CA2594665A1 - Thienopyrroles useful in the treatment of inflammation - Google Patents

Info

Publication number

CA2594665A1

CA2594665A1 CA002594665A CA2594665A CA2594665A1 CA 2594665 A1 CA2594665 A1 CA 2594665A1 CA 002594665 A CA002594665 A CA 002594665A CA 2594665 A CA2594665 A CA 2594665A CA 2594665 A1 CA2594665 A1 CA 2594665A1

Authority

CA

Canada

Prior art keywords

formula

compound

group

single bond

alkyl

Prior art date

2005-01-19

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 238000011282 treatment Methods 0.000 title claims abstract description 27
• 206010061218 Inflammation Diseases 0.000 title claims abstract description 22
• 230000004054 inflammatory process Effects 0.000 title claims abstract description 22
• 150000001875 compounds Chemical class 0.000 claims abstract description 492
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
• 230000000694 effects Effects 0.000 claims abstract description 24
• 201000010099 disease Diseases 0.000 claims abstract description 20
• 150000003839 salts Chemical class 0.000 claims abstract description 20
• 230000005764 inhibitory process Effects 0.000 claims abstract description 14
• 102000042256 MAPEG family Human genes 0.000 claims abstract description 12
• 108091077604 MAPEG family Proteins 0.000 claims abstract description 12
• 238000006243 chemical reaction Methods 0.000 claims description 144
• -1 -N3 Chemical group 0.000 claims description 82
• 125000001424 substituent group Chemical group 0.000 claims description 80
• 125000000217 alkyl group Chemical group 0.000 claims description 70
• 125000005843 halogen group Chemical group 0.000 claims description 70
• 239000000203 mixture Substances 0.000 claims description 69
• 238000000034 method Methods 0.000 claims description 63
• 238000002360 preparation method Methods 0.000 claims description 53
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 45
• 125000003118 aryl group Chemical group 0.000 claims description 39
• 125000001072 heteroaryl group Chemical group 0.000 claims description 36
• 230000008569 process Effects 0.000 claims description 35
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
• 239000003153 chemical reaction reagent Substances 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• 230000007062 hydrolysis Effects 0.000 claims description 22
• 238000006460 hydrolysis reaction Methods 0.000 claims description 22
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• 230000009467 reduction Effects 0.000 claims description 19
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• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
• 125000002947 alkylene group Chemical group 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 18
• 125000004122 cyclic group Chemical group 0.000 claims description 18
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• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 16
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 15
• 125000001246 bromo group Chemical group Br* 0.000 claims description 15
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• 125000001153 fluoro group Chemical group F* 0.000 claims description 13
• 125000001041 indolyl group Chemical group 0.000 claims description 13
• 125000002346 iodo group Chemical group I* 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
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• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
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• 239000003085 diluting agent Substances 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
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• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
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• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 6
• 125000004419 alkynylene group Chemical group 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
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
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• 239000007818 Grignard reagent Substances 0.000 claims description 5
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• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
• 150000004795 grignard reagents Chemical class 0.000 claims description 5
• 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 5
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 5
• 230000002757 inflammatory effect Effects 0.000 claims description 5
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• 239000011701 zinc Substances 0.000 claims description 5
• 206010065390 Inflammatory pain Diseases 0.000 claims description 4
• 206010037660 Pyrexia Diseases 0.000 claims description 4
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
• 239000013066 combination product Substances 0.000 claims description 4
• 229940127555 combination product Drugs 0.000 claims description 4
• 230000032050 esterification Effects 0.000 claims description 4
• 238000005886 esterification reaction Methods 0.000 claims description 4
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• 229910052725 zinc Inorganic materials 0.000 claims description 4
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 3
• 206010010741 Conjunctivitis Diseases 0.000 claims description 3
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• 230000000172 allergic effect Effects 0.000 claims description 3
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 239000001569 carbon dioxide Substances 0.000 claims description 3
• 229910002092 carbon dioxide Inorganic materials 0.000 claims description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000004474 heteroalkylene group Chemical group 0.000 claims description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 3
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 3
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• 125000005647 linker group Chemical group 0.000 claims description 3
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• 125000001624 naphthyl group Chemical group 0.000 claims description 3
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• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
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• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
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