RU2480456C2 - Фенилпиразольные производные - Google Patents

Info

Publication number

RU2480456C2

RU2480456C2 RU2010123924/04A RU2010123924A RU2480456C2 RU 2480456 C2 RU2480456 C2 RU 2480456C2 RU 2010123924/04 A RU2010123924/04 A RU 2010123924/04A RU 2010123924 A RU2010123924 A RU 2010123924A RU 2480456 C2 RU2480456 C2 RU 2480456C2

Authority

RU

Russia

Prior art keywords

phenyl

alkyl

propoxy

methylpyrrolidin

halogen

Prior art date

2007-11-13

Links

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• Global Dossier
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• OEDUIFSDODUDRK-UHFFFAOYSA-N 5-phenyl-1h-pyrazole Chemical class N1N=CC=C1C1=CC=CC=C1 OEDUIFSDODUDRK-UHFFFAOYSA-N 0.000 title abstract 2
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 103
• 150000002367 halogens Chemical group 0.000 claims abstract description 82
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 42
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 32
• 150000003839 salts Chemical class 0.000 claims abstract description 31
• 125000005843 halogen group Chemical group 0.000 claims abstract description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 19
• 239000003814 drug Substances 0.000 claims abstract description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 9
• 208000019116 sleep disease Diseases 0.000 claims abstract description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims abstract description 6
• 208000017164 Chronobiology disease Diseases 0.000 claims abstract description 6
• 206010010904 Convulsion Diseases 0.000 claims abstract description 6
• 206010012289 Dementia Diseases 0.000 claims abstract description 6
• 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 6
• 208000008589 Obesity Diseases 0.000 claims abstract description 6
• 206010039085 Rhinitis allergic Diseases 0.000 claims abstract description 6
• 201000010105 allergic rhinitis Diseases 0.000 claims abstract description 6
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims abstract description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
• 206010015037 epilepsy Diseases 0.000 claims abstract description 6
• 201000003631 narcolepsy Diseases 0.000 claims abstract description 6
• 235000020824 obesity Nutrition 0.000 claims abstract description 6
• 201000000980 schizophrenia Diseases 0.000 claims abstract description 6
• 201000002859 sleep apnea Diseases 0.000 claims abstract description 6
• 229940124597 therapeutic agent Drugs 0.000 claims abstract description 6
• 125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 claims abstract description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
• -1 4-fluorobenzylamide 1- {4- [3- (2-methylpyrrolidin-1-yl) propoxy] phenyl} -1H-pyrazole-4-carboxylic acid Chemical compound 0.000 claims description 70
• 150000008048 phenylpyrazoles Chemical class 0.000 claims description 30
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
• IABXVJILZYNSTM-GOSISDBHSA-N [1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 IABXVJILZYNSTM-GOSISDBHSA-N 0.000 claims description 7
• PJZXYQHKCKLJLX-CQSZACIVSA-N 1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carboxamide Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(N)=O)C=C1 PJZXYQHKCKLJLX-CQSZACIVSA-N 0.000 claims description 6
• PJZXYQHKCKLJLX-AWEZNQCLSA-N 1-[4-[3-[(2s)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carboxamide Chemical compound C[C@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(N)=O)C=C1 PJZXYQHKCKLJLX-AWEZNQCLSA-N 0.000 claims description 5
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
• 208000030814 Eating disease Diseases 0.000 claims description 5
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
• 235000014632 disordered eating Nutrition 0.000 claims description 5
• BPPLZEUEZFFAGT-HXUWFJFHSA-N tert-butyl 2-[2-hydroxyethyl-[1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carbonyl]amino]acetate Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N(CCO)CC(=O)OC(C)(C)C)C=C1 BPPLZEUEZFFAGT-HXUWFJFHSA-N 0.000 claims description 5
• LFKDMJJHFXXFBX-QGZVFWFLSA-N [1-[3-fluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1F LFKDMJJHFXXFBX-QGZVFWFLSA-N 0.000 claims description 4
• XNLPBUDEIFAWMZ-QGZVFWFLSA-N [1-[4-[2-[(2r)-2-methylpyrrolidin-1-yl]ethoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 XNLPBUDEIFAWMZ-QGZVFWFLSA-N 0.000 claims description 4
• NBIDEINMRVXYIS-UHFFFAOYSA-N [1-[4-[3-(2-ethylpyrrolidin-1-yl)propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound CCC1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 NBIDEINMRVXYIS-UHFFFAOYSA-N 0.000 claims description 4
• ZSEVZHHSUFXFMZ-GOSISDBHSA-N [1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-pyrrolidin-1-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCCC2)C=C1 ZSEVZHHSUFXFMZ-GOSISDBHSA-N 0.000 claims description 4
• LESTYABWGBPGNU-LJQANCHMSA-N [1-[4-[4-[(2r)-2-methylpyrrolidin-1-yl]butoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 LESTYABWGBPGNU-LJQANCHMSA-N 0.000 claims description 4
