Naphthalene derivative

• US 5,945,450 A
• Filed: 11/22/1996
• Issued: 08/31/1999
• Est. Priority Date: 05/31/1994
• Status: Expired due to Fees

• Current Assignee: Teijin Limited
• Original Assignee: Teijin Limited
• Inventors: Hasegawa, Masaichi, Takahashi, Katsushi, Komoriya, Keiji, Takenouchi, Kazuya, Takeuchi, Takahiro
• Primary Examiner(s): Kumar, Shailendra
• Application Number:
  US08/737,991
• Time in Patent Office: 1,012 Days
• Field of Search: 514/535, 514/533, 514/534, 514/561, 514/562, 514/563, 514/522, 514/381, 514/602, 514/603, 514/618, 514/619, 560/10, 560/21, 560/17, 560/43, 562/427, 562/455, 558/415, 558/416, 548/253, 564/84, 564/85, 564/86, 564/88, 564/162, 564/168
• US Class Current: 514/535
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 233/11 with carbon atoms of carboxamide groups bound to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 233/22 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 233/55 having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
• CPC Class Codes: C07C 233/65 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
• CPC Class Codes: C07C 233/75 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 233/81 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 235/38 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/42 having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
• CPC Class Codes: C07C 235/56 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/64 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/20 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 237/44 having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 255/60 at least one of the singly-bound nitrogen atoms being acylated
• CPC Class Codes: C07C 311/46 Y being a hydrogen or a carbon atom
• CPC Class Codes: C07C 323/29 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• CPC Class Codes: C07C 323/62 having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
• CPC Class Codes: C07D 257/04 : Five-membered rings

Abstract

Naphthalene derivatives represented by formula I!: ##STR1## (wherein A is a hydrogen atom, a hydroxy group, a C₇ -C₁₁ aralkyloxy group, or an alkoxy group composed of an oxy group and a C₁ -C₁₂ aliphatic or alicyclic, saturated or unsaturated hydrocarbon group where the allyl may be substituted with a C₆ -C₁₀ allyloxy group; Q represents O, S, CH₂, O--CH₂, S--CH₂, CO, or CHOR¹ ; L represents CO, CR² R³ CO, CH₂ CH₂ CO, or CH═CHCO; D represents a hydrogen atom, NO₂, NH₂, CO₂ R⁴, or a group having the following formula II!: ##STR2## (wherein G represents. a hydrogen atom, OH, SO₂ NH₂, CO₂ R⁶, CN, or a tetrazol-5-yl group); E represents a hydrogen atom, OH, SO₂ NH₂, CO₂ R⁵, CN, or a tetrazol-5-yl group; M represents a hydrogen atom, a C₁ -C₄ lower alkyl group, a nitro group, or a halogen atom; and R¹, R², R³, R⁴, R⁵ and R⁶ are, independently each other, a hydrogen atom or a C₁ -C₄ lower alkyl group);

pharmacologically acceptable salts thereof, or pharmacologically acceptable solvates thereof, which have, for example, an inhibitory effect on the production of IgE antibodies, and will be useful for prophylaxis and/or treatment of allergic diseases.

Claims

1. A naphthalene derivative having the following formula (I):

##STR126## wherein A represents a hydrogen atom, a hydroxy group, a C₇ -C₁₁ aralkyloxy group, or an alkoxy group composed of an oxy group and a C₁ -C₁₂ aliphatic or alicyclic, saturated or unsaturated hydrocarbon group in which the alkyl moiety may be substituted with a C₆ -C₁₀ aryloxy group;

O represents O, S, O--CH₂, S--CH₂, or CHOR¹ ;

L represents CO, CR² R³ CO, CH₂ CH₂ CO, or CH═

CHCO;

D represents a hydrogen atom, NO₂, NH₂, CO₂ R⁴, or a group having the following formula (II);

##STR127## wherein G represents a hydrogen atom, OH, SO₂ NH₂, CO₂ R⁶, CN or a tetrazol-5-yl group;

E represents a hydrogen atom, OH, SO₂ NH₂, CO₂ R⁵, CN, or a tetrazol-5-yl group;

M represents a hydrogen atom, a C₁ -C₄ lower alkyl group, a nitro group, or a halogen atom; and

R¹, R², R³, R⁴, R⁵ and R⁶, independently represent a hydrogen atom or a C₁ -C₄ lower alkyl group;

a pharmacologically acceptable salt thereof or a pharmacologically acceptable solvate thereof.

2. The naphthalene derivative according to claim 1 wherein E represents CO₂ R⁵ where R⁵ represents a hydrogen atom or a C₁ -C₄ lower alkyl group or a tetrazol-5-yl group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

3. The naphthalene derivative according to claim 1 wherein D represents a hydrogen atom, NO₂, NH₂ or a group represented by formula (II) wherein G represents a hydrogen atom or CO₂ R⁶, and R⁶ represents a hydrogen atom or a C₁ -C₄ lower alkyl group, the pharmacologically acceptable salt thereof or the pharmacologically acceptable solvate thereof.

