PH26585A - N-substituted-arylalkyl and arylalkylene aminoheterocyclics as cardiovascular antihistamic and antisecretory agents - Google Patents
N-substituted-arylalkyl and arylalkylene aminoheterocyclics as cardiovascular antihistamic and antisecretory agents Download PDFInfo
- Publication number
- PH26585A PH26585A PH38517A PH38517A PH26585A PH 26585 A PH26585 A PH 26585A PH 38517 A PH38517 A PH 38517A PH 38517 A PH38517 A PH 38517A PH 26585 A PH26585 A PH 26585A
- Authority
- PH
- Philippines
- Prior art keywords
- bis
- mole
- pharmaceutically acceptable
- acceptable salt
- mixture
- Prior art date
Links
- 230000001387 anti-histamine Effects 0.000 title description 5
- 230000002526 effect on cardiovascular system Effects 0.000 title description 4
- 239000002731 stomach secretion inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 236
- 238000000034 method Methods 0.000 claims description 110
- 150000003839 salts Chemical class 0.000 claims description 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 71
- -1 loweralkyl Chemical class 0.000 claims description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 26
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 150000001412 amines Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 5
- ZDYUUBIMAGBMPY-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O ZDYUUBIMAGBMPY-UHFFFAOYSA-N 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims 4
- 235000008733 Citrus aurantifolia Nutrition 0.000 claims 2
- 235000011941 Tilia x europaea Nutrition 0.000 claims 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 150000002500 ions Chemical class 0.000 claims 2
- 239000004571 lime Substances 0.000 claims 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- UKVQBONVSSLJBB-UHFFFAOYSA-N 2-pyridin-2-ylacetonitrile Chemical compound N#CCC1=CC=CC=N1 UKVQBONVSSLJBB-UHFFFAOYSA-N 0.000 claims 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 206010002383 Angina Pectoris Diseases 0.000 claims 1
- 241000251162 Carcharhinus plumbeus Species 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 108090000362 Lymphotoxin-beta Proteins 0.000 claims 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 1
- 241000009298 Trigla lyra Species 0.000 claims 1
- 102100033744 Troponin C, slow skeletal and cardiac muscles Human genes 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 210000001691 amnion Anatomy 0.000 claims 1
- 230000003257 anti-anginal effect Effects 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 235000010290 biphenyl Nutrition 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- 239000000480 calcium channel blocker Substances 0.000 claims 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 1
- 239000008279 sol Substances 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 367
- 239000007787 solid Substances 0.000 description 319
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 308
- 239000000243 solution Substances 0.000 description 308
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 302
- 239000000203 mixture Substances 0.000 description 284
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 227
- 238000002360 preparation method Methods 0.000 description 216
- 239000003921 oil Substances 0.000 description 202
- 238000004458 analytical method Methods 0.000 description 190
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 186
- 229960001701 chloroform Drugs 0.000 description 154
- 239000002904 solvent Substances 0.000 description 150
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 136
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 122
- 235000011121 sodium hydroxide Nutrition 0.000 description 122
- 229940083608 sodium hydroxide Drugs 0.000 description 118
- 239000010410 layer Substances 0.000 description 117
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 116
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 114
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 104
- 229940073584 methylene chloride Drugs 0.000 description 101
- 238000010992 reflux Methods 0.000 description 100
- 229910001868 water Inorganic materials 0.000 description 91
- 239000000706 filtrate Substances 0.000 description 78
- 239000011541 reaction mixture Substances 0.000 description 77
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 72
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 67
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 62
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 59
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 59
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 58
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- 229910000027 potassium carbonate Inorganic materials 0.000 description 57
- 229940093956 potassium carbonate Drugs 0.000 description 57
- 238000001914 filtration Methods 0.000 description 55
- 239000012458 free base Substances 0.000 description 55
- 235000011181 potassium carbonates Nutrition 0.000 description 54
- 239000000047 product Substances 0.000 description 51
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 47
- 229960004592 isopropanol Drugs 0.000 description 47
- 239000003208 petroleum Substances 0.000 description 47
- 229960003010 sodium sulfate Drugs 0.000 description 47
- 229910052938 sodium sulfate Inorganic materials 0.000 description 47
- 235000011152 sodium sulphate Nutrition 0.000 description 47
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 42
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 41
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 41
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 41
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 37
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 37
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 36
- 239000000523 sample Substances 0.000 description 34
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 31
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 29
- 229960003390 magnesium sulfate Drugs 0.000 description 29
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 29
- 235000019341 magnesium sulphate Nutrition 0.000 description 29
- 238000007792 addition Methods 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 27
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 26
- 229960000583 acetic acid Drugs 0.000 description 26
- 229940076134 benzene Drugs 0.000 description 24
