TWI542590B - 1,2-雙取代雜環化合物 - Google Patents
1,2-雙取代雜環化合物 Download PDFInfo
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- TWI542590B TWI542590B TW103127120A TW103127120A TWI542590B TW I542590 B TWI542590 B TW I542590B TW 103127120 A TW103127120 A TW 103127120A TW 103127120 A TW103127120 A TW 103127120A TW I542590 B TWI542590 B TW I542590B
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- Prior art keywords
- etoac
- phenyl
- group
- mmol
- water
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- 150000002391 heterocyclic compounds Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 201000000980 schizophrenia Diseases 0.000 claims description 15
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- 208000028017 Psychotic disease Diseases 0.000 claims description 10
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 208000014094 Dystonic disease Diseases 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 230000000698 schizophrenic effect Effects 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 208000010118 dystonia Diseases 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 4
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 4
- 206010034158 Pathological gambling Diseases 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
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- 208000019116 sleep disease Diseases 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 230000000391 smoking effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 384
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- 239000000243 solution Substances 0.000 description 222
- -1 decylamino group Chemical group 0.000 description 205
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- 239000011734 sodium Substances 0.000 description 153
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- 239000000203 mixture Substances 0.000 description 104
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 91
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
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- 125000000753 cycloalkyl group Chemical group 0.000 description 52
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000012298 atmosphere Substances 0.000 description 44
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 40
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 26
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- 125000000592 heterocycloalkyl group Chemical group 0.000 description 25
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
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- 125000006413 ring segment Chemical group 0.000 description 18
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 17
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- 238000000034 method Methods 0.000 description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- MYPFKEGUMKPGDR-UHFFFAOYSA-N 2-[4-(quinolin-2-ylmethoxy)phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OCC1=CC=C(C=CC=C2)C2=N1 MYPFKEGUMKPGDR-UHFFFAOYSA-N 0.000 description 14
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- 125000000000 cycloalkoxy group Chemical group 0.000 description 14
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 235000002639 sodium chloride Nutrition 0.000 description 13
- CEBKHWWANWSNTI-UHFFFAOYSA-N 2-methylbut-3-yn-2-ol Chemical compound CC(C)(O)C#C CEBKHWWANWSNTI-UHFFFAOYSA-N 0.000 description 12
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 12
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 12
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 12
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- 125000003282 alkyl amino group Chemical group 0.000 description 10
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- VALPUQSYTYTWHT-UHFFFAOYSA-N 4-bromo-2,2-dimethyl-5-pyridin-4-ylfuran-3-one Chemical compound O=C1C(C)(C)OC(C=2C=CN=CC=2)=C1Br VALPUQSYTYTWHT-UHFFFAOYSA-N 0.000 description 9
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- CIQHJFUWMUOUGJ-UHFFFAOYSA-N 2,2-dimethyl-5-pyridin-4-yl-4-[4-(quinolin-2-ylmethoxy)phenyl]furan-3-one Chemical compound C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C=1C(=O)C(C)(C)OC=1C1=CC=NC=C1 CIQHJFUWMUOUGJ-UHFFFAOYSA-N 0.000 description 8
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- 239000000164 antipsychotic agent Substances 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
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- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
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- MJDRELIYCROYTK-UHFFFAOYSA-N 7-pyridin-4-yl-6-[4-(quinolin-2-ylmethoxy)phenyl]-4-oxaspiro[2.4]hept-6-en-5-one Chemical compound C=1C=NC=CC=1C1=C(C=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)C(=O)OC21CC2 MJDRELIYCROYTK-UHFFFAOYSA-N 0.000 description 7
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
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- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 6
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- 125000004001 thioalkyl group Chemical group 0.000 description 6
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
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