRIQIPYSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCC1=CC=CC=C1 UXQWNSWYEJSWBM-DYRIQIPYSA-N 0.000 claims 2
• WQNDXGHRPMQDFT-BQMVMUGMSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCCC1=CC=CC=C1 WQNDXGHRPMQDFT-BQMVMUGMSA-N 0.000 claims 2
• AGGYHZMNJSBHQQ-VDRBLYDVSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-9-phenylnon-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCCCC1=CC=CC=C1 AGGYHZMNJSBHQQ-VDRBLYDVSA-N 0.000 claims 2
• WHBBPUSLNFAUJV-MRMWBXJDSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@@H]1/C=C/[C@@H](O)[C@@H](C)C=2C=CC=CC=2)C(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 WHBBPUSLNFAUJV-MRMWBXJDSA-N 0.000 claims 2
• FDEGVJDOMNZRNB-DSJWGCTQSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxy-7-phenylhept-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CC#CC1=CC=CC=C1 FDEGVJDOMNZRNB-DSJWGCTQSA-N 0.000 claims 2
• WPSRTHQPEZSMSP-DSJWGCTQSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCCC1=CC=CC=C1 WPSRTHQPEZSMSP-DSJWGCTQSA-N 0.000 claims 2
• ARNNZUVXJVDGJW-JJGIJDNGSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CC#CCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 ARNNZUVXJVDGJW-JJGIJDNGSA-N 0.000 claims 2
• UMYXRXWDPHAKGZ-YWDXQQJVSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 UMYXRXWDPHAKGZ-YWDXQQJVSA-N 0.000 claims 2
• UXQWNSWYEJSWBM-GJWBGHMGSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCC1=CC=CC=C1 UXQWNSWYEJSWBM-GJWBGHMGSA-N 0.000 claims 2
• WQNDXGHRPMQDFT-LKLUEYJESA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCCC1=CC=CC=C1 WQNDXGHRPMQDFT-LKLUEYJESA-N 0.000 claims 2
• AGGYHZMNJSBHQQ-WWTZYMIRSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-9-phenylnon-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCCCC1=CC=CC=C1 AGGYHZMNJSBHQQ-WWTZYMIRSA-N 0.000 claims 2
• UMYXRXWDPHAKGZ-XLJJWPCRSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 UMYXRXWDPHAKGZ-XLJJWPCRSA-N 0.000 claims 2
• KYVPVSMNVVVAAD-OTSVUREYSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 KYVPVSMNVVVAAD-OTSVUREYSA-N 0.000 claims 2
• SXKFGUFPKNABIY-OTSVUREYSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyloct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCCC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 SXKFGUFPKNABIY-OTSVUREYSA-N 0.000 claims 2
• WHBBPUSLNFAUJV-HXIYYJMWSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@@H]1/C=C/[C@H](O)[C@@H](C)C=2C=CC=CC=2)C(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 WHBBPUSLNFAUJV-HXIYYJMWSA-N 0.000 claims 2
• GWWAGJDSDSCGLK-RCZSKKKRSA-N 5-[3-[(5s)-3,3-difluoro-5-[(3r,4s)-3-hydroxy-4-methyl-7-phenylheptyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)CC[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CCC1=CC=CC=C1 GWWAGJDSDSCGLK-RCZSKKKRSA-N 0.000 claims 2
• DEQPIOBZNPCKJE-GLDDHKADSA-N 7-[(2R)-2-[(E,3S)-3-hydroxy-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C(/[C@@H](O)CCCCc1ccccc1)=C\[C@@H]1N(CCCCCCC(O)=O)C(=O)CC1 DEQPIOBZNPCKJE-GLDDHKADSA-N 0.000 claims 2
• CHLXVWPOHSBADP-KMMAFYGUSA-N 7-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC([C@@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)CCCC1=CC=CC=C1 CHLXVWPOHSBADP-KMMAFYGUSA-N 0.000 claims 2
• TYKCTEYDUIYVJB-BYZSIXFTSA-N 7-[(2r)-2-[(e,3r)-3-hydroxy-5-phenylpent-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C(/[C@@H](O)C#CC=1C=CC=CC=1)=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O TYKCTEYDUIYVJB-BYZSIXFTSA-N 0.000 claims 2
• IQWSFXPFHDYOFM-AEKMKHNFSA-N 7-[(2r)-2-[(e,3r)-3-hydroxy-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)CC#CC1=CC=CC=C1 IQWSFXPFHDYOFM-AEKMKHNFSA-N 0.000 claims 2
• DEQPIOBZNPCKJE-AEKMKHNFSA-N 7-[(2r)-2-[(e,3r)-3-hydroxy-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)CCCC1=CC=CC=C1 DEQPIOBZNPCKJE-AEKMKHNFSA-N 0.000 claims 2
• DBZBLAFPTDAAPH-VMNGNHSPSA-N 7-[(2r)-2-[(e,3r)-3-hydroxyhept-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#C[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O DBZBLAFPTDAAPH-VMNGNHSPSA-N 0.000 claims 2
• CHLXVWPOHSBADP-IQXLGDAYSA-N 7-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC([C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)CCCC1=CC=CC=C1 CHLXVWPOHSBADP-IQXLGDAYSA-N 0.000 claims 2
• TYKCTEYDUIYVJB-DQEWXYAXSA-N 7-[(2r)-2-[(e,3s)-3-hydroxy-5-phenylpent-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C(/[C@H](O)C#CC=1C=CC=CC=1)=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O TYKCTEYDUIYVJB-DQEWXYAXSA-N 0.000 claims 2
• IQWSFXPFHDYOFM-GLDDHKADSA-N 7-[(2r)-2-[(e,3s)-3-hydroxy-7-phenylhept-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@H](O)\C=C\[C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)CC#CC1=CC=CC=C1 IQWSFXPFHDYOFM-GLDDHKADSA-N 0.000 claims 2
• DBZBLAFPTDAAPH-AOOXPWSASA-N 7-[(2r)-2-[(e,3s)-3-hydroxyhept-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#C[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(O)=O DBZBLAFPTDAAPH-AOOXPWSASA-N 0.000 claims 2
• CHLXVWPOHSBADP-GUPMMHBCSA-N 7-[(2r)-2-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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)CCC1=CC=CC=C1 CHLXVWPOHSBADP-GUPMMHBCSA-N 0.000 claims 2
• 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 2
• 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 2
• CHLXVWPOHSBADP-FXDNMFHBSA-N 7-[(2r)-2-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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)CCC1=CC=CC=C1 CHLXVWPOHSBADP-FXDNMFHBSA-N 0.000 claims 2
• 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 2
• UJPIOOJJAAMYNA-HSFNZESZSA-N 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC([C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCCCCC(O)=O)CCCC1=CC=CC=C1 UJPIOOJJAAMYNA-HSFNZESZSA-N 0.000 claims 2
• BBUZBTBHUCTEBZ-RJCGUJTNSA-N 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCCCCC(O)=O)CCCC1=CC=CC=C1 BBUZBTBHUCTEBZ-RJCGUJTNSA-N 0.000 claims 2
• PWZMQIUUWBQDQW-HMUVLFPJSA-N 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCCCC[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O PWZMQIUUWBQDQW-HMUVLFPJSA-N 0.000 claims 2
• KWEXZQZQGLFDSE-OAEJALACSA-N 7-[(5r)-3,3-difluoro-5-[(e,3r,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC#CC[C@@H](C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O KWEXZQZQGLFDSE-OAEJALACSA-N 0.000 claims 2
• ZSUOOBFOIDLLEI-LPJXYHDHSA-N 7-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@H](C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O ZSUOOBFOIDLLEI-LPJXYHDHSA-N 0.000 claims 2
• KWEXZQZQGLFDSE-ZCKSSPOOSA-N 7-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC#CC[C@H](C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O KWEXZQZQGLFDSE-ZCKSSPOOSA-N 0.000 claims 2
• UJPIOOJJAAMYNA-YNLQGXKESA-N 7-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCCCCC(O)=O)CCC1=CC=CC=C1 UJPIOOJJAAMYNA-YNLQGXKESA-N 0.000 claims 2
• KWEXZQZQGLFDSE-PHAHAWKESA-N 7-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O KWEXZQZQGLFDSE-PHAHAWKESA-N 0.000 claims 2
• UJPIOOJJAAMYNA-ZFBSANRWSA-N 7-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCCCCC(O)=O)CCC1=CC=CC=C1 UJPIOOJJAAMYNA-ZFBSANRWSA-N 0.000 claims 2
• ZSUOOBFOIDLLEI-GPVXIOJZSA-N 7-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O ZSUOOBFOIDLLEI-GPVXIOJZSA-N 0.000 claims 2
• KWEXZQZQGLFDSE-PMCDXHSFSA-N 7-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O KWEXZQZQGLFDSE-PMCDXHSFSA-N 0.000 claims 2
• SWGQLJZBNBPGMK-UJRRBIKXSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)CCC#CC1=CC=CC=C1 Chemical compound O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCCCCC(=O)OC)CCC#CC1=CC=CC=C1 SWGQLJZBNBPGMK-UJRRBIKXSA-N 0.000 claims 2
• 101710151715 Protein 7 Proteins 0.000 claims 2
• DAJAZGMSWQEQIQ-BPZODPGYSA-N ethyl 4-[2-[(2R)-2-[(E,3S,4S)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound c1cc(C(=O)OCC)ccc1CCN1[C@@H](\C=C\[C@@H](O)[C@@H](C)CC#CCC)CCC1=O DAJAZGMSWQEQIQ-BPZODPGYSA-N 0.000 claims 2
• DAJAZGMSWQEQIQ-LRCPYKSLSA-N ethyl 4-[2-[(2r)-2-[(e,3r,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CCN1C(=O)CC[C@@H]1\C=C\[C@H](O)[C@@H](C)CC#CCC DAJAZGMSWQEQIQ-LRCPYKSLSA-N 0.000 claims 2
• DPIIPICOSBDYFN-JMQOMVKFSA-N methyl 4-[2-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(=O)OC)C=C1 DPIIPICOSBDYFN-JMQOMVKFSA-N 0.000 claims 2
• WOUCGIVTGQFWSE-FUTHQCHMSA-N methyl 4-[2-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound CCCCC[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(=O)OC)C=C1 WOUCGIVTGQFWSE-FUTHQCHMSA-N 0.000 claims 2
• WOUCGIVTGQFWSE-JUFISIKESA-N methyl 4-[2-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound CCCCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(=O)OC)C=C1 WOUCGIVTGQFWSE-JUFISIKESA-N 0.000 claims 2
• DPIIPICOSBDYFN-MPRFVXRBSA-N methyl 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(=O)OC)C=C1 DPIIPICOSBDYFN-MPRFVXRBSA-N 0.000 claims 2
• MPQNGSFETCOJTQ-CMGJWZOBSA-N methyl 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-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(C)CC#CC1=CC=CC=C1 MPQNGSFETCOJTQ-CMGJWZOBSA-N 0.000 claims 2
• ROBDZQUCFGAGKN-CMGJWZOBSA-N methyl 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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(C)CCCC1=CC=CC=C1 ROBDZQUCFGAGKN-CMGJWZOBSA-N 0.000 claims 2
• LWTJYNJWUFYPPE-CMGJWZOBSA-N methyl 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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(C)CCCC1=CC=CC=C1 LWTJYNJWUFYPPE-CMGJWZOBSA-N 0.000 claims 2
• VMFROVKJYQMOJO-TYXBMBSUSA-N methyl 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylate Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(=O)OC)S1 VMFROVKJYQMOJO-TYXBMBSUSA-N 0.000 claims 2
• AVZCAQNCYODQHK-TYXBMBSUSA-N methyl 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCC1=CC=C(C(=O)OC)S1 AVZCAQNCYODQHK-TYXBMBSUSA-N 0.000 claims 2
• ROBDZQUCFGAGKN-ALWTYZOZSA-N methyl 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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(C)CCCC1=CC=CC=C1 ROBDZQUCFGAGKN-ALWTYZOZSA-N 0.000 claims 2
• LWTJYNJWUFYPPE-ALWTYZOZSA-N methyl 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-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(C)CCCC1=CC=CC=C1 LWTJYNJWUFYPPE-ALWTYZOZSA-N 0.000 claims 2
• VMFROVKJYQMOJO-KIEQSATHSA-N methyl 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylate Chemical compound CCC#CCC(C)[C@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(=O)OC)S1 VMFROVKJYQMOJO-KIEQSATHSA-N 0.000 claims 2
• BCRHPIFEIDKGNM-CUWPLCDZSA-N methyl 5-[3-[(5R)-3,3-difluoro-5-[(E,3R,4S)-3-hydroxy-4-methyl-5-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound FC1(C(N([C@H](C1)C=C[C@@H]([C@H](CC1=CC=CC=C1)C)O)CCCC1=CC=C(S1)C(=O)OC)=O)F BCRHPIFEIDKGNM-CUWPLCDZSA-N 0.000 claims 2
• VFBYHYHGZSKRPG-XKGZKEIXSA-N methyl 5-[3-[(5R)-3,3-difluoro-5-[(E,3R,4S)-3-hydroxy-4-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound FC1(C(N([C@H](C1)C=C[C@H]([C@@H](C)C1=CC=CC=C1)O)CCCC1=CC=C(S1)C(=O)OC)=O)F VFBYHYHGZSKRPG-XKGZKEIXSA-N 0.000 claims 2
• MBEOOVLGUZLPHP-MLUCLSGHSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(=O)OC)S1 MBEOOVLGUZLPHP-MLUCLSGHSA-N 0.000 claims 2
• JETIPLMXLYZJNV-DMGQIGSTSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCCCC[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(=O)OC)S1 JETIPLMXLYZJNV-DMGQIGSTSA-N 0.000 claims 2
• ZRZLHROEQSMNNK-DYRIQIPYSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@H](O)[C@@H](C)CCC1=CC=CC=C1 ZRZLHROEQSMNNK-DYRIQIPYSA-N 0.000 claims 2
• YDVKBTDHNPLJJJ-BQMVMUGMSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@H](O)[C@@H](C)CCCC1=CC=CC=C1 YDVKBTDHNPLJJJ-BQMVMUGMSA-N 0.000 claims 2
• MMODYAGSYAJBBK-VDRBLYDVSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@H](O)[C@@H](C)CCCCC1=CC=CC=C1 MMODYAGSYAJBBK-VDRBLYDVSA-N 0.000 claims 2
• HYPYDNCMSFBYIH-MHOAMULCSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-9-phenylnon-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@H](O)[C@@H](C)CCCCCC1=CC=CC=C1 HYPYDNCMSFBYIH-MHOAMULCSA-N 0.000 claims 2
• JETIPLMXLYZJNV-IGXNXKSNSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCCCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(=O)OC)S1 JETIPLMXLYZJNV-IGXNXKSNSA-N 0.000 claims 2
• MBEOOVLGUZLPHP-OUHUKIOISA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCC#CC[C@@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(=O)OC)S1 MBEOOVLGUZLPHP-OUHUKIOISA-N 0.000 claims 2
• BCRHPIFEIDKGNM-YAZIDRQLSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-5-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@@H](O)[C@@H](C)CC1=CC=CC=C1 BCRHPIFEIDKGNM-YAZIDRQLSA-N 0.000 claims 2
• YDVKBTDHNPLJJJ-LKLUEYJESA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@@H](O)[C@@H](C)CCCC1=CC=CC=C1 YDVKBTDHNPLJJJ-LKLUEYJESA-N 0.000 claims 2
• MMODYAGSYAJBBK-WWTZYMIRSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-8-phenyloct-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@@H](O)[C@@H](C)CCCCC1=CC=CC=C1 MMODYAGSYAJBBK-WWTZYMIRSA-N 0.000 claims 2
• HYPYDNCMSFBYIH-SGVVGXDWSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-9-phenylnon-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@@H](O)[C@@H](C)CCCCCC1=CC=CC=C1 HYPYDNCMSFBYIH-SGVVGXDWSA-N 0.000 claims 2
• MBEOOVLGUZLPHP-OFQUAYIFSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(=O)OC)S1 MBEOOVLGUZLPHP-OFQUAYIFSA-N 0.000 claims 2
• VFBYHYHGZSKRPG-WDKHOGGPSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@H](O)[C@@H](C)C1=CC=CC=C1 VFBYHYHGZSKRPG-WDKHOGGPSA-N 0.000 claims 2
• BGSLXPGZDJWFFO-MBJQPMTPSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@H](O)C(C)CCCC1=CC=CC=C1 BGSLXPGZDJWFFO-MBJQPMTPSA-N 0.000 claims 2
• FQZRFQJEZXKHFT-KKYFPJMOSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-5-phenylpent-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)C#CC1=CC=CC=C1 FQZRFQJEZXKHFT-KKYFPJMOSA-N 0.000 claims 2
• SWGQLJZBNBPGMK-WEBCQVJHSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-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)CCC#CC1=CC=CC=C1 SWGQLJZBNBPGMK-WEBCQVJHSA-N 0.000 claims 2
• UGTJQNGHJLCAMK-WEBCQVJHSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxy-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@H](O)CCCCC1=CC=CC=C1 UGTJQNGHJLCAMK-WEBCQVJHSA-N 0.000 claims 2
• CXIGEXSAEJROJI-NSNJOPQOSA-N methyl 7-[(2r)-2-[(e,3r)-3-hydroxyhept-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#C[C@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC CXIGEXSAEJROJI-NSNJOPQOSA-N 0.000 claims 2
• 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 2
• BGSLXPGZDJWFFO-HECPXKJDSA-N methyl 7-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)C(C)CCCC1=CC=CC=C1 BGSLXPGZDJWFFO-HECPXKJDSA-N 0.000 claims 2
• FCFQGZGDLMMISZ-PKPZZJCKSA-N methyl 7-[(2r)-2-[(e,3s)-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(C)CC#CC)CCC1=O FCFQGZGDLMMISZ-PKPZZJCKSA-N 0.000 claims 2
• FQZRFQJEZXKHFT-IJQABYDPSA-N methyl 7-[(2r)-2-[(e,3s)-3-hydroxy-5-phenylpent-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@H](O)C#CC1=CC=CC=C1 FQZRFQJEZXKHFT-IJQABYDPSA-N 0.000 claims 2
• UGTJQNGHJLCAMK-UJRRBIKXSA-N methyl 7-[(2r)-2-[(e,3s)-3-hydroxy-7-phenylhept-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)CCCCC1=CC=CC=C1 UGTJQNGHJLCAMK-UJRRBIKXSA-N 0.000 claims 2
• CXIGEXSAEJROJI-KORIGIIASA-N methyl 7-[(2r)-2-[(e,3s)-3-hydroxyhept-1-en-4-ynyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#C[C@@H](O)\C=C\[C@H]1CCC(=O)N1CCCCCCC(=O)OC CXIGEXSAEJROJI-KORIGIIASA-N 0.000 claims 2
• 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 2
• AHIJGACYLCKNAD-TYTHLOSQSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\C(O)C(C)CC#CC1=CC=CC=C1 AHIJGACYLCKNAD-TYTHLOSQSA-N 0.000 claims 2
• FSZQXOIHLKQMEG-OPJULODUSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e)-3-hydroxy-4-methyldec-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCCC#CCC(C)C(O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC FSZQXOIHLKQMEG-OPJULODUSA-N 0.000 claims 2
• PJSIFEUPCNTOBB-GHVWOOQDSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e)-3-hydroxy-4-methyloct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCCCC(C)C(O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC PJSIFEUPCNTOBB-GHVWOOQDSA-N 0.000 claims 2
• HCKHINANORSZQG-KTRCDEGTSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e)-3-hydroxy-7-phenylhept-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\C(O)CCC#CC1=CC=CC=C1 HCKHINANORSZQG-KTRCDEGTSA-N 0.000 claims 2
• HHHCPAHHPYHYHI-CDZVJMEDSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e)-3-hydroxynon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CCCC(O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC HHHCPAHHPYHYHI-CDZVJMEDSA-N 0.000 claims 2