- 150000003891 oxalate salts Chemical class 0.000 description 22
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 20
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 20
- 239000000538 analytical sample Substances 0.000 description 19
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 19
- 238000010828 elution Methods 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 229960005419 nitrogen Drugs 0.000 description 19
- 239000007864 aqueous solution Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 18
- 229960004132 diethyl ether Drugs 0.000 description 18
- 239000012362 glacial acetic acid Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 17
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 239000003054 catalyst Substances 0.000 description 17
- 235000019441 ethanol Nutrition 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 229960001040 ammonium chloride Drugs 0.000 description 16
- 235000019270 ammonium chloride Nutrition 0.000 description 16
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 14
- DFYRUELUNQRZTB-UHFFFAOYSA-N apocynin Chemical compound COC1=CC(C(C)=O)=CC=C1O DFYRUELUNQRZTB-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 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 12
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 11
- 238000000354 decomposition reaction Methods 0.000 description 11
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 11
- 238000001819 mass spectrum Methods 0.000 description 11
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 235000001055 magnesium Nutrition 0.000 description 10
- 239000011777 magnesium Substances 0.000 description 10
- 229910052749 magnesium Inorganic materials 0.000 description 10
- 229940091250 magnesium supplement Drugs 0.000 description 10
- 235000006408 oxalic acid Nutrition 0.000 description 10
- 235000007715 potassium iodide Nutrition 0.000 description 10
- 229960004839 potassium iodide Drugs 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- 239000011630 iodine Substances 0.000 description 9
- PPMOYCFSAWURHS-UHFFFAOYSA-N lithium;n-propylpropan-1-amine Chemical compound [Li].CCCNCCC PPMOYCFSAWURHS-UHFFFAOYSA-N 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000002002 slurry Substances 0.000 description 9
- 159000000000 sodium salts Chemical class 0.000 description 9
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 8
- NLQOKCKCAKNXFS-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methyl]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)C1CCNCC1 NLQOKCKCAKNXFS-UHFFFAOYSA-N 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- 239000002808 molecular sieve Substances 0.000 description 8
- 239000008188 pellet Substances 0.000 description 8
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 8
- NIDWUZTTXGJFNN-UHFFFAOYSA-N 3-bromopropoxybenzene Chemical compound BrCCCOC1=CC=CC=C1 NIDWUZTTXGJFNN-UHFFFAOYSA-N 0.000 description 7
- 239000007818 Grignard reagent Substances 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 150000004795 grignard reagents Chemical class 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
- 235000017550 sodium carbonate Nutrition 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 229940001593 sodium carbonate Drugs 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- JCGSSOIJYPBNJE-UHFFFAOYSA-N 1-[4-(4-fluorobenzoyl)piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C(=O)C1=CC=C(F)C=C1 JCGSSOIJYPBNJE-UHFFFAOYSA-N 0.000 description 6
- PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 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 6
- 238000001704 evaporation Methods 0.000 description 6
- 239000001530 fumaric acid Substances 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000001294 propane Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000000043 antiallergic agent Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 5
- 238000005755 formation reaction Methods 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000012258 stirred mixture Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- XPHIPEXPAGCEBM-UHFFFAOYSA-N 1-(4-Hydroxy-2-methoxyphenyl)ethanone Chemical compound COC1=CC(O)=CC=C1C(C)=O XPHIPEXPAGCEBM-UHFFFAOYSA-N 0.000 description 4
- IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 4
- NEBPTMCRLHKPOB-UHFFFAOYSA-N 2,2-diphenylacetonitrile Chemical compound C=1C=CC=CC=1C(C#N)C1=CC=CC=C1 NEBPTMCRLHKPOB-UHFFFAOYSA-N 0.000 description 4
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 4
- CHWNEIVBYREQRF-UHFFFAOYSA-N 4-Ethyl-2-methoxyphenol Chemical compound CCC1=CC=C(O)C(OC)=C1 CHWNEIVBYREQRF-UHFFFAOYSA-N 0.000 description 4
- YMQPKONILWWJQG-UHFFFAOYSA-N 4-bromo-1,2-difluorobenzene Chemical compound FC1=CC=C(Br)C=C1F YMQPKONILWWJQG-UHFFFAOYSA-N 0.000 description 4
- 125000006418 4-methylphenylsulfonyl group Chemical group 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- FIMJSWFMQJGVAM-UHFFFAOYSA-N chloroform;hydrate Chemical compound O.ClC(Cl)Cl FIMJSWFMQJGVAM-UHFFFAOYSA-N 0.000 description 4
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 4
- YQTIWLBULZHLIE-UHFFFAOYSA-N ethyl 1-(benzenesulfonyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1S(=O)(=O)C1=CC=CC=C1 YQTIWLBULZHLIE-UHFFFAOYSA-N 0.000 description 4
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 4
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 4
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 235000014786 phosphorus Nutrition 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- UKIFGNQFSBXGCF-UHFFFAOYSA-N 1-(3-chloropropoxy)-2-methoxybenzene Chemical compound COC1=CC=CC=C1OCCCCl UKIFGNQFSBXGCF-UHFFFAOYSA-N 0.000 description 3
- HYOAGWAIGJXNQH-UHFFFAOYSA-N 1-bromo-1-chloropropane Chemical compound CCC(Cl)Br HYOAGWAIGJXNQH-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- JHQBLYITVCBGTO-UHFFFAOYSA-N 2-(4-fluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C=C1 JHQBLYITVCBGTO-UHFFFAOYSA-N 0.000 description 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 3
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 3
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 3
- XPYQFIISZQCINN-QVXDJYSKSA-N 4-amino-1-[(2r,3e,4s,5r)-3-(fluoromethylidene)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;hydrate Chemical compound O.O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 XPYQFIISZQCINN-QVXDJYSKSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 101150065749 Churc1 gene Proteins 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 102100038239 Protein Churchill Human genes 0.000 description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 229940043379 ammonium hydroxide Drugs 0.000 description 3
- 239000003416 antiarrhythmic agent Substances 0.000 description 3
- DULCUDSUACXJJC-UHFFFAOYSA-N benzeneacetic acid ethyl ester Natural products CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical class ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 3
- ASQCOPJFYLJCGD-UHFFFAOYSA-N ethyl 1-benzylpiperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1CC1=CC=CC=C1 ASQCOPJFYLJCGD-UHFFFAOYSA-N 0.000 description 3
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 150000002688 maleic acid derivatives Chemical class 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- WTRWBYGUMQEFFI-UHFFFAOYSA-N (4-fluorophenyl)(pyridin-4-yl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=NC=C1 WTRWBYGUMQEFFI-UHFFFAOYSA-N 0.000 description 2
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 2
- GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical compound FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 description 2
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 2
- OSPSTFKEHOVIGO-UHFFFAOYSA-N 1-(3-chloropropoxy)-3,5-dimethoxybenzene Chemical compound COC1=CC(OC)=CC(OCCCCl)=C1 OSPSTFKEHOVIGO-UHFFFAOYSA-N 0.000 description 2
- QPLCIAKHZWUUDN-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(OCCCCl)C=C1 QPLCIAKHZWUUDN-UHFFFAOYSA-N 0.000 description 2
- VYKQDWPBYULGPF-UHFFFAOYSA-N 1-benzyl-5-oxopyrrolidine-3-carboxylic acid Chemical compound O=C1CC(C(=O)O)CN1CC1=CC=CC=C1 VYKQDWPBYULGPF-UHFFFAOYSA-N 0.000 description 2
- BPPZXJZYCOETDA-UHFFFAOYSA-N 1-benzylpiperidin-4-ol Chemical compound C1CC(O)CCN1CC1=CC=CC=C1 BPPZXJZYCOETDA-UHFFFAOYSA-N 0.000 description 2
- QDFKKJYEIFBEFC-UHFFFAOYSA-N 1-bromo-3-fluorobenzene Chemical compound FC1=CC=CC(Br)=C1 QDFKKJYEIFBEFC-UHFFFAOYSA-N 0.000 description 2
- NHDODQWIKUYWMW-UHFFFAOYSA-N 1-bromo-4-chlorobenzene Chemical group ClC1=CC=C(Br)C=C1 NHDODQWIKUYWMW-UHFFFAOYSA-N 0.000 description 2
- NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 2
- HRGKYGQCSVUDHA-UHFFFAOYSA-N 1-chloro-4-(3-chloropropoxy)benzene Chemical compound ClCCCOC1=CC=C(Cl)C=C1 HRGKYGQCSVUDHA-UHFFFAOYSA-N 0.000 description 2
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical compound COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 2
- XGOIFLYQJYTUNB-UHFFFAOYSA-N 2-(3-chloropropoxy)-1,3-dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OCCCCl XGOIFLYQJYTUNB-UHFFFAOYSA-N 0.000 description 2
- PETRWTHZSKVLRE-UHFFFAOYSA-N 2-Methoxy-4-methylphenol Chemical compound COC1=CC(C)=CC=C1O PETRWTHZSKVLRE-UHFFFAOYSA-N 0.000 description 2
- JECYUBVRTQDVAT-UHFFFAOYSA-N 2-acetylphenol Chemical compound CC(=O)C1=CC=CC=C1O JECYUBVRTQDVAT-UHFFFAOYSA-N 0.000 description 2
- CLVBVRODHJFTGF-UHFFFAOYSA-N 2-piperidin-1-ylacetonitrile Chemical compound N#CCN1CCCCC1 CLVBVRODHJFTGF-UHFFFAOYSA-N 0.000 description 2
- XQDNFAMOIPNVES-UHFFFAOYSA-N 3,5-Dimethoxyphenol Chemical compound COC1=CC(O)=CC(OC)=C1 XQDNFAMOIPNVES-UHFFFAOYSA-N 0.000 description 2
- RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 2
- JSHLOPGSDZTEGQ-UHFFFAOYSA-N 3-methoxy-4-phenylmethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OCC1=CC=CC=C1 JSHLOPGSDZTEGQ-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- WWYJRCLKNLGHFQ-UHFFFAOYSA-N 3-quinolin-8-yloxypropan-1-ol Chemical compound C1=CN=C2C(OCCCO)=CC=CC2=C1 WWYJRCLKNLGHFQ-UHFFFAOYSA-N 0.000 description 2
- KUXAWJPYUAJTCG-UHFFFAOYSA-N 4-(3-chloropropoxy)-1,2-dimethoxybenzene Chemical compound COC1=CC=C(OCCCCl)C=C1OC KUXAWJPYUAJTCG-UHFFFAOYSA-N 0.000 description 2
- VTHHRADLOLKTLD-UHFFFAOYSA-N 4-(benzyloxy)-5-methoxy-2-nitrobenzoic acid Chemical compound COC1=CC(C(O)=O)=C([N+]([O-])=O)C=C1OCC1=CC=CC=C1 VTHHRADLOLKTLD-UHFFFAOYSA-N 0.000 description 2
- NPFYZDNDJHZQKY-UHFFFAOYSA-N 4-Hydroxybenzophenone Chemical compound C1=CC(O)=CC=C1C(=O)C1=CC=CC=C1 NPFYZDNDJHZQKY-UHFFFAOYSA-N 0.000 description 2
- BGVXYTPSJORVTK-UHFFFAOYSA-N 4-[bis(4-methoxyphenyl)methyl]pyridine Chemical compound C1=CC(OC)=CC=C1C(C=1C=CC(OC)=CC=1)C1=CC=NC=C1 BGVXYTPSJORVTK-UHFFFAOYSA-N 0.000 description 2
- VWCHQFWZBHRNGG-UHFFFAOYSA-N 4-[bis(4-methylphenyl)methyl]piperidine Chemical compound C1=CC(C)=CC=C1C(C=1C=CC(C)=CC=1)C1CCNCC1 VWCHQFWZBHRNGG-UHFFFAOYSA-N 0.000 description 2
- UNPKOFGAQOEDMF-UHFFFAOYSA-N 4-benzhydrylidenepiperidine Chemical compound C1CNCCC1=C(C=1C=CC=CC=1)C1=CC=CC=C1 UNPKOFGAQOEDMF-UHFFFAOYSA-N 0.000 description 2
- LUYLEMZRJQTGPM-UHFFFAOYSA-N 4-benzhydrylpiperidine Chemical compound C1CNCCC1C(C=1C=CC=CC=1)C1=CC=CC=C1 LUYLEMZRJQTGPM-UHFFFAOYSA-N 0.000 description 2
- ZWLWOTHDIGRTNE-UHFFFAOYSA-N 4-benzhydrylpyridine Chemical compound C1=CC=CC=C1C(C=1C=CN=CC=1)C1=CC=CC=C1 ZWLWOTHDIGRTNE-UHFFFAOYSA-N 0.000 description 2
- HXDOZKJGKXYMEW-UHFFFAOYSA-N 4-ethylphenol Chemical compound CCC1=CC=C(O)C=C1 HXDOZKJGKXYMEW-UHFFFAOYSA-N 0.000 description 2
- QXSAKPUBHTZHKW-UHFFFAOYSA-N 4-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C=C1 QXSAKPUBHTZHKW-UHFFFAOYSA-N 0.000 description 2
- YQUQWHNMBPIWGK-UHFFFAOYSA-N 4-isopropylphenol Chemical compound CC(C)C1=CC=C(O)C=C1 YQUQWHNMBPIWGK-UHFFFAOYSA-N 0.000 description 2
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
- WKDLWHKMVQVRNO-UHFFFAOYSA-N 5-methoxy-2-nitro-4-phenylmethoxybenzaldehyde Chemical compound COC1=CC(C=O)=C([N+]([O-])=O)C=C1OCC1=CC=CC=C1 WKDLWHKMVQVRNO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 229910014033 C-OH Inorganic materials 0.000 description 2
- 229910014570 C—OH Inorganic materials 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- WMJMABVHDMRMJA-UHFFFAOYSA-M [Cl-].[Mg+]C1CCCCC1 Chemical compound [Cl-].[Mg+]C1CCCCC1 WMJMABVHDMRMJA-UHFFFAOYSA-M 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 230000002730 additional effect Effects 0.000 description 2
- 229910001413 alkali metal ion Inorganic materials 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 230000002301 combined effect Effects 0.000 description 2
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
- UPPBZOFWXKFRHI-UHFFFAOYSA-N dichloromethane;hexane;methanol Chemical compound OC.ClCCl.CCCCCC UPPBZOFWXKFRHI-UHFFFAOYSA-N 0.000 description 2
- ZWWQRMFIZFPUAA-UHFFFAOYSA-N dimethyl 2-methylidenebutanedioate Chemical compound COC(=O)CC(=C)C(=O)OC ZWWQRMFIZFPUAA-UHFFFAOYSA-N 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 2
