JPH05505798A - 免疫抑制マクロ環状化合物 - Google Patents

免疫抑制マクロ環状化合物

Info

Publication number: JPH05505798A
Authority: JP; Japan
Prior art keywords: compound; formula; allyl; dioxa; methylvinyl
Prior art date: 1990-03-13
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

JP91505818A

Other languages

English (en)

Japanese (ja)

Inventor

ドナルド，デイビツド・キース

フアーバー，マーク

クーパー，マーチン・エドワード

Original Assignee

フアイソンズ・ピーエルシー

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.)

1990-03-13

Filing date

1991-03-13

Publication date

1993-08-26

1990-03-13 Priority claimed from GB909005672A external-priority patent/GB9005672D0/en

1990-04-17 Priority claimed from GB909008556A external-priority patent/GB9008556D0/en

1990-04-17 Priority claimed from GB909008507A external-priority patent/GB9008507D0/en

1990-04-27 Priority claimed from GB909009480A external-priority patent/GB9009480D0/en

1990-08-09 Priority claimed from GB909017447A external-priority patent/GB9017447D0/en

1990-10-25 Priority claimed from GB909023242A external-priority patent/GB9023242D0/en

1991-03-13 Application filed by フアイソンズ・ピーエルシー filed Critical フアイソンズ・ピーエルシー

1993-08-26 Publication of JPH05505798A publication Critical patent/JPH05505798A/ja

