TW200528102A - Novel medical combination treatment of obesity involving 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity - Google Patents
Novel medical combination treatment of obesity involving 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity Download PDFInfo
- Publication number
- TW200528102A TW200528102A TW093131751A TW93131751A TW200528102A TW 200528102 A TW200528102 A TW 200528102A TW 093131751 A TW093131751 A TW 093131751A TW 93131751 A TW93131751 A TW 93131751A TW 200528102 A TW200528102 A TW 200528102A
- Authority
- TW
- Taiwan
- Prior art keywords
- group
- compound
- carbon atoms
- lipase
- obesity
- Prior art date
Links
- 208000008589 Obesity Diseases 0.000 title claims abstract description 98
- 235000020824 obesity Nutrition 0.000 title claims abstract description 98
- MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical class C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 title abstract description 3
- 230000000694 effects Effects 0.000 title description 18
- 238000011284 combination treatment Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 161
- 238000011282 treatment Methods 0.000 claims abstract description 82
- 239000003814 drug Substances 0.000 claims abstract description 76
- 229940079593 drug Drugs 0.000 claims abstract description 67
- 239000005557 antagonist Substances 0.000 claims abstract description 58
- -1 panclicins Chemical compound 0.000 claims abstract description 44
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims abstract description 26
- 229960001243 orlistat Drugs 0.000 claims abstract description 26
- MVCQKIKWYUURMU-UHFFFAOYSA-N cetilistat Chemical compound C1=C(C)C=C2C(=O)OC(OCCCCCCCCCCCCCCCC)=NC2=C1 MVCQKIKWYUURMU-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229950002397 cetilistat Drugs 0.000 claims abstract description 19
- 230000003389 potentiating effect Effects 0.000 claims abstract description 14
- SIKWOTFNWURSAY-UHFFFAOYSA-N Lipstatin Natural products CCCCCCC1C(CC(CC=CCC=CCCCCC)C(=O)OC(CC(C)C)NC=O)OC1=O SIKWOTFNWURSAY-UHFFFAOYSA-N 0.000 claims abstract description 12
- OQMAKWGYQLJJIA-CUOOPAIESA-N lipstatin Chemical compound CCCCCC[C@H]1[C@H](C[C@H](C\C=C/C\C=C/CCCCC)OC(=O)[C@H](CC(C)C)NC=O)OC1=O OQMAKWGYQLJJIA-CUOOPAIESA-N 0.000 claims abstract description 12
- 230000000366 juvenile effect Effects 0.000 claims abstract description 11
- 125000001424 substituent group Chemical group 0.000 claims abstract description 10
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 150
- 239000004367 Lipase Substances 0.000 claims description 80
- 102000004882 Lipase Human genes 0.000 claims description 80
- 108090001060 Lipase Proteins 0.000 claims description 80
- 235000019421 lipase Nutrition 0.000 claims description 80
- 230000002401 inhibitory effect Effects 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 230000002265 prevention Effects 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 39
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 229920000642 polymer Polymers 0.000 claims description 25
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 24
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000000524 functional group Chemical group 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 230000003042 antagnostic effect Effects 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 241000218236 Cannabis Species 0.000 claims description 11
- 239000003112 inhibitor Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 229940126534 drug product Drugs 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 3
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 2
- 229940124802 CB1 antagonist Drugs 0.000 claims description 2
- 241000282320 Panthera leo Species 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 150000007857 hydrazones Chemical class 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 230000035772 mutation Effects 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
