摘要:
The present invention provides a compound having aggrecanase inhibitory activity and MMP-13 inhibitory activity, and useful as a therapeutic agent for osteoarthritis, rheumatoid arthritis and the like, more specifically, a cyclopropane compound of formula (1): wherein R1 is —(CH2)m—X—(CH2)n-A1 etc., wherein m and n are the same or different and each is 0 to 6, X is a single bond, etc. and A1 is a substituted C3-14 hydrocarbon ring group, etc.; R2 and R3 are the same or different and each is a hydrogen atom, —(CH2)p—X1—(CH2)q-A2, etc., wherein p and q are the same or different and each is 0 to 6, X1 is a single bond, etc. and A2 is an optionally substituted C3-14 hydrocarbon ring group, etc.; R4 is —CO2R9, etc., wherein R9 is a hydrogen atom, etc.; and R20 and R21 are the same or different and each is a hydrogen atom, —(CH2)m12—X12—(CH2)m12—R30, etc., wherein m12 and m12 are the same or different and each is 0 to 6, X12 is a single bond, etc. and R30 is a hydrogen atom, etc.; or a prodrug thereof or a pharmaceutically acceptable salt thereof.
摘要:
The invention provides the compounds of formula ( ): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, A, X, Y, a, b and n are as defined herein. Also disclosed are methods for making the compounds of formula (I) and their use in treating or preventing diseases associated with cell overproliferation and dysfunctional sphingolipid signal transduction. The invention also encompasses the use of the compounds in combination with an apoptosis-signaling ligand, such as Fas ligand. Preferably, the Fas ligand is administered in the form of a gene therapy agent.
摘要:
Novel FBPase inhibitors of the formula I and X are useful in the treatment of diabetes and other conditions associated with elevated blood glucose.
摘要:
A 2-iminoimidazole derivative represented by the formula: {wherein R1, R2 and R3 represent hydrogen, optionally substituted C1-6 alkyl, etc.; R6 represents hydrogen, C1-6 alkyl, C1-6 alkyloxycarbonyl, etc.; Y1 represents a single bond, —CH2—, etc.; Y2 represents a single bond, —CO—, etc.; and Ar represents hydrogen, a group represented by the formula: [wherein R10–R14 represent hydrogen, C1-6 alkyl, hydroxyl, C1-6 alkoxy, etc., and R11 and R12 or R12 and R13 may bond together to form a 5- to 8-membered heterocycle], etc.}or salt thereof.
摘要:
This invention describes a one pot, single-step process for the preparation of halide-free hydrophobic salts comprising polyalkylated imidazolium cations and various anions in accordance with the following structure, where R1 and R3 represent the either the same or different alkyl groups, and R2, R4, and R5 represent either hydrogen atoms, or the same or different alkyl group substituents; X represents a polyatomic anion that is the conjugate base of an acid. By simply mixing aqueous formaldehyde with an alkyl amine such as methylanune, ethylamine, n-propyl oriso-propylamine, or n-butyl-, iso-butyl, or t-butylamine, or by mixing aqueous formaldehyde with two alkyl amines (preferably one being methylamine, ethylamine, n-propyl- or iso-propylamine, or n-butyl-, isobutyl, or t-butylamine) and another being n-propyl- or isopropylaine, or n-butyl-, isbutyl, or t-butylamine), an acid (such as hexafluorophosphoric acid, trifluoroacetic acid, pentafluoropropionic, heptafluorobutyric acid, or the free acid of a bis(perfluoroalkylsulfonyprnide or tris(perfluoroalkylsulfonyl)methide as the source of the anion) and aqueous glyoxal solution, the hydrophobic ionic salts or mixtures thereof thus formed may be conveniently separated directly from the aqueous byproduct layer. Like the single cation hydrophobic salts, these mixed hydrophobic ionic liquids are non-flammable and manifest no detectable vapor pressure up to their decomposition temperature of greater than 300° C. We have also discovered that, surprisingly, ternary mixtures of dialkylated ionic liquids manifest higher ionic conductivities than a single ionic liquid of the mixture alone. This property benefits electrochemical power source applications such as batteries and capacitors. Furthermore, we have discovered that ternary mixtures of dialkylated ionic liquids absorb microwave radiation more efficiently than a single ionic liquid of the mixture alone. This property benefits microwave-induced synthetic reactions. Such physical and chemical properties make it possible to employ inexpensive mixtures of polyalkylated imidazolium cations in an advantageous manner as thermal transfer fluids, high temperature lubricants, and plasticizers, and as solvents in the areas of electrochemistry, synthetic chemistry, catalysis, and separations chemistry.
摘要:
The present application describes novel hydantoin derivatives of formula (I): or pharmaceutically acceptable salt or prodrug forms thereof, wherein L, Z0, R1, R4, R5, and R11 are defined in the present specification, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-α converting enzyme (TACE), aggrecanase, or a combination thereof.
摘要:
N-Heterocyclic derivatives of the formula (I): are described herein, as well as other N-heterocycles, as inhibitors of nitric oxide synthase. Pharmaceutical compositions containing these compounds, methods of using these compounds as inhibitors of nitric oxide synthase and processes for synthesizing these compounds are also described herein.
摘要:
N-Heterocyclic derivatives of the formula (I): are described herein, as well as other N-heterocycles, as inhibitors of nitric oxide synthase. Pharmaceutical compositions containing these compounds, methods of using these compounds as inhibitors of nitric oxide synthase and processes for synthesizing these compounds are also described herein.
摘要:
A composition comprising a compound of formula I: 1 wherein W represents O, SnullA2, or two groups, R3 and R4; bonds a and b are single or double bonds, provided that one of a and b is a single bond and the other is a double bond; c is a single or double bond, and d is a single bond, double bond, or two single bonds, provided that d is a single bond when c is a double bond, d is not a single bond when c is a single bond, and W is R3 and R4 when d is two single bonds; A1, A2, B1 and B2 are independently hydrogen, alkyl, alkenyl, aralkyl or one of the groups depicted in Scheme 1: 2 and a dithiophosphate.
摘要:
Compounds of the formula (I) ##STR1## in which A represents optionally substituted alkanediyl,R represents in each case optionally substituted cycloalkyl, aryl or benzo-fused heterocyclyl,E represents --CH.dbd. or nitrogen,Q represents oxygen, sulphur, --CH.sub.2 --O--, a single bond, or a nitrogen atom which is optionally substituted by alkyl, andX represents halogen.