ZA200006528B - Novel substituted cyclic compounds, preparation method and pharmaceutical compositions containing them. - Google Patents
Novel substituted cyclic compounds, preparation method and pharmaceutical compositions containing them. Download PDFInfo
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- ZA200006528B ZA200006528B ZA200006528A ZA200006528A ZA200006528B ZA 200006528 B ZA200006528 B ZA 200006528B ZA 200006528 A ZA200006528 A ZA 200006528A ZA 200006528 A ZA200006528 A ZA 200006528A ZA 200006528 B ZA200006528 B ZA 200006528B
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- South Africa
- Prior art keywords
- formula
- group
- substituted
- compounds
- enantiomers
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 491
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 150000001923 cyclic compounds Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 241
- 239000007858 starting material Substances 0.000 claims description 205
- 239000002253 acid Substances 0.000 claims description 100
- 150000003839 salts Chemical class 0.000 claims description 94
- 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 89
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 74
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 67
- 125000004122 cyclic group Chemical group 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- -1 cyano, nitro, amino Chemical group 0.000 claims description 42
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 230000009471 action Effects 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 239000005864 Sulphur Substances 0.000 claims description 15
- 125000006684 polyhaloalkyl group Polymers 0.000 claims description 15
- 125000005605 benzo group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 150000003254 radicals Chemical class 0.000 claims description 12
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 230000001193 melatoninergic effect Effects 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000003367 polycyclic group Polymers 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 229920002554 vinyl polymer Polymers 0.000 claims description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- 150000002790 naphthalenes Chemical class 0.000 claims description 7
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical class C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 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
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 6
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000003573 thiols Chemical class 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical class C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052684 Cerium Inorganic materials 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical group C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 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
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000000543 intermediate Substances 0.000 claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- NNWLHBCKEQMHKH-UHFFFAOYSA-N 1-methyl-3-[2-(7-methylsulfanylnaphthalen-1-yl)ethyl]urea Chemical group C1=C(SC)C=C2C(CCNC(=O)NC)=CC=CC2=C1 NNWLHBCKEQMHKH-UHFFFAOYSA-N 0.000 claims description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- YRTCKZIKGWZNCU-UHFFFAOYSA-N furo[3,2-b]pyridine Chemical class C1=CC=C2OC=CC2=N1 YRTCKZIKGWZNCU-UHFFFAOYSA-N 0.000 claims description 3
- 150000002475 indoles Chemical group 0.000 claims description 3
- JICNOTFGSVBSSV-UHFFFAOYSA-N n-[2-(7-benzylsulfanyl-3-phenylnaphthalen-1-yl)ethyl]acetamide Chemical compound C1=C2C(CCNC(=O)C)=CC(C=3C=CC=CC=3)=CC2=CC=C1SCC1=CC=CC=C1 JICNOTFGSVBSSV-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- VIMNEBUQXGHMFF-UHFFFAOYSA-N n-[2-(7-propylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical group C1=CC=C(CCNC(C)=O)C2=CC(SCCC)=CC=C21 VIMNEBUQXGHMFF-UHFFFAOYSA-N 0.000 claims description 3
- IBYCIBCRTYGCPG-UHFFFAOYSA-N n-cyclohexyl-4-(7-phenylsulfanylnaphthalen-1-yl)butanamide Chemical compound C1CCCCC1NC(=O)CCCC(C1=C2)=CC=CC1=CC=C2SC1=CC=CC=C1 IBYCIBCRTYGCPG-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 150000003222 pyridines Chemical group 0.000 claims description 3
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical class C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 3
- ZPXJKIVGYVDEDN-UHFFFAOYSA-N 2-(7-cyclopentylsulfanylnaphthalen-1-yl)-n-methylacetamide Chemical compound C1=C2C(CC(=O)NC)=CC=CC2=CC=C1SC1CCCC1 ZPXJKIVGYVDEDN-UHFFFAOYSA-N 0.000 claims description 2
- 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
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 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
- 229910019093 NaOCl Inorganic materials 0.000 claims description 2
- 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 claims description 2
- 238000007239 Wittig reaction Methods 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- 150000001263 acyl chlorides Chemical class 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 150000001540 azides Chemical class 0.000 claims description 2
- 229910002056 binary alloy Inorganic materials 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 239000003814 drug Substances 0.000 claims description 2
- QSVLGSJPOZYHMK-UHFFFAOYSA-N ethyl 1-methyl-9-[2-[(2-phenylacetyl)amino]ethyl]-3h-benzo[e]indole-2-carboxylate Chemical compound C12=C3C(C)=C(C(=O)OCC)NC3=CC=C2C=CC=C1CCNC(=O)CC1=CC=CC=C1 QSVLGSJPOZYHMK-UHFFFAOYSA-N 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
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
- 230000022244 formylation Effects 0.000 claims description 2
- 238000006170 formylation reaction Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 238000006138 lithiation reaction Methods 0.000 claims description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 2
- IKRSUVUEOJKCKD-UHFFFAOYSA-N n-[(2-benzyl-8,9-dihydro-7h-thieno[3,2-f]thiochromen-1-yl)methyl]acetamide Chemical compound S1C2=CC=C3SCCCC3=C2C(CNC(=O)C)=C1CC1=CC=CC=C1 IKRSUVUEOJKCKD-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- QOOZHYPNCOMUGU-UHFFFAOYSA-N n-[2-(2-benzyl-5-sulfanyl-1-benzofuran-3-yl)ethyl]cyclopropanecarboxamide Chemical compound C1CC1C(=O)NCCC=1C2=CC(S)=CC=C2OC=1CC1=CC=CC=C1 QOOZHYPNCOMUGU-UHFFFAOYSA-N 0.000 claims description 2
- UIWVJTHHRPYGHX-UHFFFAOYSA-N n-[2-(3-benzyl-7-methylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical group C1=C(CCNC(C)=O)C2=CC(SC)=CC=C2C=C1CC1=CC=CC=C1 UIWVJTHHRPYGHX-UHFFFAOYSA-N 0.000 claims description 2
- RBDVGQGLCRUMHS-UHFFFAOYSA-N n-[2-(5-sulfanyl-1-benzofuran-3-yl)ethyl]acetamide Chemical compound C1=C(S)C=C2C(CCNC(=O)C)=COC2=C1 RBDVGQGLCRUMHS-UHFFFAOYSA-N 0.000 claims description 2
- VNFOEJMDQTWJKD-UHFFFAOYSA-N n-[2-(7-benzylsulfanylnaphthalen-1-yl)ethyl]acetamide Chemical group C1=C2C(CCNC(=O)C)=CC=CC2=CC=C1SCC1=CC=CC=C1 VNFOEJMDQTWJKD-UHFFFAOYSA-N 0.000 claims description 2
- ZMDWAOWABWHEJS-UHFFFAOYSA-N n-[2-(7-methylsulfanyl-1,2,3,4-tetrahydronaphthalen-1-yl)ethyl]acetamide Chemical group C1CCC(CCNC(C)=O)C2=CC(SC)=CC=C21 ZMDWAOWABWHEJS-UHFFFAOYSA-N 0.000 claims description 2
- MZUIKFQBGPXOJR-UHFFFAOYSA-N n-[2-(7-methylsulfonylnaphthalen-1-yl)ethyl]acetamide Chemical group C1=C(S(C)(=O)=O)C=C2C(CCNC(=O)C)=CC=CC2=C1 MZUIKFQBGPXOJR-UHFFFAOYSA-N 0.000 claims description 2
- MTRBAXYNLVSFDY-UHFFFAOYSA-N n-[2-[5-(3-methylbutylsulfanyl)-1-benzothiophen-3-yl]ethyl]prop-2-enamide Chemical compound CC(C)CCSC1=CC=C2SC=C(CCNC(=O)C=C)C2=C1 MTRBAXYNLVSFDY-UHFFFAOYSA-N 0.000 claims description 2
- QTWDGEJYGSFEMZ-UHFFFAOYSA-N n-[2-[7-(diethylamino)naphthalen-1-yl]ethyl]-2-phenylacetamide Chemical compound C12=CC(N(CC)CC)=CC=C2C=CC=C1CCNC(=O)CC1=CC=CC=C1 QTWDGEJYGSFEMZ-UHFFFAOYSA-N 0.000 claims description 2
- HNSXAIJTBIYBHA-UHFFFAOYSA-N n-[2-[7-(hexylamino)-1,2,3,4-tetrahydronaphthalen-1-yl]ethyl]acetamide Chemical compound C1CCC(CCNC(C)=O)C2=CC(NCCCCCC)=CC=C21 HNSXAIJTBIYBHA-UHFFFAOYSA-N 0.000 claims description 2
- IARKOECUOPUDRJ-UHFFFAOYSA-N n-[3-(7-prop-1-enylsulfanyl-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]acetamide Chemical compound C1CCC(CCCNC(C)=O)C2=CC(SC=CC)=CC=C21 IARKOECUOPUDRJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000012038 nucleophile Substances 0.000 claims description 2
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 claims description 2
- 238000005949 ozonolysis reaction Methods 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 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 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000009467 reduction Effects 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
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 claims description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 8
- 150000001555 benzenes Chemical class 0.000 claims 4
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 claims 4
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 claims 2
- 241000947840 Alteromonadales Species 0.000 claims 1
- 229910015845 BBr3 Inorganic materials 0.000 claims 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims 1
- 238000007796 conventional method Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
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- XMTUHUZYESERTJ-UHFFFAOYSA-N n-[3-(5-but-3-yn-2-ylsulfanyl-1-benzofuran-3-yl)propyl]acetamide Chemical compound C#CC(C)SC1=CC=C2OC=C(CCCNC(C)=O)C2=C1 XMTUHUZYESERTJ-UHFFFAOYSA-N 0.000 description 1
- VRLCWEGFGHAICJ-UHFFFAOYSA-N n-[3-(7-bromonaphthalen-1-yl)propyl]cyclohexanecarboxamide Chemical compound C12=CC(Br)=CC=C2C=CC=C1CCCNC(=O)C1CCCCC1 VRLCWEGFGHAICJ-UHFFFAOYSA-N 0.000 description 1
- IWSNVTVNUADILW-UHFFFAOYSA-N n-[3-(7-butylsulfanylnaphthalen-1-yl)propyl]cyclohexanecarboxamide Chemical compound C12=CC(SCCCC)=CC=C2C=CC=C1CCCNC(=O)C1CCCCC1 IWSNVTVNUADILW-UHFFFAOYSA-N 0.000 description 1
- DJCXTYBURMRWMY-UHFFFAOYSA-N n-[3-(7-hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]acetamide Chemical compound C1=C(O)C=C2C(CCCNC(=O)C)CCCC2=C1 DJCXTYBURMRWMY-UHFFFAOYSA-N 0.000 description 1
- HLQOHWBCUJMQLV-UHFFFAOYSA-N n-[3-(7-hydroxynaphthalen-1-yl)propyl]acetamide Chemical compound C1=C(O)C=C2C(CCCNC(=O)C)=CC=CC2=C1 HLQOHWBCUJMQLV-UHFFFAOYSA-N 0.000 description 1
- RWWIZFRSOLUHOS-UHFFFAOYSA-N n-[3-(7-iodonaphthalen-1-yl)propyl]acetamide Chemical compound C1=C(I)C=C2C(CCCNC(=O)C)=CC=CC2=C1 RWWIZFRSOLUHOS-UHFFFAOYSA-N 0.000 description 1
- QQXXOYQVDIOHPJ-UHFFFAOYSA-N n-[3-(7-iodonaphthalen-1-yl)propyl]cyclohexanecarboxamide Chemical compound C12=CC(I)=CC=C2C=CC=C1CCCNC(=O)C1CCCCC1 QQXXOYQVDIOHPJ-UHFFFAOYSA-N 0.000 description 1
- DEDTVONKEBGOHL-UHFFFAOYSA-N n-[3-(7-prop-1-enylsulfanylnaphthalen-1-yl)propyl]acetamide Chemical compound C1=CC=C(CCCNC(C)=O)C2=CC(SC=CC)=CC=C21 DEDTVONKEBGOHL-UHFFFAOYSA-N 0.000 description 1
- AKDQYYNDCFBENU-UHFFFAOYSA-N n-[3-(7-sulfanylnaphthalen-1-yl)propyl]cyclohexanecarboxamide Chemical compound C12=CC(S)=CC=C2C=CC=C1CCCNC(=O)C1CCCCC1 AKDQYYNDCFBENU-UHFFFAOYSA-N 0.000 description 1
- PLARSOSNLHDVBY-UHFFFAOYSA-N n-[3-[7-(4-methylpent-1-yn-3-ylsulfanyl)naphthalen-1-yl]propyl]acetamide Chemical compound C1=CC=C(CCCNC(C)=O)C2=CC(SC(C(C)C)C#C)=CC=C21 PLARSOSNLHDVBY-UHFFFAOYSA-N 0.000 description 1
- XGZIJNAJGRBOFJ-UHFFFAOYSA-N n-cyclobutyl-3-(7-prop-2-ynylsulfanylnaphthalen-1-yl)propanamide Chemical compound C=1C=CC2=CC=C(SCC#C)C=C2C=1CCC(=O)NC1CCC1 XGZIJNAJGRBOFJ-UHFFFAOYSA-N 0.000 description 1
- SQVZOUHCGRUKAV-UHFFFAOYSA-N n-cyclohexyl-4-(7-hydroxynaphthalen-1-yl)butanamide Chemical compound C12=CC(O)=CC=C2C=CC=C1CCCC(=O)NC1CCCCC1 SQVZOUHCGRUKAV-UHFFFAOYSA-N 0.000 description 1
- DHYAKGRGQKEMHS-UHFFFAOYSA-N n-cyclohexyl-4-(7-iodonaphthalen-1-yl)butanamide Chemical compound C12=CC(I)=CC=C2C=CC=C1CCCC(=O)NC1CCCCC1 DHYAKGRGQKEMHS-UHFFFAOYSA-N 0.000 description 1
- XRQZEVQXLVHVDR-UHFFFAOYSA-N n-cyclohexyl-4-(7-sulfanylnaphthalen-1-yl)butanamide Chemical compound C12=CC(S)=CC=C2C=CC=C1CCCC(=O)NC1CCCCC1 XRQZEVQXLVHVDR-UHFFFAOYSA-N 0.000 description 1
- PVWCLJKTNIJRKU-UHFFFAOYSA-N n-methyl-3-(6-sulfanyl-2h-chromen-3-yl)propanamide Chemical compound SC1=CC=C2OCC(CCC(=O)NC)=CC2=C1 PVWCLJKTNIJRKU-UHFFFAOYSA-N 0.000 description 1
- GDCPLFNFIVUWSF-UHFFFAOYSA-N n-methyl-4-(5-prop-2-ynylsulfanyl-1h-indol-3-yl)butanamide Chemical compound C1=C(SCC#C)C=C2C(CCCC(=O)NC)=CNC2=C1 GDCPLFNFIVUWSF-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet 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
- 229940125670 thienopyridine Drugs 0.000 description 1
- 239000002175 thienopyridine Substances 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 description 1
- 125000004035 thiopropyl group Chemical group [H]SC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
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| 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 |
| CZ20031910A3 (cs) | 2000-12-11 | 2003-12-17 | Tularik Inc. | Sloučenina s antagonistickými účinky na CXCR3 a farmaceutický postředek |
| 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 |
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