BENZO(B)CYCLODIOXAALKANE DERIVATIVES

摘要

1. A benzo(b)cyclodioxaalkane derivatives represented by the following formula (I): wherein m represents an integer of 0 to 4; R<1>, R<2>, R<3> and R<4> independently represent a hydrogen atom, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 alkenyl; R<5> represents hydroxy or substituted or unsubstituted C1-C8 alkoxy; Y represents the following formula (II): wherein R<9> represents cyano, ethynyl or carbamoyl, and R<10> represents a hydrogen atom, or R<9> and R<10> are combined to represent a single bond (forming a double bond together with the already-existing bond), R<11> represents hydroxy, formyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted tetrazolyl, -NR<13>R<14> (wherein R<13> and R<14> independently represent a hydrogen atom, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted alkanoyl, having C1-C8 alkyl fragment, C3-C10 cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted aromatic heterocyclic group or substituted or unsubstituted aralkyl, or R<13> and R<14> are combined to represent a substituted or unsubstituted heterocyclic group together with the adjacent nitrogen atom), -COOR<15> (wherein R<15> represents a hydrogen atom, or substituted or unsubstituted C1-C8 alkyl), -CONR<16>R<17> (wherein R<16> and R<17> independently represent a hydrogen atom, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted alkanoyl, having C1-C8 alkyl fragment, substituted or unsubstituted C3-C10 cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group, or substituted or unsubstituted aralkyl, or R<16> and R<17> are combined to represent a substituted or unsubstituted heterocyclic group together with the adjacent nitrogen atom), or -CH2COOR<18> (wherein R<18> represents a hydrogen atom or substituted or unsubstituted C1-C8 alkyl), R<12> represents a hydrogen atom, or substituted or unsubstituted C1-C8 alkoxy, or R<11> and R<12> are combined together to represent -OCH2(CH2)pO- (wherein p represents an integer of 1 to 3), =CHOR<21> (wherein R<21> represents substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, or substituted or unsubstituted aralkyl), =CHCOOR<22> (wherein R<22> represents a hydrogen atom, or substituted or unsubstituted lower alkyl) or =O; the following formula (III): wherein n represents an integer of 0 to 4, X represents CH2 or O; following formula (IV): wherein R<A> represents a hydrogen atom, substituted or unsubstituted C1-C8 alkyl, or substituted or unsubstituted aralkyl; wherein aryl is selected from the group, comprising phenyl and naphthyl; aralkyl is selected from the group, comprising benzyl, phenethyl, benzhydryl, and naphthylmethyl; aromatic heterocyclic group is selected from the group, comprising furyl, thienyl, pyridyl, pirazinyl, pirimidinyl, piridazinyl, quinolyl, isoquinolyl, phtazinyl, quinazolinyl, quinoxalinyl, naphtylidinyl, pirrolyl, pirazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, indolil, indazolyl, benzimidazolyl, benzotriazolyl and purinyl; heterocyclic group, which is formed together with adjacent nitrogen atom, is selected from the group, comprising pirrodinyl, piperidino, piperazinyl, morpholino, thiomorpholino, homopiperidino, homopiperazinyl, tetrahydropiridyl, tetrahydroquinolyl and tetrahydroisoquinolyl; substituents in substituted C1-C8 alkyl, substituted C1-C8 alkoxy, substituted alkanoyl, having C1-C8 alkyl fragment, substituted C2-C8 alkenyl and substituted C3-C10cycloalkyl represents1-3 substituents, which are similar or different and selected from group, comprising C1-C8 alkyl, C2-C8alkenyl, cyano, C3-C10 cycloalkyl, C4-C10cycloalkenyl, hydroxy, C1-C8 carboxy and halogen; and substituents in substituted aryl, substituted aromatic heterocyclic group, substituted heterocyclic group, formed together with adjacent nitrogen atom, and substituted aralkyl represents 1-3 substituents, similar or different and selected from the group, comprising substituted or unsubstituted C1-C8 alkyl, hydroxy, C1-C8 alkoxy, alkanoyl, having C1-C8 alkyl fragment, carboxy, carbamoyl, trifluomethyl, amino, mono- or di- (C1-C8 alkyl)-substituted amino, cyano, nitro, and halogen, in which substituted C1-C8 alkyl has the values, defined above; or pharmaceutically acceptable salts thereof. 2. The benzo(b)cyclodioxaalkane derivatives according to Claim 1, wherein Y is the formula (II) or a pharmaceutically acceptable salt thereof. 3. The benzo(b)cyclodioxaalkane derivatives according to Claim 2, wherein R<9> is cyano; or a pharmaceutically acceptable salt thereof. 4. The benzo(b)cyclodioxaalkane derivatives according to any one of Claims 1 to 3, wherein m is 0 or 1; or a pharmaceutically acceptable salt thereof. 5. The benzo(b)cyclodioxaalkane derivatives according to any one of Claims 1 to 4, wherein all of R<1>, R<2>, R<3> and R<4> are hydrogen atoms, or one group among R<1>, R<2>, R<3> and R<4> is substituted or unsubstituted lower alkyl while other three groups are hydrogen atoms; or a pharmaceutically acceptable salt thereof. 6. The benzo(b)cyclodioxaalkane derivatives according to any one of Claims 1 to 5, wherein R<11> represents carboxy or hydroxy, or R<11> and R<12> are combined together to represent =O; or a pharmaceutically acceptable salt thereof. 7. The benzo(b)cyclodioxaalkane derivatives according to Claim 1, wherein Y is the formula (III); or a pharmaceutically acceptable salt thereof. 8. The benzo(b)cyclodioxaalkane derivatives according to Claim 7, wherein n is 1; or a pharmaceutically acceptable salt thereof. 9. The benzo(b)cyclodioxaalkane derivatives according to Claim 7 or 8, wherein X is CH2; or a pharmaceutically acceptable salt thereof. 10. A pharmaceutical composition, which comprises at least one benzo(b)cyclodioxaalkane derivatives according to Claim 1 or a pharmaceutically acceptable salt thereof. 11. Use of benzo(b)cyclodioxaalkane derivatives according to any of claims 1-9 or pharmaceutically acceptable salt thereof as a phosphodiesterase (PDE) IV inhibitor. 12. Use of benzo(b)cyclodioxaalkane derivatives according to any of claims 1-9 or pharmaceutically acceptable salt thereof to produce a phosphodiesterase (PDE) IV inhibitor.