NO324865B1 - Pyrimidinderivater, medikament inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikamenter for behandling av sykdom - Google Patents
Pyrimidinderivater, medikament inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikamenter for behandling av sykdom Download PDFInfo
- Publication number
- NO324865B1 NO324865B1 NO20032291A NO20032291A NO324865B1 NO 324865 B1 NO324865 B1 NO 324865B1 NO 20032291 A NO20032291 A NO 20032291A NO 20032291 A NO20032291 A NO 20032291A NO 324865 B1 NO324865 B1 NO 324865B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- trifluoromethyl
- bis
- phenyl
- isobutyramide
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 98
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 6
- 201000010099 disease Diseases 0.000 title claims abstract 3
- 239000003814 drug Substances 0.000 title claims description 11
- 229940079593 drug Drugs 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 5
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000003230 pyrimidines Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- -1 cyclic tertiary amine Chemical class 0.000 claims abstract description 17
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 239000002253 acid Substances 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- 229940047889 isobutyramide Drugs 0.000 claims description 19
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims description 9
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 9
- 229940044551 receptor antagonist Drugs 0.000 claims description 7
- 239000002464 receptor antagonist Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 6
- MKQPUZPYZAHOQG-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenoxy)-2-(2-morpholin-4-ylethoxy)pyrimidin-5-yl]propanamide Chemical compound C=1N=C(OCCN2CCOCC2)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MKQPUZPYZAHOQG-UHFFFAOYSA-N 0.000 claims description 4
- AASDAECXVNZWNM-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenoxy)-2-[2-(dimethylamino)ethoxy]pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=CC=C(Cl)C=1OC1=NC(OCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 AASDAECXVNZWNM-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- WQQLAXNHNONZLX-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]propanamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WQQLAXNHNONZLX-UHFFFAOYSA-N 0.000 claims description 3
- DPAAXGRQEQCVBS-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenoxy)-2-[3-(dimethylamino)propoxy]pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=CC=C(Cl)C=1OC1=NC(OCCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DPAAXGRQEQCVBS-UHFFFAOYSA-N 0.000 claims description 3
- NDXDZSNCQMEXDE-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(dimethylamino)ethoxy]-n-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(OCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NDXDZSNCQMEXDE-UHFFFAOYSA-N 0.000 claims description 3
- LTAPECFHQNBSJR-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-[3-(dimethylamino)propoxy]-4-(4-fluorophenoxy)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=C(F)C=CC=1OC1=NC(OCCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 LTAPECFHQNBSJR-UHFFFAOYSA-N 0.000 claims description 2
- XGYLAROFDBQJSA-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)Cl)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XGYLAROFDBQJSA-UHFFFAOYSA-N 0.000 claims 1
- GEJGPKWIPRGMBN-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(4-fluorophenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C=CC(F)=CC=2)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GEJGPKWIPRGMBN-UHFFFAOYSA-N 0.000 claims 1
- BWILCADSEVQKNC-UHFFFAOYSA-N 4-(2-chlorophenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylic acid Chemical compound C1CN(C)CCN1C1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)Cl)=N1 BWILCADSEVQKNC-UHFFFAOYSA-N 0.000 claims 1
- GFLURAJRBYKDIV-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-piperazin-1-ylpyrimidine-5-carboxylic acid Chemical compound CC1=CC=CC=C1OC1=NC(N2CCNCC2)=NC=C1C(O)=O GFLURAJRBYKDIV-UHFFFAOYSA-N 0.000 claims 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims 1
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 2
- 238000003756 stirring Methods 0.000 abstract 1
- 239000000460 chlorine Substances 0.000 description 77
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 68
- 239000006260 foam Substances 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 32
- 238000004587 chromatography analysis Methods 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 229910004298 SiO 2 Inorganic materials 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000010410 layer Substances 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 102100024304 Protachykinin-1 Human genes 0.000 description 16
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 16
- 238000001704 evaporation Methods 0.000 description 16
- 230000008020 evaporation Effects 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 238000000034 method Methods 0.000 description 14
- ADTNSTHKMIPKIJ-UHFFFAOYSA-N 1-[3,5-bis(trifluoromethyl)phenyl]-n-methylmethanamine Chemical compound CNCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ADTNSTHKMIPKIJ-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
- 239000007832 Na2SO4 Substances 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- 101800003906 Substance P Proteins 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 8
