Ono Pharmaceutical Co., Ltd.

Ono Pharmaceuticals Co., Ltd.

Shuichi Ohuchida

Masaaki Toda

Hiroyuki Ohno

Yoshinobu Arai

Tsumoru Miyamoto

Masaki Hayashi

Kousuke Tani

Toru Maruyama

Narito Tateishi

Kazuo Kishimoto

Yoshitaka Konishi

Yuuki Nagao

Katsuichi Shimoji

Takayuki Maruyama

Hirohisa Wakatsuka

Fumio Nambu

Shinsuke Hashimoto

Hiroyuki Ito

Hayashi Masaki

Formula (I) compounds: wherein Ris alkyl substituted by fluorine(s); Ris hydroxy, alkoxy, alkoxy substituted by phenyl, NRR, in which R, Ris (i) hydrogen, (ii) alkyl, (iii) phenyl, (iv) phenyl substituted by alkoxy or carboxyl, (v) heterocyclic ring containing nitrogen atom, (vi) alkyl substituted by phenyl, phenyl subsituted by alkoxy or carboxyl, heterocyclic ring containing nitrogen atom, (vii) the nitrogen bonded to Rand R, taken together is a saturated heterocyclic ring or amino acid residue; and non-toxic salts and acid addition salts thereof. Also, Formula (X) compounds: wherein n is 0 or 1, Ris hydrogen and chlorine, Ris R&#x2014;CH&#x2014; or R, or Rand R, taken together is alkylidene; Ris hydroxy, alkoxy, alkoxy substituted by phenyl, NRR, in which R, Ris (i) hydrogen, (ii) alkyl, (iii) phenyl, (iv) phenyl substituted by alkoxy or carboxyl, (v) heterocyclic ring containing nitrogen atom, (vi) alkyl substituted by phenyl, phenyl-substituted by alkoxy or carboxyl, heterocyclic ring containing nitrogen atom, (vii) the nitrogen bonded to Rand R, taken together is a saturated heterocyclic ring or amino acid residue, Ris (i) F&#x2014;(CH)m- or FC&#x2014;CH&#x2014;, (ii) alkyl substituted by chlorine, (iii) alkyl substituted by alkoxy, cycloalkyl, phenyl, phenoxy; Ris alkyl, alkenyl, alkoxy, alkylthio, cycloalkyl, phenyl, phenoxy. Non-toxic and acid addition salts thereof are useful to prevent and/or treat neurodegenerative disease (e.g., Alzheimer's) and neuronal dysfunction by stroke or traumatic injury (e.g., Multiple sclerosis).

Pentanoic acid derivatives

Formula (I) compounds: wherein Ris alkyl substituted by fluorine(s); Ris hydroxy, alkoxy, alkoxy substituted by phenyl, NRR, in which R, Ris (i) hydrogen, (ii) alkyl, (iii) phenyl, (iv) phenyl substituted by alkoxy or carboxyl, (v) heterocyclic ring containing nitrogen atom, (vi) alkyl substituted by phenyl, phenyl substituted by alkoxy or carboxyl, heterocyclic ring containing nitrogen atom, (vii) the nitrogen bonded to Rand R, taken together is a saturated heterocyclic ring or amino acid residue; and non-toxic salts and acid addition salts thereof. Also, Formula (X) compounds: wherein n is 0 or 1, Ris hydrogen and chlorine, Ris R&#x2014;CH&#x2014; or R, or Rand R, taken together is alkylidene; Ris hydroxy, alkoxy, alkoxy substituted by phenyl, NRR, in which R, Ris (i) hydrogen, (ii) alkyl, (iii) phenyl, (iv) phenyl substituted by alkoxy or carboxyl, (v) heterocyclic ring containing nitrogen atom, (vi) alkyl substituted by phenyl, phenyl-substituted by alkoxy or carboxyl, heterocyclic ring containing nitrogen atom, (vii) the nitrogen bonded to Rand R, taken together is a saturated heterocyclic ring or amino acid residue, Ris (i) F&#x2014;(CH)m- or FC&#x2014;CH&#x2014;, (ii) alkyl substituted by chlorine, (iii) alkyl substituted by alkoxy, cycloalkyl, phenyl, phenoxy; Ris alkyl, alkenyl, alkoxy, alkylthio, cycloalkyl, phenyl, phenoxy. Non-toxic and acid addition salts thereof are useful to prevent and/or treat neurodegenerative disease (e.g., Alzheimer's) and neuronal dysfunction by stroke or traumatic injury (e.g., Multiple sclerosis).

The compound of the formula (I): wherein Ris alkyl substituted by fluorine(s); The compounds of the present invention of the formula (I) and the compounds of the formula (X): wherein n is 0 or 1,

Sulfonamide and carboxamide derivatives and drugs containing the same as the active ingredient

&ohgr;-substituted phenyl-prostaglandin E derivatives and drugs containing the same as the active ingredient

&ohgr;-cycloalkyl-prostaglandin E2 derivatives

5-thia-&ohgr;-substituted phenyl-prostaglandin E derivatives, process for producing the same and drugs containing the same as the active ingredient

The present invention provides 11,15-O-dialkyl prostaglandin E derivatives of formula (I)

11,15-O-dialkylprostaglandin E derivatives, process for producing the same, and drugs containing the same as the active ingredient

&ohgr;-Cycloalkyl-prostaglandin E,derivatives of formula (I)

&ohgr;-Cycloalkly-prostaglandin e2 derivatives

&ohgr;-cycloalkyl-prostaglandin E1 derivatives

A benzenesulfonamide compound of the formula (I)

Benzenesulfonamide compounds

A .omega.-cycloalkyl-prostaglandin E.sub.2 derivatives of the formula (I) ##STR1## wherein R is carboxy or hydroxymethyl; R.sup.1 is oxo, methylene or halogen atom; R.sup.2 is H, OH or C1-4 alkoxy; R.sup.3 is H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkyl, C2-8 alkenyl or C2-8 alkynyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkoxy, C3-7 cycloalkyl, phenyl, or phenyl substituted by 1-3 of substituent selected from halogen atom, C1-4 alkyl, C1-4 alkoxy, nitro, trifluoromethyl; n is 0-4; and non-toxic salt thereof, prodrug thereof and cyclodextrin clathrate thereof can strongly bind on EP.sub.2 subtype receptor. Therefore, they are useful for prevention and/or treatment of immune disease (autoimmune disease, organ transplantation, etc.), asthma, abnormal bone formation, neuron cell death, liver damage, abortion, premature birth or retina neuropathy of glaucoma etc.

Cycloalkyl-prostaglandin E.sub.2 derivatives

A 3,7-dithiaprostanoic acid derivative of the formula (I) ##STR1## (wherein, R.sup.1 is OH, C1.about.6 alkyloxy, NR.sup.6 R.sup.7 (R.sup.6, R.sup.7 are H, C1.about.6 alkyl.); R.sup.2 is H, OH; R.sup.3 is single bond, C1.about.6 alkylene; R.sup.4 is (i) C1.about.8 alkyl substituted by C1.about.6 alkyloxy, halogen etc., (ii) phenyloxy, C3.about.7 cycloalkyloxy, (iii) furyl, furyloxy, thienyl, thienyloxy, naphthyl, naphthyloxy, phthalanyl, phthalanyloxy, (iv) phenyl, phenyloxy, C3.about.7 cycloalkyl, C3.about.7 cycloalkyloxy substituted by C1.about.6 alkyl etc., (v) furyl, furyloxy, thienyl, thienyloxy, naphthyl, naphthyloxy, phthalanyl, phthalanyloxy substituted by C1.about.6 alkyl etc.; R.sup.5 is H, C1.about.6 alkyl.) can bind PGE.sub.2 receptor (particularly, EP4 subtype receptor) strongly. So, they are useful for the prevention and/or treatment of immunological diseases (autoimmune diseases, rejection after organ transplantation etc.), asthma, abnormal bone formation, neuronal cell death, liver damage, nephritis, hypertension, myocardiac ischemia and sleeping disorder etc.

3,7-dithiaprostanoic acid derivative

Growing community of inventors

Osaka, Japan

Shuichi Ohuchida