182629-24-9Relevant articles and documents
EFFLUX-PUMP INHIBITORS AND THERAPEUTIC USES THEREOF
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Page/Page column 189, (2016/12/26)
The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein ASC is -N(R8)(R9)ASC-1 ASC-1 is Ring A represents a 4- to 6-membered saturated ring containing carbon atoms as ring members in addition to the nitrogen atom and wherein one CH2 moiety in ring A is optionally replaced by CH(R21) and wherein one carbon atom in ring A that is not adjacent to the nitrogen atom is optionally replaced by O, and wherein ring A is connected to X via a carbon atom; X represents a bond, -CH2- or -C(=O)-; ARl, AR2 represent independently phenyl or a 5- to 6- membered heteroaryl ring containing one to three heteroatoms selected from O, S and N, wherein AR1 is connected to LI via a carbon atom, and wherein AR2 is connected to L1 and L2 via a carbon atom; R1, R2, R3 represent independently hydrogen, halogen, cyano, hydroxyl, C1-C6alkyl, C1-C6haloalkyl, C3- C8cycloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, -C1-C6alkylene-N(R12)R13, -N(R12)R13, -C(O)OR11l, - C(O)N(R12)R13, -S(O)OR11 or phenyl; R4 represents hydroxyl, hydrogen, halogen, nitro, cyano, amino, C1-C6alkyl optionally substituted by 1 to 5 R14, C2-C6alkenyl optionally substituted by 1 to 5 R14, C2-C6alkynyl optionally substituted by 1 to 5 R14, C1-C6alkoxy optionally substituted by 1 to 5 R14, C2-C6alkenyloxy optionally substituted by 1 to 5 R14, C2-C6alkynyloxy optionally substituted by 1 to 5 R14, -C(O)OR15, -CHO, -C(O)N(R16)R17, -C1- C6alkylene-N(R9)(R16)R17, -O-Cycle-P or -O-Cycle-Q; R5, R6, R7 represent independently hydrogen, halogen, cyano, Cl-C6alkyl, C1-C6haloalkyl, Cl-C6alkoxy or C1-C6haloalkoxy; R8 represents hydrogen, methyl or ASC-1; R9 is methyl or absent, and wherein when R9 is present the respective nitrogen atom carries a positive charge; R10 represents hydrogen or methyl; Rl11 represents independently at each occurrence hydrogen or C1-C6alkyl; R12, R13 represent independently at each occurrence hydrogen or C1-C6alkyl; R14 represents independently at each occurrence halogen, cyano, hydroxyl, C1-C6alkoxy, C1-C6haloalkoxy, C3-C8cycloalkyl, -C(O)OR11, -CHO, -C(O)N(R12)R13, -C1-C6alkylene-N(R12)R13, Cycle-P, O-Cycle-P, Cycle-Q or O-Cycle-Q; Cycle-P represents independently at each occurrence a saturated or partially unsaturated C3-C8 carbocyclic ring optionally substituted by 1 to 3 R18, or a saturated or partially unsaturated C3-C8 heterocyclic ring optionally substituted by 1 to 3 Rl 8 containing carbon atoms as ring members and one or two ring members independently selected from N(R9)(R12), N(R9) and O; Cycle-Q represents independently at each occurrence phenyl optionally substituted by 1 to 3 R19 or a 5- to 6-membered heteroaryl ring containing one to four heteroatoms selected from O, S and N, optionally substituted by 1 to 3 R19; R15 represents independently at each occurrence hydrogen or C1-C6alkyl optionally substituted by 1 to 5 R14; R16 and R17 represent independently at each occurrence hydrogen or C1-C6alkyl optionally substituted by 1 to 5 R14; R18 and R19 represent independently at each occurrence halogen, cyano, hydroxyl, oxo, amino, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, Cl-C4haloalkoxy or -CO(O)R11; R20 represents independently at each occurrence hydrogen or methyl; R21 represents N(R20)2 or CH2-N(R20)2; LI represents -CH=CH-, -CH2-O-, -O-CH2-, -CH2-O-CH2-,-CH2-S-, -S-CH2-, -CH2-S(O)-, -CH2-S(O2)-, -S(O)-CH2-; -S(O2)-CH2-, -C(CH3)(CH3)-, -C(=O)-NH-, -NH-C(=O)-, -CH2-CH2-, -CH=CH-CH2-, - CH2-NH-C(=O)-, -C(=O)-NH-CH2, -C≡C-, -S(O2)-NH-CH2-, -S(02)-NH, -O-CH2-CH2-O-, -O-, -NH- CH2-, -CH2-NH-, -CH2-CH2-O-, or -NH-C(=O)-CH2-O-, or a bond; L2 represents Cl-C7alkylene, wherein one or more CH2 moieties in the alkylene are optionally replaced independently by -N(R9)(R20)-, -CH(N(R9)(R20)(R20))-, or -C(=0)-, wherein within L2 there are no adjacent C(=O) moieties or adjacent -N(R9)(R20)- moieties, and wherein the terminal moiety of L2 is not - N(R9)(R20)-, or L2 represents -O-C1-C6alkylene-, or L2 represents a bond, providing that X represents - CH2- when L2 is a bond; as well as methods of using the compounds of formula I for treating or preventing bacterial infections.
