CN1411800A - 化妆品组合物和方法 - Google Patents
化妆品组合物和方法 Download PDFInfo
- Publication number
- CN1411800A CN1411800A CN01137441A CN01137441A CN1411800A CN 1411800 A CN1411800 A CN 1411800A CN 01137441 A CN01137441 A CN 01137441A CN 01137441 A CN01137441 A CN 01137441A CN 1411800 A CN1411800 A CN 1411800A
- Authority
- CN
- China
- Prior art keywords
- pyridine
- oxoethyl
- cosmeceuticals
- bromination
- salt approved
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 58
- 238000000034 method Methods 0.000 title claims abstract description 44
- 239000002537 cosmetic Substances 0.000 title claims abstract description 42
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 436
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 229940123457 Free radical scavenger Drugs 0.000 claims abstract description 20
- 239000002516 radical scavenger Substances 0.000 claims abstract description 20
- 239000003112 inhibitor Substances 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims description 451
- 238000005893 bromination reaction Methods 0.000 claims description 392
- 230000031709 bromination Effects 0.000 claims description 335
- -1 formoxyl Chemical group 0.000 claims description 319
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 212
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 183
- 238000005660 chlorination reaction Methods 0.000 claims description 159
- 229910052757 nitrogen Inorganic materials 0.000 claims description 156
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 153
- 125000003963 dichloro group Chemical group Cl* 0.000 claims description 50
- 102000008186 Collagen Human genes 0.000 claims description 49
- 108010035532 Collagen Proteins 0.000 claims description 49
- 229920001436 collagen Polymers 0.000 claims description 49
- 230000032683 aging Effects 0.000 claims description 42
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 239000001301 oxygen Substances 0.000 claims description 33
- 150000003254 radicals Chemical class 0.000 claims description 32
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 23
- 239000003963 antioxidant agent Substances 0.000 claims description 23
- 235000006708 antioxidants Nutrition 0.000 claims description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 125000000950 dibromo group Chemical group Br* 0.000 claims description 21
- 230000000694 effects Effects 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 17
- QMHIMXFNBOYPND-UHFFFAOYSA-N 4MTO Natural products CC1=CSC=N1 QMHIMXFNBOYPND-UHFFFAOYSA-N 0.000 claims description 16
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
- SIPCFXFCVTUAID-UHFFFAOYSA-N 3-nitrothiophene Chemical compound [O-][N+](=O)C=1C=CSC=1 SIPCFXFCVTUAID-UHFFFAOYSA-N 0.000 claims description 14
- GZXDOXSIKJNUEW-UHFFFAOYSA-N 5-methylthiophene Chemical compound CC1=C=C[CH]S1 GZXDOXSIKJNUEW-UHFFFAOYSA-N 0.000 claims description 14
- 230000002101 lytic effect Effects 0.000 claims description 14
- 230000037303 wrinkles Effects 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 13
- 230000002829 reductive effect Effects 0.000 claims description 13
- 238000000354 decomposition reaction Methods 0.000 claims description 12
- XVJQABJQBJBPKG-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)OCCCC)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)OCCCC)=O XVJQABJQBJBPKG-UHFFFAOYSA-N 0.000 claims description 11
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 11
- 230000002441 reversible effect Effects 0.000 claims description 11
- BXACZVUJERBRTR-UHFFFAOYSA-N C(C)OC(=O)C1N(CCC1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O Chemical compound C(C)OC(=O)C1N(CCC1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O BXACZVUJERBRTR-UHFFFAOYSA-N 0.000 claims description 10
- GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 claims description 9
- FYBUJCUEKCGUGO-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC=C(C=C1)C(=O)NCCOCC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)C(CN1CC=C(C=C1)C(=O)NCCOCC1=CC=CC=C1)=O FYBUJCUEKCGUGO-UHFFFAOYSA-N 0.000 claims description 9
- ARFMRXJFWXXSDM-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC=C(C=C1)C(=O)NNS(=O)(=O)C)=O Chemical compound C1(=CC=CC=C1)C(CN1CC=C(C=C1)C(=O)NNS(=O)(=O)C)=O ARFMRXJFWXXSDM-UHFFFAOYSA-N 0.000 claims description 9
- 230000003796 beauty Effects 0.000 claims description 9
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 239000000865 liniment Substances 0.000 claims description 9
- 229940040145 liniment Drugs 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- MUBQMUFZUBNKGQ-UHFFFAOYSA-N propan-2-yl 2-[2-(2,4-dichlorophenyl)-2-oxoethyl]pyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CC=CN=C1CC(=O)C1=CC=C(Cl)C=C1Cl MUBQMUFZUBNKGQ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- ALUQMCBDQKDRAK-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazole Chemical compound C1C=CC=C2SCNC21 ALUQMCBDQKDRAK-UHFFFAOYSA-N 0.000 claims description 8
- 229910019142 PO4 Inorganic materials 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 claims description 8
- JIZRGGUCOQKGQD-UHFFFAOYSA-N 2-nitrothiophene Chemical compound [O-][N+](=O)C1=CC=CS1 JIZRGGUCOQKGQD-UHFFFAOYSA-N 0.000 claims description 7
- DPLUNUITYLQOJN-UHFFFAOYSA-N C(C)(C)NC(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O Chemical compound C(C)(C)NC(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O DPLUNUITYLQOJN-UHFFFAOYSA-N 0.000 claims description 7
- IYZXJIVKMUNKCW-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NCCO)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NCCO)=O IYZXJIVKMUNKCW-UHFFFAOYSA-N 0.000 claims description 7
- AIUOTABJGXUDCV-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NN)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NN)=O AIUOTABJGXUDCV-UHFFFAOYSA-N 0.000 claims description 7
- VASKIKREEIZOGO-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNC(=O)NC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNC(=O)NC1=CC=CC=C1)=O VASKIKREEIZOGO-UHFFFAOYSA-N 0.000 claims description 7
- FVRWQNRZSFXMRH-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNC1=CC=CC=C1)=O FVRWQNRZSFXMRH-UHFFFAOYSA-N 0.000 claims description 7
- QBMFXOZHMZHCSR-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O QBMFXOZHMZHCSR-UHFFFAOYSA-N 0.000 claims description 7
- ANVDRZYPSBEVON-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C1=CC=CC=C1)=O ANVDRZYPSBEVON-UHFFFAOYSA-N 0.000 claims description 7
- YRBYZBJAYRBXOX-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)CC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)CC1=CC=CC=C1)=O YRBYZBJAYRBXOX-UHFFFAOYSA-N 0.000 claims description 7
- ZNDGQPWLHZZQBY-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NNC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NNC1=CC=CC=C1)=O ZNDGQPWLHZZQBY-UHFFFAOYSA-N 0.000 claims description 7
- FPMFBSLEEJFSRN-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C1=CC=CC=C1)=O FPMFBSLEEJFSRN-UHFFFAOYSA-N 0.000 claims description 7
- XQCZGFHQDJISCB-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)CC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)CC1=CC=CC=C1)=O XQCZGFHQDJISCB-UHFFFAOYSA-N 0.000 claims description 7
- XCTUCGUUHXCYQY-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC=C(C=C1)C(=O)NNS(=O)(=O)C1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC=C(C=C1)C(=O)NNS(=O)(=O)C1=CC=CC=C1)=O XCTUCGUUHXCYQY-UHFFFAOYSA-N 0.000 claims description 7
- 239000004909 Moisturizer Substances 0.000 claims description 7
- OGCMJZXOPFGIDV-UHFFFAOYSA-N NN.C(=O)=C1CN(C=CC1)CC(=O)NC1CC1 Chemical compound NN.C(=O)=C1CN(C=CC1)CC(=O)NC1CC1 OGCMJZXOPFGIDV-UHFFFAOYSA-N 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 239000000499 gel Substances 0.000 claims description 7
- 230000001976 improved effect Effects 0.000 claims description 7
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 7
- 230000001333 moisturizer Effects 0.000 claims description 7
- 230000009759 skin aging Effects 0.000 claims description 7
- LCFKRYACWHZWJG-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)OC)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)OC)=O LCFKRYACWHZWJG-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 239000003974 emollient agent Substances 0.000 claims description 6
- 230000007760 free radical scavenging Effects 0.000 claims description 6
- 230000012010 growth Effects 0.000 claims description 6
- 229930192474 thiophene Natural products 0.000 claims description 6
- 208000012641 Pigmentation disease Diseases 0.000 claims description 5
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 5
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000003995 emulsifying agent Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 230000000474 nursing effect Effects 0.000 claims description 5
- 230000019612 pigmentation Effects 0.000 claims description 5
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 4
- 206010047141 Vasodilatation Diseases 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 239000003581 cosmetic carrier Substances 0.000 claims description 4
- 239000000839 emulsion Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 229920001296 polysiloxane Polymers 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 239000002562 thickening agent Substances 0.000 claims description 4
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 3
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical group OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 3
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 3
- 206010000496 acne Diseases 0.000 claims description 3
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 3
- 230000003444 anaesthetic effect Effects 0.000 claims description 3
- 230000003648 hair appearance Effects 0.000 claims description 3
- 239000005556 hormone Substances 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 3
- 150000002500 ions Chemical class 0.000 claims description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims description 3
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical group OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 claims description 3
- 230000002335 preservative effect Effects 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- 239000011719 vitamin A Substances 0.000 claims description 3
- 235000019155 vitamin A Nutrition 0.000 claims description 3
- 229940045997 vitamin a Drugs 0.000 claims description 3
- 208000001840 Dandruff Diseases 0.000 claims description 2
- 206010039792 Seborrhoea Diseases 0.000 claims description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 2
- 241000607479 Yersinia pestis Species 0.000 claims description 2
- 230000000202 analgesic effect Effects 0.000 claims description 2
- 239000000058 anti acne agent Substances 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 230000003712 anti-aging effect Effects 0.000 claims description 2
- 230000001387 anti-histamine Effects 0.000 claims description 2
- 230000002141 anti-parasite Effects 0.000 claims description 2
- 229940124340 antiacne agent Drugs 0.000 claims description 2
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 229940127219 anticoagulant drug Drugs 0.000 claims description 2
- 239000003429 antifungal agent Substances 0.000 claims description 2
- 229940121375 antifungal agent Drugs 0.000 claims description 2
- 239000000739 antihistaminic agent Substances 0.000 claims description 2
- 239000003096 antiparasitic agent Substances 0.000 claims description 2
- 239000002826 coolant Substances 0.000 claims description 2
- 230000004069 differentiation Effects 0.000 claims description 2
- 239000000686 essence Substances 0.000 claims description 2
- 239000003527 fibrinolytic agent Substances 0.000 claims description 2
- 206010020718 hyperplasia Diseases 0.000 claims description 2
- 150000002634 lipophilic molecules Chemical class 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000004530 micro-emulsion Substances 0.000 claims description 2
- 239000002674 ointment Substances 0.000 claims description 2
- 239000000049 pigment Substances 0.000 claims description 2
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 2
- 239000007921 spray Substances 0.000 claims description 2
- 150000003431 steroids Chemical class 0.000 claims description 2
- 229960000103 thrombolytic agent Drugs 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 5
- CWTISLMDUJNVDN-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NCCO)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NCCO)=O CWTISLMDUJNVDN-UHFFFAOYSA-N 0.000 claims 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 5
- 125000004188 dichlorophenyl group Chemical group 0.000 claims 5
- ZRBNETYZYOXTLS-UHFFFAOYSA-N ethyl 1,3-thiazolidine-4-carboxylate Chemical compound CCOC(=O)C1CSCN1 ZRBNETYZYOXTLS-UHFFFAOYSA-N 0.000 claims 5
- 206010040925 Skin striae Diseases 0.000 claims 3
- 208000031439 Striae Distensae Diseases 0.000 claims 3
- 206010042496 Sunburn Diseases 0.000 claims 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 2
- 230000001153 anti-wrinkle effect Effects 0.000 claims 2
- 206010013786 Dry skin Diseases 0.000 claims 1
- 230000002155 anti-virotic effect Effects 0.000 claims 1
- 230000037336 dry skin Effects 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 239000000516 sunscreening agent Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 157
- 238000001819 mass spectrum Methods 0.000 description 97
- 238000005160 1H NMR spectroscopy Methods 0.000 description 96
- 210000003491 skin Anatomy 0.000 description 62
- 102000004169 proteins and genes Human genes 0.000 description 38
- 108090000623 proteins and genes Proteins 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 230000003078 antioxidant effect Effects 0.000 description 22
- 230000013595 glycosylation Effects 0.000 description 20
- 238000006206 glycosylation reaction Methods 0.000 description 17
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 16
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 15
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 15
- 206010040954 Skin wrinkling Diseases 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 230000006378 damage Effects 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 102000016942 Elastin Human genes 0.000 description 12
- 108010014258 Elastin Proteins 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 102000016943 Muramidase Human genes 0.000 description 12
- 108010014251 Muramidase Proteins 0.000 description 12
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 12
- 229920002549 elastin Polymers 0.000 description 12
- 239000004325 lysozyme Substances 0.000 description 12
- 229960000274 lysozyme Drugs 0.000 description 12
- 235000010335 lysozyme Nutrition 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 11
- 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 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000008103 glucose Substances 0.000 description 11
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
- 239000011550 stock solution Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 241000700159 Rattus Species 0.000 description 9
- 238000004132 cross linking Methods 0.000 description 9
- 206010012601 diabetes mellitus Diseases 0.000 description 9
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 235000014113 dietary fatty acids Nutrition 0.000 description 8
- 239000000194 fatty acid Substances 0.000 description 8
- 229930195729 fatty acid Natural products 0.000 description 8
- 150000004665 fatty acids Chemical class 0.000 description 8
- 229960002163 hydrogen peroxide Drugs 0.000 description 8
- 235000000346 sugar Nutrition 0.000 description 8
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 230000009182 swimming Effects 0.000 description 7
- 238000002965 ELISA Methods 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 238000005336 cracking Methods 0.000 description 6
- 239000012467 final product Substances 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 5
- ISMDILRWKSYCOD-GNKBHMEESA-N C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O Chemical compound C(C1=CC=CC=C1)[C@@H]1NC(OCCCCCCCCCCCNC([C@@H](NC(C[C@@H]1O)=O)C(C)C)=O)=O ISMDILRWKSYCOD-GNKBHMEESA-N 0.000 description 5
- ZSPWIOMEYLOWLE-UHFFFAOYSA-N C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NCCCC)=O Chemical compound C1(=CC=CC=C1)NC(CN1CC(=CC=C1)C(=O)NCCCC)=O ZSPWIOMEYLOWLE-UHFFFAOYSA-N 0.000 description 5
- 229940126639 Compound 33 Drugs 0.000 description 5
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 5
- 229940125898 compound 5 Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000012545 processing Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 4
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 4
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 4
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 4
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 4
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 4
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229940127007 Compound 39 Drugs 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 102000005741 Metalloproteases Human genes 0.000 description 4
- 108010006035 Metalloproteases Proteins 0.000 description 4
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 4
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 4
- MXZNUGFCDVAXLG-CHWSQXEVSA-N [(2S)-1-[(2R)-3-methyl-2-(pyridine-4-carbonylamino)butanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@@H](NC(=O)c1ccncc1)C(=O)N1CCC[C@@H]1B(O)O MXZNUGFCDVAXLG-CHWSQXEVSA-N 0.000 description 4
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 108010055267 advanced glycation end products-bovine serum albumin Proteins 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 229940125904 compound 1 Drugs 0.000 description 4
- 229940126208 compound 22 Drugs 0.000 description 4
- 229940127573 compound 38 Drugs 0.000 description 4
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 150000007523 nucleic acids Chemical class 0.000 description 4
- 102000039446 nucleic acids Human genes 0.000 description 4
- 108020004707 nucleic acids Proteins 0.000 description 4
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 4
- 125000006327 phenyl hydrazinyl group Chemical group [H]N(*)N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 230000000171 quenching effect Effects 0.000 description 4
- 230000002000 scavenging effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 3
- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 3
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 3
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 3
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 3
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 3
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 3
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 3
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 3
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 3
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 3
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 3
- HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 229940126657 Compound 17 Drugs 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 239000004166 Lanolin Chemical class 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
- 239000005642 Oleic acid Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 102000019197 Superoxide Dismutase Human genes 0.000 description 3
- 108010012715 Superoxide dismutase Proteins 0.000 description 3
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 3
- IOSLINNLJFQMFF-XMMPIXPASA-N [(2R)-1-[[4-[[3-[(4-fluorophenyl)methylsulfanyl]phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound FC1=CC=C(CSC=2C=C(OCC3=CC=C(CN4[C@H](CCC4)CO)C=C3)C=CC=2)C=C1 IOSLINNLJFQMFF-XMMPIXPASA-N 0.000 description 3
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 3
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940126142 compound 16 Drugs 0.000 description 3
- 229940125833 compound 23 Drugs 0.000 description 3
- 229940125851 compound 27 Drugs 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 229940125878 compound 36 Drugs 0.000 description 3
- 229940125936 compound 42 Drugs 0.000 description 3
- 229940127271 compound 49 Drugs 0.000 description 3
- 229940126545 compound 53 Drugs 0.000 description 3
- 229940127113 compound 57 Drugs 0.000 description 3
- 229940125900 compound 59 Drugs 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000004744 fabric Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
- 235000019388 lanolin Nutrition 0.000 description 3
- 229940039717 lanolin Drugs 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 3
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 2
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 2
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 2
- IOQORVDNYPOZPL-VQTJNVASSA-N (5S,6R)-5-(4-chlorophenyl)-6-cyclopropyl-3-[6-methoxy-5-(4-methylimidazol-1-yl)pyridin-2-yl]-5,6-dihydro-2H-1,2,4-oxadiazine Chemical compound ClC1=CC=C(C=C1)[C@@H]1NC(=NO[C@@H]1C1CC1)C1=NC(=C(C=C1)N1C=NC(=C1)C)OC IOQORVDNYPOZPL-VQTJNVASSA-N 0.000 description 2
- SRKGZXIJDGWVAI-GVAVTCRGSA-M (e,3r)-7-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)C1=NC(C(C)(C)C)=CC(C=2C=CC(F)=CC=2)=C1\C=C\C(O)C[C@@H](O)CC([O-])=O SRKGZXIJDGWVAI-GVAVTCRGSA-M 0.000 description 2
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 2
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 2
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
- DASJDMQCPIDJIF-UHFFFAOYSA-N 2-bromo-1-(2,4-dichlorophenyl)ethanone Chemical class ClC1=CC=C(C(=O)CBr)C(Cl)=C1 DASJDMQCPIDJIF-UHFFFAOYSA-N 0.000 description 2
- RJWUMFHQJJBBOD-UHFFFAOYSA-N 2-methylheptadecane Chemical compound CCCCCCCCCCCCCCCC(C)C RJWUMFHQJJBBOD-UHFFFAOYSA-N 0.000 description 2
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 2
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 2
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- UAFDWPMBGYIREM-UHFFFAOYSA-N C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)OCCOCC1=CC=CC=C1)=O Chemical compound C1(=CC=CC=C1)C(CN1CC(=CC=C1)C(=O)OCCOCC1=CC=CC=C1)=O UAFDWPMBGYIREM-UHFFFAOYSA-N 0.000 description 2
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- QEFRNWWLZKMPFJ-ZXPFJRLXSA-N L-methionine (R)-S-oxide Chemical compound C[S@@](=O)CC[C@H]([NH3+])C([O-])=O QEFRNWWLZKMPFJ-ZXPFJRLXSA-N 0.000 description 2
- QEFRNWWLZKMPFJ-UHFFFAOYSA-N L-methionine sulphoxide Natural products CS(=O)CCC(N)C(O)=O QEFRNWWLZKMPFJ-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000012901 Milli-Q water Substances 0.000 description 2
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 2
- DCAHMIFHFFAXEC-UHFFFAOYSA-N N1(CCCC1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O Chemical compound N1(CCCC1)C(CN1CC(=CC=C1)C(=O)NNS(=O)(=O)C)=O DCAHMIFHFFAXEC-UHFFFAOYSA-N 0.000 description 2
- GZYZIKNPXCGGCQ-UHFFFAOYSA-N NN.C(=O)=C1CN(C=CC1)CC(=O)N1C(CCC1)C(=O)OCC Chemical compound NN.C(=O)=C1CN(C=CC1)CC(=O)N1C(CCC1)C(=O)OCC GZYZIKNPXCGGCQ-UHFFFAOYSA-N 0.000 description 2
- PRRKNKMOGYPOAV-UHFFFAOYSA-N NN.C(=O)=C1CN(C=CC1)CC(=O)NC(C)C Chemical compound NN.C(=O)=C1CN(C=CC1)CC(=O)NC(C)C PRRKNKMOGYPOAV-UHFFFAOYSA-N 0.000 description 2
- UBQCPDVZQZQXOA-UHFFFAOYSA-N NN.C(=O)=C1CN(C=CC1)CC(=O)O Chemical compound NN.C(=O)=C1CN(C=CC1)CC(=O)O UBQCPDVZQZQXOA-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 240000003186 Stachytarpheta cayennensis Species 0.000 description 2
- 235000009233 Stachytarpheta cayennensis Nutrition 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 2
- VJMAITQRABEEKP-UHFFFAOYSA-N [6-(phenylmethoxymethyl)-1,4-dioxan-2-yl]methyl acetate Chemical compound O1C(COC(=O)C)COCC1COCC1=CC=CC=C1 VJMAITQRABEEKP-UHFFFAOYSA-N 0.000 description 2
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 2
- 150000007513 acids Chemical group 0.000 description 2
- 108091006088 activator proteins Proteins 0.000 description 2
- 238000003483 aging Methods 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 210000001736 capillary Anatomy 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940125810 compound 20 Drugs 0.000 description 2
- 229940126086 compound 21 Drugs 0.000 description 2
- 229940125961 compound 24 Drugs 0.000 description 2
- 229940125846 compound 25 Drugs 0.000 description 2
- 229940127204 compound 29 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125807 compound 37 Drugs 0.000 description 2
- 229940126540 compound 41 Drugs 0.000 description 2
- 229940125844 compound 46 Drugs 0.000 description 2
- 229940126179 compound 72 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 201000010251 cutis laxa Diseases 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 2
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229960003966 nicotinamide Drugs 0.000 description 2
- 235000005152 nicotinamide Nutrition 0.000 description 2
- 239000011570 nicotinamide Substances 0.000 description 2
- 239000012875 nonionic emulsifier Substances 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 150000002926 oxygen Chemical class 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 230000037394 skin elasticity Effects 0.000 description 2
- 230000036548 skin texture Effects 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 210000000106 sweat gland Anatomy 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- 229940099259 vaseline Drugs 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
- ZPWIVSGEQGESFF-UHFFFAOYSA-N 2-chloro-n-cyclopropylacetamide Chemical compound ClCC(=O)NC1CC1 ZPWIVSGEQGESFF-UHFFFAOYSA-N 0.000 description 1
- VONWPEXRCLHKRJ-UHFFFAOYSA-N 2-chloro-n-phenylacetamide Chemical compound ClCC(=O)NC1=CC=CC=C1 VONWPEXRCLHKRJ-UHFFFAOYSA-N 0.000 description 1
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 241001116389 Aloe Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- KWELVGWTSMJQAC-UHFFFAOYSA-N C([ClH]CCCCCCCCCCCCCC)C=1SC=CC=1 Chemical compound C([ClH]CCCCCCCCCCCCCC)C=1SC=CC=1 KWELVGWTSMJQAC-UHFFFAOYSA-N 0.000 description 1
- JSAZLSQYDWRLNM-UHFFFAOYSA-N C1=CC=C(C=C1)COCCOC(=O)C2=CC=CC=N2 Chemical compound C1=CC=C(C=C1)COCCOC(=O)C2=CC=CC=N2 JSAZLSQYDWRLNM-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 102000006587 Glutathione peroxidase Human genes 0.000 description 1
- 108700016172 Glutathione peroxidases Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 241000208680 Hamamelis mollis Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 108010029165 Metmyoglobin Proteins 0.000 description 1
- 206010052641 Mitochondrial DNA mutation Diseases 0.000 description 1
- QVXYFZRZPFBWGF-UHFFFAOYSA-N N-(2-phenylmethoxyethyl)pyridine-2-carboxamide Chemical compound C(C1=CC=CC=C1)OCCNC(=O)C1=NC=CC=C1 QVXYFZRZPFBWGF-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- ZSEMWHCVIJETNE-UHFFFAOYSA-N N1=CC=CC2=CC(=C3C=CC=NC3=C12)S(=O)(=O)O.C(C)N1CSC2=C1C=CC=C2 Chemical compound N1=CC=CC2=CC(=C3C=CC=NC3=C12)S(=O)(=O)O.C(C)N1CSC2=C1C=CC=C2 ZSEMWHCVIJETNE-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- RXMCQRRJTRNHGL-UHFFFAOYSA-N O1C=CC=C1.C(C)(=O)Br Chemical class O1C=CC=C1.C(C)(=O)Br RXMCQRRJTRNHGL-UHFFFAOYSA-N 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 230000002292 Radical scavenging effect Effects 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000028990 Skin injury Diseases 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 206010048222 Xerosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000012874 anionic emulsifier Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GNNALEGJVYVIIH-UHFFFAOYSA-N benzene-1,2-diamine;hydrochloride Chemical class Cl.NC1=CC=CC=C1N GNNALEGJVYVIIH-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- CDQSJQSWAWPGKG-UHFFFAOYSA-N butane-1,1-diol Chemical compound CCCC(O)O CDQSJQSWAWPGKG-UHFFFAOYSA-N 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000001827 citrus limon l. burm. f. peel extract Substances 0.000 description 1
- 230000011382 collagen catabolic process Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 229960003067 cystine Drugs 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- STORWMDPIHOSMF-UHFFFAOYSA-N decanoic acid;octanoic acid;propane-1,2,3-triol Chemical compound OCC(O)CO.CCCCCCCC(O)=O.CCCCCCCCCC(O)=O STORWMDPIHOSMF-UHFFFAOYSA-N 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229940099371 diacetylated monoglycerides Drugs 0.000 description 1
- 229960005215 dichloroacetic acid Drugs 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- GPLRAVKSCUXZTP-UHFFFAOYSA-N diglycerol Chemical compound OCC(O)COCC(O)CO GPLRAVKSCUXZTP-UHFFFAOYSA-N 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000002196 ecbolic effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000007046 ethoxylation reaction Methods 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009432 framing Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 210000003780 hair follicle Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- MGIYRDNGCNKGJU-UHFFFAOYSA-N isothiazolinone Chemical compound O=C1C=CSN1 MGIYRDNGCNKGJU-UHFFFAOYSA-N 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 229940092251 lemon peel extract Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LAQFLZHBVPULPL-UHFFFAOYSA-N methyl(phenyl)silicon Chemical compound C[Si]C1=CC=CC=C1 LAQFLZHBVPULPL-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- ABIOGKAAZUBZJE-UHFFFAOYSA-N n'-(benzenesulfonyl)pyridine-2-carbohydrazide Chemical compound C=1C=CC=NC=1C(=O)NNS(=O)(=O)C1=CC=CC=C1 ABIOGKAAZUBZJE-UHFFFAOYSA-N 0.000 description 1
- SMNVYDVFDKEASB-UHFFFAOYSA-N n'-benzoylpyridine-2-carbohydrazide Chemical compound C=1C=CC=CC=1C(=O)NNC(=O)C1=CC=CC=N1 SMNVYDVFDKEASB-UHFFFAOYSA-N 0.000 description 1
- LVUQQDQCBUMCFJ-UHFFFAOYSA-N n'-methylsulfonylpyridine-2-carbohydrazide Chemical compound CS(=O)(=O)NNC(=O)C1=CC=CC=N1 LVUQQDQCBUMCFJ-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical class FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000007981 phosphate-citrate buffer Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004886 process control Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 150000005839 radical cations Chemical class 0.000 description 1
- 239000012048 reactive intermediate Substances 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 230000037075 skin appearance Effects 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 230000037067 skin hydration Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 1
