CA2686033A1 - Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof - Google Patents
Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof Download PDFInfo
- Publication number
- CA2686033A1 CA2686033A1 CA002686033A CA2686033A CA2686033A1 CA 2686033 A1 CA2686033 A1 CA 2686033A1 CA 002686033 A CA002686033 A CA 002686033A CA 2686033 A CA2686033 A CA 2686033A CA 2686033 A1 CA2686033 A1 CA 2686033A1
- Authority
- CA
- Canada
- Prior art keywords
- methylpyrrolidine
- methyl
- tartrate
- pyrrolidin
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- RGHPCLZJAFCTIK-YFKPBYRVSA-N (2s)-2-methylpyrrolidine Chemical compound C[C@H]1CCCN1 RGHPCLZJAFCTIK-YFKPBYRVSA-N 0.000 title claims abstract description 203
- 238000000034 method Methods 0.000 title claims description 167
- 230000008569 process Effects 0.000 title claims description 78
- RGHPCLZJAFCTIK-RXMQYKEDSA-N (R)-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1 RGHPCLZJAFCTIK-RXMQYKEDSA-N 0.000 title claims description 48
- 150000003892 tartrate salts Chemical class 0.000 title description 8
- MUUWQYQRBFVTIB-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1h-pyrrole Chemical compound CC1=CCCN1 MUUWQYQRBFVTIB-UHFFFAOYSA-N 0.000 claims abstract description 36
- AVAOHVDRAKDFRF-KLPPUMKISA-N (2r,3r)-2,3-dihydroxybutanedioic acid;(2r)-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1.OC(=O)[C@H](O)[C@@H](O)C(O)=O AVAOHVDRAKDFRF-KLPPUMKISA-N 0.000 claims description 176
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 162
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 136
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 claims description 135
- 239000000203 mixture Substances 0.000 claims description 130
- 239000002904 solvent Substances 0.000 claims description 112
- 239000003054 catalyst Substances 0.000 claims description 110
- 239000002585 base Substances 0.000 claims description 90
- 238000005984 hydrogenation reaction Methods 0.000 claims description 85
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 48
- 239000012458 free base Substances 0.000 claims description 35
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims description 32
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 27
- 229960001270 d- tartaric acid Drugs 0.000 claims description 25
- 230000003287 optical effect Effects 0.000 claims description 21
- 229910052697 platinum Inorganic materials 0.000 claims description 19
- 239000003446 ligand Substances 0.000 claims description 17
- 238000001914 filtration Methods 0.000 claims description 11
- XUKROCVZGZNGSI-CQSZACIVSA-N irdabisant Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=C1 XUKROCVZGZNGSI-CQSZACIVSA-N 0.000 claims description 9
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 claims description 8
- 102000004384 Histamine H3 receptors Human genes 0.000 claims description 8
- 108090000981 Histamine H3 receptors Proteins 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical group O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 claims description 7
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims description 6
- 239000000543 intermediate Substances 0.000 abstract description 23
- 238000002955 isolation Methods 0.000 abstract description 9
- 238000010963 scalable process Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 128
- 239000000243 solution Substances 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 68
- 125000000217 alkyl group Chemical group 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
- -1 C1-C6alkyl alcohol Chemical compound 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- 229910052757 nitrogen Inorganic materials 0.000 description 38
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- 150000001412 amines Chemical class 0.000 description 34
- 229910052739 hydrogen Inorganic materials 0.000 description 31
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 30
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
- 229910052736 halogen Inorganic materials 0.000 description 27
- 239000003153 chemical reaction reagent Substances 0.000 description 26
- 150000002367 halogens Chemical class 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 25
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 125000003118 aryl group Chemical group 0.000 description 22
- 239000001257 hydrogen Substances 0.000 description 22
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
- 150000003839 salts Chemical class 0.000 description 20
- RGHPCLZJAFCTIK-UHFFFAOYSA-N 2-methylpyrrolidine Chemical compound CC1CCCN1 RGHPCLZJAFCTIK-UHFFFAOYSA-N 0.000 description 19
- 125000005843 halogen group Chemical group 0.000 description 19
- 238000002360 preparation method Methods 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 17
- 125000003545 alkoxy group Chemical group 0.000 description 17
- 238000001953 recrystallisation Methods 0.000 description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 229910000029 sodium carbonate Inorganic materials 0.000 description 16
- 235000017550 sodium carbonate Nutrition 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 13
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- 150000001721 carbon Chemical group 0.000 description 11
- 239000007789 gas Substances 0.000 description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- OOGWMAIYWGZDRX-CYBMUJFWSA-N (2r)-1-[2-(6-bromonaphthalen-2-yl)ethyl]-2-methylpyrrolidine Chemical compound C[C@@H]1CCCN1CCC1=CC=C(C=C(Br)C=C2)C2=C1 OOGWMAIYWGZDRX-CYBMUJFWSA-N 0.000 description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 125000001072 heteroaryl group Chemical group 0.000 description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
- 239000012279 sodium borohydride Substances 0.000 description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 description 10
- 230000009466 transformation Effects 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 125000003710 aryl alkyl group Chemical group 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 125000000623 heterocyclic group Chemical group 0.000 description 9
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 235000015320 potassium carbonate Nutrition 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
- PCUZFDAAOXBYTO-UHFFFAOYSA-N 2-bromo-6-ethenylnaphthalene Chemical compound C1=C(C=C)C=CC2=CC(Br)=CC=C21 PCUZFDAAOXBYTO-UHFFFAOYSA-N 0.000 description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000011065 in-situ storage Methods 0.000 description 8
- 230000037361 pathway Effects 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 229910052802 copper Inorganic materials 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 229940113083 morpholine Drugs 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- FRNRXKFDZXFNKG-UHFFFAOYSA-N (6-bromonaphthalen-2-yl) trifluoromethanesulfonate Chemical compound C1=C(Br)C=CC2=CC(OS(=O)(=O)C(F)(F)F)=CC=C21 FRNRXKFDZXFNKG-UHFFFAOYSA-N 0.000 description 6
- CUMDJLVCVBQTKA-YSSOQSIOSA-N 4-methyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical class C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(CC(=O)NN=2)C)C=C1 CUMDJLVCVBQTKA-YSSOQSIOSA-N 0.000 description 6
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- 125000003158 alcohol group Chemical group 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 239000010949 copper Substances 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 5
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 5
- FJHKZEVPGYADEG-NVPAJSRCSA-N 2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-3,4-diazabicyclo[4.1.0]hept-2-en-5-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C3CC3C(=O)NN=2)C=C1 FJHKZEVPGYADEG-NVPAJSRCSA-N 0.000 description 5
- 229910015845 BBr3 Inorganic materials 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 229910000024 caesium carbonate Inorganic materials 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
- 150000003512 tertiary amines Chemical class 0.000 description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- XUKROCVZGZNGSI-AWEZNQCLSA-N 3-[4-[3-[(2s)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=C1 XUKROCVZGZNGSI-AWEZNQCLSA-N 0.000 description 4
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 4
- FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 125000002877 alkyl aryl group Chemical group 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000007822 coupling agent Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002170 ethers Chemical class 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 150000002466 imines Chemical class 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 229960004592 isopropanol Drugs 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 230000009972 noncorrosive effect Effects 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 3
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 3
- 125000004749 (C1-C6) haloalkylsulfinyl group Chemical group 0.000 description 3
- 125000004741 (C1-C6) haloalkylsulfonyl group Chemical group 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- YLDFTMJPQJXGSS-UHFFFAOYSA-N 6-bromo-2-naphthol Chemical compound C1=C(Br)C=CC2=CC(O)=CC=C21 YLDFTMJPQJXGSS-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- 238000006751 Mitsunobu reaction Methods 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 150000001299 aldehydes Chemical group 0.000 description 3