• JBNVNCQHQOLBKU-ALXVWFSLSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@H](O)C(C)CCCC1=CC=CC=C1 JBNVNCQHQOLBKU-ALXVWFSLSA-N 0.000 claims 2
• VHRJVUYFZQBEIY-CEGZRWDUSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@H](O)C(C)CC#CC)CC(F)(F)C1=O VHRJVUYFZQBEIY-CEGZRWDUSA-N 0.000 claims 2
• AVYDNIUSLHLZJM-FYBNUODKSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@H](O)CCCCC1=CC=CC=C1 AVYDNIUSLHLZJM-FYBNUODKSA-N 0.000 claims 2
• HHSQKMPZLSWQPP-AONBVXOQSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCCCC[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC HHSQKMPZLSWQPP-AONBVXOQSA-N 0.000 claims 2
• VHRJVUYFZQBEIY-FQQZZHAUSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@H](O)[C@H](C)CC#CC)CC(F)(F)C1=O VHRJVUYFZQBEIY-FQQZZHAUSA-N 0.000 claims 2
• NNQOPMDJSKGOML-SNLJXXQOSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@H](C)[C@@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC NNQOPMDJSKGOML-SNLJXXQOSA-N 0.000 claims 2
• VHRJVUYFZQBEIY-LPJXYHDHSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@H](O)[C@@H](C)CC#CC)CC(F)(F)C1=O VHRJVUYFZQBEIY-LPJXYHDHSA-N 0.000 claims 2
• HHSQKMPZLSWQPP-CPQFKCLQSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCCCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC HHSQKMPZLSWQPP-CPQFKCLQSA-N 0.000 claims 2
• JBNVNCQHQOLBKU-OAVCZXIDSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)[C@H](C)CCCC1=CC=CC=C1 JBNVNCQHQOLBKU-OAVCZXIDSA-N 0.000 claims 2
• VHRJVUYFZQBEIY-KXZRJNSZSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s,4r)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@@H](O)[C@H](C)CC#CC)CC(F)(F)C1=O VHRJVUYFZQBEIY-KXZRJNSZSA-N 0.000 claims 2
• JBNVNCQHQOLBKU-PEQASXHNSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)[C@@H](C)CCCC1=CC=CC=C1 JBNVNCQHQOLBKU-PEQASXHNSA-N 0.000 claims 2
• NNQOPMDJSKGOML-QUMINBJRSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC NNQOPMDJSKGOML-QUMINBJRSA-N 0.000 claims 2
• VHRJVUYFZQBEIY-GPVXIOJZSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyloct-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound COC(=O)CCCCCCN1[C@@H](\C=C\[C@@H](O)[C@@H](C)CC#CC)CC(F)(F)C1=O VHRJVUYFZQBEIY-GPVXIOJZSA-N 0.000 claims 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 claims 1
• LJBQBOYAUOOSLH-ZNIBZUMBSA-N 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methylnon-1-en-6-ynyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylic acid Chemical compound CCC#CCC(C)[C@@H](O)\C=C\[C@H]1CCC(=O)N1CC#CC1=CC=C(C(O)=O)S1 LJBQBOYAUOOSLH-ZNIBZUMBSA-N 0.000 claims 1
• 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 claims 1
• 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 claims 1
• 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 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
• ZECQOPFVRSEFGC-XMUVQSOXSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3r,4s)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)CC1=CC=CC=C1 ZECQOPFVRSEFGC-XMUVQSOXSA-N 0.000 claims 1
• NDBMETWZNQYRFP-YOIRJEGESA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxydec-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCCC#CCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 NDBMETWZNQYRFP-YOIRJEGESA-N 0.000 claims 1
• ZSNYVRWVRBCGAF-IGXNXKSNSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxynon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCC#CCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 ZSNYVRWVRBCGAF-IGXNXKSNSA-N 0.000 claims 1
• JMHMEEBPWHFLBX-KRPHMAJBSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-5-phenylpent-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)C1=CC=CC=C1 JMHMEEBPWHFLBX-KRPHMAJBSA-N 0.000 claims 1
• XLCABUXIRDDWSG-GJWBGHMGSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-7-phenylhept-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound C([C@H](C)[C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCC=1SC(=CC=1)C(O)=O)C#CC1=CC=CC=C1 XLCABUXIRDDWSG-GJWBGHMGSA-N 0.000 claims 1
• PBEADSCFVAUBQH-OFQUAYIFSA-N 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyldec-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylic acid Chemical compound CCCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCC1=CC=C(C(O)=O)S1 PBEADSCFVAUBQH-OFQUAYIFSA-N 0.000 claims 1
• BBUZBTBHUCTEBZ-KUOZIZRBSA-N 7-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@H](O)\C=C\[C@@H]1N(C(=O)C(F)(F)C1)CCCCCCC(O)=O)CCCC1=CC=CC=C1 BBUZBTBHUCTEBZ-KUOZIZRBSA-N 0.000 claims 1
• PWZMQIUUWBQDQW-WFPWZJHXSA-N 7-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxyoct-1-enyl]-2-oxopyrrolidin-1-yl]heptanoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCCCCCC(O)=O PWZMQIUUWBQDQW-WFPWZJHXSA-N 0.000 claims 1
• CRUNFNWPSSJCFB-QLHPQISQSA-N O[C@@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](CCCCCC1=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](CCCCCC1=CC=CC=C1)C CRUNFNWPSSJCFB-QLHPQISQSA-N 0.000 claims 1
• ZXECFDRPIPRVFB-CRODIQNZSA-N O[C@H](/C=C/[C@@H]1N(C(CC1)=O)CCCC1=CC=C(S1)C(=O)O)[C@@H](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](CCC1=CC=CC=C1)C ZXECFDRPIPRVFB-CRODIQNZSA-N 0.000 claims 1
• 239000008240 homogeneous mixture Substances 0.000 claims 1
• DPIIPICOSBDYFN-DIINUUSZSA-N methyl 4-[2-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methylnon-1-en-6-ynyl]-2-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound CCC#CC[C@H](C)[C@H](O)\C=C\[C@H]1CC(F)(F)C(=O)N1CCC1=CC=C(C(=O)OC)C=C1 DPIIPICOSBDYFN-DIINUUSZSA-N 0.000 claims 1
• JUSJTDLHSOSXJS-CMGJWZOBSA-N methyl 5-[3-[(2r)-2-[(e,3r)-3-hydroxy-4-methyl-7-phenylhept-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(C)CC#CC1=CC=CC=C1 JUSJTDLHSOSXJS-CMGJWZOBSA-N 0.000 claims 1
• JUSJTDLHSOSXJS-ALWTYZOZSA-N methyl 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-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(C)CC#CC1=CC=CC=C1 JUSJTDLHSOSXJS-ALWTYZOZSA-N 0.000 claims 1
• MPQNGSFETCOJTQ-ALWTYZOZSA-N methyl 5-[3-[(2r)-2-[(e,3s)-3-hydroxy-4-methyl-7-phenylhept-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(C)CC#CC1=CC=CC=C1 MPQNGSFETCOJTQ-ALWTYZOZSA-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
• 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
• ZRZLHROEQSMNNK-GJWBGHMGSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-[(e,3s,4s)-3-hydroxy-4-methyl-6-phenylhex-1-enyl]-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1\C=C\[C@@H](O)[C@@H](C)CCC1=CC=CC=C1 ZRZLHROEQSMNNK-GJWBGHMGSA-N 0.000 claims 1
• AVYDNIUSLHLZJM-IRAQTCESSA-N methyl 7-[(5r)-3,3-difluoro-5-[(e,3s)-3-hydroxy-7-phenylhept-1-enyl]-2-oxopyrrolidin-1-yl]heptanoate Chemical compound C1C(F)(F)C(=O)N(CCCCCCC(=O)OC)[C@H]1\C=C\[C@@H](O)CCCCC1=CC=CC=C1 AVYDNIUSLHLZJM-IRAQTCESSA-N 0.000 claims 1
• 229940124597 therapeutic agent Drugs 0.000 abstract description 11
• 206010061218 Inflammation Diseases 0.000 abstract description 6
• 208000015181 infectious disease Diseases 0.000 abstract description 6
• 230000004054 inflammatory process Effects 0.000 abstract description 6
• 206010028980 Neoplasm Diseases 0.000 abstract description 5
• 201000011510 cancer Diseases 0.000 abstract description 5
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
• 238000002513 implantation Methods 0.000 abstract description 5
• 208000035475 disorder Diseases 0.000 abstract description 4
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 145
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 144
• 239000000543 intermediate Substances 0.000 description 114
• 238000002360 preparation method Methods 0.000 description 85
• 239000011541 reaction mixture Substances 0.000 description 81
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 80
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 80
• 239000000243 solution Substances 0.000 description 79
• 239000002904 solvent Substances 0.000 description 79
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 77
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 73
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
• 125000000217 alkyl group Chemical group 0.000 description 63
• 238000004809 thin layer chromatography Methods 0.000 description 57
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 46
