BRPI0609767A2 - método de preparar um composto, composto, e, composição farmacêutica - Google Patents
método de preparar um composto, composto, e, composição farmacêutica Download PDFInfo
- Publication number
- BRPI0609767A2 BRPI0609767A2 BRPI0609767-7A BRPI0609767A BRPI0609767A2 BR PI0609767 A2 BRPI0609767 A2 BR PI0609767A2 BR PI0609767 A BRPI0609767 A BR PI0609767A BR PI0609767 A2 BRPI0609767 A2 BR PI0609767A2
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- Brazil
- Prior art keywords
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- group
- compound
- aryl
- alkyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 130
- 238000000034 method Methods 0.000 title claims abstract description 122
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 230000002159 abnormal effect Effects 0.000 claims abstract description 13
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 230000028709 inflammatory response Effects 0.000 claims abstract description 13
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 11
- 230000004663 cell proliferation Effects 0.000 claims abstract description 11
- 125000003118 aryl group Chemical group 0.000 claims description 123
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- 125000001072 heteroaryl group Chemical group 0.000 claims description 97
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 87
- 125000003545 alkoxy group Chemical group 0.000 claims description 77
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 63
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 53
- 230000027326 copulation Effects 0.000 claims description 51
- 125000004104 aryloxy group Chemical group 0.000 claims description 47
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 42
- -1 alkoxy aryloxy Chemical group 0.000 claims description 41
- 125000003282 alkyl amino group Chemical group 0.000 claims description 41
- 125000001153 fluoro group Chemical group F* 0.000 claims description 37
- 239000011701 zinc Substances 0.000 claims description 36
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 32
- 229910052725 zinc Inorganic materials 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000002837 carbocyclic group Chemical group 0.000 claims description 30
- 239000000460 chlorine Substances 0.000 claims description 30
- 239000011777 magnesium Substances 0.000 claims description 29
- 229910052749 magnesium Inorganic materials 0.000 claims description 29
- 229910052794 bromium Inorganic materials 0.000 claims description 28
- 125000002252 acyl group Chemical group 0.000 claims description 27
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 27
- 150000001768 cations Chemical class 0.000 claims description 27
- 125000005207 tetraalkylammonium group Chemical group 0.000 claims description 27
- 229910052700 potassium Inorganic materials 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 239000011734 sodium Substances 0.000 claims description 26
- 229910052708 sodium Inorganic materials 0.000 claims description 26
- 229910052801 chlorine Inorganic materials 0.000 claims description 25
- 125000003342 alkenyl group Chemical group 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 21
- 238000005984 hydrogenation reaction Methods 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 125000004442 acylamino group Chemical group 0.000 claims description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
- 125000005518 carboxamido group Chemical group 0.000 claims description 15
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 125000005647 linker group Chemical group 0.000 claims description 13
- 150000003751 zinc Chemical class 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 10
- 229910052740 iodine Inorganic materials 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 239000011593 sulfur Substances 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000005035 acylthio group Chemical group 0.000 claims description 8
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 7
- 125000005256 alkoxyacyl group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 150000001879 copper Chemical class 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000005228 aryl sulfonate group Chemical group 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 239000010949 copper Substances 0.000 claims description 5
- 238000005828 desilylation reaction Methods 0.000 claims description 5
- 125000004437 phosphorous atom Chemical group 0.000 claims description 5
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 4
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001345 alkine derivatives Chemical class 0.000 claims description 4
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims description 4
- 229910052796 boron Inorganic materials 0.000 claims description 4
- 229940125961 compound 24 Drugs 0.000 claims description 4
- 229910052802 copper Inorganic materials 0.000 claims description 4
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 4
- 239000010703 silicon Substances 0.000 claims description 4
- 229910052710 silicon Inorganic materials 0.000 claims description 4
- 229910052718 tin Inorganic materials 0.000 claims description 4
- 239000011135 tin Substances 0.000 claims description 4
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 3
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims description 3
- 229940125833 compound 23 Drugs 0.000 claims description 3
- 238000006317 isomerization reaction Methods 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 239000011574 phosphorus Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-PWCQTSIFSA-N Tritiated water Chemical compound [3H]O[3H] XLYOFNOQVPJJNP-PWCQTSIFSA-N 0.000 claims description 2
- PGTXKIZLOWULDJ-UHFFFAOYSA-N [Mg].[Zn] Chemical compound [Mg].[Zn] PGTXKIZLOWULDJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 45
- 239000003125 aqueous solvent Substances 0.000 claims 3
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 2
- 101100477602 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SIR3 gene Proteins 0.000 claims 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims 1
- OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 claims 1
- 229940127007 Compound 39 Drugs 0.000 claims 1
- 229910003251 Na K Inorganic materials 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000005741 alkyl alkenyl group Chemical group 0.000 claims 1
- 125000005122 aminoalkylamino group Chemical group 0.000 claims 1
- 229940126540 compound 41 Drugs 0.000 claims 1
- 229940125936 compound 42 Drugs 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 35
- 150000002066 eicosanoids Chemical class 0.000 abstract description 18
- 238000002360 preparation method Methods 0.000 abstract description 18
- 206010061218 Inflammation Diseases 0.000 abstract description 9
- 230000004054 inflammatory process Effects 0.000 abstract description 9
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- 150000002431 hydrogen Chemical class 0.000 description 37
- 239000000243 solution Substances 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000000543 intermediate Substances 0.000 description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 230000008569 process Effects 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 150000001299 aldehydes Chemical class 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000002243 precursor Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 12
- 125000002947 alkylene group Chemical group 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 9
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 238000003818 flash chromatography Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 229940126543 compound 14 Drugs 0.000 description 6
- 229940126214 compound 3 Drugs 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 150000002617 leukotrienes Chemical class 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 229930184725 Lipoxin Natural products 0.000 description 4
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 229940127204 compound 29 Drugs 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 150000002639 lipoxins Chemical class 0.000 description 4
- 238000006772 olefination reaction Methods 0.000 description 4
- 150000002924 oxiranes Chemical class 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 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 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- 229940126639 Compound 33 Drugs 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 3
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Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/303—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by hydrogenation of unsaturated carbon-to-carbon bonds
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Landscapes
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Rheumatology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
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| US11/093757 | 2005-03-29 | ||
| PCT/US2006/011222 WO2006105058A2 (en) | 2005-03-29 | 2006-03-28 | Trihydroxy polyunsaturated eicosanoid derivatives |
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| US7582785B2 (en) | 2002-04-01 | 2009-09-01 | University Of Southern California | Trihydroxy polyunsaturated eicosanoid derivatives |
| US7902257B2 (en) | 2002-04-01 | 2011-03-08 | University Of Southern California | Trihydroxy polyunsaturated eicosanoid |
| US8481772B2 (en) | 2002-04-01 | 2013-07-09 | University Of Southern California | Trihydroxy polyunsaturated eicosanoid derivatives |
| DK2216318T3 (en) | 2002-08-12 | 2018-12-10 | Brigham & Womens Hospital | Resolvins: Bio templates for therapeutic interventions |
| US7759395B2 (en) * | 2002-08-12 | 2010-07-20 | The Brigham And Women's Hospital, Inc. | Use of docosatrienes, resolvins and their stable analogs in the treatment of airway diseases and asthma |
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| EP1755537A4 (en) * | 2004-04-14 | 2009-12-09 | Univ Boston | METHOD AND COMPOSITIONS FOR PREVENTING OR TREATING PERIODONTOPATHIA |
| US7893106B2 (en) * | 2004-11-19 | 2011-02-22 | Martek Biosciences, Corporation | Oxylipins from stearidonic acid and γ-linolenic acid and methods of making and using the same |
| KR20070090928A (ko) * | 2004-11-19 | 2007-09-06 | 마텍 바이오싸이언스스 코포레이션 | 장쇄 다가불포화 지방산으로부터의 옥시리핀, 및 이의 제조방법 및 사용 방법 |
| US20090318394A1 (en) * | 2004-11-19 | 2009-12-24 | Julie Nauroth | Long Chain Polyunsaturated Fatty Acids and Methods of Making and Using the Same |
| US20060293288A1 (en) * | 2005-01-07 | 2006-12-28 | Serhan Charles N | Use of resolvins to treat gastrointestinal diseases |
| WO2007041440A2 (en) * | 2005-10-03 | 2007-04-12 | The Brigham And Women's Hospital, Inc. | Anti-inflammatory actions of neuroprotectin d1/protectin d1 and its natural stereoisomers |
| US8636986B2 (en) * | 2005-11-18 | 2014-01-28 | The Forsyth Institute | Treatment and prevention of bone loss using resolvins |
| WO2007090162A2 (en) * | 2006-01-31 | 2007-08-09 | Martek Biosciences Corporation | OXYLIPINS FROM STEARIDONIC ACID AND γ-LINOLENIC ACID AND METHODS OF MAKING AND USING THE SAME |
| CA2650607A1 (en) * | 2006-04-28 | 2007-11-08 | Resolvyx Pharmaceuticals, Inc. | Compositions and methods for the treatment of cardiovascular disease |
| WO2008011085A1 (en) * | 2006-07-19 | 2008-01-24 | Resolvyx Pharmaceuticals, Inc. | Compositions and methods for the treatment of mucositis |
| US20080161274A1 (en) * | 2006-10-26 | 2008-07-03 | Resolvyx Pharmaceuticals, Inc. | Compounds and methods for inhibition of bone loss |
| WO2008070129A2 (en) * | 2006-12-05 | 2008-06-12 | Resolvyx Pharmaceuticals, Inc. | Compositions and methods for the treatment of inflammatory disease |
| US20110190389A1 (en) * | 2007-02-20 | 2011-08-04 | Linda Arterburn | Oxylipins from long chain polyunsaturated fatty acids and methods of making and using the same |
| CA2699483A1 (en) * | 2007-09-14 | 2009-03-26 | Resolvyx Pharmaceuticals, Inc. | Compositions and methods for modulating immune function |
| KR20150115959A (ko) * | 2007-10-12 | 2015-10-14 | 레솔빅스 파마슈티칼즈, 인코퍼레이티드 | 안과 질환의 치료를 위한 옥실리핀 화합물 |
| US20110027841A1 (en) * | 2007-12-21 | 2011-02-03 | Martek Biosciences Corporation | Method for preparation of oxylipins |
| US20110190242A1 (en) * | 2008-09-23 | 2011-08-04 | Resolvyx Pharmaceuticals, Inc. | Compositions and methods for the treatment of inflammatory disease |
| WO2010095706A1 (ja) | 2009-02-20 | 2010-08-26 | 国立大学法人東京大学 | 新規抗炎症性化合物 |
| TW201039815A (en) * | 2009-04-13 | 2010-11-16 | Resolvyx Pharmaceuticals Inc | Compositions and methods for the treatment of inflammation |
| JP5184565B2 (ja) * | 2010-03-10 | 2013-04-17 | 独立行政法人科学技術振興機構 | 水系溶媒中での含窒素化合物の製造方法 |
| CN103396350B (zh) * | 2012-01-09 | 2014-11-05 | 浙江师范大学 | 一种利用顺式-1-卤-2-氯代烯烃合成维生素a的方法 |
| PL2887923T3 (pl) | 2012-08-24 | 2023-08-14 | Sun Pharmaceutical Industries Limited | Preparat okulistyczny polioksylipidu lub polioksylowego kwasu tłuszczowego i leczenie chorób oczu |
| AU2014205369B2 (en) | 2013-01-11 | 2018-08-09 | Massachusetts Eye And Ear Infirmary | CYP450 lipid metabolites reduce inflammation and angiogenesis |
| WO2014115098A1 (en) * | 2013-01-26 | 2014-07-31 | Mahesh Kandula | Compositions and methods for the treatment of neurological diseases and inflammation |
| US9682034B2 (en) | 2015-03-10 | 2017-06-20 | Elc Management Llc | Methods and compositions for treating skin to resolve inflammation and screening for actives that stimulate pro-resolution pathways |
| ES2895062T3 (es) | 2015-03-18 | 2022-02-17 | Forsyth Dental Infirmary For Children | Métodos para estabilizar placas ateroscleróticas usando lipoxinas, resolvinas y análogos de las mismas |
| JP2018532809A (ja) | 2015-11-10 | 2018-11-08 | サン ファーマ グローバル エフジーイー | 局所製剤およびその使用 |
| EP3950649A1 (en) * | 2015-11-23 | 2022-02-09 | Retrotope, Inc. | Site-specific isotopic labeling of 1, 4-diene systems |
| US11903998B2 (en) | 2016-05-27 | 2024-02-20 | Forsyth Dental Infirmary For Children | Compositions and methods of treating cancer using lipid agonists and receptors thereof |
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-
2005
- 2005-03-29 US US11/093,757 patent/US7582785B2/en not_active Expired - Fee Related
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2006
- 2006-03-28 MX MX2007012022A patent/MX2007012022A/es active IP Right Grant
- 2006-03-28 WO PCT/US2006/011222 patent/WO2006105058A2/en not_active Ceased
- 2006-03-28 EP EP06748789.2A patent/EP1863753B1/en not_active Not-in-force
- 2006-03-28 AU AU2006230136A patent/AU2006230136B2/en not_active Ceased
- 2006-03-28 CN CNA2006800180987A patent/CN101203481A/zh active Pending
- 2006-03-28 MX MX2014005826A patent/MX352197B/es unknown
- 2006-03-28 CA CA2603371A patent/CA2603371C/en not_active Expired - Fee Related
- 2006-03-28 JP JP2008504239A patent/JP2008538117A/ja active Pending
- 2006-03-28 BR BRPI0609767-7A patent/BRPI0609767A2/pt not_active Application Discontinuation
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2012
- 2012-06-05 JP JP2012128022A patent/JP2012162576A/ja active Pending
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2014
- 2014-03-25 JP JP2014061270A patent/JP2014122240A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1863753B1 (en) | 2017-09-20 |
| JP2008538117A (ja) | 2008-10-09 |
| MX352197B (es) | 2017-11-13 |
| WO2006105058A3 (en) | 2007-04-12 |
| JP2012162576A (ja) | 2012-08-30 |
| CN101203481A (zh) | 2008-06-18 |
| MX2007012022A (es) | 2011-06-16 |
| EP1863753A2 (en) | 2007-12-12 |
| CA2603371A1 (en) | 2006-10-05 |
| US7582785B2 (en) | 2009-09-01 |
| JP2014122240A (ja) | 2014-07-03 |
| US20050228047A1 (en) | 2005-10-13 |
| WO2006105058A2 (en) | 2006-10-05 |
| AU2006230136B2 (en) | 2011-11-03 |
| AU2006230136A1 (en) | 2006-10-05 |
| CA2603371C (en) | 2013-05-28 |
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