- 101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- WPARVBRLJFQZKP-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WPARVBRLJFQZKP-UHFFFAOYSA-N 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 6
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 5
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 5
- SFEVQUPISPQHOG-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl chloride Chemical compound ClC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SFEVQUPISPQHOG-UHFFFAOYSA-N 0.000 description 5
- ORXHUTVWOFSLEM-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenoxy)-2-methylsulfonylpyrimidin-5-yl]propanamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ORXHUTVWOFSLEM-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- GGYCFCZCVPPKRG-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxylic acid Chemical compound CSC1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)C)=N1 GGYCFCZCVPPKRG-UHFFFAOYSA-N 0.000 description 5
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 5
- SNNHLSHDDGJVDM-UHFFFAOYSA-N ethyl 4-chloro-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1Cl SNNHLSHDDGJVDM-UHFFFAOYSA-N 0.000 description 5
- 239000007903 gelatin capsule Substances 0.000 description 5
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 5
- BBSLDVCBHJLVIZ-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-fluorophenoxy)-n-methyl-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BBSLDVCBHJLVIZ-UHFFFAOYSA-N 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 102000003141 Tachykinin Human genes 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 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 4
- 239000002742 neurokinin 1 receptor antagonist Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 108060008037 tachykinin Proteins 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- PBKGYWLWIJLDGZ-UHFFFAOYSA-N 2-(dimethylamino)propan-1-ol Chemical compound OCC(C)N(C)C PBKGYWLWIJLDGZ-UHFFFAOYSA-N 0.000 description 3
- HMBVXCHFZBKNFF-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-[2-(dimethylamino)ethoxy]-4-(4-fluorophenoxy)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=C(F)C=CC=1OC1=NC(OCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HMBVXCHFZBKNFF-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
- 101710178035 Chorismate synthase 2 Proteins 0.000 description 3
- 101710152694 Cysteine synthase 2 Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 210000001130 astrocyte Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- ZHGXCAJGZVCTHU-UHFFFAOYSA-N ethyl 4-chloro-2-pyridin-4-ylpyrimidine-5-carboxylate Chemical compound N1=C(Cl)C(C(=O)OCC)=CN=C1C1=CC=NC=C1 ZHGXCAJGZVCTHU-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- CFQUTYZOGJOHDG-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(SC)=NC=C1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 CFQUTYZOGJOHDG-UHFFFAOYSA-N 0.000 description 3
- IEROYBURZCTCFW-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorophenoxy)-n-methyl-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IEROYBURZCTCFW-UHFFFAOYSA-N 0.000 description 3
- TWVKEEPGMBDVNX-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-methoxyphenoxy)-n-methyl-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound COC1=CC=CC=C1OC1=NC(S(C)(=O)=O)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 TWVKEEPGMBDVNX-UHFFFAOYSA-N 0.000 description 3
- QKESCOOVXCJKPK-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-2-methylsulfanyl-4-phenoxypyrimidine-5-carboxamide Chemical compound C=1C=CC=CC=1OC1=NC(SC)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 QKESCOOVXCJKPK-UHFFFAOYSA-N 0.000 description 3
- RNOXNNLXVDSJIM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-(2-morpholin-4-ylethoxy)pyrimidine-5-carboxamide Chemical compound C=1N=C(OCCN2CCOCC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 RNOXNNLXVDSJIM-UHFFFAOYSA-N 0.000 description 3
- AHMVWUFLHNAMIT-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(SC)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 AHMVWUFLHNAMIT-UHFFFAOYSA-N 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000000126 substance Substances 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
- 239000001993 wax Substances 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- JEAOLVJEETWDHD-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenoxy)-2-piperazin-1-ylpyrimidin-5-yl]propanamide Chemical compound C=1N=C(N2CCNCC2)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JEAOLVJEETWDHD-UHFFFAOYSA-N 0.000 description 2
- WYKVONSWOUJLND-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-[2-(dimethylamino)ethoxy]-4-(2-methylphenoxy)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(OCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WYKVONSWOUJLND-UHFFFAOYSA-N 0.000 description 2
- VLAKWOCXTBRERU-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-[2-(dimethylamino)ethylamino]-4-(4-fluorophenoxy)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=C(F)C=CC=1OC1=NC(NCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VLAKWOCXTBRERU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZAJLNGVUXCJIDJ-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxylic acid Chemical compound CC1=CC=CC=C1OC1=NC(S(C)(=O)=O)=NC=C1C(O)=O ZAJLNGVUXCJIDJ-UHFFFAOYSA-N 0.000 description 2
- XZKNJACGWIMBSP-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-pyridin-4-ylpyrimidine-5-carboxylic acid Chemical compound CC1=CC=CC=C1OC1=NC(C=2C=CN=CC=2)=NC=C1C(O)=O XZKNJACGWIMBSP-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 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
- 208000019695 Migraine disease Diseases 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000007124 Tachykinin Receptors Human genes 0.000 description 2
- 108010072901 Tachykinin Receptors Proteins 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- BUMGIEFFCMBQDG-UHFFFAOYSA-N dichlorosilicon Chemical compound Cl[Si]Cl BUMGIEFFCMBQDG-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- NOHYMMSQVRUEKN-UHFFFAOYSA-N ethyl 4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1OC1=CC=CC=C1C NOHYMMSQVRUEKN-UHFFFAOYSA-N 0.000 description 2
- NAGLAYYXLOFGPR-UHFFFAOYSA-N ethyl 4-(2-methylphenoxy)-2-pyrimidin-2-ylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(C=2N=CC=CN=2)N=C1OC1=CC=CC=C1C NAGLAYYXLOFGPR-UHFFFAOYSA-N 0.000 description 2
- IPCQJBGFNQPEOT-UHFFFAOYSA-N ethyl 4-chloro-2-pyrimidin-2-ylpyrimidine-5-carboxylate Chemical compound N1=C(Cl)C(C(=O)OCC)=CN=C1C1=NC=CC=N1 IPCQJBGFNQPEOT-UHFFFAOYSA-N 0.000 description 2
- BCZISJBETNEEGR-UHFFFAOYSA-N ethyl 6-oxo-2-pyrimidin-2-yl-1h-pyrimidine-5-carboxylate Chemical compound N1=C(O)C(C(=O)OCC)=CN=C1C1=NC=CC=N1 BCZISJBETNEEGR-UHFFFAOYSA-N 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- IXHFNEAFAWRVCF-UHFFFAOYSA-N n,2-dimethylpropanamide Chemical compound CNC(=O)C(C)C IXHFNEAFAWRVCF-UHFFFAOYSA-N 0.000 description 2
- VMUJNZBLVRQKAH-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(SC)=NC=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 VMUJNZBLVRQKAH-UHFFFAOYSA-N 0.000 description 2
- PGHBTNXZOJHJAV-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound CC1=CC=CC=C1OC1=NC(S(C)(=O)=O)=NC=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 PGHBTNXZOJHJAV-UHFFFAOYSA-N 0.000 description 2
- OVMLRCDSHYMDTL-UHFFFAOYSA-N n-[(3,5-dimethoxyphenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(SC)=NC=2)OC=2C(=CC=CC=2)C)=C1 OVMLRCDSHYMDTL-UHFFFAOYSA-N 0.000 description 2
- ONYKXDAOACOAKM-UHFFFAOYSA-N n-[(3,5-dimethoxyphenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(=NC=2)S(C)(=O)=O)OC=2C(=CC=CC=2)C)=C1 ONYKXDAOACOAKM-UHFFFAOYSA-N 0.000 description 2
- GBVAUYRPSVKAMS-UHFFFAOYSA-N n-[(3,5-dimethylphenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(SC)=NC=C1C(=O)N(C)CC1=CC(C)=CC(C)=C1 GBVAUYRPSVKAMS-UHFFFAOYSA-N 0.000 description 2
- KWAVIYLPTLQSCS-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-methoxyphenoxy)-n-methyl-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound COC1=CC=CC=C1OC1=NC(N2CCN(C)CC2)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KWAVIYLPTLQSCS-UHFFFAOYSA-N 0.000 description 2
- CWVPKHZZLZNKNE-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CWVPKHZZLZNKNE-UHFFFAOYSA-N 0.000 description 2
- KMDBZBRNBLFKNR-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-morpholin-4-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCOCC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 KMDBZBRNBLFKNR-UHFFFAOYSA-N 0.000 description 2
- JBGFKOOMNWLABT-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-piperazin-1-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCNCC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JBGFKOOMNWLABT-UHFFFAOYSA-N 0.000 description 2
- WYIFCYFEUORDQL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-thiomorpholin-4-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCSCC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WYIFCYFEUORDQL-UHFFFAOYSA-N 0.000 description 2
- HIJKMKKNNOXLIO-UHFFFAOYSA-N n-methyl-4-(2-methylphenoxy)-2-methylsulfanylpyrimidin-5-amine Chemical compound CNC1=CN=C(SC)N=C1OC1=CC=CC=C1C HIJKMKKNNOXLIO-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 239000002462 tachykinin receptor antagonist Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009529 traumatic brain injury Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- FMPVBCWFPONDEV-UHFFFAOYSA-N (3,5-dichlorophenyl)methanamine;n-[(3,5-dichlorophenyl)methyl]-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound NCC1=CC(Cl)=CC(Cl)=C1.C=1C=CC=C(C)C=1OC1=NC(SC)=NC=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 FMPVBCWFPONDEV-UHFFFAOYSA-N 0.000 description 1
- LIQSJWFBGRWREQ-UHFFFAOYSA-N 1-(3,5-dimethoxyphenyl)-N-methylmethanamine N-[(3,5-dimethoxyphenyl)methyl]-N-methyl-4-(2-methylphenoxy)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CNCC1=CC(OC)=CC(OC)=C1.COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(SC)=NC=2)OC=2C(=CC=CC=2)C)=C1 LIQSJWFBGRWREQ-UHFFFAOYSA-N 0.000 description 1
- HHXARJLFDKHCCL-UHFFFAOYSA-N 1-(3,5-dimethylphenyl)-n-methylmethanamine Chemical compound CNCC1=CC(C)=CC(C)=C1 HHXARJLFDKHCCL-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- JZUMPNUYDJBTNO-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 JZUMPNUYDJBTNO-UHFFFAOYSA-N 0.000 description 1
- NHIINYMRAFPAFG-UHFFFAOYSA-N 2-[2-(dimethylamino)ethoxy]-n-[(3,5-dimethylphenyl)methyl]-n-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(OCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C)=CC(C)=C1 NHIINYMRAFPAFG-UHFFFAOYSA-N 0.000 description 1
- SJTCCDRMPAKTOR-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[2-methyl-4-(2-methylphenoxy)pyrimidin-5-yl]propanamide Chemical compound C=1N=C(C)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SJTCCDRMPAKTOR-UHFFFAOYSA-N 0.000 description 1
- CEHBBAMHDHCNOA-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenoxy)-2-morpholin-4-ylpyrimidin-5-yl]propanamide Chemical compound C=1N=C(N2CCOCC2)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CEHBBAMHDHCNOA-UHFFFAOYSA-N 0.000 description 1