- LUPNKHXLFSSUGS-UHFFFAOYSA-M sodium;2,2-dichloroacetate Chemical compound [Na+].[O-]C(=O)C(Cl)Cl LUPNKHXLFSSUGS-UHFFFAOYSA-M 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 230000010148 water-pollination Effects 0.000 description 1
- 229940118846 witch hazel Drugs 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/52—Stabilizers
- A61K2800/522—Antioxidants; Radical scavengers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Toxicology (AREA)
- Addiction (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
Abstract
本发明涉及一类新的吡啶鎓化合物,它们具有AGE裂解剂,AGE抑制剂和自由基清除剂三重功效;本发明还涉及含此类化合物以及化妆品用载体的化妆品组合物。本发明还涉及所述化妆品组合物的使用方法。
Description
发明领域
本发明涉及一类新的吡啶鎓衍生化合物,他们具有清除自由基,裂解AGE和抑制AGE形成的三重功能,本发明还涉及含有此类化合物的化妆品组合物,所述组合物能够阻止并逆转因皮肤蛋白质高度糖基化终产物(AGE)不断积累和通过自由基作用发生的光损伤而引起的皮肤衰老进程。本发明还涉及将含本发明化合物的本发明化妆品组合物用于皮肤的方法。
参考文献
本发明的技术背景参见以下文献:
1.Boni R,Burg G:衰老中的皮肤:生理学基础,预防手段和治疗方式。Schweiz Med Wochenschr(2000)Sep.9;130(36):1271-8。
2.Odetti P,Aragno I,等:高度糖基化终产物在胶原蛋白衰老中的作用。扫描强制显微镜(Scanning Force Microscope)研究。老年学(1988);44(4):187-91。
3.Pugliese PT:皮肤的抗氧化系统。皮肤护理学(1998)Dec.10(6):401-16;quiz417-18。
4.Calabrese V,Scapagnini G等:皮肤生物表面的氧化性应激和抗氧化剂:一种能够抑制对皮肤的氧化性损伤的新抗氧化形式柠檬油。药物实验临床研究(1999);25(6):281-7。
5.Berneburg M,Plettenberg H,Krutmann J:人皮肤的光老化。光学免疫学和光学医学(2000)Dec.16(6):238-44
6.Masaki H,Okano Y,Sakurai H:高度糖基化终产物(AGE)在紫外线A(UVA)下活性氧类的产生。生物化学和生物物理学研究通讯(1997)Jun.18:235
7.Hitoshi Masaki,Yuri Okano,Hiromu Sakurai:高度糖基化终产物(AGE)在紫外线A(UVA)下活性氧类的产生,以及一种可能的细胞伤害机制。生物化学和生物物理学学报(1482)(1999)45-56
技术背景
皮肤健康、有弹性和年轻,在众多因素中,取决于几种重要的生物分子。它们是胶原蛋白和弹性蛋白。胶原蛋白形成结构框架,支持着其他皮肤结构。它赋予皮肤强度和耐力。象其他蛋白质一样,胶原蛋白由氨基酸构成。然而,它特别富含几种特殊的氨基酸:脯氨酸、羟基脯氨酸、赖氨酸和甘氨酸。弹性蛋白也是一种蛋白质,它比胶原蛋白更具拉伸性,有助于维持皮肤弹性。它含有两种特殊氨基酸:锁链赖氨酸和异锁链赖氨酸。当弹性蛋白和胶原蛋白都缺乏或受损时,皮肤就会在拉伸或折叠后变形,产生多见于老化过程的皱纹和面部松弛。
大多数现代衰老理论的中心论点是,衰老相关性退化的主要原因是细胞组分的结构性和功能性改变。目前流行的假设是自由基、糖基化或Maillard衰老理论。第一个假设认为,衰老是自由基损伤细胞组分的结果。“自由基”指外轨道有一个非配对电子或称孤电子的不稳定分子,它会无选择性与其他分子反应,从而造成脂类、DNA和蛋白质损伤。后一种假设认为衰老的主要原因是,非酶促糖基化和Maillard反应诱导大分子改性,从而形成高度糖基化终产物(AGE),继而造成细胞损伤。非酶促糖基化作用即糖与蛋白质化学连接,最终引起不可逆性蛋白质交联。虽然以上假设的产生是彼此独立的,但它们提示:实际上,自由基、糖基化和Maillard可能代表了一个单一的、更复杂的生物化学路径的部分相互作用的因素,而衰老相关性退化则是由以上三种假设同时及相互作用所致损伤的总和造成的。
皮肤是一种高度分化的复杂结构器官,当受到UV辐照时尤其容易受到自由基损伤,引起皮肤上的AGE积累,同时单线态氧和超氧化物自由基产量增加,从而损伤胶原蛋白和弹性蛋白等重要的皮肤分子。此时,由自由基清除作用形成的抗氧化环境势必使皮肤能够抵抗损伤而维持其正常的弹性和完整性。
因此,本发明主要涉及一种活性分子在化妆品中的应用,该分子能够逆转AGE交联,通过其AGE裂解作用和自由基猝灭作用在组织中形成抗氧化环境,从而显著延缓老化表现。
皮肤是人体最大的器官,占体重约15%。就其化学组成而言,皮肤的约70%为水,25%为蛋白质,2%为脂类。其余为微量矿物质、核酸、糖基氨基聚糖(glycosoaminoglyean),蛋白聚糖和多种其他化学物质。
皮肤主要包括3层:表皮,真皮和皮下组织。表皮是与外界的第一道屏障。这一层包括3种细胞:角质细胞,黑素细胞和郎氏细胞。真皮是皮肤的中间层,也是最厚的一层,含有紧致、强健的胶原蛋白(I型和III型)网络,以及弹性蛋白纤维,它们都是重要的皮肤蛋白。真皮还包含成纤维细胞、毛细血管、淋巴结、脂肪腺、汗腺和毛囊。皮下组织是皮肤的最内层,主要含脂肪细胞,起着吸震和绝热的作用,保护其下面的组织不受低温和机械伤害。
衰老是一种生物学现象,表现为皱纹和皮肤松弛。随着人的衰老,皮肤细胞分裂减缓,内层皮肤,或真皮,开始变薄。真皮下的脂肪细胞开始萎缩,再下面的支撑表层的弹性蛋白和胶原蛋白纤维网开始松懈。皮肤弹性下降;当受压时不再能弹回原位,而是松弛和形成皱纹。皮肤的保湿能力下降;汗腺和油脂分泌腺开始萎缩,使得皮肤失去了保护性的水-脂乳液。结果,皮肤变干、起屑。此外,皮肤的自我修复能力也随年龄而丧失,因此,创伤愈合变慢。由于持续的小肌肉收缩,开始出现皱眉线(眉毛之间)和鱼尾纹(自眼角发散开来)。习惯性脸部表情也会形成特征性皱纹,重力则使上述情况进一步恶化,导致下颚垂肉和眼睑下垂。由于皮肤是最容易暴露年龄的器官,皱纹、弹性组织变性和老年性干燥症的生理学和恢复越来越受到重视。皮肤衰老是一种复杂的现象,主要包括遗传性内在因素和外部衰老因素(1)。
主要有两个生物学上彼此独立的衰老过程同时发生,从而造成了皮肤衰老时的主要改变:
1.外部衰老或光衰老/外部因素和
2.内部衰老/内部因素
外部衰老或光衰老产生于皮肤遭受紫外线(UV)辐照、化学物质污染、过敏原、机械损伤等因素时。外部因素主要来自日晒中的紫外线。
内部因素通过缓慢的、不可逆的组织退化作用作用于皮肤。造成内部衰老的因素有遗传、神经(压力)、免疫、激素紊乱等。内部衰老可能表现于身体的整个表面,包括未受到太阳紫外线辐照的皮肤。前述糖基化作用在内部衰老中起着重要作用。真皮中的蛋白质即弹性蛋白和胶原蛋白与机体内的糖(特别是葡萄糖)反应,造成胶原蛋白纤维彼此黏结,并引起自由基合成。这引起了皮肤结构的改变,降低了柔性,变得更僵硬。因此,脸部皮肤最明显的改变来自内部和外部衰老过程的综合作用。
基本说来,自由基和AGE形成两大因素是最主要的皮肤皱纹催生剂。早在1912年,Maillard发现葡萄糖和核糖等还原糖会与蛋白质发应形成棕色色素,于是产生了Maillard衰老理论。Maillard反应由一系列复杂反应构成,其中,还原糖与蛋白质的氨基反应引起蛋白质交联,形成稳定的Amadori产物,该产物继续交联形成高度糖基化终产物(AGE)。具有重要生物学意义的另一特点是,即使没有游离葡萄糖,Amadori产物也会继续交联和聚合。蛋白质交联的重要性在于是其造成了真皮中的深层皱纹。AGE交联的形成也是衰老等所有蛋白质衰老严重致害过程固有的一部分。在衰老过程中,还原糖与弹性蛋白和胶原蛋白等皮肤支持蛋白质化学结合,使它们逐渐变硬,更新减缓。这种糖与胶原蛋白和弹性蛋白的非特异性、非酶促结合引起AGE的形成,即使没有游离葡萄糖存在,AGE也能继续交联和聚合。扫描强制显微镜(scanning force microscope)对AGE在胶原蛋白衰老中作用的研究发现,在大龄大鼠中,随着AGE浓度的升高,可观察到胶原蛋白纤维明显的结构变化(2)。结果,该衰老过程造成胶原蛋白弹性丧失,皮肤皱纹产生。
仅仅是葡萄糖与蛋白质氨基的共价结合尚不足以说明所看到的胶原蛋白结构改变。葡萄糖氧化和糖基化蛋白质氧化产生的氧自由基可能也直接参与了AGE形成和胶原蛋白交联。体外研究显示,胶原蛋白的高度糖基化和交联必需有氧存在。已证明,抗氧化环境和自由基清除剂可抑制或减缓AGE形成和胶原蛋白交联。还已知,自由基清除剂对于保护表皮免受环境和内源性因素产生的自由基造成的损伤致关重要(3)。
皮肤具有高度分化的复杂有序结构,特别容易因接触氧等环境刺激而受到自由基的伤害(4)。研究证明,UV辐照能增加胶原蛋白、弹性蛋白等其他皮肤蛋白质上AGE的形成。通过增加皮肤上的AGE积累,同时增加单线态氧和超氧化物的产生,造成对皮肤蛋白质的损伤,由此形成了一个恶性循环。
近年来,在揭示光老化内在机制方面已获得了实质性的进展。最近已发现,活化剂蛋白质(AP)-1和核因子(NF)-kB活化以及线粒体DNA突变会诱导基质金属蛋白酶(5)。在糖基化早期,葡萄糖等还原糖与蛋白质氨基的缩合可产生UVA光照产生的单线态氧自由基。据报道,AGE是促进皮肤光老化的重要因素之一,因其可产生O2 -,H2O2和-OH等活性氧类(6)。体外成纤维细胞研究提出了一种可能的机制:AGE在UVA辐照下产生O2 -,H2O2和-OH等活性氧类,OH则具有促进细胞损伤的作用(7)。这些自由基通过刺激皮肤细胞合成金属蛋白酶打破了皮肤的自然平衡。金属蛋白酶降解胶原蛋白,但不合成抑制皮肤蛋白降解的抗金属蛋白酶(这本是一种正常的生物反应)。单线态氧诱导的这种失衡即金属蛋白酶产生多于抗金属蛋白酶造成了皮肤胶原蛋白和弹性蛋白的降解。然后,受损胶原蛋白基质愈合不良,弹性组织变性物质积累,结果造成皮肤松弛和皱纹。
AGE受UVA辐照会增强超氧化物阴离子的产生。这是通过细胞电子转移链完成的,其中,UVA-AGE能增强了电子向基态氧的传递。继而增强了三磷酸腺苷(ATP)合成中超氧化物阴离子的形成。超氧化物歧化酶可将超氧化物阴离子转化为过氧化氢和氧。最后,铁和铜催化过氧化氢转化为毒性的羟基自由基,引起皮肤胶原蛋白和弹性蛋白降解,其后是创伤愈合不良和太阳斑形成,由此造成了皮肤的光老化。
目前化妆品市场上充斥的是针对外部老化的产品,但还没有通过抑制皮肤支持蛋白内AGE形成来针对内部老化的产品。
本发明化合物抑制高度糖基化终产物形成(在胶原蛋白等皮肤支持蛋白内)的能力与AGE裂解能力和自由基清除活性使得所述化合物在抗皮肤老化和皱纹等方面具有重大的应用潜力。因此,用这些分子可以避免皮肤老化痕迹,皱纹形成等,以及用于美容。
已知,即使给予皮肤良好的护理,仍会发生皮肤老化和形成皱纹。因此,需要一种物质来预防或治疗因AGE形成引起的皮肤老化。本发明的化合物不是肽,它们能够改变胶原蛋白和弹性蛋白内AGE交联键的形成。本发明化合物可与其他物质一同配制成化妆品制剂。
为了避免或延缓皮肤皱纹,抑制AGE形成,逆转已形成的AGE,同时通过抗氧化剂或自由基清除剂降低氧化性应激非常重要。从本质上说,能够抑制AGE形成,裂解AGE并能够减缓AGE形成,避免胶原蛋白降解的分子将是理想的候选治疗性化妆品。本发明的分子同时具有AGE抑制剂,强AGE裂解剂和自由基清除剂特性,使得它们最适合用于美容。
自由基是在其原子结构中有一个或多个非配对电子的原子或分子,因而极具反应性。哺乳动物系统的正常代谢过程不断产生自由基—反应性氧类(ROS)。ROS的外源性来源包括运动、污染(尤其是吸烟和汽车尾气)、酒精、日晒和药物(例如麻醉剂)。虽然自由基对于正常生理机制具有重要意义,其过量产生则会造成氧化性应激—这一术语通常用来描述对蛋白质、脂类和核酸等重要生物分子的氧化性损伤结果。蛋白质一直被认为容易被ROS氧化。胱氨酸等芳族氨基酸和二硫键特别容易受影响。所有生物物质都含有各种多不饱和脂肪酸,它们主要位于膜脂类中。它们极易受到ROS的破坏。
所谓抗氧化剂类化合物(又称“自由基清除剂”)是主要的抗氧化性应激防御机制。这些化合物的作用在于保护细胞膜和细胞组分不受ROS的损害。避免新自由基形成的主要抗氧化剂包括超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH Px)等酶系统。次级抗氧化剂捕捉自由基,从而避免链反应,这包括维生素E、维生素C、牛磺酸和β-胡萝卜素等营养素。抗氧化的最后一道防线是修复系统,例如甲硫氨酸亚砜(methionine sulfoxide)还原酶,它能够再生氧化蛋白质内的甲硫氨酸残基,并恢复其功能。
本发明涉及能够裂解蛋白质交联的分子。此外,它们还具有强抗氧化活性,这使得它们最适用于各种化妆品。
本发明申请人的相关中国专利申请01l112413.X,99814055.4和01112413.X显示了本发明吡啶鎓化合物的AGE裂解活性。已知,这些化合物还是良好的自由基清除剂,因而在作为AGE抑制剂之外还具有抗氧化活性。本发明化合物的AGE裂解,AGE抑制和自由基清除三重活性使它们最适用于美容用途。
发明概述
本发明目的之一是提供一类新的化合物,它们的同一分子具有a)自由基清除活性,b)AGE裂解活性和c)AGE抑制活性。
本发明目的之二是提供一种含上述化合物作为活性成分的化妆品组合物。
本发明目的之三是提供制造上述化妆品组合物的方法。
本发明目的之四是提供本发明化妆品组合物的美容使用方法。
为此,本发明提供了在化妆品用载体中包含有效量结构式I化合物或其化妆品学上认可的盐的化妆品组合物,所述化合物或其盐具有自由基清除活性,AGE裂解活性和AGE抑制活性:
其中,R1是-R4-R5或-N(R7)N(R7)R9和Y-R11;
R4选自-N(R7)R6O-,-N(R7)R6N(R7)-,-OR6O和-OR6N(R7)-,其中的R6是烃基;
其中R7选自H,烃基,包括杂芳基的芳基,同一化合物中R1和R3的R7可以相同或不同;
R2选自F,Cl,Br,I,OR7,NO2,烃基,包括杂芳基的芳基,甲酰基,酰基,C(O)NR7R10,C(O)OR7,NR7R10,N=C(R7)(R10),SR7,SO2NH2,SO2烃基和SO2芳基;
m是0,1或2;
R3选自R7,OR7,N(R7)(R10),N=C(R7)(R10),N(R7)N(R7)(R10),N(R7)N=C(R7)(R10)和CH(R7)C(O)R8,其中的R8选自R7,OR7和NR7R10;
R9选自H,烃基,包括杂芳基的芳基,C(O)R10,-SO2R10,-C(S)NHR10,-C(NH)NH(R10)和-C(O)NHR10;
R10选自H,烃基,包括杂芳基的芳基,如果同一化合物R1和R3的R10可以相同或不同,则R10与R7可以相同或不同;
Y选自O,NH,NR12,或者不存在,
R11和R12各自选自H,烃基和芳基。
X选自卤离子,乙酸根离子,高氯酸根离子,磺酸根离子,草酸根离子,柠檬酸根离子,甲苯磺酸根离子,马来酸根离子,甲磺酸根离子,碳酸根离子,亚硫酸根离子,磷酸氢根离子,膦酸根离子,磷酸根离子,BF4 -和PF6 -;
条件是:
1.当两烃基位于同一碳原子或氮原子上时,它们可以彼此连接成环结构;
2.如果R10杂芳环上含有氮原子,则它可以是季氮原子;
3.当R3是OR7且R1是-NHNH2时,R7不是烃基,而且
4.当R3是OR7,R1是N(R7)(NR7)R9且R9是C(O)R10,其中的是R10是烃基时,R7不是H。
本发明中,“烃基”表示可被取代的、通过碳碳键相连的、具有1-8个碳原子的烃基,或具有1或2个选自O、N和S杂原子的杂脂环。所述烃基可以呈线性、分支或环状,饱和或不饱和。取代基可选自F,Cl,Br,NSO芳基和I。最好不超过三取代。
本发明中,“芳基”表示可被取代的芳香族集团,含至多2环共轭或稠合的环系统,其中至少一环具有π电子系统。所述芳基包括碳环芳基,杂芳基和二芳基,以上都可以被取代。取代基可选自F,Cl,Br,I,N,S,O和直链或支链C1-C6烃基。
本发明还提供了一种上述化妆品组合物的美容使用方法。
附图简述
图1和图2显示本发明化合物的AGE抑制活性。
图1是化合物5,33和对照的SDS-PAGE(十二烷基硫酸钠-聚丙烯酰胺凝胶电泳)结果。
图2显示溶菌酶二聚体(峰1)和三聚体(峰2)形成与对照相比的程度,这是根据SDS-PAGE上各条带的光密度(OD)所做的图。
本发明的详细描述
表1A中是结构通式I中m是0或1,-COR1在3位的可用于本发明组合物的AGE裂解剂/抑制剂兼自由基清除剂化合物;表1B中是结构通式I中m是0,-COR1在4位的本发明化合物。以下是结构通式I所示化合物的代表性举例,而非本发明的限定:
二溴-N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)-吡啶鎓]肼(化合物1)
二溴-N,N′-二[3-羰基-1-(2-乙氧基-2-氧代乙基)-吡啶鎓]肼(化合物2)
二溴-N,N′-二[3-羰基-1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-吡啶鎓]肼(化合物3)
溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓(化合物4)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物5)
二溴-N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼(化合物6)
溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物7)
溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物8)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓(化合物9)
溴化1-(2-苯基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓(化合物10)
溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓(化合物11)
溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物12)
溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物13)
溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓(化合物14)
溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓(化合物15)
溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基羰基)吡啶鎓(化合物16)
溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓(化合物17)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物18)
溴化1-(2-乙氧基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓(化合物19)
氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓(化合物20)
溴化1-(2-乙氧基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓(化合物21)
溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓(化合物22)
氯化1-(2-苯基氨基-2-氧代乙基)-3-((苯甲酸基)乙基氨基羰基)吡啶鎓(化合物23)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓(化合物24)
溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓(化合物25)
氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓(化合物26)
氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓(化合物27)
溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓(化合物28)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓(化合物29)
溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓(化合物30)
溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓(化合物31)
二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼(化合物32)
二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼(化合物33)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-(1-氧-3-环己基)-乙基)-肼基羰基)-吡啶鎓(化合物34)
溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-乙基}肼基羰基)吡啶鎓(化合物35)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物36)
氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物37)
溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)-吡啶鎓(化合物38)
二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼(化合物39)
氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)-吡啶鎓(化合物40)
二氯N,N′-二[3-羰基-1-(2-异丙基氨基-2-氧代乙基)吡啶鎓]肼(化合物41)
氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基(pyridoyl))肼基羰基)-吡啶鎓(化合物42)
氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓(化合物43)
氯化1-(2-(1-吡咯烷基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物44)
氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-吡啶鎓(化合物45)
二氯N,N′-二[3-羰基-1-(2-羟基-2-氧代乙基)吡啶鎓]肼(化合物46)
氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)-5-溴吡啶鎓(化合物47)
氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基)肼基吡啶鎓(化合物48)
二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼(化合物49)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓(化合物50)
氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物51)
氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物52)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-5-溴吡啶鎓(化合物53)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓(化合物54)
溴化1-(2-(5-氯噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物55)
二氯N,N′-二[3-羰基-1-(2-(4-硝基噻吩-2-基)-2-氧代乙基)吡啶鎓]肼(化合物56)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基吡啶鎓(化合物57)
二氯N,N′-二[3-羰基-1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)吡啶鎓]肼(化合物58)
二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼(化合物59)
二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼(化合物60)
氯化1-(2-(4-乙酯基(carboethoxy)-噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物61)
二氯N,N′-二[3-羰基-1-(2-(5-氯噻吩-2-基)-2-氧代乙基)吡啶鎓]肼(化合物62)
氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物63)
溴化1-(2-(4-硝基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物64)
氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物65)
氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物66)
氯化1-(2-(5-硝基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物67)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)吡啶鎓(化合物68)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物69)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓(化合物70)
溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓(化合物71)
溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲基苯磺酰基肼基羰基)吡啶鎓(化合物72)
溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓(化合物73)
氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓(化合物74)
溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓(化合物75)
溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物76)
溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物77)
溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物78)
溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓(化合物79)
溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物80)
溴化1-(2-乙氧基-2-氧代乙基)-4-(对甲磺酰基肼基羰基)吡啶鎓(化合物81)
溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)-吡啶鎓(化合物82)
溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)-吡啶鎓(化合物83)
溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓(化合物84)
溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓(化合物85)
溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓(化合物86)
溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物87)
溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓(化合物88)
氯化1-(2-氧丙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物89)
溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物90)
溴化1-(2-(2′,4′-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓(化合物91)
溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓(化合物92)
氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓(化合物93)
氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓(化合物94)
氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物95)
溴化1-(2-(2,4-二氯苯基)-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓(化合物96)
溴化1-(2-(2,4-二氯苯基)-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓(化合物97)
溴化1-(2-苯基-2-氧代乙基)-3-(1-苯基-1-氧甲基)吡啶鎓(化合物98)
溴化1-(2-苯基-2-氧代乙基)-3-(甲氧基羰基)吡啶鎓(化合物99)
表1A-代表性吡啶鎓衍生物
(m为0或1,-COR1在3位)
化合物号 | R1 | m | -R2 | -R3 | -X |
1 | 结构(a) | 0 | - | -Ph | Br |
2 | 结构(b) | 0 | - | OEt | Br |
3 | 结构(c) | 0 | - | 2,4-二氯苯基 | Br |
4 | NHNH-(2-吡啶基) | 0 | - | OEt | Br |
5 | NHNHSO2CH3 | 0 | - | 2-噻吩基 | Br |
6 | 结构(d) | 0 | - | 2-噻吩基 | Br |
7 | NHCH2CH2OCOPh | 0 | - | OEt | Br |
8 | NHCH2CH2OCOPh | 0 | - | 2,4-二氯苯基 | Br |
9 | NHNH-(2-吡啶基) | 0 | - | 2-噻吩基 | Br |
10 | NHNH-(2-吡啶基) | 0 | - | -Ph | Br |
11 | NHNH2 | 0 | - | -Ph | Br |
12 | NHNHSO2CH3 | 0 | - | -Ph | Br |
13 | NHNHSO2CH3 | 0 | - | OEt | Br |
14 | NHNH-SO2Ph | 0 | - | -Ph | Br |
15 | NHNH-SO2Ph | 1 | 2-Cl | -Ph | Br |
16 | OCH2CH2OCOCH3 | 0 | - | -Ph | Br |
17 | OCH2CH2OCOPh | 0 | - | OEt | Br |
21 | -NHNH-SO2Ph | 0 | - | OEt | Br |
22 | -OCH2CH2OCH3 | 0 | - | 2,4-二氯苯基 | Br |
23 | -OCH2CH2OCOPh | 0 | - | -NHPh | CI |
24 | -NHNHCONHPh | 0 | - | 2-噻吩基 | Br |
25 | NHCH2CH2OCOCH3 | 0 | - | -Ph | Br |
26 | NHNHSO2Ph | 0 | - | -NHPh | CI |
27 | NHNHSO2Ph(4-CH3) | 0 | - | -NHPh | CI |
28 | OCH2CH2OCOPh | 0 | - | -Ph | Br |
29 | NHNHCOPh | 0 | - | 2-噻吩基 | Br |
30 | NHNHSO2CH2Ph | 0 | - | OEt | Br |
31 | NHNHSO2CH2Ph | 0 | - | -Ph | Br |
32 | 结构(e) | 0 | - | 2-呋喃基 | Br |
33 | 结构(f) | 0 | - | 2-噻吩基 | Cl |
34 | NHNHCOCH2CH2-环己基 | 0 | - | 2-噻吩基 | Br |
35 | NHNHCOCH2CH2-环己基 | 0 | - | -NHPh | Cl |
36 | NHCH2CH2OCO-Ph | 0 | - | 2-噻吩基 | Br |
37 | NHCH2CH2OCO-Ph | 0 | - | CH2CO2-乙基 | Cl |
38 | -NHCH2CH2OCH3 | 0 | - | -2,4-二氯苯基 | Br |
