JP2008534630A - 疼痛の軽減のためのn型カルシウムチャネルブロッカーを含む組み合わせ治療の方法 - Google Patents
疼痛の軽減のためのn型カルシウムチャネルブロッカーを含む組み合わせ治療の方法 Download PDFInfo
- Publication number
- JP2008534630A JP2008534630A JP2008504594A JP2008504594A JP2008534630A JP 2008534630 A JP2008534630 A JP 2008534630A JP 2008504594 A JP2008504594 A JP 2008504594A JP 2008504594 A JP2008504594 A JP 2008504594A JP 2008534630 A JP2008534630 A JP 2008534630A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- piperazin
- calcium channel
- pain
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000002193 Pain Diseases 0.000 title claims abstract description 120
- 230000036407 pain Effects 0.000 title claims abstract description 102
- 238000000034 method Methods 0.000 title claims abstract description 64
- 102000004129 N-Type Calcium Channels Human genes 0.000 title claims abstract description 46
- 108090000699 N-Type Calcium Channels Proteins 0.000 title claims abstract description 46
- 229940127291 Calcium channel antagonist Drugs 0.000 title abstract description 26
- 239000000480 calcium channel blocker Substances 0.000 title abstract description 26
- 238000002648 combination therapy Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 123
- 239000000203 mixture Substances 0.000 claims abstract description 86
- 229940124634 N-type calcium channel blocker Drugs 0.000 claims abstract description 30
- 230000000202 analgesic effect Effects 0.000 claims abstract description 13
- 125000001151 peptidyl group Chemical group 0.000 claims abstract description 13
- 230000007246 mechanism Effects 0.000 claims abstract description 10
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 8
- 230000000144 pharmacologic effect Effects 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 32
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 238000002646 transcutaneous electrical nerve stimulation Methods 0.000 claims description 12
- VCPMZDWBEWTGNW-UHFFFAOYSA-N 1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 VCPMZDWBEWTGNW-UHFFFAOYSA-N 0.000 claims description 9
- 108091006146 Channels Proteins 0.000 claims description 9
- 239000002671 adjuvant Substances 0.000 claims description 9
- 125000001931 aliphatic group Chemical group 0.000 claims description 8
- 229940111134 coxibs Drugs 0.000 claims description 8
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 8
- 230000002452 interceptive effect Effects 0.000 claims description 5
- YBINNPIWNMGBFX-UHFFFAOYSA-N 6,6-diphenyl-1-[4-(3-phenylprop-2-enyl)piperazin-1-yl]hexan-1-one Chemical compound C1CN(CC=CC=2C=CC=CC=2)CCN1C(=O)CCCCC(C=1C=CC=CC=1)C1=CC=CC=C1 YBINNPIWNMGBFX-UHFFFAOYSA-N 0.000 claims description 4
- PPVBMJIAJXVQFX-UHFFFAOYSA-N n,4-dibenzhydrylpiperazine-1-carboxamide Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C(=O)NC(C=1C=CC=CC=1)C1=CC=CC=C1 PPVBMJIAJXVQFX-UHFFFAOYSA-N 0.000 claims description 4
- 102000003922 Calcium Channels Human genes 0.000 claims description 3
- 108090000312 Calcium Channels Proteins 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 2
- COUUZDFDXZQPEB-UHFFFAOYSA-N 1-[4-(cyclohexylmethylamino)piperidin-1-yl]-6,6-diphenylhexan-1-one Chemical compound C1CC(NCC2CCCCC2)CCN1C(=O)CCCCC(C=1C=CC=CC=1)C1=CC=CC=C1 COUUZDFDXZQPEB-UHFFFAOYSA-N 0.000 claims 3
- FSLMXULFVDTVHG-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC(CN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 FSLMXULFVDTVHG-UHFFFAOYSA-N 0.000 claims 3
- -1 benzhydryl group Chemical group 0.000 description 55
- 238000011282 treatment Methods 0.000 description 45
- 230000000694 effects Effects 0.000 description 30
- 125000000217 alkyl group Chemical group 0.000 description 29
- 239000003814 drug Substances 0.000 description 25
- 229940079593 drug Drugs 0.000 description 23
- 229940005483 opioid analgesics Drugs 0.000 description 19
- 125000003342 alkenyl group Chemical group 0.000 description 16
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 239000000730 antalgic agent Substances 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 208000000094 Chronic Pain Diseases 0.000 description 11
- 230000008061 calcium-channel-blocking effect Effects 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 229940035676 analgesics Drugs 0.000 description 10
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 125000005647 linker group Chemical group 0.000 description 9
- 208000004454 Hyperalgesia Diseases 0.000 description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 125000002252 acyl group Chemical group 0.000 description 7
- 239000000654 additive Substances 0.000 description 7
- 230000000996 additive effect Effects 0.000 description 7
- 235000008206 alpha-amino acids Nutrition 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000000903 blocking effect Effects 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 229960002428 fentanyl Drugs 0.000 description 7
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000000829 suppository Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 208000005298 acute pain Diseases 0.000 description 6
- 150000001413 amino acids Chemical group 0.000 description 6
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 229960005489 paracetamol Drugs 0.000 description 6
- BPKIMPVREBSLAJ-QTBYCLKRSA-N ziconotide Chemical compound C([C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]2C(=O)N[C@@H]3C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CSSC2)C(N)=O)=O)CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CSSC3)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(N1)=O)CCSC)[C@@H](C)O)C1=CC=C(O)C=C1 BPKIMPVREBSLAJ-QTBYCLKRSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 5
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 150000001371 alpha-amino acids Chemical class 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000013270 controlled release Methods 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 230000010534 mechanism of action Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 229960005181 morphine Drugs 0.000 description 5
- 229960002811 ziconotide Drugs 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 4
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 4
- 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 4
- 239000000890 drug combination Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 229960001680 ibuprofen Drugs 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 description 3
- 0 *C(c1ccccc1)c1ccccc1 Chemical compound *C(c1ccccc1)c1ccccc1 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 208000026935 allergic disease Diseases 0.000 description 3
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001589 carboacyl group Chemical group 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
- 125000004122 cyclic group Chemical group 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007726 management method Methods 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 210000001032 spinal nerve Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000006024 2-pentenyl group Chemical group 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000006041 3-hexenyl group Chemical group 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 2
- 229940122361 Bisphosphonate Drugs 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 102000055006 Calcitonin Human genes 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 206010019851 Hepatotoxicity Diseases 0.000 description 2
- 208000035154 Hyperesthesia Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 208000004550 Postoperative Pain Diseases 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000001467 acupuncture Methods 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 229940125681 anticonvulsant agent Drugs 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 description 2
- 229960000794 baclofen Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
- 229960004015 calcitonin Drugs 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229960002504 capsaicin Drugs 0.000 description 2
- 235000017663 capsaicin Nutrition 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
- 229960002896 clonidine Drugs 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 2
- 229960000616 diflunisal Drugs 0.000 description 2
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 230000007686 hepatotoxicity Effects 0.000 description 2
- 231100000304 hepatotoxicity Toxicity 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000011221 initial treatment Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 229960004384 ketorolac tromethamine Drugs 0.000 description 2
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 229960005015 local anesthetics Drugs 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229960003464 mefenamic acid Drugs 0.000 description 2
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229960002009 naproxen Drugs 0.000 description 2
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 230000007383 nerve stimulation Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229940124641 pain reliever Drugs 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 150000003873 salicylate salts Chemical class 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000009044 synergistic interaction Effects 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 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
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 1
- CRDAMVZIKSXKFV-FBXUGWQNSA-N (2-cis,6-cis)-farnesol Chemical compound CC(C)=CCC\C(C)=C/CC\C(C)=C/CO CRDAMVZIKSXKFV-FBXUGWQNSA-N 0.000 description 1
- 239000000260 (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol Substances 0.000 description 1
- VLPIATFUUWWMKC-SNVBAGLBSA-N (2r)-1-(2,6-dimethylphenoxy)propan-2-amine Chemical compound C[C@@H](N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-SNVBAGLBSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical class OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- KWVFXCVHYOLFNX-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-ylmethyl)-4-[6,6-bis(4-fluorophenyl)hexyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CC=2C=C3OCOC3=CC=2)CC1 KWVFXCVHYOLFNX-UHFFFAOYSA-N 0.000 description 1
