JP2012162562A - 免疫アジュバントの調製のための化合物 - Google Patents
免疫アジュバントの調製のための化合物 Download PDFInfo
- Publication number
- JP2012162562A JP2012162562A JP2012096962A JP2012096962A JP2012162562A JP 2012162562 A JP2012162562 A JP 2012162562A JP 2012096962 A JP2012096962 A JP 2012096962A JP 2012096962 A JP2012096962 A JP 2012096962A JP 2012162562 A JP2012162562 A JP 2012162562A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- compound
- hydrogen
- formula
- Prior art date
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 77
- 239000000568 immunological adjuvant Substances 0.000 title abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims description 101
- 239000001257 hydrogen Substances 0.000 claims description 69
- 229910052739 hydrogen Inorganic materials 0.000 claims description 69
- -1 cyanoethylcarbonyl Chemical group 0.000 claims description 53
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 36
- 125000003342 alkenyl group Chemical group 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 14
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 claims description 10
- 239000013078 crystal Substances 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 230000002829 reductive effect Effects 0.000 claims description 6
- DXXHJNTXXLCKAD-UHFFFAOYSA-N P(O)(O)O.[O] Chemical group P(O)(O)O.[O] DXXHJNTXXLCKAD-UHFFFAOYSA-N 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- OYCDTPQIKJZGBS-UHFFFAOYSA-N P(O)(O)(O)=O.[O] Chemical group P(O)(O)(O)=O.[O] OYCDTPQIKJZGBS-UHFFFAOYSA-N 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 230000001590 oxidative effect Effects 0.000 claims description 4
- AEHJHUKSIUEWIP-UHFFFAOYSA-N 3,4,5,6-tetrachlorobenzene-1,2-dicarboxamide Chemical compound NC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C(N)=O AEHJHUKSIUEWIP-UHFFFAOYSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- WSCBKJKSJZLMQD-UHFFFAOYSA-N 3-chlorobenzene-1,2-dicarboxamide Chemical compound NC(=O)C1=CC=CC(Cl)=C1C(N)=O WSCBKJKSJZLMQD-UHFFFAOYSA-N 0.000 claims 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 45
- 239000000427 antigen Substances 0.000 abstract description 19
- 108091007433 antigens Proteins 0.000 abstract description 19
- 102000036639 antigens Human genes 0.000 abstract description 19
- 229960005486 vaccine Drugs 0.000 abstract description 9
- 102000008233 Toll-Like Receptor 4 Human genes 0.000 abstract description 7
- 108010060804 Toll-Like Receptor 4 Proteins 0.000 abstract description 7
- 239000000018 receptor agonist Substances 0.000 abstract description 6
- 229940044601 receptor agonist Drugs 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract description 5
- 230000001580 bacterial effect Effects 0.000 abstract description 3
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 abstract description 3
- 230000003612 virological effect Effects 0.000 abstract description 3
- 125000003277 amino group Chemical group 0.000 abstract description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 150
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 121
- 238000006243 chemical reaction Methods 0.000 description 91
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 65
- 239000011541 reaction mixture Substances 0.000 description 64
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 238000003756 stirring Methods 0.000 description 47
- 239000010410 layer Substances 0.000 description 45
- 239000000460 chlorine Substances 0.000 description 43
- 239000012044 organic layer Substances 0.000 description 43
- 238000002360 preparation method Methods 0.000 description 41
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 35
- 239000002904 solvent Substances 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 125000003118 aryl group Chemical group 0.000 description 30
- 125000001424 substituent group Chemical group 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 28
- 238000004809 thin layer chromatography Methods 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000003153 chemical reaction reagent Substances 0.000 description 23
- 125000000753 cycloalkyl group Chemical group 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 125000000304 alkynyl group Chemical group 0.000 description 21
- 230000015572 biosynthetic process Effects 0.000 description 21
- 125000001072 heteroaryl group Chemical group 0.000 description 21
- 238000004128 high performance liquid chromatography Methods 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 239000012267 brine Substances 0.000 description 18
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 17
- 239000012299 nitrogen atmosphere Substances 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 239000000463 material Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 125000001931 aliphatic group Chemical group 0.000 description 15