Status Pending legal-status Critical Current

Links

230000001506 immunosuppresive effect Effects 0.000 title claims description 7
150000002678 macrocyclic compounds Chemical class 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims description 282
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 85
238000000034 method Methods 0.000 claims description 67
CFZGEMKIQUVTCC-UHFFFAOYSA-N octacos-18-ene-2,3,10,16-tetrone Chemical compound CCCCCCCCCC=CCC(=O)CCCCCC(=O)CCCCCCC(=O)C(C)=O CFZGEMKIQUVTCC-UHFFFAOYSA-N 0.000 claims description 49
238000006243 chemical reaction Methods 0.000 claims description 41
229910052739 hydrogen Inorganic materials 0.000 claims description 32
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
125000004432 carbon atom Chemical group C* 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 25
150000002367 halogens Chemical class 0.000 claims description 25
239000000126 substance Substances 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 18
239000003153 chemical reaction reagent Substances 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
230000009467 reduction Effects 0.000 claims description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
-1 formyloxy Chemical group 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
230000001747 exhibiting effect Effects 0.000 claims description 11
230000008569 process Effects 0.000 claims description 11
229910052799 carbon Inorganic materials 0.000 claims description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 7
125000004122 cyclic group Chemical group 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
150000001408 amides Chemical class 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
230000009471 action Effects 0.000 claims description 4
125000005236 alkanoylamino group Chemical group 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
229910021529 ammonia Inorganic materials 0.000 claims description 4
150000008064 anhydrides Chemical class 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
235000019253 formic acid Nutrition 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 3
230000018044 dehydration Effects 0.000 claims description 3
238000006297 dehydration reaction Methods 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
230000002140 halogenating effect Effects 0.000 claims description 3
150000004678 hydrides Chemical class 0.000 claims description 3
125000002524 organometallic group Chemical group 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
206010062016 Immunosuppression Diseases 0.000 claims description 2
125000003172 aldehyde group Chemical group 0.000 claims description 2
239000003513 alkali Substances 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
150000001356 alkyl thiols Chemical class 0.000 claims description 2
125000004429 atom Chemical group 0.000 claims description 2
150000001540 azides Chemical group 0.000 claims description 2
239000000969 carrier Substances 0.000 claims description 2
229960003444 immunosuppressant agent Drugs 0.000 claims description 2
239000003018 immunosuppressive agent Substances 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
229910052727 yttrium Inorganic materials 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
150000003973 alkyl amines Chemical class 0.000 claims 1
150000001721 carbon Chemical group 0.000 claims 1
230000001861 immunosuppressant effect Effects 0.000 claims 1
JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 145
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 133
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 129
239000000243 solution Substances 0.000 description 126
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 118
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 111
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
239000000377 silicon dioxide Substances 0.000 description 63
239000011541 reaction mixture Substances 0.000 description 61
229920006395 saturated elastomer Polymers 0.000 description 58
235000017557 sodium bicarbonate Nutrition 0.000 description 55
229910000030 sodium bicarbonate Inorganic materials 0.000 description 55
239000003921 oil Substances 0.000 description 54
238000003756 stirring Methods 0.000 description 54
239000000284 extract Substances 0.000 description 47
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
238000004587 chromatography analysis Methods 0.000 description 44
239000003480 eluent Substances 0.000 description 44
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 33
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 32
239000012267 brine Substances 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
239000000203 mixture Substances 0.000 description 27
239000011734 sodium Substances 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
230000002411 adverse Effects 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000012141 concentrate Substances 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
239000007864 aqueous solution Substances 0.000 description 14
239000012298 atmosphere Substances 0.000 description 14
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 12
239000000725 suspension Substances 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
229960000583 acetic acid Drugs 0.000 description 11
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 11
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
239000012259 ether extract Substances 0.000 description 10
239000007921 spray Substances 0.000 description 9
RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 8
239000006260 foam Substances 0.000 description 8
239000000843 powder Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
239000010948 rhodium Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 8
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 7
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
239000007787 solid Substances 0.000 description 7
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
238000004440 column chromatography Methods 0.000 description 6
201000010099 disease Diseases 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
238000012360 testing method Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 6
239000003039 volatile agent Substances 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
201000004624 Dermatitis Diseases 0.000 description 5
238000005481 NMR spectroscopy Methods 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
229940086542 triethylamine Drugs 0.000 description 5
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
208000010668 atopic eczema Diseases 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
150000001923 cyclic compounds Chemical class 0.000 description 4
150000002170 ethers Chemical class 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
239000002609 medium Substances 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
239000001488 sodium phosphate Substances 0.000 description 4
229910000162 sodium phosphate Inorganic materials 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
238000005406 washing Methods 0.000 description 4
ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 3
239000005973 Carvone Substances 0.000 description 3
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
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UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
229910052776 Thorium Inorganic materials 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 3
239000002671 adjuvant Substances 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 3
238000001035 drying Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
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238000000605 extraction Methods 0.000 description 3
235000013305 food Nutrition 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
210000000554 iris Anatomy 0.000 description 3
239000007788 liquid Substances 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
AJZKXUWKGMUCJR-UHFFFAOYSA-N octacos-18-ene-3,10,16-trione Chemical compound CCCCCCCCCC=CCC(=O)CCCCCC(=O)CCCCCCC(=O)CC AJZKXUWKGMUCJR-UHFFFAOYSA-N 0.000 description 3
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
208000023504 respiratory system disease Diseases 0.000 description 3
229920002554 vinyl polymer Polymers 0.000 description 3
239000011701 zinc Substances 0.000 description 3
229910052725 zinc Inorganic materials 0.000 description 3
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
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VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
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241000789558 Itoa Species 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
241000282320 Panthera leo Species 0.000 description 2
239000012980 RPMI-1640 medium Substances 0.000 description 2
241000700159 Rattus Species 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
241000384512 Trachichthyidae Species 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
TXLGSLUZUKPMHL-UHFFFAOYSA-N [N].CCN(CC)S(F)(F)F Chemical compound [N].CCN(CC)S(F)(F)F TXLGSLUZUKPMHL-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
208000026935 allergic disease Diseases 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Medicinal Chemistry (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Transplantation (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Molecular Biology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

JP91505818A 1990-03-13 1991-03-13 免疫抑制マクロ環状化合物 Pending JPH05505798A (ja)

Applications Claiming Priority (13)

Application Number	Priority Date	Filing Date	Title
GB909005672A GB9005672D0 (en)	1990-03-13	1990-03-13	Compounds
GB9005672.2		1990-03-13
GB9008507.7		1990-04-17
GB909008556A GB9008556D0 (en)	1990-04-17	1990-04-17	Compounds
GB909008507A GB9008507D0 (en)	1990-04-17	1990-04-17	Compounds
GB9008556.4		1990-04-17
GB9009480.6		1990-04-27
GB909009480A GB9009480D0 (en)	1990-04-27	1990-04-27	Compounds
GB9017447.5		1990-08-09
GB909017447A GB9017447D0 (en)	1990-08-09	1990-08-09	Compounds
GB9023242.2		1990-10-25
GB909023242A GB9023242D0 (en)	1990-10-25	1990-10-25	Compounds
PCT/GB1991/000393 WO1991013889A1 (fr)	1990-03-13	1991-03-13	Composes macrocycliques immunosuppresseurs

Publications (1)

Publication Number	Publication Date
JPH05505798A true JPH05505798A (ja)	1993-08-26

Family

ID=27547078

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP91505818A Pending JPH05505798A (ja)	1990-03-13	1991-03-13	免疫抑制マクロ環状化合物

Country Status (4)

Country	Link
EP (1)	EP0594600A1 (fr)
JP (1)	JPH05505798A (fr)
IE (1)	IE910847A1 (fr)
WO (1)	WO1991013889A1 (fr)

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US5693648A (en) *	1994-09-30	1997-12-02	Merck & Co., Inc.	O-aryl, O-alkyl, O-alkenyl and O-alkynyl-macrolides having immunosuppressive activity
US6187757B1 (en)	1995-06-07	2001-02-13	Ariad Pharmaceuticals, Inc.	Regulation of biological events using novel compounds
GB9713730D0 (en) *	1997-06-30	1997-09-03	Ciba Geigy Ag	Organic compounds
PT2198858E (pt)	1998-03-26	2011-09-01	Astellas Pharma Inc	Composição farmacêutica de libertação constante que contém um macrólido como o tacrolimus
WO1999055332A1 (fr) *	1998-04-27	1999-11-04	Fujisawa Pharmaceutical Co., Ltd.	Compositions medicinales
GB9826656D0 (en)	1998-12-03	1999-01-27	Novartis Ag	Organic compounds
US7063857B1 (en)	1999-04-30	2006-06-20	Sucampo Ag	Use of macrolide compounds for the treatment of dry eye
AU783158B2 (en)	1999-08-24	2005-09-29	Ariad Pharmaceuticals, Inc.	28-epirapalogs
US7067526B1 (en)	1999-08-24	2006-06-27	Ariad Gene Therapeutics, Inc.	28-epirapalogs
WO2006115509A2 (fr)	2004-06-24	2006-11-02	Novartis Vaccines And Diagnostics Inc.	Immuno-potentialisateurs a petites molecules et analyses visant a detecter leur presence
ES2898849T3 (es)	2014-10-28	2022-03-09	Koushi Yamaguchi	Medicamento para mejorar el síndrome de hipertensión inducida por el embarazo
EP3426674A4 (fr)	2016-03-09	2019-08-14	Blade Therapeutics, Inc.	Composés céto-amides cycliques utilisés en tant que modulateurs de la calpaïne, et leurs procédés de production et d'utilisation
EP3481835A4 (fr)	2016-07-05	2020-02-26	Blade Therapeutics, Inc.	Modulateurs de calpain et leurs utilisations thérapeutiques
CN106074367A (zh) *	2016-07-20	2016-11-09	中山大学中山眼科中心	含fk506类化合物/fkbp蛋白二聚体的药物组合物及其制备方法
SG10201912574WA (en)	2016-09-28	2020-02-27	Blade Therapeutics Inc	Calpain modulators and therapeutic uses thereof
US20210228551A1 (en)	2018-08-10	2021-07-29	Koushi Yamaguchi	Therapeutic agent for humoral immunity-related diseases in maternofetal relationship
CA3123535A1 (fr)	2018-12-18	2020-06-25	Koushi Yamaguchi	Agent permettant de traiter l'infertilite, les fausses couches recurrentes et d'ameliorer la grossesse
MX2021008824A (es) *	2019-01-23	2021-10-13	Univ Johns Hopkins	Análogos no inmunosupresores de tacrolimus (fk506) y uso de los mismos.

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JP2799208B2 (ja) *	1987-12-09	1998-09-17	フアイソンズ・ピーエルシー	マクロ環状化合物
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1991
- 1991-03-13 EP EP91905827A patent/EP0594600A1/fr not_active Withdrawn
- 1991-03-13 IE IE084791A patent/IE910847A1/en unknown
- 1991-03-13 WO PCT/GB1991/000393 patent/WO1991013889A1/fr not_active Ceased
- 1991-03-13 JP JP91505818A patent/JPH05505798A/ja active Pending

Also Published As

Publication number	Publication date
IE910847A1 (en)	1991-09-25
WO1991013889A1 (fr)	1991-09-19
EP0594600A1 (fr)	1994-05-04

Publication	Publication Date	Title
EP4097097B1 (fr)	2025-01-15	Composés modulateurs de glp-1r
DE69430586T2 (de)	2002-11-21	Aminoalkanester von rapamycin
FI90550C (fi)	1994-02-25	Menetelmä valmistaa terapeuttisesti aktiivista makrosyklistä johdannaista
IE910847A1 (en)	1991-09-25	Immunosuppressive macrocyclic compounds
JPH05504944A (ja)	1993-07-29	巨大環式化合物
JPH05163280A (ja)	1993-06-29	二環式ラパマイシン
JPH06510304A (ja)	1994-11-17	大環状イムノモジュレーター
JPH06510034A (ja)	1994-11-10	アザ環式化合物、それらの製造方法、及びそれらを含む医薬組成物
JPH0813819B2 (ja)	1996-02-14	免疫抑制活性を有するｏ−ヘテロアリール、ｏ−アルキルヘテロアリール、ｏ−アルケニルヘテロアリール及びｏ−アルキニルヘテロアリールマクロライド
JPH05500215A (ja)	1993-01-21	新規大環状化合物および新規治療法
SI9620099A (sl)	1998-08-31	Diglikozilirani 1,2-dioli kot mimetiki sialil-Lewis X in sialil-Lewis A
CN101274929A (zh)	2008-10-01	凝血酶受体拮抗剂
US5179087A (en)	1993-01-12	Macrocyclic compounds
JPH01265100A (ja)	1989-10-23	２―置換アデノシン誘導体
US4619938A (en)	1986-10-28	Fatty acid derivatives of aminoalkyl nicotinic acid esters and platelet aggregation inhibitors
JPH06501920A (ja)	1994-03-03	トリシクロ化合物及びその製法並びにその物を含む医薬組成物
EP0328111A2 (fr)	1989-08-16	Inhibiteurs de métastase de cellules cancéreuses
JPH08507789A (ja)	1996-08-20	大環状アミド及び尿素免疫調節剤
JPH06500102A (ja)	1994-01-06	マクロ環状化合物
JPH10512899A (ja)	1998-12-08	Ｎ−アセチルアルデエミンの類似体、それらの調製及び使用方法
WO2016091207A1 (fr)	2016-06-16	Composé nitromidazole, procédé de préparation de ce composé et utilisation de ce composé dans la fabrication de médicaments
JPH10502058A (ja)	1998-02-24	アリール、アルキル、アルケニルおよびアルキニルマクロライド
US5296489A (en)	1994-03-22	Immunosuppressive macrocyclic compounds
JPH04217939A (ja)	1992-08-07	免疫抑制化合物
FR2646081A1 (fr)	1990-10-26