- IRIMTFNRRSYGQD-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n,2-dimethyl-n-[4-(2-methylphenoxy)-2-phenylpyrimidin-5-yl]propanamide Chemical compound C=1N=C(C=2C=CC=CC=2)N=C(OC=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IRIMTFNRRSYGQD-UHFFFAOYSA-N 0.000 description 1
- FLUULSJWDGVHNV-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[2-[3-(dimethylamino)propoxy]-4-(2-methylphenoxy)pyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(OCCCN(C)C)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 FLUULSJWDGVHNV-UHFFFAOYSA-N 0.000 description 1
- UASQCMGLUUDPOG-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-n,2-dimethylpropanamide;1-methylpiperazine Chemical compound CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)Cl)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 UASQCMGLUUDPOG-UHFFFAOYSA-N 0.000 description 1
- IUVRSNFCPNILPH-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenoxy)-2-methylsulfanylpyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=CC=C(Cl)C=1OC1=NC(SC)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IUVRSNFCPNILPH-UHFFFAOYSA-N 0.000 description 1
- DCBWOFCZJWZRCF-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(2-chlorophenoxy)-2-piperazin-1-ylpyrimidin-5-yl]-n,2-dimethylpropanamide;piperazine Chemical compound C1CNCCN1.C=1N=C(N2CCNCC2)N=C(OC=2C(=CC=CC=2)Cl)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 DCBWOFCZJWZRCF-UHFFFAOYSA-N 0.000 description 1
- MVCLRMCMSFAPKQ-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(4-fluorophenoxy)-2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]-n,2-dimethylpropanamide;1-methylpiperazine Chemical compound CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C=CC(F)=CC=2)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 MVCLRMCMSFAPKQ-UHFFFAOYSA-N 0.000 description 1
- CCJVCXTYIFDQDO-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(4-fluorophenoxy)-2-methylsulfanylpyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1C=C(F)C=CC=1OC1=NC(SC)=NC=C1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CCJVCXTYIFDQDO-UHFFFAOYSA-N 0.000 description 1
- YOXFTPLQUCBPIX-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-n-[4-(4-fluorophenoxy)-2-piperazin-1-ylpyrimidin-5-yl]-n,2-dimethylpropanamide Chemical compound C=1N=C(N2CCNCC2)N=C(OC=2C=CC(F)=CC=2)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 YOXFTPLQUCBPIX-UHFFFAOYSA-N 0.000 description 1
- KTEWTVPSSRBCMW-UHFFFAOYSA-N 2-chlorophenol;ethyl 4-(2-chlorophenoxy)-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound OC1=CC=CC=C1Cl.CCOC(=O)C1=CN=C(SC)N=C1OC1=CC=CC=C1Cl KTEWTVPSSRBCMW-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- UZWQLYCQUDCVMF-UHFFFAOYSA-N 2-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxylic acid Chemical compound CC1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)C)=N1 UZWQLYCQUDCVMF-UHFFFAOYSA-N 0.000 description 1
- LOLBDIUDMSAMQE-UHFFFAOYSA-N 3-chlorobenzenecarboperoxoic acid N-[(3,5-dimethylphenyl)methyl]-N-methyl-4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C)=CC(C)=C1 LOLBDIUDMSAMQE-UHFFFAOYSA-N 0.000 description 1
- REGPACCWCFIPKK-UHFFFAOYSA-N 4-(2-chlorophenoxy)-2-methylsulfanylpyrimidine-5-carboxylic acid Chemical compound CSC1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)Cl)=N1 REGPACCWCFIPKK-UHFFFAOYSA-N 0.000 description 1
- FYIXAZSUICLVFJ-UHFFFAOYSA-N 4-(2-chlorophenoxy)-2-methylsulfonylpyrimidine-5-carboxylic acid Chemical compound CS(=O)(=O)C1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)Cl)=N1 FYIXAZSUICLVFJ-UHFFFAOYSA-N 0.000 description 1
- KBIOGHBPFLHKFX-UHFFFAOYSA-N 4-(2-chlorophenoxy)-n-methyl-2-methylsulfanylpyrimidin-5-amine Chemical compound CNC1=CN=C(SC)N=C1OC1=CC=CC=C1Cl KBIOGHBPFLHKFX-UHFFFAOYSA-N 0.000 description 1
- BCFIJWDSPBQFGK-UHFFFAOYSA-N 4-(2-fluorophenoxy)-2-methylsulfonylpyrimidine-5-carboxylic acid Chemical compound CS(=O)(=O)C1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)F)=N1 BCFIJWDSPBQFGK-UHFFFAOYSA-N 0.000 description 1
- MFIZZBSXIGSLOX-UHFFFAOYSA-N 4-(2-methoxyphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylic acid Chemical compound COC1=CC=CC=C1OC1=NC(N2CCN(C)CC2)=NC=C1C(O)=O MFIZZBSXIGSLOX-UHFFFAOYSA-N 0.000 description 1
- KGGYWEHNSQOXFY-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylic acid Chemical compound C1CN(C)CCN1C1=NC=C(C(O)=O)C(OC=2C(=CC=CC=2)C)=N1 KGGYWEHNSQOXFY-UHFFFAOYSA-N 0.000 description 1
- WDZBQJRINYWGMV-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-phenylpyrimidine-5-carboxylic acid Chemical compound CC1=CC=CC=C1OC1=NC(C=2C=CC=CC=2)=NC=C1C(O)=O WDZBQJRINYWGMV-UHFFFAOYSA-N 0.000 description 1
- HOTXAVOSZCIZQL-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-pyrimidin-2-ylpyrimidine-5-carboxylic acid Chemical compound CC1=CC=CC=C1OC1=NC(C=2N=CC=CN=2)=NC=C1C(O)=O HOTXAVOSZCIZQL-UHFFFAOYSA-N 0.000 description 1
- ZAXUGQONWMPUKA-UHFFFAOYSA-N 4-(2-methylphenoxy)-2-thiomorpholin-4-ylpyrimidine-5-carboxylic acid Chemical compound CC1=CC=CC=C1OC1=NC(N2CCSCC2)=NC=C1C(O)=O ZAXUGQONWMPUKA-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- HEDOWVXQCRPVDH-UHFFFAOYSA-N 4-(4-fluorophenoxy)-2-methylsulfanylpyrimidine-5-carboxylic acid Chemical compound CSC1=NC=C(C(O)=O)C(OC=2C=CC(F)=CC=2)=N1 HEDOWVXQCRPVDH-UHFFFAOYSA-N 0.000 description 1
- PGQJKAPAEBMLDB-UHFFFAOYSA-N 4-(4-fluorophenoxy)-2-pyridin-4-ylpyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C(C=2C=CN=CC=2)N=C1OC1=CC=C(F)C=C1 PGQJKAPAEBMLDB-UHFFFAOYSA-N 0.000 description 1
- PLDSCIXMRVGRKT-UHFFFAOYSA-N 4-(4-fluorophenoxy)-n-methyl-2-methylsulfanylpyrimidin-5-amine Chemical compound CNC1=CN=C(SC)N=C1OC1=CC=C(F)C=C1 PLDSCIXMRVGRKT-UHFFFAOYSA-N 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010066091 Bronchial Hyperreactivity Diseases 0.000 description 1
- YZSBLPWBEDOWSK-UHFFFAOYSA-N C1=CC=CC2=[N+]([O-])NN=C21 Chemical compound C1=CC=CC2=[N+]([O-])NN=C21 YZSBLPWBEDOWSK-UHFFFAOYSA-N 0.000 description 1
- NDTGHMWAHXRKLH-UHFFFAOYSA-N C1CNCCN1.C=1N=C(N2CCNCC2)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 Chemical compound C1CNCCN1.C=1N=C(N2CCNCC2)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NDTGHMWAHXRKLH-UHFFFAOYSA-N 0.000 description 1
- QBOLEOISMPOZEA-UHFFFAOYSA-N CN(C)CCO.C=1C=CC=C(C)C=1OC1=NC(OCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C)=CC(C)=C1 Chemical compound CN(C)CCO.C=1C=CC=C(C)C=1OC1=NC(OCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C)=CC(C)=C1 QBOLEOISMPOZEA-UHFFFAOYSA-N 0.000 description 1
- RBZTTXQHRGEMAY-UHFFFAOYSA-N CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 Chemical compound CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 RBZTTXQHRGEMAY-UHFFFAOYSA-N 0.000 description 1
- NJNCJEYFVSMFLG-UHFFFAOYSA-N CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 Chemical compound CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NJNCJEYFVSMFLG-UHFFFAOYSA-N 0.000 description 1
- NXJAIHVIVVZGGL-UHFFFAOYSA-N CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 Chemical compound CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NXJAIHVIVVZGGL-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010011971 Decreased interest Diseases 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- WJCYFATVGFQQMO-UHFFFAOYSA-N N-[(3,5-dimethoxyphenyl)methyl]-2-[2-(dimethylamino)ethoxy]-N-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxamide 2-(dimethylamino)ethanol Chemical compound CN(C)CCO.COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(OCCN(C)C)=NC=2)OC=2C(=CC=CC=2)C)=C1 WJCYFATVGFQQMO-UHFFFAOYSA-N 0.000 description 1
- PHMGPFGLBRNDMQ-UHFFFAOYSA-N N-[(3,5-dimethoxyphenyl)methyl]-N-methyl-4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide 1-methylpiperazine Chemical compound CN1CCNCC1.COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(=NC=2)N2CCN(C)CC2)OC=2C(=CC=CC=2)C)=C1 PHMGPFGLBRNDMQ-UHFFFAOYSA-N 0.000 description 1
- JSEGIEOSOBJGIM-UHFFFAOYSA-N N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorophenoxy)-N-methyl-2-methylsulfonylpyrimidine-5-carboxamide 3-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JSEGIEOSOBJGIM-UHFFFAOYSA-N 0.000 description 1
- ONUYSIVFAPLBKD-UHFFFAOYSA-N N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-methoxyphenoxy)-N-methyl-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide 1-methylpiperazine Chemical compound CN1CCNCC1.COC1=CC=CC=C1OC1=NC(N2CCN(C)CC2)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ONUYSIVFAPLBKD-UHFFFAOYSA-N 0.000 description 1
- LADOBISLNJCKCT-UHFFFAOYSA-N N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-methoxyphenoxy)-N-methyl-2-methylsulfonylpyrimidine-5-carboxamide 3-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.COC1=CC=CC=C1OC1=NC(S(C)(=O)=O)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 LADOBISLNJCKCT-UHFFFAOYSA-N 0.000 description 1
- ZLZRORBJKBSPJQ-UHFFFAOYSA-N N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-fluorophenoxy)-N-methyl-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide 1-methylpiperazine Chemical compound CN1CCNCC1.C=1N=C(N2CCN(C)CC2)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ZLZRORBJKBSPJQ-UHFFFAOYSA-N 0.000 description 1
- INOHOVFKBHTJGE-UHFFFAOYSA-N N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-fluorophenoxy)-N-methyl-2-methylsulfonylpyrimidine-5-carboxamide 3-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.C=1N=C(S(C)(=O)=O)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 INOHOVFKBHTJGE-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940123821 Neurokinin 1 receptor antagonist Drugs 0.000 description 1
- 102000028517 Neuropeptide receptor Human genes 0.000 description 1
- 108070000018 Neuropeptide receptor Proteins 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JDYBLGLILZIVIB-UHFFFAOYSA-N OOC(=O)C1=CC=CC(Cl)=C1.C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 JDYBLGLILZIVIB-UHFFFAOYSA-N 0.000 description 1
- BJFUUCYMEMMPLA-UHFFFAOYSA-N OOC(=O)C1=CC=CC(Cl)=C1.COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(=NC=2)S(C)(=O)=O)OC=2C(=CC=CC=2)C)=C1 Chemical compound OOC(=O)C1=CC=CC(Cl)=C1.COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(=NC=2)S(C)(=O)=O)OC=2C(=CC=CC=2)C)=C1 BJFUUCYMEMMPLA-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- ZPHBZEQOLSRPAK-UHFFFAOYSA-N Phosphoramidon Natural products C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O ZPHBZEQOLSRPAK-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000012545 Psychophysiologic disease Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000006568 Urinary Bladder Calculi Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 230000036427 bronchial hyperreactivity Effects 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000021617 central nervous system development Effects 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- OZJBPXIHSYAVJW-UHFFFAOYSA-N ethyl 2-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxylate;2-methylphenol Chemical compound CC1=CC=CC=C1O.CCOC(=O)C1=CN=C(C)N=C1OC1=CC=CC=C1C OZJBPXIHSYAVJW-UHFFFAOYSA-N 0.000 description 1
- HPUVDLCMBDVHRE-UHFFFAOYSA-N ethyl 2-methylsulfanyl-4-phenoxypyrimidine-5-carboxylate;phenol Chemical compound OC1=CC=CC=C1.CCOC(=O)C1=CN=C(SC)N=C1OC1=CC=CC=C1 HPUVDLCMBDVHRE-UHFFFAOYSA-N 0.000 description 1
- UHPIOHRQQWPRQK-UHFFFAOYSA-N ethyl 4-(2-methoxyphenoxy)-2-methylsulfanylpyrimidine-5-carboxylate;2-methoxyphenol Chemical compound COC1=CC=CC=C1O.CCOC(=O)C1=CN=C(SC)N=C1OC1=CC=CC=C1OC UHPIOHRQQWPRQK-UHFFFAOYSA-N 0.000 description 1
- BWLRTWRGWZJUNK-UHFFFAOYSA-N ethyl 4-(2-methylphenoxy)-2-phenylpyrimidine-5-carboxylate;2-methylphenol Chemical compound CC1=CC=CC=C1O.CCOC(=O)C1=CN=C(C=2C=CC=CC=2)N=C1OC1=CC=CC=C1C BWLRTWRGWZJUNK-UHFFFAOYSA-N 0.000 description 1
- ZPPINWKQTHEBCY-UHFFFAOYSA-N ethyl 4-(2-methylphenoxy)-2-pyridin-4-ylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(C=2C=CN=CC=2)N=C1OC1=CC=CC=C1C ZPPINWKQTHEBCY-UHFFFAOYSA-N 0.000 description 1
- GQYQDXMICDAUOU-UHFFFAOYSA-N ethyl 4-(4-fluorophenoxy)-2-methylsulfanylpyrimidine-5-carboxylate;4-fluorophenol Chemical compound OC1=CC=C(F)C=C1.CCOC(=O)C1=CN=C(SC)N=C1OC1=CC=C(F)C=C1 GQYQDXMICDAUOU-UHFFFAOYSA-N 0.000 description 1
- UALJALJYRMMDFI-UHFFFAOYSA-N ethyl 4-(4-fluorophenoxy)-2-pyridin-4-ylpyrimidine-5-carboxylate;4-fluorophenol Chemical compound OC1=CC=C(F)C=C1.CCOC(=O)C1=CN=C(C=2C=CN=CC=2)N=C1OC1=CC=C(F)C=C1 UALJALJYRMMDFI-UHFFFAOYSA-N 0.000 description 1
- LXIAVLIGRIDNHQ-UHFFFAOYSA-N ethyl 4-chloro-2-methylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(C)N=C1Cl LXIAVLIGRIDNHQ-UHFFFAOYSA-N 0.000 description 1
- VXWYTPARKVGWFX-UHFFFAOYSA-N ethyl 4-chloro-2-phenylpyrimidine-5-carboxylate Chemical compound N1=C(Cl)C(C(=O)OCC)=CN=C1C1=CC=CC=C1 VXWYTPARKVGWFX-UHFFFAOYSA-N 0.000 description 1
- DOVJMJFNYVNXQZ-UHFFFAOYSA-N ethyl 6-oxo-2-pyridin-4-yl-1h-pyrimidine-5-carboxylate Chemical compound N1=C(O)C(C(=O)OCC)=CN=C1C1=CC=NC=C1 DOVJMJFNYVNXQZ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- WOKPMBWYOZGWNU-UHFFFAOYSA-N n,2-dimethyl-4-(2-methylphenoxy)pyrimidin-5-amine Chemical compound CNC1=CN=C(C)N=C1OC1=CC=CC=C1C WOKPMBWYOZGWNU-UHFFFAOYSA-N 0.000 description 1
- PFPSZGPAQFBVHZ-UHFFFAOYSA-N n-(3-chlorophenyl)-2-[(4-phenyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)sulfanyl]acetamide Chemical compound ClC1=CC=CC(NC(=O)CSC=2N(C(C=3C=CN=CC=3)=NN=2)C=2C=CC=CC=2)=C1 PFPSZGPAQFBVHZ-UHFFFAOYSA-N 0.000 description 1
- XDZSMYUWAAHHTB-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound C1CN(C)CCN1C(N=C1OC=2C(=CC=CC=2)C)=NC=C1C(=O)NCC1=CC(Cl)=CC(Cl)=C1 XDZSMYUWAAHHTB-UHFFFAOYSA-N 0.000 description 1
- BZQWJLYTYWYYDK-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 BZQWJLYTYWYYDK-UHFFFAOYSA-N 0.000 description 1
- WSYYSAIPIPLPFG-UHFFFAOYSA-N n-[(3,5-dichlorophenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(Cl)=CC(Cl)=C1 WSYYSAIPIPLPFG-UHFFFAOYSA-N 0.000 description 1
- LELZRHWLMBQJFP-UHFFFAOYSA-N n-[(3,5-dimethoxyphenyl)methyl]-2-[2-(dimethylamino)ethoxy]-n-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(OCCN(C)C)=NC=2)OC=2C(=CC=CC=2)C)=C1 LELZRHWLMBQJFP-UHFFFAOYSA-N 0.000 description 1
- IBEQUPZEHPXUAB-UHFFFAOYSA-N n-[(3,5-dimethoxyphenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound COC1=CC(OC)=CC(CN(C)C(=O)C=2C(=NC(=NC=2)N2CCN(C)CC2)OC=2C(=CC=CC=2)C)=C1 IBEQUPZEHPXUAB-UHFFFAOYSA-N 0.000 description 1
- GKPNHDDITOBOJS-UHFFFAOYSA-N n-[(3,5-dimethylphenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C)=CC(C)=C1 GKPNHDDITOBOJS-UHFFFAOYSA-N 0.000 description 1
- PTIJWQIRHANASI-UHFFFAOYSA-N n-[(3,5-dimethylphenyl)methyl]-n-methyl-4-(2-methylphenoxy)-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C)=CC(C)=C1 PTIJWQIRHANASI-UHFFFAOYSA-N 0.000 description 1
- BNEKESREZBCDLY-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(dimethylamino)ethoxy]-4-(4-fluorophenoxy)-n-methylpyrimidine-5-carboxamide Chemical compound C=1C=C(F)C=CC=1OC1=NC(OCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 BNEKESREZBCDLY-UHFFFAOYSA-N 0.000 description 1
- JOYWUTXVJJMNTM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(dimethylamino)ethylamino]-4-(2-methoxyphenoxy)-n-methylpyrimidine-5-carboxamide Chemical compound COC1=CC=CC=C1OC1=NC(NCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JOYWUTXVJJMNTM-UHFFFAOYSA-N 0.000 description 1
- PFEWXXPRIRAMNO-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(dimethylamino)ethylamino]-4-(4-fluorophenoxy)-n-methylpyrimidine-5-carboxamide Chemical compound C=1C=C(F)C=CC=1OC1=NC(NCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 PFEWXXPRIRAMNO-UHFFFAOYSA-N 0.000 description 1
- LCXKGXVCDFDPFD-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(dimethylamino)ethylamino]-n-methyl-4-(2-methylphenoxy)pyrimidine-5-carboxamide Chemical compound C=1C=CC=C(C)C=1OC1=NC(NCCN(C)C)=NC=C1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 LCXKGXVCDFDPFD-UHFFFAOYSA-N 0.000 description 1
- XJVMCALIRMIPLL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(2-chlorophenoxy)-n-methyl-2-methylsulfonylpyrimidine-5-carboxamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C(=CC=CC=2)Cl)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XJVMCALIRMIPLL-UHFFFAOYSA-N 0.000 description 1
- CWNZQKWZIPVESU-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-fluorophenoxy)-n-methyl-2-piperazin-1-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCNCC2)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CWNZQKWZIPVESU-UHFFFAOYSA-N 0.000 description 1
- JSUHDMMFGDGUKD-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-fluorophenoxy)-n-methyl-2-pyridin-4-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(C=2C=CN=CC=2)N=C(OC=2C=CC(F)=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JSUHDMMFGDGUKD-UHFFFAOYSA-N 0.000 description 1
- GZBXAEXEPYSTFC-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n,2-dimethyl-4-(2-methylphenoxy)pyrimidine-5-carboxamide Chemical compound C=1N=C(C)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GZBXAEXEPYSTFC-UHFFFAOYSA-N 0.000 description 1
- IJYUJNBSGHMBGT-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-2-(4-methylpiperazin-1-yl)-4-phenoxypyrimidine-5-carboxamide Chemical compound C=1N=C(N2CCN(C)CC2)N=C(OC=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 IJYUJNBSGHMBGT-UHFFFAOYSA-N 0.000 description 1
- JJVQNOHOCYJPRC-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-2-methylsulfonyl-4-phenoxypyrimidine-5-carboxamide Chemical compound C=1N=C(S(C)(=O)=O)N=C(OC=2C=CC=CC=2)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 JJVQNOHOCYJPRC-UHFFFAOYSA-N 0.000 description 1
- SHRINTLLPVXNSM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-phenylpyrimidine-5-carboxamide Chemical compound C=1N=C(C=2C=CC=CC=2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SHRINTLLPVXNSM-UHFFFAOYSA-N 0.000 description 1
- SMCBBJIGLWTFIL-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-pyridin-4-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(C=2C=CN=CC=2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 SMCBBJIGLWTFIL-UHFFFAOYSA-N 0.000 description 1
- VXNMGQVVKIJHAM-UHFFFAOYSA-N n-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-methyl-4-(2-methylphenoxy)-2-pyrimidin-2-ylpyrimidine-5-carboxamide Chemical compound C=1N=C(C=2N=CC=CN=2)N=C(OC=2C(=CC=CC=2)C)C=1C(=O)N(C)CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VXNMGQVVKIJHAM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- DAGCHDPMTBYVMK-UHFFFAOYSA-N n-methyl-4-(2-methylphenoxy)-2-phenylpyrimidin-5-amine Chemical compound CNC1=CN=C(C=2C=CC=CC=2)N=C1OC1=CC=CC=C1C DAGCHDPMTBYVMK-UHFFFAOYSA-N 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 239000006259 organic additive Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- BWSDNRQVTFZQQD-AYVHNPTNSA-N phosphoramidon Chemical compound O([P@@](O)(=O)N[C@H](CC(C)C)C(=O)N[C@H](CC=1[C]2C=CC=CC2=NC=1)C(O)=O)[C@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@@H]1O BWSDNRQVTFZQQD-AYVHNPTNSA-N 0.000 description 1
- 108010072906 phosphoramidon Proteins 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- LZIYBABLVXXFGZ-UHFFFAOYSA-N pyrimidine-2-carboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=NC=CC=N1 LZIYBABLVXXFGZ-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 210000003594 spinal ganglia Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000002466 tachykinin receptor agonist Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- XFLVZVGEZGRKSK-UHFFFAOYSA-N tert-butyl n-[2-methyl-4-(2-methylphenoxy)pyrimidin-5-yl]carbamate Chemical compound CC1=NC=C(NC(=O)OC(C)(C)C)C(OC=2C(=CC=CC=2)C)=N1 XFLVZVGEZGRKSK-UHFFFAOYSA-N 0.000 description 1
- DHIVKHHOCDONGI-UHFFFAOYSA-N tert-butyl n-[4-(2-methylphenoxy)-2-methylsulfanylpyrimidin-5-yl]carbamate Chemical compound CSC1=NC=C(NC(=O)OC(C)(C)C)C(OC=2C(=CC=CC=2)C)=N1 DHIVKHHOCDONGI-UHFFFAOYSA-N 0.000 description 1
- OTLSMUKJGZTSRZ-UHFFFAOYSA-N tert-butyl n-methyl-n-[2-methyl-4-(2-methylphenoxy)pyrimidin-5-yl]carbamate Chemical compound CC(C)(C)OC(=O)N(C)C1=CN=C(C)N=C1OC1=CC=CC=C1C OTLSMUKJGZTSRZ-UHFFFAOYSA-N 0.000 description 1
- CBYYXVPWDAFOOE-UHFFFAOYSA-N tert-butyl n-methyl-n-[4-(2-methylphenoxy)-2-methylsulfanylpyrimidin-5-yl]carbamate Chemical compound CSC1=NC=C(N(C)C(=O)OC(C)(C)C)C(OC=2C(=CC=CC=2)C)=N1 CBYYXVPWDAFOOE-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
-
- 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
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP00125529 | 2000-11-22 | ||
PCT/EP2001/013084 WO2002042280A2 (en) | 2000-11-22 | 2001-11-13 | Pyrimidine derivatives |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20032291L NO20032291L (no) | 2003-05-21 |
NO20032291D0 NO20032291D0 (no) | 2003-05-21 |
NO324865B1 true NO324865B1 (no) | 2007-12-17 |
Family
ID=8170446
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20032291A NO324865B1 (no) | 2000-11-22 | 2003-05-21 | Pyrimidinderivater, medikament inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikamenter for behandling av sykdom |
Country Status (31)
Country | Link |
---|---|
US (1) | US6787539B2 (es) |
EP (1) | EP1339698A2 (es) |
JP (1) | JP3993100B2 (es) |
KR (1) | KR100571337B1 (es) |
CN (1) | CN1309710C (es) |
AR (1) | AR031486A1 (es) |
AU (2) | AU2792102A (es) |
BG (1) | BG107840A (es) |
BR (1) | BR0115480A (es) |
CA (1) | CA2429570A1 (es) |
CZ (1) | CZ20031666A3 (es) |
EC (1) | ECSP034619A (es) |
GT (1) | GT200100232A (es) |
HK (1) | HK1078079A1 (es) |
HR (1) | HRP20030362A2 (es) |
HU (1) | HUP0303045A3 (es) |
IL (2) | IL155705A0 (es) |
JO (1) | JO2307B1 (es) |
MA (1) | MA26967A1 (es) |
MX (1) | MXPA03004453A (es) |
NO (1) | NO324865B1 (es) |
NZ (1) | NZ525555A (es) |
PA (1) | PA8533501A1 (es) |
PE (1) | PE20020760A1 (es) |
PL (1) | PL366394A1 (es) |
RU (1) | RU2284997C2 (es) |
SK (1) | SK7612003A3 (es) |
UY (1) | UY27034A1 (es) |
WO (1) | WO2002042280A2 (es) |
YU (1) | YU39503A (es) |
ZA (1) | ZA200303517B (es) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CZ20022413A3 (cs) * | 2000-01-31 | 2003-08-13 | Pfizer Products Inc. | Pyrimidinkarboxamidy užitečné jako inhibitory isozymů PDE4 |
WO2005047268A2 (en) * | 2003-11-10 | 2005-05-26 | X-Ceptor Therapeutics, Inc. | Substituted pyrimidine compositions and methods of use |
JP4613501B2 (ja) | 2004-03-17 | 2011-01-19 | 味の素株式会社 | 5−保護アミノピリミジン化合物の製造方法 |
JP4501015B2 (ja) | 2004-03-17 | 2010-07-14 | 味の素株式会社 | アミノピリミジン化合物の製造方法 |
JP2007534941A (ja) * | 2004-04-22 | 2007-11-29 | ザイゴ コーポレーション | 光学干渉計システムおよび光学干渉計システムを用いる方法 |
WO2005110416A2 (en) * | 2004-05-08 | 2005-11-24 | Neurogen Corporation | 4,5-disubstituted-2-aryl pyrimidines |
CA2598762A1 (en) | 2005-02-25 | 2006-08-31 | F. Hoffmann-La Roche Ag | Tablets with improved drug substance dispersibility |
DE102005027150A1 (de) * | 2005-03-12 | 2006-09-28 | Bayer Healthcare Ag | Pyrimidincarbonsäure-Derivate und ihre Verwendung |
EP2129381A1 (en) | 2007-01-24 | 2009-12-09 | Glaxo Group Limited | Pharmaceutical compositions comprising 3, 5-diamin0-6- (2, 3-dichl0phenyl) -l, 2, 4-triazine or r (-) -2, 4-diamino-5- (2, 3-dichlorophenyl) -6-fluoromethyl pyrimidine and an nk1 |
KR101032186B1 (ko) * | 2008-12-31 | 2011-05-02 | 엘에스산전 주식회사 | 정격 미세 조정이 가능한 과전류 계전기 |
WO2011053705A1 (en) * | 2009-10-30 | 2011-05-05 | Janssen Pharmaceutica Nv | Pyrimidine compounds as delta opioid receptor modulators |
JP5770198B2 (ja) * | 2009-10-30 | 2015-08-26 | ヤンセン ファーマシューティカ エヌ.ベー. | オピオイド受容体調節因子としてのフェノキシ置換ピリミジン |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57131771A (en) * | 1981-02-10 | 1982-08-14 | Mitsubishi Yuka Yakuhin Kk | Novel pyrimidine derivative |
FR2536071B1 (fr) * | 1982-11-12 | 1986-07-11 | Sanofi Sa | Sels acides de 2-piperazinopyrimidine, procede pour leur preparation et compositions pharmaceutiques en contenant |
DE3752141T2 (de) | 1986-02-24 | 1998-03-26 | Mitsui Petrochemical Ind | Mittel zur behandlung von neuropathie |
IL111960A (en) | 1993-12-17 | 1999-12-22 | Merck & Co Inc | Morpholines and thiomorpholines their preparation and pharmaceutical compositions containing them |
SG52217A1 (en) | 1993-12-29 | 1998-09-28 | Merck Sharp & Dohme | Substituted morpholine derivatives and their use as therapeutic agents |
IL112778A0 (en) | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
US5972938A (en) | 1997-12-01 | 1999-10-26 | Merck & Co., Inc. | Method for treating or preventing psychoimmunological disorders |
CZ20022413A3 (cs) * | 2000-01-31 | 2003-08-13 | Pfizer Products Inc. | Pyrimidinkarboxamidy užitečné jako inhibitory isozymů PDE4 |
-
2000
- 2000-11-13 YU YU39503A patent/YU39503A/sh unknown
-
2001
- 2001-10-15 US US09/977,586 patent/US6787539B2/en not_active Expired - Fee Related
- 2001-11-13 MX MXPA03004453A patent/MXPA03004453A/es active IP Right Grant
- 2001-11-13 CN CNB018191169A patent/CN1309710C/zh not_active Expired - Fee Related
- 2001-11-13 NZ NZ525555A patent/NZ525555A/en unknown
- 2001-11-13 BR BR0115480-0A patent/BR0115480A/pt not_active Application Discontinuation
- 2001-11-13 AU AU2792102A patent/AU2792102A/xx active Pending
- 2001-11-13 SK SK761-2003A patent/SK7612003A3/sk unknown
- 2001-11-13 WO PCT/EP2001/013084 patent/WO2002042280A2/en active IP Right Grant
- 2001-11-13 CZ CZ20031666A patent/CZ20031666A3/cs unknown
- 2001-11-13 AU AU2002227921A patent/AU2002227921B2/en not_active Ceased
- 2001-11-13 IL IL15570501A patent/IL155705A0/xx active IP Right Grant
- 2001-11-13 RU RU2003117481/04A patent/RU2284997C2/ru not_active IP Right Cessation
- 2001-11-13 CA CA002429570A patent/CA2429570A1/en not_active Abandoned
- 2001-11-13 EP EP01989463A patent/EP1339698A2/en not_active Withdrawn
- 2001-11-13 PL PL01366394A patent/PL366394A1/xx not_active Application Discontinuation
- 2001-11-13 JP JP2002544415A patent/JP3993100B2/ja not_active Expired - Fee Related
- 2001-11-13 HU HU0303045A patent/HUP0303045A3/hu unknown
- 2001-11-13 KR KR1020037006777A patent/KR100571337B1/ko not_active IP Right Cessation
- 2001-11-15 JO JO2001188A patent/JO2307B1/en active
- 2001-11-19 PE PE2001001154A patent/PE20020760A1/es not_active Application Discontinuation
- 2001-11-21 AR ARP010105423A patent/AR031486A1/es not_active Application Discontinuation
- 2001-11-21 GT GT200100232A patent/GT200100232A/es unknown
- 2001-11-21 UY UY27034A patent/UY27034A1/es not_active Application Discontinuation
- 2001-11-21 PA PA20018533501A patent/PA8533501A1/es unknown
-
2003
- 2003-05-01 IL IL155705A patent/IL155705A/en not_active IP Right Cessation
- 2003-05-07 ZA ZA200303517A patent/ZA200303517B/en unknown
- 2003-05-08 HR HR20030362A patent/HRP20030362A2/xx not_active Application Discontinuation
- 2003-05-21 NO NO20032291A patent/NO324865B1/no unknown
- 2003-05-21 EC EC2003004619A patent/ECSP034619A/es unknown
- 2003-05-22 BG BG107840A patent/BG107840A/bg unknown
- 2003-05-22 MA MA27173A patent/MA26967A1/fr unknown
-
2005
- 2005-11-11 HK HK05110085A patent/HK1078079A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP1187814B1 (en) | 5-phenyl-pyrimidine derivatives | |
NO315554B1 (no) | 4-Fenyl-pyridin-derivater, fremgangsmåte ved fremstilling og anvendelse derav, og medikament inneholdende slike derivater | |
NO324865B1 (no) | Pyrimidinderivater, medikament inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikamenter for behandling av sykdom | |
NO317264B1 (no) | 2-(3,5-Bis-trifluormetyl-fenyl)-N-metyl-N-(6-morfolin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramid | |
AU2002227921A1 (en) | Pyrimidine derivatives | |
US6274588B1 (en) | 4-phenyl-pyrimidine derivatives |