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 14
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 14
- 238000000746 purification Methods 0.000 description 14
- 239000002671 adjuvant Substances 0.000 description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- 230000008569 process Effects 0.000 description 13
- 238000010626 work up procedure Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 125000004404 heteroalkyl group Chemical group 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000007858 starting material Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical group CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- NRTYMEPCRDJMPZ-UHFFFAOYSA-N pyridine;2,2,2-trifluoroacetic acid Chemical compound C1=CC=NC=C1.OC(=O)C(F)(F)F NRTYMEPCRDJMPZ-UHFFFAOYSA-N 0.000 description 10
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- XLKOZYOVXNPWGT-UHFFFAOYSA-N 3-oxotetradecanoic acid Chemical class CCCCCCCCCCCC(=O)CC(O)=O XLKOZYOVXNPWGT-UHFFFAOYSA-N 0.000 description 8
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000000921 elemental analysis Methods 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 239000002158 endotoxin Substances 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
- 210000000987 immune system Anatomy 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 125000002723 alicyclic group Chemical group 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 230000028993 immune response Effects 0.000 description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical group CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 235000019502 Orange oil Nutrition 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 239000010502 orange oil Substances 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-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
- 235000011054 acetic acid Nutrition 0.000 description 5
- 239000012190 activator Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- ZTEGHJIXOZLSOH-UHFFFAOYSA-N n-[[di(propan-2-yl)amino]-prop-2-enoxyphosphanyl]-n-propan-2-ylpropan-2-amine Chemical group CC(C)N(C(C)C)P(N(C(C)C)C(C)C)OCC=C ZTEGHJIXOZLSOH-UHFFFAOYSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical class NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 5
- 238000012800 visualization Methods 0.000 description 5
- 239000011800 void material Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 0 C*[C@](CC*C[C@](COP(*)(OCCNC(NCCOP(*C[C@@](COCCCOC(*C)=*)NC(CC(*C)=O)=O)(N=O)=O)=*)=*)NC(CC(*C)=O)=O)*C=O Chemical compound C*[C@](CC*C[C@](COP(*)(OCCNC(NCCOP(*C[C@@](COCCCOC(*C)=*)NC(CC(*C)=O)=O)(N=O)=O)=*)=*)NC(CC(*C)=O)=O)*C=O 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 125000005265 dialkylamine group Chemical group 0.000 description 4
- POCFBDFTJMJWLG-UHFFFAOYSA-N dihydrosinapic acid methyl ester Natural products COC(=O)CCC1=CC(OC)=C(O)C(OC)=C1 POCFBDFTJMJWLG-UHFFFAOYSA-N 0.000 description 4
- 229940043279 diisopropylamine Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 238000010952 in-situ formation Methods 0.000 description 4
- 229960004592 isopropanol Drugs 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical compound [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 229940037003 alum Drugs 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- 150000002009 diols Chemical class 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002458 infectious effect Effects 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 150000002894 organic compounds Chemical class 0.000 description 3
- 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 3
- 244000052769 pathogen Species 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 238000001144 powder X-ray diffraction data Methods 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 238000010792 warming Methods 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 150000001923 cyclic compounds Chemical class 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000013480 data collection Methods 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000005191 phase separation Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- TYZYRCHEVXXLSJ-UHFFFAOYSA-N phenylmethoxymethoxymethoxymethylbenzene Chemical compound C=1C=CC=CC=1COCOCOCC1=CC=CC=C1 TYZYRCHEVXXLSJ-UHFFFAOYSA-N 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 230000000865 phosphorylative effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- WILBTFWIBAOWLN-UHFFFAOYSA-N triethyl(triethylsilyloxy)silane Chemical compound CC[Si](CC)(CC)O[Si](CC)(CC)CC WILBTFWIBAOWLN-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- VDSCKSBQISVYTQ-RTBURBONSA-N (3r)-1-[[(4r)-2-phenyl-4,5-dihydro-1,3-oxazol-4-yl]methoxy]decan-3-ol Chemical compound CCCCCCC[C@@H](O)CCOC[C@@H]1COC(C=2C=CC=CC=2)=N1 VDSCKSBQISVYTQ-RTBURBONSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- IBTSIFIGTARYRB-UHFFFAOYSA-N 1,3-dihydroxyurea Chemical compound ONC(=O)NO IBTSIFIGTARYRB-UHFFFAOYSA-N 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