- YYBPPCVVKIVDKJ-UHFFFAOYSA-N ethyl 1-(diethylcarbamoyl)piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(C(=O)N(CC)CC)CC1 YYBPPCVVKIVDKJ-UHFFFAOYSA-N 0.000 description 2
- BPSWFJWNZKIQFS-UHFFFAOYSA-N ethyl 1-benzylpiperidine-4-carboxylate;hydrochloride Chemical compound Cl.C1CC(C(=O)OCC)CCN1CC1=CC=CC=C1 BPSWFJWNZKIQFS-UHFFFAOYSA-N 0.000 description 2
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 2
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 2
- MCRPKBUFXAKDKI-UHFFFAOYSA-N ethyl pyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC=C1 MCRPKBUFXAKDKI-UHFFFAOYSA-N 0.000 description 2
- 229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 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 2
- 229960001340 histamine Drugs 0.000 description 2
- 239000002198 insoluble material Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- DGEYTDCFMQMLTH-UHFFFAOYSA-N methanol;propan-2-ol Chemical compound OC.CC(C)O DGEYTDCFMQMLTH-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- WTRWSSDZHQOPJI-UHFFFAOYSA-N methyl 1-benzyl-5-oxopyrrolidine-3-carboxylate Chemical compound O=C1CC(C(=O)OC)CN1CC1=CC=CC=C1 WTRWSSDZHQOPJI-UHFFFAOYSA-N 0.000 description 2
- OMNGJGSAPWWSHP-UHFFFAOYSA-N methyl 4-(3-chloropropoxy)benzoate Chemical compound COC(=O)C1=CC=C(OCCCCl)C=C1 OMNGJGSAPWWSHP-UHFFFAOYSA-N 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- BVWTXUYLKBHMOX-UHFFFAOYSA-N methyl vanillate Chemical compound COC(=O)C1=CC=C(O)C(OC)=C1 BVWTXUYLKBHMOX-UHFFFAOYSA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- WLCAJVVSNAVBSM-UHFFFAOYSA-N oxalic acid;piperidine Chemical compound C1CCNCC1.OC(=O)C(O)=O WLCAJVVSNAVBSM-UHFFFAOYSA-N 0.000 description 2
- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229960003424 phenylacetic acid Drugs 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 235000007686 potassium Nutrition 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 229940001474 sodium thiosulfate Drugs 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000003204 tranquilizing agent Substances 0.000 description 2
- 230000002936 tranquilizing effect Effects 0.000 description 2
- 238000009966 trimming Methods 0.000 description 2
- 238000005292 vacuum distillation Methods 0.000 description 2
- DGTVXGKAUIVOSL-UHFFFAOYSA-N (1-benzylpyrrolidin-3-yl)methanol;oxalic acid Chemical compound OC(=O)C(O)=O.C1C(CO)CCN1CC1=CC=CC=C1 DGTVXGKAUIVOSL-UHFFFAOYSA-N 0.000 description 1
- XOKVLWYBGMRAFA-UHFFFAOYSA-N (1-benzylpyrrolidin-3-yl)methyl methanesulfonate Chemical compound C1C(COS(=O)(=O)C)CCN1CC1=CC=CC=C1 XOKVLWYBGMRAFA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FBRNQFWVQHDFMW-UHFFFAOYSA-N (3,4-difluorophenyl)-pyridin-4-ylmethanone;hydrochloride Chemical compound Cl.C1=C(F)C(F)=CC=C1C(=O)C1=CC=NC=C1 FBRNQFWVQHDFMW-UHFFFAOYSA-N 0.000 description 1
- IPRCBIWIPMJXIK-UHFFFAOYSA-N (3-hydroxyphenyl)urea Chemical compound NC(=O)NC1=CC=CC(O)=C1 IPRCBIWIPMJXIK-UHFFFAOYSA-N 0.000 description 1
- NJIPZEXQNSMBMF-WLHGVMLRSA-N (e)-but-2-enedioic acid;4-[(4-fluorophenyl)-phenylmethyl]-1-(3-phenoxypropyl)piperidine Chemical compound OC(=O)\C=C\C(O)=O.C1=CC(F)=CC=C1C(C=1C=CC=CC=1)C1CCN(CCCOC=2C=CC=CC=2)CC1 NJIPZEXQNSMBMF-WLHGVMLRSA-N 0.000 description 1
- CCODOIDFURPJTR-WLHGVMLRSA-N (e)-but-2-enedioic acid;piperidine Chemical compound C1CCNCC1.OC(=O)\C=C\C(O)=O CCODOIDFURPJTR-WLHGVMLRSA-N 0.000 description 1
- SIGJLLRAYLHKKX-BTJKTKAUSA-N (z)-but-2-enedioic acid;4-methylbenzenesulfonic acid Chemical compound OC(=O)\C=C/C(O)=O.CC1=CC=C(S(O)(=O)=O)C=C1 SIGJLLRAYLHKKX-BTJKTKAUSA-N 0.000 description 1
- ALEBBAGSTXZLSK-UHFFFAOYSA-N 1,1-bis(2,5-difluorophenyl)-1-piperidin-4-ylbutan-2-one Chemical compound FC1=C(C=C(C=C1)F)C(C(CC)=O)(C1CCNCC1)C1=C(C=CC(=C1)F)F ALEBBAGSTXZLSK-UHFFFAOYSA-N 0.000 description 1
- KGRAGSWZZDKVBN-UHFFFAOYSA-N 1,1-bis(3,4-difluorophenyl)-1-piperidin-4-ylbutan-2-one Chemical compound FC=1C=C(C=CC=1F)C(C(CC)=O)(C1CCNCC1)C1=CC(=C(C=C1)F)F KGRAGSWZZDKVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- GHYCDQZHLJYSRX-UHFFFAOYSA-N 1,2-dimethoxyethane;ethyl acetate Chemical compound CCOC(C)=O.COCCOC GHYCDQZHLJYSRX-UHFFFAOYSA-N 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- QUGUFLJIAFISSW-UHFFFAOYSA-N 1,4-difluorobenzene Chemical compound FC1=CC=C(F)C=C1 QUGUFLJIAFISSW-UHFFFAOYSA-N 0.000 description 1
- FVPJPTJNQRLTJO-UHFFFAOYSA-N 1-(2-chloroethylsulfanyl)-4-fluorobenzene Chemical compound FC1=CC=C(SCCCl)C=C1 FVPJPTJNQRLTJO-UHFFFAOYSA-N 0.000 description 1
- GJXJBHLRTGDBOI-UHFFFAOYSA-N 1-(3-chloropropoxy)-2-ethoxybenzene Chemical compound CCOC1=CC=CC=C1OCCCCl GJXJBHLRTGDBOI-UHFFFAOYSA-N 0.000 description 1
- KNJPVCXGHKZYQE-UHFFFAOYSA-N 1-(3-chloropropoxy)-2-fluorobenzene Chemical compound FC1=CC=CC=C1OCCCCl KNJPVCXGHKZYQE-UHFFFAOYSA-N 0.000 description 1
- DEINSMQOQVXPJA-UHFFFAOYSA-N 1-(3-chloropropoxy)-2-methylbenzene Chemical compound CC1=CC=CC=C1OCCCCl DEINSMQOQVXPJA-UHFFFAOYSA-N 0.000 description 1
- XHXFQOVACQQRFI-UHFFFAOYSA-N 1-(3-chloropropoxy)-2-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC=C1OCCCCl XHXFQOVACQQRFI-UHFFFAOYSA-N 0.000 description 1
- CWHZJPRKVRSFCB-UHFFFAOYSA-N 1-(3-chloropropoxy)-3-fluorobenzene Chemical compound FC1=CC=CC(OCCCCl)=C1 CWHZJPRKVRSFCB-UHFFFAOYSA-N 0.000 description 1
- YHHSOJRBOXOGFK-UHFFFAOYSA-N 1-(3-chloropropoxy)-3-methylbenzene Chemical compound CC1=CC=CC(OCCCCl)=C1 YHHSOJRBOXOGFK-UHFFFAOYSA-N 0.000 description 1
- CFQZGYMLOMAPNV-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-ethyl-2-methoxybenzene Chemical compound CCC1=CC=C(OCCCCl)C(OC)=C1 CFQZGYMLOMAPNV-UHFFFAOYSA-N 0.000 description 1
- QCCAWPZLGOVCGH-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-ethylbenzene Chemical compound CCC1=CC=C(OCCCCl)C=C1 QCCAWPZLGOVCGH-UHFFFAOYSA-N 0.000 description 1
- DFFWYMMOMUTKOI-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-fluorobenzene Chemical compound FC1=CC=C(OCCCCl)C=C1 DFFWYMMOMUTKOI-UHFFFAOYSA-N 0.000 description 1
- SJZQJMFKQYZZAT-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-methoxybenzene Chemical compound COC1=CC=C(OCCCCl)C=C1 SJZQJMFKQYZZAT-UHFFFAOYSA-N 0.000 description 1
- KDVHPBONMFVFOL-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-methylsulfinylbenzene Chemical compound CS(=O)C1=CC=C(OCCCCl)C=C1 KDVHPBONMFVFOL-UHFFFAOYSA-N 0.000 description 1