• 238000005160 1H NMR spectroscopy Methods 0.000 description 40
• 238000010828 elution Methods 0.000 description 39
• 238000010898 silica gel chromatography Methods 0.000 description 39
• 239000003921 oil Substances 0.000 description 38
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 36
• 150000002148 esters Chemical class 0.000 description 36
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 239000002253 acid Substances 0.000 description 30
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 238000006243 chemical reaction Methods 0.000 description 27
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical class CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 27
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
• 238000011282 treatment Methods 0.000 description 27
• 229910052938 sodium sulfate Inorganic materials 0.000 description 26
• 235000011152 sodium sulphate Nutrition 0.000 description 26
• 101001117509 Homo sapiens Prostaglandin E2 receptor EP4 subtype Proteins 0.000 description 25
• 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 description 25
• 239000007864 aqueous solution Substances 0.000 description 25
• 238000003756 stirring Methods 0.000 description 25
• 150000001408 amides Chemical class 0.000 description 22
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 22
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 21
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 21
• 239000012267 brine Substances 0.000 description 21
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 20
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 20
• 229920006395 saturated elastomer Polymers 0.000 description 20
• 238000007792 addition Methods 0.000 description 19
• 239000002585 base Substances 0.000 description 19
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 19
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
• 150000007513 acids Chemical class 0.000 description 18
• 230000000694 effects Effects 0.000 description 18
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 18
• 239000011780 sodium chloride Substances 0.000 description 17
• 229910001868 water Inorganic materials 0.000 description 17
• 150000001733 carboxylic acid esters Chemical class 0.000 description 16
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 16
• 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 16
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
• OJOFMLDBXPDXLQ-UHFFFAOYSA-N 4-benzyl-1,3-oxazolidin-2-one Chemical class C1OC(=O)NC1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-UHFFFAOYSA-N 0.000 description 15
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 15
• 238000004128 high performance liquid chromatography Methods 0.000 description 15
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 15
• 239000012074 organic phase Substances 0.000 description 15
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 13
• 230000014759 maintenance of location Effects 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
• 239000003795 chemical substances by application Substances 0.000 description 12
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
• 238000004090 dissolution Methods 0.000 description 12
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 239000002168 alkylating agent Substances 0.000 description 11
• 229940100198 alkylating agent Drugs 0.000 description 11
• 150000001721 carbon Chemical group 0.000 description 11
• 238000009434 installation Methods 0.000 description 11
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 10
• 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 10
• 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 10
• 102100022544 Bone morphogenetic protein 7 Human genes 0.000 description 10
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• 238000003786 synthesis reaction Methods 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 235000019270 ammonium chloride Nutrition 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 125000005842 heteroatom Chemical group 0.000 description 9
• 230000011164 ossification Effects 0.000 description 9
• 239000007858 starting material Substances 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 125000001309 chloro group Chemical group Cl* 0.000 description 8
• 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 8
• 125000001624 naphthyl group Chemical group 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 239000011368 organic material Substances 0.000 description 8
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 8
• 239000012312 sodium hydride Substances 0.000 description 8
• 229910000104 sodium hydride Inorganic materials 0.000 description 8
• 125000001544 thienyl group Chemical group 0.000 description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
• CMRXZAKSZIVSCC-GSVOUGTGSA-N (5r)-3,3-difluoro-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@H]1CC(F)(F)C(=O)N1 CMRXZAKSZIVSCC-GSVOUGTGSA-N 0.000 description 7
• 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
• HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 7
• 230000005526 G1 to G0 transition Effects 0.000 description 7
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 7
• RWFPXJAUVOBOLJ-UHFFFAOYSA-N acetic acid;ethyl acetate;heptane Chemical compound CC(O)=O.CCOC(C)=O.CCCCCCC RWFPXJAUVOBOLJ-UHFFFAOYSA-N 0.000 description 7
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 238000006731 degradation reaction Methods 0.000 description 7
• 238000002716 delivery method Methods 0.000 description 7
• 230000002401 inhibitory effect Effects 0.000 description 7
• ZJJABXXVOBSIKA-UHFFFAOYSA-N methyl 5-(3-bromopropyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(CCCBr)S1 ZJJABXXVOBSIKA-UHFFFAOYSA-N 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000007254 oxidation reaction Methods 0.000 description 7
• 125000005981 pentynyl group Chemical group 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 238000000926 separation method Methods 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 6
• 206010005949 Bone cancer Diseases 0.000 description 6
• 208000018084 Bone neoplasm Diseases 0.000 description 6
• 208000001132 Osteoporosis Diseases 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
• 238000005804 alkylation reaction Methods 0.000 description 6
• 125000002947 alkylene group Chemical group 0.000 description 6
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
• 230000015556 catabolic process 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
• 125000005980 hexynyl group Chemical group 0.000 description 6
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
• 150000003951 lactams Chemical group 0.000 description 6
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
• RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 235000019731 tricalcium phosphate Nutrition 0.000 description 6
• QBZLNEZLTDIKCE-ZDUSSCGKSA-N (3s)-1-dimethoxyphosphoryl-3-methyl-6-phenylhexan-2-one Chemical compound COP(=O)(OC)CC(=O)[C@@H](C)CCCC1=CC=CC=C1 QBZLNEZLTDIKCE-ZDUSSCGKSA-N 0.000 description 5
• YTXXRLXVAZGQAL-ZCFIWIBFSA-N (7ar)-3,3-dimethyl-1,6,7,7a-tetrahydropyrrolo[1,2-c][1,3]oxazol-5-one Chemical compound C1CC(=O)N2C(C)(C)OC[C@H]21 YTXXRLXVAZGQAL-ZCFIWIBFSA-N 0.000 description 5
• VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 5
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
• 239000004215 Carbon black (E152) Substances 0.000 description 5
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
• 101100521345 Mus musculus Prop1 gene Proteins 0.000 description 5
• NIWUMFULEUZEOT-UHFFFAOYSA-N O=P1OOO1 Chemical class O=P1OOO1 NIWUMFULEUZEOT-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
• 108700017836 Prophet of Pit-1 Proteins 0.000 description 5
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 5
• AOZUYISQWWJMJC-UHFFFAOYSA-N acetic acid;methanol;hydrate Chemical compound O.OC.CC(O)=O AOZUYISQWWJMJC-UHFFFAOYSA-N 0.000 description 5
• 239000005557 antagonist Substances 0.000 description 5
• 238000010511 deprotection reaction Methods 0.000 description 5
• 230000002708 enhancing effect Effects 0.000 description 5
• 229930195733 hydrocarbon Natural products 0.000 description 5
• 150000002430 hydrocarbons Chemical class 0.000 description 5