- VHSKSVCULAEZBU-UHFFFAOYSA-N 2-phenyl-2,3-dihydro-1,3-oxazole Chemical group N1C=COC1C1=CC=CC=C1 VHSKSVCULAEZBU-UHFFFAOYSA-N 0.000 description 1
- KBSDLBVPAHQCRY-UHFFFAOYSA-N 307496-19-1 Chemical group C1CC=CCC1CC[Si](O1)(O2)O[Si](O3)(C4CCCC4)O[Si](O4)(C5CCCC5)O[Si]1(C1CCCC1)O[Si](O1)(C5CCCC5)O[Si]2(C2CCCC2)O[Si]3(C2CCCC2)O[Si]41C1CCCC1 KBSDLBVPAHQCRY-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000006538 C11 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N CC(C)(C)OC(N)=O Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- ZUSXZBBVTXUOEL-UHFFFAOYSA-N CC(C)(OP(=O)(O)O)[Si](C)(C)C Chemical compound CC(C)(OP(=O)(O)O)[Si](C)(C)C ZUSXZBBVTXUOEL-UHFFFAOYSA-N 0.000 description 1
- XATWWEFORVGYJX-UHFFFAOYSA-N CC1(CC1)C1(C)CCCC1 Chemical compound CC1(CC1)C1(C)CCCC1 XATWWEFORVGYJX-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008631 Cholera Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 208000000655 Distemper Diseases 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical class CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 208000000666 Fowlpox Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- NRVMSFKEGIGIHL-UHFFFAOYSA-N OCC1N=C(c2ccccc2)OC1 Chemical compound OCC1N=C(c2ccccc2)OC1 NRVMSFKEGIGIHL-UHFFFAOYSA-N 0.000 description 1
- 201000005702 Pertussis Diseases 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 208000000474 Poliomyelitis Diseases 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 206010039587 Scarlet Fever Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 206010043376 Tetanus Diseases 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 238000003705 background correction Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- YTFJQDNGSQJFNA-UHFFFAOYSA-L benzyl phosphate Chemical compound [O-]P([O-])(=O)OCC1=CC=CC=C1 YTFJQDNGSQJFNA-UHFFFAOYSA-L 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229910052729 chemical element Inorganic materials 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 229960005215 dichloroacetic acid Drugs 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 102000045717 human TLR4 Human genes 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 206010022000 influenza Diseases 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- DLMICMXXVVMDNV-UHFFFAOYSA-N n,n-di(propan-2-yl)propan-1-amine Chemical group CCCN(C(C)C)C(C)C DLMICMXXVVMDNV-UHFFFAOYSA-N 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- RRTXKQSFZYOTNW-UHFFFAOYSA-N n-phosphanyl-n-propan-2-ylpropan-2-amine Chemical compound CC(C)N(P)C(C)C RRTXKQSFZYOTNW-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical group [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- XMGMFRIEKMMMSU-UHFFFAOYSA-N phenylmethylbenzene Chemical group C=1C=CC=CC=1[C]C1=CC=CC=C1 XMGMFRIEKMMMSU-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- MTIQLOQTQUBOLK-UHFFFAOYSA-N silyl dihydrogen phosphite Chemical compound OP(O)O[SiH3] MTIQLOQTQUBOLK-UHFFFAOYSA-N 0.000 description 1
- 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- FGTJJHCZWOVVNH-UHFFFAOYSA-N tert-butyl-[tert-butyl(dimethyl)silyl]oxy-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)O[Si](C)(C)C(C)(C)C FGTJJHCZWOVVNH-UHFFFAOYSA-N 0.000 description 1
- KJTULOVPMGUBJS-UHFFFAOYSA-N tert-butyl-[tert-butyl(diphenyl)silyl]oxy-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C(C)(C)C)O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 KJTULOVPMGUBJS-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- LGSAOJLQTXCYHF-UHFFFAOYSA-N tri(propan-2-yl)-tri(propan-2-yl)silyloxysilane Chemical compound CC(C)[Si](C(C)C)(C(C)C)O[Si](C(C)C)(C(C)C)C(C)C LGSAOJLQTXCYHF-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000006370 trihalo methyl group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940124856 vaccine component Drugs 0.000 description 1
- 238000007794 visualization technique Methods 0.000 description 1
Images
Classifications
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/10—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/14—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with radicals substituted by oxygen atoms
-
- 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
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/141—Esters of phosphorous acids
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/141—Esters of phosphorous acids
- C07F9/1411—Esters of phosphorous acids with hydroxyalkyl compounds with further substituents on alkyl
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
