SK122194A3 - Perhydroisoindole derivatives and preparation thereof - Google Patents

Perhydroisoindole derivatives and preparation thereof Download PDF

Info

Publication number: SK122194A3
Authority: SK; Slovakia
Prior art keywords: group; diphenyl; methoxyphenyl; perhydroisoindole; hydroxy
Prior art date: 1992-04-10

Application number

SK1221-94A

Other languages

English (en)

Slovak (sk)

Inventor

Daniel Achard

Serge Grisoni

Jean-Luc Malleron

Jean-Francois Peyronel

Michel Tabart

Original Assignee

Rhone Poulenc Rorer Sa

Priority date (The priority date 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 date listed.)

1992-04-10

Filing date

1993-04-08

Publication date

1995-05-10

1993-04-08 Application filed by Rhone Poulenc Rorer Sa filed Critical Rhone Poulenc Rorer Sa

1995-05-10 Publication of SK122194A3 publication Critical patent/SK122194A3/sk

Links

ODSNARDHJFFSRH-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindole Chemical class C1CCCC2CNCC21 ODSNARDHJFFSRH-UHFFFAOYSA-N 0.000 title claims abstract description 23
238000002360 preparation method Methods 0.000 title claims abstract description 15
-1 phenyl radicals Chemical class 0.000 claims abstract description 50
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
125000005843 halogen group Chemical group 0.000 claims abstract description 14
229910052731 fluorine Inorganic materials 0.000 claims abstract description 13
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 13
150000003839 salts Chemical class 0.000 claims abstract description 13
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 60
239000000203 mixture Substances 0.000 claims description 53
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
238000000034 method Methods 0.000 claims description 48
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
229920006395 saturated elastomer Polymers 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 28
125000006239 protecting group Chemical group 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 16
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
150000001875 compounds Chemical class 0.000 claims description 9
125000003282 alkyl amino group Chemical group 0.000 claims description 8
125000004663 dialkyl amino group Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
239000011593 sulfur Chemical group 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 6
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000003277 amino group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
230000018044 dehydration Effects 0.000 claims description 4
238000006297 dehydration reaction Methods 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000002950 monocyclic group Chemical group 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
150000002902 organometallic compounds Chemical class 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
125000003367 polycyclic group Chemical group 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
GHROLIYNHYPTSN-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-(2-methoxyphenyl)-7,7-diphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound COC1=CC=CC=C1C1(O)C2CN(C(=O)OC(C)(C)C)CC2C(C=2C=CC=CC=2)(C=2C=CC=CC=2)CC1 GHROLIYNHYPTSN-UHFFFAOYSA-N 0.000 claims description 3
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 2
125000004442 acylamino group Chemical group 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 2
125000004103 aminoalkyl group Chemical group 0.000 claims description 2
125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 claims description 2
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000000904 isoindolyl group Chemical class C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
AENVFIFDTPYLLD-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydro-1h-isoindol-1-ol Chemical compound C1CCCC2C(O)NCC21 AENVFIFDTPYLLD-UHFFFAOYSA-N 0.000 claims 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
239000004927 clay Substances 0.000 claims 1
229910052744 lithium Inorganic materials 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 30
239000000543 intermediate Substances 0.000 abstract description 7
