FI113172B - Bifenyylijohdannaiset, menetelmät niiden valmistamiseksi ja niiden käyttö sekä uudet välituotteet - Google Patents
Bifenyylijohdannaiset, menetelmät niiden valmistamiseksi ja niiden käyttö sekä uudet välituotteet Download PDFInfo
- Publication number
- FI113172B FI113172B FI951417A FI951417A FI113172B FI 113172 B FI113172 B FI 113172B FI 951417 A FI951417 A FI 951417A FI 951417 A FI951417 A FI 951417A FI 113172 B FI113172 B FI 113172B
- Authority
- FI
- Finland
- Prior art keywords
- group
- ethyl
- phenylpiperazine
- phenyl
- chloro
- Prior art date
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 238000000034 method Methods 0.000 title claims description 41
- 238000002360 preparation method Methods 0.000 title claims description 15
- 239000000543 intermediate Substances 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 168
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 51
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 45
- 150000003839 salts Chemical class 0.000 claims abstract description 44
- 125000005843 halogen group Chemical group 0.000 claims abstract description 41
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 32
- 102000005962 receptors Human genes 0.000 claims abstract description 28
- 108020003175 receptors Proteins 0.000 claims abstract description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 25
- 229960003638 dopamine Drugs 0.000 claims abstract description 20
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims abstract description 19
- 230000008485 antagonism Effects 0.000 claims abstract description 19
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 16
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 14
- 208000020016 psychiatric disease Diseases 0.000 claims abstract description 14
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 11
- 102000056834 5-HT2 Serotonin Receptors Human genes 0.000 claims abstract description 9
- 108091005479 5-HT2 receptors Proteins 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 9
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 8
- 206010029333 Neurosis Diseases 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 7
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 7
- 208000015238 neurotic disease Diseases 0.000 claims abstract description 7
- 206010001488 Aggression Diseases 0.000 claims abstract description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 6
- 230000016571 aggressive behavior Effects 0.000 claims abstract description 6
- 208000012761 aggressive behavior Diseases 0.000 claims abstract description 6
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims abstract description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims abstract description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 6
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 5
- 208000004547 Hallucinations Diseases 0.000 claims abstract description 4
- 208000012545 Psychophysiologic disease Diseases 0.000 claims abstract description 4
- 230000003340 mental effect Effects 0.000 claims abstract description 4
- 125000002252 acyl group Chemical group 0.000 claims abstract description 3
- 206010012218 Delirium Diseases 0.000 claims abstract 2
- 206010020651 Hyperkinesia Diseases 0.000 claims abstract 2
- 208000000269 Hyperkinesis Diseases 0.000 claims abstract 2
- 206010036173 Poriomania Diseases 0.000 claims abstract 2
- -1 pyrrolidyl group Chemical group 0.000 claims description 402
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 claims description 383
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 236
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 108
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
- 150000001875 compounds Chemical class 0.000 claims description 89
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 61
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 29
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 23
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 230000002140 halogenating effect Effects 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical group CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 12
- HCDKVZNERMVYEO-UHFFFAOYSA-N 2,2-dibromo-1-phenylpiperazine Chemical class BrC1(Br)CNCCN1C1=CC=CC=C1 HCDKVZNERMVYEO-UHFFFAOYSA-N 0.000 claims description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 11
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 8
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 238000006460 hydrolysis reaction Methods 0.000 claims description 7
- QLWMDSAMEIJLQB-UHFFFAOYSA-N 2-phenyl-1,3,2-dioxaborinane Chemical class O1CCCOB1C1=CC=CC=C1 QLWMDSAMEIJLQB-UHFFFAOYSA-N 0.000 claims description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000006017 1-propenyl group Chemical group 0.000 claims description 5
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 5
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 5
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical compound ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 claims description 4
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004036 acetal group Chemical group 0.000 claims description 4
- 150000008065 acid anhydrides Chemical class 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 claims description 3
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- DRROABBPFVWBKW-UHFFFAOYSA-N n-(4-ethyl-4-piperazin-1-ylcyclohexa-1,5-dien-1-yl)-2-methoxy-3-phenylbenzenesulfonamide Chemical compound C1=CC(CC)(N2CCNCC2)CC=C1NS(=O)(=O)C(C=1OC)=CC=CC=1C1=CC=CC=C1 DRROABBPFVWBKW-UHFFFAOYSA-N 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 claims description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000008196 pharmacological composition Substances 0.000 claims description 3
- 239000001294 propane Substances 0.000 claims description 3
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 3
- 125000001382 thioacetal group Chemical group 0.000 claims description 3
- MHBONQZDOYFHIB-UHFFFAOYSA-N 1-(3-phenylphenyl)piperazine Chemical compound C1CNCCN1C1=CC=CC(C=2C=CC=CC=2)=C1 MHBONQZDOYFHIB-UHFFFAOYSA-N 0.000 claims description 2
- BYSQAMCFZXQDDM-UHFFFAOYSA-N 1-(4-methyl-3-phenylphenyl)piperazine Chemical compound CC1=CC=C(N2CCNCC2)C=C1C1=CC=CC=C1 BYSQAMCFZXQDDM-UHFFFAOYSA-N 0.000 claims description 2
- SPHZTIYBNUKXLD-UHFFFAOYSA-N 1-benzyl-4-(4-methyl-3-phenylphenyl)piperazine Chemical compound CC1=CC=C(N2CCN(CC=3C=CC=CC=3)CC2)C=C1C1=CC=CC=C1 SPHZTIYBNUKXLD-UHFFFAOYSA-N 0.000 claims description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 2
- CLSUSULTNCHYIB-UHFFFAOYSA-N 1-methyl-4-(4-methyl-3-phenylphenyl)piperazine Chemical compound C1CN(C)CCN1C1=CC=C(C)C(C=2C=CC=CC=2)=C1 CLSUSULTNCHYIB-UHFFFAOYSA-N 0.000 claims description 2
- BLYYIVRLKXZEAC-UHFFFAOYSA-N 2-(1,3,2-dioxaborinan-2-yl)benzaldehyde Chemical compound O=CC1=CC=CC=C1B1OCCCO1 BLYYIVRLKXZEAC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- 150000004791 alkyl magnesium halides Chemical class 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000012320 chlorinating reagent Substances 0.000 claims description 2
- 125000005145 cycloalkylaminosulfonyl group Chemical group 0.000 claims description 2
- UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 7
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical class [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 claims 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- OIFGOELLBRASGJ-UHFFFAOYSA-N 1-(2-methoxy-3-phenyl-5-piperazin-1-ylphenyl)-2-phenylethanone Chemical compound COC1=C(C(=O)CC=2C=CC=CC=2)C=C(N2CCNCC2)C=C1C1=CC=CC=C1 OIFGOELLBRASGJ-UHFFFAOYSA-N 0.000 claims 1
- VJGCZWVJDRIHNC-UHFFFAOYSA-N 1-fluoroprop-1-ene Chemical group CC=CF VJGCZWVJDRIHNC-UHFFFAOYSA-N 0.000 claims 1
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- 125000005452 alkenyloxyalkyl group Chemical group 0.000 claims 1
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims 1
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims 1
- 125000005037 alkyl phenyl group Chemical group 0.000 claims 1
- 230000003444 anaesthetic effect Effects 0.000 claims 1
- 230000037007 arousal Effects 0.000 claims 1
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- 229960002195 perazine Drugs 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 230000004970 emotional disturbance Effects 0.000 abstract description 2
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- 125000004446 heteroarylalkyl group Chemical group 0.000 abstract 2
- 208000019901 Anxiety disease Diseases 0.000 abstract 1
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- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
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- 230000005284 excitation Effects 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
- 238000005160 1H NMR spectroscopy Methods 0.000 description 166
- 229960005141 piperazine Drugs 0.000 description 142
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 122
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
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- 235000002639 sodium chloride Nutrition 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
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- 239000002904 solvent Substances 0.000 description 32
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- KPDLTBYCZXVKQN-UHFFFAOYSA-N ethyl 2-hydroxy-5-nitrobenzoate Chemical compound CCOC(=O)C1=CC([N+]([O-])=O)=CC=C1O KPDLTBYCZXVKQN-UHFFFAOYSA-N 0.000 description 1
- ZVUJZHCPBWUJBF-UHFFFAOYSA-N ethyl 3-bromo-2-chloro-5-piperazin-1-ylbenzoate hydrochloride Chemical compound Cl.BrC1=C(Cl)C(C(=O)OCC)=CC(N2CCNCC2)=C1 ZVUJZHCPBWUJBF-UHFFFAOYSA-N 0.000 description 1
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- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
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- 150000004795 grignard reagents Chemical class 0.000 description 1
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- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
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- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
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- LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
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- HWRBMQBTYDALTD-UHFFFAOYSA-N tert-butyl 4-(3-bromo-4-chloro-5-propanoylphenyl)piperazine-1-carboxylate Chemical compound BrC1=C(Cl)C(C(=O)CC)=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=C1 HWRBMQBTYDALTD-UHFFFAOYSA-N 0.000 description 1
- FZWHFAJUDVCIQQ-UHFFFAOYSA-N tert-butyl 4-[4-chloro-3-(1-fluoropropyl)-5-(2-formylphenyl)phenyl]piperazine-1-carboxylate Chemical compound ClC=1C(C(F)CC)=CC(N2CCN(CC2)C(=O)OC(C)(C)C)=CC=1C1=CC=CC=C1C=O FZWHFAJUDVCIQQ-UHFFFAOYSA-N 0.000 description 1
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- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
-
- 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
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- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/26—Radicals substituted by halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/06—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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- C—CHEMISTRY; METALLURGY
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
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- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/08—Six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- General Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
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JP8103094 | 1994-03-29 | ||
JP8103094 | 1994-03-29 | ||
JP31134794 | 1994-11-22 | ||
JP31134794 | 1994-11-22 | ||
JP33691994 | 1994-12-27 | ||
JP33691994 | 1994-12-27 |
Publications (3)
Publication Number | Publication Date |
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FI951417A0 FI951417A0 (fi) | 1995-03-24 |
FI951417A FI951417A (fi) | 1995-09-30 |
FI113172B true FI113172B (fi) | 2004-03-15 |
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Family Applications (1)
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FI951417A FI113172B (fi) | 1994-03-29 | 1995-03-24 | Bifenyylijohdannaiset, menetelmät niiden valmistamiseksi ja niiden käyttö sekä uudet välituotteet |
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US (2) | US5849912A (de) |
EP (1) | EP0675118B1 (de) |
KR (1) | KR100199638B1 (de) |
CN (2) | CN1114596C (de) |
AT (1) | ATE225780T1 (de) |
AU (1) | AU691561B2 (de) |
BR (1) | BR9500996A (de) |
CA (1) | CA2144669A1 (de) |
DE (1) | DE69528485T2 (de) |
ES (1) | ES2184772T3 (de) |
FI (1) | FI113172B (de) |
HU (1) | HUT72492A (de) |
NO (1) | NO305986B1 (de) |
NZ (1) | NZ270816A (de) |
RU (1) | RU2125051C1 (de) |
TW (1) | TW434229B (de) |
Families Citing this family (42)
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CA2144669A1 (en) * | 1994-03-29 | 1995-09-30 | Kozo Akasaka | Biphenyl derivatives |
JP3274579B2 (ja) * | 1995-01-12 | 2002-04-15 | 住友製薬株式会社 | 脳血管障害に伴う精神症候治療剤 |
GB9801392D0 (en) * | 1998-01-22 | 1998-03-18 | Smithkline Beecham Plc | Novel compounds |
SE9904724D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission I |
SE9904723D0 (sv) | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
USRE46117E1 (en) | 1999-12-22 | 2016-08-23 | Teva Pharmaceuticals International Gmbh | Modulators of dopamine neurotransmission |
GB0007907D0 (en) * | 2000-03-31 | 2000-05-17 | Merck Sharp & Dohme | Therapeutic agents |
CA2448080A1 (en) | 2001-05-22 | 2002-11-28 | Neurogen Corporation | Melanin concentrating hormone receptor ligands: substituted 1-benzyl-4-aryl piperazine analogues |
EP1935885A3 (de) * | 2001-05-22 | 2008-10-15 | Neurogen Corporation | Rezeptorliganden des melaninkonzentrierenden Hormons: substituierte 1-Benzyl-4-Aryl-Piperazinanaloga |
JP2007514764A (ja) * | 2003-12-19 | 2007-06-07 | スミスクライン・ビーチャム・コーポレイション | 化合物、組成物および方法 |
US7851629B2 (en) | 2004-06-08 | 2010-12-14 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | Disubstituted phenylpiperidines as modulators of dopamine and serotonin neurotransmission |
DE602005017784D1 (de) | 2004-06-08 | 2009-12-31 | Nsab, Filial Af Neurosearch Sweden Ab | Neue disubstituierte phenylpiperidine als modulatoren der dopamin- und serotoninneurotransmission |
CA2570064A1 (en) * | 2004-06-18 | 2005-12-29 | Neurosearch A/S | Novel alkyl substituted piperazine derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
HUE029790T2 (hu) | 2004-10-13 | 2017-04-28 | Teva Pharmaceuticals Int Gmbh | Eljárás 4-(3-metánszulfonil-fenil)-l-N-propil-piperidin elõállítására |
JP2008523075A (ja) * | 2004-12-13 | 2008-07-03 | 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 | 5ht2cレセプター関連障害の処置に有用な5ht2cレセプターのモジュレーターとしてのn−ビアリールピペラジン誘導体およびn−アリールヘテロアリールピペラジン誘導体 |
ATE544748T1 (de) | 2004-12-28 | 2012-02-15 | Kinex Pharmaceuticals Llc | Zusammensetzungen und verfahren für die behandlung von zellproliferationserkrankungen |
US7968574B2 (en) | 2004-12-28 | 2011-06-28 | Kinex Pharmaceuticals, Llc | Biaryl compositions and methods for modulating a kinase cascade |
EP1888549A2 (de) * | 2005-05-19 | 2008-02-20 | Vertex Pharmaceuticals, Inc. | Als modulatoren von ionenkanälen geeignete biaryle |
JP5388574B2 (ja) | 2005-05-31 | 2014-01-15 | バーテックス ファーマシューティカルズ インコーポレイテッド | イオンチャネルのモジュレーターとして有用なヘテロ環式類 |
SE529246C2 (sv) | 2005-10-13 | 2007-06-12 | Neurosearch Sweden Ab | Nya disubstituerade fenyl-piperidiner som modulatorer för dopaminneurotransmission |
JP5209183B2 (ja) | 2006-04-28 | 2013-06-12 | 東ソー・ファインケム株式会社 | 不純物の低減された2−シアノフェニルボロン酸又はそのエステル体の製造方法 |
CA2656564C (en) | 2006-06-29 | 2015-06-16 | Kinex Pharmaceuticals, Llc | Biaryl compositions and methods for modulating a kinase cascade |
US7939529B2 (en) * | 2007-05-17 | 2011-05-10 | Kinex Pharmaceuticals, Llc | Process for the preparation of compositions for modulating a kinase cascade and methods of use thereof |
US7935697B2 (en) * | 2006-12-28 | 2011-05-03 | Kinex Pharmaceuticals, Llc | Compositions for modulating a kinase cascade and methods of use thereof |
WO2008127188A1 (en) | 2007-04-12 | 2008-10-23 | Allbay Ab | N-oxide and/or di-n-oxide derivatives of dopamine receptor stabilizers/modulators displaying improved cardiovascular side-effects profiles |
US20100256147A1 (en) * | 2007-04-13 | 2010-10-07 | Hangauer Jr David G | Biaryl acetamide derivatives as modulators of the kinase cascade for the treatment of hearing loss, osteoporosis and cell proliferation disorders |
US8124605B2 (en) * | 2007-07-06 | 2012-02-28 | Kinex Pharmaceuticals, Llc | Compositions and methods for modulating a kinase cascade |
WO2009051848A1 (en) * | 2007-10-20 | 2009-04-23 | Kinex Pharmaceuticals, Llc | Pharmaceutical compositions for modulating a kinase cascade and methods of use thereof |
AU2008326381B2 (en) * | 2007-11-21 | 2014-10-23 | Decode Genetics Ehf | Biaryl PDE4 inhibitors for treating inflammation |
EP2222639A1 (de) | 2007-11-21 | 2010-09-01 | Decode Genetics EHF | Biaryle als pde4-inhibitoren zur behandlung von lungen- und herz-kreislauf-erkrankungen |
DE102008049675A1 (de) | 2008-09-30 | 2010-04-01 | Markus Dr. Heinrich | Verfahren zur Herstellung von 3-Aminobiphenylen |
CA2796419C (en) | 2010-04-16 | 2018-11-06 | Kinex Pharmaceuticals, Llc | Compositions and methods for the prevention and treatment of cancer |
US8841313B2 (en) | 2010-05-17 | 2014-09-23 | Boehringer Ingelheim International Gmbh | CCR2 antagonists and uses thereof |
WO2012059432A1 (en) * | 2010-11-01 | 2012-05-10 | Abbott Gmbh & Co. Kg | N-phenyl-(homo)piperazinyl-benzenesulfonyl or benzenesulfonamide compounds suitable for treating disorders that respond to the modulation of the 5-ht6 receptor |
US9586928B2 (en) | 2011-05-16 | 2017-03-07 | The Scripps Research Institute | Modulators of the nuclear hormone receptor ROR |
US8921533B2 (en) | 2011-07-25 | 2014-12-30 | Chromatin Technologies | Glycosylated valproic acid analogs and uses thereof |
GB201113538D0 (en) | 2011-08-04 | 2011-09-21 | Karobio Ab | Novel estrogen receptor ligands |
UY34503A (es) | 2011-12-08 | 2013-07-31 | Ivax Int Gmbh | ?sal de bromhidrato de pridopidina? |
AU2013243461A1 (en) | 2012-04-04 | 2014-11-06 | Teva Pharmaceuticals International Gmbh | Pharmaceutical compositions for combination therapy |
TWI664167B (zh) | 2012-08-30 | 2019-07-01 | 美商艾瑟奈克斯公司 | 用於調節激酶級聯之組成物及方法 |
WO2017127602A1 (en) * | 2016-01-22 | 2017-07-27 | Rush University Medical Center | Identification of novel small molecule beta2 integrin agonists |
WO2021007663A1 (en) | 2019-07-12 | 2021-01-21 | Canopy Growth Corporation | Cannabinoid derivatives |
Family Cites Families (13)
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IT1066857B (it) * | 1965-12-15 | 1985-03-12 | Acraf | Derivati della s ipiazolo 4.3 a piridina e processi per la loro preparazione |
US3558629A (en) * | 1967-08-31 | 1971-01-26 | Sterling Drug Inc | 2-halo-4-(1-piperazinyl)-benzaldehydes and related compounds |
US3692821A (en) * | 1970-09-09 | 1972-09-19 | Lewis H Sarett | Derivatives of 2-alkanoyloxy and 2-hydroxy-3-phenylbenzoic acid |
US4125612A (en) * | 1977-06-20 | 1978-11-14 | Schering Corporation | N-1-(p-Biphenylalkyl)piperazines and their use as anti-inflammatory agents |
JPS54128588A (en) * | 1978-03-29 | 1979-10-05 | Dainippon Pharmaceut Co Ltd | Antidepressive drugs consisting mainly of 2-(1-piperazinyl)- 4-phenylquinoline |
FR2530236B1 (fr) * | 1982-07-16 | 1985-08-02 | Delalande Sa | Nouveaux derives aminoalkyl naphtaleniques, leurs sels d'addition d'acide et le procede de preparation ainsi que l'application en therapeutique de ces derives et sels |
US4804663A (en) * | 1985-03-27 | 1989-02-14 | Janssen Pharmaceutica N.V. | 3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles |
FR2602771B1 (fr) * | 1986-08-12 | 1988-11-04 | Rhone Poulenc Sante | Nouveaux derives de la benzyl-4 piperazine, leur preparation et les compositions pharmaceutiques qui les contiennent |
EP0385237B1 (de) * | 1989-03-03 | 1994-06-29 | Dainippon Pharmaceutical Co., Ltd. | 2-(1-Piperazinyl)-4-phenylcycloalkanpyridin-Derivate, Verfahren zu deren Herstellung und pharmazeutische Zusammensetzungen, die sie enthalten |
FR2675802B1 (fr) * | 1991-04-26 | 1993-12-24 | Rhone Poulenc Rorer Sa | Antiserotonines, leur preparation et les medicaments les contenant. |
US5332743A (en) * | 1992-06-12 | 1994-07-26 | Mcneilab, Inc. | Benzyl and benzhydryl alcohols |
US5428037A (en) * | 1993-04-09 | 1995-06-27 | Syntex Pharmaceuticals, Ltd. | Heterocyclic derivatives in the treatment of Ischaemia and related diseases |
CA2144669A1 (en) * | 1994-03-29 | 1995-09-30 | Kozo Akasaka | Biphenyl derivatives |
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1995
- 1995-03-17 CA CA002144669A patent/CA2144669A1/en not_active Abandoned
- 1995-03-22 ES ES95104208T patent/ES2184772T3/es not_active Expired - Lifetime
- 1995-03-22 EP EP95104208A patent/EP0675118B1/de not_active Expired - Lifetime
- 1995-03-22 DE DE69528485T patent/DE69528485T2/de not_active Expired - Fee Related
- 1995-03-22 AT AT95104208T patent/ATE225780T1/de not_active IP Right Cessation
- 1995-03-24 AU AU15058/95A patent/AU691561B2/en not_active Ceased
- 1995-03-24 FI FI951417A patent/FI113172B/fi not_active IP Right Cessation
- 1995-03-27 NO NO951160A patent/NO305986B1/no unknown
- 1995-03-27 TW TW084102945A patent/TW434229B/zh not_active IP Right Cessation
- 1995-03-28 HU HU9500896A patent/HUT72492A/hu unknown
- 1995-03-28 RU RU95104322A patent/RU2125051C1/ru not_active IP Right Cessation
- 1995-03-28 NZ NZ270816A patent/NZ270816A/en unknown
- 1995-03-29 KR KR1019950006910A patent/KR100199638B1/ko not_active IP Right Cessation
- 1995-03-29 CN CN95103617A patent/CN1114596C/zh not_active Expired - Fee Related
- 1995-03-29 BR BR9500996-5A patent/BR9500996A/pt not_active IP Right Cessation
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1997
- 1997-05-12 US US08/855,790 patent/US5849912A/en not_active Expired - Fee Related
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1998
- 1998-10-05 US US09/166,229 patent/US6281214B1/en not_active Expired - Fee Related
-
2000
- 2000-03-10 CN CN00103862A patent/CN1290700A/zh active Pending
Also Published As
Publication number | Publication date |
---|---|
EP0675118A3 (de) | 1997-09-03 |
ES2184772T3 (es) | 2003-04-16 |
HUT72492A (en) | 1996-05-28 |
RU95104322A (ru) | 1997-04-27 |
CN1290700A (zh) | 2001-04-11 |
DE69528485T2 (de) | 2003-08-14 |
FI951417A (fi) | 1995-09-30 |
CN1117966A (zh) | 1996-03-06 |
AU1505895A (en) | 1995-10-05 |
HU9500896D0 (en) | 1995-05-29 |
DE69528485D1 (de) | 2002-11-14 |
ATE225780T1 (de) | 2002-10-15 |
KR950026866A (ko) | 1995-10-16 |
CA2144669A1 (en) | 1995-09-30 |
RU2125051C1 (ru) | 1999-01-20 |
NO951160L (no) | 1995-10-02 |
US5849912A (en) | 1998-12-15 |
US6281214B1 (en) | 2001-08-28 |
NO305986B1 (no) | 1999-08-30 |
KR100199638B1 (ko) | 1999-06-15 |
FI951417A0 (fi) | 1995-03-24 |
EP0675118B1 (de) | 2002-10-09 |
EP0675118A2 (de) | 1995-10-04 |
CN1114596C (zh) | 2003-07-16 |
AU691561B2 (en) | 1998-05-21 |
TW434229B (en) | 2001-05-16 |
NO951160D0 (no) | 1995-03-27 |
NZ270816A (en) | 1996-08-27 |
BR9500996A (pt) | 1995-10-24 |
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