51282-56-5

The synthesis of new compounds with a 1,3,4-thiadiazole structure, and their in vitro biological evaluation as inhibitors of both neuronal and inducible Nitric Oxide Synthase (nNOS and iNOS) is described. These compounds have been designed by an isosteric

An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and ---- represents a single bond or a double bond, R5 represents optionally substituted aryl or the like, Z represents - N=CHR6R7 or the like, R6 and R7 represent H, optionally substituted alkyl, optionally substituted aryl or the like, R101 and R102 together form =O, and R103 and R104 represent H, or R101 and R104 together from a bond, and R102 and R103 together form a bond.

A novel therapeutic agent for hyperlipidemia, which is an ester compound represented by the formula (1") (wherein ???R1 and R2 are each hydrogen atom or optionally substituted aryl, etc.; ???X is -COO- or -CON(R10)-; ???R3 and R4 are each hydrogen atom, C1-C6 alkyl or C1-C6 alkoxy, etc.; ???R5, R6 and R7 are each hydrogen atom, C1-C6 alkyl or C1-C6 alkoxy, etc.; ???R8 and R9 are each independently hydrogen atom, C1-C6 alkyl, -CON(R18)(R19) or -COO(R20), etc.; ???ring A, ring B and ring C are each independently aryl or heterocycle residue, etc.; ???Alk1 and Alk2 are each independently alkanediyl, etc.; ???l and m are each an integer of 0 or 1 to 3) or a prodrug thereof, or a pharmaceutically acceptable salt of either. The therapeutic agent selectively inhibits MTP in the small intestine, thus causes no such side effect as a fatty liver.

Through the examination of empirical correlations involving activation parameters for nucleophilic substitution of methyl iodide and of ethyl iodide, nucleophiles have been classified into three series: (1) nucleophiles with two equivalent reaction sites, (2) nucleophiles with a chlorine atom in the para-position, and (3) nucleophiles with a single reaction site. Three types of partial desolvation processes accompanying activation have been deduced on the basis of these classifications. A major factor determining the relative reactivity of methyl iodide to ethyl iodide in the substitution reaction of an anionic nucleophile having a single reaction site in acetonitrile (kMeI/kEtI) is suggested to be partial desolvation around the nucleophilic center on going from reactant to transition-state.