39 | 结构(g) | 0 | - | NH-环丙基 | Cl |
40 | -NHCH2CH2OCH3 | 0 | - | NH-环丙基 | Cl |
41 | 结构(h) | 0 | - | NH-异丙基 | Cl |
42 | 结构(i) | 0 | - | 2-噻吩基 | Cl |
43 | NHNHSO2CH3 | 0 | - | NH-异丙基 | Cl |
44 | NHNHSO2CH3 | 0 | - | 1-吡咯烷基 | Cl |
45 | NHNHSO2CH3 | 0 | - | 2-噻吩基 | Cl |
46 | 结构(j) | 0 | - | -OH | Cl |
47 | NHCH2CH2OCH3 | 0 | - | 2-噻吩基 | Cl |
48 | 结构(k) | 0 | - | 2-噻吩基 | Cl |
49 | 结构(l) | 0 | - | 2-噻吩基 | Cl |
50 | -NHNHSO2异丙基 | 0 | - | 2-噻吩基 | Br |
51 | -NHNHSO2CH3 | 0 | - | 结构(m) | Cl |
52 | -NHNHSO2CH3 | 0 | - | 结构(n) | Cl |
53 | -NHNHSO2CH3 | 1 | 5-Br | 2-噻吩基 | Br |
54 | -NHNHSO2C2H5 | 0 | - | 2-噻吩基 | Br |
55 | -NHNHSO2CH3 | 0 | - | 5-氯-2-噻吩基 | Br |
56 | 结构(o) | 0 | - | 4-硝基-2-噻吩基 | Cl |
57 | -NHNHSO2CH3 | 1 | 6-甲基 | 2-噻吩基 | Br |
58 | 结构(p) | 0 | - | 5-甲基-2-噻吩基 | Cl |
59 | 结构(q) | 0 | - | 结构(n) | Cl |
60 | 结构(r) | 0 | - | 2-噻吩基 | Cl |
61 | -NHNHSO2CH3 | 0 | - | 结构(s) | Cl |
62 | 结构(t) | 0 | - | 5-氯-2-噻吩基 | Cl |
63 | -NHNHSO2CH3 | 0 | - | 5-甲基-2-噻吩基 | Cl |
64 | -NHNHSO2CH3 | 0 | - | 4-硝基-2-噻吩基 | Br |
65 | -NHNHPh | 0 | - | -NHPh | Cl |
67 | -NHNHSO2CH3 | 0 | - | 5-硝基-2-噻吩基 | Cl |
68 | -NHNHSO2CH3 | 0 | - | 2-噻吩基 | Br |
69 | -NHNHPh | 0 | - | 2-噻吩基 | Br |
70 | -NHNHSO2-4-甲氧基苯基 | 0 | - | 2-噻吩基 | Br |
71 | -NHNHCONHPh | 0 | - | OEt | Br |
72 | -NHNHSO2-4-甲基苯基 | 0 | - | OEt | Br |
73 | -NHNHCONHPh | 0 | - | -Ph | Br |
74 | -NHNHSO2CH2Ph | 0 | - | -NHPh | Cl |
76 | -NHNHPh | 0 | - | -Ph | Br |
78 | -NHNHPh | 0 | - | OEt | Br |
79 | -NHNHSO2-4-甲氧基苯基 | 0 | - | -Ph | Br |
82 | NH2 | 0 | - | 2,4-二氯苯基 | Br |
83 | 四氢苯并噻唑-2-基-氨基 | 0 | - | 2,4-二氯苯基 | Br |
84 | NHCH2CH2OH | 0 | - | -Ph | Br |
85 | NH2 | 0 | - | 2-噻吩基 | Br |
86 | (对亚磺酰胺基苯基)氨基 | 0 | - | -Ph | Br |
87 | NHCH2CH2OH | 0 | - | OEt | Br |
88 | OCH(CH3)2 | 0 | - | -Ph | Br |
89 | NHCH2CH2OH | 0 | - | CH3 | Cl |
90 | NHCH2CH2OH | 0 | - | 2-噻吩基 | Br |
91 | OCH(CH3)2 | 0 | - | 2,4-二氯苯基 | Br |
92 | (4-甲基噻唑-2-基)氨基 | 0 | - | -Ph | Br |
93 | OCH2CH2CH2CH3 | 0 | - | -NHPh | Cl |
94 | OCH2CH2CH2CH3 | 0 | - | -NHPh | Cl |
95 | NHCH2CH2OH | 0 | - | -NHPh | Cl |
96 | OCH2CH2CH2CH3 | 0 | - | 2,4-二氯苯基 | Br |
97 | NHCH2CH2CH2CH3 | 0 | - | 2,4-二氯苯基 | Br |
98 | -Ph | 0 | - | -Ph | Br |
99 | OCH3 | 0 | - | -Ph | Br |
表1B-代表性吡啶鎓衍生物
(m是0,-COR1在4位)
化合物编号 | -R1 | -R2 | -R3 | -X |
18 | NHCH2CH2OCOPh | - | 2-噻吩基 | Br |
19 | NHNHSO2Ph | - | OEt | Br |
20 | NHNHSO2Ph | - | -NHPh | Cl |
66 | -NHCH2CH2OCOPh | - | -NHPh | Cl |
75 | -NHNHSO2CH3 | - | -Ph | Br |
77 | -NHCH2CH2OCOPh | - | -OEt | Br |
80 | -NHCH2CH2OCOPh | - | -Ph | Br |
81 | -NHNHSO2CH3 | - | -OEt | Br |
结构式I化合物可通过已知方法制备。例如,可如下制备化合物1:将苯甲酰甲基溴的异丙醇溶液加入N,N′-二(烟酰基)肼的甲醇溶液,回流6小时,冷却,滤出固体沉淀,用热乙酸乙酯洗涤该固体,最后用20ml甲醇∶乙酸乙酯(3∶1)纯化,得到所需化合物。
同理,代之以适当取代的吡啶衍生物,然后用合适的试剂在甲醇、乙醇、丙醇等醇溶剂和甲苯或二甲苯等高沸点溶剂中回流6-48小时进行季铵化,可得所需化合物。
可用于制备本发明化合物的取代吡啶衍生物例如:
1.N,N′-二(烟酰基)肼
2. 3-[(2-吡啶基)肼基羰基]吡啶
3. 3-[(2-甲磺酰基)肼基羰基]吡啶
4. 3-[(2-苯甲酸基)乙基氨基羰基]吡啶
5. 3-[(2-苯磺酰基)肼基羰基]吡啶
6. 3-[(2-乙酸基)乙氧基羰基]吡啶
7. 3-[(2-苯甲酸基)乙氧基羰基]吡啶
8. 3-[(2-甲氧基)乙氧基羰基]吡啶
9. 3-[(2-苯基氨基羰基)肼基羰基]吡啶
10. 3-[(2-乙酸基)乙基氨基羰基]吡啶
11. 3-[(2-(4-甲基苯磺酰基肼基羰基))]吡啶
12. 3-[(2-苯甲酰基)肼基羰基]吡啶
13. 3-[(2-苯基甲磺酰基)肼基羰基]吡啶
14. 3-[(2-(3-环己基丙酰基)肼基羰基]吡啶
15. 3-[(2-甲氧基)乙基氨基羰基]吡啶
16. 3-[1-氧-1-(2-甲氧基羰基)吡啶基]肼基吡啶
可用于本发明的季铵化试剂的例子有:
1. 2-溴乙酰基噻吩
2. 2-氯乙酰基噻吩
3.苯甲酰甲基溴
4.苯甲酰甲基氯
5. 2,4-二氯苯甲酰甲基溴
6.N-苯基氯乙酰胺
7.N-环丙基氯乙酰胺
8.溴乙酸乙酯
9.溴乙酰基呋喃
10.N-异丙基氯乙酰胺
11.N-氯乙酰基-2-吡咯烷酮
12.氯乙酸
13.N-氯乙酰基-4-乙氧基羰基噻唑烷
AGE裂解活性的体外筛选
在实验室中对本发明代表性化合物的体外AGE裂解活性进行研究:将还原糖葡萄糖与牛血清白蛋白共孵育,结果,溶液呈棕色,且荧光度升高。用荧光度作为AGE形成增加的指标。实施例1A用以下方法确认了AGE裂解活性:
材料:
牛血清白蛋白(组分V)(BSA)
葡萄糖,分析级
磷酸盐缓冲的NaCl溶液(PBS)
设备:
微滴板ELISA读数仪-Spectramax Plus(Molecular Devices,USA)
微滴板洗涤仪,(Bio-Tec Instruments,USA)
pH计
实验方法:ELISA(酶联免疫吸附试验)
将160mg/ml蛋白质即牛血清白蛋白BSA与1.6M葡萄糖溶于磷酸盐缓冲的NaCl溶液PBS。加入0.02%浓度的叠氮钠作为防腐剂。用0.22μM滤膜进行该溶液的除菌过滤,37℃老化16周。然后用PBS对该溶液进行透析,分成等份保存于-20℃。
为了测定AGE裂解活性,将以上10μg/ml的16周AGE-BSA溶液与不同浓度的待测化合物37℃孵育24小时,通过ELISA测定待测化合物的AGE裂解活性。
如下进行ELISA:
1.将不同浓度的16周AGE-BSA溶液涂在微滴板上作为标准。每个浓度一式三份。
2.将待测样品以每孔5-20ng的浓度涂在微滴板上,一式三份。
3.微滴板在37℃保温1小时。
4.然后用PBST(PBS加0.05%Tween20)洗板。
5.用5%的脱脂乳PBS溶液37℃封闭1小时。
6.用PBST洗板。
7.加入抗AGE-BSA的第一抗体,微滴板37℃保温1小时。
8.用PBST洗板。
9.加入抗兔HRPO(辣根过氧化物酶)复合物的第二抗体,微滴板37℃保温1小时。
10.用PBST洗板。
11.用OPD(二盐酸邻苯二胺)和过氧化氢显色。
12. 37℃保温15分钟后,用微滴板ELISA读数仪测定450-620nm处的OD值(光密度)。
OD450-620对照=20ng AGE-BSA不加待测化合物,于37℃保温24小时后的吸光度
OD450-620测试=20ng AGE-BSA加特定浓度待测化合物,于37℃保温24小时后的吸光度
使用具体实施例,计算了AGE裂解活性%,记录于表2。
表2
样品 | 浓度 | 裂解% |
PTB | 10mM20mM | 2747 |
化合物1 | 5mM | 13 |
化合物4 | 10mM | 30 |
化合物5 | 10mM50mM | 1668 |
化合物6 | 5mM | 53 |
化合物7 | 20mM | 36 |
化合物16 | 10mM | 16 |
化合物17 | 10mM | 19 |
化合物22 | 10mM25mM | 1341 |
化合物23 | 10mM25mM | 3790 |
化合物32 | 10mM | 14 |
化合物33 | 5mM | 20 |
化合物38 | 5mM | 17.66 |
化合物39 | 5mM | 22.8 |
化合物40 | 10mM | 12.38 |
化合物42 | 10mM | 12.51 |
化合物43 | 10mM | 10.85 |
化合物45 | 10mM | 17.53 |
化合物47 | 10mM | 32.38 |
化合物49 | 2.5mM | 85.67 |
化合物50 | 10mM | 31.45 |
化合物51 | 10mM | 20.94 |
化合物52 | 10mM | 25.34 |
化合物53 | 2.5mM | 29.36 |
化合物54 | 10mM | 33.43 |
化合物55 | 10mM | 40.85 |
化合物56 | 10mM | 75.92 |
化合物57 | 1.0mM | 77.69 |
化合物58 | 10mM | 81.95 |
化合物59 | 10mM | 20.31 |
化合物60 | 1mM | 95.36 |
化合物61 | 10mM | 25.06 |
化合物62 | 10mM | 78.41 |
化合物63 | 10mM | 25.17 |
化合物64 | 10mM | 60.94 |
化合物65 | 2.5mM | 68.35 |
化合物66 | 10mM | 19.07 |
化合物67 | 1mM | 42.01 |
化合物68 | 10mM | 92.64 |
化合物85 | 10mM | 3 |
化合物87 | 10mM | 43 |
化合物90 | 10mM | 50 |
化合物94 | 10mM | 27 |
化合物93 | 10mM | 57 |
化合物95 | 20mM | 48 |
因此,化合物4,6,23,33,39,47,49,50,53-58,60,62,64,65,67和68具有优于PTB的AGE裂解活性,化合物49,56-58,60,62,64,65,67和68的活性尤其高。实施例1B 体内AGE裂解
在某种意义上,糖尿病和衰老过程有很大的相似性,即,两者都是退行性过程,都发生例如胶原蛋白等正常蛋白质交联形成AGE的情况。AGE的形成继而引起复杂的外观变化。更稠的胶状蛋白特别容易发生非酶促糖基化,因为它们含有几种带游离氨基的糖尿病氨基酸残基,而且它们更新速度很慢,并暴露于周围葡萄糖水平。己知,高度糖基化诱导胶原蛋白的消化抑制,即降低胶原蛋白的溶解度。这种交联胶原蛋白加重了衰老表现。
为了评估结构式I化合物的AGE裂解效率,通过在雄性wister大鼠中诱导糖尿病来模拟衰老过程。给雄性wister大鼠重复注射STZ以诱导糖尿病,以此模拟衰老和AGE形成过程。在诱导发生糖尿病后,用待测的结构式I化合物处理患病大鼠,为期8周,然后测定大鼠尾筋中胶原蛋白的溶解度。选择大鼠尾筋是因为它们与皮肤胶原蛋白(即I型胶原蛋白)类似。8周的处理后,杀死“对照”和“处理”组的大鼠,将尾筋匀浆化,用盐酸消化,取各组的上清液,用Stegemann和Stalder法(临床化学学报,18(1967)267-273)分析羟基脯氨酸,表征酸溶性胶原蛋白含量。与糖尿病对照组相比,用结构式I化合物处理的大鼠表现为胶原蛋白溶解度升高。结果见以下表3
系列号 | 化合物号 | 浓度 | 与非处理对照组相比胶原蛋白溶解度升高% |
1 | 5 | 10.0mg/kg | 88.80 |
2 | 6 | 7.5mg/kg | 56.70 |
3 | 33 | 15.0mg/kg | 80.45 |
4 | 39 | 6.0mg/kg | 28.00 |
糖尿病和衰老都是正常蛋白(如胶原蛋白)发生交联的退行性过程。皮肤胶原蛋白交联会导致衰老等表现。为了测试本发明化合物裂解已形成AGE的能力,用本发明化合物对糖尿病大鼠进行了为期8周的处理。处理后,通过测定胶原蛋白溶解度来评估它们的AGE裂解活性。结果显示,结构式I化合物能够裂解胶原蛋白中形成的AGE,提高已交联胶原蛋白的溶解度。以下是结果综述。
与同龄正常对照相比,糖尿病大鼠的尾筋胶原蛋白溶解度下降,说明形成了AGE交联。用本发明化合物处理8周的大鼠表现为胶原蛋白溶解度升高,说明AGE交联被裂解。所测化合物这种裂解已形成AGE的能力在化妆品中是十分有益的。实施例1C自由基清除活性
这一方法测定与标准量的标准品或自由基清除剂抗氧化剂相比的相对自由基清除能力(清除ABTS·+,即2,2-连氮基-二(3-乙基苯并噻唑啉-6-磺酸)根自由基阳离子)。将ABTS与过氧化物酶(正铁肌红蛋白(metmyoglobin))和过氧化氢共同孵育,于是产生自由基ABTS·+。该物质呈蓝绿色,可730nm处测得。在样品中加入抗氧化剂或自由基清除剂一定程度地使颜色淡化,该程度与它们的浓度成正比。方法:缓冲液的制备:
A.磷酸盐柠檬酸盐缓冲液(pH5.0):48.5ml 0.1M柠檬酸加0.2M磷酸氢二钠至100ml。
B.磷酸盐缓冲的NaCl溶液(PBS):将40.0g NaCl,1.0g KCl,1.0g KH2PO4和3.05g Na2HPO4溶于1L milli-Q水中。用milli-Q水将200ml以上溶液稀释至1L(pH7.4-7.6)。
C.用pH7.4的磷酸盐缓冲的NaCl溶液(PBS)制备3μM的过氧化物酶储备液。
D.用pH7.4的磷酸盐缓冲的NaCl溶液(PBS)制备1.08mM的过氧化氢储备液。ABTS储备液的制备:
将一片片剂(10mg)溶于磷酸盐柠檬酸盐缓冲的NaCl溶液(pH5.0)。ABTS工作液的制备:
用PBS将5.0ml ABTS储备液稀释至20ml。辣根过氧化物酶储备液的制备:
将320μg该酶溶于2.5ml PBS。过氧化氢溶液(1.08mM)的制备:
用PBS将12μl过氧化氢(30%w/v)稀释至100ml。药物溶液的制备:
制备0.1mM的药物储备液,然后用PBS稀释至不同的浓度。ABTS自由基储备液的制备:
向18ml ABTS储备液中加入100μl辣根过氧化物酶储备液。在以上溶液中加入1.5ml过氧化氢溶液,立刻出现ABTS自由基的蓝绿色。该溶液30℃保温30分钟。对照液的制备:
将980μl ABTS自由基储备液加入eppendorf管。向其中加入100μl PBS溶液。待测液的制备:
将980μl ABTS自由基储备液加入各支eppendorf管。向其中加入100μl不同浓度的药物溶液。吸光度(OD)测定:
立即在730nm处测定对照和待测样品的吸光度,以PBS为空白。
计算:根据以下公式计算抗氧化活性%:
抗氧化活性%=[待测样品OD/对照OD*100]-100
结果见以下表3。
表3
系列号 | 化合物号 | ABTS自由基清除相对活性(%) | ||||
11.5μM | 23.0μM | 46.0μM | 92.5μM | 925μM | ||
1 | 烟酰胺 | 0.0 | 2.2 | 3.8 | 3.8 | 9.2 |
2 | 化合物5 | 47.2 | 65.6 | 83.7 | 100 | - |
3 | 化合物33 | 58.4 | 72.8 | 98.5 | 100 | - |
4 | 化合物39 | 43.0 | 62.8 | 95.6 | 98 | - |
5 | 化合物22 | 27.9 | 50.9 | 69.3 | 79.7 | 100 |
6 | 化合物8 | 40.8 | 53.7 | 72.6 | 81.2 | 100 |
7 | 化合物36 | 27.6 | 59.2 | 74.2 | 83.9 | 100 |
8 | 化合物82 | 26.0 | 44.3 | 62.7 | 75.5 | 100 |
9 | 化合物90 | 47.8 | 58.8 | 78.2 | 99.5 | 100 |
10 | 化合物4 | 58.2 | 64.3 | 69.3 | 98.6 | 100 |
11 | 化合物93 | 8.5 | 8.6 | 9.6 | 11.4 | 25.0 |
12 | 化合物56 | 43.0 | 57.2 | 71.6 | 97.7 | 100 |
13 | 化合物64 | 41.8 | 55.7 | 72.2 | 99.0 | 100 |
14 | 化合物97 | 16.5 | 27 | 37.8 | 44.5 | 97.8 |
15 | 化合物18 | 41.8 | 59.5 | 75.2 | 91.0 | 100 |
16 | 化合物27 | 43.9 | 55.5 | 75.3 | 99.6 | 100 |
17 | 化合物31 | 41.6 | 57.7 | 66.9 | 99.2 | 100 |
18 | 化合物98 | 7.1 | 26.9 | 51.1 | 78.6 | 99.1 |
19 | 化合物34 | 50.3 | 53.8 | 65.4 | 80.4 | 100 |
20 | 化合物35 | 50.5 | 63.4 | 80.9 | 90.6 | 100 |
21 | 化合物38 | 47.2 | 54.8 | 71.0 | 89.5 | 100 |
22 | 化合物45 | 53.9 | 56.2 | 78.7 | 99.8 | 100 |
23 | 化合物60 | 44.1 | 59.8 | 69.4 | 99.9 | 100 |
24 | 化合物54 | 5.22 | 15.45 | 46.82 | 77.07 | - |
25 | 化合物55 | 46.47 | 84.97 | 99.50 | 99.93 | - |
26 | 化合物63 | 10.75 | 47.20 | 88.64 | 99.18 | - |
27 | 化合物64 | 26.01 | 57.39 | 99.30 | 99.62 | - |
28 | 化合物65 | 27.67 | 59.20 | 94.14 | 100.00 | - |
29 | 化合物67 | 13.11 | 50.70 | 97.46 | 99.43 | - |
30 | 化合物68 | 38.47 | 43.54 | 89.32 | 95.07 | - |
31 | 化合物50 | 3.30 | 23.06 | 54.95 | 89.31 | - |
32 | 化合物51 | 0.00 | 21.64 | 52.82 | 83.94 | - |
本发明化合物的AGE抑制活性
除AGE裂解活性和自由基清除活性之外,本发明化合物还具有抑制AGE的活性,这使得它们适用于前文所述的各种美容用途。
实际上,a)AGE裂解剂,b)AGE抑制剂,c)自由基清除剂三重活性可用于多种抗衰老美容防治。实施例1D AGE抑制活性检测
以下方法用于测定化合物的AGE抑制效果。方法1
该方法测定化合物对体外Maillard反应的AGE抑制效果。该方法参照了美国专利5,514,676和欧洲专利公开0339496A2。
用磷酸盐缓冲液(PBS,pH7.4)制备牛血清白蛋白(BSA)、核糖和待测化合物的溶液,其中BSA和核糖的最终浓度分别为10mg/ml和500mM。在无菌条件下加入待测化合物。在该溶液中加入叠氮钠(0.02%)以防细菌生长。在另一支试管中加入相同浓度的BSA、核糖和叠氮钠以及同样的缓冲液,但是不加待测化合物,以此作为阳性对照。
37℃孵育7天,每管回收40ml样品,用PBS稀释至1mg/ml BSA浓度。用f-MAX荧光计(Molecular Device,USA)在355nM的最大激发波长和460nM最大发射波长处测定所有样品的荧光度。为了研究待测化合物对荧光的影响,将新鲜制备的化合物溶液与孵育后的前述阳性对照(即ABS+核糖)混合,使得所有组分的浓度与待测样品中的相同。
本发明测定了代表性结构式I化合物的AGE抑制活性。
表4
化合物号 | 浓度 | 抑制%(7天) |
5 | 10mM | 70 |
33 | 2.5mM | 68.4 |
7 | 10mM | 51 |
54 | 2.5mM | 46.3 |
63 | 6.25mM | 58.15 |
由此发现,前述结构式I化合物裂解AGE和清除自由基之外还能够抑制AGE。方法-II
(a)原理:
在葡萄糖或核糖等还原糖存在下,蛋白质会交联形成二聚体、三聚体等多聚体形式。这些聚合体可以根据其分子量,用多种常用方法进行分离,例如十二烷基硫酸钠聚丙烯酰胺凝胶电泳法(SDS-PAGE)。简而言之,用SDS处理蛋白质样品使其变性并带上负电荷。然后,SDS处理后的蛋白质样品在聚丙烯酰胺凝胶上电泳。蛋白质通过凝胶的迁移率直接取决于其分子量。该方法被普遍用于蛋白质的分析,可参见Sambrook,J和Russell,W(1);并在美国专利5,853,703中用于化合物的AGE裂解活性。
(b)过程:
将溶菌酶(Sigma-Aldrich,USA)、核糖和待测化合物溶于PBS,最终浓度分别为10mg/ml和0.5M。在该溶液中加入10μg/ml苯基甲基磺酰基氟(PMSF)(Boehringer Mannheim,Germany)和0.02%叠氮钠,分别用于防治蛋白酶作用和细菌生长。对另一支试管进行同样的孵育,其中含相同浓度的BSA,核糖和叠氮钠以及缓冲液,但不含待测化合物,以此作为阳性对照。溶液在37℃孵育21天。
培养后,从各反应即待测管和对照管中各取等量蛋白质上样在SDS-PAGE上。用考马斯蓝进行凝胶染色,用Gel Doc 2000(Bio Rad,USA)分析密度。SDS-PAGE的结果见图1,其中第1至6泳道代表以下内容:
泳道1:分子量标记;
泳道2:对照溶菌酶;
泳道3:溶菌酶+核糖;
泳道4:溶菌酶+核糖+化合物5(25mM)
泳道5:溶菌酶+核糖
泳道6:溶菌酶+核糖+化合物33(5mM)
在与核糖一起37℃孵育21天后,溶菌酶(AGE-溶菌酶)在SES-PAGE上呈3条主带;其中之一是原溶菌酶,另两条的分子量分别对应于原溶菌酶的二聚体和三聚体,分别标记为峰1和峰2。由于原溶菌酶的密度在对照和待测样品中保持不变,可用它进行标准化。待测化合物对AGE形成的抑制活性可通过分析与对照相比二聚体(峰1)和三聚体(峰2)形成的程度,并就各条带的光密度进行制图来分析(图2)。试验结果讨论
因此,本发明化合物具有裂解蛋白质中形成的AGE交联的活性。本发明化合物还具有猝灭自由基(自由基会对蛋白质、核酸等造成不可逆损伤)的活性。本发明化合物逆转高度糖基化终产物形成(发生于胶原蛋白等皮肤支持蛋白和角蛋白等毛发蛋白中)的活性和猝灭自由基的活性具有重要意义,使它们可用于化妆品。
本发明化合物可通过在多个重要阶段抑制皮肤状态恶化来改善皮肤外观。它能够裂解皮肤支持蛋白中已形成的高度糖基化终产物(AGE),并延迟内部老化(C.Jeanmaire等,英国皮肤学杂志2001:145:10-18)。本发明化合物还可猝灭皮肤中因UV光照、污染等产生的自由基,从而避免外部老化或光老化。猝灭自由基还可避免对蛋白质和核酸的不可逆损伤。而且,因其自由基猝灭活性,本发明化合物可降低已形成AGE产生的自由基负荷。继而,这种氧化性应激下降可减少Amadori产物形成中反应性中间体的形成。
蛋白质糖基化是一种普遍现象,皮肤水平的蛋白质糖基化已是众所周知。然而,这一现象还可能发生于其他相关部位,例如指甲或毛发,尤其是角蛋白(EP1068864A1和EP1110539A1)。
皮肤蛋白质的糖基化,尤其是胶原蛋白的糖基化,有损容貌,例如造成皮肤损伤,在皮肤相关部位(例如指甲和/或毛发)以及所有蛋白质系统中都可能同样发生因蛋白质糖基化所致的这些结果。
以下实施例是表1中本发明组合物所用化合物的制备方法。以下化合物仅是举例而非本发明范围的限定。实施例2二溴N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)吡啶鎓]肼(化合物1):
向煮沸的N,N′-二(烟酰基)肼(1.21g,0.005mol)的甲醇(20ml)溶液中加入苯甲酰甲基溴(1.99g,0.01mol)的异丙醇(10ml)溶液,该反应混合物回流6小时。真空浓缩该反应混合物(至约10ml),过滤。所得残留物用热乙酸乙酯洗涤,然后将分离所得的固体粉碎成粉末。用甲醇和乙酸乙酯(3∶1,20ml)混合物重结晶后,得一种浅黄色固体。
得率:60%
m.p.:260-262℃(分解(decomp.))
IR(KBr,cm-1):1696和1680
1H NMR(DMSOd6,400MHz)δ:11.65(2H,s),9.56(2H,s),9.21-9.16(4H,m),8.49-8.45(2H,m),8.08-8.05(4H,d),7.81-7.72(2H,m),7.68-7.64(4H,m),6.58(4H,s)
质谱(m/z):479,480
按照以上方法合成以下化合物:用相应的吡啶衍生物与适当反应试剂在甲醇、乙醇、丙醇、甲苯或二甲苯中回流6-48小时,得所需化合物:实施例3二溴N,N′-二[3-羰基-1-(2-乙氧基-2-氧代乙基)吡啶鎓]肼(化合物2):
得率:47%
m.p.:180-182℃(分解)
IR(KBr,cm-1):1744,1664
1H NMR(DMSOd6,400MHz)δ:11.65(2H,s),9.62(2H,s),9.28-9.26(2H,d),9.17-9.15(2H,m),8.47-8.44(2H,m),5.77(4H,s),4.26(4H,q),1.27(6H,t)
质谱(m/z):415,416实施例4二溴N,N′-二[3-羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)-吡啶鎓]肼(化合物3)
得率:24%
m.p.:225-227℃(decomp.)
IR(KBr,cm-1):1702,1666
1H NMR(DMSOd6,400MHz)δ:11.69(2H,s),9.58(2H,bs),9.20-9.18(4H,m),8.49-8.47(2H,m),8.17-8.15(2H,d),7.92(2H,bs),7.78-7.76(2H,d),6.50(4H,s)
质谱(m/z):615,617,618,620.实施例5溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓(化合物4)
得率:16%
m.p.:210-212℃
IR(KBr,cm-1):3140,3005,1732和1690
1H NMR(DMSOd6,400MHz)δ:9.63(1H,s),9.27(2H,d),8.49-8.45(1H,m)8.13-8.07(2H,m),7.32-7.30(1H,m),7.12-7.11(1H,m),5.77(2H,s),4.23(2H,q),1.25(3H,t)
质谱(m/z):301,302实施例6溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物5)
得率:30%
m.p:199-200℃
IR(KBr,cm-1):1714,1673
1H NMR(DMSOd6,400MHz)δ:11.38(1H,s),9.97(1H,s)9.51(1H,s),9.16(1H,d),9.06-9.04(1H,m),8.43-8.39(1H,m),8.25-8.21(2H,m),7.43-7.41(1H,t),6.45(2H,s),3.08(3H,s).
质谱(m/z):340,341,342实施例7二溴-N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼(化合物6)
得率:33%
m.p.:259-261℃(decomp.)
IR(KBr,cm-1):3330,1702,1674,1655和1626
1H NMR(DMSOd6,400MHz)δ:11.59(2H,s),9.50(2H,s),9.15-9.08(4H,m),8.40-8.36(2H,m),8.17-8.14(4H,m),7.33(2H,t),6.42(4H,s)
质谱(m/z):491,492.实施例8溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物7)
得率:85%
m.p.:132-134℃
IR(KBr,cm-1):3210,3067,1726,1687,1656
1H NMR(DMSOd6,400MHz)δ:9.46(1H,s),9.37(1H,t),9.11(1H,t),8.97(1H,d),8.33-8.29(1H,m)7.95-7.93(2H,m),7.63-7.59(1H,m),7.49-7.45(2H,m),5.65(2H,s),4.39(2H,t),4.19(2H,q),3.70-3.69(2H,m),1.20(3H,t)
质谱(m/z):357,358,359实施例9溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物8)
得率:75%
m.p.:102-104℃
IR(KBr,cm-1):1703,1685,1675
1H NMR(DMSOd6,400MHz)δ:9.41-9.37(2H,m),9.03-8.98(2H,m)8.34-8.30(1H,m),8.04(1H,d),7.91-7.89(2H,m),7.82(1H,d),7.68-7.65(1H,m),7.58-7.55(1H,m),7.43(2H,t),6.35(2H,s),4.36(2H,t),3.68-3.64(2H,m)
质谱(m/z):457,458,459,460,461,462实施例10溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓(化合物9)
得率:10%
m.p.:212-214℃(decomp)
IR(KBr,cm-1):1685,1649
1H NMR(DMSOd6,400MHz)δ:11.21(1H,bs),9.59(1H,s),9.19(2H,d),8.44(1H,t),8.27-8.24(2H,m),8.08(1H,bs),7.62(1H,bs),7.44(1H,t),6.85-6.79(2H,m),6.50(2H,s)
质谱(m/z):339,340,341实施例11溴化1-(2-苯基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓(化合物10)
得率:4%
m.p.:190℃(decomp)
IR(KBr,cm-1):1683,1670,1648
1H NMR(DMSOd6,400MHz)δ:11.14(1H,bs),9.53(1H,s),9.18-9.13(2H,m),8.45-8.42(1H,t),8.08-8.06(3H,m),7.80(1H,t),7.67(2H,t),7.62-7.55(1H,m),6.83-6.76(2H,m),6.54(2H,s)
质谱(m/z):333,334,335实施例12溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓(化合物11)
得率:15%
m.p.:215-216℃
IR(KBr,cm-1):1695,1680
1H NMR(DMSOd6,400MHz)δ:10.25(1H,s)9.65(1H,s),9.35-9.32(2H,m),8.90-8.88(1H,m)8.50-8.46(2H,d),8.21-8.17(1H,m),8.05-8.07(2H,m),6.50(2H,s),4.45(2H,s).
质谱(m/z):256,257.实施例13溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物12)
得率:35%
m.p.:227-228℃
IR(KBr,cm-1):1710,1702
1H NMR(DMSOd6,400MHz)δ:11.30,(1H,s),9.88(1H,s),9.41(1H,s),9.06-9.05(1H,d)8.98-8.96(1H,d),8.34-8.31(1H,m),7.97(2H,d),7.72-7.69(1H,t),7.59-7.56(2H,t),6.44(2H,s),2.99(3H,s)
质谱(m/z):334,335实施例14溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物13)
得率:38%
m.p:75-76℃
IR(KBr,cm-1):1739,1697
1H NMR(DMSOd6,400MHz)δ:11.39(1H,s),9.96(1H,s),9.56(1H,s),9.23(1H,d),9.06(1H,d),8.40(1H,t),5.75(2H,s),4.27-4.22(2H,q),3.08(3H,s),1.26(3H,t)
质谱(m/z):301,302,303实施例15溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓(化合物14)
得率:28%
m.p:187-188℃(dec.)
IR(KBr,cm-1):1700,1633
1H NMR(DMSOd6,400MHz)δ:11.38(1H,s),10.45(1H,s),9.33(1H,s),9.13-9.12(1H,d),8.95(1H,d),8.38(1H,t),8.05(2H,d),7.89(2H,d),7.80(1H,t),7.66(3H,t),7.57(2H,t),6.50(2H,s).
质谱(m/z):396,397,398实施例16溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓(化合物15)
得率:23%
m.p.:247-250℃(decomp)
IR(KBr,cm-1):1685,1679,
1H NMR(DMSOd6,400MHz)δ:11.12(1H,s),9.49(1H,s),9.07-9.03(1H,m),8.44(1H,t),8.07(2H,d),7.80(1H,t),7.67(2H,t),7.18(2H,t),6.87(2H,d),6.77(1H,t),6.50(2H,s).
质谱(m/z):430,431,432实施例17溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基羰基)吡啶鎓(化合物16)
得率:40%
m.p.:152-153℃
IR(KBr,cm-1):1737,1691,1635
1H NMR(DMSOd6,400MHz)δ:9.63(1H,s),9.24(1H,d),9.12(1H,d),8.43(1H,t),8.07(2H,d),7.80(1H,t),7.67(2H,t),6.59(2H,s),4.62-4.60(2H,m),4.39-4.37(2H,m),2.03(3H,s)
质谱(m/z):328,329实施例18溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓(化合物17)
得率:35%
m.p.:142-143℃
IR(KBr,cm-1):1736,1718,1636
1H NMR(DMSOd6,400MHz)δ:9.60(1H,s),9.20-9.18(1H,d),9.04-9.02(1H,d),8.33-8.29(1H,m),7.90-7.88(2H,d),7.58-7.57(1H,m),7.46-7.42(2H,m),5.67(2H,s),4.71-4.68(2H,m),4.58-4.56(2H,m),4.15(2H,q),1.16(3H,t)
质谱(m/z):358,359,360实施例19溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物18)
m.p.:210-211℃
IR(KBr,cm-1):1723,1680,1668
1H NMR(DMSOd6,400MHz)δ:9.52(1H,t),9.14(2H,d),8.50(2H,d),8.25-8.21(2H,m),8.01-7.99(2H,d),7.67(1H,t),7.55-7.51(2H,m),7.42-7.40(1H,m),6.42(1H,s)4.47-4.45(2H,t),3.77-3.73(2H,m).
质谱(m/z):395,396实施例20溴化1-(2-乙氧基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓(化合物19)
得率:60%
m.p.:171-173℃.
IR(KBr,cm-1):1745,1685,1645.
1H NMR(DMSOd6,400MHz)δ:11.41(1H,s),10.39(1H,s),9.10(2H,d),8.27(2H,d),7.82-7.80(2H,d),7.60-7.57(1H,t),7.50-7.46(2H,t),5.63(2H,s),4.18-4.12(2H,q),1.19-1.15(3H,t).
质谱(m/z):364,365,366实施例21氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓(化合物20)
得率:10%
m.p.:225-227℃.
IR(KBr,cm-1):1693,1642,1592
1H NMR(DMSOd6,400MHz)δ:11.55(1H,s),10.99(1H,s),10.49(1H,s),9.20(2H,d),8.34(2H,d),7.89(2H,d),7.73-7.64(1H,t),7.61-7.56(4H,m),7.37-7.33(2H,t),7.12-7.09(1H,t),5.73(2H,s).
质谱(m/z):411,412,413,414实施例22溴化1-(2-乙氧基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓(化合物21)
得率:75%
m.p.:145-147℃.
IR(KBr cm-1):1744,1713,1633
1H NMR(DMSOd6,400MHz)δ:11.27(1H,s),10.36(1H,s),9.28(1H,s),9.09(1H,d),8.83(1H,d),8.27-8.24(1H,m),7.82-7.79(2H,m),7.58(1H,t),7.48(2H,t),5.59(2H,s),4.17-4.12(2H,q),1.16(3H,t).
质谱(m/z):364,365,366实施例23溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓(化合物22)
得率:25%
m.p.:156-158℃.
IR(KBr,cm-1):1731,1706,1640
1H NMR(DMSOd6,400MHz)δ:9.61(1H,s),9.20(1H,d),9.13(1H,d),8.45-8.41(1H,m),8.15(1H,d),7.92(1H,d),7.78-7.76(1H,m),6.49(2H,s),4.56-4.54(2H,m),3.72-3.69(2H,q),3.31(3H,s).
质谱(m/z):368,369,370,371实施例24氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物23)
得率:70%
m.p.:171-172℃
IR(KBr,cm-1):1720,1692,1668
1H NMR:(DMSOd6,400MHz)δ:11.06(1H,s),9.67(1H,t),9.59(1H,s),9.20(1H,d),9.11(1H,d),8.36-8.32(1H,m),8.00(2H,d),7.66-7.61(3H,m),7.51(2H,t),7.34(2H,t),7.10(1H,t),5.77(2H,s),4.45(2H,t),3.76-3.72(2H,q).
质谱(m/z):404,405,406,407实施例25溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓(化合物24)
得率:30%
m.p.:202-204℃.
IR(KBr,cm-1):1718,1673
1H NMR:(DMSOd6,400MHz)δ:11.03(1H,s),9.55(1H,s),9.18(1H,d),9.10(1H,d),9.00(1H,s),8.57(1H,s),8.46-8.42(1H,t),8.25-8.22(2H,m),7.47-7.45(2H,d),7.43-7.41(1H,t),7.29-7.25(2H,t),7.0-6.96(1H,t),6.46(2H,s).
质谱(m/z):381,382,383实施例26溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓(化合物25)
得率:55%
m.p.:186-188℃
IR(KBr,cm-1):1734,1697,1679
1H NMR(DMSOd6,400MHz)δ:9.47(1H,s),9.36(1H,t),9.13-9.05(2H,m),8.42-8.38(1H,m),8.06(2H,d),7.80(1H,t),7.67(2H,t),6.54(2H,s),4.18(2H,t),3.61-3.57(2H,q),2.02(3H,s).
质谱(m/z):327,328,329.实施例27氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓(化合物26)
得率:38%
m.p.:232-234℃.
IR(KBr,cm-1):1689,1636,1596
1H NMR(DMSOd6,400MHz)δ:11.30(1H,s),10.80(1H,s),10.37(1H,s),9.29(1H,s),9.09(1H,d),8.81(1H,d),8.25-B.21(1H,t),7.82-7.80(2H,d),7.59-7.46(5H,m),7.28-7.24(2H,t),7.04-7.00(1H,t),5.62(2H,s).
质谱(m/z):411,412,413,414实施例28氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓(化合物27)
得率:48%
m.p.:205-206℃
IR(KBr,cm-1):1712,1681,1632
1H NMR(DMSOd6,400MHz)δ:11.35(1H,s),10.86(1H,s),10.36(1H,s),9.38(1H,s),9.17(1H,d),8.90(1H,d),8.34-8.30(1H,m),7.78(2H,d),7.59(2H,d),7.37-7.33(4H,m),7.11(1H,t),5.70(2H,s),2.36(3H,s).
质谱(m/z):425,426,427,428实施例29溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓(化合物28)
得率:35%
m.p.:132-134℃.
IR(KBr,cm-1):1730,1705,1690
1H NMR(DMSOd6,400MHz)δ:9.80(1H,s),9.36(1H,d),9.30(1H,d),8.58(1H,t),8.21(2H,d),8.12(2H,d),7.95(1H,t),7.85-7.80(3H,m),7.68(2H,t),6.71(2H,s),4.95-4.93(2H,m),4.82-4.80(2H,m).
质谱(m/z):390,391,392.实施例30溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓(化合物29)
得率:45%
m.p.:80-81℃
IR(KBr Cm-1):1700,1663,1631
1H NMR(DMSOd6,400MHz)δ:11.49(1H,s),10.95(1H,s),9.67(1H,s),9.34(1H,d),9.27(1H,d),8.52-8.48(1H,m),8.29-8.28(2H,m),8.00(2H,d),7.68(1H,t),7.59(2H,t),7.46(1H,t),6.63(2H,s)
质谱(m/z):366,367,368,369实施例31溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓(化合物30)
得率:50%
m.p.:147-148℃
IR(KBr,cm-1):1749,1698,1640
1H NMR(DMSOd6,400MHz)δ:11.57(1H,s),10.21(1H,s),9.75(1H,s),9.38(1H,d),9.24(1H,d),8.59-8.56(1H,m),7.67-7.65(2H,m),7.58-7.52(3H,m),5.90(2H,s),4.68(2H,s),4.45-4.39(2H,q),1.43(3H,t).
质谱(m/z):377,378,379实施例32溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓(化合物31)
得率:80%
m.p.:205-207℃
IR(KBr,Cm-1):1687,1637
1H NMR(DMSOd6,400MHz)δ:11.59(1H,s),10.20(1H,s),9.71(1H,s),9.33(1H,d),9.27(1H,d),8.62-8.59(1H,m),8.25-8.23(2H,d),7.99-7.95(1H,t),7.86-7.82(2H,t),7.67-7.65(2H,m),7.57-7.52(3H,m),6.72(2H,s),4.69(2H,s).
质谱(m/z)::410,411,412,413实施例33二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼(化合物32)
得率:23%
m.p.:267-269℃(dec)
IR(KBr,cm-1):1687,1660
1H NMR(DMSOd6,400MHz)δ:11.65(2H,s),9.56(2H,s),9.21-9.15(4H,m),8.48-8.44(2H,t),8.23(2H,s),7.74-7.73(2H,d),6.91-6.90(2H,d)6.34(4H,s)
质谱(m/z):459,460,461实施例34二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼(化合物33)
得率:35%
m.p.:275-277℃
IR(KBr,cm-1):3374,1665,1632,1410
1H NMR(DMSO d6,400MHz)δ:11.88(2H,s),9.66(2H,s),9.29-9.24(4H,m),8.48-8.44(2H,m),8.25-8.23(4H,m),7.43-7.41(2H,m),6.53(4H,s).
质谱(m/z):491,492,493,494实施例35二溴1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-(1-氧-3-环己基)-丙基)-肼基羰基)-吡啶鎓(化合物34)
得率:15%
m.p.:217-219℃(dec)
IR(KBr,cm-1):3190,1708,1667和1404
1H NMR(DMSOd6,400MHz)δ:11.07(1H,s),10.22(1H,s),9.51(1H,s),9.16-9.15(1H,d),9.06-9.04(1H,d),8.42-8.40(1H,m),8.25-8.21(2H,m),7.43-7.40(1H,m),6.44(2H,s),2.25-2.22(2H,t),1.72-1.60(5H,m),1.49-1.43(2H,q),1.24-1.10(4H,m),0.9-0.85(2H,m)
质谱(m/z):400,401,402和403实施例36溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-丙基}肼基羰基吡啶鎓(化合物35)
得率:25%
m.p:234-236℃(dec)
IR(KBr,cm-1):1689,1652和1625
1H NMR(DMSO d6,400MHz)δ:11.11(1H,s),10.95(1H,s),10.23(1H,s),9.56(1H,s),9.23-9.21(1H,d),9.06-9.04(1H,d),8.38-8.35(1H,m),7.62-7.60(2H,d),7.37-7.33(2H,t),7.12-7.09(1H,t),5.75(2H,s),2.25-2.22(2H,t),1.72-1.60(5H,m)1.49-1.43(2H,m),1.25-1.10(4H,m),0.91-0.83(2H,m)
质谱(m/z):409,410,411和412实施例37溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物36)
得率:40%
m.p.:125-127℃
IR(KBr,cm-1):1710和1675
1H NMR(DMSOd6,400MHz)δ:9.48(1H,s),9.43-9.41(1H,t),9.12-9.11(1H,d),9.05-9.02(1H,d),8.40-8.36(1H,m),8.25-8.20(2H,m),8.00-7.98(2H,m),7.68-7.64(1H,m),7.54-7.50(2H,m),7.42-7.40(1H,m),6.43(2H,s),4.46-4.43(2H,t),3.77-3.73(2H,q)
质谱(m/z):395,396,397和398实施例38氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓(化合物37)
得率:35%
m.p.:147-149℃
IR(KBr,cm-1):1743,1720,1680和1627
1H NMR(DMSOd6,400MHz)δ:9.62-9.59(1H,t),9.32-9.29(1H,s),9.05-9.03(1H,d),8.93-8.90(1H,d),8.27-8.24(1H,m),7.92-7.89(2H,d),7.59-7.55(1H,m),7.45-7.41(2H,m),5.82(2H,s),4.37-4.34(2H,t),4.08-4.03(2H,q),3.80(2H,s),3.67-3.63(2H,q),1.15-1.11(H,t),
质谱(m/z):399,400和401实施例39溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)-吡啶鎓(化合物38)
得率:70%
m.p.:93-95℃
IR(KBr,cm-1):1704,1664和1636
1H NMR(DMSO d6,400MHz)δ:9.48(1H,s),9.29(1H,bs),9.11-9.08(2H,m),8.41-8.38(1H,m),8.15-8.13(1H,d),7.92-7.91(1H,t),7.78-7.75(1H,m),6.44(2H,s)3.52(2H,bs),3.51(2H,bs),3.28(3H,s)
质谱(m/z):367,368,369和370实施例40二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼(化合物39)
得率:40%
m.p.:228-230℃
IR(KBr cm-1):1675,1636和1298
1H NMR(DMSO d6,400MHz)δ:11.85(2H,s),9.59(2H,s),9.25-9.19(4H,m),9.00-8.99(2H,d),8.39-8.36(2H,m),5.53(4H,s),2.73-2.66(2H,m),0.78-0.62(4H,m),0.53-0.49(4H,m)
质谱(m/z)437,438和439实施例41氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)-吡啶鎓(化合物40)
得率:10%
m.p.:122-124℃
IR(KBr,cm-1):1661,1633,1549和1121
1H NMR(DMSO d6,400MHz)δ:9.40(1H,s),9.08-9.02(2H,m),8.28-8.25(1H,m),5.53(2H,s),3.66-3.61(4H,m),3.39(3H,s),2.78-2.74(1H,m),0.80-0.75(2H,m),0.64-0.61(2H,m)
质谱(m/z):278,279和280实施例42二氯N,N′-二[3-羰基-1-(2-异丙基氨基-2-氧代乙基)吡啶鎓]肼(化合物41)
得率:35%
m.p.:114-116℃(dec)
IR(KBr,cm-1):1707,1668和1637
1H NMR(DMSO d6,400MHz)δ:11.84(2H,s),9.59(2H,s),9.21-9.18(4H,m),8.74-8.72(2H,d),8.39-8.35(2H,m),5.53(4H,s),3.92-3.84(2H,m),1.14-1.02(12H,d)
质谱(m/z):441,442和443实施例43氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基(pyridoyl))肼基羰基)-吡啶鎓(化合物42)
得率:56%
m.p.:233-235℃
IR(KBr,cm-1):1680,1637,1404和1293
1H NMR(DMSO d6,400MHz)δ:11.62(1H,s),11.05(1H,s),9.62(1H,s),9.24-9.23(1H,d),9.18-9.16(1H,d),8.58-8.56(1H,m),8.46-8.43(1H,m),8.26-8.24(2H,m),8.02-8.00(1H,m),7.61-7.58(1H,m),7.43-7.41(1H,m),6.51(2H,s)
质谱(m/z):401,402,403,404和405实施例44氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓(化合物43)
得率:10%
m.p.:227-229℃
IR(KBr,cm-1):1691,1670,1566和1330
1H NMR(DMSO d6,400MHz)δ:11.55(1H,s),9.94(1H,s),9.52(1H,s),9.16-9.14(1H,m),9.09-9.07(1H,m),8.72-8.70(1H,m),8.34-8.30(1H,m),5.50(2H,s),3.89-3.84(1H,m),3.11(3H,s),1.13-1.12(6H,d)
质谱(m/z):315,316和317实施例45氯化1-(2-(1-吡咯烷基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物44)
得率:21.00%
m.p.:205-207℃
IR(KBr,cm-1):1699,1646和1589
1H NMR:(DMSO d6,400MHz)δ:11.50(1H,s),9.94(1H,s),9.46(1H,s),9.11-9.06(2H,m),8.36-8.33(1H,t),5.75(2H,s),3.55-3.48(3H,m),3.10(3H,s),2.00-1.95(2H,m),1.87-1.81(2H,m)
质谱(m/z):327,328,329和330实施例46氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-吡啶鎓(化合物45)
得率:31.00%
m.p.:215-217℃
IR(KBr,cm-1):1685,1666和1635
1H NMR:(DMSO d6,400MHz)δ:11.49,(1H,s),9.96(1H,s),9.55(1H,s),9.18(1H,d),9.10(1H,d),8.43-8.39(1H,t),8.25-8.22(2H,m),7.42(1H,t)6.47(2H,s),3.09(3H,s).
质谱(m/z):340,341,342和343实施例47二氯N,N′-二[3-羰基-1-(2-羟基-2-氧代乙基)吡啶鎓]肼(化合物46)
得率:43.00%
m.p.:235-240℃(d)
IR(KBr,cm-1):1743,1700和1672
1H NMR(DMSO d6,400MHz)δ:11.89(2H,s),9.69(2H,s),9.31-9.29(2H,d),9.25-9.23(2H,d),8.43-8.39(2H,t)5.70(4H,s)
质谱(m/z):360,361,362实施例48氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)-5-溴吡啶鎓(化合物47)
得率:31.00%
m.p.:180-182℃
IR(KBr,cm-1):1661和1620
1H NMR(DMSO d6,400MHz)δ:9.58-9.54(2H,d),9.43-9.39(2H,d),8.25-8.21(2H,m),7.41(1H,t),6.43(2H,s),3.51(4H,m),3.29(3H,s).
质谱(m/z):384,385,386,387和388实施例49氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基)肼基吡啶鎓(化合物48)
得率:30.00%
m.p.:222-225℃
IR(KBr,cm-1):1726,1708和1662
1H NMR(DMSO d6,400MHz)δ:11.47(1H,s),11.23(1H,s),9.58(1H,s),9.22-9.15(3H,m),8.56-8.53(1H,d),8.46-8.43(1H,t)8.25-8.21(3H,m),7.42(1H,t),6.49(2H,s),3.95(3H,s)
质谱(m/z):425,426和427实施例50二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼(化合物49)
得率:40%
M.P.:76-80℃(dec)
IR(KBr,cm-1):1637,1513
1H NMR(DMSO d6,400MHz)δ:11.69(2H,s),9.59-9.53(2H,d),9.19(2H,m),9.05(1H,d),8.46-8.43(1H,t),8.34(1H,d),8.27-8.23(4H,m),7.45-7.41(2H,m),6.56(2H,s),6.48(2H,s),2.81(3H,s).
质谱(m/z):505,506,507.实施例51溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓(化合物50)
得率:70%
M.P:90-95℃(dec)
IR(KBr,cm-1)1638,1589
1H NMR(DMSO d6,400MHz)δ:11.27(1H,s),9.91(1H,s),9.60(1H,s),9.19-9.15(2H,m),8.42-8.36(1H,m),8.25-8.21(2H,m),7.43-7.41(1H,t),6.45(2H,s),1.35-1.34(6H,d).
质谱(m/z):368,369,370实施例52氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物51)
得率:17%
M.P:76-78℃
IR(KBr,cm-1):1684,1650,1556,1540.
1H NMR(DMSO d6,400MHz)δ:11.46(1H,s),9.55(1H,s),9.46(1H,s),9.09-9.03(2H,m),8.36-8.32(1H,t),7.33-7.29(2H,m),7.23-7.19(3H,m),5.88-5.79(2H,m),4.30-4.27(1H,d),3.76-3.73(1H,d),3.10(4H,m),2.64(1H,t),2.57-2.55(2H,d),1.85(1H,bs),1.72-1.63(2H,t),1.36-1.28(1H,q),1.13-1.03(1H,m)
质谱(m/z):431,432,433实施例53氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物52)
得率:14%
M.P:88-91℃
IR(KBr,cm-1):1735,1665,1539
1H NMR(DMSO d6,400MHz)δ:11.48(1H,s),9.96(1H,s),9.46(1H,s),9.09-9.05(2H,m),8.38-8.34(1H,t),5.94-5.80(2H,q),4.37-4.36(1H,d),4.08-4.06(2H,d),3.68-3.65(2H,m),3.09(4H,m),2.23-2.18(2H,m),2.04-1.93(3H,m),1.18-1.09(3H,t)
质谱(m/z):399,400,401实施例54溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-5-溴吡啶鎓(化合物53)
得率:54%
M.P:Above 190-195℃(dec)
IR(KBr,cm-1):1682,1557,1540,1520
1H NMR(DMSO d6,400MHz)δ:11.35(1H,s),10.01(1H,s),9.57-9.54(2H,d),9.32(1H,s),8.26-8.22(2H,m),7.42(1H,s),6.39(2H,s),3.08(3H,s)
质谱(m/z):418,419,420实施例55溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓(化合物54)
得率:69%
M.P:155-157℃
IR(KBr,cm-1):1731,1665,1637
1H NMR(DMSO d6,400MHz)δ:11.04(1H,s),9.59(1H,s),9.53(1H,s),9.18(1H,s),9.05-9.04(1H,d),8.42(1H,s),8.25-8.23(2H,m),7.43(1H,s),6.46(2H,s),4.12-4.11(2H,s),1.23(3H,s)
质谱(m/z):334,335,336实施例56溴化1-(2-(5-氯噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物55)
得率:87%
M.P:228-230℃
IR(KBr,cm-1):1708,1664,1631,1550
1H NMR(DMSO d6,400MHz)δ:11.40(1H,s),9.98(1H,s),9.50(1H,s),9.15(1H,d),9.061H,d),8.43-8.39(1H,t),8.16-8.15(1H,d),7.51-7.50(1H,d),6.41(2H,s),3.09(3H,s)
质谱(m/z):374,375,376,377实施例57二氯N,N′-二[3-羰基-1-(2-(4-硝基噻吩-2-基)-2-氧代乙基)吡啶鎓]肼(化合物56)
得率:27%
M.P:204-207℃
IR(KBr,cm-1):1681,1539,1514
1H NMR(DMSO d6,400MHz)δ:11.90(2H,s),9.63(2H,s),9.31-9.30(4H,m),9.24-9.22(2H,m),8.87(2H,s),8.49-8.46(2H,t),6.56(4H,s)
质谱(m/z):581,582,583实施例58溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基吡啶鎓(化合物57)
得率:14%
M.P:90-95℃(dec)
IR(KBr,cm-1):1677,1575
1H NMR(DMSO d6,400MHz)δ:11.32(1H,s),9.97(1H,s)9.52(1H,s),8.94-8.92(1H,d),8.32-8.24(3H,m),7.44(1H,t),6.54(2H,s),3.08(3H,s),2.79(3H,s)
质谱(m/z):354,355,356实施例59二氯N,N′-二[3-羰基-1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)吡啶鎓]肼(化合物58)
得率:37%
M.P:Above 166-168℃(dec)
IR(KBr,cm-1):1666,1500
1H NMR(DMSO d6,400MHz)6:11.73(2H,s),9.59(2H,s),9.19-9.15(4H,d)8.45-8.42(2H,t),8.06-8.05(2H,d),7.15-7.14(2H,d),6.43(4H,s),2.59(6H,s)
质谱(m/z):519,520,521,522实施例60二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼(化合物59)
得率:28%
M.P:118-120℃
IR(KBr,cm-1):1660,1510
1H NMR(DMSO d6,400MHz)δ:11.75(2H,s),9.51(2H,s),9.20-9.10(4H,m)8.43-8.40(2H,t),5.97-5.83(4H,m),4.39-4.36(2H,m),4.27-4.22(1H,q),4.12-4.05(4H,m),3.71-3.63(4H,m),3.48-3.40(1H,m),2.26-2.19(2H,m),2.05-1.91(5H,m),1.30-1.27(1H,t),1.19-1.15(5H,t)
质谱(m/z):609,610,611实施例61二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼(化合物60)
得率:54%
M.P:Above 127-129℃(dec)
IR(KBr,cm-1):1678,1513
1H NMR(DMSO d6,400MHz)δ:11.86(2H,s),9.83-9.64(4H,t),9.24-9.23(2H,s),8.82(1H,s),8.48-8.45(1H,t),8.34(1H,s)8.26-8.24(4H,m),7.44-7.42(2H,d),6.52-6.46(4H,d)
质谱(m/z):534,535,536实施例62氯化1-(2-(4-乙酯基(carboethoxy)-噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物61)
得率:29%
M.P:190-192℃
IR(KBr,cm-1):1673,1541
1H NMR(DMSO d6,400MHz)δ:11.50(1H,s),9.55(1H,s),9.48(1H,s),9.12-9.08(2H,m),8.39-8.34(1H,t),6.04-5.99(2H,m),4.94-4.91(1H,m),4.87-4.84(1H,d),4.73-4.71(1H,d),4.28-4.23(1H,q),4.14-4.09(1H,q),3.43-3.38(1H,m),3.27-3.22(1H,m),3.10(3H,s),1.30-1.27(1H,t),1.20-1.17(2H,m)
质谱(m/z):439,440,441实施例63二氯N,N′-二[3-羰基-1-(2-(5-氯噻吩-2-基)-2-氧代乙基)吡啶鎓]肼(化合物62)
得率:35%
M.P:Above 200-205℃(dec)
IR(KBr,cm-1):1674,1590,1500
1H NMR(DMSOd6,400MHz)δ:11.90(2H,s),9.64-9.61(2H,d),9.29-9.20(4H,m),8.47-8.44(2H,t),8.18-8.17(2H,d),7.51-7.50(2H,d),6.49-6.48(4H,s)
质谱(m/z):559,560,561,562,563,564实施例64氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物63)
得率:22%
M.P:196-198℃
IR(KBr,cm-1):1689,1657
1H NMR(DMSO d6,400MHz)δ:11.47(1H,s),9.98(1H,s),9.53(1H,s),9.17-9.16(1H,d),9.09-9.07(1H,d),8.42-8.38(1H,t),8.06-8.05(1H,d),7.15-7.14(1H,d),6.41(2H,s),3.09(3H,s),2.59(3H,s)
质谱(m/z):354,355,356,357实施例65溴化1-(2-(4-硝基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物64)
得率:52%
M.P:Above 200-205℃(dec)
IR(KBr,cm-1):1688,1631,1541
1H NMR(DMSO d6,400MHz)δ:11.41(1H,s),9.50(1H,s)9.309-9.306(1H,d),9.17-9.15(1H,d),9.09-9.07(1H,d),8.866-8.862(1H,d),8.45-8.41(1H,t),6.50(2H,s),3.09(3H,s)
质谱(m/z):385,386,387实施例66氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物65)
得率:45%
M.P:165-167℃
IR(KBr,cm-1):1679,1626,1600,1497
1H NMR(DMSO d6,400MHz)δ:11.18(1H,s),11.10(1H,s),9.62(1H,s),9.24-9.22(1H,d),9.17-9.15(1H,d),8.40-8.36(1H,t),8.19(1H,s),7.63-7.61(2H,d),7.37-7.33(2H,t),7.20-7.16(2H,t),7.12-7.09(1H,t),6.88-6.86(2H,d),6.78-6.74(1H,t),5.78(2H,s)
质谱(m/z):347,348,349实施例67氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物66)
得率:40%
M.P:178-180℃
IR(KBr,cm-1):1700,1666,1559
1H NMR(DMSO d6,400MHz)δ:11.13(1H,s),9.74-9.71(1H,t),9.23-9.22(2H,d),8.52-8.50(2H,d),8.01-7.99(2H,d),7.68-7.60(3H,m),7.54-7.51(2H,t),7.36-7.32(2H,t),7.12-7.08(1H,t),5.75(2H,s),4.47-4.45(2H,t),3.77-3.72(2H,q).
质谱(m/z):404,405,406实施例68氯化1-(2-(5-硝基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓(化合物67)
得率:10%
M.P:Above 105-110℃(dec)
IR(KBr,cm-1):1680,1620
1H NMR(DMSO d6,400MHz)δ:11.48(1H,s),9.98(1H,s),9.52(1H,s),9.16-9.10(2H,m),8.45-8.41(1H,t),8.35-8.34(1H,d),8.25-8.24(1H,d),6.50(2H,s),3.09(3H,s).
质谱(m/z):385,386,387实施例69溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)吡啶鎓(化合物68)
得率:22%
M.P:77-79℃
IR(KBr,cm-1):2960,1690,1673,1591
1H NMR(DMSO d6,400MHz)δ:11.76(1H,s),11.27(1H,s),9.61(1H,s),9.20-9.19(1H,d),9.07-9.05(1H,d),8.44-8.41(1H,t),8.25-8.22(2H,m),7.34-7.41(1H,m),6.46(2H,s).
质谱(m/z):394,395,396实施例70溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物69)
得率:10%
M.P:192-194℃
IR(KBr,cm-1):1669,1663,1603,
1H NMR(DMSO d6,400MHz)δ:10.99(1H,s),9.54(1H,s),9.17-9.14(2H,t),8.44-8.41(1H,t),8.25-8.22(3H,m),7.43-7.41(1H,t),7.20-7.16(2H,t),6.87-6.85(2H,d),6.79-6.75(1H,t),6.46(2H,s)
质谱(m/z):338,339,340实施例71溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓(化合物70)
得率:28%
M.P:126-128℃
IR(KBr,cm-1):1672,1653,1596
1H NMR(DMSO d6,400MHz)δ:11.34-11.33(1H,d),10.27-10.26(1H,d),9.34(1H,s),9.13-9.12(1H,d),8.94-8.92(1H,d),8.38-8.34(1H,t),8.24-8.19(2H,m),7.82-7.75(2H,m),7.42-7.40(1H,t),7.07-7.04(2H,d),6.40(2H,s),3.81(3H,s).
质谱(m/z):432,433,434实施例72溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓(化合物71)
得率:25%
M.P:183-185℃
IR(KBr,cm-1):1746,1717,1682
1H NMR(DMSO d6,400MHz)δ:11.02(1H,s),9.57(1H,s),9.22-9.21(1H,d),9.11-9.09(1H,d),9.00(1H,s),8.57(1H,s),8.44-8.41(1H,m),7.47-7.45(2H,d),7.29-7.25(2H,t),7.00-6.96(1H,t),5.74(2H,s),4.28-4.23(2H,q),1.28-1.25(3H,t).
质谱(m/z):343,344,345,346实施例73溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲基苯磺酰基肼基羰基)吡啶鎓(化合物72)
得率:54%
M.P:174-176℃
IR(KBr,cm-1):1746,1712,1634
1H NMR(DMSO d6,400MHz)δ:11.33(1H,s),10.36(1H,s),9.37(1H,s),9.18-9.16(1H,d),8.93-8.91(1H,d),8.37-8.33(1H,t),7.78-7.76(2H,d),7.37-7.35(2H,d),5.68(2H,s),4.26-4.20(2H,q),2.37(3H,s),1.27-1.23(3H,t).
质谱(m/z):378,379,380,381实施例74溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓(化合物73)
得率:70%
M.P:206-208℃
IR(KBr,cm-1):1713,1684,1634
1H NMR(DMSO d6,400MHz)δ:11.05(1H,s),9.55(1H,s),9.18-9.13(2H,m),9.02(1H,s),8.59(1H,s),8.49-8.45(1H,m),8.09-8.07(2H,d),7.84-7.80(1H,t),7.71-7.67(2H,t),7.49-7.47(2H,d),7.30-7.26(2H,t),7.01-6.97(1H,t),6.56(2H,s).
质谱(m/z):375,376,377实施例75氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓(化合物74)
得率:48%
M.P:208-210℃
IR(KBr,cm-1):1712,1681,1632
1H NMR(DMSO d6,400MHz)δ:11.46(1H,s),10.80(1H,s),9.59(1H,s),9.22-9.20(1H,d),9.08-9.06(1H,d),8.38-8.36(1H,t),7.60-7.58(2H,d),7.49(2H,m),7.39-7.34(5H,m),7.13-7.10(1H,t),5.74(2H,s),4.52(2H,s).
质谱(m/z):425,426,427,428实施例76溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓(化合物75)
得率:10%
M.P:190-192℃
IR(KBr,cm-1):1679,1630,1650
1H NMR(DMSO d6,400MHz)δ:11.54(1H,s),10.03(1H,s),9.20-9.18(2H,d),8.59-8.57(2H,d),8.10-8.08(2H,d),7.84-7.80(1H.t),7.71-7.67(2H,t),6.56(2H,s),3.08(3H,s).
质谱(m/z):334,335,336实施例77溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物76)
得率:36%
M.P:204-206℃
IR(KBr,cm-1):1686,1653,1630
1H NMR(DMSO d6,400MHz)δ:11.01(1H,s),9.53(1H,s),9.17-9.16(2H,m),8.46-8.42(1H,t),8.09-8.07(2H,d),7.82-7.78(1H,t),7.69-7.65(2H,t),7.20-7.16(2H,t),6.88-6.86(2H,d),6.79-6.75(1H,t),6.56(2H,s)
质谱(m/z):332,333实施例78溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物77)
得率:82%
M.P:154-156℃
IR(KBr,cm-1):1742,1719,1707,1675
1H NMR(DMSO d6,400MHz)δ:9.57-9.54(1H,t),9.22-9.20(2H,d),8.51-8.49(2H,d),8.00-7.98(2H,d),7.68-7.64(1H,t),7.54-7.51(2H,t),5.72(2H,s),4.47-4.44(2H,t),4.27-4.21(2H,q),3.76-3.72(2H,q),1.27-1.24.(3H,t)
质谱(m/z):357,358,359.实施例79溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓(化合物78)
得率:37%
M.P:185-187℃
IR(KBr,cm-1):1740,1690,1630.
1H NMR(DMSO d6,400MHz)δ:11.01(1H,s),9.58(1H,s),9.23-9.14(2H,m),8.42-8.39(1H,t),8.19(1H,s),7.20-7.16(2H,t),6.87-6.85(2H,d),6.78-6.75(1H,t),5.75(2H,s),4.28-4.22(2H,q),1.28-1.24(3H,t)
质谱(m/z):300,301,302.实施例80溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓(化合物79)
得率:59%
M.P:188-190℃
IR(KBr,cm-1):1671,1634,1580.
1H NMR(DMSO d6,400MHz)δ:11.26-11.25(1H,d),10.17-10.16(1H,d),9.24(1H,s),9.03-9.01(1H,d),8.87-8.85(1H,d),8.31-8.27(1H,t),7.97-7.96(2H,d),7.74-7.69(3H,m),7.60-7.56(2H,t),6.99-6.97(2H,d),6.40(2H,s),3.73(3H,s).
质谱(m/z):426,427,428,429实施例81溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓(化合物80)
得率:92%
M.P:202-204℃
IR(KBr,cm-1):1715,1692,1650
1H NMR(DMSO d6,400MHz)δ:9.55(1H,s),9.14-9.13(2H,d),8.52-8.51(2H,d),8.07-7.99(4H,m),7.80-7.51(6H,m),6.52(2H,s),4.46(2H,s),3.76-3.75(2H,s).
质谱(m/z):389,390,391,392实施例82溴化1-(2-乙氧基-2-氧代乙基)-4-[对甲磺酰基肼基羰基]吡啶鎓(化合物81)
得率:45%
M.P:94-96℃
IR(KBr,cm-1):1726,1681,1643
1H NMR(DMSO d6,400MHz)δ:11.49(1H,s),9.98(1H,s),9.23-9.21(2H,d),8.54-8.52(2H,d),5.73(2H,s),4.28-4.22(2H,q),3.09(3H,s),1.28-1.25(3H,t).
质谱(m/z):302,303,304,305.实施例83溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)-吡啶鎓(化合物82)
将烟酰胺(1.22g,0.01mol)溶于回流甲苯(40ml),加入2,4-二氯苯甲酰甲基溴(3.0g,0.012mol)的甲苯(10ml)溶液。反应混合物回流7.5小时,然后冷却。滤出固体沉淀,将其溶于甲醇,用活性炭脱色,真空浓缩至1/4体积。在冰-盐混合物中冷却,滤出沉淀固体,用甲醇洗涤(3×10ml),得纯净固体
得率:39%
m.p.:237-239℃
IR(KBr,cm-1):3331,3133,1706,1678
1H NMR(DMSO d6,400MHz)δ:9.54(1H,s),9.18-9.11(2H,m),8.67(1H,s),8.40(1H,t),8.42-8.38(2H,m),7.88(1H,s),7.75-7.72(1H,m),6.49(2H,s)
质谱(m/z):309,310,311,312,187,159
按照上述方法合成以下化合物:用相应的吡啶衍生物与合适的反应试剂一起在甲醇、乙醇、丙醇等醇溶剂和甲苯或二甲苯等高沸点溶剂中回流6-48小时,得所需化合物:实施例84溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)-吡啶鎓(化合物83)
得率:48%
m.p.:165-167℃(decomp.)
IR(KBr,cm-1):3333,1714,1684,1635
1H NMR(CD3OD,400MHz)δ:9.45(1H,s),9.27-9.24(1H,m),8.92-8.91(1H,m),8.24-8.21(1H,m),8.01-7.99(1H,m),7.72-7.71(1H,m)7.57-7.54(1H,m),2.59-2.57(4H,m),1.85(4H,m)
质谱(m/z):446,447,448,449,416,307和266实施例85溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓(化合物84)
得率:98%
m.p.:182-184℃(decomp.)
IR(KBr,cm-1):3289,3241,1690和1660
1H NMR(DMSO d6,400MHz)δ:9.47(1H,s),9.21(1H,t),9.09(2H,t),8.41-8.37(1H,m),8.08-8.04(2H,m),7.82-7.78(1H,m),7.69-7.65(2H,m),6.52(2H,s),4.86(1H,t),3.58-3.54(2H,m),3.42-3.38(2H,m)
质谱(m/z):285,242,149,119,91实施例86溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓(化合物85)
得率:35%
m.p.:212-215℃(decomp.)
IR(KBr,cm-1):3295,3126,1680,1671,1640
1H NMR(DMSO d6,400MHz)δ:9.49(1H,s),9.13-9.11(1H,d),9.07-9.05(1H,d),8.60(1H,bs),8.40-8.38(1H,m),8.25-8.19(3H,m),7.43-7.40,(1H,t),6.44(2H,s)
质谱(m/z):247,248,249,193实施例87溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓(化合物86)
得率:44%
m.p.:188-190℃
IR(KBr,cm-1):3296,1700,1679.
1H NMR(DMSO d6,400MHz)δ:11.25(1H,s),9.58(1H,s),9.25(1H,d),9.16(1H,d),8.45.(1H,t),8.10(2H,d),7.94(2H,d),7.86(2H,d),7.82(1H,t),7.68(2H,t),7.36(2H,s),6.5(2H,s)
质谱(m/z):396,277实施例88溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物87)
得率:87%
m.p.:138-140℃
IR(KBr,cm-1):1748,1669
1H NMR(CD3OD,400MHz)δ:9.43(1H,s),9.09-9.02(2H,m),8.26(1H,m), 5.64(2H,s),4.31(2H,q),3.73(2H,t),3.54(2H,t),1.32(3H,t)
质谱(m/z):251,252,165,166实施例89溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓(化合物88)
得率:46%
m.p.:172-174℃
IR(KBr,cm-1):1726,1692
1H MR(DMSOd6,400MHz)δ:9.55(1H,s),9.16(1H,d),9.08(1H,d),8.39-8.36(1H,m),8.04(2H,d),7.77(1H,t),7.64(2H,t),6.53(2H,s),5.25-5.19(1H,m),1.34(6H,d)
质谱(m/z):284,285,242实施例90氯化1-(2-甲基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物89)
得率:47%
m.p.:178-180℃
IR(KBr,cm-1):1727,1660
1H NMR(DMSOd6,400MHz)δ:9.33(1H,t),9.30(1H,s),9.06(1H,d),8.90(1H,d),8.25-8.21(1H,m),5.75(2H,s),4.84(1H,bs),3.47(2H,t),3.30(2H,t),2.23(3H,s)
质谱(m/z):223,224,225实施例91溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物90)
得率:60%
m.p.:207-209℃
IR(KBr,cm-1):1673,1656
1H NMR(DMSOd6,400MHz)δ:9.47(1H,s),9.18-9.05(3H,m),8.38-8.34(1H,m),8.23-8.19(2H,m),7.39(1H,t),6.44(2H,s),3.55-3.50(2H,m),3.40-3.37(2H,m)
质谱(m/z):291,292,293实施例92溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓(化合物91)
得率:26%
m.p.:160-162℃
IR(KBr,cm-1):1726,1705
1H NMR(DMSOd6,400MHz)δ:9.55(1H,s),9.15(1H,d),9.08(1H,d),8.40-8.36(1H,m),8.11(1H,d),7.89(1H,bs),7.75-7.72(1H,m),6.44(2H,s),5.26-5.20(1H,m),1.34(6H,d).
质谱(m/z):352,353,354,310实施例93溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓(化合物92)
得率:30%
m.p.:165-167℃
IR(KBr,cm-1):3409,3319 and 1698
1H NMR(DMSOd6,400MHz)δ:9.58(1H,s),9.22(1H,d),9.11(1H,d),8.42-8.38(1H,m),8.07(2H,d),7.81(1H,t),7.68(2H,t),6.86(1H,bs),6.56(2H,s),2.30(3H,s)
质谱(m/z):337,338,232,105.实施例94氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓(化合物93)
得率:10%
m.p.:150-152℃
IR(KBr,cm-1):3228,1742,1678(bs)
1H NMR(DMSOd6,400MHz)δ:10.96(1H,s),9.65(1H,s),9.28(1H,t),9.09(1H,d),8.37-8.34(1H,m),7.62-7.59(2H,m),7.37-7.33(2H,m),7.11(1H,t),5.79(2H,s),4.41(2H,t),1.76-1.72(2H,m),1.48-1.43(2H,m),0.94(3H,t)
质谱(m/z):314,315实施例95氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓(化合物94)
得率:37%
m.p.:182-185℃
IR(KBr,cm-1):3245,1742,1679
1H NMR(DMSOd6,400MHz)δ:10.97(1H,s),9.50(1H,s),9.24(1H,t),9.13(1H,d),9.02(1H,d),8.28-8.25(1H,m),7.57(2H,d),7.30(2H,t),7.05(1H,t),5.70(2H,s),3.30-3.26(2H,m),1.52-1.48(2H,m),1.34-1.30(2H,m),0.86(3H,t)
质谱(m/z):312,313实施例96氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基]吡啶鎓(化合物95)
得率:58%
m.p.:225-227℃
IR(KBr,cm-1):3448,3271,1702 and 1663
1H NMR(DMSOd6,400MHz)δ:11.07(1H,s),9.58(1H,s)9.35(1H,t),9.17(1H,d),9.11(1H,d),8.33-8.29(1H,m),7.60(2H,d),7.32(2H,t),7.08(1H,t),5.75(2H,s),4.90(1H,t),3.57-3.53(2H,m),3.40-3.36(2H,m)
质谱(m/z):300,301,302实施例97溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓(化合物96)
得率:38%
m.p.:154-156℃
IR(KBr,cm-1):3435,3389,1731 and 1704
1H NMR(DMSOd6,400MHz)δ:9.60(1H,s),9.21(1H,d),9.14(1H,d),8.43(1H,t),8.16(1H,d),7.92(1H,s),7.78-7.76(1H,m),6.51(2H,s),4.42(2H,t),1.76-1.72(2H,m),1.48-1.42
(2H,m),0.94(3H,t)
质谱(m/z):366,367,368,369,370实施例98溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓(化合物97)
得率:35%
m.p.:142-144℃(分解)
IR(KBr,cm-1):3382,1698,1672
1H NMR(DMSOd6,400MHz)δ:9.37(1H,s),9.07(1H,t),8.99(2H,t),8.31-8.28(1H,m),8.04(1H,d),7.82-7.81(1H,d),7.68-7.65(1H,m),6.34(2H,s),3.27-3.24(2H,m),1.47-1.43(2H,m),1.29-1.24(2H,m),0.81(3H,t)
质谱(m/z):415,416化妆品制剂
用作自由基清除剂和AGE裂解剂的制剂可在化妆品学上认可的载体中含有一种或多种浓度的化合物。本发明化合物的含量以0.005-50重量%为宜(除非另作说明,所有的分数都是重量百分比),0.25-5.0%更好。本发明组合物应根据需要用在病患部位。
适合储存和/或传递本发明新化合物的载体可以是搽剂、液剂、药膏、凝胶、霜剂、喷雾剂、敷药或其他形式,并以具有亲脂性、亲水性或两亲性为佳。合适的载体包括凡士林,甘油三脂,各种酯,脂肪醇,脂肪酸,烷撑二醇和乙醇,其中优选聚乙二醇、聚丙二醇,尤以聚乙二醇最好;如有必要,以上载体的相容性组合也可以。
而且,载体应符合所需传递系统的需要。根据常规实践,载体中还可以含有其他试剂。例如,最终的组合物可以含有各种润肤剂,乳化剂,醇,色素,香精,增稠剂(例如黄原酸胶),防腐剂,保湿剂,表面活性剂(阴离子,阳离子,非离子,两性表面活性剂组合),可改善皮肤分化和/或增生和/或色素沉着的试剂,抗寄生物剂,分散剂,遮光剂,胶凝剂,水合剂,其他抗氧化剂,典型的植物提取物(例如芦荟、柑橘、Witch Hazel、甘菊等的提取物等,例如具有收敛性、杀菌、防晒或晒黑作用的那些),肤色改善剂,硅酮,剥落剂,去角质剂,维生素A,皮肤渗透强化剂,维生素,溶血栓剂,抗凝血剂,毛细血管保护剂,激素,抗菌剂,抗病毒剂,甾体类消炎药,麻醉剂,抗脂溢性皮炎剂,抗头皮屑剂,抗痤疮剂,抗自由基剂,镇痛剂,亲脂性化合物,抗组胺药,驱虫剂,皮肤清凉剂,润滑剂,抗真菌剂或以上所述的混合物。本发明的组合物也同样可以含有渗透强化剂,例如但不限于油酸,DMSO(二甲基亚砜),醇,N-甲基吡咯烷酮,二甲基异山梨酯。其中还可以含有一种或多种其他活性成分,例如消炎药,抗生素,收敛剂,生长激素,生育酚,维生素A,自由基清除剂。实施例99
本发明化合物 0.25%w/w
油酸 10.0%w/w
丙二醇 70.0%w/w
Tween80 0.1%w/w
纯乙醇 补足100.0%w/w实施例100
本发明化合物 0.25%w/w
油酸 10.0%w/w
二氧化硅凝胶 6.0%w/w
Tween80 0.1%w/w
辛酸癸酸甘油三酯 补足100.0%w/w
(caprylic capric triglyceride)
组合物中可以另含化妆品学上认可的有机脂肪酸,其含量以生物活性有效量为宜,即0.1-10.0%;脂肪酸的加入是作为优选成分。
据信,本发明化合物与保湿剂、润肤剂、其他抗氧化剂或消炎药联用时具有协同性改善作用。实施例101
本发明化合物 0.5%w/w
脂肪酸 4.0%w/w
矿物油 5.0%w/w
硬脂酸异十六烷酯 1.0%w/w
抗氧化剂 0.05%w/w
黄原酸胶 0.2%w/w
甘油 50.0%w/w
二(四氢咪唑基)脲 0.2%w/w
柠檬皮提取物 0.02%w/w
乙醇 2.0%w/w
纯水 补足100.0%w/w
抗氧化组合物中加入保湿剂和润肤剂有助于所测皮肤的重新水合和保湿。皮肤保湿性改善被认为即可提高皮肤对自由基清除剂的吸收,又有助于自由基清除剂向活性部位的传递。
可用的润肤剂例子有:矿物油,矿脂,石蜡,纯地蜡(ceresin),地蜡(ozokerite),微晶蜡,全氢化角鲨烯,二甲基聚硅氧烷,甲基苯基聚硅氧烷,硅酮,硅酮-乙二醇共聚物,甘油三酯,乙酰化单酸甘油酯,乙氧基化甘油酯,脂肪酸的烃基酯,脂肪酸和醇,羊毛脂和羊毛脂衍生物,多元醇酯,甾醇,蜂蜡衍生物,多元醇和聚醚,以及脂肪酸的酰胺。虽然各种已知润肤剂都可用于本发明,但优选硅酮。
适合的保湿剂是已知局部使用时可提高皮肤水合度的那些,例如多元醇。合适的保湿剂例子是:甘油,丙二醇,丁二醇,双甘油,或它们的酯衍生物。然而,优选的保湿剂是甘油。
本发明的局部使用制剂可在本发明化合物之外另含一种或多种抗氧化剂,于是形成抗氧化剂混合物。“抗氧化剂”在此即包括一种抗氧化剂也包括抗氧化剂混合物。可将抗氧化剂加入各种载体以优化局部使用。
为了获得优良的霜剂、乳液、搽剂或凝胶形式的局部使用组合物,其中可含约0.001-50%w/w抗氧化剂。
本发明的局部使用组合物可制成搽剂或霜剂。自由基清除剂可与大多数用于搽剂、霜剂等合适的局部使用载体相互混合。乳化剂可用阳离子型、阴离子型、非离子型或两性型,或以上所述的混合物。优选的是非离子型乳化剂。非离子型乳化剂的例子有市售的脱水山梨醇,烷氧基化脂肪醇和烷基聚糖苷。阴离子型乳化剂包括皂,硫酸烃酯,磷酸单烃酯和磷酸双烃酯,磺酸烃酯和酰基异硫代硫酸盐。可用的两性乳化剂是氯化乳酰氨基丙基三铵。
适用于本发明的载体可包含增稠剂。合适的增稠剂例子包括例如羟乙基纤维素和羟丙基纤维素等纤维素衍生物,以及聚合丙烯酸类聚合物。
适用的防腐剂例子包括烷醇,尤其是乙醇和苄醇;对羟基苯甲酸酯;山梨酸酯;脲衍生物;和异噻唑啉酮。
本发明搽剂或霜剂可用常规已知均质化方法来制备。也可采用微液化技术,该方法包括:在高压均质仪中将霜剂和搽剂的水相与油相混合,与非高压条件下制备的霜剂和搽剂相比,该方法显著减小乳液颗粒至数微米。微液化可制备出含有效量化合物的优良稳定霜剂和搽剂而无需使用常规乳化剂和表面活性剂。
本发明局部使用组合物还可配制成微乳液,这属于乳液的一种。可用的油是矿物油和硅油。可用的醇的例子是十六烷醇,异十八烷醇,硬脂醇,十二烷醇和十二烯醇。非离子表面活性剂可以是脂肪酸,脂肪醇或乙氧基化的醇类的酯。非离子型表面活性剂的例子是聚乙二醇,肉豆蔻酸异丙酯,异十八烷酸十六烷酯,聚丙二醇,脱水山梨醇和油酸异丙酯。实施例102
本发明化合物 0.25%w/w
脂肪酸 1.5%w/w
表面活性剂 3.0%w/w
助溶剂 70.0%w/w
纯水 补100.0%w/w
本发明的局部使用组合物可配制成水包油或油包水型乳液。组合物的形式可以是多相乳液,例如水包油包水型乳液。
可将本发明组合物制成脂质体制剂。在此类组合物中,可将本发明化合物的溶液包在脂质体载体中,脂质体外壳可以是磷脂或其他合适的脂类(例如皮脂类)。为了形成局部使用组合物,然后可根据局部使用脂质体的制备方法、用途和组成,将脂质体加入前文所述的各种载体系统中。实施例103
本发明化合物 0.5%w/w
磷脂 6.0%w/w
抗氧化剂 0.5%w/w
乙醇 15.0%w/w
亲水性介质 补足100.0%w/w
还可将化合物和抗氧化剂的溶液包在聚合物载体中,外壳由合适的聚合物构成,例如由明胶、交联明胶、聚酰胺、聚丙烯酸酯等构成的载体,然后将其加入局部使用组合物中。
本发明组合物可用于一种或多种以下化妆品用途:(a)减少和防止皱纹;(b)减少和防止细线;(c)促进表皮生长;(d)避光;(e)逆转和避免皮肤色素沉着;(f)逆转和避免老年斑;(g)调理和避免干燥;(h)逆转和避免拉伸纹;(i)逆转和避免色斑;(j)皮肤护理/皮肤调理;(k)逆转和避免老年性干燥;(l)调理和避免晒伤;(m)避免和逆转胶原蛋白流失;(n)改善皮肤肌理;(o)改善肤色;(p)增强皮肤厚度;(q)缩小毛孔;(r)恢复皮肤光泽;(s)减弱疲劳痕迹;(t)减少痤疮;(u)治疗毛细管扩张和(v)改善指甲和毛发外观。
以上实施例仅是对本发明的说明而非限定。
Claims (30)
1.一种化妆品组合物,其中,在化妆品用载体中包含有效量的结构式I化合物或其化妆品学上认可的盐,所述化合物或其盐具有自由基清除活性,AGE裂解活性和AGE抑制活性
其中,R1是-R4-R5或-N(R7)N(R7)R9或Y-R11;
R4选自-N(R7)R6O-,-N(R7)R6N(R7),-OR6O和-OR6N(R7)-,其中的R6是C2-C8烃基;
其中R7选自H,烃基,包括杂芳基的芳基,同一化合物中R1和R3的R7可以相同或不同;
R2选自F,Cl,Br,I,OR7,NO2,烃基,包括杂芳基的芳基,甲酰基,酰基,C(O)NR7R10,C(O)OR7,NR7R10,N=C(R7)(R10),SR7,SO2NH2,SO2烃基和SO2芳基;
m是0,1或2;
R3选自R7,OR7,N(R7)(R10),N=C(R7)(R10),N(R7)N(R7)(R10),N(R7)N=C(R7)(R10)和CH(R7)C(O)R8,其中的R8选自R7,OR7和NR7R10;
R9选自H,烃基,包括杂芳基的芳基,C(O)R10,-SO2R10,C(S)NHR10,C(NH)NH(R10)和C(O)NHR10;
R10选自H,烃基,包括杂芳基的芳基,如果同一化合物R1和R3的R10可以相同或不同,则R10与R7可以相同或不同;
Y选自O,NH,NR12,或者不存在,
R11和R12各自选自H,烃基和芳基。
X选自卤离子,乙酸根离子,高氯酸根离子,磺酸根离子,草酸根离子,柠檬酸根离子,甲苯磺酸根离子,马来酸根离子,甲磺酸根离子,碳酸根离子,亚硫酸根离子,磷酸氢根离子,膦酸根离子,磷酸根离子,BF4 -和PF6 -;
条件是:
(i)当两烃基位于同一碳原子或氮原子上时,它们可以彼此连接成环结构;
(ii)如果R10杂芳环上含有氮原子,则它可以是季氮原子;
(iii)当R3是OR7且R1是-NHNH2时,R7不是烃基,而且
(iv)当R3是OR7,R1是N(R7)(NR7)R9且R9是C(O)R10,其中的是R10是烃基时,R7不是H。
2.根据权利要求1所述的组合物,其中所述化合物的-C(O)R1基团位于3和4位。
3.根据权利要求2所述的组合物,其中所述化合物的-C(O)R1基团位于3位。
4.根据权利要求1所述的组合物,其中m是0或1。
5.根据权利要求2所述的组合物,其中m是0或1。
6.根据权利要求3所述的组合物,其中m是0或1。
7.根据权利要求1所述的组合物,其中m是0。
8.根据权利要求2所述的组合物,其中m是0。
9.根据权利要求3所述的组合物,其中m是0。
10.根据权利要求1所述的组合物,其中X是卤离子。
11.根据权利要求1所述的组合物,其中所述化合物选自:
(a)二溴N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)-3-吡啶鎓]肼,或其他其化妆品学上认可的盐,
(b)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(c)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(d)二溴N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(e)溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(f)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(g)二溴N,N′-二[3-羰基-1-(2-(2′,4′-二氯苯基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(h)溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(i)溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(j)溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(k)溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(l)溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(m)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(n)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基)羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(o)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(p)氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(q)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(r)氯化1-(2-苯基氨基-2-氧代乙基)-3-((苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(s)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(t)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(u)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(v)氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(w)溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(x)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(y)溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(z)溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aa)二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ab)二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ac)二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ad)溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ae)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(af)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ag)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ah)氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ai)氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aj)溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-丙基}-肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ak)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(al)氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(am)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基]肼基吡啶鎓,或其他其化妆品学上认可的盐,
(an)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ao)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)-吡啶鎓,或其他其化妆品学上认可的盐,
(ap)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(aq)二氯N,N′-二[3-羰基-1-(2-(5-甲基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ar)二氯N,N′-二[3-羰基-1-(2-(5-氯-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(as)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基-吡啶鎓,或其他其化妆品学上认可的盐,
(at)二氯N,N′-二[3-羰基-1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(au)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(av)溴化1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aw)氯化1-(2-(5-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ax)溴化1-(2-(5-氯-噻吩-2基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ay)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(az)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ba)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲基磺酰基肼基羰基)-5-溴吡啶鎓,或其他其化妆品学上认可的盐,
(bb)氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bc)氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bd)氯化1-(2-(4-乙酯基噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(be)氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bf)二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(bg)氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bh)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bi)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bj)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bk)溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bl)溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bm)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bn)溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bo)溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bp)溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bq)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(br)溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bs)溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bt)溴化1-(2-乙氧基-2-氧代乙基)-4-(对甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bu)溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bv)溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bw)溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bx)溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧基乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(by)溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bz)溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ca)溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cb)氯化1-(2-氧丙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cc)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cd)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ce)溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cf)氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cg)氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ch)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ci)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cj)溴化1-(2-苯基-2-氧代乙基)-3-(1-苯基-1-氧甲基)吡啶鎓,或其他其化妆品学上认可的盐,
(ck)溴化1-(2-苯基-2-氧代乙基)-3-(甲氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐。
12.根据权利要求1所述的化合物,它可用于:
a)减少和预防皱纹,
b)减少和预防细纹,
c)促进表皮生长,
d)避光保护,
e)消退和预防皮肤色素沉着,
f)消退和预防老年斑,
g)调理和预防干燥,
h)消退和预防拉伸痕迹,
i)消退和预防色斑,
j)皮肤护理和皮肤调理,
k)减轻和预防老年性干燥,
l)调理和预防晒伤,
m)预防和逆转胶原蛋白流失,
n)改善皮肤肌理,
o)改善肤色,
p)增强皮肤厚度,
q)缩小毛孔,
r)恢复皮肤光泽,
s)消退疲劳痕迹,
t)缓解痤疮,
u)治疗毛细管扩张,
v)改善毛发和指甲的外观。
13.一种化妆品组合物,其中,在化妆品用载体中包含有有效量的权利要求1所述具有自由基清除剂,AGE裂解剂和AGE抑制剂活性的结构式I化合物或其化妆品学上认可的盐,该组合物至少具有以下功效之一:
a)减少和预防皱纹,
b)减少和预防细纹,
c)促进表皮生长,
d)避光保护,
e)消退和预防皮肤色素沉着,
f)消退和预防老年斑,
g)调理和预防干燥,
h)消退和预防拉伸痕迹,
i)消退和预防色斑,
j)皮肤护理和皮肤调理,
k)减轻和预防老年性干燥,
l)调理和预防晒伤,
m)预防和逆转胶原蛋白流失,
n)改善皮肤肌理,
o)改善肤色,
p)增强皮肤厚度,
q)缩小毛孔,
r)恢复皮肤光泽,
s)消退疲劳痕迹,
t)缓解痤疮,
u)治疗毛细管扩张,
v)改善毛发和指甲的外观。
14.根据权利要求13所述的组合物,其形式是溶液、凝胶、药膏、搽剂、霜剂、微乳液喷雾剂、悬浮液或乳剂。
15.一种逆转和预防皮肤衰老和皱纹的美容方法,包括使用包含在化妆品学上认可的载体中的有效量的权利要求1所述具有自由基清除剂,AGE裂解剂和AGE抑制剂活性的结构式I化合物或其化妆品学上认可的盐。
16.根据权利要求15所述的方法,所述的有效量可有效抗衰老。
17.根据权利要求16所述的方法,其中的衰老包括外部衰老和内部衰老。
18.根据权利要求16所述的方法,其中的衰老是外部衰老。
19.一种至少对以下现象之一有逆转和预防效果的美容方法:
i)细纹,
ii)皮肤色素沉着,
iii)老年斑,
iv)拉伸痕迹,
v)色斑,
vi)老年性干燥,
vii)预防和逆转胶原蛋白流失,
该方法包括使用包含在化妆品学上认可的载体中的有效量的权利要求1所述具有自由基清除剂,AGE裂解剂和AGE抑制剂活性的结构式I化合物或其化妆品学上认可的盐。
20.一种对皮肤干燥和/或晒伤具有护理和预防作用的美容方法,包括使用包含在化妆品学上认可的载体中的有效量的权利要求1所述具有自由基清除剂,AGE裂解剂和AGE抑制剂活性的结构式I化合物或其化妆品学上认可的盐。
21.一种可促进表皮生长和/或提供避光保护,改善皮肤肌理,改善肤色,增强皮肤厚度,缩小毛孔,恢复皮肤光泽,消退疲劳痕迹,增白,治疗毛细管扩张的美容方法,包括使用包含在化妆品学上认可的载体中的有效量的权利要求1所述具有自由基清除剂,AGE裂解剂和AGE抑制剂活性的结构式I化合物或其化妆品学上认可的盐。
22.根据权利要求15所述的方法,其中所述化合物选自:
(a)二溴N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)-3-吡啶鎓]肼,或其他其化妆品学上认可的盐,
(b)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(c)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(d)二溴N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(e)溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(f)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(g)二溴N,N′-二[3-羰基-1-(2-(2′,4′-二氯苯基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(h)溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(i)溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(j)溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(k)溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(l)溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(m)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(n)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基)羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(o)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(p)氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(q)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(r)氯化1-(2-苯基氨基-2-氧代乙基)-3-((苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(s)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(t)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(u)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(v)氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(w)溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(x)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(y)溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(z)溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aa)二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ab)二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ac)二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ad)溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ae)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(af)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ag)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ah)氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ai)氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aj)溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-丙基}-肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ak)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(al)氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(am)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基]肼基吡啶鎓,或其他其化妆品学上认可的盐,
(an)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ao)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)-吡啶鎓,或其他其化妆品学上认可的盐,
(ap)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(aq)二氯N,N′-二[3-羰基-1-(2-(5-甲基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ar)二氯N,N′-二[3-羰基-1-(2-(5-氯-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(as)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基-吡啶鎓,或其他其化妆品学上认可的盐,
(at)二氯N,N′-二[3-羰基-1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(au)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(av)溴化1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aw)氯化1-(2-(5-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ax)溴化1-(2-(5-氯-噻吩-2基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ay)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(az)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ba)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲基磺酰基肼基羰基)-5-溴吡啶鎓,或其他其化妆品学上认可的盐,
(bb)氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bc)氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bd)氯化1-(2-(4-乙酯基噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(be)氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bf)二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(bg)氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bh)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bi)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bj)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bk)溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bl)溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bm)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bn)溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bo)溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bp)溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bq)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(br)溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bs)溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bt)溴化1-(2-乙氧基-2-氧代乙基)-4-(对甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bu)溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bv)溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bw)溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bx)溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧基乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(by)溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bz)溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ca)溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cb)氯化1-(2-氧丙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cc)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cd)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ce)溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cf)氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cg)氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ch)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ci)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cj)溴化1-(2-苯基-2-氧代乙基)-3-(1-苯基-1-氧甲基)吡啶鎓,或其他其化妆品学上认可的盐,
(ck)溴化1-(2-苯基-2-氧代乙基)-3-(甲氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐。
23.根据权利要求19所述的方法,其中所述化合物选自:
(a)二溴N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)-3-吡啶鎓]肼,或其他其化妆品学上认可的盐,
(b)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(c)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(d)二溴N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(e)溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(f)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(g)二溴N,N′-二[3-羰基-1-(2-(2′,4′-二氯苯基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(h)溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(i)溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(j)溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(k)溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(l)溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(m)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(n)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基)羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(o)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(p)氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(q)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(r)氯化1-(2-苯基氨基-2-氧代乙基)-3-((苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(s)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(t)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(u)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(v)氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(w)溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(x)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(y)溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(z)溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aa)二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ab)二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ac)二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ad)溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ae)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(af)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ag)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ah)氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ai)氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aj)溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-丙基}-肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ak)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(al)氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(am)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基]肼基吡啶鎓,或其他其化妆品学上认可的盐,
(an)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ao)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)-吡啶鎓,或其他其化妆品学上认可的盐,
(ap)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(aq)二氯N,N′-二[3-羰基-1-(2-(5-甲基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ar)二氯N,N′-二[3-羰基-1-(2-(5-氯-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(as)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基-吡啶鎓,或其他其化妆品学上认可的盐,
(at)二氯N,N′-二[3-羰基-1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(au)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(av)溴化1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aw)氯化1-(2-(5-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ax)溴化1-(2-(5-氯-噻吩-2基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ay)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(az)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ba)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲基磺酰基肼基羰基)-5-溴吡啶鎓,或其他其化妆品学上认可的盐,