- OUGOONSOCAIFKF-UHFFFAOYSA-N 1-(4-amino-2,3,5-trimethylphenoxy)-3-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]propan-2-ol Chemical compound CC1=C(N)C(C)=CC(OCC(O)CN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1C OUGOONSOCAIFKF-UHFFFAOYSA-N 0.000 description 1
- JHXXWJVUBVEGPP-UHFFFAOYSA-N 1-(4-butan-2-ylpiperazin-1-yl)-3,3-diphenylpropan-1-one Chemical compound C1CN(C(C)CC)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 JHXXWJVUBVEGPP-UHFFFAOYSA-N 0.000 description 1
- VOIMJWKKQYVIGY-UHFFFAOYSA-N 1-(4-cycloheptylpiperazin-1-yl)-3,3-diphenylpropan-1-one Chemical compound C1CN(C2CCCCCC2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 VOIMJWKKQYVIGY-UHFFFAOYSA-N 0.000 description 1
- JYWIDYKOFQWLMR-UHFFFAOYSA-N 1-(4-heptylpiperazin-1-yl)-3,3-diphenylpropan-1-one Chemical compound C1CN(CCCCCCC)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 JYWIDYKOFQWLMR-UHFFFAOYSA-N 0.000 description 1
- BCKDLVZHSCRLAR-UHFFFAOYSA-N 1-(4-pentan-3-ylpiperazin-1-yl)-3,3-diphenylpropan-1-one Chemical compound C1CN(C(CC)CC)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 BCKDLVZHSCRLAR-UHFFFAOYSA-N 0.000 description 1
- MPZPVPAIGBGCJW-UHFFFAOYSA-N 1-[2-(1,3-benzodioxol-5-yloxy)ethyl]-4-[6,6-bis(4-fluorophenyl)hexyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCOC=2C=C3OCOC3=CC=2)CC1 MPZPVPAIGBGCJW-UHFFFAOYSA-N 0.000 description 1
- FMTZEPKLFACZGJ-UHFFFAOYSA-N 1-[4-(1,3-benzothiazol-2-yl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(C=2SC3=CC=CC=C3N=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 FMTZEPKLFACZGJ-UHFFFAOYSA-N 0.000 description 1
- LIYFZWGHCBXXMR-UHFFFAOYSA-N 1-[4-(1,3-benzothiazol-2-yl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C=2SC3=CC=CC=C3N=2)CC1 LIYFZWGHCBXXMR-UHFFFAOYSA-N 0.000 description 1
- GSNNUWVDLVLXJI-UHFFFAOYSA-N 1-[4-(1-adamantylmethyl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(CC23CC4CC(CC(C4)C2)C3)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 GSNNUWVDLVLXJI-UHFFFAOYSA-N 0.000 description 1
- PHGAZJJSQQSXNU-UHFFFAOYSA-N 1-[4-(1-benzylbenzimidazol-2-yl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(C=2N(C3=CC=CC=C3N=2)CC=2C=CC=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 PHGAZJJSQQSXNU-UHFFFAOYSA-N 0.000 description 1
- LMASXIHWSDRASF-UHFFFAOYSA-N 1-[4-(2,3-dichlorophenyl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound ClC1=CC=CC(N2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1Cl LMASXIHWSDRASF-UHFFFAOYSA-N 0.000 description 1
- BYPJLLQGKOIARB-UHFFFAOYSA-N 1-[4-(2-anilinoethyl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(CCNC=2C=CC=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 BYPJLLQGKOIARB-UHFFFAOYSA-N 0.000 description 1
- BXQXDBCUCOHWAV-UHFFFAOYSA-N 1-[4-(2-anilinoethyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCNC=2C=CC=CC=2)CC1 BXQXDBCUCOHWAV-UHFFFAOYSA-N 0.000 description 1
- DRBJWKBCCWABCG-UHFFFAOYSA-N 1-[4-(3,4-dimethoxybenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 DRBJWKBCCWABCG-UHFFFAOYSA-N 0.000 description 1
- YXMORHPMPDDINZ-UHFFFAOYSA-N 1-[4-(3,4-dimethylphenyl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1=C(C)C(C)=CC=C1N1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 YXMORHPMPDDINZ-UHFFFAOYSA-N 0.000 description 1
- LDTQHKVLRQRFEB-UHFFFAOYSA-N 1-[4-(3,5-dibromo-4-hydroxybenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(Br)C(O)=C(Br)C=C1C(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 LDTQHKVLRQRFEB-UHFFFAOYSA-N 0.000 description 1
- MOAUDUFIPWCRCF-UHFFFAOYSA-N 1-[4-(3,5-dichlorophenyl)piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound ClC1=CC(Cl)=CC(N2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 MOAUDUFIPWCRCF-UHFFFAOYSA-N 0.000 description 1
- JLPSMXPDEKOWNN-UHFFFAOYSA-N 1-[4-(3,5-ditert-butyl-4-hydroxybenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)N2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 JLPSMXPDEKOWNN-UHFFFAOYSA-N 0.000 description 1
- HTTLIQFTUASLKJ-UHFFFAOYSA-N 1-[4-(3,5-ditert-butyl-4-methoxybenzoyl)-2-methylpiperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1CC(C)N(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 HTTLIQFTUASLKJ-UHFFFAOYSA-N 0.000 description 1
- MBFAOOZDUTUYCE-UHFFFAOYSA-N 1-[4-(3,5-ditert-butyl-4-methoxybenzoyl)-3-methylpiperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1C(C)CN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 MBFAOOZDUTUYCE-UHFFFAOYSA-N 0.000 description 1
- IKXBGIDOAZUISA-UHFFFAOYSA-N 1-[4-(3,5-ditert-butyl-4-methoxybenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 IKXBGIDOAZUISA-UHFFFAOYSA-N 0.000 description 1
- OVQOLXYGJJAFNK-UHFFFAOYSA-N 1-[4-(3,5-ditert-butylbenzoyl)-2-methylpiperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound CC1CN(C(=O)C=2C=C(C=C(C=2)C(C)(C)C)C(C)(C)C)CCN1C(=O)CCCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 OVQOLXYGJJAFNK-UHFFFAOYSA-N 0.000 description 1
- PJBAXJSEDXDPOU-UHFFFAOYSA-N 1-[4-(3,5-ditert-butylbenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC(C(=O)N2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 PJBAXJSEDXDPOU-UHFFFAOYSA-N 0.000 description 1
- HCCUPFWMVFHHQT-UHFFFAOYSA-N 1-[4-(4-bromobenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C(=O)C=2C=CC(Br)=CC=2)CC1 HCCUPFWMVFHHQT-UHFFFAOYSA-N 0.000 description 1
- WHRDRCYBGWDOEN-UHFFFAOYSA-N 1-[4-(4-tert-butylbenzoyl)piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 WHRDRCYBGWDOEN-UHFFFAOYSA-N 0.000 description 1
- OLIMCDILRKSIGC-UHFFFAOYSA-N 1-[4-[(1-methylpiperidin-3-yl)methyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1N(C)CCCC1CN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 OLIMCDILRKSIGC-UHFFFAOYSA-N 0.000 description 1
- SNLUJUXVFVOODX-UHFFFAOYSA-N 1-[4-[(1-methylpiperidin-4-yl)methyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(C)CCC1CN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 SNLUJUXVFVOODX-UHFFFAOYSA-N 0.000 description 1
- PCUMPEOAVWVBKD-UHFFFAOYSA-N 1-[4-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 PCUMPEOAVWVBKD-UHFFFAOYSA-N 0.000 description 1
- KAXARLDIZPGNAE-UHFFFAOYSA-N 1-[4-[(3,5-ditert-butyl-4-hydroxyphenyl)methyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CN2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 KAXARLDIZPGNAE-UHFFFAOYSA-N 0.000 description 1
- WFWWRMLXRXPPQR-UHFFFAOYSA-N 1-[4-[(3,5-ditert-butyl-4-methoxyphenyl)methyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1CN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 WFWWRMLXRXPPQR-UHFFFAOYSA-N 0.000 description 1
- JXTHBTOFIPASGW-UHFFFAOYSA-N 1-[4-[2-(1,3-benzodioxol-5-yloxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(CCOC=2C=C3OCOC3=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 JXTHBTOFIPASGW-UHFFFAOYSA-N 0.000 description 1
- OPPQVYZVXUVKLS-UHFFFAOYSA-N 1-[4-[2-(1,3-benzodioxol-5-yloxy)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCOC=2C=C3OCOC3=CC=2)CC1 OPPQVYZVXUVKLS-UHFFFAOYSA-N 0.000 description 1
- RXXMUGUZIDVAAU-UHFFFAOYSA-N 1-[4-[2-(1,3-benzothiazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(CCSC=2SC3=CC=CC=C3N=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 RXXMUGUZIDVAAU-UHFFFAOYSA-N 0.000 description 1
- UYXJZQPUDGJORK-UHFFFAOYSA-N 1-[4-[2-(1,3-benzothiazol-2-ylsulfanyl)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCSC=2SC3=CC=CC=C3N=2)CC1 UYXJZQPUDGJORK-UHFFFAOYSA-N 0.000 description 1
- UTMPXRCITGTTCZ-UHFFFAOYSA-N 1-[4-[2-(2,4-dichlorophenoxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound ClC1=CC(Cl)=CC=C1OCCN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 UTMPXRCITGTTCZ-UHFFFAOYSA-N 0.000 description 1
- SNXMRAJPZLZZFT-UHFFFAOYSA-N 1-[4-[2-(2,4-dichlorophenoxy)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCOC=2C(=CC(Cl)=CC=2)Cl)CC1 SNXMRAJPZLZZFT-UHFFFAOYSA-N 0.000 description 1
- BNMXGJHLWYRVJX-UHFFFAOYSA-N 1-[4-[2-(2,4-difluorophenoxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound FC1=CC(F)=CC=C1OCCN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 BNMXGJHLWYRVJX-UHFFFAOYSA-N 0.000 description 1
- PSRGIXGZLGGOSO-UHFFFAOYSA-N 1-[4-[2-(2,4-difluorophenoxy)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCOC=2C(=CC(F)=CC=2)F)CC1 PSRGIXGZLGGOSO-UHFFFAOYSA-N 0.000 description 1
- BINLOMAVCCPIRF-UHFFFAOYSA-N 1-[4-[2-(3,4-dimethoxyphenoxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1=C(OC)C(OC)=CC=C1OCCN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 BINLOMAVCCPIRF-UHFFFAOYSA-N 0.000 description 1
- VIAUSJSHIODTCE-UHFFFAOYSA-N 1-[4-[2-(3,4-dimethoxyphenoxy)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(OC)C(OC)=CC=C1OCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 VIAUSJSHIODTCE-UHFFFAOYSA-N 0.000 description 1
- DSHHZQKOJMCVRE-UHFFFAOYSA-N 1-[4-[2-(4-amino-2,3,5-trimethylphenoxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound CC1=C(N)C(C)=CC(OCCN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C DSHHZQKOJMCVRE-UHFFFAOYSA-N 0.000 description 1
- OYWGGMZNGOFJKE-UHFFFAOYSA-N 1-[4-[2-(4-fluorophenoxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1=CC(F)=CC=C1OCCN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 OYWGGMZNGOFJKE-UHFFFAOYSA-N 0.000 description 1
- KCGXZHIKOJAOJM-UHFFFAOYSA-N 1-[4-[2-(4-fluorophenoxy)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1OCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 KCGXZHIKOJAOJM-UHFFFAOYSA-N 0.000 description 1
- WXBSKRQPBPKJQJ-UHFFFAOYSA-N 1-[4-[2-(4-methoxyphenoxy)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1=CC(OC)=CC=C1OCCN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 WXBSKRQPBPKJQJ-UHFFFAOYSA-N 0.000 description 1
- CPTKYPFGVHVBBO-UHFFFAOYSA-N 1-[4-[2-(benzylamino)ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCNCC=2C=CC=CC=2)CC1 CPTKYPFGVHVBBO-UHFFFAOYSA-N 0.000 description 1