- OEMRUVLRZCJYGC-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-methylsulfonylbenzene Chemical compound CS(=O)(=O)C1=CC=C(OCCCCl)C=C1 OEMRUVLRZCJYGC-UHFFFAOYSA-N 0.000 description 1
- IJKNDFJBFPOWSN-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(OCCCCl)C=C1 IJKNDFJBFPOWSN-UHFFFAOYSA-N 0.000 description 1
- UJKYNPWXURITTO-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-phenylbenzene Chemical group C1=CC(OCCCCl)=CC=C1C1=CC=CC=C1 UJKYNPWXURITTO-UHFFFAOYSA-N 0.000 description 1
- HVWIEPYYDGYOFP-UHFFFAOYSA-N 1-(3-chloropropoxy)-4-propan-2-ylbenzene Chemical compound CC(C)C1=CC=C(OCCCCl)C=C1 HVWIEPYYDGYOFP-UHFFFAOYSA-N 0.000 description 1
- ZKKQYFTYSOWOLI-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-[bis(4-fluorophenyl)methyl]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)C1CCN(S(=O)(=O)C=2C=CC=CC=2)CC1 ZKKQYFTYSOWOLI-UHFFFAOYSA-N 0.000 description 1
- YLQRYKULRJTYID-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-[bis(4-fluorophenyl)methylidene]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=C1CCN(S(=O)(=O)C=2C=CC=CC=2)CC1 YLQRYKULRJTYID-UHFFFAOYSA-N 0.000 description 1
- ROBBWMKVNMSDPF-UHFFFAOYSA-N 1-(benzenesulfonyl)piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1S(=O)(=O)C1=CC=CC=C1 ROBBWMKVNMSDPF-UHFFFAOYSA-N 0.000 description 1
- LHASLBSEALHFGO-ASZAQJJISA-N 1-[(4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]pyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO)OC1N1C(=O)NC(=O)C(CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1 LHASLBSEALHFGO-ASZAQJJISA-N 0.000 description 1
- DMYOHQBLOZMDLP-UHFFFAOYSA-N 1-[2-(2-hydroxy-3-piperidin-1-ylpropoxy)phenyl]-3-phenylpropan-1-one Chemical compound C1CCCCN1CC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 DMYOHQBLOZMDLP-UHFFFAOYSA-N 0.000 description 1
- RBBVSSYQKVBALO-UHFFFAOYSA-N 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCCl RBBVSSYQKVBALO-UHFFFAOYSA-N 0.000 description 1
- NXFHJDHZSSTJOV-UHFFFAOYSA-N 1-[4-(3-chloropropoxy)-3-methylphenyl]ethanone Chemical compound CC(=O)C1=CC=C(OCCCCl)C(C)=C1 NXFHJDHZSSTJOV-UHFFFAOYSA-N 0.000 description 1
- YCPYAWUAUZTIGI-UHFFFAOYSA-N 1-[4-(3-chloropropoxy)phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(OCCCCl)C=C1 YCPYAWUAUZTIGI-UHFFFAOYSA-N 0.000 description 1
- OHCPVLJEAHBMEG-UHFFFAOYSA-N 1-acetylpiperidine-4-carbonyl chloride Chemical compound CC(=O)N1CCC(C(Cl)=O)CC1 OHCPVLJEAHBMEG-UHFFFAOYSA-N 0.000 description 1
- WPIVQLSTWPOFJR-UHFFFAOYSA-N 1-benzyl-4-[bis(4-fluorophenyl)methylidene]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=C1CCN(CC=2C=CC=CC=2)CC1 WPIVQLSTWPOFJR-UHFFFAOYSA-N 0.000 description 1
- YQMXOIAIYXXXEE-UHFFFAOYSA-N 1-benzylpyrrolidin-3-ol Chemical compound C1C(O)CCN1CC1=CC=CC=C1 YQMXOIAIYXXXEE-UHFFFAOYSA-N 0.000 description 1
- MGHBDQZXPCTTIH-UHFFFAOYSA-N 1-bromo-2,4-difluorobenzene Chemical compound FC1=CC=C(Br)C(F)=C1 MGHBDQZXPCTTIH-UHFFFAOYSA-N 0.000 description 1
- NNMBNYHMJRJUBC-UHFFFAOYSA-N 1-bromo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(Br)=C1 NNMBNYHMJRJUBC-UHFFFAOYSA-N 0.000 description 1
- XLQSXGGDTHANLN-UHFFFAOYSA-N 1-bromo-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Br)C=C1 XLQSXGGDTHANLN-UHFFFAOYSA-N 0.000 description 1
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 1
- ICZVUVBVBHEQDS-UHFFFAOYSA-N 1-bromo-5-chlorocyclohexa-2,4-dien-1-ol Chemical compound OC1(Br)CC(Cl)=CC=C1 ICZVUVBVBHEQDS-UHFFFAOYSA-N 0.000 description 1
- PHHNNDKXQVKJEP-UHFFFAOYSA-N 1-bromo-5-chloropentane Chemical compound ClCCCCCBr PHHNNDKXQVKJEP-UHFFFAOYSA-N 0.000 description 1
- JTYUIAOHIYZBPB-UHFFFAOYSA-N 1-bromo-6-chlorohexane Chemical compound ClCCCCCCBr JTYUIAOHIYZBPB-UHFFFAOYSA-N 0.000 description 1
- JIEJJGMNDWIGBJ-UHFFFAOYSA-N 1-propan-2-yloxypropane Chemical compound CCCOC(C)C JIEJJGMNDWIGBJ-UHFFFAOYSA-N 0.000 description 1
- HEJLFBLJYFSKCE-UHFFFAOYSA-N 2',3'-Dihydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1O HEJLFBLJYFSKCE-UHFFFAOYSA-N 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- AGAOESUOSOGZOD-UHFFFAOYSA-N 2-(2,4-difluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C(F)=C1 AGAOESUOSOGZOD-UHFFFAOYSA-N 0.000 description 1
- UIMMFRUOZOWROM-UHFFFAOYSA-N 2-(2,5-difluorophenyl)acetonitrile Chemical compound FC1=CC=C(F)C(CC#N)=C1 UIMMFRUOZOWROM-UHFFFAOYSA-N 0.000 description 1
- RQGVZXGJKYJQSN-UHFFFAOYSA-N 2-(2-bromoethoxy)-1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1OCCBr RQGVZXGJKYJQSN-UHFFFAOYSA-N 0.000 description 1
- GNPYERUNJMDEFQ-UHFFFAOYSA-N 2-(3,4-difluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C=C1F GNPYERUNJMDEFQ-UHFFFAOYSA-N 0.000 description 1
- RBIBFYCKNFQEQI-UHFFFAOYSA-N 2-(3-chloropropoxy)benzonitrile Chemical compound ClCCCOC1=CC=CC=C1C#N RBIBFYCKNFQEQI-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- JOIYKSLWXLFGGR-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetonitrile Chemical compound FC(F)(F)C1=CC=CC(CC#N)=C1 JOIYKSLWXLFGGR-UHFFFAOYSA-N 0.000 description 1
- QNKOCFJZJWOXDE-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]acetonitrile Chemical compound FC(F)(F)C1=CC=C(CC#N)C=C1 QNKOCFJZJWOXDE-UHFFFAOYSA-N 0.000 description 1
- JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 1
- OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 description 1
- XCRCSPKQEDMVBO-UHFFFAOYSA-N 2-bromo-1,4-difluorobenzene Chemical compound FC1=CC=C(F)C(Br)=C1 XCRCSPKQEDMVBO-UHFFFAOYSA-N 0.000 description 1
- JJFOBACUIRKUPN-UHFFFAOYSA-N 2-bromoethoxybenzene Chemical compound BrCCOC1=CC=CC=C1 JJFOBACUIRKUPN-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- QDXIHHOPZFCEAP-UHFFFAOYSA-N 2-chloroethylsulfanylbenzene Chemical compound ClCCSC1=CC=CC=C1 QDXIHHOPZFCEAP-UHFFFAOYSA-N 0.000 description 1
- MOEFFSWKSMRFRQ-UHFFFAOYSA-N 2-ethoxyphenol Chemical compound CCOC1=CC=CC=C1O MOEFFSWKSMRFRQ-UHFFFAOYSA-N 0.000 description 1
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 1
- ZNCUUYCDKVNVJH-UHFFFAOYSA-N 2-isopropoxyphenol Chemical compound CC(C)OC1=CC=CC=C1O ZNCUUYCDKVNVJH-UHFFFAOYSA-N 0.000 description 1
- CLASDMKBOIFHNY-UHFFFAOYSA-N 2-methylidenepiperidine Chemical compound C=C1CCCCN1 CLASDMKBOIFHNY-UHFFFAOYSA-N 0.000 description 1
- CCZCXFHJMKINPE-UHFFFAOYSA-N 2-phenylmethoxyphenol Chemical compound OC1=CC=CC=C1OCC1=CC=CC=C1 CCZCXFHJMKINPE-UHFFFAOYSA-N 0.000 description 1
- ZVTFIBQPABQXLK-UHFFFAOYSA-N 2-piperidin-4-ylacetonitrile Chemical compound N#CCC1CCNCC1 ZVTFIBQPABQXLK-UHFFFAOYSA-N 0.000 description 1
- BXGYBSJAZFGIPX-UHFFFAOYSA-N 2-pyridin-2-ylethanol Chemical compound OCCC1=CC=CC=N1 BXGYBSJAZFGIPX-UHFFFAOYSA-N 0.000 description 1
- DZGNWHFOKDKUHL-UHFFFAOYSA-N 2-sulfonylpiperidine-4-carboxylic acid Chemical compound OC(=O)C1CCNC(=S(=O)=O)C1 DZGNWHFOKDKUHL-UHFFFAOYSA-N 0.000 description 1
- JGUZSDCMIYDGOA-UHFFFAOYSA-N 3-[4-[bis(4-fluorophenyl)methyl]piperidin-1-yl]propan-1-ol Chemical compound C1CN(CCCO)CCC1C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 JGUZSDCMIYDGOA-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 1
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
- LSQARZALBDFYQZ-UHFFFAOYSA-N 4,4'-difluorobenzophenone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(F)C=C1 LSQARZALBDFYQZ-UHFFFAOYSA-N 0.000 description 1
- CKPWJBXTVZXVHS-UHFFFAOYSA-N 4-(3-chloropropoxy)benzamide Chemical compound NC(=O)C1=CC=C(OCCCCl)C=C1 CKPWJBXTVZXVHS-UHFFFAOYSA-N 0.000 description 1
- AAZOXAMWDHMCBM-UHFFFAOYSA-N 4-(3-chloropropoxy)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(OCCCCl)C=C1 AAZOXAMWDHMCBM-UHFFFAOYSA-N 0.000 description 1
- FDDVVDQBDFMXNB-UHFFFAOYSA-N 4-(3-chloropropoxy)benzonitrile Chemical compound ClCCCOC1=CC=C(C#N)C=C1 FDDVVDQBDFMXNB-UHFFFAOYSA-N 0.000 description 1
- CTJLHZDAJAGHMG-UHFFFAOYSA-N 4-[(3,4-difluorophenyl)-(4-fluorophenyl)methyl]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=C(F)C(F)=CC=1)C1CCNCC1 CTJLHZDAJAGHMG-UHFFFAOYSA-N 0.000 description 1
- ACJREPWYHCVBBO-UHFFFAOYSA-N 4-[(3,4-difluorophenyl)-(4-fluorophenyl)methylidene]piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=C(F)C(F)=CC=1)=C1CCNCC1 ACJREPWYHCVBBO-UHFFFAOYSA-N 0.000 description 1
- PWRMQWPHCVEDOO-UHFFFAOYSA-N 4-[bis(2,4-difluorophenyl)methyl]piperidine;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C(C=1C(=CC(F)=CC=1)F)C1CCNCC1 PWRMQWPHCVEDOO-UHFFFAOYSA-N 0.000 description 1
- ZDCHJSLCOIKMCZ-UHFFFAOYSA-N 4-[bis(2,4-difluorophenyl)methyl]pyridine Chemical compound FC1=CC(F)=CC=C1C(C=1C(=CC(F)=CC=1)F)C1=CC=NC=C1 ZDCHJSLCOIKMCZ-UHFFFAOYSA-N 0.000 description 1
- VJDVAILWBYJJDC-UHFFFAOYSA-N 4-[bis(2,4-difluorophenyl)methyl]pyridine;hydrochloride Chemical compound Cl.FC1=CC(F)=CC=C1C(C=1C(=CC(F)=CC=1)F)C1=CC=NC=C1 VJDVAILWBYJJDC-UHFFFAOYSA-N 0.000 description 1
- FXXPRLLHASMHDD-UHFFFAOYSA-N 4-[bis(3,4-difluorophenyl)methylidene]piperidine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=C(F)C(F)=CC=C1C(C=1C=C(F)C(F)=CC=1)=C1CCNCC1 FXXPRLLHASMHDD-UHFFFAOYSA-N 0.000 description 1
- QMCUNTIKHWNNIV-UHFFFAOYSA-N 4-[bis(4-chlorophenyl)-hydroxymethyl]-n,n-diethylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)N(CC)CC)CCC1C(O)(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 QMCUNTIKHWNNIV-UHFFFAOYSA-N 0.000 description 1
- SKZODFKQXIOHJH-UHFFFAOYSA-N 4-[bis(4-chlorophenyl)methyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)C1CCNCC1 SKZODFKQXIOHJH-UHFFFAOYSA-N 0.000 description 1
- HCBMFRHBAUTHEN-UHFFFAOYSA-N 4-[bis(4-chlorophenyl)methylidene]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC(Cl)=CC=1)=C1CCNCC1 HCBMFRHBAUTHEN-UHFFFAOYSA-N 0.000 description 1
- JSAOIDHRAOXIEF-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methyl]-1-(2-phenoxyethyl)piperidine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)C1CCN(CCOC=2C=CC=CC=2)CC1 JSAOIDHRAOXIEF-UHFFFAOYSA-N 0.000 description 1
- UNRGAFQMZNNWLH-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methyl]-1-(3-chloropropyl)piperidine Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)C1CCN(CCCCl)CC1 UNRGAFQMZNNWLH-UHFFFAOYSA-N 0.000 description 1
- GBXMKDDNSASMGF-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methyl]-1-(4-phenoxybutyl)piperidine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)C1CCN(CCCCOC=2C=CC=CC=2)CC1 GBXMKDDNSASMGF-UHFFFAOYSA-N 0.000 description 1
- QYGTZLORLCADEX-UHFFFAOYSA-N 4-[bis(4-fluorophenyl)methylidene]piperidine;hydrobromide Chemical compound Br.C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)=C1CCNCC1 QYGTZLORLCADEX-UHFFFAOYSA-N 0.000 description 1
- GRCOXKIBNWXXGC-UHFFFAOYSA-N 4-[bis(4-methylphenyl)methyl]-1-[3-(2,6-dimethoxyphenoxy)propyl]piperidine Chemical compound COC1=CC=CC(OC)=C1OCCCN1CCC(C(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)CC1 GRCOXKIBNWXXGC-UHFFFAOYSA-N 0.000 description 1
- WYBWXDGWEUMMLI-WLHGVMLRSA-N 4-benzhydryl-1-(3-phenoxypropyl)piperidine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1CC(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1CCCOC1=CC=CC=C1 WYBWXDGWEUMMLI-WLHGVMLRSA-N 0.000 description 1
- MTYPZYPJOJRYCY-UHFFFAOYSA-N 4-benzhydrylidene-1-benzylpiperidine Chemical class C=1C=CC=CC=1CN(CC1)CCC1=C(C=1C=CC=CC=1)C1=CC=CC=C1 MTYPZYPJOJRYCY-UHFFFAOYSA-N 0.000 description 1
- FBFJHRCUWSESSI-UHFFFAOYSA-N 4-benzhydrylpiperidine;hydrochloride Chemical compound Cl.C1CNCCC1C(C=1C=CC=CC=1)C1=CC=CC=C1 FBFJHRCUWSESSI-UHFFFAOYSA-N 0.000 description 1
- QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 1
- QBLISOIWPZSVIK-UHFFFAOYSA-N 4-bromobutoxybenzene Chemical compound BrCCCCOC1=CC=CC=C1 QBLISOIWPZSVIK-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- 125000000873 4-chlorophenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C(Cl)C([H])=C1[H] 0.000 description 1
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 1
- LXBHHIZIQVZGFN-UHFFFAOYSA-N 4-hydroxy-3-methylacetophenone Chemical compound CC(=O)C1=CC=C(O)C(C)=C1 LXBHHIZIQVZGFN-UHFFFAOYSA-N 0.000 description 1
- DIRCLGLKRZLKHG-UHFFFAOYSA-N 4-hydroxybenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(O)C=C1 DIRCLGLKRZLKHG-UHFFFAOYSA-N 0.000 description 1
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
- PLWSHDGLZBEFPL-UHFFFAOYSA-N 4-phenylsulfanylbutanamide Chemical compound NC(=O)CCCSC1=CC=CC=C1 PLWSHDGLZBEFPL-UHFFFAOYSA-N 0.000 description 1
- UCDVVZZVBFQPJN-UHFFFAOYSA-N 5-methoxy-2-nitro-4-phenylmethoxybenzamide Chemical compound COC1=CC(C(N)=O)=C([N+]([O-])=O)C=C1OCC1=CC=CC=C1 UCDVVZZVBFQPJN-UHFFFAOYSA-N 0.000 description 1
- FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical group FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- HXCBKQXAXRRHQW-UHFFFAOYSA-N 7-(3-chloropropoxy)chromen-2-one Chemical compound C1=CC(=O)OC2=CC(OCCCCl)=CC=C21 HXCBKQXAXRRHQW-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- UISZWYORHKBZTP-UHFFFAOYSA-N 7-methoxy-n,n-dimethyl-1h-indazole-3-carboxamide Chemical compound COC1=CC=CC2=C1NN=C2C(=O)N(C)C UISZWYORHKBZTP-UHFFFAOYSA-N 0.000 description 1