NITRIC OXIDE RELEASING SELECTIVE CYCLOOXYGENASE-2 INHIBITORS
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Page 33, (2010/02/06)
The invention encompasses novel compounds of Formula (I) and Formula (II), which are nitric oxide-releasing prodrugs useful in the treatment of cyclooxygenase-2 mediated diseases. The invention also encompasses certain pharmaceutical compositions and meth
Synthesis of amphiphilic fullerene derivatives and their incorporation in Langmuir and Langmuir-Blodgett films
Felder, Delphine,Nava, Manuel Gutierrez,Del Pilar Carreon, Maria,Eckert, Jean-Francois,Luccisano, Michael,Schall, Corinne,Masson, Patrick,Gallani, Jean-Louis,Heinrich, Benoit,Guillon, Daniel,Nierengarten, Jean-Francois
, p. 288 - 319 (2007/10/03)
Various amphiphilic fullerene derivatives were prepared by functionalization of [5,6]fullerene-C60-Ih (C60) with malonate or bis-malonate derivatives obtained by esterification of the malonic acid mono-esters 5-7. Cyclopropafullerene 10 was obtained by protection of the carboxylic acid function of 6 as a tert-butyl ester, followed by Bingel addition to C60 and a deprotection step (Scheme 2). The preparation of 10 was also attempted directly from the malonic acid mono-ester 6 under Bingel conditions. Surprisingly, the corresponding 3'-iodo-3'H-cyclopropa[1,9][5,6]fullerene-C60-Ih-3'- carboxylate 11 was formed instead of 10 (Scheme 3). The general character of this new reaction was confirmed by the preparation of 15 and 16 from the malonic acid mono-esters 13 and 14, respectively (Scheme 4). All the other amphiphilic fullerene derivatives were prepared by taking advantage of the versatile regioselective reaction developed by Diederich and co-workers which led to macrocyclic bis-adducts of C60 by a cyclization reaction at the C-sphere with bis-malonate derivatives in a double Bingel cyclopropanation. The bis-adducts 37-39 with a carboxylic acid polar head group and four pendant long alkyl chains of different length were prepared from diol 22 and acids 5-7, respectively (Scheme 9). In addition, the amphiphilic fullerene derivatives 45, 46, 49, 54, and 55 bearing different polar head groups and compound 19 with no polar head group were synthesized (Schemes 11 - 13, 15, and 5, resp.). The ability of all these compounds to form Langmuir monolayers at the air-water interface was investigated in a systematic study. The films at the water surface were characterized by their surface pressure vs. molecular area isotherms, compression and expansion cycles, and Brewster-angle microscopy. The spreading behavior of compound 10 was not good, the two long alkyl chains in 10 being insufficient to prevent aggregation resulting from the strong fullerene-fullerene interactions. While no films could be obtained from compound 19 with no polar head group, all the corresponding amphiphilic fullerene bis-adducts showed good spreading characteristics and reversible behavior upon successive compression/expansion cycles. The encapsulation of the fullerene in a cyclic addend surrounded by four long alkyl chains is, therefore, an efficient strategy to prevent the irreversible aggregation resulting from strong fullerene-fullerene interactions usually observed for amphiphilic C60 derivatives at the air-water interface. The balance of hydrophobicity to hydrophilicity was modulated by changing the length of the surrounding alkyl chains or the nature of the polar head group. The best results in terms of film formation and stability were obtained with the compounds having the largest polar head group, i. e. 45 and 46, and dodecyl chains. Finally. the Langmuir films obtained from the amphiphilic fullerene bis-adducts were transferred onto solid substrates, yielding high-quality Langmuir-Blodgett films.