4. The naphthalene derivative according to claim 1, wherein D represents a hydrogen atom or NO₂, E represents CO₂ R⁵, and R⁵ represents a hydrogen atom or a C₁ -C₄ lower alkyl group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

5. The naphthalene derivatives according to claim 1 wherein M is a hydrogen atom, a methyl group, an ethyl group, a nitro group, a fluorine atom or a chlorine atom, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

6. The naphthalene derivatives according to claim 1, wherein R¹ -R⁶ represent, independently a hydrogen atom or a methyl group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

7. The naphthalene derivative according to any one claim of claims 1-6, wherein O represents O, S, O--CH₂, S--CH₂, or CHOR¹ where R¹ represents a hydrogen atom or a C₁ -C₄ lower alkyl group and L represents CO, CR² R³ CO or CH═

CHCO where R² and R³, independently represent a hydrogen atom or a C₁ -C₄ lower alkyl group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

8. The naphthalene derivative according to any one claim of claims 1-6, wherein O represents O, S, or CHOR¹ where R¹ represents a hydrogen atom or a C₁ -C₄ lower alkyl group and L represents CO or CR² R³ CO where R² and R³, independently represent a hydrogen atom or a C₁ -C₄ lower alkyl group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

9. The naphthalene derivative according to any one claim of claims 1-6, wherein O represents O and L represents CO or CR² R³ CO where R² and R³, independently are a hydrogen atom or a C₁ -C₄ lower alkyl group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

10. The naphthalene derivative according to any one claim of claims 1-6, wherein O represents O, S, O--CH₂ or S--CH₂ and L represents CO or CH═

CHCO, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

11. The naphthalene derivative according to any one claim of claims 1-6, wherein O represents O, S, O--CH₂ or S--CH₂, and L represents CO, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

12. The naphthalene derivatives according to any one claim of claims 1-6, wherein O represents O, and L represents CH═

CHCO, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

13. The naphthalene derivatives according to claim 1, wherein A represents a hydrogen atom;

a hydroxy group;

an alkoxy group composed of an oxy group and a C₁ -C₁₂ aliphatic or alicyclic, a saturated hydrocarbon group or a C₃ -C₁₀ aliphatic unsaturated hydrocarbon group, which can be substituted by a phenyloxy group;

a benzyloxy group;

a phenylpropyloxy group;

or a naphtylmethyloxy group, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

14. The naphthalene derivative according to any one claim of claims 1-12, wherein the substitution by O on the naphthalene ring is at the 2-position of the ring, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

15. The naphthalene derivative according to any one claim of claims 1-12, wherein substitution by O, L and D are on the benzene ring and the relative position of O and L is para, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof.

16. A pharmaceutical composition comprising the naphthalene derivatives as described in claim 1, the pharmacologically acceptable salt or the pharmacologically acceptable solvate thereof and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition according to claim 16, wherein the pharmaceutical composition is as a drug for treating an allergic disease based on an inhibitory action on the production of IgE antibodies.

18. The pharmaceutical composition according to claim 17, wherein the allergic disease is bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, anaphylactic shocks, mite allergy, pollinosis or food allergy.

19. The pharmaceutical composition according to claim 16, wherein the pharmaceutical composition is effective for the treatment of disease caused by augmented production or activity of TF.

20. The pharmaceutical composition according to claim 19, wherein the disease is DIC;

thrombosis;

occlusive arteriosclerosis;

cerebral embolism;

cerebral infarction;

pulmonary embolism;

pulmonary infarction;

angina pectoris;

myocardial infarction;

restenosis;

Buerger disease;

diseases involved in hypertrophic endometritis; and

turbidity of an artificial crystalline lens embedded for the treatment of cataract.

21. A medicine effective as a prophylactic and/or therapeutic for an allergic disease because of its inhibitory effect on the production of IgE antibody containing a napththalene derivative of claim 1, the pharmacologically acceptable salt or the pharmacologically acceptable solvate as an active ingredient(s).

22. The medicine effective as a prophylactic and/or therapeutic for an allergic disease according to claim 21 being more selectively inhibitory against the production of IgE antibody than against IgG antibody.

23. The medicine effective as a prophylactic and/or therapeutic for a disease resulting from enhanced production or activity of TF containing a naphthalene derivative of claim 1, the pharmacologically acceptable salt or the pharmacologically acceptable solvate as an active ingredient(s).

24. A naphthalene derivative having the following formula (I):

##STR128## wherein A represents a hydroxy group, a C₇ -C₁₁, aralkyloxy group, or an alkoxy group composed of an oxy group and a C₁ -C₁₂ aliphatic or alicyclic, saturated or unsaturated hydrocarbon group which the alkyl moiety may be substituted with a C₆ -C₁₀ aryloxy group;

Q represents O, S, O--CH₂, S--CH₂, or CHOR₁ ;

L represents CO, CR² R³ CO, CH₂ CH₂ CO, or CH═

CHCO;

D represents a hydrogen atom, NO₂, NH₂, CO₂ R⁴, or a group having the following formula (II);

##STR129## wherein G represents a hydrogen atom, OH, SO₂ NH₂, CO₂ R⁶, CN or a tetrazol-5-yl group;

E represents a hydrogen atom, OH, SO₂ NH₂, CO₂ R⁵, CN, or a tetrazol-5-yl group;

M represents a hydrogen atom, a C₁ -C₄ lower alkyl group, a nitro group, or a halogen atom; and

R¹, R², R³, R⁴, R⁵ and R⁶, independently represent a hydrogen atom or a C₁ -C₄ lower alkyl group;

a pharmacologically acceptable salt thereof or a pharmacologically acceptable solvate thereof.