- 125000004422 alkyl sulphonamide group Chemical group 0.000 description 3
- 125000004414 alkyl thio group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000005363 dialkylsulfonamide group Chemical group 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000002638 heterogeneous catalyst Substances 0.000 description 3
- 239000002815 homogeneous catalyst Substances 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 229940001593 sodium carbonate Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940124530 sulfonamide Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 238000000844 transformation Methods 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- JNEIFWYJFOEKIM-NUBCRITNSA-N (2r)-2-methylpyrrolidine;hydrochloride Chemical compound Cl.C[C@@H]1CCCN1 JNEIFWYJFOEKIM-NUBCRITNSA-N 0.000 description 2
- VQKIKHHXFHNXJT-SNAWJCMRSA-N (4E)-hept-4-en-2-one Chemical compound CC\C=C\CC(C)=O VQKIKHHXFHNXJT-SNAWJCMRSA-N 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- PXRXGHUTKHXUGF-UHFFFAOYSA-N 1,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1C PXRXGHUTKHXUGF-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- YHDZDIPQCVCIJS-UHFFFAOYSA-N 1-methyl-5-oxopyrrolidine-3-carboxylic acid Chemical compound CN1CC(C(O)=O)CC1=O YHDZDIPQCVCIJS-UHFFFAOYSA-N 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical group CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
- SBUXBHALPHVDFT-UHFFFAOYSA-N 1-methyltriazole-4-carboxylic acid Chemical compound CN1C=C(C(O)=O)N=N1 SBUXBHALPHVDFT-UHFFFAOYSA-N 0.000 description 2
- JLZVIWSFUPLSOR-UHFFFAOYSA-N 2,3-difluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1F JLZVIWSFUPLSOR-UHFFFAOYSA-N 0.000 description 2
- NJYBIFYEWYWYAN-UHFFFAOYSA-N 2,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1F NJYBIFYEWYWYAN-UHFFFAOYSA-N 0.000 description 2
- LBQMIAVIGLLBGW-UHFFFAOYSA-N 2,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1F LBQMIAVIGLLBGW-UHFFFAOYSA-N 0.000 description 2
- QRWZFUBHOQWUGH-UHFFFAOYSA-N 2,5-dimethylpyrazole-3-carboxylic acid Chemical compound CC=1C=C(C(O)=O)N(C)N=1 QRWZFUBHOQWUGH-UHFFFAOYSA-N 0.000 description 2
- ONOTYLMNTZNAQZ-UHFFFAOYSA-N 2,6-difluorobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1F ONOTYLMNTZNAQZ-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- YBHLETUAEBDXIP-UHFFFAOYSA-N 2-[6-[2-(2-methylpyrrolidin-1-yl)ethyl]naphthalen-2-yl]pyridazin-3-one Chemical compound CC1CCCN1CCC1=CC=C(C=C(C=C2)N3C(C=CC=N3)=O)C2=C1 YBHLETUAEBDXIP-UHFFFAOYSA-N 0.000 description 2
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
- FPENCTDAQQQKNY-UHFFFAOYSA-N 3,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1 FPENCTDAQQQKNY-UHFFFAOYSA-N 0.000 description 2
- GONAVIHGXFBTOZ-UHFFFAOYSA-N 3,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(F)=C1 GONAVIHGXFBTOZ-UHFFFAOYSA-N 0.000 description 2
- IJEUISLJVBUNRE-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C)=C1C(O)=O IJEUISLJVBUNRE-UHFFFAOYSA-N 0.000 description 2
- MQLBMCXXBLJWQO-LSDHHAIUSA-N 3-[4-[(2s)-2-methyl-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C([C@@H](C)CN1[C@@H](CCC1)C)OC(C=C1)=CC=C1C=1C=CC(=O)NN=1 MQLBMCXXBLJWQO-LSDHHAIUSA-N 0.000 description 2
- YATSWSAFQYEXPC-UHFFFAOYSA-N 4-(azetidine-1-carbonyl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(=O)N1CCC1 YATSWSAFQYEXPC-UHFFFAOYSA-N 0.000 description 2
- ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 description 2
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 description 2
- YPQYVVMLRSSTFW-OAHLLOKOSA-N 5,5-dimethyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1,4-dihydropyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2CC(C)(C)C(=O)NN=2)C=C1 YPQYVVMLRSSTFW-OAHLLOKOSA-N 0.000 description 2
- HBDLBTSITBUDIR-GOSISDBHSA-N 5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-pyridin-2-ylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)N(C=3N=CC=CC=3)N=C2)C=C1 HBDLBTSITBUDIR-GOSISDBHSA-N 0.000 description 2
- KAUQJMHLAFIZDU-UHFFFAOYSA-N 6-Hydroxy-2-naphthoic acid Chemical compound C1=C(O)C=CC2=CC(C(=O)O)=CC=C21 KAUQJMHLAFIZDU-UHFFFAOYSA-N 0.000 description 2
- 239000005725 8-Hydroxyquinoline Substances 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- 229910021120 PdC12 Inorganic materials 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000005431 alkyl carboxamide group Chemical group 0.000 description 2
- 125000005233 alkylalcohol group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 2
- 125000005432 dialkylcarboxamide group Chemical group 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000004995 haloalkylthio group Chemical group 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 231100000989 no adverse effect Toxicity 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 229960003540 oxyquinoline Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 description 2
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 2
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- ULNNAHSDFBDKQL-UHFFFAOYSA-N (2-methylpyrrolidin-1-yl)-[6-(1-propan-2-ylpiperidin-4-yl)oxynaphthalen-2-yl]methanone Chemical compound C1CN(C(C)C)CCC1OC1=CC=C(C=C(C=C2)C(=O)N3C(CCC3)C)C2=C1 ULNNAHSDFBDKQL-UHFFFAOYSA-N 0.000 description 1
- VLFBCYIJNJSNMO-UHFFFAOYSA-N (2-methylpyrrolidin-1-yl)-[6-(1-propan-2-ylpyrrolidin-3-yl)oxynaphthalen-2-yl]methanone Chemical compound C1N(C(C)C)CCC1OC1=CC=C(C=C(C=C2)C(=O)N3C(CCC3)C)C2=C1 VLFBCYIJNJSNMO-UHFFFAOYSA-N 0.000 description 1
- SZWZAJUTDGGRSA-UHFFFAOYSA-N (2-methylpyrrolidin-1-yl)-[6-[2-(1-methylpyrrolidin-2-yl)ethoxy]naphthalen-2-yl]methanone Chemical compound CC1CCCN1C(=O)C1=CC=C(C=C(OCCC2N(CCC2)C)C=C2)C2=C1 SZWZAJUTDGGRSA-UHFFFAOYSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- MXJUMDIOEIATKQ-VGAJERRHSA-N (2r)-4-methyl-2-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methylamino]pentan-1-ol Chemical compound CC(C)C[C@H](CO)NCC1=COC(C=2C=CC(OCCCN3C(CCC3)C)=CC=2)=N1 MXJUMDIOEIATKQ-VGAJERRHSA-N 0.000 description 1
- BAKHPYGIWRQPMS-QMMMGPOBSA-N (2s)-1-(3-chloropropyl)-2-methylpyrrolidine Chemical compound C[C@H]1CCCN1CCCCl BAKHPYGIWRQPMS-QMMMGPOBSA-N 0.000 description 1
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- JNEIFWYJFOEKIM-JEDNCBNOSA-N (2s)-2-methylpyrrolidine;hydrochloride Chemical compound Cl.C[C@H]1CCCN1 JNEIFWYJFOEKIM-JEDNCBNOSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- JKPOEUWWBDHLJM-UHFFFAOYSA-N (4-cyclopentylpiperazin-1-yl)-[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methanone Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(N=2)C(=O)N2CCN(CC2)C2CCCC2)C=C1 JKPOEUWWBDHLJM-UHFFFAOYSA-N 0.000 description 1
- QJGXEYKVUATUHS-FHZUCYEKSA-N (5s)-1-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]-5-(morpholin-4-ylmethyl)pyrrolidin-2-one Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3C(CC[C@H]3CN3CCOCC3)=O)N=2)C=C1 QJGXEYKVUATUHS-FHZUCYEKSA-N 0.000 description 1
- MAARRMBCEFVKNV-UHFFFAOYSA-N (6-bromonaphthalen-2-yl)methanol Chemical compound C1=C(Br)C=CC2=CC(CO)=CC=C21 MAARRMBCEFVKNV-UHFFFAOYSA-N 0.000 description 1
- UEPYMGHSTVXBBR-UHFFFAOYSA-N (6-hydroxynaphthalen-2-yl)-(2-methylpyrrolidin-1-yl)methanone Chemical compound CC1CCCN1C(=O)C1=CC=C(C=C(O)C=C2)C2=C1 UEPYMGHSTVXBBR-UHFFFAOYSA-N 0.000 description 1
- UEPYMGHSTVXBBR-LLVKDONJSA-N (6-hydroxynaphthalen-2-yl)-[(2r)-2-methylpyrrolidin-1-yl]methanone Chemical compound C[C@@H]1CCCN1C(=O)C1=CC=C(C=C(O)C=C2)C2=C1 UEPYMGHSTVXBBR-LLVKDONJSA-N 0.000 description 1
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 description 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
- VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical class C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
- JNIUWOAGHFYNFX-UHFFFAOYSA-N 1-(azepan-1-yl)-2-[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]ethanone Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CC(=O)N3CCCCCC3)N=2)C=C1 JNIUWOAGHFYNFX-UHFFFAOYSA-N 0.000 description 1
- OOGWMAIYWGZDRX-UHFFFAOYSA-N 1-[2-(6-bromonaphthalen-2-yl)ethyl]-2-methylpyrrolidine Chemical compound CC1CCCN1CCC1=CC=C(C=C(Br)C=C2)C2=C1 OOGWMAIYWGZDRX-UHFFFAOYSA-N 0.000 description 1
- UTOFVZDXQIZNEV-UHFFFAOYSA-N 1-[2-[4-[4-(azetidin-1-ylsulfonyl)phenyl]phenyl]ethyl]-2-methylpyrrolidine Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCC2)C=C1 UTOFVZDXQIZNEV-UHFFFAOYSA-N 0.000 description 1
- NRRFNKOLUDFTRI-UHFFFAOYSA-N 1-[2-[4-[4-(aziridin-1-ylsulfonyl)phenyl]phenyl]ethyl]-2-methylpyrrolidine Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CC2)C=C1 NRRFNKOLUDFTRI-UHFFFAOYSA-N 0.000 description 1
- FHWHVTPFLXCNAN-UHFFFAOYSA-N 1-[3-[[1-(2-methylpyrrolidin-1-yl)-2,3-dihydro-1h-inden-5-yl]oxy]propyl]azepane Chemical compound CC1CCCN1C1C2=CC=C(OCCCN3CCCCCC3)C=C2CC1 FHWHVTPFLXCNAN-UHFFFAOYSA-N 0.000 description 1
- OHHHDZVNWSQHRX-UHFFFAOYSA-N 1-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-3-(trifluoromethyl)-[1]benzofuro[3,2-c]pyrazole Chemical compound CC1CCCN1CCCOC1=CC=C(N2C=3C4=CC=CC=C4OC=3C(=N2)C(F)(F)F)C=C1 OHHHDZVNWSQHRX-UHFFFAOYSA-N 0.000 description 1
- MTEJPTWNCZVBCB-GOSISDBHSA-N 1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-5-phenyl-3-(trifluoromethyl)pyrazole Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(=CC(=N2)C(F)(F)F)C=2C=CC=CC=2)C=C1 MTEJPTWNCZVBCB-GOSISDBHSA-N 0.000 description 1
- DJIYYLVVVMSUAB-UHFFFAOYSA-N 1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidin-3-ol Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CC(O)CCC2)C=C1 DJIYYLVVVMSUAB-UHFFFAOYSA-N 0.000 description 1
- LJGLUGFCMXPVPW-UHFFFAOYSA-N 1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpyrrolidin-3-ol Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CC(O)CC2)C=C1 LJGLUGFCMXPVPW-UHFFFAOYSA-N 0.000 description 1
- WBGBHEOFCXFUCP-UHFFFAOYSA-N 1-[4-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperazin-1-yl]propan-1-one Chemical compound C1CN(C(=O)CC)CCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 WBGBHEOFCXFUCP-UHFFFAOYSA-N 0.000 description 1
- GYBIMJYZUHYUMC-UHFFFAOYSA-N 1-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]piperidin-2-one Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3C(CCCC3)=O)N=2)C=C1 GYBIMJYZUHYUMC-UHFFFAOYSA-N 0.000 description 1
- AFJUZMFLQFYZLM-UHFFFAOYSA-N 1-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]pyrrolidin-2-one Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3C(CCC3)=O)N=2)C=C1 AFJUZMFLQFYZLM-UHFFFAOYSA-N 0.000 description 1
- NHJPEEGMXXGEBF-UHFFFAOYSA-N 1-[[4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-thiazol-5-yl]methyl]pyrrolidin-2-one Chemical compound CC1CCCN1CCCOC1=CC=C(C=2SC(CN3C(CCC3)=O)=C(C)N=2)C=C1 NHJPEEGMXXGEBF-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- NXMXETCTWNXSFG-UHFFFAOYSA-N 1-methoxypropan-2-amine Chemical compound COCC(C)N NXMXETCTWNXSFG-UHFFFAOYSA-N 0.000 description 1
- NJLMTCGYPBTHBH-MRXNPFEDSA-N 1-methyl-4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridin-2-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)N(C)C=C2)C=C1 NJLMTCGYPBTHBH-MRXNPFEDSA-N 0.000 description 1
- WIGRVUWJNPVKPB-UHFFFAOYSA-N 1-methylpyrrolidin-1-ium;chloride Chemical compound Cl.CN1CCCC1 WIGRVUWJNPVKPB-UHFFFAOYSA-N 0.000 description 1
- VTDIWMPYBAVEDY-UHFFFAOYSA-N 1-propylpiperidine Chemical compound CCCN1CCCCC1 VTDIWMPYBAVEDY-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 1
- LJMZRBZETLXDSO-UHFFFAOYSA-N 1h-thieno[3,2-c]pyrazole Chemical compound N1N=CC2=C1C=CS2 LJMZRBZETLXDSO-UHFFFAOYSA-N 0.000 description 1
- FVBMQXFSNPPRRM-OAHLLOKOSA-N 2,6-dimethyl-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(=NN(C)C(=O)C=2)C)C=C1 FVBMQXFSNPPRRM-OAHLLOKOSA-N 0.000 description 1
- ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical group CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 1
- LBRODLJSFLEILM-MRXNPFEDSA-N 2-(2-fluoroethyl)-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NN(CCF)C(=O)C=C2)C=C1 LBRODLJSFLEILM-MRXNPFEDSA-N 0.000 description 1
- QBWTYVZNFJLATQ-MRXNPFEDSA-N 2-(2-hydroxyethyl)-6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NN(CCO)C(=O)C=C2)C=C1 QBWTYVZNFJLATQ-MRXNPFEDSA-N 0.000 description 1
- DLAXWULAMBVPFO-LJQANCHMSA-N 2-(3-methylpyridin-2-yl)-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)N(C=3C(=CC=CN=3)C)N=C2)C=C1 DLAXWULAMBVPFO-LJQANCHMSA-N 0.000 description 1
- ZKBYTERDWDMGKM-LJQANCHMSA-N 2-(6-methylpyridin-2-yl)-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)N(C=3N=C(C)C=CC=3)N=C2)C=C1 ZKBYTERDWDMGKM-LJQANCHMSA-N 0.000 description 1
- XJXVTWVCPPFVSK-QGZVFWFLSA-N 2-(methoxymethyl)-5-[2-methyl-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound O=C1N(COC)N=CC(C=2C(=CC(OCCCN3[C@@H](CCC3)C)=CC=2)C)=C1 XJXVTWVCPPFVSK-QGZVFWFLSA-N 0.000 description 1
- MURCULVYVOMYIO-MRXNPFEDSA-N 2-(methoxymethyl)-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound O=C1N(COC)N=CC(C=2C=CC(OCCCN3[C@@H](CCC3)C)=CC=2)=C1 MURCULVYVOMYIO-MRXNPFEDSA-N 0.000 description 1
- XQUJSUWRBCSBFV-UHFFFAOYSA-N 2-[1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidin-4-yl]ethyl propanoate Chemical compound C1CC(CCOC(=O)CC)CCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 XQUJSUWRBCSBFV-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- AFEMXVRMEKINAU-CQSZACIVSA-N 2-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]-5-(6-oxo-1h-pyridazin-3-yl)benzonitrile Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=C1C#N AFEMXVRMEKINAU-CQSZACIVSA-N 0.000 description 1
- KCIYWCPQEYZGEN-UHFFFAOYSA-N 2-[3-chloro-4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-4-(piperidin-1-ylmethyl)-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3CCCCC3)N=2)C=C1Cl KCIYWCPQEYZGEN-UHFFFAOYSA-N 0.000 description 1
- GILKBQCOPIMAEM-UHFFFAOYSA-N 2-[3-fluoro-4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-4-(piperidin-1-ylmethyl)-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3CCCCC3)N=2)C=C1F GILKBQCOPIMAEM-UHFFFAOYSA-N 0.000 description 1
- ADTARRIQWGUIIA-BULQSVBWSA-N 2-[4-[(2s)-2-methyl-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-3,4-diazabicyclo[4.1.0]hept-2-en-5-one Chemical compound C([C@@H](COC=1C=CC(=CC=1)C=1C2CC2C(=O)NN=1)C)N1CCC[C@H]1C ADTARRIQWGUIIA-BULQSVBWSA-N 0.000 description 1
- JTSICMHLVMRZHE-UHFFFAOYSA-N 2-[4-[2-(2-methylpyrrolidin-1-yl)ethoxy]phenyl]-4-(2-piperidin-1-ylethyl)-1,3-oxazole Chemical compound CC1CCCN1CCOC1=CC=C(C=2OC=C(CCN3CCCCC3)N=2)C=C1 JTSICMHLVMRZHE-UHFFFAOYSA-N 0.000 description 1
- WOBFYDQOWISFGB-UHFFFAOYSA-N 2-[4-[2-(2-methylpyrrolidin-1-yl)ethoxy]phenyl]-4-(piperidin-1-ylmethyl)-1,3-oxazole Chemical compound CC1CCCN1CCOC1=CC=C(C=2OC=C(CN3CCCCC3)N=2)C=C1 WOBFYDQOWISFGB-UHFFFAOYSA-N 0.000 description 1
- TVQOPOFOVDRXDY-UHFFFAOYSA-N 2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-thiazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2SC=CN=2)C=C1 TVQOPOFOVDRXDY-UHFFFAOYSA-N 0.000 description 1
- OPRUZIPKIZFVAH-UHFFFAOYSA-N 2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-4-(1,2,4-triazol-1-ylmethyl)-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3N=CN=C3)N=2)C=C1 OPRUZIPKIZFVAH-UHFFFAOYSA-N 0.000 description 1
- VQMORLQXGCQWCH-UHFFFAOYSA-N 2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-4-(2-piperidin-1-ylethyl)-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CCN3CCCCC3)N=2)C=C1 VQMORLQXGCQWCH-UHFFFAOYSA-N 0.000 description 1
- FFQSFTFDGXJPNB-UHFFFAOYSA-N 2-[4-[3-(4-methylpiperidin-1-yl)propoxy]phenyl]-4-[(2-methylpyrrolidin-1-yl)methyl]-1,3-oxazole Chemical compound CC1CCCN1CC1=COC(C=2C=CC(OCCCN3CCC(C)CC3)=CC=2)=N1 FFQSFTFDGXJPNB-UHFFFAOYSA-N 0.000 description 1
- CZICCXAAPOYXFV-RWBZWWBESA-N 2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-3,4-diazabicyclo[4.2.0]oct-2-en-5-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C3CCC3C(=O)NN=2)C=C1 CZICCXAAPOYXFV-RWBZWWBESA-N 0.000 description 1
- VRXXUAQLNCEEKD-LJQANCHMSA-N 2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-phenylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(C=CC(=N2)C=2C=CC=CC=2)=O)C=C1 VRXXUAQLNCEEKD-LJQANCHMSA-N 0.000 description 1
- PARRMVNWSHSWDQ-GOSISDBHSA-N 2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6-pyridin-3-ylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(C=CC(=N2)C=2C=NC=CC=2)=O)C=C1 PARRMVNWSHSWDQ-GOSISDBHSA-N 0.000 description 1
- NWGZYITUWLUUNZ-QGZVFWFLSA-N 2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]phthalazin-1-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(C3=CC=CC=C3C=N2)=O)C=C1 NWGZYITUWLUUNZ-QGZVFWFLSA-N 0.000 description 1
- LVMYXFKLEZRGEU-UHFFFAOYSA-N 2-[4-[4-(2-methylpiperidin-1-yl)butoxy]phenyl]-4-[(2-methylpyrrolidin-1-yl)methyl]-1,3-oxazole Chemical compound CC1CCCN1CC1=COC(C=2C=CC(OCCCCN3C(CCCC3)C)=CC=2)=N1 LVMYXFKLEZRGEU-UHFFFAOYSA-N 0.000 description 1
- ZHLYRLQPXCWIGE-UHFFFAOYSA-N 2-[4-[4-(azepan-1-yl)butoxy]phenyl]-4-[(2-methylpyrrolidin-1-yl)methyl]-1,3-oxazole Chemical compound CC1CCCN1CC1=COC(C=2C=CC(OCCCCN3CCCCCC3)=CC=2)=N1 ZHLYRLQPXCWIGE-UHFFFAOYSA-N 0.000 description 1
- VXNUKDKPQFLYQI-UHFFFAOYSA-N 2-[6-(2-hydroxyethyl)naphthalen-2-yl]pyridazin-3-one Chemical compound C1=CC2=CC(CCO)=CC=C2C=C1N1N=CC=CC1=O VXNUKDKPQFLYQI-UHFFFAOYSA-N 0.000 description 1
- WQWLKFXVOHIYHD-UHFFFAOYSA-N 2-[acetyl-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]ethyl acetate Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N(CCOC(C)=O)C(C)=O)C=C1 WQWLKFXVOHIYHD-UHFFFAOYSA-N 0.000 description 1
- ALRJKWXWOUPSJY-UHFFFAOYSA-N 2-[methyl-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]ethyl propanoate Chemical compound C1=CC(S(=O)(=O)N(C)CCOC(=O)CC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 ALRJKWXWOUPSJY-UHFFFAOYSA-N 0.000 description 1
- BNGPVKSKKYIJCR-UHFFFAOYSA-N 2-chloro-1,3-dimethylimidazolidine;hydrochloride Chemical compound [Cl-].CN1CC[NH+](C)C1Cl BNGPVKSKKYIJCR-UHFFFAOYSA-N 0.000 description 1
- DPGSPRJLAZGUBQ-UHFFFAOYSA-N 2-ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(C=C)OC1(C)C DPGSPRJLAZGUBQ-UHFFFAOYSA-N 0.000 description 1
- QJAUWCVZCCDKQC-OAHLLOKOSA-N 2-methyl-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)N(C)N=C2)C=C1 QJAUWCVZCCDKQC-OAHLLOKOSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- VHKZHZYOGPESQF-HZPDHXFCSA-N 2-methyl-6-[4-[(2r)-2-methyl-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C([C@H](C)CN1[C@@H](CCC1)C)OC(C=C1)=CC=C1C=1C=CC(=O)N(C)N=1 VHKZHZYOGPESQF-HZPDHXFCSA-N 0.000 description 1
- DQRNZHILJYYHDA-UHFFFAOYSA-N 2-methyl-n-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]tetrazol-5-amine Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CNC3=NN(C)N=N3)N=2)C=C1 DQRNZHILJYYHDA-UHFFFAOYSA-N 0.000 description 1
- ZPOFDAAHFMDKCQ-UHFFFAOYSA-N 2-tert-butyl-4-[4-(3-chloropropoxy)phenyl]-3-oxopiperazine-1-carboxylic acid Chemical compound O=C1C(C(C)(C)C)N(C(O)=O)CCN1C1=CC=C(OCCCCl)C=C1 ZPOFDAAHFMDKCQ-UHFFFAOYSA-N 0.000 description 1
- FLPWWXBAXVHEAF-UHFFFAOYSA-N 3,5-dimethyl-4-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylmorpholine Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2C(COCC2C)C)C=C1 FLPWWXBAXVHEAF-UHFFFAOYSA-N 0.000 description 1
- RLWRGDZXZWQERU-UHFFFAOYSA-N 3-(methoxymethyl)-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidine Chemical compound C1C(COC)CCCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 RLWRGDZXZWQERU-UHFFFAOYSA-N 0.000 description 1
- FGDCRCAFBZISKP-QVKFZJNVSA-N 3-[(6r)-6-[(2r)-2-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl]benzamide Chemical compound C[C@@H]1CCCN1[C@H]1CC2=CC=C(C=3C=C(C=CC=3)C(N)=O)C=C2CC1 FGDCRCAFBZISKP-QVKFZJNVSA-N 0.000 description 1
- OONJZWLCIBZROJ-FOIQADDNSA-N 3-[(6r)-6-[(2r)-2-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl]pyridine Chemical compound C[C@@H]1CCCN1[C@H]1CC2=CC=C(C=3C=NC=CC=3)C=C2CC1 OONJZWLCIBZROJ-FOIQADDNSA-N 0.000 description 1
- FGDCRCAFBZISKP-VFNWGFHPSA-N 3-[(6s)-6-[(2r)-2-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl]benzamide Chemical compound C[C@@H]1CCCN1[C@@H]1CC2=CC=C(C=3C=C(C=CC=3)C(N)=O)C=C2CC1 FGDCRCAFBZISKP-VFNWGFHPSA-N 0.000 description 1
- OONJZWLCIBZROJ-QRWLVFNGSA-N 3-[(6s)-6-[(2r)-2-methylpyrrolidin-1-yl]-5,6,7,8-tetrahydronaphthalen-2-yl]pyridine Chemical compound C[C@@H]1CCCN1[C@@H]1CC2=CC=C(C=3C=NC=CC=3)C=C2CC1 OONJZWLCIBZROJ-QRWLVFNGSA-N 0.000 description 1
- WGBQXIANYLTAHQ-CYBMUJFWSA-N 3-[2-fluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C(F)=C1 WGBQXIANYLTAHQ-CYBMUJFWSA-N 0.000 description 1
- VSCYFWPBZANBSJ-CQSZACIVSA-N 3-[2-methoxy-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C=1C=C(C2=NNC(=O)C=C2)C(OC)=CC=1OCCCN1CCC[C@H]1C VSCYFWPBZANBSJ-CQSZACIVSA-N 0.000 description 1
- WPIHJKLZPYZLQY-GFCCVEGCSA-N 3-[3,5-dibromo-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=C(Br)C=C(C2=NNC(=O)C=C2)C=C1Br WPIHJKLZPYZLQY-GFCCVEGCSA-N 0.000 description 1
- CVWBBUYUSWNUBE-GFCCVEGCSA-N 3-[3,5-difluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=C(F)C=C(C2=NNC(=O)C=C2)C=C1F CVWBBUYUSWNUBE-GFCCVEGCSA-N 0.000 description 1
- KXBFYMJHAIYKEO-GFCCVEGCSA-N 3-[3,5-difluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=C(F)C=C(C=2CCC(=O)NN=2)C=C1F KXBFYMJHAIYKEO-GFCCVEGCSA-N 0.000 description 1
- PRRSHLNBJKWQGK-CYBMUJFWSA-N 3-[3-fluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=C1F PRRSHLNBJKWQGK-CYBMUJFWSA-N 0.000 description 1
- AJVJWYWJYHVAEF-CYBMUJFWSA-N 3-[3-fluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2CCC(=O)NN=2)C=C1F AJVJWYWJYHVAEF-CYBMUJFWSA-N 0.000 description 1
- CNZWZBXBLOLCGI-CQSZACIVSA-N 3-[3-methoxy-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound COC1=CC(C2=NNC(=O)C=C2)=CC=C1OCCCN1CCC[C@H]1C CNZWZBXBLOLCGI-CQSZACIVSA-N 0.000 description 1
- SZIITWTXIFGKTM-UKRRQHHQSA-N 3-[4-[(2r)-2-hydroxy-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1C[C@@H](O)COC1=CC=C(C2=NNC(=O)C=C2)C=C1 SZIITWTXIFGKTM-UKRRQHHQSA-N 0.000 description 1
- SZIITWTXIFGKTM-HIFRSBDPSA-N 3-[4-[(2s)-2-hydroxy-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1C[C@H](O)COC1=CC=C(C2=NNC(=O)C=C2)C=C1 SZIITWTXIFGKTM-HIFRSBDPSA-N 0.000 description 1
- SZIITWTXIFGKTM-AFYYWNPRSA-N 3-[4-[2-hydroxy-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CC(O)COC1=CC=C(C2=NNC(=O)C=C2)C=C1 SZIITWTXIFGKTM-AFYYWNPRSA-N 0.000 description 1
- PXYUUQSMMYUYSP-CQSZACIVSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2CCC(=O)NN=2)C=C1 PXYUUQSMMYUYSP-CQSZACIVSA-N 0.000 description 1
- CITBWOHPECEAHH-DIAVIDTQSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4-pyridin-2-yl-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(CC(=O)NN=2)C=2N=CC=CC=2)C=C1 CITBWOHPECEAHH-DIAVIDTQSA-N 0.000 description 1
- IUXXMWRCYIUEAV-QGZVFWFLSA-N 3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-5-pyridin-2-yl-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C(C=3N=CC=CC=3)=C2)C=C1 IUXXMWRCYIUEAV-QGZVFWFLSA-N 0.000 description 1
- IOJNMGYMVOAFSY-CYBMUJFWSA-N 3-[6-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]pyridin-3-yl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C=C2)C=N1 IOJNMGYMVOAFSY-CYBMUJFWSA-N 0.000 description 1
- CJXDYDZOCQJOHH-UHFFFAOYSA-N 3-methoxy-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidine Chemical compound C1C(OC)CCCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 CJXDYDZOCQJOHH-UHFFFAOYSA-N 0.000 description 1
- CYMMIBYZLYQCNI-MRXNPFEDSA-N 3-methyl-1-[3-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6,7-dihydro-5h-cyclopenta[d]pyridazin-4-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=CC(C=2C=3CCCC=3C(=O)N(C)N=2)=C1 CYMMIBYZLYQCNI-MRXNPFEDSA-N 0.000 description 1
- UWTSXZWYSKCDHZ-LJQANCHMSA-N 3-methyl-1-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4,5-dihydrobenzo[g]indazole Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C=3C4=CC=CC=C4CCC=3C(C)=N2)C=C1 UWTSXZWYSKCDHZ-LJQANCHMSA-N 0.000 description 1
- OVNSLCAMMBQZNV-CQSZACIVSA-N 3-methyl-4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(=NNC(=O)C=2)C)C=C1 OVNSLCAMMBQZNV-CQSZACIVSA-N 0.000 description 1
- XYYPREBRWZRCHI-CYBMUJFWSA-N 3-methyl-4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-6h-[1,2]oxazolo[3,4-d]pyridazin-7-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C3=C(C)ON=C3C(=O)NN=2)C=C1 XYYPREBRWZRCHI-CYBMUJFWSA-N 0.000 description 1
- IOBNDNZQHVJSNG-OAHLLOKOSA-N 4,4-dimethyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1,5-dihydropyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(CC(=O)NN=2)(C)C)C=C1 IOBNDNZQHVJSNG-OAHLLOKOSA-N 0.000 description 1
- OAEQWHHLMLBHKM-UHFFFAOYSA-N 4-(2-ethoxyethyl)-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidine Chemical compound C1CC(CCOCC)CCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 OAEQWHHLMLBHKM-UHFFFAOYSA-N 0.000 description 1
- CZXCABIHBSXRSA-UHFFFAOYSA-N 4-(2-methoxyethyl)-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidine Chemical compound C1CC(CCOC)CCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 CZXCABIHBSXRSA-UHFFFAOYSA-N 0.000 description 1
- KDXBUGVEBHNALP-UHFFFAOYSA-N 4-(ethoxymethyl)-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidine Chemical compound C1CC(COCC)CCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 KDXBUGVEBHNALP-UHFFFAOYSA-N 0.000 description 1
- NKLYAXCOQOLLCQ-UHFFFAOYSA-N 4-(methoxymethyl)-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidine Chemical compound C1CC(COC)CCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 NKLYAXCOQOLLCQ-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- NBRAOZWEXKSBOO-UHFFFAOYSA-N 4-[(2-methylimidazol-1-yl)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3C(=NC=C3)C)N=2)C=C1 NBRAOZWEXKSBOO-UHFFFAOYSA-N 0.000 description 1
- MKRMKSJGXZFWNE-UHFFFAOYSA-N 4-[(2-methylpiperidin-1-yl)methyl]-2-[4-[3-(4-propan-2-ylpiperazin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound C1CN(C(C)C)CCN1CCCOC1=CC=C(C=2OC=C(CN3C(CCCC3)C)N=2)C=C1 MKRMKSJGXZFWNE-UHFFFAOYSA-N 0.000 description 1
- LTONYMMLXUDUCO-UHFFFAOYSA-N 4-[(2-methylpyrrolidin-1-yl)methyl]-2-[4-[2-[4-(2-pyrrolidin-1-ylethyl)piperazin-1-yl]ethoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CC1=COC(C=2C=CC(OCCN3CCN(CCN4CCCC4)CC3)=CC=2)=N1 LTONYMMLXUDUCO-UHFFFAOYSA-N 0.000 description 1
- BKMNYNXNJWWTNP-UHFFFAOYSA-N 4-[(2-methylpyrrolidin-1-yl)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3C(CCC3)C)N=2)C=C1 BKMNYNXNJWWTNP-UHFFFAOYSA-N 0.000 description 1
- YDDQCXAPCITSEB-TUXUZCGSSA-N 4-[(2-methylpyrrolidin-1-yl)methyl]-2-[4-[3-[(2s)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CC1=COC(C=2C=CC(OCCCN3[C@@H](CCC3)CN3CCCC3)=CC=2)=N1 YDDQCXAPCITSEB-TUXUZCGSSA-N 0.000 description 1
- OORBCVVMCCCLCX-UHFFFAOYSA-N 4-[(4,4-difluoropiperidin-1-yl)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3CCC(F)(F)CC3)N=2)C=C1 OORBCVVMCCCLCX-UHFFFAOYSA-N 0.000 description 1
- LKIVJUICEOCHOA-UHFFFAOYSA-N 4-[(4-benzylpiperidin-1-yl)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3CCC(CC=4C=CC=CC=4)CC3)N=2)C=C1 LKIVJUICEOCHOA-UHFFFAOYSA-N 0.000 description 1
- ANFLESLGSBVVBI-UHFFFAOYSA-N 4-[(7,8-dimethyl-1-azaspiro[4.4]nonan-1-yl)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-thiazole Chemical compound C1C(C)C(C)CC11N(CC=2N=C(SC=2)C=2C=CC(OCCCN3C(CCC3)C)=CC=2)CCC1 ANFLESLGSBVVBI-UHFFFAOYSA-N 0.000 description 1
- MGAOIHKFYJUIQV-UHFFFAOYSA-N 4-[(benzylamino)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole-5-carboxylic acid Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC(=C(CNCC=3C=CC=CC=3)N=2)C(O)=O)C=C1 MGAOIHKFYJUIQV-UHFFFAOYSA-N 0.000 description 1
- LGOQRBKZKBVQAV-OAHLLOKOSA-N 4-[2-methyl-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)NN=C2)C(C)=C1 LGOQRBKZKBVQAV-OAHLLOKOSA-N 0.000 description 1
- JIIBJQIKVFEDKB-GFCCVEGCSA-N 4-[3,5-dibromo-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=C(Br)C=C(C2=CC(=O)NN=C2)C=C1Br JIIBJQIKVFEDKB-GFCCVEGCSA-N 0.000 description 1
- LIEAKONJVOLXFZ-HUUCEWRRSA-N 4-[4-[(2r)-2-methyl-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C([C@H](C)CN1[C@@H](CCC1)C)OC(C=C1)=CC=C1C=1C=NNC(=O)C=1 LIEAKONJVOLXFZ-HUUCEWRRSA-N 0.000 description 1
- LIEAKONJVOLXFZ-LSDHHAIUSA-N 4-[4-[(2s)-2-methyl-3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C([C@@H](C)CN1[C@@H](CCC1)C)OC(C=C1)=CC=C1C=1C=NNC(=O)C=1 LIEAKONJVOLXFZ-LSDHHAIUSA-N 0.000 description 1
- SGXBDTBGPKQMMY-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(2-phenoxyethyl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCCOC=2C=CC=CC=2)C=C1 SGXBDTBGPKQMMY-UHFFFAOYSA-N 0.000 description 1
- HGGKXVUGCGTWOV-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(2-phenylethyl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCCC=2C=CC=CC=2)C=C1 HGGKXVUGCGTWOV-UHFFFAOYSA-N 0.000 description 1
- MFEHXBMUMVTLGM-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(2-propan-2-yloxyethyl)benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCOC(C)C)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 MFEHXBMUMVTLGM-UHFFFAOYSA-N 0.000 description 1
- UGQLSCQODWXECY-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(3-phenylpropyl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCCCC=2C=CC=CC=2)C=C1 UGQLSCQODWXECY-UHFFFAOYSA-N 0.000 description 1
- RRAGUTZCGCIMCD-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(oxan-4-yl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC2CCOCC2)C=C1 RRAGUTZCGCIMCD-UHFFFAOYSA-N 0.000 description 1
- ZPDFUHYGJHQXCU-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(oxan-4-ylmethyl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC2CCOCC2)C=C1 ZPDFUHYGJHQXCU-UHFFFAOYSA-N 0.000 description 1
- ZGOCUSARZBRNRQ-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(pyridin-2-ylmethyl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2N=CC=CC=2)C=C1 ZGOCUSARZBRNRQ-UHFFFAOYSA-N 0.000 description 1
- OCIPCWTVWGKYNX-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(pyridin-3-ylmethyl)benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2C=NC=CC=2)C=C1 OCIPCWTVWGKYNX-UHFFFAOYSA-N 0.000 description 1
- GFVHSUSDHYYGAK-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-[2-(2-oxoimidazolidin-1-yl)ethyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCCN2C(NCC2)=O)C=C1 GFVHSUSDHYYGAK-UHFFFAOYSA-N 0.000 description 1
- ZKZIRWPTHHTCTI-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-[3-(2-oxopyrrolidin-1-yl)propyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCCCN2C(CCC2)=O)C=C1 ZKZIRWPTHHTCTI-UHFFFAOYSA-N 0.000 description 1
- YXURDWGSQHJHOK-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-[[4-(trifluoromethoxy)phenyl]methyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2C=CC(OC(F)(F)F)=CC=2)C=C1 YXURDWGSQHJHOK-UHFFFAOYSA-N 0.000 description 1
- RFAXDYWZHZWHAW-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-phenylbenzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC=CC=2)C=C1 RFAXDYWZHZWHAW-UHFFFAOYSA-N 0.000 description 1
- WLCWEBJKGPIJRI-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC(C)C)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 WLCWEBJKGPIJRI-UHFFFAOYSA-N 0.000 description 1
- ZIIXOXVBEACGII-UHFFFAOYSA-N 4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(N)(=O)=O)C=C1 ZIIXOXVBEACGII-UHFFFAOYSA-N 0.000 description 1
- DNVBBWNTRFFIHW-CQSZACIVSA-N 4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)NN=C2)C=C1 DNVBBWNTRFFIHW-CQSZACIVSA-N 0.000 description 1
- DSOCNSKXJFUCKY-VNCLNFNDSA-N 4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2,4a,5,6,7,7a-hexahydrocyclopenta[d]pyridazin-1-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C3CCCC3C(=O)NN=2)C=C1 DSOCNSKXJFUCKY-VNCLNFNDSA-N 0.000 description 1
- IZNDREQWHAUAMX-UHFFFAOYSA-N 4-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylmorpholine Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCOCC2)C=C1 IZNDREQWHAUAMX-UHFFFAOYSA-N 0.000 description 1
- UDXGLACYKPNKKG-UHFFFAOYSA-N 4-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperazin-2-one Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CC(=O)NCC2)C=C1 UDXGLACYKPNKKG-UHFFFAOYSA-N 0.000 description 1
- YEWASCRBETZGFV-TUXUZCGSSA-N 4-[[(2s)-1-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]pyrrolidin-2-yl]methyl]morpholine Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3[C@@H](CCC3)CN3CCOCC3)N=2)C=C1 YEWASCRBETZGFV-TUXUZCGSSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- NNWGLWSBNAYSRF-YUWPFLFCSA-N 4-[[(4ar,8as)-3,4,4a,5,6,7,8,8a-octahydro-1h-isoquinolin-2-yl]methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CN3C[C@H]4CCCC[C@@H]4CC3)N=2)C=C1 NNWGLWSBNAYSRF-YUWPFLFCSA-N 0.000 description 1
- FEBQLWBPGQAPHE-OAHLLOKOSA-N 4-ethyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound CCC1=CC(=O)NN=C1C(C=C1)=CC=C1OCCCN1[C@H](C)CCC1 FEBQLWBPGQAPHE-OAHLLOKOSA-N 0.000 description 1
- QFWKZYMWFOWKMN-MRXNPFEDSA-N 4-methoxy-2-(methoxymethyl)-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound O=C1N(COC)N=CC(C=2C=CC(OCCCN3[C@@H](CCC3)C)=CC=2)=C1OC QFWKZYMWFOWKMN-MRXNPFEDSA-N 0.000 description 1
- GIILJVCOKXTBKH-CQSZACIVSA-N 4-methoxy-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C1=NNC(=O)C(C=2C=CC(OCCCN3[C@@H](CCC3)C)=CC=2)=C1OC GIILJVCOKXTBKH-CQSZACIVSA-N 0.000 description 1
- LGNDCEVHWBKYHG-UHFFFAOYSA-N 4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-thiazole-5-carboxylic acid Chemical compound CC1CCCN1CCCOC1=CC=C(C=2SC(=C(C)N=2)C(O)=O)C=C1 LGNDCEVHWBKYHG-UHFFFAOYSA-N 0.000 description 1
- REOJELNRUGHANJ-OAHLLOKOSA-N 4-methyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(=CC(=O)NN=2)C)C=C1 REOJELNRUGHANJ-OAHLLOKOSA-N 0.000 description 1
- FIIDVVUUWRJXLF-UHFFFAOYSA-N 4-phenylmethoxyaniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC=C1 FIIDVVUUWRJXLF-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- CTTXKQLIKRECBX-UHFFFAOYSA-N 5-[(4-cyclopentylpiperazin-1-yl)methyl]-4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC(CN3CCN(CC3)C3CCCC3)=C(C)N=2)C=C1 CTTXKQLIKRECBX-UHFFFAOYSA-N 0.000 description 1
- SRWDXYXZNVIWLX-QGZVFWFLSA-N 5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-propan-2-ylpyridazin-3-one Chemical compound O=C1N(C(C)C)N=CC(C=2C=CC(OCCCN3[C@@H](CCC3)C)=CC=2)=C1 SRWDXYXZNVIWLX-QGZVFWFLSA-N 0.000 description 1
- HBDLBTSITBUDIR-SFHVURJKSA-N 5-[4-[3-[(2s)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-pyridin-2-ylpyridazin-3-one Chemical compound C[C@H]1CCCN1CCCOC1=CC=C(C2=CC(=O)N(C=3N=CC=CC=3)N=C2)C=C1 HBDLBTSITBUDIR-SFHVURJKSA-N 0.000 description 1
- SOFLHSZGYGTBLR-MRXNPFEDSA-N 5-methoxy-2-(methoxymethyl)-4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound O=C1N(COC)N=CC(OC)=C1C(C=C1)=CC=C1OCCCN1[C@H](C)CCC1 SOFLHSZGYGTBLR-MRXNPFEDSA-N 0.000 description 1
- DTMJRGRXYMQQFI-OAHLLOKOSA-N 5-methyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NNC(=O)C(C)=C2)C=C1 DTMJRGRXYMQQFI-OAHLLOKOSA-N 0.000 description 1
- JRROSJDFFYPDNV-YSSOQSIOSA-N 5-methyl-3-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2CC(C)C(=O)NN=2)C=C1 JRROSJDFFYPDNV-YSSOQSIOSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- YNVCMSXVHXXVJI-CYBMUJFWSA-N 6-[3,5-difluoro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-methylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=C(F)C=C(C2=NN(C)C(=O)C=C2)C=C1F YNVCMSXVHXXVJI-CYBMUJFWSA-N 0.000 description 1
- FKZPHHNJWMTMNN-CQSZACIVSA-N 6-[3-chloro-4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-methylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NN(C)C(=O)C=C2)C=C1Cl FKZPHHNJWMTMNN-CQSZACIVSA-N 0.000 description 1
- AUEHJIRPPASYIB-OAHLLOKOSA-N 6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-(2,2,2-trifluoroethyl)-4,5-dihydropyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2CCC(=O)N(CC(F)(F)F)N=2)C=C1 AUEHJIRPPASYIB-OAHLLOKOSA-N 0.000 description 1
- LIGQMVRHFOCWBV-OAHLLOKOSA-N 6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-(2,2,2-trifluoroethyl)pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NN(CC(F)(F)F)C(=O)C=C2)C=C1 LIGQMVRHFOCWBV-OAHLLOKOSA-N 0.000 description 1
- LPOASHGXLCAYTN-GOSISDBHSA-N 6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-pyridin-2-yl-4,5-dihydropyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2CCC(=O)N(N=2)C=2N=CC=CC=2)C=C1 LPOASHGXLCAYTN-GOSISDBHSA-N 0.000 description 1
- BLZQWQXNRGJXFS-GOSISDBHSA-N 6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-pyridin-2-ylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NN(C(=O)C=C2)C=2N=CC=CC=2)C=C1 BLZQWQXNRGJXFS-GOSISDBHSA-N 0.000 description 1
- JFHYZQNXNHZARY-QGZVFWFLSA-N 6-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-pyrimidin-2-ylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C2=NN(C(=O)C=C2)C=2N=CC=CN=2)C=C1 JFHYZQNXNHZARY-QGZVFWFLSA-N 0.000 description 1
- NPMCAVBMOTZUPD-UHFFFAOYSA-N 6-bromonaphthalene-2-carboxylic acid Chemical compound C1=C(Br)C=CC2=CC(C(=O)O)=CC=C21 NPMCAVBMOTZUPD-UHFFFAOYSA-N 0.000 description 1
- GLBASUMNZKAODE-MRXNPFEDSA-N 6-cyclopropyl-2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(C=CC(=N2)C2CC2)=O)C=C1 GLBASUMNZKAODE-MRXNPFEDSA-N 0.000 description 1
- DACDBRYFJUJEAA-LJQANCHMSA-N 6-methyl-2-(3-methylpyridin-2-yl)-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(=NN(C(=O)C=2)C=2C(=CC=CN=2)C)C)C=C1 DACDBRYFJUJEAA-LJQANCHMSA-N 0.000 description 1
- XJZOUNXUYKNAPM-MRXNPFEDSA-N 6-methyl-2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(C=CC(C)=N2)=O)C=C1 XJZOUNXUYKNAPM-MRXNPFEDSA-N 0.000 description 1
- ZROXYPDPKXBHHW-GOSISDBHSA-N 6-methyl-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-pyridin-2-ylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(=NN(C(=O)C=2)C=2N=CC=CC=2)C)C=C1 ZROXYPDPKXBHHW-GOSISDBHSA-N 0.000 description 1
- ZQDOWOVAAAKHRL-QGZVFWFLSA-N 6-methyl-5-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-2-thiophen-3-ylpyridazin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2C(=NN(C(=O)C=2)C2=CSC=C2)C)C=C1 ZQDOWOVAAAKHRL-QGZVFWFLSA-N 0.000 description 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
- VVCUOMJCOUZPMM-UHFFFAOYSA-N 7-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-3,4-dihydro-2h-5,1$l^{6},2-benzoxathiazepine 1,1-dioxide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=C3C(S(NCCO3)(=O)=O)=CC=2)C=C1 VVCUOMJCOUZPMM-UHFFFAOYSA-N 0.000 description 1
- LUOZEWPJSYBORW-UHFFFAOYSA-N 7-methylquinolin-8-ol Chemical compound C1=CC=NC2=C(O)C(C)=CC=C21 LUOZEWPJSYBORW-UHFFFAOYSA-N 0.000 description 1
- OKPSVYHYNXVYED-UHFFFAOYSA-N 7-propylquinolin-8-ol Chemical compound C1=CC=NC2=C(O)C(CCC)=CC=C21 OKPSVYHYNXVYED-UHFFFAOYSA-N 0.000 description 1
- SDGOJXHIOGBNPR-UHFFFAOYSA-N 8-[3-(2-methylpyrrolidin-1-yl)propoxy]-4,4a,5,6-tetrahydro-2h-benzo[h]cinnolin-3-one Chemical compound CC1CCCN1CCCOC1=CC=C(C=2C(CC(=O)NN=2)CC2)C2=C1 SDGOJXHIOGBNPR-UHFFFAOYSA-N 0.000 description 1
- QBTUTPWIRYNKEB-CQSZACIVSA-N 8-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]-5,6-dihydro-2h-benzo[h]cinnolin-3-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C2C3=NNC(=O)C=C3CCC2=C1 QBTUTPWIRYNKEB-CQSZACIVSA-N 0.000 description 1
- FUSIKFQZDFZEIR-CQSZACIVSA-N 8-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]-5,6-dihydro-3h-benzo[f]cinnolin-2-one Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C2C3=CC(=O)NN=C3CCC2=C1 FUSIKFQZDFZEIR-CQSZACIVSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 125000006847 BOC protecting group Chemical group 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 241000907681 Morpho Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- PVCJKHHOXFKFRP-UHFFFAOYSA-N N-acetylethanolamine Chemical compound CC(=O)NCCO PVCJKHHOXFKFRP-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910010066 TiC14 Inorganic materials 0.000 description 1
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- DPHCVKTYEZTCGI-UHFFFAOYSA-N [1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidin-2-yl]methanol Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2C(CCCC2)CO)C=C1 DPHCVKTYEZTCGI-UHFFFAOYSA-N 0.000 description 1
- SDGXQKSCPBQFKH-UHFFFAOYSA-N [1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidin-3-yl]methanol Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CC(CO)CCC2)C=C1 SDGXQKSCPBQFKH-UHFFFAOYSA-N 0.000 description 1
- LPDOMUVYEQYJCK-UHFFFAOYSA-N [1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpiperidin-4-yl]methanol Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCC(CO)CC2)C=C1 LPDOMUVYEQYJCK-UHFFFAOYSA-N 0.000 description 1
- LCKXFJATMXIQEG-UHFFFAOYSA-N [1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpyrrolidin-2-yl]methanol Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N2C(CCC2)CO)C=C1 LCKXFJATMXIQEG-UHFFFAOYSA-N 0.000 description 1
- XMAVGXGXSXXODU-UHFFFAOYSA-N [1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpyrrolidin-2-yl]methyl propanoate Chemical compound CCC(=O)OCC1CCCN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 XMAVGXGXSXXODU-UHFFFAOYSA-N 0.000 description 1
- BQWZZUKJOABMFG-YANBTOMASA-N [2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]-[(2s)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]methanone Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(N=2)C(=O)N2[C@@H](CCC2)CN2CCCC2)C=C1 BQWZZUKJOABMFG-YANBTOMASA-N 0.000 description 1
- JOOJZFQXQSJDAT-UHFFFAOYSA-N [2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]-piperidin-1-ylmethanone Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(N=2)C(=O)N2CCCCC2)C=C1 JOOJZFQXQSJDAT-UHFFFAOYSA-N 0.000 description 1
- PWQMVJLCQFERFZ-UHFFFAOYSA-N [2-methyl-2-[[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]propyl] propanoate Chemical compound C1=CC(S(=O)(=O)NC(C)(C)COC(=O)CC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 PWQMVJLCQFERFZ-UHFFFAOYSA-N 0.000 description 1
- PRDBLLIPPDOICK-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methanamine Chemical compound NCC1=CC=C(C(F)(F)F)C=C1 PRDBLLIPPDOICK-UHFFFAOYSA-N 0.000 description 1
- QOYSQXXMGPDHBK-UHFFFAOYSA-N [4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-5-yl]-morpholin-4-ylmethanone Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC(=C(C)N=2)C(=O)N2CCOCC2)C=C1 QOYSQXXMGPDHBK-UHFFFAOYSA-N 0.000 description 1
- QOYSQXXMGPDHBK-QGZVFWFLSA-N [4-methyl-2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1,3-oxazol-5-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2OC(=C(C)N=2)C(=O)N2CCOCC2)C=C1 QOYSQXXMGPDHBK-QGZVFWFLSA-N 0.000 description 1
- OIPZVNOEURHNRX-QGZVFWFLSA-N [4-methyl-2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1,3-thiazol-5-yl]-morpholin-4-ylmethanone Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(C=2SC(=C(C)N=2)C(=O)N2CCOCC2)C=C1 OIPZVNOEURHNRX-QGZVFWFLSA-N 0.000 description 1
- QOYSQXXMGPDHBK-KRWDZBQOSA-N [4-methyl-2-[4-[3-[(2s)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-1,3-oxazol-5-yl]-morpholin-4-ylmethanone Chemical compound C[C@H]1CCCN1CCCOC1=CC=C(C=2OC(=C(C)N=2)C(=O)N2CCOCC2)C=C1 QOYSQXXMGPDHBK-KRWDZBQOSA-N 0.000 description 1
- XIQKGKGIPVEEGK-UHFFFAOYSA-N [4-methyl-2-[6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl]-1,3-thiazol-5-yl]-morpholin-4-ylmethanone Chemical compound CC1CCCN1CCCOC1=CC=C(C=2SC(=C(C)N=2)C(=O)N2CCOCC2)C=N1 XIQKGKGIPVEEGK-UHFFFAOYSA-N 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- 239000012445 acidic reagent Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000005456 alcohol based solvent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- 150000003935 benzaldehydes Chemical class 0.000 description 1
- HDMLEZIULSIPQX-UHFFFAOYSA-N benzenesulfonic acid;2-methylpyrrolidine Chemical compound CC1CCCN1.OS(=O)(=O)C1=CC=CC=C1 HDMLEZIULSIPQX-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- AVKNGPAMCBSNSO-UHFFFAOYSA-N cyclohexylmethanamine Chemical compound NCC1CCCCC1 AVKNGPAMCBSNSO-UHFFFAOYSA-N 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- JQKJEPJLCSCBGW-UHFFFAOYSA-N dibutoxy(ethenyl)borane Chemical compound CCCCOB(C=C)OCCCC JQKJEPJLCSCBGW-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000007701 flash-distillation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 239000003395 histamine H3 receptor antagonist Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- SYFVCILCVBDQIK-UHFFFAOYSA-N methyl 2-[[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]acetate Chemical compound C1=CC(S(=O)(=O)NCC(=O)OC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 SYFVCILCVBDQIK-UHFFFAOYSA-N 0.000 description 1
- FMHBARORGRUHDM-UHFFFAOYSA-N methyl 2-[[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]propanoate Chemical compound C1=CC(S(=O)(=O)NC(C)C(=O)OC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 FMHBARORGRUHDM-UHFFFAOYSA-N 0.000 description 1
- HDLWYVVTBKDAQA-UHFFFAOYSA-N methyl 4-hydroxy-1-[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylpyrrolidine-2-carboxylate Chemical compound COC(=O)C1CC(O)CN1S(=O)(=O)C1=CC=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=C1 HDLWYVVTBKDAQA-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 1
- ZNUNHSALNZAAKI-UHFFFAOYSA-N n,n-bis(2-hydroxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N(CCO)CCO)C=C1 ZNUNHSALNZAAKI-UHFFFAOYSA-N 0.000 description 1
- CJRMUTTUKRVTAY-UHFFFAOYSA-N n,n-bis(2-methoxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(CCOC)CCOC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 CJRMUTTUKRVTAY-UHFFFAOYSA-N 0.000 description 1
- CEXJLCPGRGREOU-UHFFFAOYSA-N n,n-diethyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(CC)CC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 CEXJLCPGRGREOU-UHFFFAOYSA-N 0.000 description 1
- USQBDGHXHXLCNE-UHFFFAOYSA-N n,n-dimethyl-1-[4-[4-[4-[(2-methylpyrrolidin-1-yl)methyl]-1,3-oxazol-2-yl]phenoxy]butyl]pyrrolidin-3-amine Chemical compound CC1CCCN1CC1=COC(C=2C=CC(OCCCCN3CC(CC3)N(C)C)=CC=2)=N1 USQBDGHXHXLCNE-UHFFFAOYSA-N 0.000 description 1
- FDPGOPOKKSRVOC-UHFFFAOYSA-N n-(1-hydroxy-2-methylpropan-2-yl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC(C)(C)CO)C=C1 FDPGOPOKKSRVOC-UHFFFAOYSA-N 0.000 description 1
- IEHNOTDWNHHFOS-UHFFFAOYSA-N n-(1-hydroxypropan-2-yl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC(CO)C)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 IEHNOTDWNHHFOS-UHFFFAOYSA-N 0.000 description 1
- KAJGYUWXZNAHPI-UHFFFAOYSA-N n-(2-ethoxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCOCC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 KAJGYUWXZNAHPI-UHFFFAOYSA-N 0.000 description 1
- CBDTYYURZFRVGJ-UHFFFAOYSA-N n-(2-hydroxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(CCO)C(C)C)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 CBDTYYURZFRVGJ-UHFFFAOYSA-N 0.000 description 1
- AGCIOOMGRVAGJA-UHFFFAOYSA-N n-(2-methoxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-(oxan-4-ylmethyl)benzenesulfonamide Chemical compound C=1C=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=CC=1S(=O)(=O)N(CCOC)CC1CCOCC1 AGCIOOMGRVAGJA-UHFFFAOYSA-N 0.000 description 1
- ALARFOCTQMTSGX-UHFFFAOYSA-N n-(2-methoxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]-n-propan-2-ylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C(C)C)CCOC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 ALARFOCTQMTSGX-UHFFFAOYSA-N 0.000 description 1
- ZLGFDPBROZZHML-UHFFFAOYSA-N n-(2-methoxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCCOC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 ZLGFDPBROZZHML-UHFFFAOYSA-N 0.000 description 1
- TVYQPSDQCZEZER-UHFFFAOYSA-N n-(2-methoxyethyl)-n-(2-methylpropyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(CC(C)C)CCOC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 TVYQPSDQCZEZER-UHFFFAOYSA-N 0.000 description 1
- MYOAZOUXICOKKO-UHFFFAOYSA-N n-(2-methoxyethyl)-n-methyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)CCOC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 MYOAZOUXICOKKO-UHFFFAOYSA-N 0.000 description 1
- SFUGFWNYJPRZJD-UHFFFAOYSA-N n-(4-fluorophenyl)-2-[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]acetamide Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CC(=O)NC=3C=CC(F)=CC=3)N=2)C=C1 SFUGFWNYJPRZJD-UHFFFAOYSA-N 0.000 description 1
- YVKKENUWMVYTDD-UHFFFAOYSA-N n-(4-fluorophenyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC=2C=CC(F)=CC=2)C=C1 YVKKENUWMVYTDD-UHFFFAOYSA-N 0.000 description 1
- VMRZWFRMMGFKRO-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]-n-propylacetamide Chemical compound C=1OC(C=2C=CC(OCCCN3C(CCC3)C)=CC=2)=NC=1CC(=O)N(CCC)CC1CC1 VMRZWFRMMGFKRO-UHFFFAOYSA-N 0.000 description 1
- WZGAHLQHGNAMCJ-UHFFFAOYSA-N n-(cyclopropylmethyl)-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-n-propyl-1,3-oxazole-4-carboxamide Chemical compound C=1OC(C=2C=CC(OCCCN3C(CCC3)C)=CC=2)=NC=1C(=O)N(CCC)CC1CC1 WZGAHLQHGNAMCJ-UHFFFAOYSA-N 0.000 description 1
- COTQUFSBYWGOIV-UHFFFAOYSA-N n-(cyclopropylmethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC2CC2)C=C1 COTQUFSBYWGOIV-UHFFFAOYSA-N 0.000 description 1
- MECMPJWDYLIPKR-UHFFFAOYSA-N n-(cyclopropylmethyl)-n-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]propan-1-amine Chemical compound C=1OC(C=2C=CC(OCCCN3C(CCC3)C)=CC=2)=NC=1CN(CCC)CC1CC1 MECMPJWDYLIPKR-UHFFFAOYSA-N 0.000 description 1
- OPSAGXZWIWATAU-UHFFFAOYSA-N n-(cyclopropylmethyl)-n-[[4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-5-yl]methyl]propan-1-amine Chemical compound O1C(C=2C=CC(OCCCN3C(CCC3)C)=CC=2)=NC(C)=C1CN(CCC)CC1CC1 OPSAGXZWIWATAU-UHFFFAOYSA-N 0.000 description 1
- ZVDFVBIRGMUENQ-UHFFFAOYSA-N n-[(3,4-dichlorophenyl)methyl]-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2C=C(Cl)C(Cl)=CC=2)C=C1 ZVDFVBIRGMUENQ-UHFFFAOYSA-N 0.000 description 1
- HDTSBZPPVIRGSH-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2C=C(Cl)C=C(Cl)C=2)C=C1 HDTSBZPPVIRGSH-UHFFFAOYSA-N 0.000 description 1
- DCECSLFSIJPIDQ-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole-4-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(N=2)C(=O)NCC=2C=CC(F)=CC=2)C=C1 DCECSLFSIJPIDQ-UHFFFAOYSA-N 0.000 description 1
- FKJIUGCNOYFZRS-UHFFFAOYSA-N n-[(4-fluorophenyl)methyl]-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2C=CC(F)=CC=2)C=C1 FKJIUGCNOYFZRS-UHFFFAOYSA-N 0.000 description 1
- UZXAUBGMLBEYHS-UHFFFAOYSA-N n-[(4-methylphenyl)methyl]-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC=2C=CC(C)=CC=2)C=C1 UZXAUBGMLBEYHS-UHFFFAOYSA-N 0.000 description 1
- OJPIRGUOVXCSRY-UHFFFAOYSA-N n-[1-(hydroxymethyl)cyclopentyl]-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC2(CO)CCCC2)C=C1 OJPIRGUOVXCSRY-UHFFFAOYSA-N 0.000 description 1
- XLIZGFWRVQNTBE-UHFFFAOYSA-N n-[2-(4-fluorophenyl)ethyl]-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCCC=2C=CC(F)=CC=2)C=C1 XLIZGFWRVQNTBE-UHFFFAOYSA-N 0.000 description 1
- JUUUXBBZOCXTET-UHFFFAOYSA-N n-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]methyl]aniline Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CNC=3C=CC=CC=3)N=2)C=C1 JUUUXBBZOCXTET-UHFFFAOYSA-N 0.000 description 1
- SWRKPBJSPWFJDH-UHFFFAOYSA-N n-[[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-thiazol-4-yl]methyl]-n-propylbutan-2-amine Chemical compound CCCN(C(C)CC)CC1=CSC(C=2C=CC(OCCCN3C(CCC3)C)=CC=2)=N1 SWRKPBJSPWFJDH-UHFFFAOYSA-N 0.000 description 1
- SOFAPWCQUDLUBN-UHFFFAOYSA-N n-benzhydryl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC(C=2C=CC=CC=2)C=2C=CC=CC=2)C=C1 SOFAPWCQUDLUBN-UHFFFAOYSA-N 0.000 description 1
- IZYIGHJNXIGJLW-UHFFFAOYSA-N n-benzyl-4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole-5-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC(=C(C)N=2)C(=O)NCC=2C=CC=CC=2)C=C1 IZYIGHJNXIGJLW-UHFFFAOYSA-N 0.000 description 1
- NKQGWIKZNFWKQF-UHFFFAOYSA-N n-benzyl-n-(2-hydroxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)N(CCO)CC=2C=CC=CC=2)C=C1 NKQGWIKZNFWKQF-UHFFFAOYSA-N 0.000 description 1
- YAQDYYKNVZIREK-UHFFFAOYSA-N n-benzyl-n-(2-methoxyethyl)-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=CC=1S(=O)(=O)N(CCOC)CC1=CC=CC=C1 YAQDYYKNVZIREK-UHFFFAOYSA-N 0.000 description 1
- CLYUDPHBQXTMKX-UHFFFAOYSA-N n-benzyl-n-ethyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C=1C=C(C=2C=CC(CCN3C(CCC3)C)=CC=2)C=CC=1S(=O)(=O)N(CC)CC1=CC=CC=C1 CLYUDPHBQXTMKX-UHFFFAOYSA-N 0.000 description 1
- VRMVSYUYAWQPOU-UHFFFAOYSA-N n-cyclobutyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC2CCC2)C=C1 VRMVSYUYAWQPOU-UHFFFAOYSA-N 0.000 description 1
- KIARYUXZSJOOIF-UHFFFAOYSA-N n-cyclohexyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC2CCCCC2)C=C1 KIARYUXZSJOOIF-UHFFFAOYSA-N 0.000 description 1
- WVYVWKPFJBUUAE-HXUWFJFHSA-N n-cyclohexyl-5-methyl-2-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]pyrazole-3-carboxamide Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(=CC(C)=N2)C(=O)NC2CCCCC2)C=C1 WVYVWKPFJBUUAE-HXUWFJFHSA-N 0.000 description 1
- YWCBBOQXMPVSLD-UHFFFAOYSA-N n-cyclopentyl-2-[2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazol-4-yl]acetamide Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC=C(CC(=O)NC3CCCC3)N=2)C=C1 YWCBBOQXMPVSLD-UHFFFAOYSA-N 0.000 description 1
- HMOCEPWTZSRYTB-UHFFFAOYSA-N n-cyclopentyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC2CCCC2)C=C1 HMOCEPWTZSRYTB-UHFFFAOYSA-N 0.000 description 1
- FORUEZLTXSBDIM-UHFFFAOYSA-N n-cyclopentyl-4-methyl-2-[4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl]-1,3-oxazole-5-carboxamide Chemical compound CC1CCCN1CCCOC1=CC=C(C=2OC(=C(C)N=2)C(=O)NC2CCCC2)C=C1 FORUEZLTXSBDIM-UHFFFAOYSA-N 0.000 description 1
- FKUDQYZICIADCS-UHFFFAOYSA-N n-cyclopropyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC2CC2)C=C1 FKUDQYZICIADCS-UHFFFAOYSA-N 0.000 description 1
- KCWBLQLQPMZHOJ-UHFFFAOYSA-N n-ethyl-4-[4-(2-pyrrolidin-1-ylethyl)phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCC)=CC=C1C(C=C1)=CC=C1CCN1CCCC1 KCWBLQLQPMZHOJ-UHFFFAOYSA-N 0.000 description 1
- GQLPRIVQAONOIR-UHFFFAOYSA-N n-ethyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NCC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 GQLPRIVQAONOIR-UHFFFAOYSA-N 0.000 description 1
- RQZFDZYMDZGQOS-UHFFFAOYSA-N n-heptan-4-yl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC(CCC)CCC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 RQZFDZYMDZGQOS-UHFFFAOYSA-N 0.000 description 1
- OSNJEBSXZKKDLG-UHFFFAOYSA-N n-methyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 OSNJEBSXZKKDLG-UHFFFAOYSA-N 0.000 description 1
- PETDBDGHXCNFOL-UHFFFAOYSA-N n-tert-butyl-4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]benzenesulfonamide Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NC(C)(C)C)C=C1 PETDBDGHXCNFOL-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- BMRZLWYQXYKVRW-UHFFFAOYSA-N piperidine;pyrrolidin-2-one Chemical compound C1CCNCC1.O=C1CCCN1 BMRZLWYQXYKVRW-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 125000000075 primary alcohol group Chemical group 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
- 239000002469 receptor inverse agonist Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 102220060025 rs141586345 Human genes 0.000 description 1
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical class OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- BFFLLBPMZCIGRM-QMMMGPOBSA-N tert-butyl (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CO BFFLLBPMZCIGRM-QMMMGPOBSA-N 0.000 description 1
- ZSBNHRJPLRVNGO-UHFFFAOYSA-N tert-butyl 2-[[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]acetate Chemical compound CC1CCCN1CCC1=CC=C(C=2C=CC(=CC=2)S(=O)(=O)NCC(=O)OC(C)(C)C)C=C1 ZSBNHRJPLRVNGO-UHFFFAOYSA-N 0.000 description 1
- XJHKRDSLSGRKDO-UHFFFAOYSA-N tert-butyl 2-[[4-[4-[2-(2-methylpyrrolidin-1-yl)ethyl]phenyl]phenyl]sulfonylamino]propanoate Chemical compound C1=CC(S(=O)(=O)NC(C)C(=O)OC(C)(C)C)=CC=C1C(C=C1)=CC=C1CCN1C(C)CCC1 XJHKRDSLSGRKDO-UHFFFAOYSA-N 0.000 description 1
- PTEHWBIWKFLJPG-UHFFFAOYSA-N tert-butyl 3-oxo-4-(4-phenylmethoxyphenyl)piperazine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CCN1C(C=C1)=CC=C1OCC1=CC=CC=C1 PTEHWBIWKFLJPG-UHFFFAOYSA-N 0.000 description 1
- GTYRZGSKTZTHMF-UHFFFAOYSA-N tert-butyl 4-(4-hydroxyphenyl)-3-oxopiperazine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(O)C=C1 GTYRZGSKTZTHMF-UHFFFAOYSA-N 0.000 description 1
- JZUHHDAETNVMRM-UHFFFAOYSA-N tert-butyl 4-[4-(3-chloropropoxy)phenyl]-3-oxopiperazine-1-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(OCCCCl)C=C1 JZUHHDAETNVMRM-UHFFFAOYSA-N 0.000 description 1
- JXTYKQBGXKLDLY-GOSISDBHSA-N tert-butyl 4-[4-[3-[(2r)-2-methylpyrrolidin-1-yl]propoxy]phenyl]-3-oxopiperazine-1-carboxylate Chemical compound C[C@@H]1CCCN1CCCOC1=CC=C(N2C(CN(CC2)C(=O)OC(C)(C)C)=O)C=C1 JXTYKQBGXKLDLY-GOSISDBHSA-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
- IDCYNZYRRJOLCA-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)-n-[2-oxo-2-(4-phenylmethoxyanilino)ethyl]carbamate Chemical compound C1=CC(NC(=O)CN(CCO)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC=C1 IDCYNZYRRJOLCA-UHFFFAOYSA-N 0.000 description 1
- 150000003526 tetrahydroisoquinolines Chemical class 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cosmetics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US92735607P | 2007-05-03 | 2007-05-03 | |
US60/927,356 | 2007-05-03 | ||
PCT/US2008/005702 WO2008137087A1 (en) | 2007-05-03 | 2008-05-02 | Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2686033A1 true CA2686033A1 (en) | 2008-11-13 |
Family
ID=39688886
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002686033A Abandoned CA2686033A1 (en) | 2007-05-03 | 2008-05-02 | Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP2152669A1 (ru) |
JP (1) | JP5698887B2 (ru) |
KR (1) | KR20100017565A (ru) |
CN (1) | CN101679237A (ru) |
AU (1) | AU2008248168B2 (ru) |
BR (1) | BRPI0810330A2 (ru) |
CA (1) | CA2686033A1 (ru) |
EA (1) | EA019031B1 (ru) |
IL (1) | IL201627A (ru) |
MX (1) | MX2009011787A (ru) |
NZ (1) | NZ580948A (ru) |
UA (1) | UA99913C2 (ru) |
WO (1) | WO2008137087A1 (ru) |
ZA (1) | ZA200907643B (ru) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2397283T3 (es) | 2006-07-25 | 2013-03-06 | Cephalon, Inc. | Derivados de piridizinona |
US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
EP2752406A1 (en) * | 2008-01-30 | 2014-07-09 | Cephalon, Inc. | Substituted pyridazine derivatives which have histamine H3 antagonist activity |
EP3237408B1 (en) * | 2014-12-23 | 2018-10-31 | Cephalon, Inc. | Methods for preparing fused bicyclic 2, 4-diaminopyrimidine derivatives |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3329974A1 (de) | 1983-08-19 | 1985-02-28 | Bayer Ag, 5090 Leverkusen | Herstellung von hydrierten nitrilkautschuken |
DE3433392A1 (de) | 1984-09-12 | 1986-03-20 | Bayer Ag, 5090 Leverkusen | Hydrierung nitrilgruppenhaltiger ungesaettigter polymerer |
FR2714849B1 (fr) | 1994-01-13 | 1996-04-05 | Inst Francais Du Petrole | Procédé de préparation d'un catalyseur d'hydrogénation soluble en phase liquide organique. |
DE4403479A1 (de) | 1994-02-04 | 1995-08-10 | Basf Ag | Verfahren zur Herstellung von Hydroxylammoniumsalzen |
WO2004024707A2 (en) * | 2002-09-16 | 2004-03-25 | Abbott Laboratories | Process for preparing amine type substituted benzofurans |
US7153889B2 (en) | 2002-11-12 | 2006-12-26 | Abbott Laboratories | Bicyclic-substituted amines as histamine-3 receptor ligands |
CN100543050C (zh) | 2004-03-08 | 2009-09-23 | 独立行政法人科学技术振兴机构 | 高分子担载金属簇组合物 |
US7145005B2 (en) | 2004-05-12 | 2006-12-05 | Abbott Laboratories | 2-(6-{2-[(2R)-2-Methyl-1-pyrrolidin-1-yl]-ethyl}-2-naphthalen-2-yl)-2H-pyridazin-3-one salts and their preparation |
ES2299074T3 (es) | 2004-06-02 | 2008-05-16 | F. Hoffmann-La Roche Ag | Derivados de naftaleno utiles como ligandos del receptor 3 de la histamina. |
WO2006059778A1 (ja) | 2004-12-01 | 2006-06-08 | Banyu Pharmaceutical Co., Ltd. | 置換ピリドン誘導体 |
JP2008524252A (ja) | 2004-12-17 | 2008-07-10 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Cns障害の処置のためのテトラヒドロイソキノリン化合物 |
JP2008526895A (ja) | 2005-01-21 | 2008-07-24 | シェーリング コーポレイション | ヒスタミンh3アンタゴニストとして有用なイミダゾールおよびベンゾイミダゾール誘導体 |
CA2602336A1 (en) | 2005-03-31 | 2006-10-05 | Ucb Pharma S.A. | Compounds comprising an oxazole or thiazole moiety, processes for making them, and their uses |
GB0514812D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
CA2627234A1 (en) | 2005-10-27 | 2007-05-03 | Ucb Pharma, S.A. | Compounds comprising a lactam or a lactam derivative moiety, processes for making them, and their uses |
WO2007094962A2 (en) | 2006-02-09 | 2007-08-23 | Athersys, Inc. | Pyrazoles for the treatment of obesity and other cns disorders |
WO2007099423A1 (en) | 2006-03-02 | 2007-09-07 | Pfizer Products Inc. | 1-pyrrolidine indane derivatives as histamine-3 receptor antagonists |
US20090163482A1 (en) | 2006-03-13 | 2009-06-25 | Mchardy Stanton Furst | Tetralines antagonists of the h-3 receptor |
WO2008005338A1 (en) | 2006-06-29 | 2008-01-10 | Arena Pharmaceuticals, Inc. | Modulators of the histamine h3-receptor useful for the treatment of disorders related thereto |
ES2397283T3 (es) * | 2006-07-25 | 2013-03-06 | Cephalon, Inc. | Derivados de piridizinona |
-
2008
- 2008-05-02 AU AU2008248168A patent/AU2008248168B2/en not_active Ceased
- 2008-05-02 EA EA200971019A patent/EA019031B1/ru not_active IP Right Cessation
- 2008-05-02 CN CN200880021225A patent/CN101679237A/zh active Pending
- 2008-05-02 MX MX2009011787A patent/MX2009011787A/es active IP Right Grant
- 2008-05-02 WO PCT/US2008/005702 patent/WO2008137087A1/en active Application Filing
- 2008-05-02 CA CA002686033A patent/CA2686033A1/en not_active Abandoned
- 2008-05-02 UA UAA200912476A patent/UA99913C2/ru unknown
- 2008-05-02 EP EP08754205A patent/EP2152669A1/en not_active Withdrawn
- 2008-05-02 KR KR1020097025141A patent/KR20100017565A/ko not_active Application Discontinuation
- 2008-05-02 NZ NZ580948A patent/NZ580948A/en not_active IP Right Cessation
- 2008-05-02 BR BRPI0810330-5A2A patent/BRPI0810330A2/pt not_active IP Right Cessation
- 2008-05-02 JP JP2010507416A patent/JP5698887B2/ja not_active Expired - Fee Related
-
2009
- 2009-10-19 IL IL201627A patent/IL201627A/en not_active IP Right Cessation
- 2009-10-30 ZA ZA2009/07643A patent/ZA200907643B/en unknown
Also Published As
Publication number | Publication date |
---|---|
WO2008137087A1 (en) | 2008-11-13 |
JP5698887B2 (ja) | 2015-04-08 |
IL201627A0 (en) | 2010-05-31 |
CN101679237A (zh) | 2010-03-24 |
JP2010526142A (ja) | 2010-07-29 |
AU2008248168A1 (en) | 2008-11-13 |
AU2008248168B2 (en) | 2013-03-21 |
BRPI0810330A2 (pt) | 2014-10-14 |
NZ580948A (en) | 2011-04-29 |
EA019031B1 (ru) | 2013-12-30 |
ZA200907643B (en) | 2014-03-26 |
EA200971019A1 (ru) | 2010-04-30 |
UA99913C2 (ru) | 2012-10-25 |
IL201627A (en) | 2014-06-30 |
KR20100017565A (ko) | 2010-02-16 |
EP2152669A1 (en) | 2010-02-17 |
MX2009011787A (es) | 2009-11-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20100121055A1 (en) | Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof | |
JP6392888B2 (ja) | ヒストン脱アセチル化酵素6阻害剤としての新規化合物およびこれを含む薬剤学的組成物 | |
CN103354808B (zh) | 抗病毒化合物 | |
JP6117430B2 (ja) | 選択的ヒストン脱アセチル化酵素抑制剤としての新規化合物およびこれを含む薬剤学的組成物 | |
RU2351589C2 (ru) | Производные n-[фенил(алкилпиперидин-2-ил)метил]бензамида и их применение в терапии | |
WO2000017163A1 (fr) | Derives de cyanophenyle | |
AU1679099A (en) | 4-(2-keto-1-benzimidazolinyl)piperidine compounds as orl1-receptor agonists | |
JP2012519196A (ja) | スルホニル化されたテトラヒドロアゾロピラジンおよびその医薬としての使用 | |
KR20100093103A (ko) | 고지혈증 또는 동맥경화증과 같은 질환의 치료에 유용한 cετρ 억제제로서의 1,2-이치환된 4-벤질아미노-피롤리딘 유도체 | |
CN111770918B (zh) | Trpc6的抑制剂 | |
CA2686033A1 (en) | Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof | |
ZA200407414B (en) | Piperidine or 8-aza-bicyclo[3.2.1]oct-3-yl derivatives useful as modulators of chemokine receptor activity (especially CCR5). | |
KR20230158007A (ko) | 항바이러스 화합물 | |
Zhou et al. | Approach to Chiral 1-Substituted Isoquinolone and 3-Substituted Isoindolin-1-one by Addition–Cyclization Process | |
Icelo-Ávila et al. | Synthesis of 6-methyl-3, 4-dihydropyrazinones using an Ugi 4-CR/allenamide cycloisomerization protocol | |
CA2791431A1 (en) | Derivatives of aminoindanes, their preparation and their application in therapeutics | |
ZA200700950B (en) | Pyrrole derivatives, their preparation and their therapeutic use | |
CA2500115A1 (en) | Heterocyclic substituted piperazines for the treatment of schizophrenia | |
WO2021071803A1 (en) | Aryl heterobicyclic compounds as kv1.3 potassium shaker channel blockers | |
AU2005252178A1 (en) | Histamine H3 receptor agents, preparation and therapeutic uses | |
Vega-Penaloza et al. | Stereoselective synthesis of chiral pyrrolidine derivatives of (+)-α-pinene containing a β-amino acid moiety | |
García‐Mingüens et al. | Nitroprolinates as Nucleophiles in Michael‐type Additions and Acylations. Synthesis of Enantiomerically Enriched Fused Amino‐pyrrolidino‐[1, 2‐a] pyrazinones and‐diketopiperazines | |
JP2010526142A5 (ru) | ||
AU2006316609A1 (en) | Modulators of the H3 receptor useful for the treatment of disorders related thereto | |
RU2817736C1 (ru) | Новые соединения в качестве ингибитора гистондеацетилазы 6 и фармацевтическая композиция, содержащая их |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request |
Effective date: 20130319 |
|
FZDE | Discontinued |
Effective date: 20160504 |