TWI376378B - Purine compounds - Google Patents
Purine compounds Download PDFInfo
- Publication number
- TWI376378B TWI376378B TW098141555A TW98141555A TWI376378B TW I376378 B TWI376378 B TW I376378B TW 098141555 A TW098141555 A TW 098141555A TW 98141555 A TW98141555 A TW 98141555A TW I376378 B TWI376378 B TW I376378B
- Authority
- TW
- Taiwan
- Prior art keywords
- methyl
- compound
- pharmaceutically acceptable
- phenyl
- acceptable salt
- Prior art date
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- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 94
- 150000003839 salts Chemical class 0.000 claims description 42
- -1 tetrahydrofuranyl fluorenylmethyl Chemical group 0.000 claims description 29
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 208000002193 Pain Diseases 0.000 claims description 17
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 208000006820 Arthralgia Diseases 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 206010006002 Bone pain Diseases 0.000 claims description 7
- 210000000988 bone and bone Anatomy 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 4
- 229910052707 ruthenium Inorganic materials 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 101150010802 CVC2 gene Proteins 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000002923 oximes Chemical class 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 239000000460 chlorine Substances 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 26
- 239000002904 solvent Substances 0.000 description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 239000007789 gas Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000000556 agonist Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 101710187022 Cannabinoid receptor 2 Proteins 0.000 description 9
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 8
- 238000010586 diagram Methods 0.000 description 8
- 239000012972 dimethylethanolamine Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000012267 brine Substances 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 5
- 210000003127 knee Anatomy 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 4
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 4
- 238000005227 gel permeation chromatography Methods 0.000 description 4
- 230000008570 general process Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- OEAJNZQFAHZXAB-UHFFFAOYSA-N 1,4-dioxane;methane Chemical compound C.C1COCCO1 OEAJNZQFAHZXAB-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 101000875075 Homo sapiens Cannabinoid receptor 2 Proteins 0.000 description 3
- 101000875074 Rattus norvegicus Cannabinoid receptor 2 Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229930182558 Sterol Natural products 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- QECQLMGRLZYSEW-UHFFFAOYSA-N decoxybenzene Chemical compound CCCCCCCCCCOC1=CC=CC=C1 QECQLMGRLZYSEW-UHFFFAOYSA-N 0.000 description 3
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 150000004885 piperazines Chemical class 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 235000003702 sterols Nutrition 0.000 description 3
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 2
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 206010065390 Inflammatory pain Diseases 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- WJYJULOBJLLPER-UHFFFAOYSA-N copper(1+);trifluoromethane Chemical compound [Cu+].F[C-](F)F WJYJULOBJLLPER-UHFFFAOYSA-N 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 238000002309 gasification Methods 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229950008882 polysorbate Drugs 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 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
- 150000003432 sterols Chemical class 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000010455 vermiculite Substances 0.000 description 2
- 235000019354 vermiculite Nutrition 0.000 description 2
- 229910052902 vermiculite Inorganic materials 0.000 description 2
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
- RQXXCWHCUOJQGR-UHFFFAOYSA-N 1,1-dichlorohexane Chemical compound CCCCCC(Cl)Cl RQXXCWHCUOJQGR-UHFFFAOYSA-N 0.000 description 1
- MPQOMCMWZWRHPX-UHFFFAOYSA-N 1,2,3-trifluoroanthracene Chemical compound C1=CC=C2C=C(C(F)=C(C(F)=C3)F)C3=CC2=C1 MPQOMCMWZWRHPX-UHFFFAOYSA-N 0.000 description 1
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
- KGTRJWNQPJUJEH-UHFFFAOYSA-N 1-(dichloroamino)-3-iminourea Chemical compound ClN(NC(=O)N=N)Cl KGTRJWNQPJUJEH-UHFFFAOYSA-N 0.000 description 1
- KBSPJIWZDWBDGM-UHFFFAOYSA-N 1-Methylpyrene Chemical compound C1=C2C(C)=CC=C(C=C3)C2=C2C3=CC=CC2=C1 KBSPJIWZDWBDGM-UHFFFAOYSA-N 0.000 description 1
- SKYXZSVBBFFJQQ-UHFFFAOYSA-N 1-methyl-2h-pyrazine Chemical compound CN1CC=NC=C1 SKYXZSVBBFFJQQ-UHFFFAOYSA-N 0.000 description 1
- DNTQTNXUBQIWFE-UHFFFAOYSA-N 1-sulfanylpiperazine Chemical compound SN1CCNCC1 DNTQTNXUBQIWFE-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- JOWBFITYYIZBFK-UHFFFAOYSA-N 2,2-bis(sulfanyl)acetamide Chemical compound NC(=O)C(S)S JOWBFITYYIZBFK-UHFFFAOYSA-N 0.000 description 1
- BHNQPLPANNDEGL-UHFFFAOYSA-N 2-(4-octylphenoxy)ethanol Chemical compound CCCCCCCCC1=CC=C(OCCO)C=C1 BHNQPLPANNDEGL-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- NUCHSOWNRSBTJL-UHFFFAOYSA-N 2-methylpyrimidine-4,5-diamine Chemical compound CC1=NC=C(N)C(N)=N1 NUCHSOWNRSBTJL-UHFFFAOYSA-N 0.000 description 1
- WXBXQUFGRJEKPL-UHFFFAOYSA-N 2-methylundecan-2-amine Chemical compound CCCCCCCCCC(C)(C)N WXBXQUFGRJEKPL-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Immunology (AREA)
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13858908P | 2008-12-18 | 2008-12-18 |
Publications (2)
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|---|---|
| TW201024296A TW201024296A (en) | 2010-07-01 |
| TWI376378B true TWI376378B (en) | 2012-11-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW098141555A TWI376378B (en) | 2008-12-18 | 2009-12-04 | Purine compounds |
Country Status (29)
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|---|---|
| US (1) | US8252798B2 (enExample) |
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Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2543216T3 (es) * | 2009-03-13 | 2015-08-17 | Katholieke Universiteit Leuven, K.U. Leuven R&D | Moduladores de tiazolopirimidina como agentes inmunosupresores |
| KR20200008045A (ko) | 2009-08-28 | 2020-01-22 | 아레나 파마슈티칼스, 인크. | 칸나비노이드 수용체 조절제 |
| RU2012141536A (ru) * | 2010-03-17 | 2014-04-27 | Ф. Хоффманн-Ля Рош Аг | Имидазопиридины, композиции и способы применения |
| AR080711A1 (es) * | 2010-03-31 | 2012-05-02 | Lilly Co Eli | Compuesto de piperazin-purina composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para el tratamiento o prevencion del dolor |
| KR101432411B1 (ko) * | 2010-03-31 | 2014-08-20 | 일라이 릴리 앤드 캄파니 | Ｃｂ2 효능제로서 사용되는 퓨린 화합물 |
| CN103209695A (zh) | 2010-09-15 | 2013-07-17 | 弗·哈夫曼-拉罗切有限公司 | 氮杂苯并噻唑化合物、组合物及应用方法 |
| KR20140009259A (ko) | 2010-11-19 | 2014-01-22 | 에프. 호프만-라 로슈 아게 | 피라졸로피리딘 및 tyk2 억제제로서 이의 용도 |
| JP6043733B2 (ja) | 2011-02-25 | 2016-12-14 | アリーナ ファーマシューティカルズ， インコーポレイテッド | カンナビノイド受容体モジュレーター |
| MX346533B (es) | 2011-02-25 | 2017-03-14 | Arena Pharm Inc | Formas cristalinas y procesos para la preparacion de azaciclos condensados (moduladores de receptores canabinoides). |
| US9597340B2 (en) | 2011-02-25 | 2017-03-21 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| WO2013041539A1 (en) * | 2011-09-20 | 2013-03-28 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
| US9067943B2 (en) * | 2011-11-25 | 2015-06-30 | Hoffmann-La Roche Inc. | [1,2,3]triazolo[4,5-D]pyrimidine derivatives |
| PH12015500315B1 (en) * | 2012-08-16 | 2019-08-07 | Janssen Pharmaceutica Nv | Substituted pyrozales as n-type calcium channel blockers |
| WO2014120748A1 (en) | 2013-01-30 | 2014-08-07 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as hdm2 inhibitors |
| HRP20171099T1 (hr) * | 2013-05-02 | 2017-10-06 | F. Hoffmann - La Roche Ag | Derivati pirolo[2,3-d]pirimidina kao agonisti cb2 receptora |
| US9453002B2 (en) | 2013-08-16 | 2016-09-27 | Janssen Pharmaceutica Nv | Substituted imidazoles as N-type calcium channel blockers |
| WO2017052394A1 (en) * | 2015-09-23 | 2017-03-30 | Uniwersytet Jagielloński | Imidazopyridine compounds and their use as 5-ht6 receptor ligands |
| WO2018137176A1 (en) * | 2017-01-25 | 2018-08-02 | Eli Lilly And Company | Treatment for nonalcoholic steatohepatitis and fibrosis |
| WO2017184412A1 (en) | 2016-04-18 | 2017-10-26 | Eli Lilly And Company | Purine cannabinoid agonist for treating nonalcoholic steatohepatitis and fibrosis |
| WO2017181317A1 (en) * | 2016-04-18 | 2017-10-26 | Eli Lilly And Company | Treatment for nonalcoholic steatohepatitis and fibrosis |
| JP7071342B6 (ja) * | 2016-12-21 | 2023-12-20 | リサーチ トライアングル インスティテュート | 改善されたバイオアベイラビリティを有するジアリールプリン誘導体 |
| EP3621619B1 (en) | 2017-05-08 | 2023-06-28 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of visceral pain |
| WO2024017227A1 (zh) * | 2022-07-21 | 2024-01-25 | 长春金赛药业有限责任公司 | 取代的稠环大麻素受体化合物及其应用 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60260579A (ja) * | 1984-01-13 | 1985-12-23 | Yoshitomi Pharmaceut Ind Ltd | プリン誘導体 |
| IL87149A (en) | 1987-07-20 | 1994-05-30 | Merck & Co Inc | 6-Piperazinyl derivatives of purine and its 3- and 9-deaza isosteres, their preparation and pharmaceutical compositions containing them |
| US5057517A (en) * | 1987-07-20 | 1991-10-15 | Merck & Co., Inc. | Piperazinyl derivatives of purines and isosteres thereof as hypoglycemic agents |
| GB0003960D0 (en) * | 2000-02-18 | 2000-04-12 | Pfizer Ltd | Purine derivatives |
| WO2003022214A2 (en) | 2001-09-06 | 2003-03-20 | Millennium Pharmaceuticals, Inc. | Piperazine and homopiperazine compounds |
| US20030139427A1 (en) * | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
| US7129239B2 (en) * | 2002-10-28 | 2006-10-31 | Pfizer Inc. | Purine compounds and uses thereof |
| US20040224962A1 (en) * | 2003-05-09 | 2004-11-11 | Pfizer Inc | Pharmaceutical composition for the treatment of obesity or to facilitate or promote weight loss |
| US20050043327A1 (en) * | 2003-08-21 | 2005-02-24 | Pfizer Inc | Pharmaceutical composition for the prevention and treatment of addiction in a mammal |
| WO2005067546A2 (en) | 2004-01-13 | 2005-07-28 | Ambit Biosciences Corporation | Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases |
| KR20070054737A (ko) * | 2004-10-22 | 2007-05-29 | 화이자 프로덕츠 인코포레이티드 | 퓨린 화합물의 제조 방법 |
| US20070032493A1 (en) | 2005-05-26 | 2007-02-08 | Synta Pharmaceuticals Corp. | Method for treating B cell regulated autoimmune disorders |
| JP5231251B2 (ja) * | 2006-02-02 | 2013-07-10 | ミレニアム ファーマシューティカルズ， インコーポレイテッド | Ｅ１活性化酵素の阻害剤 |
| US20120295915A1 (en) * | 2009-11-24 | 2012-11-22 | Chaudhari Amita M | Azabenzimidazoles as fatty acid synthase inhibitors |
| AR080711A1 (es) * | 2010-03-31 | 2012-05-02 | Lilly Co Eli | Compuesto de piperazin-purina composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para el tratamiento o prevencion del dolor |
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