- UHNHTTIUNATJKL-UHFFFAOYSA-N n-methylmethanesulfonamide Chemical group CNS(C)(=O)=O UHNHTTIUNATJKL-UHFFFAOYSA-N 0.000 claims 1
- YPJKMVATUPSWOH-UHFFFAOYSA-N nitrooxidanyl Chemical compound [O][N+]([O-])=O YPJKMVATUPSWOH-UHFFFAOYSA-N 0.000 claims 1
- 125000001725 pyrenyl group Chemical group 0.000 claims 1
- 229940044551 receptor antagonist Drugs 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 claims 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
- 229940127470 Lipase Inhibitors Drugs 0.000 abstract description 15
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 abstract description 2
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract 1
- 240000004308 marijuana Species 0.000 abstract 1
- 229940040461 lipase Drugs 0.000 description 60
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 32
- 125000003545 alkoxy group Chemical group 0.000 description 19
- 125000001072 heteroaryl group Chemical group 0.000 description 18
- 229910052736 halogen Inorganic materials 0.000 description 17
- 241000700159 Rattus Species 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 150000002367 halogens Chemical class 0.000 description 16
- 150000002430 hydrocarbons Chemical group 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 239000000546 pharmaceutical excipient Substances 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- AHLBNYSZXLDEJQ-UHFFFAOYSA-N N-formyl-L-leucylester Natural products CCCCCCCCCCCC(OC(=O)C(CC(C)C)NC=O)CC1OC(=O)C1CCCCCC AHLBNYSZXLDEJQ-UHFFFAOYSA-N 0.000 description 12
- 108050006759 Pancreatic lipases Proteins 0.000 description 12
- 102000019280 Pancreatic lipases Human genes 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 239000003925 fat Substances 0.000 description 12
- 229940116369 pancreatic lipase Drugs 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 230000004584 weight gain Effects 0.000 description 11
- 235000019786 weight gain Nutrition 0.000 description 11
- 229930003827 cannabinoid Natural products 0.000 description 10
- 239000003557 cannabinoid Substances 0.000 description 10
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 10
- 208000007683 Pediatric Obesity Diseases 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 239000000902 placebo Substances 0.000 description 8
- 229940068196 placebo Drugs 0.000 description 8
- 210000003462 vein Anatomy 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
- 239000003693 atypical antipsychotic agent Substances 0.000 description 5
- 229940127236 atypical antipsychotics Drugs 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 230000004580 weight loss Effects 0.000 description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- UNBMQQNYLCPCHS-UHFFFAOYSA-N Ebelactone B Natural products CCC(C)C(O)C(C)C(=O)C(C)C=C(C)CC(C)C1OC(=O)C1CC UNBMQQNYLCPCHS-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- UNBMQQNYLCPCHS-VYNDPHDASA-N ebelactone b Chemical compound CC[C@@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)\C=C(/C)C[C@H](C)[C@@H]1OC(=O)[C@H]1CC UNBMQQNYLCPCHS-VYNDPHDASA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 3
- 108050007331 Cannabinoid receptor Proteins 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 244000141218 Alpinia officinarum Species 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LYISDADPVOHJBJ-UHFFFAOYSA-N Galangin 3-methyl ether Natural products O1C2=CC(O)=CC(O)=C2C(=O)C(OC)=C1C1=CC=CC=C1 LYISDADPVOHJBJ-UHFFFAOYSA-N 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 229940122055 Serine protease inhibitor Drugs 0.000 description 2
- 101710102218 Serine protease inhibitor Proteins 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000006267 biphenyl group Chemical group 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229940065144 cannabinoids Drugs 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 238000011866 long-term treatment Methods 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000003176 neuroleptic agent Substances 0.000 description 2
- 229960005017 olanzapine Drugs 0.000 description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000005871 repellent Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- FFJDKPPKQMVSSS-GNOQXXQHSA-N (Z)-octadec-9-enoic acid propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O FFJDKPPKQMVSSS-GNOQXXQHSA-N 0.000 description 1
- INQSMEFCAIHTJG-UHFFFAOYSA-N 1,3-dimethyl-7h-purine-2,6-dione;hydrate Chemical group O.O=C1N(C)C(=O)N(C)C2=C1NC=N2 INQSMEFCAIHTJG-UHFFFAOYSA-N 0.000 description 1
- XIRPMPKSZHNMST-UHFFFAOYSA-N 1-ethenyl-2-phenylbenzene Chemical group C=CC1=CC=CC=C1C1=CC=CC=C1 XIRPMPKSZHNMST-UHFFFAOYSA-N 0.000 description 1
- IGGDKDTUCAWDAN-UHFFFAOYSA-N 1-vinylnaphthalene Chemical compound C1=CC=C2C(C=C)=CC=CC2=C1 IGGDKDTUCAWDAN-UHFFFAOYSA-N 0.000 description 1
- ZYDUNXCLPOKBNQ-UHFFFAOYSA-N 2,2,6,6-tetramethyl-1,3-dihydropyridine Chemical compound CC1(C)CC=CC(C)(C)N1 ZYDUNXCLPOKBNQ-UHFFFAOYSA-N 0.000 description 1
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical class C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
- UPELHUMVIWYFQA-UHFFFAOYSA-N 2-(trifluoromethyl)benzenecarboximidamide Chemical compound NC(=N)C1=CC=CC=C1C(F)(F)F UPELHUMVIWYFQA-UHFFFAOYSA-N 0.000 description 1
- UWRZIZXBOLBCON-UHFFFAOYSA-N 2-phenylethenamine Chemical compound NC=CC1=CC=CC=C1 UWRZIZXBOLBCON-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- 208000014825 Abnormal muscle tone Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- FMMWHPNWAFZXNH-UHFFFAOYSA-N Benz[a]pyrene Chemical compound C1=C2C3=CC=CC=C3C=C(C=C3)C2=C2C3=CC=CC2=C1 FMMWHPNWAFZXNH-UHFFFAOYSA-N 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 1
- WGKXXLFKCWZELR-UHFFFAOYSA-N C[NH+](C)C.CCC=C(C)C([O-])=O Chemical compound C[NH+](C)C.CCC=C(C)C([O-])=O WGKXXLFKCWZELR-UHFFFAOYSA-N 0.000 description 1
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 1
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 1
- 229940122820 Cannabinoid receptor antagonist Drugs 0.000 description 1
- 235000008697 Cannabis sativa Nutrition 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- WOISDAHQBUYEAF-UHFFFAOYSA-N Ebelactone A Natural products CCC(C)C(O)C(C)C(=O)C(C)C=C(C)CC(C)C1OC(=O)C1C WOISDAHQBUYEAF-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 208000007530 Essential hypertension Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 206010056465 Food craving Diseases 0.000 description 1
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 1
- 102100031416 Gastric triacylglycerol lipase Human genes 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 241000958270 Kitasatospora aburaviensis Species 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
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 101710181812 Methionine aminopeptidase Proteins 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- 101150020251 NR13 gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 206010033307 Overweight Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 241001298228 Pyramidula rupestris Species 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241000946767 Streptomyces toxytricini Species 0.000 description 1
- 241000278713 Theora Species 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 description 1
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 1
- 235000021068 Western diet Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-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
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- MPMBRWOOISTHJV-UHFFFAOYSA-N but-1-enylbenzene Chemical compound CCC=CC1=CC=CC=C1 MPMBRWOOISTHJV-UHFFFAOYSA-N 0.000 description 1
- 239000003536 cannabinoid receptor antagonist Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- JKZWPSHYNAEPAA-UHFFFAOYSA-N cyanocarbamic acid Chemical compound OC(=O)NC#N JKZWPSHYNAEPAA-UHFFFAOYSA-N 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000021316 daily nutritional intake Nutrition 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000013367 dietary fats Nutrition 0.000 description 1
- 235000019621 digestibility Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- NIKLARYSRFBLLS-UHFFFAOYSA-N ethene;1h-imidazole Chemical compound C=C.C1=CNC=N1 NIKLARYSRFBLLS-UHFFFAOYSA-N 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004175 fluorobenzyl group Chemical group 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229920000140 heteropolymer Polymers 0.000 description 1
- 230000000742 histaminergic effect Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 206010021654 increased appetite Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000007830 nerve conduction Effects 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate group Chemical group [N+](=O)([O-])[O-] NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
- 208000001797 obstructive sleep apnea Diseases 0.000 description 1
- 239000003538 oral antidiabetic agent Substances 0.000 description 1
- 229940127209 oral hypoglycaemic agent Drugs 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical class O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000002203 pretreatment Methods 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
- 230000005180 public health Effects 0.000 description 1
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000002295 serotoninergic effect Effects 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229940117972 triolein Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 125000002348 vinylic group Chemical group 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Child & Adolescent Psychology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03103961 | 2003-10-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200528102A true TW200528102A (en) | 2005-09-01 |
Family
ID=34486362
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW093131751A TW200528102A (en) | 2003-10-24 | 2004-10-20 | Novel medical combination treatment of obesity involving 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1680106B1 (https=) |
| JP (1) | JP2007509110A (https=) |
| CN (2) | CN1921849A (https=) |
| AR (1) | AR046132A1 (https=) |
| AT (1) | ATE438394T1 (https=) |
| AU (1) | AU2004283055A1 (https=) |
| BR (1) | BRPI0415463A (https=) |
| CA (1) | CA2543342A1 (https=) |
| DE (1) | DE602004022445D1 (https=) |
| MX (1) | MXPA06004390A (https=) |
| RU (1) | RU2006117639A (https=) |
| TW (1) | TW200528102A (https=) |
| WO (1) | WO2005039566A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080039996A (ko) * | 2005-08-17 | 2008-05-07 | 솔베이 파머슈티컬스 게엠베하 | 칼륨 채널 억제 화합물의 사용 방법 |
| CN102731418B (zh) * | 2012-07-15 | 2015-03-11 | 浙江大学 | 1-取代-1h-1,2,4-三氮唑-甲酰胺衍生物及其制备和用途 |
| CN113166068B (zh) * | 2018-11-20 | 2024-08-16 | 上海科技大学 | MmpL3抑制剂、组合物及其用途 |
| CN117551046B (zh) * | 2023-11-17 | 2025-10-28 | 广东药科大学附属第一医院 | 二氨基脲类hsl抑制剂、制备方法及其用途 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DZ3335A1 (fr) * | 2000-03-23 | 2001-09-27 | Solvay Pharm Bv | Derives de 4,5-dihydro-1h-pyrazole ayant une activite antagoniste de cb1 |
| PL363751A1 (en) * | 2001-03-22 | 2004-11-29 | Solvay Pharmaceuticals B.V. | 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity |
| KR100903760B1 (ko) * | 2001-09-21 | 2009-06-19 | 솔베이 파마슈티칼스 비. 브이 | Ｃｂ1-길항 작용을 가지는 신규한4,5-디하이드로-1ｈ-피라졸 유도체 |
| IL157704A0 (en) * | 2001-09-21 | 2004-03-28 | Solvay Pharm Bv | 4,5-dihydro-1h-pyrazole derivatives having potent cbi-antagonistic activity |
| SE0104330D0 (sv) * | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| GB0202015D0 (en) * | 2002-01-29 | 2002-03-13 | Hoffmann La Roche | Piperazine Derivatives |
| AU2003209388A1 (en) * | 2002-01-29 | 2003-09-02 | Merck And Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
| TW200412942A (en) * | 2002-08-06 | 2004-08-01 | Abbott Lab | Appetite control method |
| US20040122033A1 (en) * | 2002-12-10 | 2004-06-24 | Nargund Ravi P. | Combination therapy for the treatment of obesity |
| RU2344132C2 (ru) * | 2003-06-20 | 2009-01-20 | Ф.Хоффманн-Ля Рош Аг | 2-аминобензотиазолы в качестве обратных агонистов рецепторов cb1 |
| MXPA06002064A (es) * | 2003-10-20 | 2006-05-19 | Solvay Pharm Bv | Derivados e 1h imidazol como moduladores del receptor cannabinoide. |
| MXPA06004434A (es) * | 2003-10-24 | 2006-06-20 | Solvay Pharm Gmbh | Usos medicos novedosos de compuestos que muestran actividad antagonista cb1 y tratamiento de combinacion que involucra tales compuestos. |
-
2004
- 2004-10-20 TW TW093131751A patent/TW200528102A/zh unknown
- 2004-10-20 AR ARP040103804A patent/AR046132A1/es unknown
- 2004-10-22 AT AT04791282T patent/ATE438394T1/de not_active IP Right Cessation
- 2004-10-22 CA CA002543342A patent/CA2543342A1/en not_active Abandoned
- 2004-10-22 RU RU2006117639/15A patent/RU2006117639A/ru unknown
- 2004-10-22 WO PCT/EP2004/052618 patent/WO2005039566A1/en not_active Ceased
- 2004-10-22 AU AU2004283055A patent/AU2004283055A1/en not_active Abandoned
- 2004-10-22 CN CNA2004800300871A patent/CN1921849A/zh active Pending
- 2004-10-22 EP EP04791282A patent/EP1680106B1/en not_active Expired - Lifetime
- 2004-10-22 DE DE602004022445T patent/DE602004022445D1/de not_active Expired - Fee Related
- 2004-10-22 JP JP2006536092A patent/JP2007509110A/ja not_active Withdrawn
- 2004-10-22 MX MXPA06004390A patent/MXPA06004390A/es not_active Application Discontinuation
- 2004-10-22 CN CNA2004800301164A patent/CN1997364A/zh active Pending
- 2004-10-22 BR BRPI0415463-0A patent/BRPI0415463A/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007509110A (ja) | 2007-04-12 |
| CA2543342A1 (en) | 2005-05-06 |
| EP1680106B1 (en) | 2009-08-05 |
| DE602004022445D1 (de) | 2009-09-17 |
| BRPI0415463A (pt) | 2006-12-19 |
| RU2006117639A (ru) | 2007-12-10 |
| EP1680106A1 (en) | 2006-07-19 |
| AU2004283055A1 (en) | 2005-05-06 |
| CN1997364A (zh) | 2007-07-11 |
| WO2005039566A1 (en) | 2005-05-06 |
| ATE438394T1 (de) | 2009-08-15 |
| AR046132A1 (es) | 2005-11-23 |
| MXPA06004390A (es) | 2006-06-14 |
| CN1921849A (zh) | 2007-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Das et al. | A survey of the structures of US FDA approved combination drugs | |
| Oparil | Newly emerging pharmacologic differences in angiotensin II receptor blockers | |
| US20220280470A1 (en) | Treatment for tumors driven by metabolic dysfuction | |
| US12403114B2 (en) | Cannabinoid acid ester compositions and uses thereof | |
| EP2285366B1 (fr) | Molecules inhibant une voie metabolique impliquant la proteine tyrosine kinase syk et procede d'identification de ces molecules | |
| US12419846B2 (en) | Biomarkers of METAP2 inhibitors and applications thereof | |
| TW201136916A (en) | New uses | |
| US20050124660A1 (en) | Novel medical uses of compounds showing CB1-antagonistic activity and combination treatment involving said compounds | |
| KR20040032141A (ko) | 제약 복합제제 | |
| CN101365435A (zh) | 有机化合物的组合产品 | |
| WO2006105117A2 (en) | Method of treating disorders and conditions using peripherally-restricted antagonists and inhibitors | |
| JP2007513872A (ja) | Ｃｂ１拮抗作用を示す化合物の新規の医学的用途および前記化合物を伴う組み合わせ治療 | |
| TW200528102A (en) | Novel medical combination treatment of obesity involving 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity | |
| WO2006118212A1 (ja) | 膵炎の予防および治療剤 | |
| US20050143441A1 (en) | Novel medical combination treatment of obesity involving 4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity | |
| KR101758208B1 (ko) | HNF4-α 길항제 및 이의 용도 | |
| TW200530219A (en) | Novel medical uses of compounds showing CB1-antagonistic activity and combination treatment involving said compounds | |
| Kondo et al. | The discovery of Samsca®(Tolvaptan): the first oral nonpeptide vasopressin receptor antagonist | |
| HK1101275A (en) | Novel medical uses of compounds showing cb1-antagonistic activity and combination treatment involving said compounds | |
| WO2010148179A1 (en) | Method of treating a disorder associated with mtp |