• 150000002576 ketones Chemical class 0.000 description 5
• 229910052744 lithium Inorganic materials 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 5
• 238000006772 olefination reaction Methods 0.000 description 5
• 239000008177 pharmaceutical agent Substances 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 235000011149 sulphuric acid Nutrition 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 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 4
• ASZIHXOIQJBLRA-JTQLQIEISA-N (2s)-2-methyl-5-phenylpentanoic acid Chemical compound OC(=O)[C@@H](C)CCCC1=CC=CC=C1 ASZIHXOIQJBLRA-JTQLQIEISA-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 4
• 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 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
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 4
• 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 4
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 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
• 108010049955 Bone Morphogenetic Protein 4 Proteins 0.000 description 4
• 206010065687 Bone loss Diseases 0.000 description 4
• 102100024505 Bone morphogenetic protein 4 Human genes 0.000 description 4
• 238000010485 C−C bond formation reaction Methods 0.000 description 4
• YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
• 101000711796 Homo sapiens Sclerostin Proteins 0.000 description 4
• 101150109738 Ptger4 gene Proteins 0.000 description 4
• 102100034201 Sclerostin Human genes 0.000 description 4
• 239000003263 anabolic agent Substances 0.000 description 4
• 230000000844 anti-bacterial effect Effects 0.000 description 4
• 229940088710 antibiotic agent Drugs 0.000 description 4
• 229940121375 antifungal agent Drugs 0.000 description 4
• 239000012298 atmosphere Substances 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
• 125000005622 butynylene group Chemical group 0.000 description 4
• 229920001429 chelating resin Polymers 0.000 description 4
• 239000012230 colorless oil Substances 0.000 description 4
• 238000005115 demineralization Methods 0.000 description 4
• 230000002328 demineralizing effect Effects 0.000 description 4
• 229940043279 diisopropylamine Drugs 0.000 description 4
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 125000002541 furyl group Chemical group 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 239000007943 implant Substances 0.000 description 4
• 230000001939 inductive effect Effects 0.000 description 4
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• HQGPKMSGXAUKHT-SCSAIBSYSA-N methyl (2r)-5-oxopyrrolidine-2-carboxylate Chemical compound COC(=O)[C@H]1CCC(=O)N1 HQGPKMSGXAUKHT-SCSAIBSYSA-N 0.000 description 4
• RBPGZMFYWCBLOA-SCSAIBSYSA-N methyl (4r)-4-amino-2,2-difluoro-5-hydroxypentanoate Chemical compound COC(=O)C(F)(F)C[C@@H](N)CO RBPGZMFYWCBLOA-SCSAIBSYSA-N 0.000 description 4
• 239000002480 mineral oil Substances 0.000 description 4
• 235000010446 mineral oil Nutrition 0.000 description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 description 4
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 4
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 229940044601 receptor agonist Drugs 0.000 description 4
• 239000000018 receptor agonist Substances 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000006722 reduction reaction Methods 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 239000011347 resin Substances 0.000 description 4
• 229920005989 resin Polymers 0.000 description 4
• 239000012047 saturated solution Substances 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 235000009518 sodium iodide Nutrition 0.000 description 4
• 239000012453 solvate Substances 0.000 description 4
• 241000894007 species Species 0.000 description 4
• 230000004936 stimulating effect Effects 0.000 description 4
• 238000013268 sustained release Methods 0.000 description 4
• 239000012730 sustained-release form Substances 0.000 description 4
• 125000003718 tetrahydrofuranyl group Chemical group 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
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
• JRIIYTZWUDBBIA-ZETCQYMHSA-N (2s)-2-methylhept-4-ynoic acid Chemical compound CCC#CC[C@H](C)C(O)=O JRIIYTZWUDBBIA-ZETCQYMHSA-N 0.000 description 3
• NNOBZVFETZOWPZ-LPHOPBHVSA-N (2s)-n-[(1r)-2-hydroxy-1-phenylethyl]-2-methyl-5-phenylpentanamide Chemical compound C([C@H](C)C(=O)N[C@@H](CO)C=1C=CC=CC=1)CCC1=CC=CC=C1 NNOBZVFETZOWPZ-LPHOPBHVSA-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
• 238000004293 19F NMR spectroscopy Methods 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
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 208000006386 Bone Resorption Diseases 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
• 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 3
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 208000029725 Metabolic bone disease Diseases 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• 229910020667 PBr3 Inorganic materials 0.000 description 3
• 102000019307 Sclerostin Human genes 0.000 description 3
• 108050006698 Sclerostin Proteins 0.000 description 3
• 230000009471 action Effects 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
• 229940124325 anabolic agent Drugs 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
• 230000010072 bone remodeling Effects 0.000 description 3
• 230000024279 bone resorption Effects 0.000 description 3
• 230000037118 bone strength Effects 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 3
• 239000003153 chemical reaction reagent 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
• 239000007819 coupling partner Substances 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 230000008025 crystallization Effects 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 229960001251 denosumab Drugs 0.000 description 3
• 230000001419 dependent effect Effects 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
• 238000005516 engineering process Methods 0.000 description 3
• 230000032050 esterification Effects 0.000 description 3
• 238000005886 esterification reaction Methods 0.000 description 3
• JYMITPUGWUFJDL-LBPRGKRZSA-N ethyl (2s)-2-methyl-5-phenylpentanoate Chemical compound CCOC(=O)[C@@H](C)CCCC1=CC=CC=C1 JYMITPUGWUFJDL-LBPRGKRZSA-N 0.000 description 3
• 239000000945 filler Substances 0.000 description 3
• 238000011065 in-situ storage Methods 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 229910052500 inorganic mineral Inorganic materials 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 150000002690 malonic acid derivatives Chemical class 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• QPVPNNZDPILPAJ-SECBINFHSA-N methyl 5-[3-[(5r)-3,3-difluoro-5-(hydroxymethyl)-2-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)C(F)(F)C[C@@H]1CO QPVPNNZDPILPAJ-SECBINFHSA-N 0.000 description 3
• 235000010755 mineral Nutrition 0.000 description 3
• 239000011707 mineral Substances 0.000 description 3
• 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 3
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
• 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 3
• 150000007524 organic acids Chemical class 0.000 description 3
• IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 3
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 125000006413 ring segment Chemical group 0.000 description 3
• 229950008358 rivenprost Drugs 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
• 235000019345 sodium thiosulphate Nutrition 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 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
• 210000001519 tissue Anatomy 0.000 description 3
• NNOBZVFETZOWPZ-APWZRJJASA-N (2r)-n-[(1r)-2-hydroxy-1-phenylethyl]-2-methyl-5-phenylpentanamide Chemical compound C([C@@H](C)C(=O)N[C@@H](CO)C=1C=CC=CC=1)CCC1=CC=CC=C1 NNOBZVFETZOWPZ-APWZRJJASA-N 0.000 description 2
• QBZLNEZLTDIKCE-CYBMUJFWSA-N (3r)-1-dimethoxyphosphoryl-3-methyl-6-phenylhexan-2-one Chemical compound COP(=O)(OC)CC(=O)[C@H](C)CCCC1=CC=CC=C1 QBZLNEZLTDIKCE-CYBMUJFWSA-N 0.000 description 2
• ICLVZMMFKWCSMR-COBSHVIPSA-N (5r)-5-(1-ethoxyethoxymethyl)-3,3-difluoropyrrolidin-2-one Chemical compound CCOC(C)OC[C@H]1CC(F)(F)C(=O)N1 ICLVZMMFKWCSMR-COBSHVIPSA-N 0.000 description 2
• IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 2
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-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
• 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 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
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• KAKLBMRMSLJPSY-UHFFFAOYSA-N 5-(3-bromopropyl)thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(CCCBr)S1 KAKLBMRMSLJPSY-UHFFFAOYSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• 208000010392 Bone Fractures Diseases 0.000 description 2
• 206010006002 Bone pain Diseases 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
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 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
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-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
• 241001465754 Metazoa Species 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 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
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
• 241001447056 Uristes Species 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 239000002671 adjuvant Substances 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
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 229930192649 bafilomycin Natural products 0.000 description 2
• XDHNQDDQEHDUTM-UHFFFAOYSA-N bafliomycin A1 Natural products COC1C=CC=C(C)CC(C)C(O)C(C)C=C(C)C=C(OC)C(=O)OC1C(C)C(O)C(C)C1(O)OC(C(C)C)C(C)C(O)C1 XDHNQDDQEHDUTM-UHFFFAOYSA-N 0.000 description 2
• 230000008901 benefit Effects 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
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 230000033558 biomineral tissue development Effects 0.000 description 2
• 230000036983 biotransformation Effects 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
• 238000013375 chromatographic separation Methods 0.000 description 2
• 229950009003 cilengitide Drugs 0.000 description 2
• AMLYAMJWYAIXIA-VWNVYAMZSA-N cilengitide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N(C)C(=O)[C@H]1CC1=CC=CC=C1 AMLYAMJWYAIXIA-VWNVYAMZSA-N 0.000 description 2
• MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
• 230000001054 cortical effect Effects 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 238000005520 cutting process Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 2
• CAMKJDNOGYICRO-UHFFFAOYSA-N diethyl 2-hex-2-ynylpropanedioate Chemical compound CCCC#CCC(C(=O)OCC)C(=O)OCC CAMKJDNOGYICRO-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
• VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 2
• JYMITPUGWUFJDL-GFCCVEGCSA-N ethyl (2r)-2-methyl-5-phenylpentanoate Chemical compound CCOC(=O)[C@H](C)CCCC1=CC=CC=C1 JYMITPUGWUFJDL-GFCCVEGCSA-N 0.000 description 2
• 238000011049 filling Methods 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 238000005227 gel permeation chromatography Methods 0.000 description 2
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
• 239000010931 gold Substances 0.000 description 2
• 229910052737 gold Inorganic materials 0.000 description 2
• 238000000227 grinding Methods 0.000 description 2
• 125000004438 haloalkoxy group Chemical group 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 230000001976 improved effect Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 102000006495 integrins Human genes 0.000 description 2
• 108010044426 integrins Proteins 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
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 239000003456 ion exchange resin Substances 0.000 description 2
• 229920003303 ion-exchange polymer Polymers 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 238000011068 loading method Methods 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
• 239000011159 matrix material Substances 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• HNNUQHJWFIPTLJ-UHFFFAOYSA-N methyl 4-(2-bromoethyl)benzoate Chemical compound COC(=O)C1=CC=C(CCBr)C=C1 HNNUQHJWFIPTLJ-UHFFFAOYSA-N 0.000 description 2
• CAIABKQJRSATCK-GFCCVEGCSA-N methyl 4-[2-[(5r)-3,3-difluoro-5-(hydroxymethyl)-2-oxopyrrolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)C(F)(F)C[C@@H]1CO CAIABKQJRSATCK-GFCCVEGCSA-N 0.000 description 2
• KANCLAAJRIEZAJ-UHFFFAOYSA-N methyl 5-(3-hydroxypropyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(CCCO)S1 KANCLAAJRIEZAJ-UHFFFAOYSA-N 0.000 description 2
• QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-UHFFFAOYSA-N 0.000 description 2
• RRHYSKYKKVDLSG-ARLHGKGLSA-N methyl 7-[(5r)-5-(1-ethoxyethoxymethyl)-3,3-difluoro-2-oxopyrrolidin-1-yl]heptanoate Chemical compound CCOC(C)OC[C@H]1CC(F)(F)C(=O)N1CCCCCCC(=O)OC RRHYSKYKKVDLSG-ARLHGKGLSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 230000000269 nucleophilic effect Effects 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 238000006053 organic reaction Methods 0.000 description 2
• 238000010883 osseointegration Methods 0.000 description 2
• 230000004072 osteoblast differentiation Effects 0.000 description 2
• 230000000278 osteoconductive effect Effects 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-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
• 230000036961 partial effect Effects 0.000 description 2
• XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
• 208000028169 periodontal disease Diseases 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 235000019260 propionic acid Nutrition 0.000 description 2
• 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 2
• 239000000376 reactant Substances 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
• 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
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• XZPVPNZTYPUODG-UHFFFAOYSA-M sodium;chloride;dihydrate Chemical compound O.O.[Na+].[Cl-] XZPVPNZTYPUODG-UHFFFAOYSA-M 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
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• 229940126585 therapeutic drug Drugs 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
• 230000008733 trauma Effects 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-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
• 230000007306 turnover Effects 0.000 description 2
• 239000011800 void material Substances 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• 238000010626 work up procedure Methods 0.000 description 2
• 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-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 1
• ASZIHXOIQJBLRA-SNVBAGLBSA-N (2r)-2-methyl-5-phenylpentanoic acid Chemical compound OC(=O)[C@H](C)CCCC1=CC=CC=C1 ASZIHXOIQJBLRA-SNVBAGLBSA-N 0.000 description 1
• HKDYMZFUGOUTRY-JTQLQIEISA-N (2s)-2-methyl-5-phenylpent-4-ynoic acid Chemical compound OC(=O)[C@@H](C)CC#CC1=CC=CC=C1 HKDYMZFUGOUTRY-JTQLQIEISA-N 0.000 description 1
• YVZVHNPTRCHYEY-LURJTMIESA-N (2s)-2-methylhex-4-ynoic acid Chemical compound CC#CC[C@H](C)C(O)=O YVZVHNPTRCHYEY-LURJTMIESA-N 0.000 description 1
• HZNDJOPODWAYMU-QMMMGPOBSA-N (2s)-2-methyloct-4-ynoic acid Chemical compound CCCC#CC[C@H](C)C(O)=O HZNDJOPODWAYMU-QMMMGPOBSA-N 0.000 description 1
• VFCUJHFLFHQCRD-PFIOQAQVSA-N (2z,4z)-n-[(e)-3-[(3e,6s,7r,9s)-7,13-dihydroxy-6-methyl-11-oxo-10-oxabicyclo[10.4.0]hexadeca-1(12),3,13,15-tetraen-9-yl]prop-1-enyl]hepta-2,4-dienamide Chemical compound O=C1O[C@@H](C/C=C/NC(=O)/C=C\C=C/CC)C[C@@H](O)[C@@H](C)C\C=C\CC2=CC=CC(O)=C21 VFCUJHFLFHQCRD-PFIOQAQVSA-N 0.000 description 1
• OJOFMLDBXPDXLQ-VIFPVBQESA-N (4s)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-VIFPVBQESA-N 0.000 description 1
• IRGQSKCEOHGTRA-MRVPVSSYSA-N (5r)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3,3-difluoropyrrolidin-2-one Chemical compound CC(C)(C)[Si](C)(C)OC[C@H]1CC(F)(F)C(=O)N1 IRGQSKCEOHGTRA-MRVPVSSYSA-N 0.000 description 1
• HDBCZVUQHIWDAD-RITPCOANSA-N (6s,7ar)-6-fluoro-3,3-dimethyl-1,6,7,7a-tetrahydropyrrolo[1,2-c][1,3]oxazol-5-one Chemical compound C1[C@H](F)C(=O)N2C(C)(C)OC[C@H]21 HDBCZVUQHIWDAD-RITPCOANSA-N 0.000 description 1
• FSJWCMSIXNCBLO-RXMQYKEDSA-N (7ar)-6,6-difluoro-3,3-dimethyl-7,7a-dihydro-1h-pyrrolo[1,2-c][1,3]oxazol-5-one Chemical compound C1C(F)(F)C(=O)N2C(C)(C)OC[C@H]21 FSJWCMSIXNCBLO-RXMQYKEDSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 description 1