- AHDUATGBAKNZPE-UHFFFAOYSA-N 1-[4-[2-(dipropylamino)ethyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(CCN(CCC)CCC)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 AHDUATGBAKNZPE-UHFFFAOYSA-N 0.000 description 1
- VIASYJOUNFCJCN-UHFFFAOYSA-N 1-[4-[2-[(4-chlorophenyl)methylamino]ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCNCC=2C=CC(Cl)=CC=2)CC1 VIASYJOUNFCJCN-UHFFFAOYSA-N 0.000 description 1
- CDYDWCPPDZIFJI-UHFFFAOYSA-N 1-[4-[2-[(4-tert-butylphenyl)methylamino]ethyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(C(C)(C)C)=CC=C1CNCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 CDYDWCPPDZIFJI-UHFFFAOYSA-N 0.000 description 1
- QHSLTWMAYPJDHE-UHFFFAOYSA-N 1-[4-[3,5-bis(trifluoromethyl)benzoyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C(=O)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CC1 QHSLTWMAYPJDHE-UHFFFAOYSA-N 0.000 description 1
- AOHLSLQKXPWNJV-UHFFFAOYSA-N 1-[4-[3,5-ditert-butyl-4-[2-(dimethylamino)ethoxy]benzoyl]piperazin-1-yl]-6,6-bis(4-fluorophenyl)hexan-1-one Chemical compound C1=C(C(C)(C)C)C(OCCN(C)C)=C(C(C)(C)C)C=C1C(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 AOHLSLQKXPWNJV-UHFFFAOYSA-N 0.000 description 1
- UCMNJPVQPHPMBY-UHFFFAOYSA-N 1-[4-[3-(4-amino-2,3,5-trimethylphenoxy)-2-hydroxypropyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound CC1=C(N)C(C)=CC(OCC(O)CN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C UCMNJPVQPHPMBY-UHFFFAOYSA-N 0.000 description 1
- XAAKCCGKBSELMY-UHFFFAOYSA-N 1-[4-[3-(dimethylamino)propyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1CN(CCCN(C)C)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 XAAKCCGKBSELMY-UHFFFAOYSA-N 0.000 description 1
- QXWKSDUCOMOKND-UHFFFAOYSA-N 1-[4-[4-[(4-fluorophenyl)methyl]phenyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1=CC(F)=CC=C1CC1=CC=C(N2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 QXWKSDUCOMOKND-UHFFFAOYSA-N 0.000 description 1
- YAKJSSNUJBUIOJ-UHFFFAOYSA-N 1-[4-[bis(4-fluorophenyl)methoxy]butyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC(CN2CCN(CCCCOC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 YAKJSSNUJBUIOJ-UHFFFAOYSA-N 0.000 description 1
- DJGIKHDXGINION-UHFFFAOYSA-N 1-[4-[cyclopropyl-(4-fluorophenyl)methyl]piperazin-1-yl]-3,3-diphenylpropan-1-one Chemical compound C1=CC(F)=CC=C1C(N1CCN(CC1)C(=O)CC(C=1C=CC=CC=1)C=1C=CC=CC=1)C1CC1 DJGIKHDXGINION-UHFFFAOYSA-N 0.000 description 1
- CWOYRMQVUCWPTB-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexanoyl]-4-(3,5-ditert-butyl-4-hydroxybenzoyl)piperazin-2-one Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)N2CC(=O)N(C(=O)CCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 CWOYRMQVUCWPTB-UHFFFAOYSA-N 0.000 description 1
- QVUSIJOIPBNJJJ-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexanoyl]-4-(3,5-ditert-butyl-4-methoxybenzoyl)piperazin-2-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1CC(=O)N(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 QVUSIJOIPBNJJJ-UHFFFAOYSA-N 0.000 description 1
- OSGOHAVUPVXVKI-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-(2-phenoxyethyl)piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCOC=2C=CC=CC=2)CC1 OSGOHAVUPVXVKI-UHFFFAOYSA-N 0.000 description 1
- CWFLQNPJVNOFTA-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-(2-phenylsulfanylethyl)piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCSC=2C=CC=CC=2)CC1 CWFLQNPJVNOFTA-UHFFFAOYSA-N 0.000 description 1
- OANLFJVXKYVMDB-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-(3,4,5-trimethoxybenzoyl)piperazin-2-one Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CC(=O)N(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 OANLFJVXKYVMDB-UHFFFAOYSA-N 0.000 description 1
- AKEOQIGPKJVFBH-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-(3,5-ditert-butyl-4-methoxybenzoyl)piperazin-2-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1CC(=O)N(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 AKEOQIGPKJVFBH-UHFFFAOYSA-N 0.000 description 1
- ALKNWKFWYPAJOU-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-(9h-thioxanthen-9-yl)piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(C2C3=CC=CC=C3SC3=CC=CC=C32)CC1 ALKNWKFWYPAJOU-UHFFFAOYSA-N 0.000 description 1
- NSQDOOVDRZZCIH-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine-2-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CN2CC(N(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)C(O)=O)=C1 NSQDOOVDRZZCIH-UHFFFAOYSA-N 0.000 description 1
- UPTFULKJNIHEGP-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,4-dimethoxyphenyl)methyl]piperazine Chemical compound C1=C(OC)C(OC)=CC=C1CN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 UPTFULKJNIHEGP-UHFFFAOYSA-N 0.000 description 1
- XVQGPTPHXYSOOC-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,5-ditert-butyl-4-methoxyphenyl)methyl]piperazin-2-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1CN1CC(=O)N(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 XVQGPTPHXYSOOC-UHFFFAOYSA-N 0.000 description 1
- XRYLRSPQAGGXGI-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,5-ditert-butyl-4-methoxyphenyl)methyl]piperazine Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1CN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 XRYLRSPQAGGXGI-UHFFFAOYSA-N 0.000 description 1
- GQDFRLDUWXFTSJ-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,5-ditert-butylphenyl)methyl]piperazine Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC(CN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 GQDFRLDUWXFTSJ-UHFFFAOYSA-N 0.000 description 1
- LARUGYACKUHGCL-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(4-bromophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CC=2C=CC(Br)=CC=2)CC1 LARUGYACKUHGCL-UHFFFAOYSA-N 0.000 description 1
- VMZTXEFNNUROEK-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(4-tert-butylphenyl)methyl]piperazine Chemical compound C1=CC(C(C)(C)C)=CC=C1CN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 VMZTXEFNNUROEK-UHFFFAOYSA-N 0.000 description 1
- NYUPHTOUBKXRLC-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[2-(2,4-dichlorophenoxy)ethyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCOC=2C(=CC(Cl)=CC=2)Cl)CC1 NYUPHTOUBKXRLC-UHFFFAOYSA-N 0.000 description 1
- LUJHSABVZDOEFE-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[2-(2,4-difluorophenoxy)ethyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCOC=2C(=CC(F)=CC=2)F)CC1 LUJHSABVZDOEFE-UHFFFAOYSA-N 0.000 description 1
- DVFKAVGLLGEJFY-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[2-(3,4,5-trimethoxyphenoxy)ethyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC(OCCN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 DVFKAVGLLGEJFY-UHFFFAOYSA-N 0.000 description 1
- NRUOUYDMPDQQRN-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[2-(3,4-dimethoxyphenoxy)ethyl]piperazine Chemical compound C1=C(OC)C(OC)=CC=C1OCCN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 NRUOUYDMPDQQRN-UHFFFAOYSA-N 0.000 description 1
- AJKNMIVMHRLNMM-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[2-(4-fluorophenoxy)ethyl]piperazine Chemical compound C1=CC(F)=CC=C1OCCN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 AJKNMIVMHRLNMM-UHFFFAOYSA-N 0.000 description 1
- XKSHBLAXIXLMSK-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[2-(4-methoxyphenoxy)ethyl]piperazine Chemical compound C1=CC(OC)=CC=C1OCCN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 XKSHBLAXIXLMSK-UHFFFAOYSA-N 0.000 description 1
- JEVNGJOBFVDKBM-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[[3,5-bis(trifluoromethyl)phenyl]methyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CC1 JEVNGJOBFVDKBM-UHFFFAOYSA-N 0.000 description 1
- OVTQHHRONODWCD-UHFFFAOYSA-N 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[[4-(trifluoromethoxy)phenyl]methyl]piperazine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CC=2C=CC(OC(F)(F)F)=CC=2)CC1 OVTQHHRONODWCD-UHFFFAOYSA-N 0.000 description 1
- HJRPKCUMFDYICI-UHFFFAOYSA-N 1-[9,9-bis(4-fluorophenyl)nonyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine Chemical compound COC1=C(OC)C(OC)=CC(CN2CCN(CCCCCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 HJRPKCUMFDYICI-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical compound C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 1
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
- LSMCZRHVZVUYQM-UHFFFAOYSA-N 2-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]ethylsulfanyl]-1,3-benzothiazole Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCSC=2SC3=CC=CC=C3N=2)CC1 LSMCZRHVZVUYQM-UHFFFAOYSA-N 0.000 description 1
- WSOVBGDKBQSKDA-UHFFFAOYSA-N 2-[4-(3,3-diphenylpropanoyl)piperazin-1-yl]-n-methyl-n-phenylacetamide Chemical compound C=1C=CC=CC=1N(C)C(=O)CN(CC1)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 WSOVBGDKBQSKDA-UHFFFAOYSA-N 0.000 description 1
- MBLRTKXFRMCWNN-UHFFFAOYSA-N 2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-1,3-benzothiazole Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(C=2SC3=CC=CC=C3N=2)CC1 MBLRTKXFRMCWNN-UHFFFAOYSA-N 0.000 description 1
- NAYFHNYQVWMGPO-UHFFFAOYSA-N 2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-n-[(3,4,5-trimethoxyphenyl)methyl]ethanamine Chemical compound COC1=C(OC)C(OC)=CC(CNCCN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 NAYFHNYQVWMGPO-UHFFFAOYSA-N 0.000 description 1
- ILKLNJALSWEXDH-UHFFFAOYSA-N 2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]pyrimidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(C=2N=CC=CN=2)CC1 ILKLNJALSWEXDH-UHFFFAOYSA-N 0.000 description 1
