IE73236B1 - Macrocyclic lactam prokinetic agents - Google Patents
Macrocyclic lactam prokinetic agentsInfo
- Publication number
- IE73236B1 IE73236B1 IE921045A IE921045A IE73236B1 IE 73236 B1 IE73236 B1 IE 73236B1 IE 921045 A IE921045 A IE 921045A IE 921045 A IE921045 A IE 921045A IE 73236 B1 IE73236 B1 IE 73236B1
- Authority
- IE
- Ireland
- Prior art keywords
- oxy
- methyl
- hexopyranosyl
- trideoxy
- ribo
- Prior art date
Links
- 150000003951 lactams Chemical class 0.000 title claims description 12
- 239000002325 prokinetic agent Substances 0.000 title description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 142
- -1 lactam compounds Chemical class 0.000 claims abstract description 47
- 238000000034 method Methods 0.000 claims abstract description 23
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims abstract description 6
- QIVRQFJRUABARQ-UHFFFAOYSA-N pentadec-14-en-7-one Chemical compound CCCCCCC(=O)CCCCCCC=C QIVRQFJRUABARQ-UHFFFAOYSA-N 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229960003276 erythromycin Drugs 0.000 claims description 33
- QBEKGNIWIHIMOM-UHFFFAOYSA-N tridec-12-en-5-one Chemical compound CCCCC(=O)CCCCCCC=C QBEKGNIWIHIMOM-UHFFFAOYSA-N 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 24
- 229930006677 Erythromycin A Natural products 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 150000002118 epoxides Chemical class 0.000 claims description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 230000005176 gastrointestinal motility Effects 0.000 claims description 6
- VUXXXYMMZBAUSE-UHFFFAOYSA-N pentadecan-7-one Chemical compound CCCCCCCCC(=O)CCCCCC VUXXXYMMZBAUSE-UHFFFAOYSA-N 0.000 claims description 6
- 210000000813 small intestine Anatomy 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000005676 cyclic carbonates Chemical class 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- IDRYSCOQVVUBIJ-UHFFFAOYSA-N Erythromycin-B Natural products CC1C(OC2C(C(CC(C)O2)N(C)C)O)C(C)(O)CC(C)C(=O)C(C)C(O)C(C)C(CC)OC(=O)C(C)C1OC1CC(C)(OC)C(O)C(C)O1 IDRYSCOQVVUBIJ-UHFFFAOYSA-N 0.000 claims description 4
- MWFRKHPRXPSWNT-UHFFFAOYSA-N Erythromycin-C Natural products CC1C(OC2C(C(CC(C)O2)N(C)C)O)C(C)(O)CC(C)C(=O)C(C)C(O)C(O)(C)C(CC)OC(=O)C(C)C1OC1CC(C)(O)C(O)C(C)O1 MWFRKHPRXPSWNT-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 241000282412 Homo Species 0.000 claims description 2
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 2
- 230000002269 spontaneous effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 230000002708 enhancing effect Effects 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 48
- 239000000543 intermediate Substances 0.000 abstract description 6
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 3
- 230000004936 stimulating effect Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 210
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 135
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 99
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 70
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 60
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 52
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 47
- 239000011541 reaction mixture Substances 0.000 description 43
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Natural products O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 39
- 239000000047 product Substances 0.000 description 35
- 235000017557 sodium bicarbonate Nutrition 0.000 description 35
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 35
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- 239000012267 brine Substances 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 29
- 239000010410 layer Substances 0.000 description 28
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 27
- 235000011114 ammonium hydroxide Nutrition 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 239000000908 ammonium hydroxide Substances 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000011521 glass Substances 0.000 description 21
- 229960000583 acetic acid Drugs 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 17
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 229910021529 ammonia Inorganic materials 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 229940079593 drug Drugs 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 230000004899 motility Effects 0.000 description 13
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 230000002496 gastric effect Effects 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 150000004820 halides Chemical class 0.000 description 10
- 230000008602 contraction Effects 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 229940086542 triethylamine Drugs 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