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000272517 Anseriformes Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101150043532 CISH gene Proteins 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 101100317380 Danio rerio wnt4a gene Proteins 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 101000941450 Lasioglossum laticeps Lasioglossin-1 Proteins 0.000 description 1
- 102100034724 Lipocalin-1 Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 241000206607 Porphyra umbilicalis Species 0.000 description 1
- 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 1
- 241000283984 Rodentia Species 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920001079 Thiokol (polymer) Polymers 0.000 description 1
- 101150010310 WNT-4 gene Proteins 0.000 description 1
- 102000052548 Wnt-4 Human genes 0.000 description 1
- 108700020984 Wnt-4 Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- YLPLVVAXXZWTIR-UHFFFAOYSA-N [1-(4-methylphenyl)sulfonylpyrrolidin-3-yl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1 YLPLVVAXXZWTIR-UHFFFAOYSA-N 0.000 description 1
- PJSHGCIAJMCRGP-UHFFFAOYSA-N [3-(3-chloropropoxy)phenyl]urea Chemical compound NC(=O)NC1=CC=CC(OCCCCl)=C1 PJSHGCIAJMCRGP-UHFFFAOYSA-N 0.000 description 1
- LVTQNSHNUOIMDK-UHFFFAOYSA-N acetonitrile;dichloromethane;hexane Chemical compound CC#N.ClCCl.CCCCCC LVTQNSHNUOIMDK-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003710 aryl alkyl group Chemical class 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- GHQPBDDZGPAVJP-UHFFFAOYSA-N azanium;methanol;hydroxide Chemical compound N.O.OC GHQPBDDZGPAVJP-UHFFFAOYSA-N 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical class C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- WIRUZQNBHNAMAB-UHFFFAOYSA-N benzene;cyclohexane Chemical compound C1CCCCC1.C1=CC=CC=C1 WIRUZQNBHNAMAB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000003218 coronary vasodilator agent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- YVPJFAHPSNUGOV-UHFFFAOYSA-N cyclohexylsulfamic acid;hydrate Chemical compound O.OS(=O)(=O)NC1CCCCC1 YVPJFAHPSNUGOV-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- MRHLFZXYRABVOZ-UHFFFAOYSA-N diphenyl(pyridin-4-yl)methanol Chemical compound C=1C=CC=CC=1C(C=1C=CN=CC=1)(O)C1=CC=CC=C1 MRHLFZXYRABVOZ-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- KHDOTPVDSFBNMG-UHFFFAOYSA-N ethanol;pyridine Chemical compound CCO.C1=CC=NC=C1 KHDOTPVDSFBNMG-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- VUILWWLHMVLGCX-UHFFFAOYSA-N ethyl 1-(3-phenoxypropyl)piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1CCCOC1=CC=CC=C1 VUILWWLHMVLGCX-UHFFFAOYSA-N 0.000 description 1
- UGAYXZQYGHSZPJ-UHFFFAOYSA-N ethyl 1-(3-phenoxypropyl)piperidine-4-carboxylate;oxalic acid Chemical compound OC(=O)C(O)=O.C1CC(C(=O)OCC)CCN1CCCOC1=CC=CC=C1 UGAYXZQYGHSZPJ-UHFFFAOYSA-N 0.000 description 1
- HJFLMHXJHDEFND-UHFFFAOYSA-N ethyl 1-(benzenesulfonyl)piperidine-3-carboxylate Chemical compound C1C(C(=O)OCC)CCCN1S(=O)(=O)C1=CC=CC=C1 HJFLMHXJHDEFND-UHFFFAOYSA-N 0.000 description 1
- QOUKNBDQCOOULH-UHFFFAOYSA-N ethyl 1-benzylpiperidine-3-carboxylate;hydrobromide Chemical compound Br.C1C(C(=O)OCC)CCCN1CC1=CC=CC=C1 QOUKNBDQCOOULH-UHFFFAOYSA-N 0.000 description 1
- AWPMWZHWVKXADV-UHFFFAOYSA-N ethyl 2-(4-hydroxy-3-methoxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(O)C(OC)=C1 AWPMWZHWVKXADV-UHFFFAOYSA-N 0.000 description 1
- BYUAKZHGSIPRDR-UHFFFAOYSA-N ethyl 2-[4-(3-chloropropoxy)-3-methoxyphenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(OCCCCl)C(OC)=C1 BYUAKZHGSIPRDR-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- RPWXYCRIAGBAGY-UHFFFAOYSA-N ethyl 2-pyridin-3-ylacetate Chemical compound CCOC(=O)CC1=CC=CN=C1 RPWXYCRIAGBAGY-UHFFFAOYSA-N 0.000 description 1
- LTCHKFQMPAGJLR-UHFFFAOYSA-N ethyl 3-(3-chloropropoxy)benzoate Chemical compound CCOC(=O)C1=CC=CC(OCCCCl)=C1 LTCHKFQMPAGJLR-UHFFFAOYSA-N 0.000 description 1
- MWSMNBYIEBRXAL-UHFFFAOYSA-N ethyl 3-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=CC(O)=C1 MWSMNBYIEBRXAL-UHFFFAOYSA-N 0.000 description 1
- TZDFSADZWOUTMD-UHFFFAOYSA-N ethyl 4-(2-chloroethoxy)benzoate Chemical compound CCOC(=O)C1=CC=C(OCCCl)C=C1 TZDFSADZWOUTMD-UHFFFAOYSA-N 0.000 description 1
- RKIMFICEWCXBCE-UHFFFAOYSA-N ethyl 7-hydroxy-4-oxochromene-2-carboxylate Chemical compound C1=C(O)C=C2OC(C(=O)OCC)=CC(=O)C2=C1 RKIMFICEWCXBCE-UHFFFAOYSA-N 0.000 description 1
- WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 1
- NBEMQPLNBYYUAZ-UHFFFAOYSA-N ethyl acetate;propan-2-one Chemical compound CC(C)=O.CCOC(C)=O NBEMQPLNBYYUAZ-UHFFFAOYSA-N 0.000 description 1
- BECNKUVYBNETOM-UHFFFAOYSA-N ethyl n-(4-hydroxyphenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C(O)C=C1 BECNKUVYBNETOM-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- HJLHTTJLVALHOP-UHFFFAOYSA-N hexane;hydron;chloride Chemical class Cl.CCCCCC HJLHTTJLVALHOP-UHFFFAOYSA-N 0.000 description 1
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- WOFDVDFSGLBFAC-UHFFFAOYSA-N lactonitrile Chemical compound CC(O)C#N WOFDVDFSGLBFAC-UHFFFAOYSA-N 0.000 description 1
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 238000003328 mesylation reaction Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- XGDZEDRBLVIUMX-UHFFFAOYSA-N methyl 2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C=C1 XGDZEDRBLVIUMX-UHFFFAOYSA-N 0.000 description 1
- VTGQWPRIFPILSC-UHFFFAOYSA-N methyl 2-[4-(3-chloropropoxy)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(OCCCCl)C=C1 VTGQWPRIFPILSC-UHFFFAOYSA-N 0.000 description 1
- SJSPWXDMJNLLKK-UHFFFAOYSA-N methyl 4-(3-chloropropoxy)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OCCCCl)C(OC)=C1 SJSPWXDMJNLLKK-UHFFFAOYSA-N 0.000 description 1
- VTKOQROAAPSESX-UHFFFAOYSA-N methyl 4-(4-chlorobutoxy)benzoate Chemical compound COC(=O)C1=CC=C(OCCCCCl)C=C1 VTKOQROAAPSESX-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- FTNFEHXDETWERN-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-2,6-dimethyl-5-[(4-propan-2-yloxyphenyl)methyl]pyrimidin-4-amine Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 FTNFEHXDETWERN-UHFFFAOYSA-N 0.000 description 1
