JP2006526021A5

JP2006526021A5 -

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Publication number: JP2006526021A5
Authority: JP; Japan
Prior art keywords: compound; disorder; composition; group; alkyl
Prior art date: 2004-05-20
Legal status : Pending

Application number

JP2006514901A

Other languages

English (en)

Japanese (ja)

Other versions

JP2006526021A (ja

Filing date

2004-05-20

Publication date

2007-08-02

2004-05-20 Application filed filed Critical

2004-05-20 Priority claimed from PCT/US2004/015760 external-priority patent/WO2005035504A2/en

2006-11-16 Publication of JP2006526021A publication Critical patent/JP2006526021A/ja

2007-08-02 Publication of JP2006526021A5 publication Critical patent/JP2006526021A5/ja

Status Pending legal-status Critical Current

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150000001875 compounds Chemical class 0.000 claims description 261
239000000203 mixture Substances 0.000 claims description 117
125000000217 alkyl group Chemical group 0.000 claims description 78
-1 aralkoxy Chemical group 0.000 claims description 68
150000003839 salts Chemical class 0.000 claims description 51
125000003118 aryl group Chemical group 0.000 claims description 45
239000012453 solvate Substances 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 43
229910052739 hydrogen Inorganic materials 0.000 claims description 43
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
125000003710 aryl alkyl group Chemical group 0.000 claims description 36
125000000753 cycloalkyl group Chemical group 0.000 claims description 29
125000001072 heteroaryl group Chemical group 0.000 claims description 28
125000000623 heterocyclic group Chemical group 0.000 claims description 28
125000001424 substituent group Chemical group 0.000 claims description 24
125000004475 heteroaralkyl group Chemical group 0.000 claims description 23
150000002431 hydrogen Chemical class 0.000 claims description 22
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
208000008589 Obesity Diseases 0.000 claims description 20
208000030814 Eating disease Diseases 0.000 claims description 19
208000019454 Feeding and Eating disease Diseases 0.000 claims description 19
235000014632 disordered eating Nutrition 0.000 claims description 19
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 18
235000020824 obesity Nutrition 0.000 claims description 18
208000035475 disorder Diseases 0.000 claims description 17
239000003937 drug carrier Substances 0.000 claims description 17
239000008194 pharmaceutical composition Substances 0.000 claims description 17
208000032841 Bulimia Diseases 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical class 0.000 claims description 16
206010006550 Bulimia nervosa Diseases 0.000 claims description 15
125000004414 alkyl thio group Chemical group 0.000 claims description 14
239000002830 appetite depressant Substances 0.000 claims description 14
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 13
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 13
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 12
208000030159 metabolic disease Diseases 0.000 claims description 12
102000004877 Insulin Human genes 0.000 claims description 11
108090001061 Insulin Proteins 0.000 claims description 11
125000002252 acyl group Chemical group 0.000 claims description 11
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 11
229940125396 insulin Drugs 0.000 claims description 11
125000004104 aryloxy group Chemical group 0.000 claims description 10
229940079593 drug Drugs 0.000 claims description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
125000003435 aroyl group Chemical group 0.000 claims description 9
239000003795 chemical substances by application Substances 0.000 claims description 9
208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 8
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 8
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 8
125000005110 aryl thio group Chemical group 0.000 claims description 8
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
239000000556 agonist Substances 0.000 claims description 7
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
208000018459 dissociative disease Diseases 0.000 claims description 7
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 7
125000005368 heteroarylthio group Chemical group 0.000 claims description 7
230000001225 therapeutic effect Effects 0.000 claims description 7
206010003805 Autism Diseases 0.000 claims description 6
208000020706 Autistic disease Diseases 0.000 claims description 6
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
239000000883 anti-obesity agent Substances 0.000 claims description 6
229940125710 antiobesity agent Drugs 0.000 claims description 6
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 6
230000000392 somatic effect Effects 0.000 claims description 6
208000000103 Anorexia Nervosa Diseases 0.000 claims description 5
208000001613 Gambling Diseases 0.000 claims description 5
125000002947 alkylene group Chemical group 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
206010012601 diabetes mellitus Diseases 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
230000001568 sexual effect Effects 0.000 claims description 5
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims description 4
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
229940118148 Aldose reductase inhibitor Drugs 0.000 claims description 4
RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 claims description 4
206010010219 Compulsions Diseases 0.000 claims description 4
QTQMRBZOBKYXCG-MHZLTWQESA-N GW 1929 Chemical compound N([C@@H](CC1=CC=C(C=C1)OCCN(C)C=1N=CC=CC=1)C(O)=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 QTQMRBZOBKYXCG-MHZLTWQESA-N 0.000 claims description 4
206010034158 Pathological gambling Diseases 0.000 claims description 4
229940100389 Sulfonylurea Drugs 0.000 claims description 4
239000003288 aldose reductase inhibitor Substances 0.000 claims description 4
125000004171 alkoxy aryl group Chemical group 0.000 claims description 4
125000005466 alkylenyl group Chemical group 0.000 claims description 4
ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
229960001761 chlorpropamide Drugs 0.000 claims description 4
229960004580 glibenclamide Drugs 0.000 claims description 4
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims description 4
229960003105 metformin Drugs 0.000 claims description 4
239000002660 neuropeptide Y receptor antagonist Substances 0.000 claims description 4
239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 4
HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 claims description 4
229960001641 troglitazone Drugs 0.000 claims description 4
GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 claims description 4
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims description 3
208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
206010020772 Hypertension Diseases 0.000 claims description 3
229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 3
229940123659 Sorbitol dehydrogenase inhibitor Drugs 0.000 claims description 3
229960002632 acarbose Drugs 0.000 claims description 3
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims description 3
206010022489 Insulin Resistance Diseases 0.000 claims description 2
239000005557 antagonist Substances 0.000 claims description 2
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 2
125000004474 heteroalkylene group Chemical group 0.000 claims description 2
239000003112 inhibitor Substances 0.000 claims description 2
KIWSYRHAAPLJFJ-DNZSEPECSA-N n-[(e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enyl]pyridine-3-carboxamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/CNC(=O)C1=CC=CN=C1 KIWSYRHAAPLJFJ-DNZSEPECSA-N 0.000 claims description 2
150000002825 nitriles Chemical class 0.000 claims description 2
229960005095 pioglitazone Drugs 0.000 claims description 2
YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 4
238000004519 manufacturing process Methods 0.000 claims 3
230000037303 wrinkles Effects 0.000 claims 3
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 317
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 155
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 100
238000000034 method Methods 0.000 description 98
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 53
239000011347 resin Substances 0.000 description 53
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XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
239000000047 product Substances 0.000 description 39
239000000243 solution Substances 0.000 description 38
239000002904 solvent Substances 0.000 description 38
235000019439 ethyl acetate Nutrition 0.000 description 36
239000007787 solid Substances 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 32
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
229920006395 saturated elastomer Polymers 0.000 description 20
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 19
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
229910052757 nitrogen Inorganic materials 0.000 description 18
239000012267 brine Substances 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
125000004432 carbon atom Chemical group C* 0.000 description 15
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
239000012044 organic layer Substances 0.000 description 14
238000012746 preparative thin layer chromatography Methods 0.000 description 14
229910052717 sulfur Inorganic materials 0.000 description 13
239000007788 liquid Substances 0.000 description 12
239000003921 oil Substances 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
239000010410 layer Substances 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000002253 acid Substances 0.000 description 10
239000002552 dosage form Substances 0.000 description 10
229910052760 oxygen Inorganic materials 0.000 description 10
239000001301 oxygen Substances 0.000 description 10
238000003756 stirring Methods 0.000 description 10
239000000126 substance Substances 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 9
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235000017557 sodium bicarbonate Nutrition 0.000 description 9
239000011593 sulfur Substances 0.000 description 9
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230000037396 body weight Effects 0.000 description 8
125000004356 hydroxy functional group Chemical group O* 0.000 description 8
102000005962 receptors Human genes 0.000 description 8
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SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 7
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238000003556 assay Methods 0.000 description 7
208000015114 central nervous system disease Diseases 0.000 description 7
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229940002612 prodrug Drugs 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
238000010992 reflux Methods 0.000 description 7
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239000000725 suspension Substances 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
238000005406 washing Methods 0.000 description 7
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
201000010099 disease Diseases 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000000463 material Substances 0.000 description 6
239000002464 receptor antagonist Substances 0.000 description 6
229940044551 receptor antagonist Drugs 0.000 description 6
125000006413 ring segment Chemical group 0.000 description 6
FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
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125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
239000003480 eluent Substances 0.000 description 5
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
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JP2006514901A 2003-05-22 2004-05-20 肥満およびｃｎｓ障害を治療する選択的ｄ１／ｄ５レセプタアンタゴニストとしての５ｈ−ベンゾ［ｄ］ナフト［２，１−ｂ］アゼピン誘導体 Pending JP2006526021A (ja)