CN102015683B - 取代的吲哚衍生物 - Google Patents
取代的吲哚衍生物 Download PDFInfo
- Publication number
- CN102015683B CN102015683B CN200980115064.3A CN200980115064A CN102015683B CN 102015683 B CN102015683 B CN 102015683B CN 200980115064 A CN200980115064 A CN 200980115064A CN 102015683 B CN102015683 B CN 102015683B
- Authority
- CN
- China
- Prior art keywords
- base
- methyl
- dimethylamino
- ethyl
- piperidin
- 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.)
- Expired - Fee Related
Links
- 150000002475 indoles Chemical class 0.000 title claims abstract description 50
- 229940054051 antipsychotic indole derivative Drugs 0.000 title claims abstract description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 55
- 238000000034 method Methods 0.000 claims abstract description 32
- 108010020615 nociceptin receptor Proteins 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 12
- 239000002585 base Substances 0.000 claims description 218
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 217
- 238000006243 chemical reaction Methods 0.000 claims description 99
- -1 normal-butyl Chemical group 0.000 claims description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 76
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 73
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 71
- 239000002904 solvent Substances 0.000 claims description 59
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 55
- 230000002829 reductive effect Effects 0.000 claims description 48
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
- 150000001412 amines Chemical class 0.000 claims description 20
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 208000002193 Pain Diseases 0.000 claims description 16
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 15
- 102000048266 Nociceptin Human genes 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 235000019253 formic acid Nutrition 0.000 claims description 15
- PULGYDLMFSFVBL-SMFNREODSA-N nociceptin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 PULGYDLMFSFVBL-SMFNREODSA-N 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims description 13
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 12
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 11
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 230000036407 pain Effects 0.000 claims description 10
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 9
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 7
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 7
- 238000005859 coupling reaction Methods 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 5
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 5
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 150000007530 organic bases Chemical class 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 claims description 4
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002091 cationic group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 230000013016 learning Effects 0.000 claims description 4
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 239000012317 TBTU Substances 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 230000037406 food intake Effects 0.000 claims description 3
- 230000015654 memory Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 230000001777 nootropic effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 239000012279 sodium borohydride Substances 0.000 claims description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 206010006895 Cachexia Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000008589 Obesity Diseases 0.000 claims description 2
- 208000004880 Polyuria Diseases 0.000 claims description 2
- 208000003251 Pruritus Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000009205 Tinnitus Diseases 0.000 claims description 2
- 239000001961 anticonvulsive agent Substances 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 208000010877 cognitive disease Diseases 0.000 claims description 2
- 229950001902 dimevamide Drugs 0.000 claims description 2
- 230000035619 diuresis Effects 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 208000016354 hearing loss disease Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- MFKASPDBGNVCQS-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-3-(1h-indol-3-yl)-n-methylpropanamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)CCC1=CNC2=CC=CC=C12 MFKASPDBGNVCQS-UHFFFAOYSA-N 0.000 claims description 2
- 239000002858 neurotransmitter agent Substances 0.000 claims description 2
- 239000002664 nootropic agent Substances 0.000 claims description 2
- 235000020824 obesity Nutrition 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 231100000886 tinnitus Toxicity 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 23
- 150000002576 ketones Chemical class 0.000 claims 19
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 11
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 9
- 239000003513 alkali Substances 0.000 claims 6
- 150000001408 amides Chemical class 0.000 claims 6
- DPFWUAYMRGTMAM-UHFFFAOYSA-N 2-fluoro-1-methylindole Chemical compound C1=CC=C2N(C)C(F)=CC2=C1 DPFWUAYMRGTMAM-UHFFFAOYSA-N 0.000 claims 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims 3
- 239000011707 mineral Substances 0.000 claims 3
- 235000010755 mineral Nutrition 0.000 claims 3
- 230000004048 modification Effects 0.000 claims 3
- 238000012986 modification Methods 0.000 claims 3
- GRIOMWQLXUWOJG-UHFFFAOYSA-N n-methyl-1h-indole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)NC)=CC2=C1 GRIOMWQLXUWOJG-UHFFFAOYSA-N 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 230000003533 narcotic effect Effects 0.000 claims 2
- 208000024891 symptom Diseases 0.000 claims 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- ASFAFOSQXBRFMV-LJQANCHMSA-N 3-n-(2-benzyl-1,3-dihydroxypropan-2-yl)-1-n-[(1r)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]benzene-1,3-dicarboxamide Chemical compound N([C@H](C)C=1C=CC(F)=CC=1)C(=O)C(C=1)=CC(N(C)S(C)(=O)=O)=CC=1C(=O)NC(CO)(CO)CC1=CC=CC=C1 ASFAFOSQXBRFMV-LJQANCHMSA-N 0.000 claims 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims 1
- 206010011878 Deafness Diseases 0.000 claims 1
- 206010052804 Drug tolerance Diseases 0.000 claims 1
- 208000012661 Dyskinesia Diseases 0.000 claims 1
- 239000008896 Opium Substances 0.000 claims 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims 1
- 230000000996 additive effect Effects 0.000 claims 1
- 239000012964 benzotriazole Substances 0.000 claims 1
- 208000024732 dysthymic disease Diseases 0.000 claims 1
- 208000026500 emaciation Diseases 0.000 claims 1
- 125000001033 ether group Chemical group 0.000 claims 1
- 235000013305 food Nutrition 0.000 claims 1
- 230000026781 habituation Effects 0.000 claims 1
- 230000010370 hearing loss Effects 0.000 claims 1
- 231100000888 hearing loss Toxicity 0.000 claims 1
- 230000000926 neurological effect Effects 0.000 claims 1
- 229960001027 opium Drugs 0.000 claims 1
- 230000008855 peristalsis Effects 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 239000011574 phosphorus Substances 0.000 claims 1
- 235000015320 potassium carbonate Nutrition 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 abstract description 16
- 125000001041 indolyl group Chemical group 0.000 abstract description 12
- 230000008569 process Effects 0.000 abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 112
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 94
- 239000000243 solution Substances 0.000 description 80
- 239000011541 reaction mixture Substances 0.000 description 72
- 239000000047 product Substances 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 239000000203 mixture Substances 0.000 description 48
- 125000000217 alkyl group Chemical group 0.000 description 46
- 235000019439 ethyl acetate Nutrition 0.000 description 44
- 238000004809 thin layer chromatography Methods 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 125000003118 aryl group Chemical group 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 150000003839 salts Chemical class 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- 125000001072 heteroaryl group Chemical group 0.000 description 18
- 239000007832 Na2SO4 Substances 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 17
- 235000011054 acetic acid Nutrition 0.000 description 16
- 239000012043 crude product Substances 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 125000006239 protecting group Chemical group 0.000 description 13
- 239000003643 water by type Substances 0.000 description 13
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 239000007789 gas Substances 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 108090000622 Nociceptin Proteins 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 10
- 150000001768 cations Chemical class 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000002877 alkyl aryl group Chemical group 0.000 description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 8
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000007429 general method Methods 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 102000051367 mu Opioid Receptors Human genes 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000001308 synthesis method Methods 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- 108020001612 μ-opioid receptors Proteins 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 150000004795 grignard reagents Chemical class 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- KHGMAFLCMFOPIR-UHFFFAOYSA-N n,n-dimethyl-4-phenylpiperidin-4-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC=CC=1C1(N(C)C)CCNCC1 KHGMAFLCMFOPIR-UHFFFAOYSA-N 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 108090000137 Opioid Receptors Proteins 0.000 description 4
- 102000003840 Opioid Receptors Human genes 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000003502 anti-nociceptive effect Effects 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000013058 crude material Substances 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- VYFGXPJVUSTGGP-UHFFFAOYSA-N n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CSC=1C1(N(C)C)CCNCC1 VYFGXPJVUSTGGP-UHFFFAOYSA-N 0.000 description 4
- 229940005483 opioid analgesics Drugs 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- BYZGXEGZFLNLMO-UHFFFAOYSA-N 1-(2-aminoethyl)-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.C=1C=CSC=1C1(N(C)C)CCN(CCN)CC1 BYZGXEGZFLNLMO-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- MVCIMEGPCAVHOK-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]-2,3-dihydroindole-3-carboxylic acid Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)CC(C(O)=O)C2=C1 MVCIMEGPCAVHOK-UHFFFAOYSA-N 0.000 description 3
- HHVOXWSYIFASSV-UHFFFAOYSA-N 1-benzyl-4-(dimethylamino)piperidine-4-carbonitrile Chemical compound C1CC(N(C)C)(C#N)CCN1CC1=CC=CC=C1 HHVOXWSYIFASSV-UHFFFAOYSA-N 0.000 description 3
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 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
- 201000010099 disease Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 150000002391 heterocyclic compounds Chemical class 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 3
- LADGLPXYBPWSHC-UHFFFAOYSA-N n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound C=1C=CSC=1C1(N(C)C)CCNCC1 LADGLPXYBPWSHC-UHFFFAOYSA-N 0.000 description 3
- OCXWOKQQQRIQKQ-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-5-fluoro-n-methyl-1h-indole-2-carboxamide Chemical compound C1CN(CCN(C)C(=O)C=2NC3=CC=C(F)C=C3C=2)CCC1(N(C)C)C1=CC=CC=C1 OCXWOKQQQRIQKQ-UHFFFAOYSA-N 0.000 description 3
- AUKNFZRIIILDET-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n-methyl-1h-indole-6-carboxamide Chemical compound C1CN(CCN(C)C(=O)C=2C=C3NC=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 AUKNFZRIIILDET-UHFFFAOYSA-N 0.000 description 3
- WIZSXFXXNUWCOE-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethyl]-3-(1h-indol-3-yl)-4-methylpentanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)NCCN(CC1)CCC1(N(C)C)C1=CC=CS1 WIZSXFXXNUWCOE-UHFFFAOYSA-N 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 208000021722 neuropathic pain Diseases 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000000159 protein binding assay Methods 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- FXVUWJJCTNMRII-UHFFFAOYSA-N tert-butyl 4-(dimethylamino)-4-thiophen-2-ylpiperidine-1-carboxylate Chemical compound C=1C=CSC=1C1(N(C)C)CCN(C(=O)OC(C)(C)C)CC1 FXVUWJJCTNMRII-UHFFFAOYSA-N 0.000 description 3
- GJGLBUZZTLPCOT-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)-n-methylcarbamate Chemical compound OCCCN(C)C(=O)OC(C)(C)C GJGLBUZZTLPCOT-UHFFFAOYSA-N 0.000 description 3
- MSWTVSDFEYSRMQ-UHFFFAOYSA-N tert-butyl n-methyl-n-(2-oxoethyl)carbamate Chemical compound O=CCN(C)C(=O)OC(C)(C)C MSWTVSDFEYSRMQ-UHFFFAOYSA-N 0.000 description 3
- JBAKABOTZNERRZ-UHFFFAOYSA-N tert-butyl n-methyl-n-(3-oxopropyl)carbamate Chemical compound O=CCCN(C)C(=O)OC(C)(C)C JBAKABOTZNERRZ-UHFFFAOYSA-N 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 2
- LYGPZEATHDSVTP-UHFFFAOYSA-N 1-[2-[(1-benzyl-5-methoxy-2-methylindol-3-yl)methyl-methylamino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound CC1=C(CN(C)CCN2CCC(CC2)(N(C)C)C=2C=CC=CC=2)C2=CC(OC)=CC=C2N1CC1=CC=CC=C1 LYGPZEATHDSVTP-UHFFFAOYSA-N 0.000 description 2
- KDAPWPPEWBALMZ-UHFFFAOYSA-N 1-[2-[(5-chloro-1h-indol-3-yl)methyl-methylamino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1NC2=CC=C(Cl)C=C2C=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 KDAPWPPEWBALMZ-UHFFFAOYSA-N 0.000 description 2
- ZOUCEMVEMBRLAS-UHFFFAOYSA-N 1-[2-[(5-chloro-1h-indol-3-yl)methylamino]ethyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound C1CN(CCNCC=2C3=CC(Cl)=CC=C3NC=2)CCC1(N(C)C)C1=CC=CS1 ZOUCEMVEMBRLAS-UHFFFAOYSA-N 0.000 description 2
- RYTISKJHIGCPNM-UHFFFAOYSA-N 1-[2-[(5-methoxy-1h-indol-3-yl)methylamino]ethyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound C12=CC(OC)=CC=C2NC=C1CNCCN(CC1)CCC1(N(C)C)C1=CC=CS1 RYTISKJHIGCPNM-UHFFFAOYSA-N 0.000 description 2
- XKPOKDKPDLQOGR-UHFFFAOYSA-N 1-[2-[1h-indol-3-ylmethyl(methyl)amino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1NC2=CC=CC=C2C=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 XKPOKDKPDLQOGR-UHFFFAOYSA-N 0.000 description 2
- VEFZTKZLWLNPEU-UHFFFAOYSA-N 1-[2-[1h-indol-4-ylmethyl(methyl)amino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1C=CC=2NC=CC=2C=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 VEFZTKZLWLNPEU-UHFFFAOYSA-N 0.000 description 2
- ZECNAZWWPHRNLQ-UHFFFAOYSA-N 1-[2-[1h-indol-6-ylmethyl(methyl)amino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1C=C2C=CNC2=CC=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 ZECNAZWWPHRNLQ-UHFFFAOYSA-N 0.000 description 2
- BDJATFZBJRQJSS-UHFFFAOYSA-N 1-benzyl-4-butyl-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CC1=CC=CC=C1 BDJATFZBJRQJSS-UHFFFAOYSA-N 0.000 description 2
- FBXWTUBCGRRDCA-UHFFFAOYSA-N 1-benzyl-4-phenyl-4-pyrrolidin-1-ylpiperidine Chemical compound C=1C=CC=CC=1CN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 FBXWTUBCGRRDCA-UHFFFAOYSA-N 0.000 description 2
- QYTCSUCLFRIBLQ-UHFFFAOYSA-N 1-benzyl-4-pyrrolidin-1-ylpiperidine-4-carbonitrile Chemical compound C1CC(C#N)(N2CCCC2)CCN1CC1=CC=CC=C1 QYTCSUCLFRIBLQ-UHFFFAOYSA-N 0.000 description 2
- UPCGCKVYJLDAKD-UHFFFAOYSA-N 1-benzyl-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCN1CC1=CC=CC=C1 UPCGCKVYJLDAKD-UHFFFAOYSA-N 0.000 description 2
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- FFFIRKXTFQCCKJ-UHFFFAOYSA-N 2,4,6-trimethylbenzoic acid Chemical compound CC1=CC(C)=C(C(O)=O)C(C)=C1 FFFIRKXTFQCCKJ-UHFFFAOYSA-N 0.000 description 2
- VIKBNMWOLLIQPG-UHFFFAOYSA-N 2-methyldecanedioic acid Chemical compound OC(=O)C(C)CCCCCCCC(O)=O VIKBNMWOLLIQPG-UHFFFAOYSA-N 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
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- ALYNCZNDIQEVRV-PZFLKRBQSA-N 4-amino-3,5-ditritiobenzoic acid Chemical compound [3H]c1cc(cc([3H])c1N)C(O)=O ALYNCZNDIQEVRV-PZFLKRBQSA-N 0.000 description 2
- TWODFGOGZSJGFF-UHFFFAOYSA-N 4-butyl-n,n-dimethyl-1-[2-(methylamino)ethyl]piperidin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.CCCCC1(N(C)C)CCN(CCNC)CC1 TWODFGOGZSJGFF-UHFFFAOYSA-N 0.000 description 2
- CELGPXSFFNRYAY-UHFFFAOYSA-N 4-phenyl-4-pyrrolidin-1-ylpiperidine Chemical compound C1CCCN1C1(C=2C=CC=CC=2)CCNCC1 CELGPXSFFNRYAY-UHFFFAOYSA-N 0.000 description 2
- PVDACOZHKAXJAS-UHFFFAOYSA-N 4-phenyl-4-pyrrolidin-1-ylpiperidine;dihydrochloride Chemical compound Cl.Cl.C1CCCN1C1(C=2C=CC=CC=2)CCNCC1 PVDACOZHKAXJAS-UHFFFAOYSA-N 0.000 description 2
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 2
- BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 2
- GLTZHSDOJGAPGU-UHFFFAOYSA-N 6-chloro-n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n-methyl-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CN(CCN(C)C(=O)C2C3=C(C4=CC(Cl)=CC=C4N3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 GLTZHSDOJGAPGU-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- OKJIRPAQVSHGFK-UHFFFAOYSA-N N-acetylglycine Chemical compound CC(=O)NCC(O)=O OKJIRPAQVSHGFK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 230000001598 anti-natriuretic effect Effects 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 125000003943 azolyl group Chemical group 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- ICGXIHNNQZEWLP-UHFFFAOYSA-N benzyl 4-(dimethylamino)-4-phenylpiperidine-1-carboxylate Chemical compound C1CC(N(C)C)(C=2C=CC=CC=2)CCN1C(=O)OCC1=CC=CC=C1 ICGXIHNNQZEWLP-UHFFFAOYSA-N 0.000 description 2
- UVWITLQIZVFWJG-UHFFFAOYSA-N benzyl 4-phenyl-4-pyrrolidin-1-ylpiperidine-1-carboxylate Chemical compound C1CC(C=2C=CC=CC=2)(N2CCCC2)CCN1C(=O)OCC1=CC=CC=C1 UVWITLQIZVFWJG-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 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 2
