Abstract:
Disclosed are thyclotides, which are oligomers, each comprising (a) from about 8 to about 25 monomer units of formula (I) and (b) from 0 to about 24 monomer units of formula (II): wherein B is a nucleobase, which can be the same or different at each occurrence, or a pharmaceutically acceptable salt thereof. The thyclotides are soluble in water, bind strongly to complementary DNA and RNA, and are cell permeable. The thyclotides are useful as reagents for antisense and antigene applications, and as probes in molecular diagnostics and microarrays.
Abstract:
The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
Abstract:
The present invention relates to a compound of formula (I). Provided is also a method of killing a cell that comprises administering the compound of formula (I). Provided is also a method of treating cancer or diabetes in a mammal that comprises administering the compound of formula I and respective pharmaceutical compositions thereof.
Abstract:
Disclosed is use of a compound having a structure according to general formula (I) defined below, in the manufacture of a medicament to treat and/or prevent a parasitic infection or infestation in a mammalian subject wherein X 1 = N or CH or C=O (X 2 = NH) or C=S (X 2 = NH) or C-OR 1 or C-halogen or C-azide; X 2 = N or CR 1 or C-halogen or CS(O) n R 1 where n = 0-2 or a (C) m linker where m = 1-3 between X 2 and X 6 or C-X 5 X 6 (in which case X 5 X 6 at C6 (purine numbering) is replaced by H or NHR 1 or O or OR 1 or S or SR 1 ); X 3 = N or CH or C-NO 2 ; X 4 = N or CH or C-NO 2 or C-NR 1 R 2 or an amidine derivative or a guanidinium derivative; X 5 = O or NR 1 or CR 1 R 2 ; X 6 = OR 1 or O-acyl or 0-S(O) n R 1 or NR 1 R 2 or NH-acyl or N(Acyl) 2 or NH-OS(O) 2 R 1 or NH-S(O) n R 1 where n = 0-2 or a hydrazone derivative or an oxime derivative, but if X 5 = O, X 6 cannot = O or X 5 X 6 is an amidine or an N-substituted pyridine or substituted guanidine; Y = H or NH 2 or NR 1 R 2 or -O (X 3 = NH) or OR 1 or F or Cl or Br or I or CR 1 R 2 R 3 or S(O) n R 1 where n = 0-2 or azide or X 5 X 6 (in which case X 5 X 6 at C6 (purine numbering) is replaced by H or NHR 1 or O or OR 1 or S or SR 1 ); R 1 , R 2 , R 3 are independently selected from the group consisting of H or (optionally substituted), alkyl, alkenyl or alkynyl or aryl or aralkyl where the substituents may be selected from H, OH, NH 2 , halogen, N 3 , CN, CHO, COOR', C0NR' 2 , OR, NE' 2 , SR', NR'NR' 2 , NR'OR', NO 2 and R' is alkyl, alkenyl, alkynyl, aralkyl, acyl, sulfonyl; Z = H or substituted (alkyl or alkenyl or alkynyl or aralkyl) or a sugar derivative of general formula (II) in the ß-configuration where: B is the nucleobase from Formula (I); X 7 = CH 2 or O or NR 1 or S; R 4 = H or OH or OR 1 or halogen or azide or a phosphate derivative; R 5 = H or F or CH 3 ; R 6 = H or OH or OR 1 or halogen or azide or a phosphate derivative; and R 7 = H or halogen or R 1 or a derivative of an amino acid or PO 3 H 2 or P 2 O 6 H 3 or P 3 O 9 H 4 or a methylene derivative of P 2 O 6 H 3 or P 3 O 9 H 4 or a masked phosphate or a phosphonate derivative (5'-O replaced with CH 2 ).
Abstract translation:本发明公开了具有下述通式(I)结构的化合物在制备用于治疗和/或预防哺乳动物受试者的寄生虫感染或侵染的药物中的用途,其中X < = N或CH或C = O(X 2 N = NH)或C = S(X 2 N = NH)或C-OR 1 或C-卤素或C-叠氮化物; X 2 = N或CR 1或C - 卤素或CS(O)n R 1 R 1其中n = 0-2或其中在X 2和X 6或CX 5之间的m = 1-3的(C)m < (在这种情况下)C6(嘌呤编号)的X 5 X 6取代为H或NHR 1 或O或OR 1或S或SR 1); X 3 = N或CH或C-NO 2; X 4 = N或CH或C-NO 2或C-NR 1 R 2或脒衍生物 或胍衍生物; X 5 = O或NR 1或CR 1 R 2 2; 或者O - 酰基或0-S(O)n R 1或NR 1, 或者NH-酰基或N(酰基)2或NH-OS(O)2 R 2, 其中n = 0-2或腙衍生物或肟衍生物,但如果X C6(嘌呤编号)的5个X 6位被H或NHR 1或O或OR 1取代,或S或 SR 1 SUB>); R 1,R 2,R 3,R 3独立地选自H或(任选取代的),烷基,烯基或炔基或 芳基或芳烷基,其中取代基可以选自H,OH,NH 2,卤素,N 3,CN,CHO,COOR',C0NR' / SUB,OR,NE'2,SR',NR'NR'2,NR'OR',NO 2和R' 烷基,烯基,炔基,芳烷基,酰基,磺酰基; Z = H或通式(II)的取代的(烷基或烯基或炔基或芳烷基)或糖衍生物,其中:B是式(I)的核碱基; X 7或CH 2或O或NR 1或S; R 4 = H或OH或OR 1或卤素或叠氮化物或磷酸酯衍生物; R 5 = H或F或CH 3; R 6 = H或OH或OR 1或卤素或叠氮化物或磷酸酯衍生物; 和R 7 = H或卤素或R 1或氨基酸或PO 3 H 2的衍生物, 或者P u> 2 sub> 3 sub> 3或3 sub> 3 sub> > 4 sub>或者P 2 O 3 H 3或S 3 O 3的亚甲基衍生物, 或者掩蔽的磷酸盐或膦酸盐衍生物(5'-O被CH 2取代)。
Abstract:
The invention relates to compounds of the formula (I) and to pharmaceutically acceptable salts, solvates, prodrugs and metabolites thereof, wherein W, Z, R and R , are as defined herein. The invention also relates to methods of treating Hepatitis C virus in mammals by administering the compounds of formula (I), and to pharmaceutical compositions for treating such disorders, which contain the compounds of formula (I). The invention also relates to methods of preparing the compounds of formula (I).
Abstract:
The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction ("TR-PCR"). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
Abstract:
Disclosed herein are methods directed generally to the control of neural activity and for selectively and controllably inducing the in vivo genetic expression of one or more naturally occurring genetically encoded molecules in mammals. More particularly, the present invention selectively activates or derepresses genes encoding for specific naturally occurring molecules such as neurotrophic factors through the administration of carbon monoxide dependent guanylyl cyclase modulating purine derivatives. The methods of the present invention may be used to affect a variety of cellular and neurological activities and to therapeutically or prophylactically treat a wide variety of neurodegenerative, neurological, and cellular disorders.
Abstract:
A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1', 2' or 3'-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.