- XHXVAJHZTIXQQD-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-5-[(4-butoxyphenyl)methyl]-2,6-dimethylpyrimidin-4-amine Chemical compound C1=CC(OCCCC)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 XHXVAJHZTIXQQD-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- XITQUSLLOSKDTB-UHFFFAOYSA-N nitrofen Chemical compound C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C(Cl)C=C1Cl XITQUSLLOSKDTB-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- RZZIKHSWRWWPAN-UHFFFAOYSA-N oxolane-2-carbonitrile Chemical compound N#CC1CCCO1 RZZIKHSWRWWPAN-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229960003540 oxyquinoline Drugs 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- SKFLCXNDKRUHTA-UHFFFAOYSA-N phenyl(pyridin-4-yl)methanone Chemical compound C=1C=NC=CC=1C(=O)C1=CC=CC=C1 SKFLCXNDKRUHTA-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- ROFVJSWBDQUQGW-UHFFFAOYSA-N piperidin-1-ium;bromide Chemical compound Br.C1CCNCC1 ROFVJSWBDQUQGW-UHFFFAOYSA-N 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- SAALQYKUFCIMHR-UHFFFAOYSA-N propan-2-ol;2-propan-2-yloxypropane Chemical compound CC(C)O.CC(C)OC(C)C SAALQYKUFCIMHR-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical class 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- DKZBBWMURDFHNE-UHFFFAOYSA-N trans-coniferylaldehyde Natural products COC1=CC(C=CC=O)=CC=C1O DKZBBWMURDFHNE-UHFFFAOYSA-N 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D227/00—Heterocyclic compounds containing rings having one nitrogen atom as the only ring hetero atom, according to more than one of groups C07D203/00 - C07D225/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15439088A | 1988-02-10 | 1988-02-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
PH26585A true PH26585A (en) | 1992-08-19 |
Family
ID=22551174
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PH38517A PH26585A (en) | 1988-02-10 | 1989-04-27 | N-substituted-arylalkyl and arylalkylene aminoheterocyclics as cardiovascular antihistamic and antisecretory agents |
Country Status (3)
Country | Link |
---|---|
KR (1) | KR890012971A (ko) |
AU (1) | AU629535B2 (ko) |
PH (1) | PH26585A (ko) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU629534B2 (en) * | 1988-02-24 | 1992-10-08 | A.H. Robins Company, Incorporated | New methods and related compounds |
FI905325A0 (fi) * | 1989-10-30 | 1990-10-29 | Syntex Inc | Foerfarande foer framstaellning av benzylpyrrolidinderivat vilka aer aktiva som dopamin-agonister. |
US6004980A (en) * | 1990-06-01 | 1999-12-21 | Merrell Pharmaceuticals, Inc. | (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol |
JP2869512B2 (ja) * | 1990-06-01 | 1999-03-10 | メレルダウファーマスーティカルズ インコーポレイテッド | (+)―α―(2,3―ジメトキシフェニル)―1―[2―(4―フルオロフェニル)エチル]―4―ピペリジンメタノール |
MY108616A (en) * | 1990-10-10 | 1996-10-31 | Schering Corp | Pyridine and pyridine n-oxide derivatives of diaryl methyl piperidines of piperazines, and compositions and methods of use thereof |
DE4111861A1 (de) * | 1991-04-11 | 1992-10-15 | Schwabe Willmar Gmbh & Co | Benzopyranone, verfahren zu ihrer herstellung und verwendung |
US6028083A (en) * | 1997-07-25 | 2000-02-22 | Hoechst Marion Roussel, Inc. | Esters of (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemethanol |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4810713A (en) * | 1985-12-20 | 1989-03-07 | A. H. Robins Company, Incorporated | Arylalkyl-heterocyclic amines, n-substituted by aryloxyalkyl groups used in a method for allergy treatment |
DE3600390A1 (de) * | 1986-01-09 | 1987-07-16 | Hoechst Ag | Diarylalkyl-substituierte alkylamine, verfahren zu ihrer herstellung, ihre verwendung sowie sie enthaltende arzneimittel |
IL78939A (en) * | 1986-01-17 | 1990-04-29 | Robins Co Inc A H | Pharmaceutical compositions containing n-substituted arylalkyl-and arylalkylene-piperidines and tetrahydropyridines and certain such novel compounds |
-
1989
- 1989-02-10 KR KR1019890001515A patent/KR890012971A/ko not_active Application Discontinuation
- 1989-02-10 AU AU29823/89A patent/AU629535B2/en not_active Ceased
- 1989-04-27 PH PH38517A patent/PH26585A/en unknown
Also Published As
Publication number | Publication date |
---|---|
KR890012971A (ko) | 1989-09-20 |
AU2982389A (en) | 1989-08-10 |
AU629535B2 (en) | 1992-10-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0235463A2 (en) | N-substituted-arylalkyl and arylalkylene piperidines as cardiovascular antihistaminic and antisecretory agents | |
US4950674A (en) | Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a method for allergy treatment | |
AP279A (en) | 4 substituted piperidine derivatives, processes for their preparation pharmaceutical compositions containing them and their use in therapy. | |
US5070087A (en) | Aryl(alkyland alkylene)-N-((phenoxy and phenylthio)alkyl) aminoheterocyclics as cardiovascular, anthihistaminic, antisecretory and antiallergy agents | |
CA1073925A (en) | Sulphur-containing arylamine derivatives | |
KR900005368B1 (ko) | N-치환된-아릴알킬 및 아릴알킬렌 아미노헤테로사이클릭 화합물 | |
CA2606262C (en) | Novel histamine h3-receptor ligands and their therapeutic applications | |
DE60033964T2 (de) | Phenoxypropanolamin-derivate, ihre herstellung und therapeutische verwendung | |
US4994460A (en) | Agents for treatment of brain ischemia | |
EP0869792A2 (en) | 4-substituted piperidine analogs and their use as subtype selective nmda receptor antagonists | |
JPS61100563A (ja) | 1‐[(アミノアルキルおよびアミノアルキルアミノ)カルボニルおよびチオカルボニル]‐α,α‐ジアリールピロリジン、ピペリジンおよびホモピペリジンアセトアミドおよびアセトニトリル | |
PH26585A (en) | N-substituted-arylalkyl and arylalkylene aminoheterocyclics as cardiovascular antihistamic and antisecretory agents | |
EP1978959B1 (en) | Piperidine and piperazine derivatives | |
US4650874A (en) | N-(aralkoxybenzyl)-4(benzhydryl) piperidines | |
EP0576766A1 (en) | Propanolamine derivatives, their preparation and use | |
JPH02121964A (ja) | 1‐〔(ジアリ―ルメトキシ)アルキル〕‐ピロリジン類及び‐ピペリジン類 | |
EP0147909B1 (en) | Aryloxy-n-(aminoalkyl)-1-pyrrolidine and piperidine carboxamides and carbothioamides having antiarrhythmic activity | |
US5486527A (en) | Anticholinergic agents | |
AU629534B2 (en) | New methods and related compounds | |
EP1976525B1 (en) | Piperidine and piperazine derivatives | |
CA1291995C (en) | N-substituted-arylalkyl and arylalkylene aminoheterocyclics as cardiovascular antihistaminic and antisecretory agents | |
US4218455A (en) | 1-(4-Fluorophenyl)-4-[1,2,3,6-tetrahydro-4-(phenylthio)-1-pyridinyl]-butanones and related sulfoxides and sulfones | |
DE2107871B2 (de) | 1-phenyl-4-amino-cyclohex-2-en-1 carbonsaeureester, verfahren zu deren herstellung und diese enthaltende analgetisch wirksame arzneimittel | |
US20100256162A1 (en) | Piperazine and Piperidine Derivatives | |
HU188059B (en) | Process for producing benzylazole derivatives |