Suntory Limited

Nippon Soda Co., Ltd.

Japan Science and Technology Agency

Kyoto University

Daiichi Suntory Pharma Co., Ltd.

Nagoya City University

Masaji Ishiguro

Takashi Nakatsuka

Hiromitsu Iwata

Rie Tanaka

Hidekazu Inoue

Yasuo Yamada

Tetsuo Shimamoto

Gozoh Tsujimoto

Kazuto Sekiuchi

Takayoshi Suzuki

Osamu Miyahara

Naoki Miyata

Kiyoharu Nakayama

Masahiro Imoto

Mie Hata

Kenichi Noguchi

Tsutomu Kaku

Akira Kaneko

Takuro Yoshida

Akira Hirasawa

Yoshiyuki Takahara

Disclosed is a novel aralkyl carboxylic acid compound which has an agonistic activity on GPR-120 and/or GPR-40, particularly GPR-120, and is therefore useful as an appetite regulator, an anti-obesity agent, a therapeutic agent for diabetes, a pancreatic beta differentiating cell growth enhancer, a therapeutic agent for metabolic syndrome, a therapeutic agent for a gastrointestinal disease, a therapeutic agent for a neuropathy, a therapeutic agent for a mental disorder, a therapeutic agent for a pulmonary disease, a therapeutic agent for a pituitary hormone secretion disorder or a lipid flavoring/seasoning agent. The aralkyl carboxylic acid compound is represented by the general formula (I). (I) wherein the ring Q represents a pyridyl or the like; Rrepresents a Calkyl group or the like; Rrepresents a hydrogen atom, a Calkyl group or a Calkoxy group; m and n independently represent an integer of 1 to 5; and X represents an oxygen atom, a sulfur atom or &#x2014;NR&#x2014; [wherein Rrepresents a hydrogen atom or a Calkyl group]. 

G-protein-conjugated receptor agonist

An azetidinone derivative represented by the general formula (1)(wherein ORis a protected hydroxyl group; Ris a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group or a substituted or unsubstituted aromatic group) is reacted with an ester compound represented by the formula (2)(wherein CORis an esterified carboxyl group; X and Y are the same or different and represent individually a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted alkenylthio group, a substituted or unsubstituted aralkylthio group, a substituted or unsubstituted arylthio group, a substituted or unsubstituted alkyloxy group, a substituted or unsubstituted alkenyloxy group, a substituted or unsubstituted aralkyloxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted silyloxy group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted heterocyclic-thio group, a substituted or unsubstituted heterocyclic-oxy group, a substituted or unsubstituted acyl group, a substituted or unsubstituted ester group, a substituted or unsubstituted thio ester group, a substituted or unsubstituted amide group, a substituted or unsubstituted amino group, a hydrogen atom or halogen atom, or are taken together with each other to form a substituted or unsubstituted cycloalkan-2-on-1-yl group) in the presence of zinc and copper compounds to synthesis a 4-substituted azetidinone derivative represented by the formula (3)(wherein OR, COR, X and Y are as defined above).

Process for synthesizing 4-substituted azetidinone derivatives

A carbapenem derivative represented by the following formula (I), ##STR1## wherein R.sub.1 represents a hydrogen atom, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, R.sub.2 indicates a hydrogen atom or a protective group for a carboxyl group, and R.sub.3 is a methyl group or an ethyl group; or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising this carbapenem derivative or a salt thereof as an active ingredient. The carbapenem derivative exhibits a wide and strong antimicrobial activity, particularly a strong antimicrobial activity against MRSA. An intermediate compound for preparing the carbapenem derivative is also disclosed.

1'S, 5R, 6R-carbapenem derivatives and antimicrobial agents comprising

Production method of optically active trans-vinylsulfide alcohol

Antibiotic penem compounds are represented by the following formula: ##STR1## wherein R represents a group of the general formula: ##STR2## in which R.sub.1 is a hydrogen atom or linear or branched C.sub.1 --C.sub.6 alkyl group, R.sub.2 is a particular substituted or unsubstituted alkyl, aryl or aralkyl group, n is an integer of 1-6, Y is a 5- or 6-membered heterocyclic aliphatic group having 1 or 2 oxygen atoms in the ring thereof, and Z is a specific 5-substituted 2-oxo-1,3-dioxolen-4-yl group. Antibiotic compositions for oral administration are also described.

Antibacterial penem esters derivatives

Method of desilylating a silylether compound by reacting a silylether compound of the general formula (I): ##STR1## or a salt thereof with an amine hydrogen fluoride salt or a pyridine hydrogen fluoride salt in an organic solvent to produce a compound of the general formula (IV): ##STR2## According to this method, silylether compounds that are labile under strong acidic or basic conditions can be desilylated efficiently using inexpensive reagents.

Method of desilylating silylether compounds

Penem compounds

Antibacterial penem compounds

Novel penem compounds of the formula, ##STR1## wherein R is hydrogen or allyl, and A is an aliphatic 5- or 6-membered heterocyclic group having one or two oxygens in the ring and their pharmaceutically acceptable salts are produced from the compounds of the formula, ##STR2## wherein A is the same as above and respective R.sup.1 and R.sup.2 are protective groups for hydroxyl and carboxyl groups, through several steps. The compounds and their salts are useful as antibacterial agents.

Penem derivatives production and use thereof

A process for producing 3-[1'-(R)-hydroxyethyl]-4-acyloxyazetidinone from 3-[1'-(R)-hydroxyethyl]-4-alkyl (or aryl) thioazetidinone using a copper salt of aliphatic or aromatic carboxylic acid is disclosed. The process is an effective route for producing 3-[1'-(R)-hydroxyethyl]-4-acyloxyazetidinone, and intermediate for synthesizing penems or carbapenems, without using a mercury salt which can cause an environmental hazard.

Process for the preparation of 4-acyloxy-2-azetidinone derivatives

A penem compound represented by the general formula: ##STR1## (wherein R denotes hydrogen or allyl group, A denotes oxygen atom or methylene group and B denotes methylene, ethylene or carbonyl group) or a pharmacologically acceptable salt is produced through several processes. The compound exhibits stronger activities against wide variety of gram-positive and gram-negative bacteria as compared with known penem compounds.

Penem compounds, and use thereof

A process for preparing an optically active tetrahydro-2-furoic acid is disclosed. The process comprises (i) reacting (.+-.)-tetrahydro-2-furoic acid with an optically active amine resolver of the following formula (I): ##STR1## wherein R.sub.1 is a lower alkyl group and R.sub.2 represents an alkyl group or ar aryl group, provided that R.sub.1 and R.sub.2 are different from each other, thus producing an optically active diastereomer salt, and (ii) decomposing the diastereomer salt. According to the process, a high purity, optically active tetrahydro-2-furoic acid can be prepared at a high yield using an amine resolver. The amine resolver can be recovered at a high yield and high purity.

Process for preparing optically active tetrahydro-2-furoic acid

Growing community of inventors

Takarazuka, Japan

Masaji Ishiguro