ω-substituted phenyl-prostaglandin E derivatives and drugs containing the same as the active ingredient
AssigneeOno Pharmaceutical Co., Ltd.
InventorsToru Maruyama, Shuichi Ohuchida
Life of this patent
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Abstract
A ω-substituted phenyl-prostaglandin of formula (I), a process for the preparation thereof, a mediciament comprising it as active ingredient (all symbols have the same meaning as described in the specification). The compounds of the formula (I) bind strongly in PGE2 receptor (especially subtype EP4) and therefore are useful for the prophylaxis and/or treatment of immune diseases (autoimmune diseases (amyotrophic lateral sclerosis (ALS) etc.), post-transplantation graft rejection, etc.), asthma, abnormal bone formation, neurocyte death, pulmopathy, hepatopathy, etc. They are also related to sleeping disorders and platelet coagulations, and therefore they are also applicable to these diseases.
Claims24
An ω-substituted phenyl-prostaglandin E derivative of formula (I)
- (wherein
- A is C2˜8 alkylene, C2˜8 alkenylene, C1˜4 alkylene-phenylene or C2˜4 alkenylene-phenylene,
- R1 is hydroxy, C1˜6 alkyloxy, C1˜6 alkyloxy-C1˜6 alkyloxy, HO—C1˜6 alkyloxy or a formula of NR6R7 (wherein R6 and R7 are each independently hydrogen atom or C1˜4 alkyl), R2 is oxo, halogen or a group of formula R8—COO— (wherein R8 is hydrogen, C1˜4 alkyl, phenyl or phenyl(C1˜4 alkyl), C1˜4 alkyloxy, HOOC—C1˜4 alkyl, C1˜4 alkyloxy-carbonyl-C1˜4 alkyl, HOOC—C2˜4 alkenyl or C1˜4 alkyloxy-carbonyl-C2˜4 alkenyl),
- R3 is hydrogen or hydroxy,
- R4 is C1˜4 alkylene,
- R5 is phenyl substituted by the following groups:
- i) 1˜3 groups selected from
- C1˜4 alkyloxy-C1˜4 alkyl,
- C2˜4 alkenyloxy-C1˜4 alkyl,
- C2˜4 alkynyloxy-C1˜4 alkyl,
- C3˜7 cycloalkyloxy-C1˜4 alkyl,
- C3˜7 cycloalkyl(C1˜4 alkyloxy)-C1˜4 alkyl,
- phenyloxy-C1˜4 alkyl,
- phenyl-C1˜4 alkyloxy-C1˜4 alkyl,
- C1˜4 alkylthio-C1˜4 alkyl,
- C2˜4 alkenylthio-C1˜4 alkyl;
- C2˜4 alkynylthio-C1˜4 alkyl;
- C3˜7 cycloalkylthio-C1˜4 alkyl,
- C3˜7 cycloalkyl(C1˜4 alkylthio)-C1˜4 alkyl,
- phenylthio-C1˜4 alkyl and
- phenyl-C1˜4 alkylthio-C1˜4 alkyl,
- ii) C1˜4 alkyloxy-C1˜4 alkyl and C1˜4 alkyl,
- C1˜4 alkyloxy-C1˜4 alkyl and C1˜4 alkyloxy,
- C1˜4 alkyloxy-C1˜4 alkyl and hydroxy,
- C1˜4 alkyloxy-C1˜4 alkyl and halogen,
- C1˜4 alkylthio-C1˜4 alkyl and C1˜4 alkyl,
- C1˜4 alkylthio-C1˜4 alkyl and C1˜4 alkyloxy,
- C1˜4 alkylthio-C1˜4 alkyl and hydroxy or
- C1˜4 alkylthio-C1˜4 alkyl and halogen
- iii) mono halo-C1˜4 alkyl or hydroxy-C1˜4 alkyl, or
- iv) C1˜4 alkyl and hydroxy;
- and
- wherein is a bond or a double bond,
- and when R2 is R8—COO—, R8 is C1˜6 alkyloxy, C1˜6 alkyloxy-C1˜6 alkyloxy or HO—C1˜6 alkyloxy and the bond in the 8-9 position is a double bond),
- a non-toxic salt thereof or a cyclodextrin clathrate thereof.
Dependencies are inferred from the claim text.