• XXTBGKDWFYXGDZ-KJCKJCAZSA-N (z)-7-[(1r,2r,3r,5r)-5-chloro-3-hydroxy-2-[(e,4s)-4-hydroxy-4-(1-prop-2-enylcyclobutyl)but-1-enyl]cyclopentyl]hept-5-enoic acid Chemical compound C([C@H](O)C1(CC=C)CCC1)\C=C\[C@H]1[C@H](O)C[C@@H](Cl)[C@@H]1C\C=C/CCCC(O)=O XXTBGKDWFYXGDZ-KJCKJCAZSA-N 0.000 description 1
• JYHIHHYYXXKTTJ-JSFHDESQSA-N (z,4z)-n-[(e)-3-[(3z,6e)-5,16-dihydroxy-4,8-dimethyl-10,14-dioxo-9,13-dioxabicyclo[13.4.0]nonadeca-1(15),3,6,16,18-pentaen-12-yl]prop-1-enyl]-4-methoxyiminobut-2-enamide Chemical compound O=C1OC(C/C=C/NC(=O)/C=C\C=N/OC)CC(=O)OC(C)\C=C\C(O)\C(C)=C/CC2=CC=CC(O)=C21 JYHIHHYYXXKTTJ-JSFHDESQSA-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
• ATWLRNODAYAMQS-UHFFFAOYSA-N 1,1-dibromopropane Chemical compound CCC(Br)Br ATWLRNODAYAMQS-UHFFFAOYSA-N 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 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
• HMVYYTRDXNKRBQ-UHFFFAOYSA-N 1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 description 1
• RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
• 125000005940 1,4-dioxanyl group Chemical group 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
• LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-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
• 229940044613 1-propanol Drugs 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
• VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-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
• 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
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• ASZIHXOIQJBLRA-UHFFFAOYSA-N 2-methyl-5-phenylpentanoic acid Chemical compound OC(=O)C(C)CCCC1=CC=CC=C1 ASZIHXOIQJBLRA-UHFFFAOYSA-N 0.000 description 1
• JRIIYTZWUDBBIA-UHFFFAOYSA-N 2-methylhept-4-ynoic acid Chemical compound CCC#CCC(C)C(O)=O JRIIYTZWUDBBIA-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
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 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
• XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-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
• AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 description 1
• 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
• JYZXGURJKNAFPT-ZWKOTPCHSA-M 5-[3-[(2s)-2-[(3r)-3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound C([C@@H]1CC[C@@H](O)CC=2C=C(C=CC=2)C(F)(F)F)CC(=O)N1CCCC1=CC=C(C([O-])=O)S1 JYZXGURJKNAFPT-ZWKOTPCHSA-M 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
• BYHDDXPKOZIZRV-UHFFFAOYSA-N 5-phenylpentanoic acid Chemical compound OC(=O)CCCCC1=CC=CC=C1 BYHDDXPKOZIZRV-UHFFFAOYSA-N 0.000 description 1
• VSHULXBTMXBAAP-UHFFFAOYSA-N 5-phenylpentanoyl chloride Chemical compound ClC(=O)CCCCC1=CC=CC=C1 VSHULXBTMXBAAP-UHFFFAOYSA-N 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 229910015845 BBr3 Inorganic materials 0.000 description 1
• OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
• 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
• 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 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
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 102000004171 Cathepsin K Human genes 0.000 description 1
• 108090000625 Cathepsin K Proteins 0.000 description 1
• 229930186147 Cephalosporin Natural products 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
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
• 238000006646 Dess-Martin oxidation reaction Methods 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
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• VMEJANRODATDOF-UHFFFAOYSA-N Diphyllin Chemical compound C1=C2OCOC2=CC(C=2C=3C(=O)OCC=3C(O)=C3C=C(C(=CC3=2)OC)OC)=C1 VMEJANRODATDOF-UHFFFAOYSA-N 0.000 description 1
• 102000002045 Endothelin Human genes 0.000 description 1
• 108050009340 Endothelin Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 101000640020 Homo sapiens Sodium channel protein type 11 subunit alpha 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
• 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
• 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
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
• 239000002145 L01XE14 - Bosutinib Substances 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• FJHHZXWJVIEFGJ-UHFFFAOYSA-N N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2OC=NN=2)C=C1 FJHHZXWJVIEFGJ-UHFFFAOYSA-N 0.000 description 1
• VWEMTNDGVRHRAJ-WUJWULDRSA-N N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylhept-4-ynamide Chemical compound OC[C@@H](C1=CC=CC=C1)NC(C(CC#CCC)C)=O VWEMTNDGVRHRAJ-WUJWULDRSA-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
• 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
• 238000003527 Peterson olefination reaction Methods 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
• 102000001332 SRC Human genes 0.000 description 1
• 206010061363 Skeletal injury Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 102100033974 Sodium channel protein type 11 subunit alpha Human genes 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 102000003566 TRPV1 Human genes 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
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 101150016206 Trpv1 gene Proteins 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102100040247 Tumor necrosis factor Human genes 0.000 description 1
• 238000007239 Wittig reaction Methods 0.000 description 1
• 208000027418 Wounds and injury Diseases 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
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
• 239000003522 acrylic cement Substances 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 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
• 150000004703 alkoxides 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
• 208000026935 allergic disease Diseases 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical group BrCC=C BHELZAPQIKSEDF-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
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 210000001909 alveolar process Anatomy 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 230000000202 analgesic effect Effects 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 238000010719 annulation reaction Methods 0.000 description 1
• 230000003160 anti-catabolic effect Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 238000011444 antiresorptive therapy Methods 0.000 description 1
• 229930193106 apicularen Natural products 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 229930193499 archazolide Natural products 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 1
• 229950010993 atrasentan Drugs 0.000 description 1
• 230000003416 augmentation Effects 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
• 229960004099 azithromycin Drugs 0.000 description 1
• MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 230000009286 beneficial effect Effects 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
• BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 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
• 230000037396 body weight Effects 0.000 description 1
• 230000018678 bone mineralization Effects 0.000 description 1
• 230000010478 bone regeneration Effects 0.000 description 1
• 230000008416 bone turnover Effects 0.000 description 1
• UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 description 1
• 229960003736 bosutinib Drugs 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 239000003152 bradykinin antagonist Substances 0.000 description 1
• 229960003150 bupivacaine Drugs 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 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
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 229940124587 cephalosporin Drugs 0.000 description 1
• 150000001780 cephalosporins Chemical class 0.000 description 1
• 150000001782 cephems Chemical class 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
• 229960003405 ciprofloxacin Drugs 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 229960002626 clarithromycin Drugs 0.000 description 1
• AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
• VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
• 229960004022 clotrimazole Drugs 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 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
• DJZCTUVALDDONK-HQMSUKCRSA-N concanamycin A Chemical compound O1C(=O)\C(OC)=C\C(\C)=C\[C@@H](C)[C@@H](O)[C@@H](CC)[C@@H](O)[C@H](C)C\C(C)=C\C=C\[C@H](OC)[C@H]1[C@@H](C)[C@@H](O)[C@H](C)[C@]1(O)O[C@H](\C=C\C)[C@@H](C)[C@H](O[C@@H]2O[C@H](C)[C@@H](OC(N)=O)[C@H](O)C2)C1 DJZCTUVALDDONK-HQMSUKCRSA-N 0.000 description 1
• DJZCTUVALDDONK-UHFFFAOYSA-N concanamycin A Natural products O1C(=O)C(OC)=CC(C)=CC(C)C(O)C(CC)C(O)C(C)CC(C)=CC=CC(OC)C1C(C)C(O)C(C)C1(O)OC(C=CC)C(C)C(OC2OC(C)C(OC(N)=O)C(O)C2)C1 DJZCTUVALDDONK-UHFFFAOYSA-N 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229960002448 dasatinib Drugs 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000003247 decreasing effect Effects 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
• 230000003413 degradative effect Effects 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 230000005595 deprotonation Effects 0.000 description 1
• 238000010537 deprotonation reaction Methods 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 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 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 125000005959 diazepanyl group Chemical group 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 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
• 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
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• RFXQCUDAHXPYOF-UHFFFAOYSA-N diphyllin Natural products COc1cc2c(c3ccc4OCOc4c3)c5C(=O)OCc5c(O)c2cc1O RFXQCUDAHXPYOF-UHFFFAOYSA-N 0.000 description 1
• 229960002819 diprophylline Drugs 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• 235000019800 disodium phosphate Nutrition 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004821 distillation 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
• 229960004679 doxorubicin Drugs 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 125000005610 enamide group Chemical group 0.000 description 1
• ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 229960003276 erythromycin Drugs 0.000 description 1
• UMYZHWLYICNGRQ-UHFFFAOYSA-N ethanol;heptane Chemical compound CCO.CCCCCCC UMYZHWLYICNGRQ-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
• 229960004884 fluconazole Drugs 0.000 description 1
• 239000011737 fluorine Substances 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
• 239000007789 gas Substances 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 210000000569 greater omentum Anatomy 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
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-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
• 150000004678 hydrides Chemical class 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
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 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
• 230000006872 improvement Effects 0.000 description 1
• 238000000099 in vitro assay 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
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 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
• 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
• 230000000155 isotopic effect Effects 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
• 229960004130 itraconazole Drugs 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 229960003376 levofloxacin Drugs 0.000 description 1
• 239000012035 limiting reagent Substances 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
• AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
• JYHIHHYYXXKTTJ-UHFFFAOYSA-N lobatamide C Natural products O=C1OC(CC=CNC(=O)C=CC=NOC)CC(=O)OC(C)C=CC(O)C(C)=CCC2=CC=CC(O)=C21 JYHIHHYYXXKTTJ-UHFFFAOYSA-N 0.000 description 1
• 239000003120 macrolide antibiotic agent Substances 0.000 description 1
• 229940041033 macrolides Drugs 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 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
• 238000001819 mass spectrum Methods 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229960000485 methotrexate Drugs 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
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 239000004570 mortar (masonry) Substances 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
• 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
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 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
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 238000005580 one pot reaction Methods 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000000399 orthopedic effect Effects 0.000 description 1
• 230000002188 osteogenic effect Effects 0.000 description 1
• 230000002138 osteoinductive effect Effects 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
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 229920002866 paraformaldehyde Polymers 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
• 239000008188 pellet Substances 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
• 239000008194 pharmaceutical composition Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 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
• 239000003757 phosphotransferase inhibitor 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
• 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
• 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
• 239000004926 polymethyl methacrylate Substances 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
• 229960005335 propanol Drugs 0.000 description 1
• YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
• 150000003180 prostaglandins Chemical class 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
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 229960001549 ropivacaine Drugs 0.000 description 1
• 102220262397 rs772216758 Human genes 0.000 description 1
• VFCUJHFLFHQCRD-UHFFFAOYSA-N salicylihalamide A Natural products O=C1OC(CC=CNC(=O)C=CC=CCC)CC(O)C(C)CC=CCC2=CC=CC(O)=C21 VFCUJHFLFHQCRD-UHFFFAOYSA-N 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• OUKYUETWWIPKQR-UHFFFAOYSA-N saracatinib Chemical compound C1CN(C)CCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 OUKYUETWWIPKQR-UHFFFAOYSA-N 0.000 description 1
• 229950009919 saracatinib Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
• 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
• 230000035945 sensitivity Effects 0.000 description 1
• 238000007493 shaping process Methods 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
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 239000003195 sodium channel blocking agent Substances 0.000 description 1
• 210000004872 soft tissue Anatomy 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
• 238000001228 spectrum Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 108010087686 src-Family Kinases Proteins 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000000758 substrate 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
• 238000000967 suction filtration Methods 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 230000002483 superagonistic effect Effects 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 238000003419 tautomerization reaction Methods 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
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 229960003604 testosterone Drugs 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
• 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
• 238000010257 thawing Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 230000004797 therapeutic response Effects 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
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 210000003781 tooth socket Anatomy 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 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
• 238000009966 trimming Methods 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
• 210000000689 upper leg Anatomy 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229950003684 zibotentan Drugs 0.000 description 1