• 208000035475 disorder Diseases 0.000 claims description 4
• 208000013403 hyperactivity Diseases 0.000 claims description 4
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 4
• PZRVQACPBLRYTI-MRXNPFEDSA-N n-(2-hydroxyethyl)-1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carboxamide Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)NCCO)C=C1 PZRVQACPBLRYTI-MRXNPFEDSA-N 0.000 claims description 4
• ZJHLDPLSPGJKEZ-UHFFFAOYSA-N n-(4-fluorophenyl)-1-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]pyrazole-4-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)NC=2C=CC(F)=CC=2)C=C1 ZJHLDPLSPGJKEZ-UHFFFAOYSA-N 0.000 claims description 4
• BRZFMWDQFKUEDE-UHFFFAOYSA-N n-tert-butyl-1-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]pyrazole-4-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)NC(C)(C)C)C=C1 BRZFMWDQFKUEDE-UHFFFAOYSA-N 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• IOBVIKDKHCLPAO-OQHSHRKDSA-N (2-hydroxymorpholin-4-yl)-[1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]methanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CC(O)OCC2)C=C1 IOBVIKDKHCLPAO-OQHSHRKDSA-N 0.000 claims description 3
• SCKKOMYFTDYWGT-QGZVFWFLSA-N (3,3-difluoropyrrolidin-1-yl)-[1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]methanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CC(F)(F)CC2)C=C1 SCKKOMYFTDYWGT-QGZVFWFLSA-N 0.000 claims description 3
• SSBHPAUGOXDRHP-LJQANCHMSA-N (4-methylpiperazin-1-yl)-[1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]methanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCN(C)CC2)C=C1 SSBHPAUGOXDRHP-LJQANCHMSA-N 0.000 claims description 3
• IOYFUVZDUCGFFS-LJQANCHMSA-N [1-[2-methyl-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C(C)=C1 IOYFUVZDUCGFFS-LJQANCHMSA-N 0.000 claims description 3
• NGDMWZZOKWJGLN-QGZVFWFLSA-N [1-[3-bromo-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1Br NGDMWZZOKWJGLN-QGZVFWFLSA-N 0.000 claims description 3
• BRVUSSWNVFHYNK-UHFFFAOYSA-N [1-[4-[3-(2,2-difluoropyrrolidin-1-yl)propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound FC1(F)CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 BRVUSSWNVFHYNK-UHFFFAOYSA-N 0.000 claims description 3
• JSCSNWVFRVXHDR-UHFFFAOYSA-N [1-[4-[3-(2,2-dimethylpyrrolidin-1-yl)propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound CC1(C)CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 JSCSNWVFRVXHDR-UHFFFAOYSA-N 0.000 claims description 3
• XWMYYUNTNLBZJN-UHFFFAOYSA-N [1-[4-[3-(3-methylpyrrolidin-1-yl)propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C1C(C)CCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 XWMYYUNTNLBZJN-UHFFFAOYSA-N 0.000 claims description 3
• NKTQIIIJPHVFEB-LJQANCHMSA-N [1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-(1,4-oxazepan-4-yl)methanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCCC2)C=C1 NKTQIIIJPHVFEB-LJQANCHMSA-N 0.000 claims description 3
• IABXVJILZYNSTM-SFHVURJKSA-N [1-[4-[3-[(2s)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazol-4-yl]-morpholin-4-ylmethanone Chemical compound C[C@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCOCC2)C=C1 IABXVJILZYNSTM-SFHVURJKSA-N 0.000 claims description 3
• KXSKGQURHNIXQH-UHFFFAOYSA-N azetidin-1-yl-[1-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]pyrazol-4-yl]methanone Chemical compound CC1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N2CCC2)C=C1 KXSKGQURHNIXQH-UHFFFAOYSA-N 0.000 claims description 3
• VPKQGRLCYMSVED-UHFFFAOYSA-N morpholin-4-yl-[1-[4-(3-piperidin-1-ylpropoxy)phenyl]pyrazol-4-yl]methanone Chemical compound C1=NN(C=2C=CC(OCCCN3CCCCC3)=CC=2)C=C1C(=O)N1CCOCC1 VPKQGRLCYMSVED-UHFFFAOYSA-N 0.000 claims description 3
• PEWUJQSDWONAOM-UHFFFAOYSA-N morpholin-4-yl-[1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyrazol-4-yl]methanone Chemical compound C1=NN(C=2C=CC(OCCCN3CCCC3)=CC=2)C=C1C(=O)N1CCOCC1 PEWUJQSDWONAOM-UHFFFAOYSA-N 0.000 claims description 3
• QIYOBDVDGIIVEJ-GOSISDBHSA-N n,n-bis(2-hydroxyethyl)-1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carboxamide Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N(CCO)CCO)C=C1 QIYOBDVDGIIVEJ-GOSISDBHSA-N 0.000 claims description 3
• ROQMVNDSPDGQJP-UHFFFAOYSA-N n,n-dimethyl-1-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]pyrazole-4-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)N(C)C)C=C1 ROQMVNDSPDGQJP-UHFFFAOYSA-N 0.000 claims description 3
• GRQMLKRQGYDTPY-UHFFFAOYSA-N n-(4-fluorophenyl)-1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyrazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=CN(C=2C=CC(OCCCN3CCCC3)=CC=2)N=C1 GRQMLKRQGYDTPY-UHFFFAOYSA-N 0.000 claims description 3
• KTFZYZYJJHRYCS-UHFFFAOYSA-N n-(4-methylphenyl)-1-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]pyrazole-4-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)NC=2C=CC(C)=CC=2)C=C1 KTFZYZYJJHRYCS-UHFFFAOYSA-N 0.000 claims description 3