- 239000005695 Ammonium acetate Substances 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- 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 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229940043376 ammonium acetate Drugs 0.000 description 6
- 235000019257 ammonium acetate Nutrition 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 6
- 231100000673 dose–response relationship Toxicity 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 239000007868 Raney catalyst Substances 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 210000001198 duodenum Anatomy 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 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 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-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
- 206010021333 Ileus paralytic Diseases 0.000 description 4
- 206010021518 Impaired gastric emptying Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000009102 absorption Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- PBWZKZYHONABLN-UHFFFAOYSA-N difluoroacetic acid Chemical compound OC(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-N 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- 210000003238 esophagus Anatomy 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229940099584 lactobionate Drugs 0.000 description 4
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 4
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- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
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- 239000008351 acetate buffer Substances 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
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- 238000004458 analytical method Methods 0.000 description 3
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- RMIBJVUYNZSLSD-UHFFFAOYSA-N bis[(1,1,1,3,3,3-hexafluoro-2-phenylpropan-2-yl)oxy]-diphenyl-$l^{4}-sulfane Chemical compound C=1C=CC=CC=1C(C(F)(F)F)(C(F)(F)F)OS(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C(F)(F)F)(C(F)(F)F)C1=CC=CC=C1 RMIBJVUYNZSLSD-UHFFFAOYSA-N 0.000 description 3
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- 239000008101 lactose Substances 0.000 description 3
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 3
- 229960004503 metoclopramide Drugs 0.000 description 3
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- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
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- 229910003446 platinum oxide Inorganic materials 0.000 description 3
- 239000002798 polar solvent Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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- 239000007909 solid dosage form Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
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- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 210000002417 xiphoid bone Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Polyamides (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Cephalosporin Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68283691A | 1991-04-09 | 1991-04-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE921045A1 IE921045A1 (en) | 1992-10-21 |
| IE73236B1 true IE73236B1 (en) | 1997-05-21 |
Family
ID=24741372
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE921045A IE73236B1 (en) | 1991-04-09 | 1992-04-02 | Macrocyclic lactam prokinetic agents |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US5538961A (OSRAM) |
| EP (1) | EP0579770B1 (OSRAM) |
| JP (1) | JPH06509326A (OSRAM) |
| KR (1) | KR100222014B1 (OSRAM) |
| AT (1) | ATE139697T1 (OSRAM) |
| AU (1) | AU663089B2 (OSRAM) |
| CA (1) | CA2103913A1 (OSRAM) |
| DE (1) | DE69211845T2 (OSRAM) |
| DK (1) | DK0579770T3 (OSRAM) |
| ES (1) | ES2091471T3 (OSRAM) |
| GR (1) | GR3020853T3 (OSRAM) |
| IE (1) | IE73236B1 (OSRAM) |
| IL (1) | IL101504A (OSRAM) |
| PT (1) | PT100357B (OSRAM) |
| WO (1) | WO1992018134A1 (OSRAM) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1122261A3 (en) * | 2000-01-31 | 2001-09-26 | Pfizer Products Inc. | 13 and 14-membered antibacterial macrolides |
| WO2001060833A2 (en) | 2000-02-18 | 2001-08-23 | Kosan Biosciences, Inc. | Motilide compounds |
| US6734292B1 (en) | 2000-08-17 | 2004-05-11 | The Kitasato Institute | Pseudoerythromycin derivatives |
| AU2002225724A1 (en) * | 2000-12-01 | 2002-07-08 | Kosan Biosciences, Inc. | Motilide compounds |
| US20020094962A1 (en) * | 2000-12-01 | 2002-07-18 | Gary Ashley | Motilide compounds |
| PT1532131E (pt) * | 2002-08-29 | 2009-02-18 | Pfizer | Compostos motilidos |
| CA2498507A1 (en) * | 2002-09-12 | 2004-03-25 | Eli D. Ehrenpreis | Monitoring and diagnosis of gastric emptying and gastroparesis |
| CA2528375C (en) | 2003-06-18 | 2013-11-19 | Tranzyme Pharma, Inc. | Macrocyclic antagonists of the motilin receptor |
| US20050113319A1 (en) * | 2003-08-26 | 2005-05-26 | Christopher Carreras | 11-Deoxy-6,9-ether erythromycin compounds |
| US7407941B2 (en) * | 2003-08-26 | 2008-08-05 | Pfizer, Inc. | N-desmethyl-N-substituted-11-deoxyerythromycin compounds |
| US7211568B2 (en) * | 2003-12-18 | 2007-05-01 | Kosan Biosciences Incorporated | 9-Desoxoerythromycin compounds as prokinetic agents |
| US7582611B2 (en) | 2005-05-24 | 2009-09-01 | Pfizer Inc. | Motilide compounds |
| JP2009518396A (ja) * | 2005-12-08 | 2009-05-07 | ファイザー・インク | エリスロマイシン化合物の３’−ジメチルアミノ基を脱メチルする方法 |
| WO2008033328A2 (en) | 2006-09-11 | 2008-03-20 | Tranzyme Pharma, Inc. | Macrocyclic antagonists of the motilin receptor for treatment of gastrointestinal dysmotility disorders |
| MX2009005977A (es) | 2006-12-05 | 2009-06-17 | Pfizer | Polimorfos de motilida. |
| US20080287371A1 (en) * | 2007-05-17 | 2008-11-20 | Tranzyme Pharma Inc. | Macrocyclic antagonists of the motilin receptor for modulation of the migrating motor complex |
| JP6138118B2 (ja) | 2011-07-29 | 2017-05-31 | ケンブリッジ エピジェネティクス リミテッド | ヌクレオチド修飾の検出方法 |
| ES2786984T3 (es) | 2012-11-30 | 2020-10-14 | Cambridge Epigenetix Ltd | Agente oxidante para nucleótidos modificados |
| CN115057794B (zh) * | 2022-07-07 | 2023-11-17 | 桂林理工大学 | 一种可见光诱导铈催化氧化酰胺去甲基化的方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4512982A (en) * | 1984-04-13 | 1985-04-23 | Pfizer Inc. | 9α-Aza-9α-homoerythromycin compounds, pharmaceutical composition and therapeutic method |
| US4518590A (en) * | 1984-04-13 | 1985-05-21 | Pfizer Inc. | 9α-Aza-9α-homoerythromycin compounds, pharmaceutical compositions and therapeutic method |
| DE3689758T2 (de) * | 1985-08-31 | 1994-08-18 | Kitasato Inst | Erythromycinderivat und Verfahren zu dessen Herstellung. |
| US5008249A (en) * | 1985-08-31 | 1991-04-16 | Kitasato Kenkyusho | Therapeutic method of stimulating digestive tract contractile motion in mammals |
| US5106961A (en) * | 1987-05-26 | 1992-04-21 | Eli Lilly And Company | Erythromycin ring-contracted derivatives |
| US4958010A (en) * | 1988-02-16 | 1990-09-18 | Bristol-Myers Company | Epipodophyllotoxin glucoside lactam derivatives |
| US4920102A (en) * | 1988-04-18 | 1990-04-24 | Eli Lilly And Company | Method for treating gastrointestinal disorders |
| US5202434A (en) * | 1991-04-05 | 1993-04-13 | Merck & Co., Inc. | 8a-aza-8a-homoerythromycin lactams |
| US5189159A (en) * | 1992-04-02 | 1993-02-23 | Merck & Co., Inc. | 8a-AZA-8a-homoerythromycin cyclic iminoethers |
-
1992
- 1992-03-30 AT AT92911585T patent/ATE139697T1/de not_active IP Right Cessation
- 1992-03-30 AU AU19103/92A patent/AU663089B2/en not_active Ceased
- 1992-03-30 CA CA002103913A patent/CA2103913A1/en not_active Abandoned
- 1992-03-30 WO PCT/US1992/002590 patent/WO1992018134A1/en not_active Ceased
- 1992-03-30 EP EP92911585A patent/EP0579770B1/en not_active Expired - Lifetime
- 1992-03-30 ES ES92911585T patent/ES2091471T3/es not_active Expired - Lifetime
- 1992-03-30 KR KR1019930703026A patent/KR100222014B1/ko not_active Expired - Fee Related
- 1992-03-30 JP JP4511370A patent/JPH06509326A/ja active Pending
- 1992-03-30 US US08/108,659 patent/US5538961A/en not_active Expired - Fee Related
- 1992-03-30 DK DK92911585.5T patent/DK0579770T3/da active
- 1992-03-30 DE DE69211845T patent/DE69211845T2/de not_active Expired - Fee Related
- 1992-04-02 IE IE921045A patent/IE73236B1/en not_active IP Right Cessation
- 1992-04-06 IL IL101504A patent/IL101504A/en not_active IP Right Cessation
- 1992-04-08 PT PT100357A patent/PT100357B/pt not_active IP Right Cessation
-
1996
- 1996-08-22 GR GR960402210T patent/GR3020853T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0579770A1 (en) | 1994-01-26 |
| CA2103913A1 (en) | 1992-10-10 |
| PT100357B (pt) | 1999-06-30 |
| IE921045A1 (en) | 1992-10-21 |
| DE69211845T2 (de) | 1997-01-23 |
| ATE139697T1 (de) | 1996-07-15 |
| IL101504A (en) | 1998-04-05 |
| GR3020853T3 (en) | 1996-11-30 |
| ES2091471T3 (es) | 1996-11-01 |
| EP0579770B1 (en) | 1996-06-26 |
| AU1910392A (en) | 1992-11-17 |
| IL101504A0 (en) | 1992-12-30 |
| JPH06509326A (ja) | 1994-10-20 |
| WO1992018134A1 (en) | 1992-10-29 |
| US5538961A (en) | 1996-07-23 |
| KR100222014B1 (ko) | 1999-10-01 |
| EP0579770A4 (OSRAM) | 1994-03-30 |
| DE69211845D1 (de) | 1996-08-01 |
| AU663089B2 (en) | 1995-09-28 |
| PT100357A (pt) | 1993-07-30 |
| DK0579770T3 (da) | 1996-11-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |