Daiichi Sankyo Company, Limited

Sankyo Company, Limited

Takayoshi Nagasaki

Nobuyuki Ohkawa

Tomio Kimura

Atsuhiro Sugidachi

Osamu Ando

Akira Nakao

Kouki Iida

Takanori Yamazaki

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

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Tokyo, Japan

Takayoshi Nagasaki