230000000694 effects Effects 0.000 abstract description 6
239000005557 antagonist Substances 0.000 abstract description 5
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 abstract 1
230000001681 protective effect Effects 0.000 abstract 1
150000003254 radicals Chemical class 0.000 abstract 1
ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 133
239000000243 solution Substances 0.000 description 94
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
239000011541 reaction mixture Substances 0.000 description 41
238000002844 melting Methods 0.000 description 40
230000008018 melting Effects 0.000 description 40
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 37
239000013078 crystal Substances 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
229910052943 magnesium sulfate Inorganic materials 0.000 description 30
235000019341 magnesium sulphate Nutrition 0.000 description 30
239000000725 suspension Substances 0.000 description 29
239000000047 product Substances 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 20
239000000741 silica gel Substances 0.000 description 20
229910002027 silica gel Inorganic materials 0.000 description 20
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 18
239000011780 sodium chloride Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 18
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000007787 solid Substances 0.000 description 15
LFDLEAOOBNTQGK-USVPWNMWSA-N (3as,4s,7as)-4-(2-methoxyphenyl)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-ol;hydrochloride Chemical compound Cl.COC1=CC=CC=C1[C@@]1(O)[C@@H]2CNC[C@@H]2C(C=2C=CC=CC=2)(C=2C=CC=CC=2)CC1 LFDLEAOOBNTQGK-USVPWNMWSA-N 0.000 description 14
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
102100024304 Protachykinin-1 Human genes 0.000 description 14
101800003906 Substance P Proteins 0.000 description 14
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
239000002253 acid Substances 0.000 description 13
238000002329 infrared spectrum Methods 0.000 description 13
239000008259 solid foam Substances 0.000 description 13
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
238000001033 granulometry Methods 0.000 description 12
239000012074 organic phase Substances 0.000 description 11
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
125000003118 aryl group Chemical group 0.000 description 9
150000002518 isoindoles Chemical class 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
238000000354 decomposition reaction Methods 0.000 description 8
238000010828 elution Methods 0.000 description 8
SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
235000019270 ammonium chloride Nutrition 0.000 description 7
239000012153 distilled water Substances 0.000 description 7
239000002245 particle Substances 0.000 description 7
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
239000006260 foam Substances 0.000 description 6
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
IVEWTCACRDEAOB-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetic acid Chemical compound COC1=CC=CC=C1CC(O)=O IVEWTCACRDEAOB-UHFFFAOYSA-N 0.000 description 5
230000002411 adverse Effects 0.000 description 5
150000002431 hydrogen Chemical class 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
238000010992 reflux Methods 0.000 description 5
238000000926 separation method Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
GRZXYQUMNHMMSP-RTWAWAEBSA-N tert-butyl (3as,7as)-7-oxo-4,4-diphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound C=1C=CC=CC=1C1([C@@H]2[C@H](C(CC1)=O)CN(C2)C(=O)OC(C)(C)C)C1=CC=CC=C1 GRZXYQUMNHMMSP-RTWAWAEBSA-N 0.000 description 5
GTXFJLYNMBNGSW-UHFFFAOYSA-N (2-benzyl-4-oxo-7,7-diphenyl-1,3,3a,5,6,7a-hexahydroisoindol-5-yl) acetate Chemical compound C1C2C(=O)C(OC(=O)C)CC(C=3C=CC=CC=3)(C=3C=CC=CC=3)C2CN1CC1=CC=CC=C1 GTXFJLYNMBNGSW-UHFFFAOYSA-N 0.000 description 4
NUSLQDOXLCYVTQ-ZETCQYMHSA-N (2s)-2-(2-methoxyphenyl)propanoic acid Chemical compound COC1=CC=CC=C1[C@H](C)C(O)=O NUSLQDOXLCYVTQ-ZETCQYMHSA-N 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