• JTFNUJVNNVEWOB-UHFFFAOYSA-N n-tert-butyl-1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]pyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC(C)(C)C)C=NN1C(C=C1)=CC=C1OCCCN1CCCC1 JTFNUJVNNVEWOB-UHFFFAOYSA-N 0.000 claims description 3
• ULYGNJDYFKUSCV-UHFFFAOYSA-N n-tert-butyl-1-[4-[3-(2,5-dimethylpyrrolidin-1-yl)propoxy]phenyl]pyrazole-4-carboxamide Chemical compound CC1CCC(C)N1CCCOC1=CC=C(N2N=CC(=C2)C(=O)NC(C)(C)C)C=C1 ULYGNJDYFKUSCV-UHFFFAOYSA-N 0.000 claims description 3
• KIYXNAQGDBHYKC-UHFFFAOYSA-N n-tert-butyl-1-[4-[3-(diethylamino)propoxy]phenyl]pyrazole-4-carboxamide Chemical compound C1=CC(OCCCN(CC)CC)=CC=C1N1N=CC(C(=O)NC(C)(C)C)=C1 KIYXNAQGDBHYKC-UHFFFAOYSA-N 0.000 claims description 3
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• 239000004480 active ingredient Substances 0.000 claims description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
• TYMPTWLKVMOQKK-GOSISDBHSA-N n-[2-(2-hydroxyethoxy)ethyl]-1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carboxamide Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(=C2)C(=O)NCCOCCO)C=C1 TYMPTWLKVMOQKK-GOSISDBHSA-N 0.000 claims description 2
• 230000000069 prophylactic effect Effects 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 11
• SIEIGJDWYNJTAX-OAHLLOKOSA-N 1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-4-carbaldehyde Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2N=CC(C=O)=C2)C=C1 SIEIGJDWYNJTAX-OAHLLOKOSA-N 0.000 claims 1
• JTSRPXNPVLMJLB-UHFFFAOYSA-N 2H-pyridin-2-ide Chemical compound N1=[C-]C=CC=C1 JTSRPXNPVLMJLB-UHFFFAOYSA-N 0.000 claims 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 1
• 239000004471 Glycine Substances 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 abstract description 243
• 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 68
• 239000000126 substance Substances 0.000 abstract description 15
• 229920006395 saturated elastomer Polymers 0.000 abstract description 10
• 230000000694 effects Effects 0.000 abstract description 7
• 230000020595 eating behavior Effects 0.000 abstract description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 12
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 4
• 206010000117 Abnormal behaviour Diseases 0.000 abstract 1
• 230000036461 convulsion Effects 0.000 abstract 1
• 230000003449 preventive effect Effects 0.000 abstract 1
• 208000022925 sleep disturbance Diseases 0.000 abstract 1
• 238000002360 preparation method Methods 0.000 description 115
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
• 238000000034 method Methods 0.000 description 92
• 238000006243 chemical reaction Methods 0.000 description 88
• 239000002904 solvent Substances 0.000 description 74
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
• 230000009977 dual effect Effects 0.000 description 68
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 65
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 64
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 55
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
• 239000000203 mixture Substances 0.000 description 52
• 239000011541 reaction mixture Substances 0.000 description 51
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
• 238000012360 testing method Methods 0.000 description 47
• 239000000243 solution Substances 0.000 description 36
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• 230000002829 reductive effect Effects 0.000 description 32
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 30
• 125000003118 aryl group Chemical group 0.000 description 27
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 24
• 102000004384 Histamine H3 receptors Human genes 0.000 description 24
• 108090000981 Histamine H3 receptors Proteins 0.000 description 24
• 238000005859 coupling reaction Methods 0.000 description 24
• 125000001072 heteroaryl group Chemical group 0.000 description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 238000010898 silica gel chromatography Methods 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• 239000007787 solid Substances 0.000 description 18
• 239000012044 organic layer Substances 0.000 description 17
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
• 241000700159 Rattus Species 0.000 description 15
• 230000027455 binding Effects 0.000 description 15
• 238000009833 condensation Methods 0.000 description 14
• 230000005494 condensation Effects 0.000 description 14
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 13
• 230000035484 reaction time Effects 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• UTRJNWWLPXDHJU-GFCCVEGCSA-N (2r)-1-[3-(4-iodophenoxy)propyl]-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(I)C=C1 UTRJNWWLPXDHJU-GFCCVEGCSA-N 0.000 description 12
• RGHPCLZJAFCTIK-RXMQYKEDSA-N (R)-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1 RGHPCLZJAFCTIK-RXMQYKEDSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 12
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