CN111825733A - 大环内酯及其制备和使用方法 - Google Patents
大环内酯及其制备和使用方法 Download PDFInfo
- Publication number
- CN111825733A CN111825733A CN202010566628.3A CN202010566628A CN111825733A CN 111825733 A CN111825733 A CN 111825733A CN 202010566628 A CN202010566628 A CN 202010566628A CN 111825733 A CN111825733 A CN 111825733A
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- CN
- China
- Prior art keywords
- optionally substituted
- group
- alkyl
- hydrogen
- carbocyclyl
- Prior art date
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- 239000003120 macrolide antibiotic agent Substances 0.000 title claims abstract description 109
- 229940041033 macrolides Drugs 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title abstract description 32
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 372
- 239000001257 hydrogen Substances 0.000 claims description 364
- 125000000217 alkyl group Chemical group 0.000 claims description 299
- 125000000623 heterocyclic group Chemical group 0.000 claims description 266
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 197
- -1 hydroxy, substituted hydroxy, amino, substituted amino Chemical group 0.000 claims description 189
- 125000001072 heteroaryl group Chemical group 0.000 claims description 175
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 162
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 155
- 125000003107 substituted aryl group Chemical group 0.000 claims description 110
- 125000000304 alkynyl group Chemical group 0.000 claims description 106
- 125000003342 alkenyl group Chemical group 0.000 claims description 105
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 101
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 93
- 150000001875 compounds Chemical class 0.000 claims description 87
- 229910052736 halogen Inorganic materials 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 67
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 64
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 53
- 125000004122 cyclic group Chemical group 0.000 claims description 46
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- 229910052717 sulfur Inorganic materials 0.000 claims description 39
- 125000002947 alkylene group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 31
- 125000004419 alkynylene group Chemical group 0.000 claims description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 26
- 125000004450 alkenylene group Chemical group 0.000 claims description 24
- 125000005647 linker group Chemical group 0.000 claims description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 16
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 12
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 8
- 150000001720 carbohydrates Chemical class 0.000 claims description 8
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 5
- 150000005676 cyclic carbonates Chemical class 0.000 claims description 4
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 24
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 238000005710 macrocyclization reaction Methods 0.000 abstract description 57
- 238000005859 coupling reaction Methods 0.000 abstract description 38
- 230000008878 coupling Effects 0.000 abstract description 36
- 238000010168 coupling process Methods 0.000 abstract description 36
- 230000015572 biosynthetic process Effects 0.000 abstract description 21
- 238000003786 synthesis reaction Methods 0.000 abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 13
- 208000035473 Communicable disease Diseases 0.000 abstract description 12
- 208000027866 inflammatory disease Diseases 0.000 abstract description 12
- 239000000543 intermediate Substances 0.000 abstract description 8
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 abstract 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 241
- 125000005842 heteroatom Chemical group 0.000 description 98
- 125000004432 carbon atom Chemical group C* 0.000 description 97
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 51
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 46
- 229910052799 carbon Inorganic materials 0.000 description 44
- 229910052757 nitrogen Inorganic materials 0.000 description 43
- 125000005843 halogen group Chemical group 0.000 description 38
- 150000002576 ketones Chemical class 0.000 description 37
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- 235000002639 sodium chloride Nutrition 0.000 description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- 239000002585 base Substances 0.000 description 29
- 125000004404 heteroalkyl group Chemical group 0.000 description 29
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 28
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 25
- 150000001412 amines Chemical class 0.000 description 25
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- 239000003921 oil Substances 0.000 description 25
- 239000000047 product Substances 0.000 description 25
- 238000007792 addition Methods 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 24
- 125000001424 substituent group Chemical group 0.000 description 24
- 239000001301 oxygen Substances 0.000 description 22
- 238000012545 processing Methods 0.000 description 22
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 21
- 229920002554 vinyl polymer Polymers 0.000 description 21
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 20
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 description 19
- 239000002243 precursor Substances 0.000 description 19
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 18
- 125000003277 amino group Chemical group 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 125000001188 haloalkyl group Chemical group 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 125000000753 cycloalkyl group Chemical group 0.000 description 17
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 17
- 230000004048 modification Effects 0.000 description 17
- 238000012986 modification Methods 0.000 description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 17
- 239000011593 sulfur Substances 0.000 description 17
- 239000003755 preservative agent Substances 0.000 description 16
- 150000002466 imines Chemical class 0.000 description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 239000011737 fluorine Substances 0.000 description 14
- 229910052731 fluorine Inorganic materials 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 230000009466 transformation Effects 0.000 description 14
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 description 13
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 125000001153 fluoro group Chemical group F* 0.000 description 13
- 208000015181 infectious disease Diseases 0.000 description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 description 13
- 230000000269 nucleophilic effect Effects 0.000 description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
- 150000002678 macrocyclic compounds Chemical class 0.000 description 12
- 238000000844 transformation Methods 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 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 11
- 229920002472 Starch Polymers 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 125000001309 chloro group Chemical group Cl* 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 11
- 235000019698 starch Nutrition 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound 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 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- 125000001246 bromo group Chemical group Br* 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 238000006073 displacement reaction Methods 0.000 description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 10
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 229940032147 starch Drugs 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 150000007970 thio esters Chemical class 0.000 description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 8
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 238000006268 reductive amination reaction Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 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 7
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- 239000002202 Polyethylene glycol Substances 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 229930006000 Sucrose Natural products 0.000 description 7
- 235000010443 alginic acid Nutrition 0.000 description 7
- 229920000615 alginic acid Polymers 0.000 description 7
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- 238000007306 functionalization reaction Methods 0.000 description 7
- 239000008101 lactose Substances 0.000 description 7
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 7
- 125000000466 oxiranyl group Chemical group 0.000 description 7
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- 150000008163 sugars Chemical class 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
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- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
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- 150000004820 halides Chemical class 0.000 description 6
- 150000004677 hydrates Chemical class 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 238000007239 Wittig reaction Methods 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000000783 alginic acid Substances 0.000 description 4
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- 150000004781 alginic acids Chemical class 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
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- 230000000712 assembly Effects 0.000 description 4
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- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
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- C07D498/02—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 two hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
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- 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
- C07D498/02—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 two hetero rings
- C07D498/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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| US201361808441P | 2013-04-04 | 2013-04-04 | |
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| US201361832639P | 2013-06-07 | 2013-06-07 | |
| US61/832,639 | 2013-06-07 | ||
| US201461946604P | 2014-02-28 | 2014-02-28 | |
| US61/946,604 | 2014-02-28 | ||
| CN201480031522.6A CN105246334A (zh) | 2013-04-04 | 2014-04-04 | 大环内酯及其制备和使用方法 |
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| CN201480031522.6A Division CN105246334A (zh) | 2013-04-04 | 2014-04-04 | 大环内酯及其制备和使用方法 |
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| CN111825733A true CN111825733A (zh) | 2020-10-27 |
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