- PRFCNFBEYSWBGY-UHFFFAOYSA-N 2-[4-[[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]methyl]-2,6-ditert-butylphenoxy]-n,n-dimethylethanamine Chemical compound C1=C(C(C)(C)C)C(OCCN(C)C)=C(C(C)(C)C)C=C1CN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 PRFCNFBEYSWBGY-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- SZJRFKXXIWHDPB-UHFFFAOYSA-N 3,3-diphenyl-1-(4-propan-2-ylpiperazin-1-yl)propan-1-one Chemical compound C1CN(C(C)C)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 SZJRFKXXIWHDPB-UHFFFAOYSA-N 0.000 description 1
- XWIQZCMTXWBRIC-UHFFFAOYSA-N 3,3-diphenyl-1-[4-(1-phenylethyl)piperazin-1-yl]propan-1-one Chemical compound C=1C=CC=CC=1C(C)N(CC1)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 XWIQZCMTXWBRIC-UHFFFAOYSA-N 0.000 description 1
- HSBMCZLHMONMJF-UHFFFAOYSA-N 3,3-diphenyl-1-[4-(2-phenylsulfanylethyl)piperazin-1-yl]propan-1-one Chemical compound C1CN(CCSC=2C=CC=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 HSBMCZLHMONMJF-UHFFFAOYSA-N 0.000 description 1
- KPOYPTPVTLILDV-UHFFFAOYSA-N 3,3-diphenyl-1-[4-(4-phenylphenyl)piperazin-1-yl]propan-1-one Chemical compound C1CN(C=2C=CC(=CC=2)C=2C=CC=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 KPOYPTPVTLILDV-UHFFFAOYSA-N 0.000 description 1
- DIQTUUXPQAXWLH-UHFFFAOYSA-N 3,3-diphenyl-1-[4-(4-trimethylsilylphenyl)piperazin-1-yl]propan-1-one Chemical compound C1=CC([Si](C)(C)C)=CC=C1N1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 DIQTUUXPQAXWLH-UHFFFAOYSA-N 0.000 description 1
- HBAPFBGTSWKLIB-UHFFFAOYSA-N 3,3-diphenyl-1-[4-(pyridin-4-ylmethyl)piperazin-1-yl]propan-1-one Chemical compound C1CN(CC=2C=CN=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 HBAPFBGTSWKLIB-UHFFFAOYSA-N 0.000 description 1
- HHNGCXXODFPAPN-UHFFFAOYSA-N 3,3-diphenyl-1-[4-[2-(2,3,5,6-tetrafluorophenoxy)ethyl]piperazin-1-yl]propan-1-one Chemical compound FC1=CC(F)=C(F)C(OCCN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1F HHNGCXXODFPAPN-UHFFFAOYSA-N 0.000 description 1
- HYEVGEADMJRJCY-UHFFFAOYSA-N 3,3-diphenyl-1-[4-[2-(3,4,5-trimethoxyphenoxy)ethyl]piperazin-1-yl]propan-1-one Chemical compound COC1=C(OC)C(OC)=CC(OCCN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 HYEVGEADMJRJCY-UHFFFAOYSA-N 0.000 description 1
- GDEDKPHEBVAMIZ-UHFFFAOYSA-N 3,3-diphenyl-1-[4-[phenyl(thiophen-2-yl)methyl]piperazin-1-yl]propan-1-one Chemical compound C1CN(C(C=2SC=CC=2)C=2C=CC=CC=2)CCN1C(=O)CC(C=1C=CC=CC=1)C1=CC=CC=C1 GDEDKPHEBVAMIZ-UHFFFAOYSA-N 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
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- NCVPFKGNCDYGND-UHFFFAOYSA-N 4-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]ethoxy]-2,3,6-trimethylaniline Chemical compound CC1=C(N)C(C)=CC(OCCN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1C NCVPFKGNCDYGND-UHFFFAOYSA-N 0.000 description 1
- ITSLOYOUMFJGNK-UHFFFAOYSA-N 4-[6,6-bis(4-fluorophenyl)hexanoyl]-1-(3,5-ditert-butyl-4-methoxybenzoyl)piperazin-2-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1C(=O)CN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 ITSLOYOUMFJGNK-UHFFFAOYSA-N 0.000 description 1
- COKCFPZZAWMJSF-UHFFFAOYSA-N 4-[6,6-bis(4-fluorophenyl)hexanoyl]-1-[(3,4,5-trimethoxyphenyl)methyl]piperazin-2-one Chemical compound COC1=C(OC)C(OC)=CC(CN2C(CN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=O)=C1 COKCFPZZAWMJSF-UHFFFAOYSA-N 0.000 description 1
- KHACYUFNZGHCOQ-UHFFFAOYSA-N 4-[6,6-bis(4-fluorophenyl)hexanoyl]-1-[(3,5-ditert-butyl-4-methoxyphenyl)methyl]piperazin-2-one Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1CN1C(=O)CN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 KHACYUFNZGHCOQ-UHFFFAOYSA-N 0.000 description 1
- VHUOZRBECXGDFH-UHFFFAOYSA-N 4-[6,6-bis(4-fluorophenyl)hexanoyl]-1-[2-(4-fluorophenoxy)ethyl]piperazin-2-one Chemical compound C1=CC(F)=CC=C1OCCN1C(=O)CN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 VHUOZRBECXGDFH-UHFFFAOYSA-N 0.000 description 1
- PHYMYYKBDVGTRI-UHFFFAOYSA-N 4-[6,6-bis(4-fluorophenyl)hexyl]-1-[(3,4,5-trimethoxyphenyl)methyl]piperazin-2-one Chemical compound COC1=C(OC)C(OC)=CC(CN2C(CN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=O)=C1 PHYMYYKBDVGTRI-UHFFFAOYSA-N 0.000 description 1
- MYIQYYKACSYYJO-UHFFFAOYSA-N 4-[6,6-bis(4-fluorophenyl)hexyl]-1-[(3,4,5-trimethoxyphenyl)methyl]piperazine-2-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CN2C(CN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)C(O)=O)=C1 MYIQYYKACSYYJO-UHFFFAOYSA-N 0.000 description 1
- HBQGTGNLAHZYCY-UHFFFAOYSA-N 4-[[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]methyl]-2,6-dibromophenol Chemical compound C1=C(Br)C(O)=C(Br)C=C1CN1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 HBQGTGNLAHZYCY-UHFFFAOYSA-N 0.000 description 1
- LGWUJYVVGNWGQS-UHFFFAOYSA-N 4-[[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]methyl]-2,6-dimethoxyphenol Chemical compound COC1=C(O)C(OC)=CC(CN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 LGWUJYVVGNWGQS-UHFFFAOYSA-N 0.000 description 1
- AMMLIKZUXHUTJS-UHFFFAOYSA-N 4-[[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]methyl]-2,6-ditert-butylphenol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CN2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 AMMLIKZUXHUTJS-UHFFFAOYSA-N 0.000 description 1
- XMAXPBOXNATPQN-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-(4-pyrimidin-2-ylpiperazin-1-yl)hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C=2N=CC=CN=2)CC1 XMAXPBOXNATPQN-UHFFFAOYSA-N 0.000 description 1
- QGSGSHFXGZXJFU-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-(1-hydroxy-2h-pyridine-4-carbonyl)piperazin-1-yl]hexan-1-one Chemical compound C1=CN(O)CC=C1C(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 QGSGSHFXGZXJFU-UHFFFAOYSA-N 0.000 description 1
- FZJIZFZMYRGIEH-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-(2-phenoxyethyl)piperazin-1-yl]hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCOC=2C=CC=CC=2)CC1 FZJIZFZMYRGIEH-UHFFFAOYSA-N 0.000 description 1
- PHHJNFJKXGYWPD-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-(2-phenylsulfanylethyl)piperazin-1-yl]hexan-1-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(CCSC=2C=CC=CC=2)CC1 PHHJNFJKXGYWPD-UHFFFAOYSA-N 0.000 description 1
- CDIUZULUXKSCMT-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-(3,4,5-trimethoxybenzoyl)piperazin-1-yl]hex-5-en-1-one Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCN(CC2)C(=O)CCCC=C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 CDIUZULUXKSCMT-UHFFFAOYSA-N 0.000 description 1
- YYKXKCPJBKZHFW-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-(4-hydroxy-3,5-dimethoxybenzoyl)piperazin-1-yl]hexan-1-one Chemical compound COC1=C(O)C(OC)=CC(C(=O)N2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 YYKXKCPJBKZHFW-UHFFFAOYSA-N 0.000 description 1
- JMYWPLIZPDJINL-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[2-(3,4,5-trimethoxyphenoxy)ethyl]piperazin-1-yl]hexan-1-one Chemical compound COC1=C(OC)C(OC)=CC(OCCN2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 JMYWPLIZPDJINL-UHFFFAOYSA-N 0.000 description 1
- ZNBKTONPFWDASM-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[2-(4-methoxyphenoxy)ethyl]piperazin-1-yl]hexan-1-one Chemical compound C1=CC(OC)=CC=C1OCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 ZNBKTONPFWDASM-UHFFFAOYSA-N 0.000 description 1
- KUNYFKGGZDHOGV-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[2-[(3,4,5-trimethoxyphenyl)methylamino]ethyl]piperazin-1-yl]hexan-1-one Chemical compound COC1=C(OC)C(OC)=CC(CNCCN2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 KUNYFKGGZDHOGV-UHFFFAOYSA-N 0.000 description 1
- IBRJEYGHSMJUGO-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[2-[(4-fluorophenyl)methylamino]ethyl]piperazin-1-yl]hexan-1-one Chemical compound C1=CC(F)=CC=C1CNCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 IBRJEYGHSMJUGO-UHFFFAOYSA-N 0.000 description 1
- UFPIIRIZGUYSCA-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[2-[(4-methylphenyl)methylamino]ethyl]piperazin-1-yl]hexan-1-one Chemical compound C1=CC(C)=CC=C1CNCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 UFPIIRIZGUYSCA-UHFFFAOYSA-N 0.000 description 1
- AEQLFICAFUJLAB-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[2-[(4-propan-2-ylphenyl)methylamino]ethyl]piperazin-1-yl]hexan-1-one Chemical compound C1=CC(C(C)C)=CC=C1CNCCN1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 AEQLFICAFUJLAB-UHFFFAOYSA-N 0.000 description 1
- NCALEGZCXVEGNC-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-1-[4-[4-(trifluoromethoxy)benzoyl]piperazin-1-yl]hexan-2-one Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCC(=O)CN1CCN(C(=O)C=2C=CC(OC(F)(F)F)=CC=2)CC1 NCALEGZCXVEGNC-UHFFFAOYSA-N 0.000 description 1
- SJQWGRRXLOQUBP-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-5-hydroxy-1-[4-(3,4,5-trimethoxybenzoyl)piperazin-1-yl]hexan-1-one Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCN(CC2)C(=O)CCCC(O)C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 SJQWGRRXLOQUBP-UHFFFAOYSA-N 0.000 description 1
- JYODDRMVGKQHFY-UHFFFAOYSA-N 6,6-bis(4-fluorophenyl)-6-hydroxy-1-[4-(3,4,5-trimethoxybenzoyl)piperazin-1-yl]hexan-1-one Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCN(CC2)C(=O)CCCCC(O)(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 JYODDRMVGKQHFY-UHFFFAOYSA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- JFFFKDHHNGBVFT-UHFFFAOYSA-N 7-phenylheptan-1-amine Chemical compound NCCCCCCCC1=CC=CC=C1 JFFFKDHHNGBVFT-UHFFFAOYSA-N 0.000 description 1
- SCHFZKZGOXKHME-UHFFFAOYSA-N 9,9-bis(4-fluorophenyl)-1-[4-[(3,4,5-trimethoxyphenyl)methyl]piperazin-1-yl]nonan-1-one Chemical compound COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C(=O)CCCCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1 SCHFZKZGOXKHME-UHFFFAOYSA-N 0.000 description 1
- HJUAMXQYAKKEQL-UHFFFAOYSA-N 9,9-diphenyl-1-[4-[(3,4,5-trimethoxyphenyl)methyl]piperazin-1-yl]nonan-1-one Chemical compound COC1=C(OC)C(OC)=CC(CN2CCN(CC2)C(=O)CCCCCCCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 HJUAMXQYAKKEQL-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000000003 Breakthrough pain Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 108010016626 Dipeptides Proteins 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- 102000004016 L-Type Calcium Channels Human genes 0.000 description 1
- 108090000420 L-Type Calcium Channels Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 description 1
- JAQUASYNZVUNQP-USXIJHARSA-N Levorphanol Chemical compound C1C2=CC=C(O)C=C2[C@]23CCN(C)[C@H]1[C@@H]2CCCC3 JAQUASYNZVUNQP-USXIJHARSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 206010040021 Sensory abnormalities Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 102000003691 T-Type Calcium Channels Human genes 0.000 description 1
- 108090000030 T-Type Calcium Channels Proteins 0.000 description 1
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DNDSVBYIWSIFKN-UHFFFAOYSA-N [4-[4-[bis(4-fluorophenyl)methoxy]butyl]piperazin-1-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCN(CCCCOC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 DNDSVBYIWSIFKN-UHFFFAOYSA-N 0.000 description 1
- ZUOJOEMYFVKOPG-UHFFFAOYSA-N [4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-(3,5-ditert-butyl-4-hydroxyphenyl)methanone Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)N2CCN(CCCCCC(C=3C=CC(F)=CC=3)C=3C=CC(F)=CC=3)CC2)=C1 ZUOJOEMYFVKOPG-UHFFFAOYSA-N 0.000 description 1
- DQYMRJZVWUVEHQ-UHFFFAOYSA-N [4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-(3,5-ditert-butyl-4-methoxyphenyl)methanone Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C(=O)N1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 DQYMRJZVWUVEHQ-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229960001391 alfentanil Drugs 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 description 1
- 229960001736 buprenorphine Drugs 0.000 description 1
- GMTYREVWZXJPLF-AFHUBHILSA-N butorphanol D-tartrate Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O.N1([C@@H]2CC3=CC=C(C=C3[C@@]3([C@]2(CCCC3)O)CC1)O)CC1CCC1 GMTYREVWZXJPLF-AFHUBHILSA-N 0.000 description 1
- 229960001590 butorphanol tartrate Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000007942 carboxylates Chemical group 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 1
- 229960002286 clodronic acid Drugs 0.000 description 1
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 1
- 229960003120 clonazepam Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 150000001934 cyclohexanes Chemical class 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960000632 dexamfetamine Drugs 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 1
- 229960004193 dextropropoxyphene Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229960003461 dezocine Drugs 0.000 description 1
- VTMVHDZWSFQSQP-VBNZEHGJSA-N dezocine Chemical compound C1CCCC[C@H]2CC3=CC=C(O)C=C3[C@]1(C)[C@H]2N VTMVHDZWSFQSQP-VBNZEHGJSA-N 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- 229940085304 dihydropyridine derivative selective calcium channel blockers with mainly vascular effects Drugs 0.000 description 1
- 125000004925 dihydropyridyl group Chemical class N1(CC=CC=C1)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- AIJBJWQSZXTWLZ-UHFFFAOYSA-N ethyl 1-[6,6-bis(4-fluorophenyl)hexyl]-4-[(3,4,5-trimethoxyphenyl)methyl]piperazine-2-carboxylate Chemical compound C1CN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)C(C(=O)OCC)CN1CC1=CC(OC)=C(OC)C(OC)=C1 AIJBJWQSZXTWLZ-UHFFFAOYSA-N 0.000 description 1
- LDPMLQFNGFUQGN-UHFFFAOYSA-N ethyl 4-[6,6-bis(4-fluorophenyl)hexyl]-1-[(3,4,5-trimethoxyphenyl)methyl]piperazine-2-carboxylate Chemical compound C1CN(CC=2C=C(OC)C(OC)=C(OC)C=2)C(C(=O)OCC)CN1CCCCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 LDPMLQFNGFUQGN-UHFFFAOYSA-N 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229940043259 farnesol Drugs 0.000 description 1
- 229930002886 farnesol Natural products 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229940013688 formic acid Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 230000037427 ion transport Effects 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
- 229960001848 lamotrigine Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229960003406 levorphanol Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229940072082 magnesium salicylate Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 229960001344 methylphenidate Drugs 0.000 description 1
- 229960003404 mexiletine Drugs 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 229960001165 modafinil Drugs 0.000 description 1
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- HHCHJWLKJRNCGO-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-2-[4-(3,3-diphenylpropanoyl)piperazin-1-yl]acetamide Chemical compound CC1=CC=CC(C)=C1NC(=O)CN1CCN(C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 HHCHJWLKJRNCGO-UHFFFAOYSA-N 0.000 description 1
- LSUAEPIZKSXCLP-UHFFFAOYSA-N n-[2-[4-(3,3-diphenylpropanoyl)piperazin-1-yl]ethyl]-3,4,5-trimethoxybenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NCCN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 LSUAEPIZKSXCLP-UHFFFAOYSA-N 0.000 description 1
- IEZUPBJDCXBYMI-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]-2-oxoethyl]-4-chlorobenzamide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C(=O)CNC(=O)C=2C=CC(Cl)=CC=2)CC1 IEZUPBJDCXBYMI-UHFFFAOYSA-N 0.000 description 1
- LHLNEAHNUCOGMT-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]-2-oxoethyl]-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C(=O)CNC(=O)C=2C=CC(F)=CC=2)CC1 LHLNEAHNUCOGMT-UHFFFAOYSA-N 0.000 description 1
- QIZTUXBMCKTHOD-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]-2-oxoethyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NCC(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 QIZTUXBMCKTHOD-UHFFFAOYSA-N 0.000 description 1
- FQBJMRJSMNYLJI-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]-2-oxoethyl]-4-propan-2-ylbenzamide Chemical compound C1=CC(C(C)C)=CC=C1C(=O)NCC(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 FQBJMRJSMNYLJI-UHFFFAOYSA-N 0.000 description 1
- KALIUZCWZNSFOJ-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]-2-oxoethyl]-4-tert-butylbenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)NCC(=O)N1CCN(C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 KALIUZCWZNSFOJ-UHFFFAOYSA-N 0.000 description 1
- FWQMYVBRNFZZSJ-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]-2-oxoethyl]benzamide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCC(=O)N1CCN(C(=O)CNC(=O)C=2C=CC=CC=2)CC1 FWQMYVBRNFZZSJ-UHFFFAOYSA-N 0.000 description 1
- QARZAPLUFNCNOL-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-2-oxoethyl]-4-chlorobenzamide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(C(=O)CNC(=O)C=2C=CC(Cl)=CC=2)CC1 QARZAPLUFNCNOL-UHFFFAOYSA-N 0.000 description 1
- LRIXGBSUPQSJQG-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-2-oxoethyl]-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(C(=O)CNC(=O)C=2C=CC(F)=CC=2)CC1 LRIXGBSUPQSJQG-UHFFFAOYSA-N 0.000 description 1
- ZYBSCUTTXWUZQV-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-2-oxoethyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NCC(=O)N1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 ZYBSCUTTXWUZQV-UHFFFAOYSA-N 0.000 description 1
- ZCVSFUHOLIUBBT-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-2-oxoethyl]-4-propan-2-ylbenzamide Chemical compound C1=CC(C(C)C)=CC=C1C(=O)NCC(=O)N1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 ZCVSFUHOLIUBBT-UHFFFAOYSA-N 0.000 description 1
- GKWAMLSFXCMPNL-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-2-oxoethyl]-4-tert-butylbenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)NCC(=O)N1CCN(CCCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 GKWAMLSFXCMPNL-UHFFFAOYSA-N 0.000 description 1
- JYRQTNDCLYJCAF-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]-2-oxoethyl]benzamide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(C(=O)CNC(=O)C=2C=CC=CC=2)CC1 JYRQTNDCLYJCAF-UHFFFAOYSA-N 0.000 description 1
- WLBFVQZVEJNLKW-UHFFFAOYSA-N n-[2-[4-[6,6-bis(4-fluorophenyl)hexyl]piperazin-1-yl]ethyl]aniline Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCCCN1CCN(CCNC=2C=CC=CC=2)CC1 WLBFVQZVEJNLKW-UHFFFAOYSA-N 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- YZLZPSJXMWGIFH-BCXQGASESA-N nalbuphine hydrochloride Chemical compound [H+].[Cl-].C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@@H]3O)CN2CC1CCC1 YZLZPSJXMWGIFH-BCXQGASESA-N 0.000 description 1
- 229960001513 nalbuphine hydrochloride Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 229940121367 non-opioid analgesics Drugs 0.000 description 1
- 238000011457 non-pharmacological treatment Methods 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229960001158 nortriptyline Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 229940051877 other opioids in atc Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 1
- 229960001816 oxcarbazepine Drugs 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960005118 oxymorphone Drugs 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 229940124583 pain medication Drugs 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229940046231 pamidronate Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 125000005543 phthalimide group Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 description 1
- 229960003634 pimozide Drugs 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229940020463 prialt Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- GGCSSNBKKAUURC-UHFFFAOYSA-N sufentanil Chemical group C1CN(CCC=2SC=CC=2)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 GGCSSNBKKAUURC-UHFFFAOYSA-N 0.000 description 1
- 229960004739 sufentanil Drugs 0.000 description 1
- 150000003457 sulfones Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical group 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- GZJRWHRCEFHVQN-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-(3,3-diphenylpropanoyl)piperazin-1-yl]ethoxy]-2,3,6-trimethylphenyl]carbamate Chemical compound CC1=C(NC(=O)OC(C)(C)C)C(C)=CC(OCCN2CCN(CC2)C(=O)CC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C GZJRWHRCEFHVQN-UHFFFAOYSA-N 0.000 description 1
- DEOPQFVATDITAI-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-[6,6-bis(4-fluorophenyl)hexanoyl]piperazin-1-yl]ethoxy]-2,3,6-trimethylphenyl]carbamate Chemical compound CC1=C(NC(=O)OC(C)(C)C)C(C)=CC(OCCN2CCN(CC2)C(=O)CCCCC(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)=C1C DEOPQFVATDITAI-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 1
- 229960001918 tiagabine Drugs 0.000 description 1
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 description 1
- 229960000488 tizanidine Drugs 0.000 description 1
- 229960002872 tocainide Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- CRDAMVZIKSXKFV-UHFFFAOYSA-N trans-Farnesol Natural products CC(C)=CCCC(C)=CCCC(C)=CCO CRDAMVZIKSXKFV-UHFFFAOYSA-N 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- KYLIMUJRJDIPPF-UHFFFAOYSA-N trisalicylate Chemical compound O=C1OC2=CC=CC=C2C(=O)OC2=CC=CC=C2C(=O)OC2=CC=CC=C12 KYLIMUJRJDIPPF-UHFFFAOYSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
本発明は、疼痛の処置において有用な組成物および方法に関する。それは、異なる機序によって働く活性構成要素と組み合わせられるN型カルシウムチャネルブロッカーである活性構成要素を有する組成物を含む。N型カルシウムチャネルブロッカーの好ましいクラスが同定される。本発明はまた、N型カルシウムチャネルブロッカーおよびN型カルシウムチャネルを遮断する以外の機序によって働く少なくとも一つの疼痛緩和治療的化合物または非薬理学的プロトコールによって、疼痛緩和を必要とする被験体を並行して処置する段階を含む、疼痛を処置するための方法に関する。
N型カルシウムチャネルは、主に神経に局在し、これらのチャネルを介するイオン輸送を阻害するチャネルブロッカーと呼ばれる化合物は、疼痛を含む様々な状態に対する処置として説明されている。N型カルシウムチャネルを遮断する特定のペプチジル化合物は、疼痛を軽減することが公知である。例えば、ジコノチド(プリアルト(商標))は、N型カルシウムチャネルを阻害することが示されておりかつ重度の慢性疼痛を処置するために使用されるペプチジル天然産物の合成バージョンである。「Ziconotide: Neuronal Calcium Channel Blocker for Severe Chronic Pain」, G. P. Miljanich, Current Medical Chemistry, vol. 11(23), pp. 3029-3040 (Dec. 2004)を参照されたい。Textbook of Pain, 4th ed., P.D. Wall and R. Melzack, ed., Elsevier Science, pg.1236 (2003);およびwww.fda.gov/cder/foi/label/2004/021060lbl.pdfでオンラインで利用できるプリアルト(商標)におけるFDAラベル情報も参照されたい。ジコノチドは、その使用者によって必要とされるオピオイド疼痛薬の量を低減し得る;しかしながら、それは、生体利用性における難しい問題を抱えており、経口的に、または典型的な筋内注射もしくは静脈内注射によってさえも、投与することができない。そのため、ジノコチドは、脊髄における後角に直接的に緩徐に送達するポンプデバイスによって、髄腔内にのみ投与され、そこで、後角の表層(Rexed層IおよびII)における一次侵害受容性(A-δおよびC)求心性神経上に位置するN型カルシウムチャネルに結合することによって作用すると考えられている。ジコノチドは、脊髄に直接的に送達されるが、それは、しばしば、オピオイドなどのその他の非常に強力な疼痛緩和剤との組み合わせにおいて使用される。さらに、ジコノチドの使用は、その他の公知の薬に反応しない重度の慢性疼痛問題の非常に狭いカテゴリーに対してのみ適当である。
本発明は、N型カルシウムチャネル遮断化合物の疼痛緩和効果が、N型カルシウムチャネルを遮断する以外の機序によって働く化合物および処置の疼痛緩和効果と組み合わせられる場合に強化されるという観察に基づく。したがって、N型カルシウムチャネルブロッカーは、疼痛緩和の強化を提供するためにその他の疼痛緩和治療と組み合わせられ得、組み合わせは、疼痛緩和薬剤の単一のタイプに対する依存性の増加に関連するリスクを最小にする。例えば、オピオイドの過剰な使用は、依存および耐性をもたらし得る;公知の選択的COX-2阻害剤は、有害な心事故のリスクを増加させることが疑われている;COX-1およびCOX-2の両方を阻害するほとんどの化合物は、抗凝固活性を有し、胃腸出血を引き起こす傾向があり、アセトアミノフェンなどのその他の鎮痛剤は、しばしば、肝毒性などの副作用を示す。したがって、これらの因子は、任意の一つの鎮痛剤について安全に使用できる投薬量を頻繁に限定する。
疼痛は、多くの形式で現れ、それを処理するための手法は、罹患した個人の健康および快適性に必須である。疼痛は、多くの形式を取るため、疼痛の処置も、処置を患者の必要性に合わせられるように、多くの形式を取る必要がある。例えば、急性疼痛に対する処置は、迅速に機能する必要があるが、有害作用が速やかに消えるように、急性疼痛を処置する薬物を患者の体から速やかに取り除くことが望ましい場合がある。慢性疼痛は、より長く持続する効果を有する薬物を必要とし得る;これらは、迅速に作用する必要はない場合があるが、慢性疼痛は持続的な処置を要求するため、特定の副作用およびその他の薬との相互作用が、慢性疼痛に対する処置において、より問題である場合がある。一次疼痛処置プロトコールの有効性を圧倒する突出疼痛は、最大量の一次処置ですでに投薬治療された患者に投与され得る即効性処置を必要とし得る。かつ、極度の疼痛は、その他のより良い選択肢が存在しない場合に、実質的な有害作用を有する薬物の使用を正当化し得る;オピオイドは、依存性の発生に関して公知の潜在性を有する疼痛緩和剤の例であるが、それでも重度の疼痛を処置するために必須である。
式中、各々のm1およびm2は、独立に0〜5であり;
m3は、0〜2であり;
R1、R2、およびR3の各々は、独立に非干渉置換基(noninterfering substituent)であり;
Zは、NまたはCHであり;
n1およびn2の各々は、独立に0または1であり;
X1およびX2は、リンカーであり;かつ
Wは、ArまたはCyであり、
Arは、一つまたは二つの置換されたまたは非置換の芳香族環またはヘテロ芳香族環を示し、かつ
Cyは、一つもしくは二つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分を示す、または一つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分および一つの置換されたもしくは非置換の芳香族部分もしくはヘテロ芳香族部分からなる。
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(2-フェニルスルファニル-エチル)-ピペラジン-1-イル]-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-[2-(4-フルオロ-フェノキシ)-エチル]-ピペラジン;
1-{4-[2-(ベンゾ[1,3]ジオキソール-5-イルオキシ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(2-フェニルスルファニル-エチル)-ピペラジン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-[2-(4-メトキシ-フェノキシ)-エチル]-ピペラジン;
1-{4-[2-(2,4-ジフルオロ-フェノキシ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(2-フェノキシ-エチル)-ピペラジン-1-イル]-ヘキサン-1-オン;
1-{4-[2-(2,4-ジクロロ-フェノキシ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-{4-[2-(4-メトキシ-フェノキシ)-エチル]-ピペラジン-1-イル}-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(2-フェノキシ-エチル)-ピペラジン;
6,6-ビス-(4-フルオロ-フェニル)-1-{4-[2-(3,4,5-トリメトキシ-フェノキシ)-エチル]-ピペラジン-1-イル}-ヘキサン-1-オン;
1-{4-[2-(ベンゾチアゾール-2-イルスルファニル)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
[4-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-エトキシ)-2,3,6-トリメチル-フェニル]-カルバミン酸tert-ブチルエステル;
4-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-エトキシ)-2,3,6-トリメチル-フェニルアミン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-[2-(2,4-ジクロロ-フェノキシ)-エチル]-ピペラジン;
[2-(4-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イルメチル}-2,6-ジ-tert-ブチル-フェノキシ)-エチル]-ジメチル-アミン;
4-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イルメチル}-2,6-ジ-tert-ブチル-フェノール;
1-[4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンジル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンジル)-ピペラジン;
{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-(3,5-ジ-tert-ブチル-4-メトキシ-フェニル)-メタノン;
1-{4-[3,5-ジ-tert-ブチル-4-(2-ジメチルアミノ-エトキシ)-ベンゾイル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-ベンゾ[1,3]ジオキソール-5-イルメチル-4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,5-ジ-tert-ブチル-ベンジル)-ピペラジン;
{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-(3,5-ジ-tert-ブチル-4-ヒドロキシ-フェニル)-メタノン;
1-[4-(3,5-ジ-tert-ブチル-4-ヒドロキシ-ベンジル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(3,5-ジブロモ-4-ヒドロキシ-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-4-ヒドロキシ-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(4-tert-ブチル-ベンジル)-ピペラジン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(9H-チオキサンテン-9-イル)-ピペラジン;
2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-ベンゾチアゾール;
6,6-ビス-(4-フルオロ-フェニル)-1-(4-ピリミジン-2-イル-ピペラジン-1-イル)-ヘキサン-1-オン;
2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-ピリミジン;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(9H-チオキサンテン-9-イル)-ピペラジン-1-イル]-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-2-カルボン酸エチルエステル;
6,6-ビス-(4-フルオロ-フェニル)-1-{4-[2-(3,4,5-トリメトキシ-ベンジルアミノ)-エチル]-ピペラジン-1-イル}-ヘキサン-1-オン;
9,9-ビス-(4-フルオロ-フェニル)-1-[4-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-1-イル]-ノナン-1-オン;
(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-エチル)-フェニル-アミン;
1-[9,9-ビス-(4-フルオロ-フェニル)-ノニル]-4-(3,4,5-トリメトキシ-ベンジル)-ピペラジン;
(4-{4-[ビス-(4-フルオロ-フェニル)-メトキシ]-ブチル}-ピペラジン-1-イル)-(3,4,5-トリメトキシ-フェニル)-メタノン;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(4-トリフルオロメトキシ-ベンゾイル)-ピペラジン-1-イル]-ヘキサン-2-オン;
1-[4-(4-ブロモ-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-5-ヒドロキシ-1-[4-(3,4,5-トリメトキシ-ベンゾイル)-ピペラジン-1-イル]-ヘキサン-1-オン;
1-{4-[ビス-(4-フルオロ-フェニル)-メトキシ]-ブチル}-4-(3,4,5-トリメトキシ-ベンジル)-ピペラジン;
6,6-ビス-(4-フルオロ-フェニル)-6-ヒドロキシ-1-[4-(3,4,5-トリメトキシ-ベンゾイル)-ピペラジン-1-イル]-ヘキサン-1-オン;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-1-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-2-カルボン酸;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-1-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-2-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンゾイル)-ピペラジン-2-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,4,5-トリメトキシ-ベンゾイル)-ピペラジン-2-オン;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-1-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-2-オン;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-1-(3,5-ジ-tert-ブチル-4-メトキシ-ベンジル)-ピペラジン-2-オン;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-1-[2-(4-フルオロ-フェノキシ)-エチル]-ピペラジン-2-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンゾイル)-ピペラジン-2-オン;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-1-(3,5-ジ-tert-ブチル-4-メトキシ-ベンゾイル)-ピペラジン-2-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンジル)-ピペラジン-2-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-4-(3,5-ジ-tert-ブチル-4-ヒドロキシ-ベンゾイル)-ピペラジン-2-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(3,4,5-トリメトキシ-ベンゾイル)-ピペラジン-1-イル]-hex-5-エン-1-オン;
1-{4-[2-(3,4-ジメトキシ-フェノキシ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-[2-(3,4-ジメトキシ-フェノキシ)-エチル]-ピペラジン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-2-カルボン酸;
4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-1-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-2-カルボン酸エチルエステル;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,4-ジメトキシ-ベンジル)-ピペラジン;
1-[4-(3,4-ジメトキシ-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[2-(ベンゾ[1,3]ジオキソール-5-イルオキシ)-エチル]-4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-[2-(3,4,5-トリメトキシ-フェノキシ)-エチル]-ピペラジン;
1-(4-アミノ-2,3,5-トリメチル-フェノキシ)-3-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-プロパン-2-オール;
1-{4-[3-(4-アミノ-2,3,5-トリメチル-フェノキシ)-2-ヒドロキシ-プロピル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-(4-ベンゾチアゾール-2-イル-ピペラジン-1-イル)-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(3,5-ビス-トリフルオロメチル-ベンジル)-ピペラジン;
1-[4-(3,5-ビス-トリフルオロメチル-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(4-tert-ブチル-ベンゾイル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(4-ブロモ-ベンジル)-ピペラジン;
2-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-エチルスルファニル)-ベンゾチアゾール;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(4-ヒドロキシ-3,5-ジメトキシ-ベンゾイル)-ピペラジン-1-イル]-ヘキサン-1-オン;
4-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イルメチル}-2,6-ジブロモ-フェノール;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-(4-トリフルオロメトキシ-ベンジル)-ピペラジン;
(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-エチル)-(3,4,5-トリメトキシ-ベンジル)-アミン;
1-{4-[2-(4-フルオロ-フェノキシ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(2-フェニルアミノ-エチル)-ピペラジン-1-イル]-ヘキサン-1-オン;
1-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-4-[2-(2,4-ジフルオロ-フェノキシ)-エチル]-ピペラジン;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-2-オキソ-エチル)-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-クロロ-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-メチル-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-イソプロピル-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-tert-ブチル-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-フルオロ-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-2-オキソ-エチル)-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-クロロ-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-メチル-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-イソプロピル-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-tert-ブチル-ベンズアミド;
N-(2-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキサノイル]-ピペラジン-1-イル}-2-オキソ-エチル)-4-フルオロ-ベンズアミド;
1-[4-(2-ベンジルアミノ-エチル)-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-{4-[2-(4-クロロ-ベンジルアミノ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-{4-[2-(4-メチル-ベンジルアミノ)-エチル]-ピペラジン-1-イル}-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-{4-[2-(4-イソプロピル-ベンジルアミノ)-エチル]-ピペラジン-1-イル}-ヘキサン-1-オン;
1-{4-[2-(4-tert-ブチル-ベンジルアミノ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-{4-[2-(4-フルオロ-ベンジルアミノ)-エチル]-ピペラジン-1-イル}-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
6,6-ビス-(4-フルオロ-フェニル)-1-[4-(1-ヒドロキシ-ピリジン-4-カルボニル)-ピペラジン-1-イル]-ヘキサン-1-オン;
4-{4-[6,6-ビス-(4-フルオロ-フェニル)-ヘキシル]-ピペラジン-1-イルメチル}-2,6-ジメトキシ-フェノール;
9,9-ジフェニル-1-[4-(3,4,5-トリメトキシ-ベンジル)-ピペラジン-1-イル]-ノナン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンゾイル)-2-メチル-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-4-メトキシ-ベンゾイル)-3-メチル-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-ベンゾイル)-2-メチル-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン;および
1-[4-(4-tert-ブチル-ベンゾイル)-2-メチル-ピペラジン-1-イル]-6,6-ビス-(4-フルオロ-フェニル)-ヘキサン-1-オン。
これらの化合物の塩も、対イオンが薬学的に許容される限り、有用である。
1-{4-[4-(4-フルオロ-ベンジル)-フェニル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-[4-(3,5-ジ-tert-ブチル-4-ヒドロキシ-ベンジル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-{4-[3-(4-アミノ-2,3,5-トリメチル-フェノキシ)-2-ヒドロキシ-プロピル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-(4-アダマンタン-1-イルメチル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
1-(4-ベンゾチアゾール-2-イル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
3,3-ジフェニル-1-{4-[2-(3,4,5-トリメトキシ-フェノキシ)-エチル]-ピペラジン-1-イル}-プロパン-1-オン;
1-{4-[2-(3,4-ジメトキシ-フェノキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-{4-[2-(ベンゾチアゾール-2-イルスルファニル)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
N-(2,6-ジメチル-フェニル)-2-[4-(3,3-ジフェニル-プロピオニル)-ピペラジン-1-イル]-アセトアミド;
2-[4-(3,3-ジフェニル-プロピオニル)-ピペラジン-1-イル]-N-メチル-N-フェニル-アセトアミド;
3,3-ジフェニル-1-[4-(1-フェニル-エチル)-ピペラジン-1-イル]-プロパン-1-オン;
1-[4-(2-ジアリルアミノ-エチル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-[4-(2-ジプロピルアミノ-エチル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-(4-sec-ブチル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
1-[4-(1-エチル-プロピル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-[4-(1-メチル-ピペリジン-3-イルメチル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-(4-ヘプチル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
3,3-ジフェニル-1-(4-ピリジン-4-イルメチル-ピペラジン-1-イル)-プロパン-1-オン;
1-[4-(3,5-ジクロロ-フェニル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-(4-シクロヘプチル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
1-[4-(3,4-ジメチル-フェニル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-(4-ビフェニル-4-イル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
1-[4-(2,3-ジクロロ-フェニル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
1-[4-(1-メチル-ピペリジン-4-イルメチル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
N-{2-[4-(3,3-ジフェニル-プロピオニル)-ピペラジン-1-イル]-エチル}-3,4,5-トリメトキシ-ベンズアミド;
1-(4-イソプロピル-ピペラジン-1-イル)-3,3-ジフェニル-プロパン-1-オン;
1-[4-(3-ジメチルアミノ-プロピル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
3,3-ジフェニル-1-[4-(4-トリメチルシラニル-フェニル)-ピペラジン-1-イル]-プロパン-1-オン;
3,3-ジフェニル-1-[4-(2-フェニルアミノ-エチル)-ピペラジン-1-イル]-プロパン-1-オン;
1-{4-[2-(2,4-ジフルオロ-フェノキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
3,3-ジフェニル-1-{4-[2-(2,3,5,6-テトラフルオロ-フェノキシ)-エチル]-ピペラジン-1-イル}-プロパン-1-オン;
1-[4-(1-ベンジル-1H-ベンゾイミダゾール-2-イル)-ピペラジン-1-イル]-3,3-ジフェニル-プロパン-1-オン;
3,3-ジフェニル-1-[4-(フェニル-チオフェン-2-イル-メチル)-ピペラジン-1-イル]-プロパン-1-オン;
1-{4-[シクロプロピル-(4-フルオロ-フェニル)-メチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
(4-{2-[4-(3,3-ジフェニル-プロピオニル)-ピペラジン-1-イル]-エトキシ}-2,3,6-トリメチル-フェニル)-カルバミン酸tert-ブチルエステル;
1-{4-[2-(4-アミノ-2,3,5-トリメチル-フェノキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-{4-[2-(4-メトキシ-フェノキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-{4-[2-(ベンゾ[1,3]ジオキソール-5-イルオキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-{4-[2-(2,4-ジクロロ-フェノキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;
1-{4-[2-(4-フルオロ-フェノキシ)-エチル]-ピペラジン-1-イル}-3,3-ジフェニル-プロパン-1-オン;および
3,3-ジフェニル-1-[4-(2-フェニルスルファニル-エチル)-ピペラジン-1-イル]-プロパン-1-オン;ならびに
その塩。
SNLラットにおける触覚過敏および温熱性痛覚過敏に対するN型カルシウムチャネルブロッカーおよびモルフィンの相互作用の評価:イソボログラフィー(isobolographic)分析
触覚過敏および温熱性痛覚過敏に対する二つの薬物(1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オンなどのN型ブロッカーおよびモルフィン)の相互作用を、脊髄神経結紮(SNL)ラットにおいて測定する。各々のエンドポイントに対する用量応答曲線は、化合物の各々に対して確立されており、A50値(最大効果50%を産生する用量)は公知である。計算A50値の比に基づいて、薬物の固定比を採用する。混合物に関する用量応答曲線を、触覚および温熱性エンドポイントに対して生成し、薬物組み合わせが相乗的であるかまたは単純に加法的であるかどうかを決定するために、イソボログラフィー分析を採用する。オスのスプラーグドーリーラットに、SNLまたは擬似外科手術を受けさせ、外科手術の10日後にテストする。各々の用量応答曲線は、4つのデータポイント(用量)を必要とし、各々の用量に対して、8匹のラットを使用する。動物を、時間経過およびピーク効果の時間を確立するために注射後10分、20分、30分、45分、および60分にテストし、用量応答曲線を、ピーク効果の時間に集められたデータから生成する。N型ブロッカー+モルフィン(固定比)に対する別個の曲線を、触覚過敏および温熱性痛覚過敏について作成する。
慢性疼痛を経験している被験体における疼痛の処置のための組成物を、N型カルシウムチャネルブロッカーをNSAIDと混和することによって調製する。N型カルシウムチャネルブロッカーは、1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オンであり、NSAIDは、イブプロフェンである。二つの化合物を混合する;活性化合物の相対量を、投与される各々の投薬量に基づいて決定する。充填剤および結合剤を添加し、混合物を、400 mgのイブプロフェンおよびN型カルシウムチャネルブロッカーの有効用量を送達するサイズの錠剤に形成する。
慢性疼痛を経験している被験体を同定する。実施例2の組成物を、被験体に提供し、適切な疼痛緩和を得るために必要に応じて6時間おきに一つの錠剤を摂取するように被験体を指導する。
6,6-ジフェニル-1-[4-(3-フェニル-2-プロペン-1-イル)-ピペラジン-1-イル]ヘキサン-1-オンであるN型カルシウムチャネルブロッカーを、経口投与用に調剤し、各々の錠剤が化合物の単位投薬量を含むように、錠剤へと形成する。重度の疼痛を経験している被験体を同定する。経皮的送達を介してフェンタニルの有効量を提供するように作られるフェンタニルパッチを、被験体の皮膚に貼る。N型カルシウムチャネルブロッカーを含む一つの錠剤を、最初の12時間の間に3時間おきに被験体に投与する。その後、被験体を、疼痛を軽減するために必要なだけN型カルシウムチャネルブロッカーの錠剤を自己投与するように指導する。フェンタニルパッチは、その製造業者によって提供される推奨スケジュールに従って置き換えられる。
アミトリプチリンの低用量(1日あたり一つの50 mg丸剤)を、糖尿病性神経障害および吐き気を経験している被験体に投与する。N型カルシウムチャネルブロッカー、6,6-ジフェニル-1-[4-(シクロヘキシルメチルアミノ)-ピペラジン-1-イル]ヘキサン-1-オンの有効量を、標準的な制御放出製剤を使用して、坐剤として投与する。
重度の手術後疼痛を経験している被験体を、連続IV点滴として静脈内に投与される、N型カルシウムチャネルブロッカー、6,6-ビス-(4-フルオロフェニル)-1-[4-(3,4,5-トリメトキシフェニルメチル)ピペラジン-1-イル]ヘキサンの有効量で処置する。患者に、必要に応じて自己投与できるモルフィンの患者管理供給を提供し、アセトアミノフェン錠剤を、6時間ごとに500 mgの速度で定期的に投与する。
Claims (32)
- 非ペプチジルN型カルシウムチャネルブロッカーまたはその薬学的に許容される塩である第一の化合物とN型カルシウムチャネル遮断以外の機序を介して疼痛を軽減する第二の化合物との組み合わせを含み、組み合わせが疼痛を軽減するのに効果的である、疼痛の軽減のための組成物。
- N型カルシウムチャネルブロッカーが、四環系もしくは五環系のチャネルブロッカー、またはその薬学的に許容される塩である、請求項1記載の組成物。
- N型カルシウムチャネルブロッカーが、式(1)の化合物またはその薬学的に許容される塩である、請求項1記載の組成物:
式中、各々のm1およびm2は、独立に0〜5であり;
m3は、0〜2であり;
R1、R2、およびR3の各々は、独立に非干渉置換基(noninterfering substituent)であり;
Zは、NまたはCHであり;
n1およびn2の各々は、独立に0または1であり;
X1およびX2は、リンカーであり;かつ
Wは、ArまたはCyであり、
Arは、一つまたは二つの置換されたまたは非置換の芳香族環またはヘテロ芳香族環を示し、かつ
Cyは、一つもしくは二つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分を示す、または一つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分および一つの置換されたもしくは非置換の芳香族部分もしくはヘテロ芳香族部分からなる。 - Zが、CHである、請求項3記載の組成物。
- Zが、Nである、請求項3記載の組成物。
- N型カルシウムチャネルブロッカーが、
1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オン;
6,6-ジフェニル-1-[4-(3-フェニル-2-プロペン-1-イル)-ピペラジン-1-イル]ヘキサン-1-オン;
6,6-ジフェニル-1-[4-(シクロヘキシルメチルアミノ)-ピペリジン-1-イル]ヘキサン-1-オン;
6,6-ビス-(4-フルオロフェニル)-1-[4-(3,4,5-トリメトキシフェニルメチル)ピペラジン-1-イル]ヘキサン;もしくは
4-ベンズヒドリル-ピペラジン-1-カルボン酸ベンズヒドリル-アミド;または
その薬学的に許容される塩である、
請求項1記載の組成物。 - N型カルシウムチャネルブロッカーが、1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オン、またはその薬学的に許容される塩である、請求項1記載の組成物。
- 経口的にまたは非経口的に投与される、請求項1記載の組成物。
- 組成物が、経粘膜的にまたは経皮的に投与される、請求項1記載の組成物。
- 第二の化合物が、NSAIDである、請求項1〜9のいずれか一項記載の組成物。
- 第二の化合物が、選択的COX-2阻害剤である、請求項1〜9のいずれか一項記載の組成物。
- 第二の化合物が、オピオイドである、請求項1〜9のいずれか一項記載の組成物。
- 第二の化合物が、アジュバント鎮痛剤である、請求項1〜9のいずれか一項記載の組成物。
- 被験体において疼痛を改善するための方法であって、そのような改善を必要とする被験体に非ペプチジルN型カルシウムチャネルブロッカーである第一の化合物を投与する段階、および該被験体にN型カルシウムチャネル遮断以外の機序によって疼痛を改善する第二の化合物を投与する段階を含み、該化合物が、組み合わせにおいて該疼痛を改善するのに効果的である量において投与される方法。
- 第一の化合物が、四環系もしくは五環系のチャネルブロッカー、またはその薬学的に許容される塩である、請求項14記載の方法。
- 第一の化合物が、式(1)の化合物またはその薬学的に許容される塩を含む、請求項14記載の方法:
式中、各々のm1およびm2は、独立に0〜5であり;
m3は、0〜2であり;
R1、R2、およびR3の各々は、独立に非干渉置換基であり;
Zは、NまたはCHであり;
n1およびn2の各々は、独立に0または1であり;
X1およびX2は、リンカーであり;かつ
Wは、ArまたはCyであり、
Arは、一つまたは二つの置換されたまたは非置換の芳香族環またはヘテロ芳香族環を示し、かつ
Cyは、一つもしくは二つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分を示す、または一つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分および一つの置換されたもしくは非置換の芳香族部分もしくはヘテロ芳香族部分からなる。 - 式(1)におけるZが、CHである、請求項14記載の方法。
- 式(1)におけるZが、Nである、請求項14記載の方法。
- 第一の化合物が、
1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オン;
6,6-ジフェニル-1-[4-(3-フェニル-2-プロペン-1-イル)-ピペラジン-1-イル]ヘキサン-1-オン;
6,6-ジフェニル-1-[4-(シクロヘキシルメチルアミノ)-ピペリジン-1-イル]ヘキサン-1-オン;
6,6-ビス-(4-フルオロフェニル)-1-[4-(3,4,5-トリメトキシフェニルメチル)ピペラジン-1-イル]ヘキサン;もしくは
4-ベンズヒドリル-ピペラジン-1-カルボン酸ベンズヒドリル-アミド;または
その薬学的に許容される塩である、
請求項14記載の方法。 - 第一の化合物が、1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オン、またはその薬学的に許容される塩である、請求項14記載の方法。
- 第一および第二の化合物が、実質的に同時に投与される、請求項14記載の方法。
- 第一および第二の化合物が、別個に投与される、請求項14記載の方法。
- 第二の化合物が、NSAIDである、請求項14〜22のいずれか一項記載の方法。
- 第二の化合物が、選択的COX-2阻害剤である、請求項14〜22のいずれか一項記載の方法。
- 第二の化合物が、オピオイドである、請求項14〜25のいずれか一項記載の方法。
- 第二の化合物が、アジュバント鎮痛剤である、請求項14〜25のいずれか一項記載の方法。
- 被験体に非ペプチジルN型カルシウムチャネルブロッカーを投与する段階、および同じ被験体に疼痛を軽減する少なくとも一つの非薬理学的治療的プロトコールを並行して投与する段階を含む、被験体において疼痛を軽減するための方法。
- 非ペプチジルN型カルシウムチャネルブロッカーが、四環系または五環系のチャネルブロッカーである、請求項27記載の方法。
- 非ペプチジルN型カルシウムチャネルブロッカーが、式(1)の化合物またはその薬学的に許容される塩を含む、請求項27記載の方法:
式中、各々のm1およびm2は、独立に0〜5であり;
m3は、0〜2であり;
R1、R2、およびR3の各々は、独立に非干渉置換基であり;
Zは、NまたはCHであり;
n1およびn2の各々は、独立に0または1であり;
X1およびX2は、リンカーであり;かつ
Wは、ArまたはCyであり、
Arは、一つまたは二つの置換されたまたは非置換の芳香族環またはヘテロ芳香族環を示し、かつ
Cyは、一つもしくは二つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分を示す、または一つの置換されたもしくは非置換の脂肪族環部分もしくは複素環部分および一つの置換されたもしくは非置換の芳香族部分もしくはヘテロ芳香族部分からなる。 - N型カルシウムチャネルブロッカーが、以下からなる群より選択される、請求項27記載の方法:
1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オン;
6,6-ジフェニル-1-[4-(3-フェニル-2-プロペン-1-イル)-ピペラジン-1-イル]ヘキサン-1-オン;
6,6-ジフェニル-1-[4-(シクロヘキシルメチルアミノ)-ピペリジン-1-イル]ヘキサン-1-オン;
6,6-ビス-(4-フルオロフェニル)-1-[4-(3,4,5-トリメトキシフェニルメチル)ピペラジン-1-イル]ヘキサン;もしくは
4-ベンズヒドリル-ピペラジン-1-カルボン酸ベンズヒドリル-アミド;または
その薬学的に許容される塩。 - N型カルシウムチャネルブロッカーが、1-(4-ベンズヒドリルピペラジン-1-イル)-3,3-ジフェニルプロパン-1-オン、またはその薬学的に許容される塩である、請求項27記載の方法。
- 非薬理学的治療的プロトコールが、経皮的電気神経刺激(TENS)または経皮性電気神経刺激(PENS)である、請求項27記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US66982005P | 2005-04-08 | 2005-04-08 | |
PCT/CA2006/000545 WO2006105670A1 (en) | 2005-04-08 | 2006-04-10 | Combination therapy comprising an n-type calcium channel blocker for the alleviation of pain |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2008534630A true JP2008534630A (ja) | 2008-08-28 |
Family
ID=37073075
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008504594A Pending JP2008534630A (ja) | 2005-04-08 | 2006-04-10 | 疼痛の軽減のためのn型カルシウムチャネルブロッカーを含む組み合わせ治療の方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20080300262A1 (ja) |
EP (1) | EP1871372A4 (ja) |
JP (1) | JP2008534630A (ja) |
CA (1) | CA2603926A1 (ja) |
WO (1) | WO2006105670A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015503583A (ja) * | 2012-01-04 | 2015-02-02 | ウェルズリー ファーマスーティカルズ、エルエルシー | 排尿頻度を減少させるための延長放出製剤およびその使用の方法 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200611217A (en) * | 2005-12-06 | 2006-04-01 | Shin Hwa Biotech Co Ltd | Human model for indexing nerve paths (locus) having corresponding relations and method for indexing |
PL387984A1 (pl) * | 2009-05-07 | 2010-11-08 | Instytut Medycyny Doświadczalnej I Klinicznej Im. Mirosława Mossakowskiego Pan | Nowe kompozycje substancji leczniczych do leczenia bólów przewlekłych |
US8536181B2 (en) | 2009-11-06 | 2013-09-17 | Aerpio Therapeutics Inc. | Prolyl hydroxylase inhibitors |
US8409560B2 (en) * | 2011-03-08 | 2013-04-02 | Zalicus Pharmaceuticals Ltd. | Solid dispersion formulations and methods of use thereof |
US8591944B2 (en) * | 2011-03-08 | 2013-11-26 | Zalicus Pharmaceuticals Ltd. | Solid dispersion formulations and methods of use thereof |
EP3145925B1 (en) * | 2014-05-19 | 2020-11-04 | Boehringer Ingelheim Animal Health USA Inc. | Anthelmintic compounds |
GB201516183D0 (en) * | 2015-09-14 | 2015-10-28 | Calchan Ltd | Novel pharmaceutical composition |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10147520A (ja) * | 1996-10-09 | 1998-06-02 | Gruenenthal Gmbh | トラマドール及びカルシウム− チャンネル拮抗物質を含有する組合せ製剤 |
JP2002519372A (ja) * | 1998-06-30 | 2002-07-02 | ニューロメド テクノロジーズ, インコーポレイテッド | カルシウムチャネル遮断薬 |
JP2003518064A (ja) * | 1999-12-20 | 2003-06-03 | ニューロメド テクノロジーズ, インコーポレイテッド | 置換ピペラジンおよびピペリジンカルシウムチャネルブロッカー |
WO2003066040A1 (fr) * | 2002-02-05 | 2003-08-14 | Ajinomoto Co.,Inc. | Compositions medicinales contenant une gabapentine ou une pregabaline et antagoniste a canal de calcium de type n |
WO2004012749A1 (en) * | 2002-08-05 | 2004-02-12 | Protexeon Limited | An analgesic agent for newborn or fetal subjects |
WO2005013914A2 (en) * | 2003-08-08 | 2005-02-17 | Vertex Pharmaceuticals Incorporated | Heteroarylaminosulfonylphenyl derivatives for use as sodium or calcium channel blockers in the treatment of pain |
JP2006507284A (ja) * | 2002-10-24 | 2006-03-02 | セルジーン・コーポレーション | 疼痛を治療、改変および管理するための免疫調節化合物の使用方法および組成物 |
JP2006522741A (ja) * | 2003-04-08 | 2006-10-05 | ニューロームド テクノロジーズ、インク. | 2つのベンズヒドリル部分を有するカルシウムチャンネルブロッカー |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3694533A (en) * | 1970-06-23 | 1972-09-26 | Paul S Kelsey | Method for making slab-faced and headed panels including corners or returns |
SE9702564D0 (sv) * | 1997-07-02 | 1997-07-02 | Astra Ab | New compounds |
US6251918B1 (en) * | 1997-08-11 | 2001-06-26 | Warner-Lambert Company | Aniline derivatives as calcium channel blockers |
TWI245035B (en) * | 1998-06-26 | 2005-12-11 | Ono Pharmaceutical Co | Amino acid derivatives and a pharmaceutical composition comprising the derivatives |
US6943168B2 (en) * | 1998-06-30 | 2005-09-13 | Neuromed Technologies Inc. | Calcium channel inhibitors comprising benzhydril spaced from piperazine |
US7186726B2 (en) * | 1998-06-30 | 2007-03-06 | Neuromed Pharmaceuticals Ltd. | Preferentially substituted calcium channel blockers |
US6310059B1 (en) * | 1998-06-30 | 2001-10-30 | Neuromed Technologies, Inc. | Fused ring calcium channel blockers |
US20040259866A1 (en) * | 1998-06-30 | 2004-12-23 | Snutch Terrance P. | Calcium channel blockers comprising two benzhydril moieties |
US20040266784A1 (en) * | 1998-06-30 | 2004-12-30 | Snutch Terrance P. | Calcium channel inhibitors comprising benzhydril spaced from piperazine |
US6316440B1 (en) * | 1998-07-30 | 2001-11-13 | Warner-Lambert Company | Reduced dipeptide analogues as calcium channel antagonists |
AU4329399A (en) * | 1998-07-30 | 2000-02-21 | Warner-Lambert Company | Tyrosine-derived compounds as calcium channel antagonists |
US6267945B1 (en) * | 1998-12-18 | 2001-07-31 | Neuromed Technologies, Inc. | Farnesol-related calcium channel blockers |
AU5568300A (en) * | 1999-06-23 | 2001-01-09 | Ajinomoto Co., Inc. | Novel dihydropyridine derivative |
SE0004053D0 (sv) * | 2000-11-06 | 2000-11-06 | Astrazeneca Ab | N-type calcium channel antagonists for the treatment of pain |
SE0004056D0 (sv) * | 2000-11-06 | 2000-11-06 | Astrazeneca Ab | N-type calcium channel antagonists for the treatment of pain |
US20030199523A1 (en) * | 2002-02-28 | 2003-10-23 | Snutch Terrance P. | Heterocyclic calcium in channel blockers |
US20050203142A1 (en) * | 2002-10-24 | 2005-09-15 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain |
US7270949B2 (en) * | 2003-01-07 | 2007-09-18 | Neuromed Pharmaceuticals Ltd. | Fluorescence based T-type channel assay |
GB0309509D0 (en) * | 2003-04-25 | 2003-06-04 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
AU2004243511A1 (en) * | 2003-05-30 | 2004-12-09 | Neuromed Technologies, Inc | 3-aminomethyl-pyrrolidines as N-type calcium channel blockers |
CA2543312A1 (en) * | 2003-10-24 | 2005-05-06 | Celgene Corporation | Methods and compositions comprising thalidomide for treatment of fibromyalgia |
-
2006
- 2006-04-10 WO PCT/CA2006/000545 patent/WO2006105670A1/en active Search and Examination
- 2006-04-10 EP EP06741375A patent/EP1871372A4/en not_active Withdrawn
- 2006-04-10 CA CA002603926A patent/CA2603926A1/en not_active Abandoned
- 2006-04-10 US US11/910,909 patent/US20080300262A1/en not_active Abandoned
- 2006-04-10 JP JP2008504594A patent/JP2008534630A/ja active Pending
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10147520A (ja) * | 1996-10-09 | 1998-06-02 | Gruenenthal Gmbh | トラマドール及びカルシウム− チャンネル拮抗物質を含有する組合せ製剤 |
JP2002519372A (ja) * | 1998-06-30 | 2002-07-02 | ニューロメド テクノロジーズ, インコーポレイテッド | カルシウムチャネル遮断薬 |
JP2003518064A (ja) * | 1999-12-20 | 2003-06-03 | ニューロメド テクノロジーズ, インコーポレイテッド | 置換ピペラジンおよびピペリジンカルシウムチャネルブロッカー |
WO2003066040A1 (fr) * | 2002-02-05 | 2003-08-14 | Ajinomoto Co.,Inc. | Compositions medicinales contenant une gabapentine ou une pregabaline et antagoniste a canal de calcium de type n |
WO2004012749A1 (en) * | 2002-08-05 | 2004-02-12 | Protexeon Limited | An analgesic agent for newborn or fetal subjects |
JP2006507284A (ja) * | 2002-10-24 | 2006-03-02 | セルジーン・コーポレーション | 疼痛を治療、改変および管理するための免疫調節化合物の使用方法および組成物 |
JP2006522741A (ja) * | 2003-04-08 | 2006-10-05 | ニューロームド テクノロジーズ、インク. | 2つのベンズヒドリル部分を有するカルシウムチャンネルブロッカー |
WO2005013914A2 (en) * | 2003-08-08 | 2005-02-17 | Vertex Pharmaceuticals Incorporated | Heteroarylaminosulfonylphenyl derivatives for use as sodium or calcium channel blockers in the treatment of pain |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015503583A (ja) * | 2012-01-04 | 2015-02-02 | ウェルズリー ファーマスーティカルズ、エルエルシー | 排尿頻度を減少させるための延長放出製剤およびその使用の方法 |
JP2017031172A (ja) * | 2012-01-04 | 2017-02-09 | ウェルズリー ファーマスーティカルズ、エルエルシー | 排尿頻度を減少させるための延長放出製剤およびその使用の方法 |
Also Published As
Publication number | Publication date |
---|---|
WO2006105670A8 (en) | 2006-12-14 |
WO2006105670A1 (en) | 2006-10-12 |
EP1871372A1 (en) | 2008-01-02 |
EP1871372A4 (en) | 2010-06-02 |
US20080300262A1 (en) | 2008-12-04 |
CA2603926A1 (en) | 2006-10-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11413258B2 (en) | Methods for treating cancer | |
US20080300262A1 (en) | Combination Therapy for Relief of Pain | |
ES2285733T3 (es) | Agente antipruritico. | |
CA2104873C (en) | Compositions and methods of treatment of sympathetically maintained pain | |
USRE41998E1 (en) | Compositions and methods of treatment of sympathetically maintained pain | |
US20060074058A1 (en) | Combination of dpp iv inhibitor and a cardiovascular compound | |
KR19990044182A (ko) | 말초 활성 통각과민 치료용 아편제 | |
JP2002506047A (ja) | Nmdaレセプター拮抗薬及び麻酔性鎮痛薬を含む鎮痛組成物。 | |
WO2006049312A1 (ja) | 神経因性疼痛治療剤 | |
AU2005208871B2 (en) | Enhancement of ampakine-induced facilitation of synaptic responses by cholinesterase inhibitors | |
US20180028594A1 (en) | Peripheral kappa opioid receptor agonists for hard tissue pain | |
US6537991B1 (en) | Method of treating a peripheral neuropathic pain | |
AU2013216864A1 (en) | Combination of muscarinic receptor antagonists and beta- 3 adrenoceptor agonists for treating overactive bladder | |
KR19990036248A (ko) | 마약성 진통제의 의존·내성 형성 억제제 | |
CA2543312A1 (en) | Methods and compositions comprising thalidomide for treatment of fibromyalgia | |
US20070259945A1 (en) | Method for treating pain | |
TW201118084A (en) | The use of an opioid receptor antagonist for the treatment or prevention of gastrointestinal tract disorders | |
JP4362457B2 (ja) | 神経因性疼痛治療剤 | |
ES2198136T3 (es) | Empleo de derivados de tetrahidropiridinas (o 4-hidroxipiperidinas)-butilazoles en la elaboracion de un medicamento para el tratamiento del dolor. | |
EP4175639B1 (en) | Masitinib for the treatment of castrate-resistant prostate cancer | |
EP1702627A1 (en) | Analgesic combination of sodium channel blockers with opioid antagonists | |
JPWO2004052399A1 (ja) | 局所麻酔用組成物 | |
JP6714225B2 (ja) | 肝細胞癌の予防又は治療のための医薬 | |
US20090270400A1 (en) | Painkilling association comprising a dihydroimidazopyrazine derivative | |
JP2003518492A (ja) | オピオイド鎮痛剤とトリメブチンとの組合わせ |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090226 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110817 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111117 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120402 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120903 |