- C07F9/2404—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/2408—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic of hydroxyalkyl compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
本発明に従い、本明細書で使用する以下の用語は、明示的に別段の定めをした場合を除き、以下の意味に定義される。
(a)構造:
[式中、
R1aは、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、シクロアルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、ヘテロシクロアルキル、ヘテロシクロアルケニル、ヘテロシクロアルキニル、アリール、ヘテロアリール、亜リン酸の酸素保護基、またはリン酸の酸素の保護基であり;および
R2aおよびR2bは各々独立して、水素または適当な窒素保護基であるか、またはR2aおよびR2bは一緒になって、5-または6-員ヘテロ環を形成し;(このとき、R2aおよびR2bは同時に水素でない);]
を有する化合物とホスゲンを適当な条件下で反応させ、
構造:
を有するウレイド二量体の形成を達成する
(b)工程(a)で形成したウレイド二量体(2)を適当な条件下で脱保護し、構造:
を有する部分的に脱保護された二量体(3)の形成を達成する
(c)工程(b)で形成された部分的に脱保護された二量体と適当な試薬を適当な条件下で反応させ、構造:
を有する保護された二量体(4)の形成を達成する
(d)工程(c)で形成された二量体を1つ以上の適当な試薬で適当な条件下で処理し、構造:
を有するナトリウム塩の形成を達成する
を含む。
を有する化合物の精製には、クロマトグラフ分離および塩基での処理が含まれる。ある例示の実施形態において、該精製工程には、(i)イオン交換クロマトグラフィー、(ii)C-4 Kromasil溶出、および(iii)NaOAc水溶液での処理が含まれる。ある例示の実施形態において、該精製工程には、(i)Biotage KP-シリカクロマトグラフィー、(ii)Biotage KP HS-C18 クロマトグラフィー、および(iii)NaOAc水溶液での処理が含まれる。
[式中、
R1aは、水素、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、シクロアルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、ヘテロシクロアルキル、ヘテロシクロアルケニル、ヘテロシクロアルキニル、アリール、ヘテロアリールまたは亜リン酸の酸素保護基またはリン酸の酸素の保護基であり;および
R2aおよびR2bは各々独立して、水素もしくは適当な窒素保護基であるか、またはR2aおよびR2bは一緒になって、5-または6-員ヘテロ環を形成し;(このとき、R2aおよびR2bは同時に水素でない);]
を有する化合物は、工程:
(a)構造:
を有するアルコールと、構造:
[式中、-OX1は適当な離脱基を示す];
を有する部分的に保護された適当なジオールを反応させて、構造:
を有するアルコール形成する
(b)アルコール8と適当なドデカン酸誘導体を適当な条件下で反応させて、構造:
を有するエステルを形成する
(c)エステル9を適当な条件下で脱保護して、構造:
を有するヒドロキシルアミンを形成する
(d)ヒドロキシルアミン10を適当な条件下で部分的に保護し、構造:
[式中R2aおよびR2bは上記に定義される];
を有するアルコールを形成する
(e)アルコール11を1つ以上の適当な試薬で適当な条件下で処理し、構造:
[式中、R1aは、水素、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、シクロアルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、ヘテロシクロアルキル、ヘテロシクロアルケニル、ヘテロシクロアルキニル、アリールまたはヘテロアリール、亜リン酸の酸素保護基またはリン酸の酸素の保護基であり;および
R3aおよびR3bは各々独立して、水素もしくは適当な窒素保護基であるか、またはR3aおよびR3bは一緒になって、5-または6-員ヘテロ環を形成し;(このときR3aおよびR3bは同時に水素でない)]
を有するリン酸エステルの形成を達成する;および
(f)12を適当な条件下で部分的に脱保護し、アミン1:
の形成を達成する、
を含む方法により調製される。
(i)構造:
[式中、R4aおよびR4bは独立して低級アルキルである]
を有するホスホロアミダス酸(phosphoramidous acid)エステルのin situ形成; および
(ii)構造:
[式中、R1a、R2a、R2b、R3aおよびR3bは上記に定義される]
を有するホスホン酸エステルのin situ形成
が含まれる。
を有する。
[式中、R3aおよびR3bは各々独立して、水素または適当な窒素保護基であるか、またはR3aおよびR3bは一緒になって、5-または6-員ヘテロ環を形成し;(このときR3aおよびR3bは同時に水素でない)]
を有する保護されたエタノールアミンとの反応が含まれる。ある例示の実施形態において、R3aおよびR3bは各々独立して、水素、アルキル、アルケニル、-C(=O)Rx、-C(=O)ORx、-SRx、SO2Rxであるか、またはR3aおよびR3bは一緒になって、構造=CRxRyを有する基を形成し(このときR3aおよびR3bは同時に水素でない)、RxおよびRyは各々独立して、水素、アルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、シクロアルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、ヘテロシクロアルキル、ヘテロシクロアルケニル、ヘテロシクロアルキニル、ヘテロ脂肪族、ヘテロ脂環、アリール、ヘテロアリール、-C(=O)RAまたは-ZRA、Zは-O-、-S-、-NRBであり、RAおよびRBは各々独立して、水素、またはアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルケニル、シクロアルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、ヘテロシクロアルキル、ヘテロシクロアルケニル、ヘテロシクロアルキニル、ヘテロ脂肪族、ヘテロ脂環、アリールまたはヘテロアリール基である。ある例示の実施形態において、R3aは水素であり、R3bは-C(=O)ORxであり、Rxはアリールアルキルである。他の例示の実施形態において、R3aは水素であり、R3bは-C(=O)ORxであり、Rxは9-フルオレニルメチル(すなわち、R3bはFmocである)である。
ことが含まれる。ある例示の実施形態において、該酸化剤はH2O2である。
を有する化合物に関する。
本発明の化合物およびそれらの調製は、これらの化合物が調製されまたは使用されるいくつかの過程を説明する実施例によって、さらに理解されることができる。しかし当然のことながら、これらの実施例は本発明を限定しない。本発明のバリエーションは、本明細書および特許請求の範囲に記載される本発明の範囲内に含まれると考えられる。
ER-028695の分析データ: 1H-NMR(CDCl3, 400MHz)δ0.88(t, J=7.1Hz, 3H), 1.2-1.5(m, 12H), 1.57(bs, 1H), 1.6-1.7(m, 1H), 1.8-1.9(m, 1H), 2.45(s, 3H), 3.7-3.8(m, 1H), 4.1-4.2(m, 1H), 4.2-4.3(m, 1H), 7.35, (d, J=7.8Hz, 2H), 7.80(d, J=7.8Hz, 2H). MS-APESI(M+Na)C17H28NaO4Sの計算値: 351.16 実測値: 351.23. HPLC: ER-028695:ER-817864 比率 87.11%:11.71%.
2.376Kgの精製したER-806158をヘプタン(8.121Kg)に溶かし、清潔な乾燥した22Lの反応器に窒素雰囲気下で移し、続いて攪拌した。該澄明黄色溶液を、0.5時間毎に〜4℃で段階的に-15℃まで冷却した。得られた白色懸濁液を-15℃でさらに1時間攪拌し、続いて冷却したろ過漏斗およびろ紙で、真空で、該ろ過ケーク上に窒素ブランケットをして、ろ過した。該所望の固体を、冷却したヘプタン(-12.3℃、1.387Kg)で洗浄し、上記のようにろ過し、該ろ過ケークを真空下で、該固体上を窒素ブランケットしながら、14時間13分間(T=14.9〜18.8℃)維持した。該反応器の、残りのER-806158を溶かす該母液、洗浄液、および該溶媒を、リサイクルのために合わせた。
入手: 2.068Kg、収率87.0%
ER-806158の分析データ
・ 純度: 99.84 wt/wt%
・ キラル純度: 99.72%e.e.
・ KF: 0.21%
・ ヘプタン: 268ppm
・ 1H-NMR(CDCl3)δ0.88(t, J=6.9Hz, 3H), 1.2-1.6(m, 12H), 1.6-1.7(m, 1H), 1.7-1.8(m, 1H), 3.21(bs, 1H), 3.6-3.7(m, 3H), 3.7-3.8(m, 2H), 3.5-3.6(m, 2 H), 4.2-4.3(m, 1H), 4.5(m, 2H), 7.42, (t, J=7.6Hz, 2H), 7.49, (dd, J=6.9, 7.8Hz, 1H), 7.95(d, J=7.3Hz, 2H).
・ 元素分析(EA): C30H59NO6の計算値: C, 72.04; H, 9.37; N; 4.20 実測値: C, 71.83; H, 9.30; N, 4.08.
・ m.p.(DSC)開始、26.7℃; 最高、29.5℃.
ER-819059の分析データ
・ HPLC分析: 99.76面積%.
・ KF: 0.36%
・ ヘプタン: 725ppm
・ 1H-NMR(CDCl3) δ0.881(t, J=7.1Hz, 3H), 0.884(t, J=6.9Hz, 3H), 1.2-1.3(m, 26H), 1.5-1.6(m, 2H), 1.6-1.7(m, 2H), 1.8-1.9(m, 2H), 2.28(t, J=7.6Hz, 2H), 3.4-3.6(m, 3H), 3.69(dd, J=3.7, 9.6Hz, 1H), 4.3-4.6(m, 3 H), 5.0(m, 1H), 7.43, (t, J=7.6Hz, 2H), 7.51, (dd, J=6.0, 7.3Hz, 1H), 7.95(d, J=6.0Hz, 2H).