- 230000027455 binding Effects 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- FYAQQULBLMNGAH-UHFFFAOYSA-N hexane-1-sulfonic acid Chemical compound CCCCCCS(O)(=O)=O FYAQQULBLMNGAH-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000000543 intermediate Substances 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
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 235000019136 lipoic acid Nutrition 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 230000006742 locomotor activity Effects 0.000 description 2
- 229960002510 mandelic acid Drugs 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- QXAUTQFAWKKNLM-UHFFFAOYSA-N methyl indole-3-carboxylate Chemical compound C1=CC=C2C(C(=O)OC)=CNC2=C1 QXAUTQFAWKKNLM-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 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 2
- QBRNECYIHXRKNB-UHFFFAOYSA-N n,n-dimethyl-1-[2-(methylamino)ethyl]-4-phenylpiperidin-4-amine Chemical compound C1CN(CCNC)CCC1(N(C)C)C1=CC=CC=C1 QBRNECYIHXRKNB-UHFFFAOYSA-N 0.000 description 2
- LUMAGIGUMWPJFQ-UHFFFAOYSA-N n,n-dimethyl-1-[2-(methylamino)ethyl]-4-phenylpiperidin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CCNC)CCC1(N(C)C)C1=CC=CC=C1 LUMAGIGUMWPJFQ-UHFFFAOYSA-N 0.000 description 2
- JMSLKESKTAAQCQ-UHFFFAOYSA-N n,n-dimethyl-1-[3-(methylamino)propyl]-4-thiophen-2-ylpiperidin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CCCNC)CCC1(N(C)C)C1=CC=CS1 JMSLKESKTAAQCQ-UHFFFAOYSA-N 0.000 description 2
- LZJCNZXEVTXKSL-UHFFFAOYSA-N n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1C=CC=CC=1C1(N(C)C)CCNCC1 LZJCNZXEVTXKSL-UHFFFAOYSA-N 0.000 description 2
- DSFBRRNSTBKUNM-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-2-(6-fluoro-1h-indol-3-yl)-n-methylacetamide Chemical compound C1CN(CCN(C)C(=O)CC=2C3=CC=C(F)C=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 DSFBRRNSTBKUNM-UHFFFAOYSA-N 0.000 description 2
- DRSGCOMYBWFHBZ-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n,1-dimethylindole-6-carboxamide Chemical compound C=1C=C2C=CN(C)C2=CC=1C(=O)N(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 DRSGCOMYBWFHBZ-UHFFFAOYSA-N 0.000 description 2
- YEJTVAXRWBWLGQ-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-2-(6-fluoro-1h-indol-3-yl)-n-methylacetamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)CC1=CNC2=CC(F)=CC=C12 YEJTVAXRWBWLGQ-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 2
- 229960004127 naloxone Drugs 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical class NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 2
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- ACAJZVZKPGMTSC-UHFFFAOYSA-N tert-butyl 4-(dimethylamino)-4-phenylpiperidine-1-carboxylate Chemical compound C=1C=CC=CC=1C1(N(C)C)CCN(C(=O)OC(C)(C)C)CC1 ACAJZVZKPGMTSC-UHFFFAOYSA-N 0.000 description 2
- COVRYKGBHLVHIR-UHFFFAOYSA-N tert-butyl 4-cyano-4-(dimethylamino)piperidine-1-carboxylate Chemical compound CN(C)C1(C#N)CCN(C(=O)OC(C)(C)C)CC1 COVRYKGBHLVHIR-UHFFFAOYSA-N 0.000 description 2
- FXERUYFGHBHWNN-UHFFFAOYSA-N tert-butyl n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n-methylcarbamate Chemical compound C1CN(CCN(C)C(=O)OC(C)(C)C)CCC1(N(C)C)C1=CC=CC=C1 FXERUYFGHBHWNN-UHFFFAOYSA-N 0.000 description 2
- FOEKWOGKNLTMGX-UHFFFAOYSA-N tert-butyl n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethyl]carbamate Chemical compound C=1C=CSC=1C1(N(C)C)CCN(CCNC(=O)OC(C)(C)C)CC1 FOEKWOGKNLTMGX-UHFFFAOYSA-N 0.000 description 2
- GJSBIMHVOGHHQN-UHFFFAOYSA-N tert-butyl n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-n-methylcarbamate Chemical compound CCCCC1(N(C)C)CCN(CCN(C)C(=O)OC(C)(C)C)CC1 GJSBIMHVOGHHQN-UHFFFAOYSA-N 0.000 description 2
- VUIUAIFYQUYFQX-UHFFFAOYSA-N tert-butyl n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-n-methylcarbamate Chemical compound C1CN(CCCN(C)C(=O)OC(C)(C)C)CCC1(N(C)C)C1=CC=CC=C1 VUIUAIFYQUYFQX-UHFFFAOYSA-N 0.000 description 2
- TWKSNLQQGGOJDN-UHFFFAOYSA-N tert-butyl n-[3-[tert-butyl(dimethyl)silyl]oxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCO[Si](C)(C)C(C)(C)C TWKSNLQQGGOJDN-UHFFFAOYSA-N 0.000 description 2
- KKJIPWGIECUIGY-UHFFFAOYSA-N tert-butyl n-methyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]carbamate Chemical compound C1CN(CCN(C)C(=O)OC(C)(C)C)CCC1(C=1C=CC=CC=1)N1CCCC1 KKJIPWGIECUIGY-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 229960002663 thioctic acid Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 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
- BJMUOUXGBFNLSN-UHFFFAOYSA-N 1,2-dimethylindole Chemical group C1=CC=C2N(C)C(C)=CC2=C1 BJMUOUXGBFNLSN-UHFFFAOYSA-N 0.000 description 1
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 1
- NXILIHONWRXHFA-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC(C(O)=O)C1 NXILIHONWRXHFA-UHFFFAOYSA-N 0.000 description 1
- BPRZKJJPHKRYFH-UHFFFAOYSA-N 1-[2-(1h-indol-3-ylmethylamino)ethyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound C1CN(CCNCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CS1 BPRZKJJPHKRYFH-UHFFFAOYSA-N 0.000 description 1
- CLTCEERPDHANHV-UHFFFAOYSA-N 1-[2-(1h-indol-5-ylmethylamino)ethyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound C1CN(CCNCC=2C=C3C=CNC3=CC=2)CCC1(N(C)C)C1=CC=CS1 CLTCEERPDHANHV-UHFFFAOYSA-N 0.000 description 1
- KDDGRKMLSAKHDH-UHFFFAOYSA-N 1-[2-[(1,2-dimethylindol-3-yl)methylamino]ethyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound C1CN(CCNCC=2C3=CC=CC=C3N(C)C=2C)CCC1(N(C)C)C1=CC=CS1 KDDGRKMLSAKHDH-UHFFFAOYSA-N 0.000 description 1
- VHSKKUSQBLXPFP-UHFFFAOYSA-N 1-[2-[(1-benzyl-5-methoxy-2-methylindol-3-yl)methylamino]ethyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound CC1=C(CNCCN2CCC(CC2)(N(C)C)C=2SC=CC=2)C2=CC(OC)=CC=C2N1CC1=CC=CC=C1 VHSKKUSQBLXPFP-UHFFFAOYSA-N 0.000 description 1
- YSGWYMIEOCTQNJ-UHFFFAOYSA-N 1-[2-[(5-bromo-1h-indol-3-yl)methyl-methylamino]ethyl]-4-butyl-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)CC1=CNC2=CC=C(Br)C=C12 YSGWYMIEOCTQNJ-UHFFFAOYSA-N 0.000 description 1
- NLMGZWMPAJIATG-UHFFFAOYSA-N 1-[2-[(5-bromo-1h-indol-3-yl)methyl-methylamino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1NC2=CC=C(Br)C=C2C=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 NLMGZWMPAJIATG-UHFFFAOYSA-N 0.000 description 1
- NSGZTYVDEIVMNX-UHFFFAOYSA-N 1-[2-[1h-indol-5-ylmethyl(methyl)amino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1C=C2NC=CC2=CC=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 NSGZTYVDEIVMNX-UHFFFAOYSA-N 0.000 description 1
- ZFMRHHQMBQAHTE-UHFFFAOYSA-N 1-[2-[[2-(4-fluorophenyl)-1h-indol-3-yl]methyl-methylamino]ethyl]-n,n-dimethyl-4-phenylpiperidin-4-amine Chemical compound C=1C=C(F)C=CC=1C=1NC2=CC=CC=C2C=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 ZFMRHHQMBQAHTE-UHFFFAOYSA-N 0.000 description 1
- ZKIJPVQJIMGDAN-UHFFFAOYSA-N 1-[3-[(1,2-dimethylindol-3-yl)methyl-methylamino]propyl]-n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine Chemical compound CC=1N(C)C2=CC=CC=C2C=1CN(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CS1 ZKIJPVQJIMGDAN-UHFFFAOYSA-N 0.000 description 1
- YKONAAJIUWYMAA-UHFFFAOYSA-N 1-[3-[4-(dimethylamino)-4-phenylpiperidine-1-carbonyl]-2,3-dihydroindol-1-yl]-3-(1h-indol-3-yl)-4-methylpentan-1-one Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)N(C1=CC=CC=C11)CC1C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 YKONAAJIUWYMAA-UHFFFAOYSA-N 0.000 description 1
- HJSBDIRAQGXBDE-UHFFFAOYSA-N 1-[3-[4-(dimethylamino)-4-phenylpiperidine-1-carbonyl]piperidin-1-yl]-3-(1h-indol-3-yl)-4-methylpentan-1-one Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)N(C1)CCCC1C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 HJSBDIRAQGXBDE-UHFFFAOYSA-N 0.000 description 1
- FQXOBOSLXVTBSY-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-2-[1h-indol-5-ylmethyl(methyl)amino]-3-methylbutan-1-one Chemical compound C=1C=C2NC=CC2=CC=1CN(C)C(C(C)C)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 FQXOBOSLXVTBSY-UHFFFAOYSA-N 0.000 description 1
- YSAOGFDRRKYHOM-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-2-[1h-indol-6-ylmethyl(methyl)amino]-3-methylbutan-1-one Chemical compound C=1C=C2C=CNC2=CC=1CN(C)C(C(C)C)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 YSAOGFDRRKYHOM-UHFFFAOYSA-N 0.000 description 1
- CMLQUCODDTWZDU-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-(1h-indol-3-ylmethylamino)propan-1-one Chemical compound C1CN(C(=O)CCNCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 CMLQUCODDTWZDU-UHFFFAOYSA-N 0.000 description 1
- LWFZHTTWEMCKBU-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-(1h-indol-5-ylmethylamino)propan-1-one Chemical compound C1CN(C(=O)CCNCC=2C=C3C=CNC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 LWFZHTTWEMCKBU-UHFFFAOYSA-N 0.000 description 1
- JNUGYWAMGKYHBT-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-(1h-indol-6-ylmethylamino)propan-1-one Chemical compound C1CN(C(=O)CCNCC=2C=C3NC=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 JNUGYWAMGKYHBT-UHFFFAOYSA-N 0.000 description 1
- OTGSTEWKYINAAQ-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-(1h-indol-7-ylmethylamino)propan-1-one Chemical compound C1CN(C(=O)CCNCC=2C=3NC=CC=3C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 OTGSTEWKYINAAQ-UHFFFAOYSA-N 0.000 description 1
- GYLONEDXBRCYEJ-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-methyl-2-(methylamino)butan-1-one Chemical compound C1CN(C(=O)C(C(C)C)NC)CCC1(N(C)C)C1=CC=CC=C1 GYLONEDXBRCYEJ-UHFFFAOYSA-N 0.000 description 1
- HLEFKMDOGCEYPG-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-(1h-indol-7-ylmethylamino)ethanone Chemical compound C1CN(C(=O)CNCC=2C=3NC=CC=3C=CC=2)CCC1(N(C)C)C1=CC=CS1 HLEFKMDOGCEYPG-UHFFFAOYSA-N 0.000 description 1
- BCYQDRPOCUWCPY-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-(methylamino)-2-phenylethanone;trihydrochloride Chemical compound Cl.Cl.Cl.C=1C=CC=CC=1C(NC)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 BCYQDRPOCUWCPY-UHFFFAOYSA-N 0.000 description 1
- JQJZLNSSBKQOHA-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-[1h-indol-5-ylmethyl(methyl)amino]-2-phenylethanone Chemical compound C=1C=C2NC=CC2=CC=1CN(C)C(C=1C=CC=CC=1)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 JQJZLNSSBKQOHA-UHFFFAOYSA-N 0.000 description 1
- ALTLNTCEEWXHFM-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-[1h-indol-6-ylmethyl(methyl)amino]-2-phenylethanone Chemical compound C=1C=C2C=CNC2=CC=1CN(C)C(C=1C=CC=CC=1)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 ALTLNTCEEWXHFM-UHFFFAOYSA-N 0.000 description 1
- VAOHLWNZGWBTOK-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-(1h-indol-3-ylmethylamino)-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C2=CC=CC=C2NC=1)C1=CC=CC=C1 VAOHLWNZGWBTOK-UHFFFAOYSA-N 0.000 description 1
- JQCGTOPHNOILMA-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-(1h-indol-4-ylmethylamino)-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C=2C=CNC=2C=CC=1)C1=CC=CC=C1 JQCGTOPHNOILMA-UHFFFAOYSA-N 0.000 description 1
- BQTPPLVLVUXUAO-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-(1h-indol-5-ylmethylamino)-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C=C2C=CNC2=CC=1)C1=CC=CC=C1 BQTPPLVLVUXUAO-UHFFFAOYSA-N 0.000 description 1
- NGSDKBRWYABHLJ-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-(1h-indol-6-ylmethylamino)-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C=C2NC=CC2=CC=1)C1=CC=CC=C1 NGSDKBRWYABHLJ-UHFFFAOYSA-N 0.000 description 1
- JEPBJURQHYMQRJ-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-(1h-indol-7-ylmethylamino)-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C=2NC=CC=2C=CC=1)C1=CC=CC=C1 JEPBJURQHYMQRJ-UHFFFAOYSA-N 0.000 description 1
- FEAFRQQLILMLAZ-UHFFFAOYSA-N 1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-[(2-methyl-1h-indol-3-yl)methylamino]-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C2=CC=CC=C2NC=1C)C1=CC=CC=C1 FEAFRQQLILMLAZ-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical group C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 1
- SBNOTUDDIXOFSN-UHFFFAOYSA-N 1h-indole-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=CC2=C1 SBNOTUDDIXOFSN-UHFFFAOYSA-N 0.000 description 1
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 1
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 description 1
- DDETZPFDEHDRDK-UHFFFAOYSA-N 2,3-dihydro-1h-indol-3-yl-[4-(dimethylamino)-4-phenylpiperidin-1-yl]methanone;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(C(=O)C2C3=CC=CC=C3NC2)CCC1(N(C)C)C1=CC=CC=C1 DDETZPFDEHDRDK-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- VLHGDCJIDNVRFM-UHFFFAOYSA-N 2-(4-fluorophenyl)-1h-indole Chemical group C1=CC(F)=CC=C1C1=CC2=CC=CC=C2N1 VLHGDCJIDNVRFM-UHFFFAOYSA-N 0.000 description 1
- YVVSBJJLDVHWOP-UHFFFAOYSA-N 2-(5-bromo-1h-indol-3-yl)-n-[1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-n-methylacetamide Chemical compound C=1NC2=CC=C(Br)C=C2C=1CC(=O)N(C)C(C(C)C)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 YVVSBJJLDVHWOP-UHFFFAOYSA-N 0.000 description 1
- RKTAVFFBVGTPFO-UHFFFAOYSA-N 2-(5-bromo-1h-indol-3-yl)-n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-n-methylacetamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)CC=1C2=CC(Br)=CC=C2NC=1)C1=CC=CC=C1 RKTAVFFBVGTPFO-UHFFFAOYSA-N 0.000 description 1
- UFFVTHIGFLDOSG-UHFFFAOYSA-N 2-(5-bromo-1h-indol-3-yl)-n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-n-methylacetamide Chemical compound C1CN(CCCN(C)C(=O)CC=2C3=CC(Br)=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 UFFVTHIGFLDOSG-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- COABPHLHHQAKPL-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-2-phenylacetic acid Chemical compound CC(C)(C)OC(=O)N(C)C(C(O)=O)C1=CC=CC=C1 COABPHLHHQAKPL-UHFFFAOYSA-N 0.000 description 1
- WDDVPCQEPCXUAB-UHFFFAOYSA-N 2-amino-1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethanone Chemical compound C=1C=CSC=1C1(N(C)C)CCN(C(=O)CN)CC1 WDDVPCQEPCXUAB-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- KLTIMEXKPRJOIS-UHFFFAOYSA-N 2-chloro-1-methyl-2H-pyridine hydroiodide Chemical compound I.CN1C=CC=CC1Cl KLTIMEXKPRJOIS-UHFFFAOYSA-N 0.000 description 1
- FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical group N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 1
- FHQYOYXBMOXDKF-UHFFFAOYSA-N 3-(1h-indol-3-yl)-4-methylpentanoic acid Chemical compound C1=CC=C2C(C(CC(O)=O)C(C)C)=CNC2=C1 FHQYOYXBMOXDKF-UHFFFAOYSA-N 0.000 description 1
- JTNQFJPZRTURSI-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)NC(CC(O)=O)C1=CC=CC=C1 JTNQFJPZRTURSI-UHFFFAOYSA-N 0.000 description 1
- WCFJUSRQHZPVKY-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NCCC(O)=O WCFJUSRQHZPVKY-UHFFFAOYSA-N 0.000 description 1
- UAEZTZNNZHFTOI-UHFFFAOYSA-N 3-[(5-bromo-1h-indol-3-yl)methylamino]-1-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-phenylpropan-1-one Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NCC=1C2=CC(Br)=CC=C2NC=1)C1=CC=CC=C1 UAEZTZNNZHFTOI-UHFFFAOYSA-N 0.000 description 1
- JLCNZVOEOBPAMD-UHFFFAOYSA-N 3-amino-1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propan-1-one;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=CC=1C1(N(C)C)CCN(C(=O)CCN)CC1 JLCNZVOEOBPAMD-UHFFFAOYSA-N 0.000 description 1
- XPUAXAVJMJDPDH-UHFFFAOYSA-N 3-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid Chemical compound CC(C)C(C(O)=O)N(C)C(=O)OC(C)(C)C XPUAXAVJMJDPDH-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- OIGJFFBFVWAOQF-UHFFFAOYSA-N 4-butyl-1-[2-[1h-indol-3-ylmethyl(methyl)amino]ethyl]-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)CC1=CNC2=CC=CC=C12 OIGJFFBFVWAOQF-UHFFFAOYSA-N 0.000 description 1
- KKGAVFRTLHYQQY-UHFFFAOYSA-N 4-butyl-1-[2-[1h-indol-4-ylmethyl(methyl)amino]ethyl]-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)CC1=CC=CC2=C1C=CN2 KKGAVFRTLHYQQY-UHFFFAOYSA-N 0.000 description 1
- XUTWLQPWQKMMPT-UHFFFAOYSA-N 4-butyl-1-[2-[1h-indol-5-ylmethyl(methyl)amino]ethyl]-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)CC1=CC=C(NC=C2)C2=C1 XUTWLQPWQKMMPT-UHFFFAOYSA-N 0.000 description 1
- UUPIYCXVMFYPIB-UHFFFAOYSA-N 4-butyl-1-[2-[1h-indol-6-ylmethyl(methyl)amino]ethyl]-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)CC1=CC=C(C=CN2)C2=C1 UUPIYCXVMFYPIB-UHFFFAOYSA-N 0.000 description 1
- VACZJZGEJIAJDM-UHFFFAOYSA-N 4-butyl-1-[2-[1h-indol-7-ylmethyl(methyl)amino]ethyl]-n,n-dimethylpiperidin-4-amine Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)CC1=CC=CC2=C1NC=C2 VACZJZGEJIAJDM-UHFFFAOYSA-N 0.000 description 1
- NIMDOOVAVKGOED-UHFFFAOYSA-N 4-butyl-n,n-dimethylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.CCCCC1(N(C)C)CCNCC1 NIMDOOVAVKGOED-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical group C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical group BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- MYTGFBZJLDLWQG-UHFFFAOYSA-N 5-chloro-1h-indole Chemical group ClC1=CC=C2NC=CC2=C1 MYTGFBZJLDLWQG-UHFFFAOYSA-N 0.000 description 1
- WTXBRZCVLDTWLP-UHFFFAOYSA-N 5-fluoro-1H-indole-2-carboxylic acid Chemical compound FC1=CC=C2NC(C(=O)O)=CC2=C1 WTXBRZCVLDTWLP-UHFFFAOYSA-N 0.000 description 1
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical group FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
- CSYUSWFKMPDNHA-UHFFFAOYSA-N 5-methoxy-n-methyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]-1h-indole-2-carboxamide Chemical compound C=1C2=CC(OC)=CC=C2NC=1C(=O)N(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 CSYUSWFKMPDNHA-UHFFFAOYSA-N 0.000 description 1
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical group COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 1
- JRVZKDNDWBJNGG-UHFFFAOYSA-N 6-(dimethylamino)-n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-1h-indole-2-carboxamide Chemical compound N1C2=CC(N(C)C)=CC=C2C=C1C(=O)NCCC(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 JRVZKDNDWBJNGG-UHFFFAOYSA-N 0.000 description 1
- YTYIMDRWPTUAHP-UHFFFAOYSA-N 6-Chloroindole Chemical group ClC1=CC=C2C=CNC2=C1 YTYIMDRWPTUAHP-UHFFFAOYSA-N 0.000 description 1
- RFCJPBAODMJWMN-UHFFFAOYSA-N 6-chloro-n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-n-methyl-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)C1C2=C(C3=CC(Cl)=CC=C3N2)CCC1)C1=CC=CC=C1 RFCJPBAODMJWMN-UHFFFAOYSA-N 0.000 description 1
- WPBBIGOJMRHATB-UHFFFAOYSA-N 6-chloro-n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxoethyl]-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CN(C(=O)CNC(=O)C2C3=C(C4=CC(Cl)=CC=C4N3)CCC2)CCC1(N(C)C)C1=CC=CS1 WPBBIGOJMRHATB-UHFFFAOYSA-N 0.000 description 1
- QWIDTDGIUZUSAV-UHFFFAOYSA-N 6-chloro-n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethyl]-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CN(CCNC(=O)C2C3=C(C4=CC(Cl)=CC=C4N3)CCC2)CCC1(N(C)C)C1=CC=CS1 QWIDTDGIUZUSAV-UHFFFAOYSA-N 0.000 description 1
- FLEQQRZULRUEJL-UHFFFAOYSA-N 6-chloro-n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CN(C(=O)CCNC(=O)C2C3=C(C4=CC(Cl)=CC=C4N3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 FLEQQRZULRUEJL-UHFFFAOYSA-N 0.000 description 1
- IEBIASOFAJZGHQ-UHFFFAOYSA-N 6-chloro-n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-n-methyl-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CN(CCCN(C)C(=O)C2C3=C(C4=CC(Cl)=CC=C4N3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 IEBIASOFAJZGHQ-UHFFFAOYSA-N 0.000 description 1
- FWMUPOWGAHEENI-UHFFFAOYSA-N 6-chloro-n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NC(=O)C1C2=C(C3=CC(Cl)=CC=C3N2)CCC1)C1=CC=CC=C1 FWMUPOWGAHEENI-UHFFFAOYSA-N 0.000 description 1
- NEKIRBYWRRMNCU-UHFFFAOYSA-N 6-chloro-n-methyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CCC(C2=CC(Cl)=CC=C2N2)=C2C1C(=O)N(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 NEKIRBYWRRMNCU-UHFFFAOYSA-N 0.000 description 1
- YYFFEPUCAKVRJX-UHFFFAOYSA-N 6-fluoro-1h-indole Chemical group FC1=CC=C2C=CNC2=C1 YYFFEPUCAKVRJX-UHFFFAOYSA-N 0.000 description 1
- QYTHXOJFJVKOGA-UHFFFAOYSA-N 6-methoxy-1,2-dimethylindole Chemical group COC1=CC=C2C=C(C)N(C)C2=C1 QYTHXOJFJVKOGA-UHFFFAOYSA-N 0.000 description 1
- UUNKRAWCQSWCJE-UHFFFAOYSA-N 6-propan-2-yl-1h-indole Chemical group CC(C)C1=CC=C2C=CNC2=C1 UUNKRAWCQSWCJE-UHFFFAOYSA-N 0.000 description 1
- 241000937413 Axia Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 0 CC(C)(C)OC(N(CC1C(OC)=*)c2c1cccc2)=O Chemical compound CC(C)(C)OC(N(CC1C(OC)=*)c2c1cccc2)=O 0.000 description 1
- VOWZQOSRBMJMJM-UHFFFAOYSA-N CC(C)(C)OC([n]1c2ccccc2c(C(OC)=O)c1)=O Chemical compound CC(C)(C)OC([n]1c2ccccc2c(C(OC)=O)c1)=O VOWZQOSRBMJMJM-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000017228 Gastrointestinal motility disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 229910019093 NaOCl Inorganic materials 0.000 description 1
- 102000001490 Opioid Peptides Human genes 0.000 description 1
- 108010093625 Opioid Peptides Proteins 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
- NVOGFRXWGAVSLM-UHFFFAOYSA-N [1-[(5-bromo-1h-indol-3-yl)methyl]piperidin-3-yl]-[4-(dimethylamino)-4-phenylpiperidin-1-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C4=CC(Br)=CC=C4NC=3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 NVOGFRXWGAVSLM-UHFFFAOYSA-N 0.000 description 1
- XWUXKOBUMKZCOA-UHFFFAOYSA-N [1-[6-(dimethylamino)-1h-indole-2-carbonyl]piperidin-3-yl]-[4-(dimethylamino)-4-phenylpiperidin-1-yl]methanone Chemical compound N1C2=CC(N(C)C)=CC=C2C=C1C(=O)N(C1)CCCC1C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 XWUXKOBUMKZCOA-UHFFFAOYSA-N 0.000 description 1
- KATXFFKQRFCEBH-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1-methylindole-4-carbonyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CCC2)C(=O)C=2C=3C=CN(C)C=3C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 KATXFFKQRFCEBH-UHFFFAOYSA-N 0.000 description 1
- RXNZLPGBMMQLRF-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1-methylindole-6-carbonyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CCC2)C(=O)C=2C=C3N(C)C=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 RXNZLPGBMMQLRF-UHFFFAOYSA-N 0.000 description 1
- HMJLHRJJUCXXKE-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-3-ylmethyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C4=CC=CC=C4NC=3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 HMJLHRJJUCXXKE-UHFFFAOYSA-N 0.000 description 1
- RRQWPNAJLOBZFS-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-4-ylmethyl)-2,3-dihydroindol-3-yl]methanone Chemical compound C1CN(C(=O)C2C3=CC=CC=C3N(CC=3C=4C=CNC=4C=CC=3)C2)CCC1(N(C)C)C1=CC=CC=C1 RRQWPNAJLOBZFS-UHFFFAOYSA-N 0.000 description 1
- YVHLILKGLMMUJH-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-4-ylmethyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C=4C=CNC=4C=CC=3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 YVHLILKGLMMUJH-UHFFFAOYSA-N 0.000 description 1
- GFHQKOAVSRDWOG-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-5-ylmethyl)-2,3-dihydroindol-3-yl]methanone Chemical compound C1CN(C(=O)C2C3=CC=CC=C3N(CC=3C=C4C=CNC4=CC=3)C2)CCC1(N(C)C)C1=CC=CC=C1 GFHQKOAVSRDWOG-UHFFFAOYSA-N 0.000 description 1
- IYIPJVXPVODFNE-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-5-ylmethyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C=C4C=CNC4=CC=3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 IYIPJVXPVODFNE-UHFFFAOYSA-N 0.000 description 1
- BEAUTPUCMHLZOU-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-6-ylmethyl)-2,3-dihydroindol-3-yl]methanone Chemical compound C1CN(C(=O)C2C3=CC=CC=C3N(CC=3C=C4NC=CC4=CC=3)C2)CCC1(N(C)C)C1=CC=CC=C1 BEAUTPUCMHLZOU-UHFFFAOYSA-N 0.000 description 1
- RGYHXUSEJNQGNH-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-6-ylmethyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C=C4NC=CC4=CC=3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 RGYHXUSEJNQGNH-UHFFFAOYSA-N 0.000 description 1
- HRUHMEILUDYGEE-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indol-7-ylmethyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C=4NC=CC=4C=CC=3)CCC2)CCC1(N(C)C)C1=CC=CC=C1 HRUHMEILUDYGEE-UHFFFAOYSA-N 0.000 description 1
- YMPDVNSPZVKEPM-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indole-3-carbonyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CCC2)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 YMPDVNSPZVKEPM-UHFFFAOYSA-N 0.000 description 1
- SOZRBQJOENTOFF-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(1h-indole-6-carbonyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CCC2)C(=O)C=2C=C3NC=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 SOZRBQJOENTOFF-UHFFFAOYSA-N 0.000 description 1
- SIRVUXCRPLVHSJ-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-(5-fluoro-1h-indole-2-carbonyl)piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CCC2)C(=O)C=2NC3=CC=C(F)C=C3C=2)CCC1(N(C)C)C1=CC=CC=C1 SIRVUXCRPLVHSJ-UHFFFAOYSA-N 0.000 description 1
- IIEXSAAGCXUIFG-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-[(2-methyl-1h-indol-3-yl)methyl]piperidin-3-yl]methanone Chemical compound C1CN(C(=O)C2CN(CC=3C4=CC=CC=C4NC=3C)CCC2)CCC1(N(C)C)C1=CC=CC=C1 IIEXSAAGCXUIFG-UHFFFAOYSA-N 0.000 description 1
- UINDZYKBRQCYQQ-UHFFFAOYSA-N [4-(dimethylamino)-4-phenylpiperidin-1-yl]-[1-[(6-methoxy-1,2-dimethylindol-3-yl)methyl]piperidin-3-yl]methanone Chemical compound CC=1N(C)C2=CC(OC)=CC=C2C=1CN(C1)CCCC1C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 UINDZYKBRQCYQQ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 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
- 238000007112 amidation reaction Methods 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940089206 anhydrous dextrose Drugs 0.000 description 1
- 230000001539 anorectic effect Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- SJSWRKNSCWKNIR-UHFFFAOYSA-N azane;dihydrochloride Chemical compound N.Cl.Cl SJSWRKNSCWKNIR-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- POMVSFNBRWJNLM-UHFFFAOYSA-N cyclohexane-1,4-dione;ethane-1,2-diol Chemical compound OCCO.O=C1CCC(=O)CC1 POMVSFNBRWJNLM-UHFFFAOYSA-N 0.000 description 1
- 150000001934 cyclohexanes Chemical class 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 102000048124 delta Opioid Receptors Human genes 0.000 description 1
- 108700023159 delta Opioid Receptors Proteins 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- QEWYKACRFQMRMB-UHFFFAOYSA-M fluoroacetate Chemical compound [O-]C(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-M 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 230000000917 hyperalgesic effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical class [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 102000048260 kappa Opioid Receptors Human genes 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- ORGKXXNYFKQYHY-UHFFFAOYSA-N methyl n-(2-oxoethyl)carbamate Chemical compound COC(=O)NCC=O ORGKXXNYFKQYHY-UHFFFAOYSA-N 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- HPALGCLEZMFERL-UHFFFAOYSA-N n,1-dimethyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]indole-4-carboxamide Chemical compound C=1C=CC=2N(C)C=CC=2C=1C(=O)N(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 HPALGCLEZMFERL-UHFFFAOYSA-N 0.000 description 1
- PFKZXDIAFGJXRE-UHFFFAOYSA-N n,1-dimethyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]indole-6-carboxamide Chemical compound C=1C=C2C=CN(C)C2=CC=1C(=O)N(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 PFKZXDIAFGJXRE-UHFFFAOYSA-N 0.000 description 1
- LBWORDJQGWJNIV-UHFFFAOYSA-N n,n-dimethyl-1-[2-[(6-propan-2-yl-1h-indol-3-yl)methylamino]ethyl]-4-thiophen-2-ylpiperidin-4-amine Chemical compound C=1NC2=CC(C(C)C)=CC=C2C=1CNCCN(CC1)CCC1(N(C)C)C1=CC=CS1 LBWORDJQGWJNIV-UHFFFAOYSA-N 0.000 description 1
- GNPVJIFEFLHDSX-UHFFFAOYSA-N n,n-dimethyl-1-[2-[methyl-[(2-phenyl-1h-indol-3-yl)methyl]amino]ethyl]-4-phenylpiperidin-4-amine Chemical compound C=1C=CC=CC=1C=1NC2=CC=CC=C2C=1CN(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 GNPVJIFEFLHDSX-UHFFFAOYSA-N 0.000 description 1
- DPBLFSCCCOOSFP-UHFFFAOYSA-N n,n-dimethyl-1-[3-(methylamino)propyl]-4-phenylpiperidin-4-amine;hydrochloride Chemical compound Cl.C1CN(CCCNC)CCC1(N(C)C)C1=CC=CC=C1 DPBLFSCCCOOSFP-UHFFFAOYSA-N 0.000 description 1
- LUEQQZZOGSYPIX-UHFFFAOYSA-N n,n-dimethyl-1-[3-(methylamino)propyl]-4-phenylpiperidin-4-amine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CCCNC)CCC1(N(C)C)C1=CC=CC=C1 LUEQQZZOGSYPIX-UHFFFAOYSA-N 0.000 description 1
- SYLOJLHNCSMACS-UHFFFAOYSA-N n,n-dimethyl-1-[3-[methyl-[(6-propan-2-yl-1h-indol-3-yl)methyl]amino]propyl]-4-thiophen-2-ylpiperidin-4-amine Chemical compound C=1NC2=CC(C(C)C)=CC=C2C=1CN(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CS1 SYLOJLHNCSMACS-UHFFFAOYSA-N 0.000 description 1
- DKBOXZKCEURFLC-UHFFFAOYSA-N n,n-dimethyl-4-phenylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=1C=CC=CC=1C1(N(C)C)CCNCC1 DKBOXZKCEURFLC-UHFFFAOYSA-N 0.000 description 1
- CZPSILGHDHXWLL-UHFFFAOYSA-N n,n-dimethyl-4-thiophen-2-ylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C=1C=CSC=1C1(N(C)C)CCNCC1 CZPSILGHDHXWLL-UHFFFAOYSA-N 0.000 description 1
- UPKPAUGOGQNUBO-UHFFFAOYSA-N n-(1h-indol-3-ylmethyl)-n-methyl-2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethanamine Chemical compound C=1NC2=CC=CC=C2C=1CN(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 UPKPAUGOGQNUBO-UHFFFAOYSA-N 0.000 description 1
- WHPUOCIHYFGMNF-UHFFFAOYSA-N n-(1h-indol-4-ylmethyl)-n-methyl-2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethanamine Chemical compound C=1C=CC=2NC=CC=2C=1CN(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 WHPUOCIHYFGMNF-UHFFFAOYSA-N 0.000 description 1
- VYSSJRDKBQZKTF-UHFFFAOYSA-N n-(1h-indol-5-ylmethyl)-n-methyl-2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethanamine Chemical compound C=1C=C2NC=CC2=CC=1CN(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 VYSSJRDKBQZKTF-UHFFFAOYSA-N 0.000 description 1
- TYQMMKLALSYDTP-UHFFFAOYSA-N n-(1h-indol-6-ylmethyl)-n-methyl-2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethanamine Chemical compound C=1C=C2C=CNC2=CC=1CN(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 TYQMMKLALSYDTP-UHFFFAOYSA-N 0.000 description 1
- GAABETLKGAITEG-UHFFFAOYSA-N n-[1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-(6-fluoro-1h-indol-3-yl)-n-methylacetamide Chemical compound C=1NC2=CC(F)=CC=C2C=1CC(=O)N(C)C(C(C)C)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 GAABETLKGAITEG-UHFFFAOYSA-N 0.000 description 1
- NQMWXUUEHKFPEG-UHFFFAOYSA-N n-[1-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-n-methyl-3-(1-methylindol-3-yl)propanamide Chemical compound C=1N(C)C2=CC=CC=C2C=1CCC(=O)N(C)C(C(C)C)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 NQMWXUUEHKFPEG-UHFFFAOYSA-N 0.000 description 1
- WBRQGMKWLSEVKP-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-3-(1h-indol-3-yl)-n-methylbutanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C)CC(=O)N(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 WBRQGMKWLSEVKP-UHFFFAOYSA-N 0.000 description 1
- UIAJQHBBPBSLKM-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-3-(1h-indol-3-yl)-n-methylpropanamide Chemical compound C1CN(CCN(C)C(=O)CCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 UIAJQHBBPBSLKM-UHFFFAOYSA-N 0.000 description 1
- HQHFLAUGVFKIKN-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n,1-dimethylindole-4-carboxamide Chemical compound C=1C=CC=2N(C)C=CC=2C=1C(=O)N(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 HQHFLAUGVFKIKN-UHFFFAOYSA-N 0.000 description 1
- KDANUGPBSZKUOD-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n-methyl-1h-indole-3-carboxamide Chemical compound C1CN(CCN(C)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 KDANUGPBSZKUOD-UHFFFAOYSA-N 0.000 description 1
- MRMINGKQKGDQDR-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-phenylpiperidin-1-yl]ethyl]-n-methyl-3-(1-methylindol-3-yl)propanamide Chemical compound C=1N(C)C2=CC=CC=C2C=1CCC(=O)N(C)CCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 MRMINGKQKGDQDR-UHFFFAOYSA-N 0.000 description 1
- ZYLBJKIDORMUGU-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-2-(6-fluoro-1h-indol-3-yl)-n-methylacetamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)CC=1C2=CC=C(F)C=C2NC=1)C1=CC=CC=C1 ZYLBJKIDORMUGU-UHFFFAOYSA-N 0.000 description 1
- SMKXKSNHHFGICR-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-3-(1h-indol-3-yl)-n,4-dimethylpentanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)N(C)C(C=1C=CC=CC=1)C(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 SMKXKSNHHFGICR-UHFFFAOYSA-N 0.000 description 1
- VNXITMYPJWWBFD-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-3-(1h-indol-3-yl)-n-methylpropanamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)CCC=1C2=CC=CC=C2NC=1)C1=CC=CC=C1 VNXITMYPJWWBFD-UHFFFAOYSA-N 0.000 description 1
- QJPALPYRPIBZSR-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-n,1-dimethylindole-6-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)C=1C=C2N(C)C=CC2=CC=1)C1=CC=CC=C1 QJPALPYRPIBZSR-UHFFFAOYSA-N 0.000 description 1
- MHJQCCHLMLTKGW-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-n-methyl-1h-indole-6-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)C=1C=C2NC=CC2=CC=1)C1=CC=CC=C1 MHJQCCHLMLTKGW-UHFFFAOYSA-N 0.000 description 1
- RTCUPXGSGWIATH-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxo-1-phenylethyl]-n-methyl-3-(1-methylindol-3-yl)propanamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)C(N(C)C(=O)CCC=1C2=CC=CC=C2N(C)C=1)C1=CC=CC=C1 RTCUPXGSGWIATH-UHFFFAOYSA-N 0.000 description 1
- JOWOSPXBNIZBNA-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxoethyl]-1-methylindole-4-carboxamide Chemical compound C1CN(C(=O)CNC(=O)C=2C=3C=CN(C)C=3C=CC=2)CCC1(N(C)C)C1=CC=CS1 JOWOSPXBNIZBNA-UHFFFAOYSA-N 0.000 description 1
- HHOAUHAHPCQOHF-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxoethyl]-1-methylindole-6-carboxamide Chemical compound C1CN(C(=O)CNC(=O)C=2C=C3N(C)C=CC3=CC=2)CCC1(N(C)C)C1=CC=CS1 HHOAUHAHPCQOHF-UHFFFAOYSA-N 0.000 description 1
- PVYPFTSGPZXUHZ-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-2-oxoethyl]-3-(1h-indol-3-yl)-4-methylpentanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)NCC(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 PVYPFTSGPZXUHZ-UHFFFAOYSA-N 0.000 description 1
- PNVPLLLHSRDFHJ-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethyl]-1-methylindole-4-carboxamide Chemical compound C1CN(CCNC(=O)C=2C=3C=CN(C)C=3C=CC=2)CCC1(N(C)C)C1=CC=CS1 PNVPLLLHSRDFHJ-UHFFFAOYSA-N 0.000 description 1
- QCBPXYNWVMFNKC-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethyl]-1-methylindole-6-carboxamide Chemical compound C1CN(CCNC(=O)C=2C=C3N(C)C=CC3=CC=2)CCC1(N(C)C)C1=CC=CS1 QCBPXYNWVMFNKC-UHFFFAOYSA-N 0.000 description 1
- VZYVXBJALGHHJT-UHFFFAOYSA-N n-[2-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]ethyl]-3-(1h-indol-3-yl)propanamide Chemical compound C1CN(CCNC(=O)CCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CS1 VZYVXBJALGHHJT-UHFFFAOYSA-N 0.000 description 1
- OYIAGNRYBAASMM-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-3-(1h-indol-3-yl)-n-methylbutanamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)CC(C)C1=CNC2=CC=CC=C12 OYIAGNRYBAASMM-UHFFFAOYSA-N 0.000 description 1
- ZPFNIZCIQOZOPI-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-5-fluoro-n-methyl-1h-indole-2-carboxamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)C1=CC2=CC(F)=CC=C2N1 ZPFNIZCIQOZOPI-UHFFFAOYSA-N 0.000 description 1
- WAOFYSGKNIMWQS-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-6-chloro-n-methyl-2,3,4,9-tetrahydro-1h-carbazole-1-carboxamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)C1C(NC=2C3=CC(Cl)=CC=2)=C3CCC1 WAOFYSGKNIMWQS-UHFFFAOYSA-N 0.000 description 1
- KMHITLDUKFOHTP-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-n,1-dimethylindole-4-carboxamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)C1=CC=CC2=C1C=CN2C KMHITLDUKFOHTP-UHFFFAOYSA-N 0.000 description 1
- PTMURHVIDHJPCA-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-n,1-dimethylindole-6-carboxamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)C1=CC=C(C=CN2C)C2=C1 PTMURHVIDHJPCA-UHFFFAOYSA-N 0.000 description 1
- IKXXRUBDVFRXDP-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-n-methyl-1h-indole-3-carboxamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)C1=CNC2=CC=CC=C12 IKXXRUBDVFRXDP-UHFFFAOYSA-N 0.000 description 1
- GLCZPFDEYWMONR-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-n-methyl-1h-indole-6-carboxamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)C1=CC=C(C=CN2)C2=C1 GLCZPFDEYWMONR-UHFFFAOYSA-N 0.000 description 1
- NMSOJWMJTQSVNP-UHFFFAOYSA-N n-[2-[4-butyl-4-(dimethylamino)piperidin-1-yl]ethyl]-n-methyl-3-(1-methylindol-3-yl)propanamide Chemical compound C1CC(CCCC)(N(C)C)CCN1CCN(C)C(=O)CCC1=CN(C)C2=CC=CC=C12 NMSOJWMJTQSVNP-UHFFFAOYSA-N 0.000 description 1
- XTYBSKXSGFCFBZ-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-1-methylindole-4-carboxamide Chemical compound C1CN(C(=O)CCNC(=O)C=2C=3C=CN(C)C=3C=CC=2)CCC1(N(C)C)C1=CC=CC=C1 XTYBSKXSGFCFBZ-UHFFFAOYSA-N 0.000 description 1
- QGICUUQRMXEHTM-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-1-methylindole-6-carboxamide Chemical compound C1CN(C(=O)CCNC(=O)C=2C=C3N(C)C=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 QGICUUQRMXEHTM-UHFFFAOYSA-N 0.000 description 1
- VHJZPFNSWCIEQN-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-1h-indole-6-carboxamide Chemical compound C1CN(C(=O)CCNC(=O)C=2C=C3NC=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 VHJZPFNSWCIEQN-UHFFFAOYSA-N 0.000 description 1
- XVNUCENNRDACMO-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-3-(1-methylindol-3-yl)propanamide Chemical compound C1CN(C(=O)CCNC(=O)CCC=2C3=CC=CC=C3N(C)C=2)CCC1(N(C)C)C1=CC=CC=C1 XVNUCENNRDACMO-UHFFFAOYSA-N 0.000 description 1
- LNGWPRJVFQFWJY-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-3-(1h-indol-3-yl)-4-methylpentanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)NCCC(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 LNGWPRJVFQFWJY-UHFFFAOYSA-N 0.000 description 1
- FRBUQNSPGTVHCG-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-3-(1h-indol-3-yl)butanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C)CC(=O)NCCC(=O)N(CC1)CCC1(N(C)C)C1=CC=CC=C1 FRBUQNSPGTVHCG-UHFFFAOYSA-N 0.000 description 1
- KYPHPSYQIKVNMB-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]-3-oxopropyl]-3-(1h-indol-3-yl)propanamide Chemical compound C1CN(C(=O)CCNC(=O)CCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 KYPHPSYQIKVNMB-UHFFFAOYSA-N 0.000 description 1
- YIWJJFHLJUYFOE-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-3-(1h-indol-3-yl)-n-methylbutanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C)CC(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 YIWJJFHLJUYFOE-UHFFFAOYSA-N 0.000 description 1
- NKRUDLBDHSUMHC-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-3-(1h-indol-3-yl)-n-methylpropanamide Chemical compound C1CN(CCCN(C)C(=O)CCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CC=C1 NKRUDLBDHSUMHC-UHFFFAOYSA-N 0.000 description 1
- AZFWIKXSFCNGKO-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-5-fluoro-n-methyl-1h-indole-2-carboxamide Chemical compound C1CN(CCCN(C)C(=O)C=2NC3=CC=C(F)C=C3C=2)CCC1(N(C)C)C1=CC=CC=C1 AZFWIKXSFCNGKO-UHFFFAOYSA-N 0.000 description 1
- AUNRTQYRVMMBMW-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-n,1-dimethylindole-6-carboxamide Chemical compound C=1C=C2C=CN(C)C2=CC=1C(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 AUNRTQYRVMMBMW-UHFFFAOYSA-N 0.000 description 1
- PZCMWHFSGXZJIQ-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-n-methyl-1h-indole-6-carboxamide Chemical compound C1CN(CCCN(C)C(=O)C=2C=C3NC=CC3=CC=2)CCC1(N(C)C)C1=CC=CC=C1 PZCMWHFSGXZJIQ-UHFFFAOYSA-N 0.000 description 1
- CBYIBZYVMYPRKT-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-phenylpiperidin-1-yl]propyl]-n-methyl-3-(1-methylindol-3-yl)propanamide Chemical compound C=1N(C)C2=CC=CC=C2C=1CCC(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CC=C1 CBYIBZYVMYPRKT-UHFFFAOYSA-N 0.000 description 1
- UUINSZJHKNDHJE-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-1-methylindole-4-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NC(=O)C=1C=2C=CN(C)C=2C=CC=1)C1=CC=CC=C1 UUINSZJHKNDHJE-UHFFFAOYSA-N 0.000 description 1
- NSNDQWKRCDZOGF-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-1-methylindole-6-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NC(=O)C=1C=C2N(C)C=CC2=CC=1)C1=CC=CC=C1 NSNDQWKRCDZOGF-UHFFFAOYSA-N 0.000 description 1
- DRRVWYOGVMYIGT-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-1h-indole-6-carboxamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NC(=O)C=1C=C2NC=CC2=CC=1)C1=CC=CC=C1 DRRVWYOGVMYIGT-UHFFFAOYSA-N 0.000 description 1
- HIPVTTDXDCPWFC-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-2-(6-fluoro-1h-indol-3-yl)acetamide Chemical compound C1CC(N(C)C)(C=2SC=CC=2)CCN1C(=O)CC(NC(=O)CC=1C2=CC=C(F)C=C2NC=1)C1=CC=CC=C1 HIPVTTDXDCPWFC-UHFFFAOYSA-N 0.000 description 1
- KYFSKWCCMKARSR-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-3-(1h-indol-3-yl)-4-methylpentanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)NC(C=1C=CC=CC=1)CC(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 KYFSKWCCMKARSR-UHFFFAOYSA-N 0.000 description 1
- YODOIDVIGVUTEH-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]-3-oxo-1-phenylpropyl]-3-(1h-indol-3-yl)butanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C)CC(=O)NC(C=1C=CC=CC=1)CC(=O)N(CC1)CCC1(N(C)C)C1=CC=CS1 YODOIDVIGVUTEH-UHFFFAOYSA-N 0.000 description 1
- FZMBEKXWDVRUJH-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-3-(1h-indol-3-yl)-n,4-dimethylpentanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C(C)C)CC(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CS1 FZMBEKXWDVRUJH-UHFFFAOYSA-N 0.000 description 1
- CSBJIVRXMQZCCJ-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-3-(1h-indol-3-yl)-n-methylbutanamide Chemical compound C=1NC2=CC=CC=C2C=1C(C)CC(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CS1 CSBJIVRXMQZCCJ-UHFFFAOYSA-N 0.000 description 1
- DMYHYIJJGIAJNA-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-3-(1h-indol-3-yl)-n-methylpropanamide Chemical compound C1CN(CCCN(C)C(=O)CCC=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CS1 DMYHYIJJGIAJNA-UHFFFAOYSA-N 0.000 description 1
- UTQMQAMMIOHWSQ-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-5-fluoro-n-methyl-1h-indole-2-carboxamide Chemical compound C1CN(CCCN(C)C(=O)C=2NC3=CC=C(F)C=C3C=2)CCC1(N(C)C)C1=CC=CS1 UTQMQAMMIOHWSQ-UHFFFAOYSA-N 0.000 description 1
- AAXNKGAAWBMLOD-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-n,1-dimethylindole-4-carboxamide Chemical compound C=1C=CC=2N(C)C=CC=2C=1C(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CS1 AAXNKGAAWBMLOD-UHFFFAOYSA-N 0.000 description 1
- HBEYVGSNZMPYTN-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-n,1-dimethylindole-6-carboxamide Chemical compound C=1C=C2C=CN(C)C2=CC=1C(=O)N(C)CCCN(CC1)CCC1(N(C)C)C1=CC=CS1 HBEYVGSNZMPYTN-UHFFFAOYSA-N 0.000 description 1
- TUJIEIMFVPLVBB-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-n-methyl-1h-indole-3-carboxamide Chemical compound C1CN(CCCN(C)C(=O)C=2C3=CC=CC=C3NC=2)CCC1(N(C)C)C1=CC=CS1 TUJIEIMFVPLVBB-UHFFFAOYSA-N 0.000 description 1
- WNXBAJLYLKOQPR-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-n-methyl-1h-indole-6-carboxamide Chemical compound C1CN(CCCN(C)C(=O)C=2C=C3NC=CC3=CC=2)CCC1(N(C)C)C1=CC=CS1 WNXBAJLYLKOQPR-UHFFFAOYSA-N 0.000 description 1
- GOYYNMOBABTKPZ-UHFFFAOYSA-N n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-n-methyl-3-(1-methylindol-3-yl)propanamide Chemical compound C1CN(CCCN(C)C(=O)CCC=2C3=CC=CC=C3N(C)C=2)CCC1(N(C)C)C1=CC=CS1 GOYYNMOBABTKPZ-UHFFFAOYSA-N 0.000 description 1
- QPYIFXJBMIUTSG-UHFFFAOYSA-N n-methyl-2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethanamine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CCNC)CCC1(C=1C=CC=CC=1)N1CCCC1 QPYIFXJBMIUTSG-UHFFFAOYSA-N 0.000 description 1
- NOWKSZRSMXHPHY-UHFFFAOYSA-N n-methyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]-1h-indole-3-carboxamide Chemical compound C=1NC2=CC=CC=C2C=1C(=O)N(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 NOWKSZRSMXHPHY-UHFFFAOYSA-N 0.000 description 1
- YLLVZWAITXFEII-UHFFFAOYSA-N n-methyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]-1h-indole-6-carboxamide Chemical compound C=1C=C2C=CNC2=CC=1C(=O)N(C)CCN(CC1)CCC1(C=1C=CC=CC=1)N1CCCC1 YLLVZWAITXFEII-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000035778 pathophysiological process Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- SGQDWDWJCYEUNC-UHFFFAOYSA-N piperidin-1-ium-4-ylazanium;dichloride Chemical compound Cl.Cl.NC1CCNCC1 SGQDWDWJCYEUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000002400 pro-nociceptive effect Effects 0.000 description 1
- IXRIKXJQFYIWSW-UHFFFAOYSA-N propan-1-one Chemical compound CC[C+]=O IXRIKXJQFYIWSW-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000010409 stress-induced analgesia Effects 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 1
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 1
- VZBXXQSJOQFMRO-UHFFFAOYSA-N tert-butyl n-[3-[4-(dimethylamino)-4-thiophen-2-ylpiperidin-1-yl]propyl]-n-methylcarbamate Chemical compound C=1C=CSC=1C1(N(C)C)CCN(CCCN(C)C(=O)OC(C)(C)C)CC1 VZBXXQSJOQFMRO-UHFFFAOYSA-N 0.000 description 1
- HLUNSGKOHGMTRR-UHFFFAOYSA-N tert-butyl n-[3-[tert-butyl(dimethyl)silyl]oxypropyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CCCO[Si](C)(C)C(C)(C)C HLUNSGKOHGMTRR-UHFFFAOYSA-N 0.000 description 1
- GBLIHCLLFDOPKL-UHFFFAOYSA-N tert-butyl n-methyl-n-[2-(4-phenyl-4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]carbamate;trihydrochloride Chemical compound Cl.Cl.Cl.C1CN(CCN(C)C(=O)OC(C)(C)C)CCC1(C=1C=CC=CC=1)N1CCCC1 GBLIHCLLFDOPKL-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 108020001588 κ-opioid receptors Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Nutrition Science (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08003238 | 2008-02-22 | ||
| EP08003238.6 | 2008-02-22 | ||
| PCT/EP2009/001232 WO2009103552A1 (en) | 2008-02-22 | 2009-02-20 | Substituted indole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102015683A CN102015683A (zh) | 2011-04-13 |
| CN102015683B true CN102015683B (zh) | 2015-08-05 |
Family
ID=39449548
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200980115064.3A Expired - Fee Related CN102015683B (zh) | 2008-02-22 | 2009-02-20 | 取代的吲哚衍生物 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US20090215828A1 (enExample) |
| EP (1) | EP2254883B1 (enExample) |
| JP (1) | JP5635914B2 (enExample) |
| CN (1) | CN102015683B (enExample) |
| AR (1) | AR070398A1 (enExample) |
| AU (1) | AU2009216920B2 (enExample) |
| CA (1) | CA2716270C (enExample) |
| CL (1) | CL2009000404A1 (enExample) |
| IL (1) | IL207684A (enExample) |
| MX (1) | MX2010009045A (enExample) |
| PE (1) | PE20091490A1 (enExample) |
| RU (1) | RU2500677C2 (enExample) |
| WO (1) | WO2009103552A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR070398A1 (es) | 2008-02-22 | 2010-03-31 | Gruenenthal Chemie | Derivados sustituidos de indol |
| US8580841B2 (en) | 2008-07-23 | 2013-11-12 | Arena Pharmaceuticals, Inc. | Substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid derivatives useful in the treatment of autoimmune and inflammatory disorders |
| CN105816453B (zh) | 2008-08-27 | 2021-03-05 | 艾尼纳制药公司 | 用于治疗自身免疫性病症和炎性病症的作为s1p1受体激动剂的经取代的三环酸衍生物 |
| TW201020247A (en) * | 2008-11-06 | 2010-06-01 | Gruenenthal Gmbh | Substituierte disulfonamide |
| SG182610A1 (en) | 2010-01-27 | 2012-08-30 | Arena Pharm Inc | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| CA2789480A1 (en) | 2010-03-03 | 2011-09-09 | Arena Pharmaceuticals, Inc. | Processes for the preparation of s1p1 receptor modulators and crystalline forms thereof |
| EP2566327B1 (en) | 2010-05-07 | 2017-03-29 | Glaxosmithkline LLC | Indoles |
| KR20140095073A (ko) | 2011-11-04 | 2014-07-31 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 치료 방법 |
| JO3425B1 (ar) | 2013-07-15 | 2019-10-20 | Novartis Ag | مشتقات البابيريدينيل-اندول واستخدامها كعامل متمم لمثبطات b |
| US11007175B2 (en) | 2015-01-06 | 2021-05-18 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| BR112017027656B1 (pt) | 2015-06-22 | 2023-12-05 | Arena Pharmaceuticals, Inc. | Hábito cristalino de placa livre de sal de l-arginina de ácido (r)-2-(7-(4- ciclopentil-3-(trifluorometil)benzilóxi)- 1,2,3,4-tetra-hidrociclo-penta[b]indol-3- il)acético, composição farmacêutica que o compreende, seus usos e método de preparação do mesmo |
| MX2019005679A (es) | 2016-11-18 | 2019-08-14 | Merck Sharp & Dohme | Derivados de indol de utilidad como inhibidores de diacilglicerido o-aciltransferasa 2. |
| CA3053418A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| JP2020507610A (ja) | 2017-02-16 | 2020-03-12 | アリーナ ファーマシューティカルズ， インコーポレイテッド | 腸管外症状を伴う炎症性腸疾患の治療のための化合物および方法 |
| AU2018231120B2 (en) * | 2017-03-10 | 2022-06-23 | Rutgers, The State University Of New Jersey | Indole derivatives as efflux pump inhibitors |
| BR112020024762A2 (pt) | 2018-06-06 | 2021-03-23 | Arena Pharmaceuticals, Inc. | métodos de tratamento de condições relacionadas ao receptor s1p1 |
| CN119751336A (zh) | 2018-09-06 | 2025-04-04 | 艾尼纳制药公司 | 可用于治疗自身免疫性病症和炎性病症的化合物 |
| US20240408064A1 (en) * | 2021-10-15 | 2024-12-12 | Genetolead Inc. | Ras inhibitors, compositions and methods of use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6107329A (en) * | 1995-06-06 | 2000-08-22 | Pfizer, Inc. | Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as glycogen phosphorylase inhibitors |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1586817A (en) * | 1977-12-01 | 1981-03-25 | Wyeth John & Brother Ltd | Indole derivatives |
| DE60026581T2 (de) * | 1999-12-20 | 2006-12-28 | Eli Lilly And Co., Indianapolis | Indolderivate zur behandlung von depression und angstzuständen |
| DE10153346A1 (de) * | 2001-10-29 | 2004-04-22 | Grünenthal GmbH | Substituierte Indole |
| DE10252650A1 (de) | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Cyclohexyl-Harnstoff-Derivate |
| DE10252666A1 (de) | 2002-11-11 | 2004-08-05 | Grünenthal GmbH | N-Piperidyl-cyclohexan-Derivate |
| WO2005047253A1 (en) * | 2003-11-12 | 2005-05-26 | Lg Life Sciences Ltd. | Melanocortin receptor agonists |
| GB0510810D0 (en) * | 2005-05-26 | 2005-06-29 | Novartis Ag | Organic compounds |
| CA2641817A1 (en) * | 2006-02-01 | 2007-08-09 | Solvay Pharmaceuticals Gmbh | Novel dual nk2/nk3-antagonists, pharmaceutical compositions comprising them and processes for their preparation |
| US20070219214A1 (en) * | 2006-02-01 | 2007-09-20 | Solvay Pharmaceuticals Gmbh | Dual NK2/NK3-antagonists, pharmaceutical compositions comprising them, and processes for their preparation |
| CA2682483A1 (en) * | 2007-03-29 | 2008-10-09 | Novartis Ag | 3-imidazolyl-indoles for the treatment of proliferative diseases |
| AR070398A1 (es) | 2008-02-22 | 2010-03-31 | Gruenenthal Chemie | Derivados sustituidos de indol |
-
2009
- 2009-02-16 AR ARP090100544A patent/AR070398A1/es not_active Application Discontinuation
- 2009-02-19 US US12/388,977 patent/US20090215828A1/en not_active Abandoned
- 2009-02-20 WO PCT/EP2009/001232 patent/WO2009103552A1/en not_active Ceased
- 2009-02-20 MX MX2010009045A patent/MX2010009045A/es active IP Right Grant
- 2009-02-20 RU RU2010138838/04A patent/RU2500677C2/ru not_active IP Right Cessation
- 2009-02-20 CN CN200980115064.3A patent/CN102015683B/zh not_active Expired - Fee Related
- 2009-02-20 JP JP2010547116A patent/JP5635914B2/ja not_active Expired - Fee Related
- 2009-02-20 AU AU2009216920A patent/AU2009216920B2/en not_active Ceased
- 2009-02-20 CL CL2009000404A patent/CL2009000404A1/es unknown
- 2009-02-20 EP EP09713555.2A patent/EP2254883B1/en not_active Not-in-force
- 2009-02-20 CA CA2716270A patent/CA2716270C/en not_active Expired - Fee Related
- 2009-02-20 PE PE2009000247A patent/PE20091490A1/es not_active Application Discontinuation
-
2010
- 2010-08-19 IL IL207684A patent/IL207684A/en not_active IP Right Cessation
-
2012
- 2012-12-11 US US13/710,604 patent/US9206156B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6107329A (en) * | 1995-06-06 | 2000-08-22 | Pfizer, Inc. | Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as glycogen phosphorylase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| US20090215828A1 (en) | 2009-08-27 |
| AU2009216920A1 (en) | 2009-08-27 |
| PE20091490A1 (es) | 2009-09-26 |
| JP5635914B2 (ja) | 2014-12-03 |
| HK1149762A1 (en) | 2011-10-14 |
| AR070398A1 (es) | 2010-03-31 |
| EP2254883A1 (en) | 2010-12-01 |
| JP2011512374A (ja) | 2011-04-21 |
| AU2009216920B2 (en) | 2013-06-13 |
| US20130116283A1 (en) | 2013-05-09 |
| CA2716270C (en) | 2016-01-19 |
| EP2254883B1 (en) | 2014-11-26 |
| IL207684A (en) | 2015-08-31 |
| CN102015683A (zh) | 2011-04-13 |
| US9206156B2 (en) | 2015-12-08 |
| RU2010138838A (ru) | 2012-03-27 |
| MX2010009045A (es) | 2010-09-24 |
| CL2009000404A1 (es) | 2010-04-16 |
| CA2716270A1 (en) | 2009-08-27 |
| IL207684A0 (en) | 2010-12-30 |
| RU2500677C2 (ru) | 2013-12-10 |
| WO2009103552A1 (en) | 2009-08-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102015683B (zh) | 取代的吲哚衍生物 | |
| ES2309373T3 (es) | Derivados de 1-aminociclohexano-4-sustituidos utiles como ligandos del receptor orl1 y del receptor mu-opioide. | |
| US6998409B2 (en) | Substituted 2-pyridine cyclohexane-1,4-diamine compounds | |
| JP5366832B2 (ja) | スピロ環式シクロヘキサン誘導体 | |
| CN1972929A (zh) | 治疗偏头痛的杂环类cgrp拮抗剂 | |
| US20050096376A1 (en) | Substituted 3-pyrrolidine-indole derivatives | |
| CN101356174B (zh) | 吲哚-3-基-羰基-螺-哌啶衍生物 | |
| ES2395430T3 (es) | Derivados de ciclohexil-1,4-diamina sustituidos con heteroarilo | |
| US20110009379A1 (en) | Indolinone compound | |
| CA2563017C (en) | Substituted cyclohexylacetic acid derivatives | |
| JP4208139B2 (ja) | 置換された４−アミノシクロヘキサノール | |
| JP5650637B2 (ja) | （ヘテロ−）アリール−シクロヘキサン誘導体 | |
| CA2738749A1 (en) | Melanocortin receptor antagonist compounds, process for preparing them and use thereof in human medicine and cosmetics | |
| JP5492189B2 (ja) | Ｃｃｒ１０アンタゴニストである２−スルホニルアミノ−４−ヘテロアリールブチロアミド | |
| CN101547923A (zh) | 作为via受体拮抗剂的螺环-哌啶衍生物 | |
| CN101273046B (zh) | 作为加压素受体拮抗剂的吲哚-3-基-羰基氮杂螺环衍生物 | |
| HK1149762B (en) | Substituted indole derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150805 Termination date: 20190220 |