Systems for transdermal administration of beta-lactam antibiotics

摘要

A compound of structure 1 ** Formula ** in which X is selected from O, S, CH2, and NH; Y is selected from H, OH, NHCHO, OCOCH3, OCH3, OC2H5, CH3SO3, NO2, CN, CF3, OCF3, F, Br, I, and Cl; ** Formula ** in which Z is S; -X1 is selected from -H, -OH, -OCH3, -OC2H5, OC3H7, -CONH2, -CH2OCONH2, -CH2OCOCH3, -OCOCH3, - CH2OCOCH3, -CH2OCH3, -CH3, -C2H5, -C3H7, -C4H9, C5H11 , C6H13, -Cl, -F, -Br, -I, -HC = CHCH3, -HC = CH2, -CH2OCH3, ** Formula ** in which R5 is selected from H, CONH2, CH2CH2N (CH3) 2, CH2CH2N (CH2CH3) 2, Cl, F, Br, I, alkyl residues having 1 to 12 carbon atoms, alkyloxy residues having 1 to 12 carbon atoms, alkenyl residues having up to 12 carbon atoms, and alkynyl residues having up to 12 carbon atoms; Rs- is selected from: ** Formula ** R61OOCCH (NHR71) (CH2) nCONH-, R61OOCCH (NHR7) (CH2) nSCONH-, CF3SCH2CONH-, CF3CH2CONH-, CHF2SCH2CONH-, CH2FSCH2CONCH-, NH2COCH-, NH2COCH-2, NH2COCH-, NH2COCH-2, NH2COCH-, NH2COCH-, NH2COCH-, NH2COCH-, NH2CHCH-2, CH2COCH-, NH2CHCH-2, CH2COCH-, NH2CHCH-2, CH2COCH-, NH2CHCH-2, CH2COCH-, NH2COCH-, NH2COCH-, NH2COCH-, NH2CHCH-2, CH2COCH-, NH2CHCH-2, CH2COCH- (NH2COCH-) , CH2SCH2CONH-, CNCH2SCH2CONH-, CH3 (CH2) nCONH-, R71N = C (NR71) CH2CH2S-, R71N = C (NHR71) NHCO-, CH3C (Cl) = CHCH2SCH2CONH-, (CH3) 2C (OR61) -, CNCH2CONH-, CNCH2CH2S-, R71N = C (NR71) CH2CH2S-, CH2 = CHCH2SCH2CONH-, CH3CH (OH) -, CH3CH (OR81) -, CH3CH (Y11) -, (CH3) 2CH-, CH3CH2- , and CH3 (CH2) nCH = CH (CH2) mCONH-, or Rs and Y taken together are R61OCH2C (R51) =, in which n and m each independently are selected from 0, 1, 2, 3, 4, 5, and 6; X31 is selected from H, N3, SO3W, F, Cl, Br, I, OH, OCH3, OC2H5, CH3, and C2H5; X41 is N or CH; X51 is selected from CH2, S, O, and NH; R51 is selected from H, -CONH2, CH2CH2N (CH3) 2, CH2CH2N (CH2CH3) 2, CH2CH2OR61, Cl, F, Br, I, alkyl residues having 1 to 12 carbon atoms, alkyloxy residues having 1 to 12 carbon atoms, alkenyl residues having up to 12 carbon atoms, alkynyl residues having up to 12 carbon atoms, aryl residues, and heteroaryl residues; R61 is selected from H, F, Cl, Br, I, 2-oxo-1-imidazolidinyl, alkyl residues having 1 to 12 carbon atoms, alkyloxy residues having 1 to 12 carbon atoms, alkenyl residues having up to 12 carbon atoms, alkynyl residues having up to 12 carbon atoms, aryl residues (phenyl, 5-indanyl, 2,3-dihydro-1H-inden-5-yl) and heteroaryl residues (4-hydroxy-1,5 -naphthyridin-3-yl); R71 is selected from H, F, Cl, Br, I, CH3NHCOCH2CH (NHR81) CO, R51N = C (NHR61) NHCO-, COCH3, COR61, PO (OR51) OR61, alkyl residues having 1 to 12 atoms of carbon, alkyloxy residues having 1 to 12 carbon atoms, alkenyl residues having 1 to 12 carbon atoms, alkynyl residues having 1 to 12 carbon atoms, aryl residues, and heteroaryl residues; R81 is selected from the group consisting of H, F, Cl, Br, I, CH3, C2H5, CF3, CH2CH2 F, CH2CH2Cl, CH2CH2Br, CH2CH2I, CH2CHF2, CH2CF3, CH2F, CH2Cl, CH2Br, CH2I, C3H7, C4H9, C5H9 , CONH2, and CH2OCONH2; Y11, Y21, Y31 and Y41 each independently are selected from H, OH, OW, OCOW, OCOCH3, CH3, C2H5, C3H7, C4H9, SO3R61, CH2COOR81, OCH3, OC2H5, CH3SO3, NO2, CN, CF3, OCF3, CH = CHCONHCH2COOW, CH2 (CH2) nNR51R61, CH2 (CH2) nOR61, CH (CONH2) NHR61, COOR51, F, Br, I, and Cl; -W is selected from alkyl residues having 1 to 12 carbon atoms, alkyloxy residues having 1 to 12 carbon atoms, alkenyl residues having up to 12 carbon atoms, alkynyl residues having up to 12 carbon atoms, residues aryl, heteroaryl residues ** Formula **