・ MS-APESI(M+H)C32H54NO4の計算値: 516.41 実測値: 516.48
・ TLC:(シリカゲルF254):MTBE/ヘプタン=1/1; ER-819059のRf=0.51
ER-819302-00の分析データ
・ 1H-NMR(CDCl3)δ 0.89(t, J=6.9Hz, 6H), 1.2-1.3(m, 26H), 1.46(s, 9 H), 1.5-1.7(m, 4 H), 1.7-1.8(m, 1 H), 1.8-1.9(m, 1H), 2.30(t, J=7.6Hz, 6H), 3.3-3.4(m, 1H), 3.48(td, J=6.9, 9.6Hz, 1H), 3.5-3.6(m, 2 H), 3.69(td, J=6.1, 7.1Hz, 1H), 3.76(d, J=8.2Hz, 2H), 5.0-5.1(m, 1H), 5.2(bs, 1H).
・ MS-APESI(M+Na) C30H59NNaO6の計算値: 552.42 実測値: 552.52
・ KF=0.30%
・ ヘプタン=6034ppm;MTBE=検出なし
ER-819344の分析データ
・ 1H-NMR(CDCl3)δ 0.85-0.90(m, 6H), 1.20-1.36(m, 26H), 1.40-1.65(m, 4H), 1.44(s, 9H), 1.70-1.83(m, 2H), 2.27(t, J=7.6Hz, 2H), 3.37-3.57(m, 6H), 3.90-4.00(m, 1H), 4.03-4.10(m, 1H), 4.11-4.24(m, 3H), 4.35-4.40(m, 2H), 4.50-4.60(m, 2H), 4.94-5.0(m, 1H), 5.05-5.15(m, 1H), 5.22-5.27(m, 1H), 5.30-5.40(m, 1H), 5.85-6.0(m, 2H), 6.01-6.05(m, 1H), 7.30(dd, J=7.3, 7.8Hz, 2H), 7.40(dd, J=7.3, 7.8Hz, 2H), 7.61(d, J=7.8Hz, 2H), 7.76(d, J=7.3Hz, 2H).
・ 31P-NMR(CDCl3, 測定なし)0.172, 0.564(2つのジアステレオマー)
・ MS-APESI(M+Na) C50H79N2NaO11Pの計算値: 937.53 実測値: 937.65.
ER-820116の分析データ
・ 1H-NMR(CDCl3)δ0.870(m, 6H), 1.176(d, J=8.0 Hz, 12H), 1.254-1.282(b, 28H), 1.428(b, 9H), 1.528(b, 2H), 1.603(b, 2H), 1.790(m, 2H), 2.265(t, J=7.0 Hz, 2H), 3.431(m, 2H), 3.481(m, 2H), 3.600(m, 2H), 3.751(b, 2H), 3.847(b, 1H), 3.847- 4.208(m, 2H), 4.950(b, 1H), 5.126(d, J=10Hz, 1H), 5.286(dd, J=17 Hz, J’=1.5 Hz, 1H), 5.898-5.989(m, 1H)
・ 31P-NMR(CDCl3, 測定)148.449および148.347(2 ジアステレオマー)
・ MS-APESI(M+H) C39H78N2O7Pの計算値: 717.55, 実測値: 717.66.
ER-821843の分析データ
・ 31P-NMR(CDCl3, 測定)δ 139.832, 139.868, 140.170, 140.327(4 ジアステレオマー)
・ MS-APESI(M+Na) C30H59NNaO6の計算値: 552.42 実測値: マスデータなし
ER-819409の分析データ
・ MeOH: 検出されず
・ MTBE: 検出されず
・ MeCN: 185ppm
・ ヘプタン: 1718ppm
・ 1H-NMR(CDCl3)δ0.88(t, J=6.9Hz, 12H), 1.20-1.37(m, 52H), 1.44(s, 18H), 1.45-1.72(m, 8H), 1.76-1.85(m, 4H), 2.28(t, J=7.6Hz, 4H), 3.38-3.58(m, 12H), 3.85-3.97(m, 2H), 3.98-4.20(m, 8H), 4.53-4.58(m, 4H), 4.95-5.0(m, 2H), 5.18-5.28(m, 2H), 5.26(dd, J=1.4, 10.5Hz, 2H), 5.37(dd, J=0.9, 16.9Hz, 2H), 5.62-5.85(m, 2H), 5.87-5.99(m, 2H).
・ MS-APESI(M+Na) C71H136N4NaO19P2の計算値: 1433.92 実測値: 1433.98.
ER-807284の分析データ
・1H-NMR(CDCl3)δ0.85-0.95(m, 12H), 1.20-1.35(m, 52H), 1.45-1.65(m, 8H), 1.70-1.85(m, 4H), 2.25-2.65(bs, 4H), 2.28(t, J=7.6Hz, 4H), 3,20-3.27(m, 2H), 3.30-3.60(m, 12H), 3.98-4.22(m, 10H), 4.50-4.60(m, 4H), 4.95-5.05(m, 2H), 5.27(dd, J=0.9, 10.5Hz, 2H), 5.38(dd, J=0.9, 16.9Hz, 2H), 5.90-6.0(m, 2H).
・MS-APESI(M+H)C61H121N4O15P2の計算値: 1211.83 実測値: 1211.97.
結晶性ER-806158のFTIR吸収スペクトルをニート結晶性粉末について記録した。結晶性ER-806158のIR吸収スペクトルは図5に示される。
Claims (34)
- 式(15):
Aは-(CH2)x-O-または共有結合であり;
nは0または1であり;
xは1〜6であり;
R1aは水素、C1〜C6アルキル基、C3〜C6アルケニル基、C3〜C6アルキニル基、または亜リン酸の酸素保護基またはリン酸の酸素の保護基であり;
R2aおよびR2bの一方はHおよび他方は一価の窒素保護基であるか; またはR2aおよびR2bは一緒になって、二価の窒素保護基であり;
Aが-(CH2)x-O-であるとき、R3aおよびR3bの一方はHであり、他方は一価の窒素保護基であるか、またはR3aおよびR3bは一緒になって、二価の窒素保護基であり;
Aが共有結合であるとき、R3aおよびR3bはC1〜C6アルキル基であるか、またはR3aおよびR3bは一緒になって、-(CH2)4-、-(CH2)5-、または-(CH2)2O(CH2)2-であり;
R4はC5〜C12アルキル基またはC5〜C12アルケニル基であり; および
R5は、C5〜C15アルキル基またはC5〜C15アルケニル基である]
の化合物またはその塩。 - 式中、R2aおよびR2bまたはR3aおよびR3bの該窒素保護基が、Boc、Fmoc、TROC、TMS-エチルカルボニル、シアノエチルカルボニル、アリルオキシカルボニル、(C6H5)2C=、テトラクロロフタルアミド、またはアジドからなる群から独立して選択される、請求項1の化合物。
- 式中、R2aおよびR2bに結合する窒素の保護基が、酸性、塩基性、酸化的、および還元的条件から選ばれる第1条件下で除去することができ; およびR3aおよびR3bに結合する窒素の該保護基が、該1条件とは異なる残りの3つの条件から選択される第2条件下で除去することができる、請求項1の化合物。
- 式中、Aが-(CH2)2-O-であり; nが0であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項1の化合物。
- 式中、Aが-(CH2)2-O-であり; nが1であり; R4がC7アルキルであり; およびR5がC11アルキルである、請求項1の化合物。
- 式中、Aが共有結合であり、nが0であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項1の化合物。
- 式中、Aが共有結合であり、nが0であり; R3aおよびR3bが各々イソプロピルであり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項1の化合物。
- 式中、Aが-(CH2)2-O-であり; nが0であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項1の化合物。
- 式中、R2aおよびR2bの該窒素保護基がBoc、Fmoc、TROC、TMS-エチルカルボニル、シアノエチルカルボニル、アリルオキシカルボニル、(C6H5)2C=、テトラクロロフタルアミド、またはアジドからなる群から独立して選択される、請求項13の化合物。
- 式中、nが1であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項13の化合物。
- 式中、nが1であり; R1aがアリルであり; R2aが水素であり; R2cがBocであり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項13の化合物。
- 式中、nが1であり; R2aが水素であり; R2cが-C(O)CH2C(O)R6であり; R4がC7アルキルであり; R5がC11アルキルであり;およびR6がC11アルキルである、請求項13の化合物。
- 式中、nが0であり; R1aがアリルであり; R2aが水素であり; R2cがBocであり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項13の化合物。
- 式中、nが1であり; R1aがアリルであり; R2aが水素であり; R2cが水素であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項13の化合物。
- 式中、nが0であり; R1aがアリルであり; R2aが水素であり; R2cが-C(O)CH2C(O)R6であり; R4がC7アルキルであり; R5がC11アルキルであり;およびR6がC11アルキルである、請求項13の化合物。
- 式中、R2aおよびR2bの該窒素保護基がBoc、Fmoc、TROC、TMS-エチルカルボニル、シアノエチルカルボニル、アリルオキシカルボニル、(C6H5)2C=、テトラクロロフタルアミド、またはアジドからなる群から独立して選択される、請求項25の化合物。
- 式中、Rが水素であり; R2aおよびR2bが水素であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項25の化合物。
- 、式中、Rが水素であり; R2aが水素であり; R2bが窒素保護基であり; R4がC7アルキルであり;およびR5がC11アルキルである、請求項25の化合物。
- 三斜晶系結晶系およびP1空間群である、結晶性ER-806158、(R)-1-(((R)-4,5-ジヒドロ-2-フェニルオキサゾール-4-イル)メトキシ)デカン-3-オ-ル。
- 結晶格子パラメーター:
a = 4.6047(11)Å α = 106.008(4)°
b = 8.1161(19)Å β = 95.604(4)°
c = 13.579(3)Å γ = 98.696(4)°
体積 = 477.0(2)Å3およびZ = 1
を特徴とする、請求項33の結晶性ER-806158、(R)-1-(((R)-4,5-ジヒドロ-2-フェニルオキサゾール-4-イル)メトキシ)デカン-3-オ-ル。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US69532405P | 2005-06-30 | 2005-06-30 | |
US60/695,324 | 2005-06-30 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008519603A Division JP5214446B2 (ja) | 2005-06-30 | 2006-06-30 | 免疫アジュバントの調製のための化合物 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014206710A Division JP2015051978A (ja) | 2005-06-30 | 2014-10-07 | 免疫アジュバントの調製のための化合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012162562A true JP2012162562A (ja) | 2012-08-30 |
JP5923373B2 JP5923373B2 (ja) | 2016-05-24 |
Family
ID=37192315
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008519603A Active JP5214446B2 (ja) | 2005-06-30 | 2006-06-30 | 免疫アジュバントの調製のための化合物 |
JP2012096962A Active JP5923373B2 (ja) | 2005-06-30 | 2012-04-20 | 免疫アジュバントの調製のための化合物 |
JP2014206710A Withdrawn JP2015051978A (ja) | 2005-06-30 | 2014-10-07 | 免疫アジュバントの調製のための化合物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008519603A Active JP5214446B2 (ja) | 2005-06-30 | 2006-06-30 | 免疫アジュバントの調製のための化合物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014206710A Withdrawn JP2015051978A (ja) | 2005-06-30 | 2014-10-07 | 免疫アジュバントの調製のための化合物 |
Country Status (10)
Country | Link |
---|---|
US (5) | US7683200B2 (ja) |
EP (3) | EP2292628A3 (ja) |
JP (3) | JP5214446B2 (ja) |
KR (1) | KR101294455B1 (ja) |
