Styrene derivatives

• US 5,514,711 A
• Filed: 01/05/1995
• Issued: 05/07/1996
• Est. Priority Date: 10/15/1991
• Status: Expired due to Fees

• Current Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Original Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Inventors: Nakamura, Hideo, Takayanagi, Hisao, Oshino, Toshiko, Sugawara, Koichi, Hara, Hiroto, Kitano, Yasunori
• Primary Examiner(s): BRUST, JOSEPH
• Application Number:
  US08/369,263
• Time in Patent Office: 488 Days
• Field of Search: 558/401, 558/403, 514/523, 514/521
• US Class Current: 514/521
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07C 255/40 the carbon skeleton being further substituted by doubly-bound oxygen atoms
• CPC Class Codes: C07C 255/41 the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
• CPC Class Codes: C07C 317/46 the carbon skeleton being further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 45/45 by condensation
• CPC Class Codes: C07C 45/54 of compounds containing doubly bound oxygen atoms, e.g. esters
• CPC Class Codes: C07C 45/562 with nitrogen as the only hetero atom
• CPC Class Codes: C07C 45/71 being hydroxy groups
• CPC Class Codes: C07C 47/575 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 49/825 all hydroxy groups bound to the ring
• CPC Class Codes: C07C 49/835 having unsaturation outside an aromatic ring
• CPC Class Codes: C07C 49/84 containing ether groups, groups, groups, or groups

Abstract

Styrene derivatives of the following general formula (I): ##STR1## or pharmaceutically acceptable salts thereof. A pharmaceutical composition useful as anticancer agent, which comprises the above compound as an essential component, is also provided.

Claims

1. A styrene derivative of the following formula (I):

##STR146## wherein R¹ represents a cyano group;

R² represents --CONR⁹ R¹⁰ wherein R⁹ and R¹⁰ independently each represent a hydrogen atom or ##STR147## (in which n represents 0 or an integer of from 1 to 5, and X^l, X² and X³ independently each represent a hydrogen atom, halogen atom, C₁ -C₅ alkyl group, C₁ -C₅ alkoxy group, hydroxy group, nitro group or cyano group), with the proviso that R⁹ and R¹⁰ don'"'"'t represent hydrogen atom at the same time;

R³ represents &

hydrogen atom, C₁ -C₅ alkyl group or hydroxy group; and

R⁴, R⁵, R⁶, R⁷ and R⁸ independently each represent (1) a hydrogen atom, (2) hydroxy group, (3) halogen atom, (4) C₁ -C₅ alkoxy group, (5) nitro group, (6) cyano group, (7) --NR¹² R¹³ wherein R¹² and R¹³ independently each represent a hydrogen atom, C₁ -C₅ alkyl group or benzoyl group, (8) --SOpR¹⁴ wherein p represents 0, 1 or 2, and R¹⁴ represents a C₁ -C₅ alkyl group or phenyl group, (9) --COR¹⁵ wherein R¹⁵ represents a hydrogen atom, C₁ -C₅ alkyl group, C₁ -C₅ alkoxy group, hydroxy group, phenyl group, phenoxy group or --NHR¹⁶ (in which R¹⁶ represents a C₁ -C₅ alkyl group or phenyl group), or (10) a C₁ -C₅ alkyl group optionally substituted by a halogen atom;

with the proviso that at least one of R⁴ to R⁸ is a hydroxy group, and that when R³ is a hydrogen atom and R⁴ to R⁸ independently each represent a hydrogen atom, hydroxy group, C₁ -C₅ alkoxy group, --NR¹² R¹³ (in which R¹² and R¹³ are as defined above), or C₁ -C₅ alkyl group, then R² represents --CONR⁹ R¹⁰ wherein R⁹ represents a hydrogen atom and R¹⁰ represents ##STR148## (in which Z represents a C₁ -C₅ alkyl group, halogen atom, nitro group or cyano group),

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1, wherein R² represents --CONR⁹ R¹⁰ wherein R⁹ is a hydrogen atom and R¹⁰ represents ##STR149## (in which X¹ represents a hydrogen atom, halogen atom, C₁ -C₅ alkyl group, nitro group or cyano group, X² and X³ each represent a hydrogen atom, and n represents 0) represents;

and

R⁴, R⁵, R⁶, R⁷ and R⁸ independently each represent a hydrogen atom, hydroxy group, halogen atom, C₁ -C₅ alkoxy group, nitro group, cyano group, --SO₂ R¹⁴ (in which R¹⁴ represents a C₁ -C₅ alkyl group), --COR¹⁵ (in which R¹⁵ represents a hydroxy group), or a C₁ -C₅ alkyl group optionally substituted by a halogen atom;

with the proviso that at least one of R⁴ to R⁵ is a hydroxy group, and that when R^S is a hydrogen atom and R⁴ to R⁸ independently each represent a hydrogen atom, hydroxy group, C₁ -C₅ alkoxy group or C₁ -C₅ alkyl group, then R² is --CON⁹ R¹⁰ wherein R⁹ represents a hydrogen atom and R¹⁰ represents ##STR150## (in which Z represents a C₁ -C₅ alkyl group, halogen atom, nitro group or cyano group).

3. A compound according to claim 2, wherein R² represents --CONR⁹ R¹⁰ wherein R⁹ represents a hydrogen atom and R¹⁰ represents ##STR151## (in which X¹ represents a hydrogen atom, halogen atom, C₁ -C₅ alkyl group, nitro group or cyano group, X² and X³ each represent hydrogen atom and n represents 0);

R³ represents a hydrogen atom or hydroxy group;

R⁴ and R⁸ independently each represent a hydrogen atom, halogen atom or nitro group;

R⁵ and R⁷ independently each represent a hydroxy group, halogen atom, C₁ -C₅ alkoxy group, nitro group, cyano group, SO₂ R¹⁴ (in which R¹⁴ represents a C₁ -C₅ alkyl group), --COR¹⁵ (in which R¹⁵ represents a hydroxy group), or a C₁ -C₅ alkyl group optionally substituted by a halogen atom; and

R⁶ represents a hydroxy group;

with the proviso that when R³, R⁴ and R⁸ are each a hydrogen atom and R⁵ and R⁷ independently each represent a hydroxy group, C₁ -C₅ alkoxy group or C₁ -C₅ alkyl group, then R² is --CONR⁹ R¹⁰ wherein R⁹ represents a hydrogen atom and R¹⁰ represents ##STR152## (in which Z represents a C₁ -C₅ alkyl group, halogen atom, nitro group or cyano group).

4. A compound according to claim 3, in which R² represents --CONR⁹ R¹⁰ wherein R⁹ represents a hydrogen atom and R¹⁰ represents ##STR153## (in which Z represents a hydrogen atom or halogen atom);

R⁴ represents a hydrogen atom;

R⁵ represents a hydroxy group, halogen atom, C₁ -C₅ alkoxy group or C₁ -C₅ alkyl group; and

R⁷ represents a halogen atom, cyano group or C₁ -C₅ alkyl group;

with the proviso that when R³ and R⁸ are a hydrogen atom and R⁵ represents a hydroxy group, C₁ -C₅ alkoxy group or C₁ -C₅ alkyl group and R⁷ represents a C₁ -C₅ alkyl group, then Z is a halogen atom.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier therefor.

6. An anticancer agent comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier therefor.