JP2002514619A - 新しい置換環状化合物、これらの製造方法及びこれらを含む薬剤組成物 - Google Patents
新しい置換環状化合物、これらの製造方法及びこれらを含む薬剤組成物Info
- Publication number
- JP2002514619A JP2002514619A JP2000548299A JP2000548299A JP2002514619A JP 2002514619 A JP2002514619 A JP 2002514619A JP 2000548299 A JP2000548299 A JP 2000548299A JP 2000548299 A JP2000548299 A JP 2000548299A JP 2002514619 A JP2002514619 A JP 2002514619A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- group
- compound
- ethyl
- substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims description 611
- 238000000034 method Methods 0.000 title claims description 83
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 230000008569 process Effects 0.000 title claims description 4
- 150000001923 cyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 265
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 57
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000007858 starting material Substances 0.000 claims description 411
- -1 polycyclic radical Chemical class 0.000 claims description 105
- 239000002253 acid Substances 0.000 claims description 93
- 150000003839 salts Chemical class 0.000 claims description 92
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 84
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 76
- 150000007513 acids Chemical class 0.000 claims description 68
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
- 229910052757 nitrogen Chemical group 0.000 claims description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
- 125000001424 substituent group Chemical group 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 125000005605 benzo group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 14
- 239000011593 sulfur Chemical group 0.000 claims description 14
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 14
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 13
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 13
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 230000001193 melatoninergic effect Effects 0.000 claims description 12
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000006684 polyhaloalkyl group Polymers 0.000 claims description 11
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 10
- 230000009471 action Effects 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- 125000004434 sulfur atom Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
- 150000003573 thiols Chemical class 0.000 claims description 8
- 229920002554 vinyl polymer Polymers 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 7
- TYFWDOQGHVONSS-UHFFFAOYSA-N n-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(SC)=CC=C21 TYFWDOQGHVONSS-UHFFFAOYSA-N 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000006267 biphenyl group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- OUUWATVJTLBCFV-UHFFFAOYSA-N n-acetyl-n-ethylacetamide Chemical compound CCN(C(C)=O)C(C)=O OUUWATVJTLBCFV-UHFFFAOYSA-N 0.000 claims description 6
- 125000003367 polycyclic group Chemical group 0.000 claims description 6
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 6
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical class C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 5
- 150000002790 naphthalenes Chemical class 0.000 claims description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 5
- 125000006685 (C1-C6) polyhaloalkyl group Chemical group 0.000 claims description 4
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 claims description 4
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical group C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 claims description 4
- YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical class C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- YRTCKZIKGWZNCU-UHFFFAOYSA-N furo[3,2-b]pyridine Chemical class C1=CC=C2OC=CC2=N1 YRTCKZIKGWZNCU-UHFFFAOYSA-N 0.000 claims description 4
- VHUITCKFPJTFHR-UHFFFAOYSA-N n-[2-(7-methylsulfinylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=C(S(C)=O)C=C2C(CCNC(=O)C)=CC=CC2=C1 VHUITCKFPJTFHR-UHFFFAOYSA-N 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical class C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 4
- NNWLHBCKEQMHKH-UHFFFAOYSA-N 1-methyl-3-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]urea Chemical compound C1=C(SC)C=C2C(CCNC(=O)NC)=CC=CC2=C1 NNWLHBCKEQMHKH-UHFFFAOYSA-N 0.000 claims description 3
- IHFOOJPQLJKXMS-UHFFFAOYSA-N 2,2,2-trifluoro-n-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=CC=C(CCNC(=O)C(F)(F)F)C2=CC(SC)=CC=C21 IHFOOJPQLJKXMS-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- RYHHJKDZGCJFNO-UHFFFAOYSA-N n-[(2-benzyl-5-but-3-enylsulfanyl-1-benzothiophen-3-yl)methyl]acetamide Chemical compound S1C2=CC=C(SCCC=C)C=C2C(CNC(=O)C)=C1CC1=CC=CC=C1 RYHHJKDZGCJFNO-UHFFFAOYSA-N 0.000 claims description 3
- FCEZAIOOMFGMKT-UHFFFAOYSA-N n-[(6-morpholin-4-yl-2-phenyl-2h-chromen-3-yl)methyl]acetamide Chemical compound CC(=O)NCC1=CC2=CC(N3CCOCC3)=CC=C2OC1C1=CC=CC=C1 FCEZAIOOMFGMKT-UHFFFAOYSA-N 0.000 claims description 3
- GVZAZUVBWVAYJU-UHFFFAOYSA-N n-[2-(1-hydroxy-4-methyl-2,3-dihydro-1h-benzo[f]quinolin-10-yl)ethyl]-2-phenylacetamide Chemical compound CN1CCC(O)C(C=23)=C1C=CC3=CC=CC=2CCNC(=O)CC1=CC=CC=C1 GVZAZUVBWVAYJU-UHFFFAOYSA-N 0.000 claims description 3
- UIWVJTHHRPYGHX-UHFFFAOYSA-N n-[2-(3-benzyl-7-methylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=C(CCNC(C)=O)C2=CC(SC)=CC=C2C=C1CC1=CC=CC=C1 UIWVJTHHRPYGHX-UHFFFAOYSA-N 0.000 claims description 3
- VNFOEJMDQTWJKD-UHFFFAOYSA-N n-[2-(7-benzylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=C2C(CCNC(=O)C)=CC=CC2=CC=C1SCC1=CC=CC=C1 VNFOEJMDQTWJKD-UHFFFAOYSA-N 0.000 claims description 3
- PDZOLEHADYMJAF-UHFFFAOYSA-N n-[2-(7-benzylsulfonylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=C2C(CCNC(=O)C)=CC=CC2=CC=C1S(=O)(=O)CC1=CC=CC=C1 PDZOLEHADYMJAF-UHFFFAOYSA-N 0.000 claims description 3
- IJBYSBWGZKMBMG-UHFFFAOYSA-N n-[2-(7-ethylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(SCC)=CC=C21 IJBYSBWGZKMBMG-UHFFFAOYSA-N 0.000 claims description 3
- DWNGHLJHDQQWIL-UHFFFAOYSA-N n-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]butanamide Chemical compound C1=C(SC)C=C2C(CCNC(=O)CCC)=CC=CC2=C1 DWNGHLJHDQQWIL-UHFFFAOYSA-N 0.000 claims description 3
- HIXXCXUIVMDINM-UHFFFAOYSA-N n-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]cyclopropanecarboxamide Chemical compound C12=CC(SC)=CC=C2C=CC=C1CCNC(=O)C1CC1 HIXXCXUIVMDINM-UHFFFAOYSA-N 0.000 claims description 3
- VIMNEBUQXGHMFF-UHFFFAOYSA-N n-[2-(7-propylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=CC=C(CCNC(C)=O)C2=CC(SCCC)=CC=C21 VIMNEBUQXGHMFF-UHFFFAOYSA-N 0.000 claims description 3
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 3
- 150000003222 pyridines Chemical group 0.000 claims description 3
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims description 2
- 241000872931 Myoporum sandwicense Species 0.000 claims description 2
- 229910019093 NaOCl Inorganic materials 0.000 claims description 2
- 238000007239 Wittig reaction Methods 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 229910002056 binary alloy Inorganic materials 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 150000001879 copper Chemical class 0.000 claims description 2
- 239000007822 coupling agent Substances 0.000 claims description 2
- 230000017858 demethylation Effects 0.000 claims description 2
- 238000010520 demethylation reaction Methods 0.000 claims description 2
- CCNMBWHBCPEJLZ-UHFFFAOYSA-N ethyl 10-[3-(cyclohexanecarbonylamino)propyl]-1-methyl-3h-benzo[f]thiochromene-3-carboxylate Chemical compound C12=C3C(C)=CC(C(=O)OCC)SC3=CC=C2C=CC=C1CCCNC(=O)C1CCCCC1 CCNMBWHBCPEJLZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- UQFMIKXFTGAGQE-UHFFFAOYSA-N n-(4-butylsulfanyl-2,3-dihydro-1h-phenalen-2-yl)propanamide Chemical compound C1=CC=C2CC(NC(=O)CC)CC3=C2C1=CC=C3SCCCC UQFMIKXFTGAGQE-UHFFFAOYSA-N 0.000 claims description 2
- OGKVLOAXRUZCCW-UHFFFAOYSA-N n-[(2-benzyl-6-ethyl-7h-thieno[3,2-f]quinolin-1-yl)methyl]acetamide Chemical compound CCN1CC=CC(C=2C=3CNC(C)=O)=C1C=CC=2SC=3CC1=CC=CC=C1 OGKVLOAXRUZCCW-UHFFFAOYSA-N 0.000 claims description 2
- RUSMUZHLWFEVKH-UHFFFAOYSA-N n-[2-(1-methyl-2-phenyl-5-propylsulfanylpyrrolo[2,3-b]pyridin-3-yl)ethyl]acetamide Chemical compound CC(=O)NCCC=1C2=CC(SCCC)=CN=C2N(C)C=1C1=CC=CC=C1 RUSMUZHLWFEVKH-UHFFFAOYSA-N 0.000 claims description 2
- MCDZFOHNKRGHNW-UHFFFAOYSA-N n-[2-(7-benzylsulfanylnaphthalen-1-yl)ethyl]heptanamide Chemical compound C1=C2C(CCNC(=O)CCCCCC)=CC=CC2=CC=C1SCC1=CC=CC=C1 MCDZFOHNKRGHNW-UHFFFAOYSA-N 0.000 claims description 2
- VUVZFIMHVADDLL-UHFFFAOYSA-N n-[2-(7-benzylsulfinylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=C2C(CCNC(=O)C)=CC=CC2=CC=C1S(=O)CC1=CC=CC=C1 VUVZFIMHVADDLL-UHFFFAOYSA-N 0.000 claims description 2
- ZMDWAOWABWHEJS-UHFFFAOYSA-N n-[2-(7-methylsulfanyl-1,2,3,4-tetrahydronaphthalen-1-yl)ethyl]acetamide Chemical compound C1CCC(CCNC(C)=O)C2=CC(SC)=CC=C21 ZMDWAOWABWHEJS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000012038 nucleophile Substances 0.000 claims description 2
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 238000005949 ozonolysis reaction Methods 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 2
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 6
- 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 claims 3
- 150000001555 benzenes Chemical class 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 claims 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims 1
- JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 claims 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims 1
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 1
- 238000009833 condensation Methods 0.000 claims 1
- 230000005494 condensation Effects 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
- ZNQFZPCFVNOXJQ-UHFFFAOYSA-N n-acetyl-n-methylacetamide Chemical compound CC(=O)N(C)C(C)=O ZNQFZPCFVNOXJQ-UHFFFAOYSA-N 0.000 claims 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- 239000000047 product Substances 0.000 description 79
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 57
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- 238000002844 melting Methods 0.000 description 49
- 230000008018 melting Effects 0.000 description 49
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- BAOCCULSMYKVBN-UHFFFAOYSA-N o-[3-(acetamidomethyl)-2-benzyl-1,4-benzodioxin-6-yl] furan-2-carbothioate Chemical compound O1C2=CC=C(OC(=S)C=3OC=CC=3)C=C2OC(CNC(=O)C)=C1CC1=CC=CC=C1 BAOCCULSMYKVBN-UHFFFAOYSA-N 0.000 description 1
- RWMCSGHSARUDEZ-UHFFFAOYSA-N o-[3-[3-(methylamino)-3-oxopropyl]-2h-chromen-6-yl] 2-morpholin-4-ylethanethioate Chemical compound C=1C=C2OCC(CCC(=O)NC)=CC2=CC=1OC(=S)CN1CCOCC1 RWMCSGHSARUDEZ-UHFFFAOYSA-N 0.000 description 1
- AUBFARDDANAQOL-UHFFFAOYSA-N o-[6-benzoyl-8-[2-(propylcarbamoylamino)ethyl]naphthalen-2-yl] 4-(trifluoromethyl)benzenecarbothioate Chemical compound C1=C2C(CCNC(=O)NCCC)=CC(C(=O)C=3C=CC=CC=3)=CC2=CC=C1OC(=S)C1=CC=C(C(F)(F)F)C=C1 AUBFARDDANAQOL-UHFFFAOYSA-N 0.000 description 1
- NHFQXKKJSLFXFD-UHFFFAOYSA-N o-[8-[(butanoylamino)methyl]-6-thiophen-2-ylnaphthalen-2-yl] but-2-enethioate Chemical compound C=1C2=CC=C(OC(=S)C=CC)C=C2C(CNC(=O)CCC)=CC=1C1=CC=CS1 NHFQXKKJSLFXFD-UHFFFAOYSA-N 0.000 description 1
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
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- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
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- OOUDGASLVJPZBX-UHFFFAOYSA-N propan-2-yl 9-(acetamidomethyl)-1-methyl-8,9-dihydro-7h-thieno[3,2-f]chromene-2-carboxylate Chemical compound O1CCC(CNC(C)=O)C2=C(C(=C(C(=O)OC(C)C)S3)C)C3=CC=C21 OOUDGASLVJPZBX-UHFFFAOYSA-N 0.000 description 1
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940125670 thienopyridine Drugs 0.000 description 1
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- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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Classifications
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| FR98/05957 | 1998-05-12 | ||
| FR9805957A FR2778662B1 (fr) | 1998-05-12 | 1998-05-12 | Nouveaux composes cycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| PCT/FR1999/001100 WO1999058495A1 (fr) | 1998-05-12 | 1999-05-10 | Nouveaux composes cycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
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| JP2002514619A true JP2002514619A (ja) | 2002-05-21 |
| JP2002514619A5 JP2002514619A5 (https=) | 2006-07-13 |
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| JP2000548300A Pending JP2002514620A (ja) | 1998-05-12 | 1999-05-10 | 新しい置換環状化合物、これらの製造方法及びこれらを含む薬剤組成物 |
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| JP (2) | JP2002514619A (https=) |
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| BR (2) | BR9911783A (https=) |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009514828A (ja) * | 2005-11-03 | 2009-04-09 | エフ.ホフマン−ラ ロシュ アーゲー | 5−ht6阻害剤としてのアリールスルホニルクロマン類、タンパク質キナーゼ阻害剤としてのインドリルマレイミド誘導体 |
| JP2018502888A (ja) * | 2015-01-20 | 2018-02-01 | エックスオーシー ファーマシューティカルズ インコーポレイテッドXoc Pharmaceuticals, Inc | エルゴリン化合物およびその使用 |
Families Citing this family (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPO274596A0 (en) * | 1996-10-04 | 1996-10-31 | Armstrong, Stuart Maxwell | Method for the treatment of neurological or neuropsychiatric disorders |
| FR2778662B1 (fr) * | 1998-05-12 | 2000-06-16 | Adir | Nouveaux composes cycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US6569879B2 (en) * | 2000-02-18 | 2003-05-27 | Merck & Co., Inc. | Aryloxyacetic acids for diabetes and lipid disorders |
| FR2814165B1 (fr) * | 2000-09-15 | 2002-11-22 | Adir | Nouveaux derives biphenyles substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| MXPA03005152A (es) | 2000-12-11 | 2004-10-14 | Tularik Inc | Antogonista de cxcr3. |
| US6794379B2 (en) | 2001-06-06 | 2004-09-21 | Tularik Inc. | CXCR3 antagonists |
| FR2853649B1 (fr) * | 2003-04-09 | 2006-07-14 | Servier Lab | Nouveaux derives d'isoquinoleine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| FR2857011B1 (fr) * | 2003-07-04 | 2005-09-16 | Servier Lab | Nouveaux derives du benzothiophene 2-thiosubstitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| GB0330042D0 (en) | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions them |
| GB0330043D0 (en) | 2003-12-24 | 2004-01-28 | Pharmacia Italia Spa | Pyrrolo [2,3-b] pyridine derivatives active as kinase inhibitors process for their preparation and pharmaceutical compositions comprising them |
| KR100823805B1 (ko) * | 2004-05-05 | 2008-04-21 | 에프. 호프만-라 로슈 아게 | 5-ht6 수용체, 5-ht2a 수용체 또는 둘다를 조절하기에유용한 아릴설포닐 벤조다이옥산 |
| WO2006019497A2 (en) * | 2004-06-17 | 2006-02-23 | Neurocrine Biosciences, Inc. | Sleep-inducing compounds and methods related thereto |
| US7939538B2 (en) | 2004-06-28 | 2011-05-10 | Amgen Inc. | Compounds, compositions and methods for prevention and treatment of inflammatory and immunoregulatory disorders and diseases |
| US7375102B2 (en) | 2004-06-28 | 2008-05-20 | Amgen Sf, Llc | Tetrahydroquinazolin-4(3H)-one-related and tetrahydropyrido[2,3-D]pyrimidin-4(3H)-one-related compounds, compositions and methods for their use |
| US7271271B2 (en) | 2004-06-28 | 2007-09-18 | Amgen Sf, Llc | Imidazolo-related compounds, compositions and methods for their use |
| MX2007007482A (es) * | 2004-12-21 | 2007-07-20 | Hoffmann La Roche | Derivados de tetralina e indano y usos de los mismos como antagonistas de 5-ht. |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009514828A (ja) * | 2005-11-03 | 2009-04-09 | エフ.ホフマン−ラ ロシュ アーゲー | 5−ht6阻害剤としてのアリールスルホニルクロマン類、タンパク質キナーゼ阻害剤としてのインドリルマレイミド誘導体 |
| JP2018502888A (ja) * | 2015-01-20 | 2018-02-01 | エックスオーシー ファーマシューティカルズ インコーポレイテッドXoc Pharmaceuticals, Inc | エルゴリン化合物およびその使用 |
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