Daiichi Sankyo Company, Limited

Sankyo Company, Limited

Sankko Company, Limited

Nobuyuki Ohkawa

Norio Nakamura

Takeshi Oshima

Yasuteru Iijima

Masaaki Miyamoto

Takayoshi Nagasaki

Tomio Kimura

Atsuhiro Sugidachi

Osamu Ando

Shinji Tanaka

Hideki Kobayashi

Toshio Kaneko

Keiji Saito

Osamu Iwamoto

Hideki Kubota

Katsuyoshi Nakajima

Akira Nakao

Hiroyuki Tsuruoka

Masami Arai

Nobuya Kurikawa

Tsuyoshi Soneda

Natsumi Nishihama

Momoko Ogitani

Wataru Saitoh

Naoki Terasaka

Daisuke Takano

Junya Kawai

Tomohiro Honda

Yuma Umezaki

Takanori Yamazaki

Kouki Iida

Toshio Onoda

An object of the present invention is to provide a compound that has a specific chemical structure having an activation effect on SIRT6 and is useful as an active component for preventing and treating inflammatory diseases, and the present invention relates to a compound represented by Formula (1) or a pharmaceutically acceptable salt thereof,

Urea compound having substituent

A compound represented by the general formula (I) or a pharmacologically acceptable salt thereof has an excellent LCAT-activating effect and is useful as an active ingredient in a therapeutic or prophylactic agent for arteriosclerosis, arteriosclerotic heart disease, coronary heart disease (including heart failure, myocardial infarction, angina pectoris, cardiac ischemia, cardiovascular disturbance, and restenosis caused by angiogenesis), cerebrovascular disease (including stroke and cerebral infarction), peripheral vascular disease (including diabetic vascular complications), dyslipidemia, hypo-HDL-cholesterolemia, or renal disease, particularly, an anti-arteriosclerotic agent, wherein R is an optionally substituted aryl group or an optionally substituted heteroaryl group. 

Piperidinylpyrazolopyridine derivative

To provide potassium salts of substituted cycloalkene derivatives, which suppress the production of an inflammatory mediator caused by intracellular signal transduction or cell activation induced by endotoxin, and crystals thereof. The present invention provides potassium (2-chloro-4-fluorophenyl){[(2R,3R,8R)-7-(ethoxycarbonyl)-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]deca-6-en-8-yl]sulfonyl}azanide and potassium (2-bromo-4-fluorophenyl){[(2R,3R,8R)-7-(ethoxycarbonyl)-2,3-bis(hydroxymethyl)-1,4-dioxaspiro[4.5]deca-6-en-8-yl]sulfonyl}azanide, each of which suppresses the production of an inflammatory mediator caused by intracellular signal transduction or cell activation induced by endotoxin, crystals thereof, and a pharmaceutical containing any of the same, and a prophylactic and/or therapeutic agent for sepsis containing any of the same.

Crystals of substituted cycloalkene derivatives

A compound of formula (I) Wherein X, Y, ring A, ring B, l, m, R, R, Rand Rare as defined herein, to supress intracellular signal transduction or cell activation induced by endotoxin and to suppress cell responses due to the intracellular signal transduction and cell activation such as an excess generation of inflammatory mediators such as TNF-&#x3b1;, pharmacologically acceptable salts therefor, a preparation method therefor, and a medicament containing the aforementioned substituted cycloalkene derivative as an active ingredient which is superior in prophylaxis and/or treatment of diseases such as sepsis (septic shock, disseminated intravascular coagulation, multiple organ failure and the like), that are associated with intracellular signal transduction or cell activation induced by endotoxin and to cell responses to the intracellular signal transduction and cell activation.