JKYNCKNIVHDOKU-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydroisoindol-1-one Chemical class C1CCCC2C(=O)NCC21 JKYNCKNIVHDOKU-UHFFFAOYSA-N 0.000 description 4
UPEWDRCXLROYOF-UHFFFAOYSA-N 2-(2-methoxyphenyl)acetyl chloride Chemical compound COC1=CC=CC=C1CC(Cl)=O UPEWDRCXLROYOF-UHFFFAOYSA-N 0.000 description 4
LFDLEAOOBNTQGK-UHFFFAOYSA-N 4-(2-methoxyphenyl)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-ol;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C1(O)C2CNCC2C(C=2C=CC=CC=2)(C=2C=CC=CC=2)CC1 LFDLEAOOBNTQGK-UHFFFAOYSA-N 0.000 description 4
206010006482 Bronchospasm Diseases 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
FCPRDUXJWIUVPZ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=CC=[C-]1 FCPRDUXJWIUVPZ-UHFFFAOYSA-M 0.000 description 4
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 4
239000002904 solvent Substances 0.000 description 4
CIJLMNDNUOEELM-URBRKQAFSA-N (3as,7as)-7,7-diphenyl-2,3,3a,5,6,7a-hexahydro-1h-isoindol-4-one;hydrochloride Chemical compound Cl.O=C([C@@H]1CNC[C@@H]11)CCC1(C=1C=CC=CC=1)C1=CC=CC=C1 CIJLMNDNUOEELM-URBRKQAFSA-N 0.000 description 3
AWWGCTHFNOCGCA-SCLBCKFNSA-N (4s,5s)-3-[2-(2-methoxyphenyl)acetyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one Chemical compound COC1=CC=CC=C1CC(=O)N1C(=O)O[C@@H](C=2C=CC=CC=2)[C@@H]1C AWWGCTHFNOCGCA-SCLBCKFNSA-N 0.000 description 3
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
206010020751 Hypersensitivity Diseases 0.000 description 3
208000001953 Hypotension Diseases 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
230000007815 allergy Effects 0.000 description 3
230000003042 antagnostic effect Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000003480 eluent Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
230000036543 hypotension Effects 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
DJPHMDFRLSRANE-PYYUSEHKSA-N tert-butyl (3as,4s,7as)-4-fluoro-4-(2-methoxyphenyl)-7,7-diphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound COC1=CC=CC=C1[C@@]1(F)[C@@H]2CN(C(=O)OC(C)(C)C)C[C@@H]2C(C=2C=CC=CC=2)(C=2C=CC=CC=2)CC1 DJPHMDFRLSRANE-PYYUSEHKSA-N 0.000 description 3
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COCNDHOPIHDTHK-UHFFFAOYSA-N 5-methoxyindole-3-acetic acid Chemical compound COC1=CC=C2NC=C(CC(O)=O)C2=C1 COCNDHOPIHDTHK-UHFFFAOYSA-N 0.000 description 1
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150000002688 maleic acid derivatives Chemical class 0.000 description 1
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PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
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125000000168 pyrrolyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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230000007017 scission Effects 0.000 description 1
230000028327 secretion Effects 0.000 description 1
PMOBWAXBGUSOPS-UHFFFAOYSA-N selenium tetrafluoride Chemical compound F[Se](F)(F)F PMOBWAXBGUSOPS-UHFFFAOYSA-N 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
SFZCNBIFKDRMGX-UHFFFAOYSA-N sulfur hexafluoride Chemical compound FS(F)(F)(F)(F)F SFZCNBIFKDRMGX-UHFFFAOYSA-N 0.000 description 1
229960000909 sulfur hexafluoride Drugs 0.000 description 1
QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
DOFWPVHNCPKPNB-SWFBWHSRSA-N tert-butyl (3as,4s,7as)-4-hydroxy-4,7,7-triphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound C1([C@]2(O)CCC([C@@H]3[C@H]2CN(C3)C(=O)OC(C)(C)C)(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC=C1 DOFWPVHNCPKPNB-SWFBWHSRSA-N 0.000 description 1
PQBHWMIAFOOBFS-UHFFFAOYSA-N tert-butyl 6-acetyloxy-7-oxo-4,4-diphenyl-1,3,3a,5,6,7a-hexahydroisoindole-2-carboxylate Chemical compound C12CN(C(=O)OC(C)(C)C)CC2C(=O)C(OC(=O)C)CC1(C=1C=CC=CC=1)C1=CC=CC=C1 PQBHWMIAFOOBFS-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
XIRDWFIDMQZDEU-UHFFFAOYSA-N tetrafluoro(phenyl)-$l^{5}-phosphane Chemical compound FP(F)(F)(F)C1=CC=CC=C1 XIRDWFIDMQZDEU-UHFFFAOYSA-N 0.000 description 1
125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
238000010792 warming Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Indole Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

SK1221-94A 1992-04-10 1993-04-08 Perhydroisoindole derivatives and preparation thereof SK122194A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FR929204391A FR2689889B1 (fr)	1992-04-10	1992-04-10	Nouveaux derives de perhydroisoindole, et leur preparation.
PCT/FR1993/000351 WO1993021154A1 (fr)	1992-04-10	1993-04-08	Nouveaux derives de perhydroisoindole, et leur preparation

Publications (1)

Publication Number	Publication Date
SK122194A3 true SK122194A3 (en)	1995-05-10

Family

ID=9428708

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1221-94A SK122194A3 (en)	1992-04-10	1993-04-08	Perhydroisoindole derivatives and preparation thereof

Country Status (23)

Country	Link
US (1)	US5463077A (cs)
EP (1)	EP0635002B1 (cs)
JP (1)	JPH07505409A (cs)
KR (1)	KR950700879A (cs)
AT (1)	ATE168674T1 (cs)
AU (1)	AU667365B2 (cs)
CA (1)	CA2133841A1 (cs)
CZ (1)	CZ284596B6 (cs)
DE (1)	DE69319902T2 (cs)
DK (1)	DK0635002T3 (cs)
ES (1)	ES2118954T3 (cs)
FI (1)	FI105022B (cs)
FR (1)	FR2689889B1 (cs)
HU (1)	HUT71330A (cs)
IL (2)	IL105256A0 (cs)
MX (1)	MX9301985A (cs)
NO (1)	NO300418B1 (cs)
PL (1)	PL172753B1 (cs)
RU (1)	RU2120438C1 (cs)
SK (1)	SK122194A3 (cs)
TW (1)	TW224969B (cs)
WO (1)	WO1993021154A1 (cs)
ZA (1)	ZA932528B (cs)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2689888B1 (fr) *	1992-04-10	1994-06-10	Rhone Poulenc Rorer Sa	Nouveaux derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent.
FR2703679B1 (fr) *	1993-04-05	1995-06-23	Rhone Poulenc Rorer Sa	Nouveaux derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent.
TW365603B (en) *	1993-07-30	1999-08-01	Rhone Poulenc Rorer Sa	Novel perhydroisoindole derivatives, their preparation and pharmaceutical compositions which contain them
FR2710913B1 (fr) *	1993-10-07	1995-11-24	Rhone Poulenc Rorer Sa	Nouveaux dérivés de perhydroisoindole, leur préparation et les compositions pharmaceutiques qui les contiennent.
FR2709752B1 (fr) *	1993-07-30	1995-10-06	Rhone Poulenc Rorer Sa	Nouveaux dérivés de perhydroisoindole, leur préparation et les compositions pharmaceutiques qui les contiennent.
CN100391945C (zh) *	2005-05-31	2008-06-04	浙江大学	一种s-(-)-吲哚啉-2-羧酸的合成方法
WO2013004766A1 (en)	2011-07-04	2013-01-10	Ferrari Giulio	Nk-1 receptor antagonists for treating corneal neovascularisation
US20210015834A1 (en)	2018-02-26	2021-01-21	Ospedale San Raffaele S.R.L.	Nk-1 antagonists for use in the treatment of ocular pain
WO2021180885A1 (en)	2020-03-11	2021-09-16	Ospedale San Raffaele S.R.L.	Treatment of stem cell deficiency

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4042707A (en) *	1976-02-19	1977-08-16	E. I. Du Pont De Nemours And Company	3α-Arylhydroisoindoles
DE3617183A1 (de) *	1985-11-16	1987-05-27	Bayer Ag	Substituierte benzylether
FR2654726B1 (fr) *	1989-11-23	1992-02-14	Rhone Poulenc Sante	Nouveaux derives de l'isoindolone et leur preparation.
FR2654725B1 (fr) *	1989-11-23	1992-02-14	Rhone Poulenc Sante	Nouveaux derives de l'isoindolone, leur preparation et les compositions pharmaceutiques qui les contiennent.
FR2676443B1 (fr) *	1991-05-17	1993-08-06	Rhone Poulenc Rorer Sa	Nouveaux derives de perhydroisoindole et leur preparation.

1992
- 1992-04-10 FR FR929204391A patent/FR2689889B1/fr not_active Expired - Fee Related
1993
- 1993-04-01 IL IL105256A patent/IL105256A0/xx unknown
- 1993-04-01 IL IL10525697A patent/IL105256A/xx not_active IP Right Cessation
- 1993-04-06 MX MX9301985A patent/MX9301985A/es not_active IP Right Cessation
- 1993-04-08 AT AT93909004T patent/ATE168674T1/de active
- 1993-04-08 JP JP5518040A patent/JPH07505409A/ja active Pending
- 1993-04-08 DE DE69319902T patent/DE69319902T2/de not_active Expired - Fee Related
- 1993-04-08 CZ CZ942483A patent/CZ284596B6/cs unknown
- 1993-04-08 US US08/313,120 patent/US5463077A/en not_active Expired - Fee Related
- 1993-04-08 PL PL93305359A patent/PL172753B1/pl unknown
- 1993-04-08 WO PCT/FR1993/000351 patent/WO1993021154A1/fr not_active Ceased
- 1993-04-08 AU AU39564/93A patent/AU667365B2/en not_active Ceased
- 1993-04-08 ZA ZA932528A patent/ZA932528B/xx unknown
- 1993-04-08 SK SK1221-94A patent/SK122194A3/sk unknown
- 1993-04-08 DK DK93909004T patent/DK0635002T3/da active
- 1993-04-08 EP EP93909004A patent/EP0635002B1/fr not_active Expired - Lifetime
- 1993-04-08 CA CA002133841A patent/CA2133841A1/fr not_active Abandoned
- 1993-04-08 RU RU94045867A patent/RU2120438C1/ru active
- 1993-04-08 HU HU9402912A patent/HUT71330A/hu unknown
- 1993-04-08 ES ES93909004T patent/ES2118954T3/es not_active Expired - Lifetime
- 1993-04-09 TW TW082102663A patent/TW224969B/zh active
1994
- 1994-10-05 NO NO943738A patent/NO300418B1/no unknown
- 1994-10-06 KR KR1019940703537A patent/KR950700879A/ko not_active Withdrawn
- 1994-10-07 FI FI944728A patent/FI105022B/fi active

Also Published As

Publication number	Publication date
CZ284596B6 (cs)	1999-01-13
FI944728A0 (fi)	1994-10-07
HUT71330A (en)	1995-11-28
FR2689889B1 (fr)	1994-06-10
JPH07505409A (ja)	1995-06-15
DE69319902D1 (de)	1998-08-27
FI944728L (fi)	1994-10-07
CZ248394A3 (en)	1995-11-15
ES2118954T3 (es)	1998-10-01
EP0635002B1 (fr)	1998-07-22
DE69319902T2 (de)	1999-03-18
IL105256A0 (en)	1993-08-18
WO1993021154A1 (fr)	1993-10-28
NO943738D0 (no)	1994-10-05
NO943738L (no)	1994-10-05
NO300418B1 (no)	1997-05-26
EP0635002A1 (fr)	1995-01-25
IL105256A (en)	1997-08-14
RU2120438C1 (ru)	1998-10-20
AU3956493A (en)	1993-11-18
FR2689889A1 (fr)	1993-10-15
TW224969B (cs)	1994-06-11
HU9402912D0 (en)	1995-01-30
US5463077A (en)	1995-10-31
DK0635002T3 (da)	1999-02-22
FI105022B (fi)	2000-05-31
KR950700879A (ko)	1995-02-20
ATE168674T1 (de)	1998-08-15
ZA932528B (en)	1993-10-28
MX9301985A (es)	1994-05-31
CA2133841A1 (fr)	1993-10-28
AU667365B2 (en)	1996-03-21
PL172753B1 (en)	1997-11-28
RU94045867A (ru)	1996-09-10

Publication	Publication Date	Title
AU667214B2 (en)	1996-03-14	Perhydroisoindole derivatives as P substance antagonists
US5624950A (en)	1997-04-29	Perhydroisoindole derivatives as substance P antagonists
US5451601A (en)	1995-09-19	Perhydroisoindole derivatives and pharmaceutical compositions containing them
US5508433A (en)	1996-04-16	Derivatives of perhydroisoindole and preparation thereof
RU2012559C1 (ru)	1994-05-15	Производные изоиндолона в виде (3 аr, 7 аr)- или (3 аrs, 7 аrs)-форм или их смесей или их гидрохлориды, являющиеся антагонистами вещества р
US5739351A (en)	1998-04-14	Perhydroisoindole derivatives as substance P antagonists
SK126693A3 (en)	1994-05-11	Novel derivatives of thiopyranopyrrole and preparation thereof
CZ244993A3 (en)	1994-03-16	Novel thiopyrrole derivatives, process of their preparation and pharmaceutical preparations in which they are comprised
HU214574B (hu)	1998-04-28	Eljárás izoindolonszármazékok előállítására
SK122194A3 (en)	1995-05-10	Perhydroisoindole derivatives and preparation thereof
SK123595A3 (en)	1996-06-05	Perhydroisoindole derivatives, preparation thereof and pharmaceutical compositions containing same