JP2016540792A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2016540792A5 JP2016540792A5 JP2016539896A JP2016539896A JP2016540792A5 JP 2016540792 A5 JP2016540792 A5 JP 2016540792A5 JP 2016539896 A JP2016539896 A JP 2016539896A JP 2016539896 A JP2016539896 A JP 2016539896A JP 2016540792 A5 JP2016540792 A5 JP 2016540792A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- alkyl
- phenyl
- methyl
- 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.)
- Granted
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 165
- 125000000623 heterocyclic group Chemical group 0.000 claims description 123
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 92
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 84
- -1 ethylene, propylene, butylene, pentylene, hexylene, heptylene Chemical group 0.000 claims description 82
- 150000001875 compounds Chemical class 0.000 claims description 80
- 125000000304 alkynyl group Chemical group 0.000 claims description 69
- 125000003118 aryl group Chemical group 0.000 claims description 69
- 125000003342 alkenyl group Chemical group 0.000 claims description 64
- HSFWRNGVRCDJHI-UHFFFAOYSA-N Acetylene Chemical compound C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 51
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 48
- 229910052731 fluorine Inorganic materials 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 47
- 229920006395 saturated elastomer Polymers 0.000 claims description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims description 46
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 45
- 229910052801 chlorine Inorganic materials 0.000 claims description 45
- 239000000460 chlorine Substances 0.000 claims description 45
- IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 claims description 44
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 claims description 44
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- 229910052740 iodine Inorganic materials 0.000 claims description 42
- 229910052794 bromium Inorganic materials 0.000 claims description 41
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 36
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 35
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 35
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 34
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 32
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 claims description 31
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 30
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 239000001301 oxygen Substances 0.000 claims description 30
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 28
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 28
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 28
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 28
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 28
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 28
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 28
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 28
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 28
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 28
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 28
- 229910052717 sulfur Inorganic materials 0.000 claims description 28
- 239000011593 sulfur Substances 0.000 claims description 28
- 125000005842 heteroatom Chemical group 0.000 claims description 27
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 27
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 25
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 24
- 125000001624 naphthyl group Chemical group 0.000 claims description 23
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 20
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 20
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 17
- 229930192474 thiophene Natural products 0.000 claims description 16
- CGHIBGNXEGJPQZ-UHFFFAOYSA-N 1-hexyne Chemical compound CCCCC#C CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 claims description 15
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 15
- 125000004429 atom Chemical group 0.000 claims description 15
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 14
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 14
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 14
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 14
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 claims description 14
- 239000012964 benzotriazole Substances 0.000 claims description 14
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 14
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 14
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 14
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 14
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 14
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 claims description 14
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 14
- 150000003536 tetrazoles Chemical class 0.000 claims description 14
- 150000003852 triazoles Chemical class 0.000 claims description 14
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical group CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 claims description 13
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 10
- YVXHZKKCZYLQOP-UHFFFAOYSA-N hept-1-yne Chemical compound CCCCCC#C YVXHZKKCZYLQOP-UHFFFAOYSA-N 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 150000003222 pyridines Chemical class 0.000 claims description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 150000002460 imidazoles Chemical class 0.000 claims description 4
- 150000003235 pyrrolidines Chemical class 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- AJFDBNQQDYLMJN-UHFFFAOYSA-N n,n-diethylacetamide Chemical compound CCN(CC)C(C)=O AJFDBNQQDYLMJN-UHFFFAOYSA-N 0.000 claims description 3
- 150000007530 organic bases Chemical class 0.000 claims description 3
- VSRBKQFNFZQRBM-UHFFFAOYSA-N tuaminoheptane Chemical compound CCCCCC(C)N VSRBKQFNFZQRBM-UHFFFAOYSA-N 0.000 claims description 3
- 229960003986 tuaminoheptane Drugs 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 230000003796 beauty Effects 0.000 claims 15
- 125000001424 substituent group Chemical group 0.000 claims 15
- 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 claims 8
- 239000000203 mixture Substances 0.000 claims 7
- 239000012453 solvate Substances 0.000 claims 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- 238000006243 chemical reaction Methods 0.000 claims 4
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- 208000004454 Hyperalgesia Diseases 0.000 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical group CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical group CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims 2
- 150000001556 benzimidazoles Chemical group 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 150000001879 copper Chemical class 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000012046 mixed solvent Substances 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical group CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 claims 1
- OHWJECJFVKKZMR-UHFFFAOYSA-N 3-[4-[(1-benzyltriazol-4-yl)methyl]piperazin-1-yl]phenol Chemical compound OC1=CC(=CC=C1)N1CCN(CC2=CN(CC3=CC=CC=C3)N=N2)CC1 OHWJECJFVKKZMR-UHFFFAOYSA-N 0.000 claims 1
- WMSIZSKZBUCEHA-UHFFFAOYSA-N 3-[4-[(1-phenylpyrazol-4-yl)methyl]piperazin-1-yl]phenol Chemical compound C1(=CC=CC=C1)N1N=CC(=C1)CN1CCN(CC1)C=1C=C(C=CC1)O WMSIZSKZBUCEHA-UHFFFAOYSA-N 0.000 claims 1
- PYDAINOAXWAHNN-UHFFFAOYSA-N 3-[4-[(1-phenyltriazol-4-yl)methyl]piperazin-1-yl]aniline Chemical compound C1(=CC=CC=C1)N1N=NC(=C1)CN1CCN(CC1)C=1C=C(N)C=CC=1 PYDAINOAXWAHNN-UHFFFAOYSA-N 0.000 claims 1
- UWMOCXBIPRMODY-UHFFFAOYSA-N 3-[4-[(1-phenyltriazol-4-yl)methyl]piperazin-1-yl]phenol Chemical compound C1(=CC=CC=C1)N1N=NC(=C1)CN1CCN(CC1)C=1C=C(C=CC1)O UWMOCXBIPRMODY-UHFFFAOYSA-N 0.000 claims 1
- IJCQVTXTRTXCKQ-UHFFFAOYSA-N 3-[4-[(1-pyridin-2-yltriazol-4-yl)methyl]piperazin-1-yl]phenol Chemical compound OC1=CC(=CC=C1)N1CCN(CC2=CN(N=N2)C2=NC=CC=C2)CC1 IJCQVTXTRTXCKQ-UHFFFAOYSA-N 0.000 claims 1
- 206010058019 Cancer Pain Diseases 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims 1
- 208000035154 Hyperesthesia Diseases 0.000 claims 1
- 206010065390 Inflammatory pain Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- SYOXPLIPOYMWBH-SZPZYZBQSA-N N-[3-[(1R,5S)-3-[(1-phenyltriazol-4-yl)methyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]phenyl]methanesulfonamide Chemical compound C1(=CC=CC=C1)N1N=NC(=C1)CN1C[C@H]2CC[C@@H](C1)N2C=1C=C(C=CC=1)NS(=O)(=O)C SYOXPLIPOYMWBH-SZPZYZBQSA-N 0.000 claims 1
- JZYNQHYPIINROR-UHFFFAOYSA-N N-[3-[4-[(1-benzylpyrazol-4-yl)methyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound C(C1=CC=CC=C1)N1N=CC(=C1)CN1CCN(CC1)C=1C=C(C=CC1)NS(=O)(=O)C JZYNQHYPIINROR-UHFFFAOYSA-N 0.000 claims 1
- FMROZDQOXRRQBA-UHFFFAOYSA-N N-[3-[4-[(1-benzyltriazol-4-yl)methyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound C(C1=CC=CC=C1)N1N=NC(=C1)CN1CCN(CC1)C=1C=C(C=CC=1)NS(=O)(=O)C FMROZDQOXRRQBA-UHFFFAOYSA-N 0.000 claims 1
- RFNRKHAVTQDMLR-UHFFFAOYSA-N N-[3-[4-[(1-phenylpyrazol-4-yl)methyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound C1(=CC=CC=C1)N1N=CC(=C1)CN1CCN(CC1)C=1C=C(C=CC1)NS(=O)(=O)C RFNRKHAVTQDMLR-UHFFFAOYSA-N 0.000 claims 1
- LKIFLEOHZPMIIU-UHFFFAOYSA-N N-[3-[4-[(1-phenyltriazol-4-yl)methyl]-1,4-diazepan-1-yl]phenyl]methanesulfonamide Chemical compound C1(=CC=CC=C1)N1N=NC(=C1)CN1CCN(CCC1)C=1C=C(C=CC1)NS(=O)(=O)C LKIFLEOHZPMIIU-UHFFFAOYSA-N 0.000 claims 1
- ZHODOIJXILJEIM-UHFFFAOYSA-N N-[3-[4-[(1-phenyltriazol-4-yl)methyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(=CC=C1)N1CCN(CC2=CN(N=N2)C2=CC=CC=C2)CC1 ZHODOIJXILJEIM-UHFFFAOYSA-N 0.000 claims 1
- KHBBVGYFILAJEY-UHFFFAOYSA-N N-[3-[4-[(1-pyridin-2-ylpyrazol-4-yl)methyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound N1=C(C=CC=C1)N1N=CC(=C1)CN1CCN(CC1)C=1C=C(C=CC1)NS(=O)(=O)C KHBBVGYFILAJEY-UHFFFAOYSA-N 0.000 claims 1
- CHLUHDHVLQKJKU-UHFFFAOYSA-N N-[3-[4-[[1-(pyridin-2-ylmethyl)pyrazol-4-yl]methyl]piperazin-1-yl]phenyl]methanesulfonamide Chemical compound N1=C(C=CC=C1)CN1N=CC(=C1)CN1CCN(CC1)C=1C=C(C=CC=1)NS(=O)(=O)C CHLUHDHVLQKJKU-UHFFFAOYSA-N 0.000 claims 1
- NIQUJZPSSVJAIE-UHFFFAOYSA-N N-[3-[[1-[(1-phenyltriazol-4-yl)methyl]azetidin-3-yl]amino]phenyl]methanesulfonamide Chemical compound C1(=CC=CC=C1)N1N=NC(=C1)CN1CC(C1)NC=1C=C(C=CC=1)NS(=O)(=O)C NIQUJZPSSVJAIE-UHFFFAOYSA-N 0.000 claims 1
- RGZCRYIYASEKFV-UHFFFAOYSA-N N-[3-[methyl-[1-[(1-phenyltriazol-4-yl)methyl]azetidin-3-yl]amino]phenyl]methanesulfonamide Chemical compound CN(C=1C=C(C=CC=1)NS(=O)(=O)C)C1CN(C1)CC=1N=NN(C=1)C1=CC=CC=C1 RGZCRYIYASEKFV-UHFFFAOYSA-N 0.000 claims 1
- UAYOVMSZGIRNQP-UHFFFAOYSA-N N-[3-[methyl-[1-[(1-phenyltriazol-4-yl)methyl]pyrrolidin-3-yl]amino]phenyl]methanesulfonamide Chemical compound CN(C1CCN(CC2=CN(N=N2)C2=CC=CC=C2)C1)C1=CC=CC(NS(C)(=O)=O)=C1 UAYOVMSZGIRNQP-UHFFFAOYSA-N 0.000 claims 1
- CWPXACFCIXQDQI-UHFFFAOYSA-N N-[6-[4-[[1-(2-fluorophenyl)triazol-4-yl]methyl]piperazin-1-yl]pyridin-2-yl]propanamide Chemical compound FC1=C(C=CC=C1)N1N=NC(=C1)CN1CCN(CC1)C1=CC=CC(=N1)NC(CC)=O CWPXACFCIXQDQI-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 206010053552 allodynia Diseases 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 206010027599 migraine Diseases 0.000 claims 1
- 208000004296 neuralgia Diseases 0.000 claims 1
- 208000021722 neuropathic pain Diseases 0.000 claims 1
- 239000003586 protic polar solvent Substances 0.000 claims 1
- 235000010378 sodium ascorbate Nutrition 0.000 claims 1
- 229960005055 sodium ascorbate Drugs 0.000 claims 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims 1
- 125000005017 substituted alkenyl group Chemical group 0.000 claims 1
- 239000003981 vehicle Substances 0.000 claims 1
- 208000009935 visceral pain Diseases 0.000 claims 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 18
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 9
- 0 CN(*)C1CN(C)C1 Chemical compound CN(*)C1CN(C)C1 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 108020001612 μ-opioid receptors Proteins 0.000 description 2
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 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
- HWTLFOPXWFNIAJ-JAMMHHFISA-N CN1C2CN(C)C[C@@H]1CC2 Chemical compound CN1C2CN(C)C[C@@H]1CC2 HWTLFOPXWFNIAJ-JAMMHHFISA-N 0.000 description 1
- RXYPXQSKLGGKOL-UHFFFAOYSA-N CN1CCN(C)CC1 Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 102000051367 mu Opioid Receptors Human genes 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13384006.6 | 2013-12-20 | ||
| EP13384006 | 2013-12-20 | ||
| PCT/EP2014/078852 WO2015092009A1 (en) | 2013-12-20 | 2014-12-19 | Piperazine derivatives having multimodal activity against pain |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016540792A JP2016540792A (ja) | 2016-12-28 |
| JP2016540792A5 true JP2016540792A5 (enExample) | 2018-02-01 |
| JP6553615B2 JP6553615B2 (ja) | 2019-07-31 |
Family
ID=49998042
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016539896A Expired - Fee Related JP6553615B2 (ja) | 2013-12-20 | 2014-12-19 | 疼痛に対して多重モードの活性を有するピペラジン誘導体 |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US10351535B2 (enExample) |
| EP (1) | EP3083563A1 (enExample) |
| JP (1) | JP6553615B2 (enExample) |
| KR (1) | KR20160098506A (enExample) |
| CN (1) | CN105829287B (enExample) |
| AU (1) | AU2014368368C1 (enExample) |
| CA (1) | CA2932051A1 (enExample) |
| IL (1) | IL245808B (enExample) |
| MA (1) | MA39145B1 (enExample) |
| MX (1) | MX2016008130A (enExample) |
| MY (1) | MY179509A (enExample) |
| PH (1) | PH12016500978A1 (enExample) |
| RU (1) | RU2709482C1 (enExample) |
| SG (1) | SG10201805267UA (enExample) |
| TN (1) | TN2016000203A1 (enExample) |
| UA (1) | UA120754C2 (enExample) |
| WO (1) | WO2015092009A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2018000418A (es) * | 2015-07-29 | 2018-08-14 | Esteve Labor Dr | Derivados de amida que tienen actividad multimodal contra el dolor. |
| JP2018525363A (ja) * | 2015-07-29 | 2018-09-06 | ラボラトリオス・デル・デエレ・エステベ・エセ・ア | 疼痛に対する多様な活性を有する置換アミド誘導体 |
| JP2019516736A (ja) * | 2016-05-20 | 2019-06-20 | エステベ ファーマシューティカルズ，エセ．アー． | 疼痛に対する多様な活性を有するテトラヒドロピラン誘導体およびチオピラン誘導体 |
| EP3600289A4 (en) | 2017-03-21 | 2020-08-05 | Temple University - Of The Commonwealth System of Higher Education | 5-HYDROXYTRYPTAMINE RECEPTOR 7 MODULATORS AND THE USE OF THESE AS THERAPEUTIC AGENTS |
| EP3600290B1 (en) * | 2017-03-21 | 2025-06-04 | Temple University - Of The Commonwealth System of Higher Education | Novel modulators of the sigma-2 receptor and their method of use |
| SMT202200134T1 (it) | 2018-03-08 | 2022-05-12 | Incyte Corp | Composti di amminopirazindiolo come inibitori di pi3k-y |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| JP7249428B2 (ja) * | 2018-10-31 | 2023-03-30 | アコンディシオナミエント タルラセンス | 疼痛に対して活性があるピペラジニル及びピペリジニルキナゾリン－４（３ｈ）－オン誘導体 |
| EP3753932A1 (en) * | 2019-06-17 | 2020-12-23 | Esteve Pharmaceuticals, S.A. | Substituted bicyclic derivatives having multimodal activity against pain |
| WO2022187206A1 (en) * | 2021-03-01 | 2022-09-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Dual-target mu opioid and dopamine d3 receptors ligands; preparation and use thereof |
| WO2024105225A1 (en) | 2022-11-18 | 2024-05-23 | Universitat De Barcelona | Synergistic combinations of a sigma receptor 1 (s1r) antagonist and a soluble epoxide hydrolase inhibitor (sehi) and their use in the treatment of pain |
| CN117800942B (zh) * | 2023-12-13 | 2025-04-25 | 徐州医科大学 | 一种噻吩哌嗪酰胺类衍生物、组合物及其应用 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2580648B1 (fr) * | 1985-04-17 | 1987-05-15 | Adir | Nouveaux derives du triazole, leur procede de preparation et les compositions pharmaceutiques les renfermant |
| EP0241053B1 (en) * | 1986-02-27 | 1992-11-11 | Duphar International Research B.V | Aryl-substituted (n-piperidinyl)-methyl- and (n-piperazinyl) methylazoles having antipsychotic properties |
| SE0103818D0 (sv) * | 2001-11-15 | 2001-11-15 | Astrazeneca Ab | Chemical compounds |
| US7262194B2 (en) | 2002-07-26 | 2007-08-28 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
| EP2009005A4 (en) * | 2006-04-19 | 2010-06-02 | Astellas Pharma Inc | AZOLECARBOXAMIDE DERIVATIVE |
| US7678791B2 (en) | 2006-07-12 | 2010-03-16 | Cumbre Ip Ventures, L.P. | Nitroheteroaryl-containing rifamycin derivatives |
| PE20080405A1 (es) * | 2006-07-21 | 2008-06-18 | Irm Llc | COMPUESTOS Y COMPOSICIONES COMO INHIBIDORES DE ITPKb |
| CA2668210C (en) * | 2006-10-31 | 2013-03-12 | Schering Corporation | Anilinopiperazine derivatives and methods of use thereof |
| CN101573353B (zh) * | 2006-12-27 | 2014-08-06 | 塞诺菲-安万特股份有限公司 | 取代的异喹啉和异喹啉酮衍生物 |
| EP1982714A1 (en) * | 2007-04-16 | 2008-10-22 | Laboratorios del Dr. Esteve S.A. | Pyrano-pyrazole-amines |
| MX2009011149A (es) * | 2007-04-16 | 2009-10-30 | Gruenenthal Gmbh | Ligandos de receptor de vainilloide novedosos y el uso de los mismos para la produccion de sustancias farmaceuticas. |
| US8202873B2 (en) * | 2007-05-11 | 2012-06-19 | Eli Lilly And Company | 2-[4-(pyrazol-4-ylalkyl)piperazin-1-yl]-3-phenyl pyrazines as 5-HT7 receptor antagonists |
| WO2008157844A1 (en) | 2007-06-21 | 2008-12-24 | Forest Laboratories Holdings Limited | Novel piperazine derivatives as inhibitors of stearoyl-coa desaturase |
| TW200914020A (en) | 2007-08-28 | 2009-04-01 | Lilly Co Eli | Substituted piperazinyl pyrazines and pyridines as 5-HT7 receptor antagonists |
| EP3564240B1 (en) | 2007-08-31 | 2022-04-06 | Purdue Pharma L.P. | Piperidine intermediates |
| WO2010046780A2 (en) | 2008-10-22 | 2010-04-29 | Institut Pasteur Korea | Anti viral compounds |
| CN102271681B (zh) * | 2008-11-04 | 2014-11-12 | 凯莫森特里克斯股份有限公司 | Cxcr7调节剂 |
| US8853202B2 (en) * | 2008-11-04 | 2014-10-07 | Chemocentryx, Inc. | Modulators of CXCR7 |
| EP2375899B1 (en) | 2009-01-12 | 2015-02-25 | Array Biopharma Inc. | Piperidine-containing compounds and use thereof in the treatment of diabetes |
| KR20120140658A (ko) | 2010-02-12 | 2012-12-31 | 파마사이언스 인크. | Ｉａｐ ｂｉｒ 도메인 결합 화합물 |
| EP2395003A1 (en) | 2010-05-27 | 2011-12-14 | Laboratorios Del. Dr. Esteve, S.A. | Pyrazole compounds as sigma receptor inhibitors |
| JP2013528180A (ja) * | 2010-05-28 | 2013-07-08 | ジーイー・ヘルスケア・リミテッド | 放射性標識化合物及びその製造方法 |
-
2014
- 2014-12-19 EP EP14815384.4A patent/EP3083563A1/en not_active Withdrawn
- 2014-12-19 AU AU2014368368A patent/AU2014368368C1/en not_active Ceased
- 2014-12-19 CN CN201480069503.2A patent/CN105829287B/zh not_active Expired - Fee Related
- 2014-12-19 RU RU2016129110A patent/RU2709482C1/ru not_active IP Right Cessation
- 2014-12-19 US US15/106,423 patent/US10351535B2/en not_active Expired - Fee Related
- 2014-12-19 SG SG10201805267UA patent/SG10201805267UA/en unknown
- 2014-12-19 MA MA39145A patent/MA39145B1/fr unknown
- 2014-12-19 JP JP2016539896A patent/JP6553615B2/ja not_active Expired - Fee Related
- 2014-12-19 TN TN2016000203A patent/TN2016000203A1/en unknown
- 2014-12-19 UA UAA201607879A patent/UA120754C2/uk unknown
- 2014-12-19 MX MX2016008130A patent/MX2016008130A/es unknown
- 2014-12-19 WO PCT/EP2014/078852 patent/WO2015092009A1/en not_active Ceased
- 2014-12-19 MY MYPI2016701867A patent/MY179509A/en unknown
- 2014-12-19 CA CA2932051A patent/CA2932051A1/en not_active Abandoned
- 2014-12-19 KR KR1020167019809A patent/KR20160098506A/ko not_active Ceased
-
2016
- 2016-05-24 IL IL245808A patent/IL245808B/en active IP Right Grant
- 2016-05-25 PH PH12016500978A patent/PH12016500978A1/en unknown
-
2019
- 2019-05-30 US US16/426,024 patent/US10745361B2/en not_active Expired - Fee Related
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2016540792A5 (enExample) | ||
| ES2829270T3 (es) | Derivados de sulfonamida aromáticos | |
| JP6370368B2 (ja) | Ｂｒｄ４阻害剤としてのインドリノン類似体 | |
| JP5871896B2 (ja) | Ｂ−ｒａｆキナーゼインヒビター | |
| JP6495908B2 (ja) | ピリジノン | |
| JP5991974B2 (ja) | 新規アミノピラゾロキナゾリン | |
| RU2016129110A (ru) | Производные пиперазина, характеризующиеся мультимодальной активностью в отношении боли | |
| JP2017502010A5 (enExample) | ||
| AU2013207252A1 (en) | Carbamate compounds and pharmaceutical compositions thereof | |
| ES2926158T3 (es) | Derivados de 2-oxo-tiazol como inhibidores de a2a y compuestos para su uso en el tratamiento de cánceres | |
| KR20150082314A (ko) | 트라이아졸로피라진 | |
| WO2011144622A1 (en) | 1h - imidazo [4, 5 - c] quinolines | |
| JP2013504543A5 (enExample) | ||
| CN103328442A (zh) | 可用于治疗代谢性和炎性疾病的氮杂环丁烷衍生物 | |
| WO2018210729A1 (en) | Aromatic sulfonamide derivatives as antagonists or negative allosteric modulators of p2x4 receptor | |
| KR20180097732A (ko) | 3-((헤테로-)아릴)-8-아미노-2-옥소-1,3-디아자-스파이로-[4.5]-데칸 유도체 | |
| JP2016540793A5 (enExample) | ||
| EP2870145B1 (en) | Indene derivatives, their preparation and use as medicaments | |
| JP6329961B2 (ja) | 置換ピラゾロ［３，４−ｄ］ピリミジン化合物、その製造及びシグマ受容体リガンドとしての使用 | |
| JP2015521994A5 (enExample) | ||
| JP2014503570A (ja) | 新規な５−アルキニル−ピリジン | |
| JP6844822B2 (ja) | 疼痛に対して活性を有する置換モルホリン誘導体 | |
| JP5936147B2 (ja) | 新規な５−アルキニル−ピリジン | |
| AU2016272220B2 (en) | 2-(1-heteroarylpiperazin-4-yl)methyl-1,4-benzodioxane derivatives as alpha2C antagonists | |
| CA3022793C (en) | Aromatic sulfonamide derivatives |