Substituted cycloalkene derivative

Compounds having activity against production of an inflammatory cytokine of formula (I)': A&#x2032; is pyrrole; Ris phenyl or naphthyl; Ris pyridyl or pyrimidinyl; Ris (IIa)&#x2032;, (IIb)&#x2032; or (IIc)&#x2032;: m&#x2032; is 1; E&#x2032; is nitrogen; D&#x2032; is &#x3e;C(R)&#x2014;, Ris hydrogen, Substituent &#x3b1;&#x2032; or Substituent &#x3b2;&#x2032;; B&#x2032; is nitrogen-containing 5-membered heterocyclic; Ris 1 to 3 substituents from Substituent &#x3b1;&#x2032;, Substituent &#x3b2;&#x2032; and Substituent &#x3b3;&#x2032;; Rand Rare bonded to two atoms of the pyrrole adjacent to the pyrrole atom bonded to R; Substituent &#x3b1;&#x2032; is hydroxyl, nitro, cyano, halogen, alkoxy, halogeno alkoxy, alkylthio, halogeno alkylthio or &#x2014;NRR; Rand Rare hydrogen, alkyl, alkenyl, alkynyl, aralkyl or alkylsulfonyl, or Rand Rwith the nitrogen atom form a heterocyclyl; Substituent &#x3b2;&#x2032; is alkyl, alkenyl, alkynyl, aralkyl or cycloalkyl; Substituent &#x3b3;&#x2032; is oxo, hydroxyimino, alkoxyimino, alkylene, alkylenedioxy, alkylsulfinyl, alkylsulfonyl, aryl, aryloxy, alkylidenyl or aralkylidenyl.

Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses

A method of treating a PAF-mediated pathology or for treating or preventing psoriasis, nephritis, asthma, inflammation or shock by administering an effective amount of a PAF antagonist of the formula ##STR1## wherein R.sup.1 and R.sup.2 are each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5 ; R.sup.5 is an unsubstituted or substituted C.sub.6 -C.sub.14 carbocyclic aryl of an aromatic heterocyclic having from 5 to 14 ring atoms, of which from 1 to 5 are hetero-atoms selected from the group consisting of nitrogen, oxygen and sulfur, the heterocyclic group being unsubstituted or substituted; R.sup.3 is hydrogen, a C.sub.1 -C.sub.6 alkyl, cyano, or --R.sup.5 ; X is oxygen or sulfur; A is a 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B is a C.sub.1 -C.sub.6 alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is an unsubstituted or substituted phenyl group.

Method of treating a PAF-mediated pathology or for treating or

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 is each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5, wherein R.sup.5 is optionally substituted aryl or aromatic heterocyclic; R.sup.3 is hydrogen, alkyl, cyano or --R.sup.5 ; X is oxygen or sulfur A is 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B' is alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl: and R.sup.4 is optionally substituted phenyl and pharmaceutically acceptable salts thereof have valuable PAF antagonist activity.

N-acryloylpiperazine compounds

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 is each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5, wherein R.sup.5 is optionally substituted aryl or aromatic heterocyclic; R.sup.3 is hydrogen, alkyl, cyano or --R.sup.5 ; X is oxygen or sulfur; A a 1,4-homopiperazin-1,4-diyl; B' is alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is optionally substituted phenyl and pharmaceutically acceptable salts thereof have valuable PAF antagonist activity, and may be prepared by reacting a compound containing the homopiperazine part of the molecule with a compound containing the other part of the molecule.

N-acryloylpiperazine derivatives, their preparation and their use of PAF

Compounds of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 is each --R.sup.5, --CH.dbd.CH--R.sup.5 or --C.tbd.C--R.sup.5, wherein R.sup.5 is optionally substituted aryl or aromatic heterocyclic; R.sup.3 is hydrogen, alkyl, cyano or --R.sup.5 ; X is oxygen or sulfur; A is 1,4-piperazin-1,4-diyl or a 1,4-homopiperazin-1,4-diyl; B' is alkylene, carbonyl, thiocarbonyl, sulfinyl or sulfonyl; and R.sup.4 is optionally substituted phenyl and pharmaceutically acceptable salts thereof have valuable PAF antagonist activity, and may be prepared by reacting a compound containing the piperazine or homopiperazine part of the molecular with a compound containing the other part of the molecule.

N-acryloylpiperazine derivatives, their preparation and their use as PAF

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Tokyo, Japan

Nobuyuki Ohkawa