Abstract:
Provided herein are processes for synthesizing dihydropyridophthalazinone derivatives, such as for example, 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one and its stereoisomers, which are potent poly(ADP-ribose)polymerase (PARP) inhibitors as well as novel synthetic intermediate compounds.
Abstract:
Provided herein are (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt forms, including crystalline forms, and methods of their preparation. Pharmaceutical compositions comprising a (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt are also provided, as are methods of using (8S,9R)-5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one tosylate salt to treat a disease or condition, such as a cancer.
Abstract:
An automated system captures multiple digital images of a sample, from different viewing areas of the sample. The images are analyzed and a test result may be reported based on the count of cells in all of the digital images. The system may be especially applicable to the testing of samples having low cell concentrations, as the variability between tests may be reduced as compared with a system that bases its test results on only a single image of the sample. The system may count the cells in a first digital image of the sample, and may capture or analyze one or more additional digital images only when it is recognized that additional measurements are needed to ensure adequate accuracy and repeatability of the test.
Abstract:
The invention provides novel compositions comprising imidazoquinoline compounds. Also provided are methods of administering the compositions in an effective amount to enhance the immune response of a subject. Further provided are novel compositions and methods of administering the compositions in combination with (an) other agent(s).
Abstract:
Semi-synthetic glycopeptides having antibacterial activity are described. Also described are processes of preparing such semi-synthetic glycopeptides by chemical modification of a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in mild acidic medium to give the amino acid-4 monosaccharide; protection of the amino groups in the molecule; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also included are the process of conversion of the amide group in amino acid-3 on these scaffolds to various acylureas, acylamide, acylsulfonamide, acylsulfonylurea derivatives and aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid-7 through Mannich reaction procedures. Further provided herein are pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, including bacterial infections.
Abstract:
Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi-synthetic glycopeptides described herein are made by chemical modification of the a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; conversion of the amide group in amino acid-3 on these scaffolds to various acylamide, acylsulfonamide, acylsulfonylurea derivatives; aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid-7 through Mannich reaction; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.
Abstract:
Semi-synthetic glycopeptides having antibacterial activity are based on modifications of the eremomycin, A82846B, vancomycin, teicoplanin, and A-40,926 scaffolds, in particular, acylation of the sugar moieties on these scaffolds with certain acyl groups; and/or conversion of an acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides; or having a combination of an alkylation modification of the amino substituent on the amino-substituted sugar moiety on these scaffolds with certain alkyl groups or acylation modification of the amino substituent on the amino-substituted sugar moiety on this scaffold with certain alkyl groups, and conversion of the acid moiety on the macrocyclic ring of this scaffolds to certain substituted amides. Also provided are methods for the synthesis of the compounds, pharmaceutical compositions containing the compounds, and methods of use of the compounds for the treatment and/or prophylaxis of diseases, especially bacterial infections.
Abstract:
A compound having the structure set forth in Formula (I) or Formula (II): wherein the variables Y, R1, R2, R3, and R4 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
Abstract:
Compounds of the formula wherein Ra is H; substituted or unsubstituted alkyl (1-10C); substituted or unsubstituted alkenyl (2-10C); substituted or unsubstituted alkynyl (2-10C); substituted or unsubstituted aryl (4-14C); substituted or unsubstituted arylalkyl (5-20C); or ORa is replaced by H; Rb is H or halogen; Rc is H or a protecting group; Rd is methyl, unsubstituted alkyl (3-10C); substituted alkyl (1-10C); substituted or unsubstituted alkynyl (2-10C); substituted or unsubstituted aryl (4-14C); substituted or unsubstituted arylalkyl (5-20C); substituted or unsubstituted arylalkenyl (5-20C); substituted or unsubstituted arylalkynyl (5-20C); substituted or unsubstituted amidoarylalkyl (5-20C); substituted or unsubstituted amidoarylalkenyl (5-20C); or substituted or unsubstituted amidoarylalkynyl (5-20C); Re is H or a protecting group; L is methylene or carbonyl; T is —O—, —N(R)—, —N(OR)—, —N(NHCOR)—, —N(N═CHR)—, or —N(NHR)— wherein R is H or Ra as defined above, with the proviso that when L is methylene, T is —O—; one of Z and Y is H and the other is OH, protected OH, or amino, mono- or dialkylamino, protected amino, or an amino heterocycle or Z and Y together are ═O, ═NOH or a derivatized oxime; including any pharmaceutically acceptable salts thereof and any stereoisomeric forms and mixtures of stereoisomeric forms thereof, are antimicrobial agents.
Abstract translation:下式的化合物其中R a a为H; 取代或未取代的烷基(1-10C); 取代或未取代的烯基(2-10C); 取代或未取代的炔基(2-10C); 取代或未取代的芳基(4-14C); 取代或未取代的芳基烷基(5-20℃); 或OR被替换为H; R b是H或卤素; R c是H或保护基; R d是甲基,未取代的烷基(3-10C); 取代的烷基(1-10C); 取代或未取代的炔基(2-10C); 取代或未取代的芳基(4-14C); 取代或未取代的芳基烷基(5-20℃); 取代或未取代的芳基烯基(5-20℃); 取代或未取代的芳基炔基(5-20℃); 取代或未取代的酰氨基芳基烷基(5-20℃); 取代或未取代的酰氨基芳基烯基(5-20℃); 或取代或未取代的酰氨基芳基炔基(5-20℃); R e是H或保护基; L是亚甲基或羰基; T是-O - , - N(R) - , - N(OR) - , - N(NHCOR) - , - N(N-CHR) - 或-N(NHR) 如上所定义,条件是当L是亚甲基时,T是-O-; Z和Y之一是H,另一个是OH,保护的OH或氨基,单或二烷基氨基,保护的氨基或氨基杂环,或Z和Y一起是-O,-NOH或衍生化的肟; 包括其任何药学上可接受的盐和其立体异构体形式及其立体异构形式的混合物均为抗微生物剂。
Abstract:
A platform that supports a sample plate such as a microtiter plate, a multi-well plate of any size, or a glass slide with sample spots distributed over its surface, and presents the plate for assay detection by a movable scanning head that has a field depth on the millimeter scale is leveled or otherwise adjusted in a planar orientation by an apparatus that includes a rocker plate, position sensors, and motorized risers arranged on the apparatus to provide the rocker plate with tilting capability along either or both or two orthogonal axes.