CN (3) | CN101213199B (ja) |
AU (1) | AU2006265986B2 (ja) |
CA (1) | CA2611721C (ja) |
HK (1) | HK1183863A1 (ja) |
IL (3) | IL187819A (ja) |
WO (1) | WO2007005583A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015051978A (ja) * | 2005-06-30 | 2015-03-19 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 免疫アジュバントの調製のための化合物 |
JP2015533366A (ja) * | 2012-10-19 | 2015-11-24 | ザ・カウンシル・オヴ・ザ・クイーンズランド・インスティテュート・オヴ・メディカル・リサーチ | 改良されたヒトヘルペスウイルス免疫療法 |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7915238B2 (en) * | 1999-02-01 | 2011-03-29 | Eisai R & D Management Co., Ltd. | Immunomodulatory compounds and methods of use thereof |
US20040006242A1 (en) * | 1999-02-01 | 2004-01-08 | Hawkins Lynn D. | Immunomodulatory compounds and method of use thereof |
EP2240435B1 (en) * | 2007-12-18 | 2012-08-01 | Eisai R&D Management Co., Ltd. | Reagents and methods for the beta-keto amide synthesis of a synthetic precursor to immunological adjuvant e6020 |
CA2784447A1 (en) | 2009-12-22 | 2011-06-30 | Sanofi Pasteur Limited | Adjuvanted immunogenic compositions and related methods |
WO2012042003A1 (en) * | 2010-09-30 | 2012-04-05 | Eurocine Vaccines Ab | Improved vaccine compositions |
US9327021B2 (en) | 2010-11-15 | 2016-05-03 | Sanofi Pasteur Limited | Immunogenic compositions |
MX2013006255A (es) | 2010-12-03 | 2015-08-05 | Sanofi Pasteur Ltd | Composicion para inmunizacion contra streptococcus pneumoniae. |
WO2013184900A2 (en) | 2012-06-06 | 2013-12-12 | Sanofi Pasteur Biologics, Llc | Immunogenic compositions and related methods |
EP2912045A4 (en) | 2012-10-29 | 2016-07-13 | Molecular Transfer Inc | POLYCATION METHYL PHOSPHOLIPIDES FOR IMPROVED RELEASE OF NUCLEIC ACIDS IN EUKARYOTIC CELLS |
EP2742952A1 (en) | 2012-12-17 | 2014-06-18 | Eurocine Vaccines AB | Influenza vaccine composition |
EP2958889B1 (en) | 2013-02-25 | 2017-03-22 | The Scripps Research Institute | Neoseptins: small molecule adjuvants |
US9622483B2 (en) | 2014-02-19 | 2017-04-18 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
US11039621B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
US11039620B2 (en) | 2014-02-19 | 2021-06-22 | Corning Incorporated | Antimicrobial glass compositions, glasses and polymeric articles incorporating the same |
US10772946B2 (en) | 2015-10-13 | 2020-09-15 | Sanofi Pasteur | Immunogenic compositions against S. aureus |
WO2017137085A1 (en) | 2016-02-11 | 2017-08-17 | Sanofi Pasteur | Meningitidis vaccines comprising subtilinases |
KR20230034936A (ko) * | 2020-04-06 | 2023-03-10 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 면역 반응을 생성하는 백신, 아쥬반트 및 방법 |
WO2022090359A1 (en) | 2020-10-28 | 2022-05-05 | Sanofi Pasteur | Liposomes containing tlr4 agonist, preparation and uses thereof |
WO2023056089A1 (en) | 2021-10-03 | 2023-04-06 | Eisai R&D Management Co., Ltd. | Immunological adjuvant formulations comprising tlr4 agonist e6020 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002535411A (ja) * | 1999-02-01 | 2002-10-22 | エーザイ株式会社 | 免疫アジュバント化合物 |
WO2003099195A2 (en) * | 2002-05-28 | 2003-12-04 | Eisai Co., Ltd. | Immunomodulatory compounds and methods of use thereof |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1993004672A1 (en) * | 1991-09-11 | 1993-03-18 | Pitman-Moore, Inc. | Method for enhancing the immune system in a host employing liposome-encapsulated polypeptides |
AU5543294A (en) * | 1993-10-29 | 1995-05-22 | Pharmos Corp. | Submicron emulsions as vaccine adjuvants |
US6551600B2 (en) | 1999-02-01 | 2003-04-22 | Eisai Co., Ltd. | Immunological adjuvant compounds compositions and methods of use thereof |
US6835721B2 (en) * | 1999-02-01 | 2004-12-28 | Eisai Co., Ltd. | Immunomodulatory compounds and methods of use thereof |
WO2000067788A2 (en) * | 1999-05-06 | 2000-11-16 | Genetics Institute, Inc. | Use of soluble costimulatory molecules to enhance immune responses |
EP1307466B1 (en) * | 2000-07-31 | 2005-11-16 | Eisai Co., Ltd. | Immunological adjuvant compounds |
JP4176021B2 (ja) * | 2002-03-05 | 2008-11-05 | セルメディシン株式会社 | 固体化組織免疫アジュバント |
CN1535726A (zh) * | 2003-04-11 | 2004-10-13 | 上海欣安基因免疫与疫苗研究开发有限 | 一种分子佐剂、其制备方法以及含该分子佐剂的基因疫苗 |
CN101213199B (zh) | 2005-06-30 | 2013-12-18 | 卫材R&D管理有限公司 | 用于制备免疫佐剂的化合物 |
-
2006
- 2006-06-30 CN CN2006800239637A patent/CN101213199B/zh active Active
- 2006-06-30 EP EP10012396A patent/EP2292628A3/en not_active Withdrawn
- 2006-06-30 CA CA2611721A patent/CA2611721C/en active Active
- 2006-06-30 US US11/477,936 patent/US7683200B2/en active Active
- 2006-06-30 AU AU2006265986A patent/AU2006265986B2/en active Active
- 2006-06-30 KR KR1020087002446A patent/KR101294455B1/ko active IP Right Grant
- 2006-06-30 EP EP16192172.1A patent/EP3138844B1/en active Active
- 2006-06-30 JP JP2008519603A patent/JP5214446B2/ja active Active
- 2006-06-30 CN CN201210359517.0A patent/CN103012169B/zh active Active
- 2006-06-30 EP EP06785934.8A patent/EP1910387B1/en active Active
- 2006-06-30 CN CN201210358141.1A patent/CN103012304B/zh active Active
- 2006-06-30 WO PCT/US2006/025536 patent/WO2007005583A1/en active Application Filing
-
2007
- 2007-12-02 IL IL187819A patent/IL187819A/en active IP Right Grant
-
2010
- 2010-02-02 US US12/698,686 patent/US8198474B2/en active Active
-
2011
- 2011-05-26 IL IL213173A patent/IL213173A0/en active IP Right Grant
- 2011-05-26 IL IL213174A patent/IL213174A/en active IP Right Grant
-
2012
- 2012-04-20 JP JP2012096962A patent/JP5923373B2/ja active Active
- 2012-05-10 US US13/468,634 patent/US8519170B2/en active Active
-
2013
- 2013-07-22 US US13/947,593 patent/US8754236B2/en active Active
- 2013-10-03 HK HK13111246.4A patent/HK1183863A1/xx unknown
-
2014
- 2014-05-05 US US14/269,659 patent/US8962857B2/en active Active
- 2014-10-07 JP JP2014206710A patent/JP2015051978A/ja not_active Withdrawn
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002535411A (ja) * | 1999-02-01 | 2002-10-22 | エーザイ株式会社 | 免疫アジュバント化合物 |
WO2003099195A2 (en) * | 2002-05-28 | 2003-12-04 | Eisai Co., Ltd. | Immunomodulatory compounds and methods of use thereof |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015051978A (ja) * | 2005-06-30 | 2015-03-19 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 免疫アジュバントの調製のための化合物 |
JP2015533366A (ja) * | 2012-10-19 | 2015-11-24 | ザ・カウンシル・オヴ・ザ・クイーンズランド・インスティテュート・オヴ・メディカル・リサーチ | 改良されたヒトヘルペスウイルス免疫療法 |
JP2018075034A (ja) * | 2012-10-19 | 2018-05-17 | ザ・カウンシル・オヴ・ザ・クイーンズランド・インスティテュート・オヴ・メディカル・リサーチ | 改良されたヒトヘルペスウイルス免疫療法 |
JP2019030331A (ja) * | 2012-10-19 | 2019-02-28 | ザ・カウンシル・オヴ・ザ・クイーンズランド・インスティテュート・オヴ・メディカル・リサーチ | 改良されたヒトヘルペスウイルス免疫療法用タンパク質 |
JP2021036882A (ja) * | 2012-10-19 | 2021-03-11 | ザ・カウンシル・オヴ・ザ・クイーンズランド・インスティテュート・オヴ・メディカル・リサーチ | 改良されたヒトヘルペスウイルス免疫療法用タンパク質 |
JP7110302B2 (ja) | 2012-10-19 | 2022-08-01 | ザ・カウンシル・オヴ・ザ・クイーンズランド・インスティテュート・オヴ・メディカル・リサーチ | 改良されたヒトヘルペスウイルス免疫療法用タンパク質 |
US11896665B2 (en) | 2012-10-19 | 2024-02-13 | The Council Of The Queensland Institute Of Medical Research | Human herpesvirus immunotherapy |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5923373B2 (ja) | 免疫アジュバントの調製のための化合物 | |
JPH10507462A (ja) | エピポドフィロトキシンの水溶性誘導体、その製法、薬剤としてのその用途および抗癌治療におけるその意図的使用 | |
TW202136227A (zh) | 合成方法及中間體 | |
US8049023B2 (en) | Reagents and methods for the beta-keto amide synthesis of a synthetic precursor to immunological adjuvant E6020 | |
NO178729B (no) | Terapeutisk aktive sukkerderivater | |
CN117903223A (zh) | 一种二糖结构化合物及其制备方法与应用 | |
CN102443032A (zh) | 制备抗病毒组合物的方法及其中间体的应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131126 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140124 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140708 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160205 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20160219 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160418 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5923373 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |