TW200407141A

TW200407141A - Method for treating cancer

Method for treating cancer Download PDF

Info

Publication number: TW200407141A
Authority: TW; Taiwan
Prior art keywords: group; methyl; trimethoxyphenyl; substituted; amino
Prior art date: 2002-04-12

Application number

TW092108179A

Other languages

English (en)

Chinese (zh)

Inventor

Chikage Mataki

Tatsuhiko Kodama

Takeshi Doi

Masahiro Tamura

Toshiaki Oda

Yamazaki Yukiyoshi

Nishikawa Masahiro

Takemura Shunji

Ohkuch Masao

Original Assignee

Kowa Co

Priority date

2002-04-12

Filing date

2003-04-09

Publication date

2004-05-16

2003-04-09 Application filed by Kowa Co filed Critical Kowa Co

2004-05-16 Publication of TW200407141A publication Critical patent/TW200407141A/zh

Links

206010028980 Neoplasm Diseases 0.000 title claims abstract description 59
201000011510 cancer Diseases 0.000 title claims abstract description 29
238000000034 method Methods 0.000 title claims description 45
-1 cyclic amine compound Chemical class 0.000 claims abstract description 289
150000003839 salts Chemical class 0.000 claims abstract description 68
125000000217 alkyl group Chemical group 0.000 claims abstract description 43
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
125000003118 aryl group Chemical group 0.000 claims abstract description 31
125000005843 halogen group Chemical group 0.000 claims abstract description 31
125000003545 alkoxy group Chemical group 0.000 claims abstract description 28
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 19
239000003814 drug Substances 0.000 claims abstract description 17
125000000304 alkynyl group Chemical group 0.000 claims abstract description 16
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 16
125000004475 heteroaralkyl group Chemical group 0.000 claims abstract description 15
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 13
125000003342 alkenyl group Chemical group 0.000 claims abstract description 11
238000001415 gene therapy Methods 0.000 claims abstract description 7
229910052736 halogen Inorganic materials 0.000 claims abstract 3
125000002252 acyl group Chemical group 0.000 claims abstract 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 405
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 338
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 233
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 225
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 124
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 92
239000000203 mixture Substances 0.000 claims description 71
150000001412 amines Chemical class 0.000 claims description 50
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 49
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 34
125000004076 pyridyl group Chemical group 0.000 claims description 34
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 30
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 29
125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 29
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 25
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
OKWNDHFPWXJEHM-UHFFFAOYSA-N 2-(3,4,5-trimethoxyphenyl)pyridine Chemical compound COC1=C(OC)C(OC)=CC(C=2N=CC=CC=2)=C1 OKWNDHFPWXJEHM-UHFFFAOYSA-N 0.000 claims description 18
125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
125000003277 amino group Chemical group 0.000 claims description 17
102000003964 Histone deacetylase Human genes 0.000 claims description 14
108090000353 Histone deacetylase Proteins 0.000 claims description 14
125000004429 atom Chemical group 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 claims description 12
239000012453 solvate Substances 0.000 claims description 10
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 7
229940079593 drug Drugs 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
150000003254 radicals Chemical class 0.000 claims description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 5
239000003112 inhibitor Substances 0.000 claims description 5
229940030010 trimethoxybenzene Drugs 0.000 claims description 5
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 4
SFDJOSRHYKHMOK-UHFFFAOYSA-N nitramide Chemical compound N[N+]([O-])=O SFDJOSRHYKHMOK-UHFFFAOYSA-N 0.000 claims description 4
JIIKREQRELFKLL-UHFFFAOYSA-N 4-(piperidin-1-ylmethyl)-2-(3,4,5-trimethoxyphenyl)pyridine Chemical compound COC1=C(OC)C(OC)=CC(C=2N=CC=C(CN3CCCCC3)C=2)=C1 JIIKREQRELFKLL-UHFFFAOYSA-N 0.000 claims description 3
OQLKNTOKMBVBKV-UHFFFAOYSA-N hexamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCCOC1=CC=C(C(N)=N)C=C1 OQLKNTOKMBVBKV-UHFFFAOYSA-N 0.000 claims description 3
229960001915 hexamidine Drugs 0.000 claims description 3
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
125000004149 thio group Chemical group *S* 0.000 claims description 3
241000790917 Dioxys <bee> Species 0.000 claims description 2
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
125000005915 C6-C14 aryl group Chemical group 0.000 claims 5
239000003937 drug carrier Substances 0.000 claims 3
125000004446 heteroarylalkyl group Chemical group 0.000 claims 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 3
230000001737 promoting effect Effects 0.000 claims 3
GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 claims 2
239000013543 active substance Substances 0.000 claims 2
125000005530 alkylenedioxy group Chemical group 0.000 claims 2
150000002367 halogens Chemical class 0.000 claims 2
QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 claims 2
125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
MVKDNXIKAWKCCS-UHFFFAOYSA-N 3-methyl-1h-pyridin-2-one Chemical compound CC1=CC=CN=C1O MVKDNXIKAWKCCS-UHFFFAOYSA-N 0.000 claims 1
NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 claims 1
229940122964 Deacetylase inhibitor Drugs 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
239000003276 histone deacetylase inhibitor Substances 0.000 abstract description 10
229940121372 histone deacetylase inhibitor Drugs 0.000 abstract description 5
150000001875 compounds Chemical class 0.000 description 433
238000002360 preparation method Methods 0.000 description 313
230000015572 biosynthetic process Effects 0.000 description 260
238000003786 synthesis reaction Methods 0.000 description 258
