162271-10-5

Heck vinylation of 2-bromo-6-methyl-3-substituted pyridines using η3-allylpalladium chloride dimer/P(o-Tol)3 complex/toluene and dimethylacetamide (DMA) as co-solvent with methyl acrylate is reported. Electronic and steric effects were investigated engaging diversely 2-bromo-3,6-disubstituted pyridines. As application, a new synthesis of the 6-methyl cyclopenta[b]pyridinone building-block connecting Heck vinylation, alkene reduction and Dieckmann condensation is described.

The invention relates to a compound of formula (I) wherein X1 to X4 and RC to RG are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

The present application provides novel inhibitors of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase, metabolites thereof, and phannaceutically acceptable salts or prodrugs thereof. Also provided are methods for preparing these compounds. A therapeutically effective amount of one or more of the compounds of formula (I) is useful in treating diseases resulting from dysregulation of the kynurenine pathway. Compounds of formula (I) act by inhibiting the enzymatic activity or expression of indoleamine 2,3-dioxygenase-1 and/or indoleamine 2,3-dioxygenase-2 and/or tryptophan 2,3-dioxygenase.

The synthesis of 2-α-styrylpyridines has been carried out by using the coupling of polyoxygenated N-tosylhydrazones with various 2-halopyridines. We demonstrated that the use of a catalytic amount of PdCl2(MeCN) 2 in combination with a bidentate ferrocene DPPF or a monodentate alkyl phosphine tBu2MeP-HBF4 constitutes an efficient protocol for this coupling, providing 2-α-styrylpyridines 2 in satisfactory to good yields. Among several polyoxygenated derivatives 2 evaluated, compound 2aa was found to exhibit excellent antiproliferative and antimitotic activities comparable to that of the reference compound isoCA-4. The Royal Society of Chemistry 2013.

The present invention provides novel conformationally-defined macrocyclic compounds that can function as selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, bone disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

The first total synthesis of pterocellin A (1) was achieved in 10 linear steps from commercially available kojic acid (6) and 2-bromo-3-pyridinol (11) in a convergent sequence. The key constructive steps are a directed lithiation to couple two pyridines a

The present invention provides an excellent squalene synthase inhibitor. Specifically, it provides a compound (I) represented by the following formula, a salt thereof or a hydrate of them. Wherein R1 represents an optionally substituted vinyl group or an aromatic ring which may be substituted; ???n is an integer of 0 to 2; ???X, Y and Z are the same as or different from each other and each represents an optionally substituted carbon atom, or an optionally substituted nitrogen a tom, sulfuratomoroxygenatom, and Y optionally represents a single bond, and when Y represents the single bond, the ring to which X, Y and Z belong is a 5-membered ring; ???CyA represents a 5- to 14 membered non-aromatic cyclic amino groupornon-aromatic cyclic amidogroupwhichmaybe substituted, and the non-aromatic cyclic amino group or the non-aromatic cyclic amido group optionally having an oxygen atom or a sulfur atom; ???W represents a chain expressed by(1) optionally substituted -CH2-CH2-,(2) optionally substituted -CH=CH-,(3) -C≡C-,(4) an optionally substituted phenylene group,(5) a single bond,(6) -NH-CO-,(7) -CO-NH-,(8) -NH-CH2-,(9) -CH2-NH-,(10) -CH2-CO-,(11) -CO-CH2-,(12) -O-(CH2)m-,(13) -(CH2)m-O- (where m represents an integer of 0 to 5),(14) -O-CH2-CR2=,(15) -O-CH2-CHR2- (where R2 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom),(16) -NH-S(O)1-,(17) -S(O)1-NH-,(18) CH2-S(O)1-, or(19) -S(O)2-CH2- (where 1 represents 0, 1, or 2); and ???A represents a group having any of the following structural formulae: (wherein R3 and R4 represent independently a hydrogen atom or an optionally substituted C1-6 alkyl group, or combine through a carbon chain optionally containing a heteroatom to form a ring; ???R5 and R6 represent independently a hydrogen atom or an optionally substituted C1-6 alkyl group, or combine through a carbon chain optionally containing a heteroatom to form a ring; ???R7 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, a hydroxyl group, an alkoxy group, a halogen atom or an optionally substituted amino group; ???R8 represents a hydrogen atom, a hydroxyl group, an alkoxy group, a halogen atom or an optionally substituted amino group; ???B1 represents an optionally substituted carbon atom, or an optionallysubstitutednitrogenatom, oxygen atom or sulfur atom; ???B2 represents an optionally substituted carbon atom or nitrogen atom; ???a and b represent an integer of 0 to 4, provided that a+b is an integer of 0 to 4; ???c represents 0 or 1; and----- represents a single bond or a double bond, provided that when c is 1 in which A is a quinuclidine having R8 represented by the case where R8 is a hydrogen atom or a hydroxyl group; Arl is an aromatic heterocycle; and W is one of (1) to (3), (6) to (11) and (16) to (19) are excluded).

A reporter system reflecting the transport process that transports GPI-anchored proteins to the cell wall was constructed and compounds inhibiting this process were discovered. Further, genes conferring resistance to the above compounds were identified and methods of screening for compounds that inhibit the activity of the proteins encoded by these genes were developed.Therefore, through the novel compounds, the present invention showed that antifungal agents having a novel mechanism, i.e. inhibiting the process that transports GPI-anchored proteins to the cell wall, could be achieved.

The present invention provides an excellent squalene synthesizing enzyme inhibitor. Specifically, it provides a compound (I) represented by the following formula, a salt thereof or a hydrate of them. In which R1 represents (1) hydrogen atom or (2) hydroxyl group; HAr represents an aromatic heterocycle which may be substituted with 1 to 3 groups; Ar represents an optionally substituted aromatic ring; W represents a chain represented by (1) —CH2—CH2— which may be substituted, (2) —CH=CH— which may be substituted, (3) —C≡C—, (4) —NH—CO—, (5) —CO—NH—, (6) —NH—CH2—, (7) —CH2—NH—, (8) —CH2—CO—, (9) —CO—CH2—, (10) —NH—S(O)l—, (11) —S(O)l—NH—, (12) —CH2—S(O)— or (13) —S(O)l—CH2— (l denotes 0, 1 or 2); and X represents a chain represented by (1) a single bond, (2) an optionally substituted C1-6 alkylene chain, (3) an optionally substituted C2-6 alkenylene chain, (4) an optionally substituted C2-6 alkynylene chain, (5) a formula —Q— (wherein Q represents oxygen atom, sulfur atom, CO or N(R2) (wherein R2 represents a C1-6 alkyl group or a C1-6 alkoxy group)), (6) —NH—CO—, (7) —CO—NH—, (8) —NH—CH2—, (9) —CH2—NH—, (10) —CH2—CO—, (11) —CO—CH2—, (12) —NH—S(O)m—, (13) —S(O)m—NH—, (14) —CH2—S(O)m—, (15) —S(O)m—CH2— (wherein m denotes 0, 1 or 2) or (16) —(CH2)n—O— (wherein n denotes an integer from 1 to 6).