(bb)氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bc)氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bd)氯化1-(2-(4-乙酯基噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(be)氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bf)二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(bg)氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bh)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bi)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bj)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bk)溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bl)溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bm)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bn)溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bo)溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bp)溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bq)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(br)溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bs)溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bt)溴化1-(2-乙氧基-2-氧代乙基)-4-(对甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bu)溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bv)溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bw)溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bx)溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧基乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(by)溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bz)溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ca)溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cb)氯化1-(2-氧丙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cc)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cd)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ce)溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cf)氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cg)氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ch)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ci)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cj)溴化1-(2-苯基-2-氧代乙基)-3-(1-苯基-1-氧甲基)吡啶鎓,或其他其化妆品学上认可的盐,
(ck)溴化1-(2-苯基-2-氧代乙基)-3-(甲氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐。
24.根据权利要求20所述的方法,其中所述化合物选自:
(a)二溴N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)-3-吡啶鎓]肼,或其他其化妆品学上认可的盐,
(b)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(c)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(d)二溴N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(e)溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(f)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(g)二溴N,N′-二[3-羰基-1-(2-(2′,4′-二氯苯基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(h)溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(i)溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(j)溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(k)溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(l)溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(m)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(n)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基)羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(o)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(p)氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(q)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(r)氯化1-(2-苯基氨基-2-氧代乙基)-3-((苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(s)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(t)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(u)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(v)氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(w)溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(x)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(y)溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(z)溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aa)二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ab)二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ac)二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ad)溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ae)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(af)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ag)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ah)氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ai)氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aj)溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-丙基}-肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ak)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(al)氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(am)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基]肼基吡啶鎓,或其他其化妆品学上认可的盐,
(an)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ao)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)-吡啶鎓,或其他其化妆品学上认可的盐,
(ap)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(aq)二氯N,N′-二[3-羰基-1-(2-(5-甲基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ar)二氯N,N′-二[3-羰基-1-(2-(5-氯-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(as)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基-吡啶鎓,或其他其化妆品学上认可的盐,
(at)二氯N,N′-二[3-羰基-1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(au)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(av)溴化1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aw)氯化1-(2-(5-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ax)溴化1-(2-(5-氯-噻吩-2基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ay)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(az)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ba)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲基磺酰基肼基羰基)-5-溴吡啶鎓,或其他其化妆品学上认可的盐,
(bb)氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bc)氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bd)氯化1-(2-(4-乙酯基噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(be)氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bf)二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(bg)氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bh)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bi)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bj)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bk)溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bl)溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bm)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bn)溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bo)溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bp)溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bq)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(br)溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bs)溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bt)溴化1-(2-乙氧基-2-氧代乙基)-4-(对甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bu)溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bv)溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bw)溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bx)溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧基乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(by)溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bz)溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ca)溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cb)氯化1-(2-氧丙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cc)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cd)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ce)溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cf)氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cg)氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ch)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ci)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cj)溴化1-(2-苯基-2-氧代乙基)-3-(1-苯基-1-氧甲基)吡啶鎓,或其他其化妆品学上认可的盐,
(ck)溴化1-(2-苯基-2-氧代乙基)-3-(甲氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐。
25.根据权利要求21所述的方法,其中所述化合物选自:
(a)二溴N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)-3-吡啶鎓]肼,或其他其化妆品学上认可的盐,
(b)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(2-吡啶基)肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(c)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(d)二溴N,N′-二[3-羰基-1-(2-苯基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(e)溴化1-(2-苯基-2-氧代乙基)-3-(肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(f)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(g)二溴N,N′-二[3-羰基-1-(2-(2′,4′-二氯苯基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(h)溴化1-(2-苯基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(i)溴化1-(2-乙氧基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(j)溴化1-(2-苯基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(k)溴化1-(2-苯基-2-氧代乙基)-2-氯-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(l)溴化1-(2-噻吩-2′-基-2-氧代乙基)-4-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(m)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(n)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙氧基)羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(o)溴化1-(2-乙氧基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(p)氯化1-(2-苯基氨基-2-氧代乙基)-4-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(q)溴化1-(2-(2′,4′-二氯苯基)-2-氧代乙基)-3-(2-(甲氧基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(r)氯化1-(2-苯基氨基-2-氧代乙基)-3-((苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(s)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(t)溴化1-(2-苯基-2-氧代乙基)-3-(2-(乙酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(u)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(v)氯化1-(2-苯基氨基-2-氧代乙基)-3-((4-甲基苯基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(w)溴化1-(2-苯基-2-氧代乙基)-3-(2-(苯甲酸基)乙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(x)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(苯基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(y)溴化1-(2-乙氧基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(z)溴化1-(2-苯基-2-氧代乙基)-3-((苯基甲基)磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aa)二溴N,N′-二[3-羰基-1-(2-呋喃-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ab)二氯N,N′-二[3-羰基-1-(2-噻吩-2′-基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ac)二氯N,N′-二[3-羰基-1-(2-环丙基氨基-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ad)溴化1-(2′,4′-二氯苯基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ae)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-甲氧基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(af)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ag)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-(2-(2-氯-3-吡啶甲酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ah)氯化1-(2-环丙基氨基-2-氧代乙基)-3-(2-甲氧基乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ai)氯化1-(2-异丙基氨基-2-氧代乙基)-3-(2-甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aj)溴化1-(2-苯基氨基-2-氧代乙基)-3-({2-(1-氧-3-环己基)-丙基}-肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ak)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-[2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(al)氯化1-(4-乙氧基-2,4-二氧丁基)-3-(2-(苯甲酸基)乙基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(am)氯化1-(2-噻吩-2′-基-2-氧代乙基)-3-[1-氧-1-(2-甲氧基羰基)吡啶基]肼基吡啶鎓,或其他其化妆品学上认可的盐,
(an)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-5-氨基羰基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ao)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(三氟甲磺酰基肼基羰基)-吡啶鎓,或其他其化妆品学上认可的盐,
(ap)二氯1-[1-(2-噻吩-2′-基-2-氧代乙基)-6-甲基-3-羰基吡啶鎓]-2-[1-(2-噻吩-2′-基-2-氧代乙基)-3-羰基吡啶鎓]肼,或其他其化妆品学上认可的盐,
(aq)二氯N,N′-二[3-羰基-1-(2-(5-甲基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(ar)二氯N,N′-二[3-羰基-1-(2-(5-氯-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(as)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲磺酰基肼基羰基)-6-甲基-吡啶鎓,或其他其化妆品学上认可的盐,
(at)二氯N,N′-二[3-羰基-1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(au)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(av)溴化1-(2-(4-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(aw)氯化1-(2-(5-硝基-噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ax)溴化1-(2-(5-氯-噻吩-2基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ay)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(乙氧基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(az)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(异丙基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ba)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-(甲基磺酰基肼基羰基)-5-溴吡啶鎓,或其他其化妆品学上认可的盐,
(bb)氯化1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bc)氯化1-(2-(5-甲基噻吩-2-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bd)氯化1-(2-(4-乙酯基噻唑烷-3-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(be)氯化1-(2-(4-苄基哌啶-1-基)-2-氧代乙基)-3-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bf)二氯N,N′-二[3-羰基-1-(2-(2-乙氧基羰基吡咯烷-1-基)-2-氧代乙基)吡啶鎓]肼,或其他其化妆品学上认可的盐,
(bg)氯化1-(2-苯基氨基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bh)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bi)溴化1-(2-噻吩-2-基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bj)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bk)溴化1-(2-乙氧基-2-氧代乙基)-3-(对甲苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bl)溴化1-(2-苯基-2-氧代乙基)-3-(苯基氨基羰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bm)氯化1-(2-苯基氨基-2-氧代乙基)-3-(苄基磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bn)溴化1-(2-苯基-2-氧代乙基)-4-(甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bo)溴化1-(2-苯基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bp)溴化1-(2-乙氧基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bq)溴化1-(2-乙氧基-2-氧代乙基)-3-(苯基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(br)溴化1-(2-苯基-2-氧代乙基)-3-(对甲氧基苯磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bs)溴化1-(2-苯基-2-氧代乙基)-4-[2-(苯甲酸基)乙基氨基羰基]吡啶鎓,或其他其化妆品学上认可的盐,
(bt)溴化1-(2-乙氧基-2-氧代乙基)-4-(对甲磺酰基肼基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bu)溴化3-羰基氨基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bv)溴化3-(四氢苯并噻唑-2-基)氨基羰基-1-(2-(2,4-二氯苯基)-2-氧代乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(bw)溴化1-(2-苯基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bx)溴化3-羰基氨基-1-(2-噻吩-2′-基-2-氧基乙基)吡啶鎓,或其他其化妆品学上认可的盐,
(by)溴化1-(2-苯基-2-氧代乙基)-3-((对亚磺酰氨基苯基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(bz)溴化1-(2-乙氧基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ca)溴化1-(2-苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cb)氯化1-(2-氧丙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cc)溴化1-(2-噻吩-2′-基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cd)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(异丙氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ce)溴化1-(2-苯基-2-氧代乙基)-3-((4-甲基噻唑-2-基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cf)氯化1-(2-苯基氨基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cg)氯化1-(2-苯基氨基-2-氧代乙基)-3-((2-羟基乙基)氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ch)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(ci)溴化1-(2-(2,4-二氯苯基-2-氧代乙基)-3-(正丁基氨基羰基)吡啶鎓,或其他其化妆品学上认可的盐,
(cj)溴化1-(2-苯基-2-氧代乙基)-3-(1-苯基-1-氧甲基)吡啶鎓,或其他其化妆品学上认可的盐,
(ck)溴化1-(2-苯基-2-氧代乙基)-3-(甲氧基羰基)吡啶鎓,或其他其化妆品学上认可的盐。
26.根据权利要求1所述的化妆品组合物,其中所述化合物的浓度为0.005-50重量%。
27.根据权利要求26所述的化妆品组合物,其中所述化合物的浓度为0.25-5.0重量%。
28.一种化妆品组合物,含有权利要求1所述的结构式I化合物或其化妆品学上认可的盐和一种或多种以下物质:润肤剂,乳化剂,可改善皮肤分化和/或增生和/或色素沉着的试剂,抗寄生物剂,防腐剂,醇,香精,增稠剂,保湿剂,色素,硅酮,剥落剂,去角质剂,维生素A,防晒剂,皮肤渗透强化剂,消炎药,维生素,溶血栓剂,抗凝血剂,毛细血管保护剂,其他抗氧化剂,激素,抗菌剂,抗病毒剂,甾体类消炎药,麻醉剂,抗脂溢性皮炎剂,抗头皮屑剂,抗痤疮剂,抗自由基剂,镇痛剂,亲脂性化合物,抗组胺药,驱虫剂,皮肤清凉剂,润滑剂,抗真菌剂或以上所述的混合物。
29.一种美容方法,包括使用有效量的权利要求28所述组合物。
30.结构式I化合物或其化妆品学上认可的盐的用途,即将其包含在化妆品用载体中用于制造化妆品,
其中,R1是-R4-R5或-N(R7)N(R7)R9;
R4选自-N(R7)R6O-,-N(R7)R6N(R7),-OR6O和-OR6N(R7)-,其中的R6是C2-C8烃基;
其中R7选自H,烃基,包括杂芳基的芳基,同一化合物中R1和R3的R7可以相同或不同;
R2选自F,Cl,Br,I,OR7,NO2,烃基,包括杂芳基的芳基,甲酰基,酰基,C(O)NR7R10,C(O)OR7,NR7R10,N=C(R7)(R10),SR7,SO2NH2,SO2烃基和SO2芳基;
m是0,1或2;
R3选自R7,OR7,N(R7)(R10),N=C(R7)(R10),N(R7)N(R7)(R10),N(R7)N=C(R7)(R10)和CH(R7)C(O)R8,其中的R8选自R7,OR7和NR7R10;
R9选自H,烃基,包括杂芳基的芳基,C(O)R10,-SO2R10,C(S)NHR10,C(NH)NH(R10)和C(O)NHR10;
R10选自H,烃基,包括杂芳基的芳基,如果同一化合物R1和R3的R10可以相同或不同,则R10与R7可以相同或不同;
X选自卤离子,乙酸根离子,高氯酸根离子,磺酸根离子,草酸根离子,柠檬酸根离子,甲苯磺酸根离子,马来酸根离子,甲磺酸根离子,碳酸根离子,亚硫酸根离子,磷酸氢根离子,膦酸根离子,磷酸根离子,BF4 -和PF6 -;
条件是:
(i)当两烃基位于同一碳原子或氮原子上时,它们可以彼此连接成环结构;
(ii)如果R10杂芳环上含有氮原子,则它可以是季氮原子;
(iii)当R3是OR7且R1是-NHNH2时,R7不是烃基,而且
(iv)当R3是OR7,R1是N(R7)(NR7)R9且R9是C(O)R10,其中的是R10是烃基时,R7不是H。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN605/CAL/2001 | 2001-10-19 | ||
IN605KO2001 | 2001-10-19 | ||
IN620/CAL/2001 | 2001-11-01 | ||
IN620KO2001 | 2001-11-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1411800A true CN1411800A (zh) | 2003-04-23 |
Family
ID=26324887
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN01137441A Pending CN1411800A (zh) | 2001-10-19 | 2001-11-12 | 化妆品组合物和方法 |
CN01137440A Pending CN1411809A (zh) | 2001-10-19 | 2001-11-12 | 吡啶鎓衍生物用于治疗应用中的用法和组合物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN01137440A Pending CN1411809A (zh) | 2001-10-19 | 2001-11-12 | 吡啶鎓衍生物用于治疗应用中的用法和组合物 |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1304101A1 (zh) |
JP (1) | JP2003137783A (zh) |
CN (2) | CN1411800A (zh) |
CZ (1) | CZ20014034A3 (zh) |
HU (2) | HUP0104831A2 (zh) |
PL (1) | PL350649A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105190309A (zh) * | 2013-03-15 | 2015-12-23 | 宝洁公司 | 用于由皮肤生物标记测量氧化应激反应和氧化损坏的非侵入性方法 |
CN109640934A (zh) * | 2016-09-16 | 2019-04-16 | 宝洁公司 | 增加毛发健康化合物的吸收和耐洗性的方法 |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2243389T3 (es) * | 2001-03-21 | 2005-12-01 | Torrent Pharmaceuticals Ltd | Compuestos de piridinio utiles para el tratamiento de enfermedades relacionadas con los age. |
EP1631248A1 (en) * | 2003-05-30 | 2006-03-08 | Gianfranco De Paoli Ambrosi | A formulation for chemical peeling |
GB0328314D0 (en) * | 2003-12-05 | 2004-01-07 | Univ Bath | Therapeutics |
GB0403864D0 (en) * | 2004-02-20 | 2004-03-24 | Ucl Ventures | Modulator |
JP5508656B2 (ja) * | 2004-07-16 | 2014-06-04 | 太陽化学株式会社 | 最終糖化産物生成阻害組成物 |
JP2007161662A (ja) * | 2005-12-15 | 2007-06-28 | Pola Chem Ind Inc | アドバンスド・グリケーション・エンドプロダクツ分解用の化粧料 |
JP2007161660A (ja) * | 2005-12-15 | 2007-06-28 | Pola Chem Ind Inc | アドバンスド・グリケーション・エンドプロダクツを分解するための化粧料とその製造法 |
JP2007161661A (ja) * | 2005-12-15 | 2007-06-28 | Pola Chem Ind Inc | アドバンスド・グリケーション・エンドプロダクツを分解するための化粧料とその製造法 |
JP2007161663A (ja) * | 2005-12-15 | 2007-06-28 | Pola Chem Ind Inc | AGEs分解化粧料 |
GB0605949D0 (en) * | 2006-03-24 | 2006-05-03 | Quest Int Serv Bv | Milk product for skin treatment |
FR2918570B1 (fr) * | 2007-07-09 | 2012-10-05 | Engelhard Lyon | DIGLYCATION DES AGEs. |
BRPI1006611A2 (pt) * | 2009-05-07 | 2016-04-19 | Torrent Pharmaceuticals Ltd | "n' -(metilsulfonil)-1 - [tiofen-2-il]-1, 4-dihidropiridina -3- carbohidrazida, composto de fórmula (i), composição farmacêutica, método de tratamento de uma neuropatia e uso de um composto" |
EP2668161B1 (en) * | 2011-01-26 | 2014-11-26 | Roche Diagniostics GmbH | Method and substances for preparation of n-substituted pyridinium compounds |
FR3046171B1 (fr) * | 2015-12-23 | 2020-02-21 | L'oreal | Composition comprenant un ou plusieurs composes pyridinium double particuliers, utilisation et procedes de mise en oeuvre |
WO2023230205A1 (en) | 2022-05-25 | 2023-11-30 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
US11919860B1 (en) | 2023-10-06 | 2024-03-05 | King Faisal University | 1-2(-(substituted phenyl)-2-oxoethyl)-4-(isopropoxycarbonyl)pyridin-1-ium bromides as anti-tubercular agents |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU227523B1 (en) * | 1999-10-06 | 2011-07-28 | Torrent Pharmaceuticals Ltd | Pyridinium derivatives for the management of aging-related and diabetic vascular complications, process for their preparation and therapeutic uses thereof |
CN1329597A (zh) * | 1999-10-06 | 2002-01-02 | 托伦脱药品有限公司 | 治疗糖尿病及衰老相关性血管性并发症的吡啶鎓衍生物 |
-
2001
- 2001-11-09 HU HU0104831A patent/HUP0104831A2/hu unknown
- 2001-11-09 JP JP2001344128A patent/JP2003137783A/ja active Pending
- 2001-11-09 HU HU0104832A patent/HUP0104832A2/hu unknown
- 2001-11-09 CZ CZ20014034A patent/CZ20014034A3/cs unknown
- 2001-11-12 CN CN01137441A patent/CN1411800A/zh active Pending
- 2001-11-12 EP EP01204295A patent/EP1304101A1/en not_active Withdrawn
- 2001-11-12 PL PL01350649A patent/PL350649A1/xx not_active Application Discontinuation
- 2001-11-12 CN CN01137440A patent/CN1411809A/zh active Pending
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105190309A (zh) * | 2013-03-15 | 2015-12-23 | 宝洁公司 | 用于由皮肤生物标记测量氧化应激反应和氧化损坏的非侵入性方法 |
CN105190309B (zh) * | 2013-03-15 | 2018-07-03 | 宝洁公司 | 用于由皮肤生物标记测量氧化应激反应和氧化损坏的非侵入性方法 |
CN109640934A (zh) * | 2016-09-16 | 2019-04-16 | 宝洁公司 | 增加毛发健康化合物的吸收和耐洗性的方法 |
Also Published As
Publication number | Publication date |
---|---|
CZ20014034A3 (cs) | 2003-06-18 |
PL350649A1 (en) | 2003-04-22 |
HUP0104831A2 (hu) | 2003-08-28 |
JP2003137783A (ja) | 2003-05-14 |
CN1411809A (zh) | 2003-04-23 |
HU0104831D0 (en) | 2002-01-28 |
EP1304101A1 (en) | 2003-04-23 |
HUP0104832A2 (en) | 2003-08-28 |
HU0104832D0 (en) | 2002-01-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1411800A (zh) | 化妆品组合物和方法 | |
CN1259316C (zh) | 用于老龄相关性和糖尿病性血管系统并发症的杂环类化合物 | |
CN1259032C (zh) | 用于防止过氧化物引起的皮肤损害的化妆品或皮肤用制剂 | |
CN1290825C (zh) | 邻位、间位取代的双芳基化合物、它们的制备方法、它们作为药物的用途和含有它们的药物制剂 | |
CN1203089C (zh) | 新化合物 | |
CN1237979C (zh) | 褐指藻提取物促进皮肤细胞的蛋白酶体活性的用途 | |
CN1152871C (zh) | 用于增强分子伴娘素产生的羟胺衍生物及其制备 | |
CN1184425A (zh) | 5-取代-3-(1,2,3,6-四氢吡啶-4-基)-和3-(哌啶-4-基)-1h-吲哚:新型5-ht1f激动剂 | |
CN1176640A (zh) | 微粒体甘油三酯转移蛋白的抑制剂和方法 | |
CN1348442A (zh) | 新的磺胺化合物及其应用 | |
CN1639138A (zh) | 联苯基甲基-噻唑烷二酮及其类似物以及它们作为PPAR-γ激活剂的用途 | |
CN1662216A (zh) | 含有模拟视黄酸皮肤作用的化合物的皮肤调理组合物 | |
CN1171394A (zh) | 新的脲衍生物及其制法和医药用途 | |
CN100345827C (zh) | 双环芳族化合物 | |
CN1159302C (zh) | 三嗪衍生物,其制备及应用 | |
CN1148346C (zh) | 肼衍生物 | |
CN1794988A (zh) | 用于治疗血管渗透性过高疾病的方法 | |
CN1617706A (zh) | 用于防止皮肤受到过氧化物损害的化妆品或皮肤病学制剂 | |
CN1652746A (zh) | 外用皮肤增白剂 | |
CN1275979A (zh) | 用作尿激酶抑制剂的异喹啉化合物 | |
CN1236354A (zh) | 芳基或杂芳基取代的联苯基衍生物以及含有它们的药物和化妆品组合物 | |
CN1214022C (zh) | 维他命d类似物 | |
CN1280818A (zh) | 环形烯胺作为防光剂的应用 | |
CN1267418C (zh) | 二芳基硒化合物及其在人药或兽药和在化妆品方面的用途 | |
CN1852696A (zh) | 含有二乙氨基羟基苯甲酰基苯甲酸己酯的粉状制剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |