JP2016540792A5 - - Google Patents
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- 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
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- 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
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- 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
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| CN107922384A (zh) * | 2015-07-29 | 2018-04-17 | 埃斯蒂文博士实验室股份有限公司 | 对疼痛具有多模式活性的酰胺衍生物 |
| CA2991937A1 (en) | 2015-07-29 | 2017-02-02 | Laboratorios Del Dr. Esteve, S.A. | Substituted amide derivatives having multimodal activity against pain |
| TN2018000355A1 (en) * | 2016-05-20 | 2020-06-15 | Esteve Pharmaceuticals Sa | Tetrahydropyran and thiopyran derivatives having multimodal activity against pain. |
| MA49019A (fr) * | 2017-03-21 | 2020-02-05 | Univ Temple | Nouveaux modulateurs du récepteur sigma 2 et leur procédé d'utilisation |
| MA49017A (fr) | 2017-03-21 | 2020-02-05 | Univ Temple | Modulateurs du récepteur 7 de la 5-hydroxytryptamine et utilisation de ces derniers en tant qu'agents thérapeutiques |
| BR112020018094A2 (pt) | 2018-03-08 | 2020-12-22 | Incyte Corporation | Compostos de aminopirazina diol como inibidores de pi3k-¿ |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| AR116934A1 (es) * | 2018-10-31 | 2021-06-30 | Esteve Pharmaceuticals Sa | Derivados de piperazinil y piperidinil-quinazolin-4(3h)-ona que tienen actividad contra el dolor |
| 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 |
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| 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 |
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| 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 |
| JP5182088B2 (ja) * | 2006-04-19 | 2013-04-10 | アステラス製薬株式会社 | アゾールカルボキサミド誘導体 |
| WO2008008480A2 (en) | 2006-07-12 | 2008-01-17 | Cumbre Pharmaceuticals Inc. | Nitroheteroaryl-containing rifamycin derivatives |
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| CA2668210C (en) | 2006-10-31 | 2013-03-12 | Schering Corporation | Anilinopiperazine derivatives and methods of use thereof |
| EP2114920A1 (en) * | 2006-12-27 | 2009-11-11 | Sanofi-Aventis | Substituted isoquinoline and isoquinolinone derivatives |
| EP1982714A1 (en) * | 2007-04-16 | 2008-10-22 | Laboratorios del Dr. Esteve S.A. | Pyrano-pyrazole-amines |
| CA2683461A1 (en) | 2007-04-16 | 2008-10-23 | Gruenenthal Gmbh | Novel vanilloid receptor ligands and the use thereof for the production of pharmaceuticals |
| JP5210375B2 (ja) | 2007-05-11 | 2013-06-12 | イーライ リリー アンド カンパニー | ５−ｈｔ７受容体拮抗薬としての２−［４−（ピラゾール−４−イルアルキル）ピペラジン−１−イル］−３−フェニルピラジンおよびピリジンならびに３−［４−（ピラゾール−４−イルアルキル）ピペラジン−１−イル］−２−フェニルピリジン |
| US7842696B2 (en) | 2007-06-21 | 2010-11-30 | Forest Laboratories Holdings Limited | 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 |
| TW201322983A (zh) | 2007-08-31 | 2013-06-16 | Purdue Pharma Lp | 經取代之喹□啉型哌啶化合物及其用途 |
| WO2010046780A2 (en) | 2008-10-22 | 2010-04-29 | Institut Pasteur Korea | Anti viral compounds |
| MX2011004490A (es) * | 2008-11-04 | 2011-07-20 | Chemocentryx Inc | Moduladores de cxcr7. |
| US8853202B2 (en) * | 2008-11-04 | 2014-10-07 | Chemocentryx, Inc. | Modulators of CXCR7 |
| WO2010080864A1 (en) | 2009-01-12 | 2010-07-15 | Array Biopharma Inc. | Piperidine-containing compounds and use thereof |
| WO2011098904A1 (en) | 2010-02-12 | 2011-08-18 | Aegera Therapeutics, Inc. | Iap bir domain binding compounds |
| EP2395003A1 (en) * | 2010-05-27 | 2011-12-14 | Laboratorios Del. Dr. Esteve, S.A. | Pyrazole compounds as sigma receptor inhibitors |
| WO2011150183A1 (en) | 2010-05-28 | 2011-12-01 | Ge Healthcare Limited | Radiolabeled compounds and methods thereof |
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- 2014-12-19 EP EP14815384.4A patent/EP3083563A1/en not_active Withdrawn
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