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 198
238000005481 NMR spectroscopy Methods 0.000 description 157
101150041968 CDC13 gene Proteins 0.000 description 154
125000004744 butyloxycarbonyl group Chemical group 0.000 description 144
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 117
239000000843 powder Substances 0.000 description 104
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
239000002585 base Substances 0.000 description 79
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 66
238000004519 manufacturing process Methods 0.000 description 63
238000012360 testing method Methods 0.000 description 60
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
238000005160 1H NMR spectroscopy Methods 0.000 description 55
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 53
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
239000000243 solution Substances 0.000 description 47
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 44
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 42
239000012458 free base Substances 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 31
239000003921 oil Substances 0.000 description 29
OHEDMAIVEXQCOZ-UHFFFAOYSA-N piperidine;dihydrochloride Chemical compound Cl.Cl.C1CCNCC1 OHEDMAIVEXQCOZ-UHFFFAOYSA-N 0.000 description 29
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 28
238000010992 reflux Methods 0.000 description 28
239000002904 solvent Substances 0.000 description 28
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
239000012267 brine Substances 0.000 description 27
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
210000004027 cell Anatomy 0.000 description 24
239000012044 organic layer Substances 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000002253 acid Substances 0.000 description 22
229910000027 potassium carbonate Inorganic materials 0.000 description 22
238000009833 condensation Methods 0.000 description 21
230000005494 condensation Effects 0.000 description 21
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 17
MDZVMZTXIHCNCQ-UHFFFAOYSA-N piperidine;trihydrochloride Chemical compound Cl.Cl.Cl.C1CCNCC1 MDZVMZTXIHCNCQ-UHFFFAOYSA-N 0.000 description 17
SBGHNDCBGPREJJ-UHFFFAOYSA-N 4-(chloromethyl)-2-(3,4,5-trimethoxyphenyl)pyridine Chemical compound COC1=C(OC)C(OC)=CC(C=2N=CC=C(CCl)C=2)=C1 SBGHNDCBGPREJJ-UHFFFAOYSA-N 0.000 description 16
108090000623 proteins and genes Proteins 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
150000001805 chlorine compounds Chemical class 0.000 description 15
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 13
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 13
239000000047 product Substances 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
239000006188 syrup Substances 0.000 description 13
235000020357 syrup Nutrition 0.000 description 13
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
239000003513 alkali Substances 0.000 description 11
125000005805 dimethoxy phenyl group Chemical group 0.000 description 11
VEIWYFRREFUNRC-UHFFFAOYSA-N hydron;piperidine;chloride Chemical compound [Cl-].C1CC[NH2+]CC1 VEIWYFRREFUNRC-UHFFFAOYSA-N 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 10
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 10
230000014509 gene expression Effects 0.000 description 10
229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
235000017557 sodium bicarbonate Nutrition 0.000 description 10
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 9
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
239000003480 eluent Substances 0.000 description 9
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 9
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 8
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 8
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 8
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 8
UPMRLMOBRSDTLI-UHFFFAOYSA-N 3-(chloromethyl)-5-(3,4,5-trimethoxyphenyl)pyridine Chemical compound COC1=C(OC)C(OC)=CC(C=2C=C(CCl)C=NC=2)=C1 UPMRLMOBRSDTLI-UHFFFAOYSA-N 0.000 description 7
DRVDQUYTYFCSRR-UHFFFAOYSA-N 5-[3-(chloromethyl)phenyl]-1,2,3-trimethoxybenzene Chemical compound COC1=C(OC)C(OC)=CC(C=2C=C(CCl)C=CC=2)=C1 DRVDQUYTYFCSRR-UHFFFAOYSA-N 0.000 description 7
208000026310 Breast neoplasm Diseases 0.000 description 7
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 7
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
229910000831 Steel Inorganic materials 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
239000013078 crystal Substances 0.000 description 7
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 7
239000010410 layer Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
239000010959 steel Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
VWVZFHRDLPHBEG-UHFFFAOYSA-N 1-(chloromethyl)-4-methylsulfanylbenzene Chemical group CSC1=CC=C(CCl)C=C1 VWVZFHRDLPHBEG-UHFFFAOYSA-N 0.000 description 6
WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-UHFFFAOYSA-N 0.000 description 6
OGIQUQKNJJTLSZ-UHFFFAOYSA-N 4-butylaniline Chemical compound CCCCC1=CC=C(N)C=C1 OGIQUQKNJJTLSZ-UHFFFAOYSA-N 0.000 description 6
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
239000012467 final product Substances 0.000 description 6
239000007789 gas Substances 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000010898 silica gel chromatography Methods 0.000 description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 6
125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 5
125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
206010006187 Breast cancer Diseases 0.000 description 5
208000005718 Stomach Neoplasms Diseases 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 5
229940073608 benzyl chloride Drugs 0.000 description 5
206010017758 gastric cancer Diseases 0.000 description 5
230000012010 growth Effects 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
239000011777 magnesium Substances 0.000 description 5
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
238000000746 purification Methods 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000003381 stabilizer Substances 0.000 description 5
201000011549 stomach cancer Diseases 0.000 description 5
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