Quinazoline compounds and antihypertensives

• US 4,734,418 A
• Filed: 12/06/1985
• Issued: 03/29/1988
• Est. Priority Date: 12/14/1984
• Status: Expired due to Fees

• Current Assignee: Mitsui Chemicals Incorporated (Mitsui Chemicals)
• Original Assignee: Mitsui Petrochemical Industries, Ltd.
• Inventors: Watanabe, Kazuyuki, Kato, Koji, Ohno, Hiroyasu, Saruta, Sakae, Kumakura, Mikio, Yokoyama, Keiichi, Nishina, Takashi, Kitahara, Takumi, Awaya, Akira, Nakano, Takuo
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Cassatt, Barbara
• Application Number:
  US06/805,905
• Time in Patent Office: 844 Days
• Field of Search: 544/284, 544/279, 544/280, 514/215, 514/218, 514/260, 514/258, 540/575, 540/521
• US Class Current: 514/252.16
• CPC Class Codes: C07D 239/95 with hetero atoms directly attached in positions 2 and 4
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems

Abstract

Disclosed herein is an antihypertensive preparation containing, as an active component, a novel quinazoline derivative represented by the following general formula or a salt thereof: ##STR1## wherein R¹⁰⁰ means a hydrogen atom or methoxy group, R²⁰⁰ and R³⁰⁰ denote individually a hydrogen atom or lower alkoxy group, R⁴⁰⁰ is a hydrogen atom or amino group, l stands for 2 or 3, and Het is a specific hetero ring group.

Claims

1. A quinazoline compound represented by the following formula I or a pharmacologically acceptable salt thereof:

##STR237## wherein R¹⁰⁰ means a hydrogen atom or methoxy group, R²⁰⁰ and R³⁰⁰ denote individually a hydrogen atom or lower alkoxy group, R⁴⁰⁰ is a hydrogen atom or amino group, l stands for 2 or 3, and Het is represented by any one of the following formulae;

##STR238## wherein, in the formula II, either single or double bond is formed between the 3- and 4-positions, R² means a hydrogen atom or a lower alkyl, aralkyl in which alkyl is C₁ -C₄ and aryl is phenyl, cyano or formyl group, R³ denotes a hydrogen atom or a lower alkoxycarbonyl or phenyl group, R⁴ is a hydrogen atom or a lower alkyl, lower cycloalkyl, hydroxy--substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy-substituted lower alkyl, phenyl or aralkyl in which alkyl is C₁ -C₄ and aryl is phenyl and X stands for an oxygen or sulfur atom,

in the formula III, either single or double bond is formed between the 2- and 3-positions, and R⁵ means a hydrogen atom or a lower alkyl group,

in the formula IV, R⁶ and R⁷ means individually a hydrogen atom or a lower alkyl group,

in the formula V, R⁸ and R⁹ mean individually a hydrogen atom or a lower alkyl group,

in the formula VI, m stands for 2 or 3, and R¹⁰ means a hydrogen atom or a lower alkyl group,

in the formula VIII, R¹¹, R¹² and R¹³ mean individually a hydrogen atom or a lower alkyl group,

in the formula X, R¹⁶ means a lower alkyl group, and

in the formula XIV, R²⁵ means a C₅ -C₈ alkyl, C₄ -C₇ cycloalkyl, hydroxy-substituted lower alkyl group, lower alkoxy-substituted lower alkyl, di(lower alkylamino)-substituted lower alkyl or aralkyl in which alkyl is C₁ -C₄ and aryl is phenyl.

13. An antihypertensive preparation comprising, as an active component, an effective amount of a quinazoline compound according to claim 1 and a pharmacologically acceptable carrier therefor.

17. An antihypertensive preparation according to claim 13 also comprising a pharmaceutically acceptable carrier.

18. An antihypertensive preparation according to claim 13 also comprising a second antihypertensive component, a diuretic or a combination of another active antihypertensive component and a diuretic.

2. A quinazoline compound represented by the following formula I'"'"' or a pharmacologically acceptable salt thereof:

##STR239## wherein R¹⁰⁰ means a hydrogen atom or a methoxy group, l stands for 2 or 3, and Het is represented by any one of the following formulae;

##STR240## wherein, in the formula II, either single or double bond is formed between the 3- and 4-positions, R² means a hydrogen atom or a lower alkyl, aralkyl in which alkyl is C₁ -C₄ and aryl is phenyl, cyano or formyl group, R³ denotes a hydrogen atom or a lower alkoxycarbonyl or phenyl group, R⁴ is a hydrogen atom or a lower alkyl, lower cycloalkyl, hydroxy-substituted lower alkyl, lower alkoxy-substituted lower alkyl, phenyl or aralkyl in which alkyl is C₁ -C₄ and aryl is phenyl, and X stands for an oxygen or sulfur atom,

in the formula III, either single or double bond is formed between the 2- and 3-positions, and R⁵ means a hydrogen atom or a lower alkyl group,

in the formula IV, R⁶ and R⁷ mean individually a hydrogen atom or a lower alkyl group,

in the formula V, R⁸ and R⁹ mean individually a hydrogen atom or a lower alkyl group,

in the formula VI, m stands for 2 or 3, and R¹⁰ means a hydrogen atom or a lower alkyl group,

in the formula VIII, R¹¹, R¹² and R¹³ mean individually a hydrogen atom or a lower alkyl group, and

in the formula X, R¹⁶ means a lower alkyl group.

5. The compound as claimed in claim 2, wherein Het is represented by the formula II in which either single or double bond is formed between the 3- and 4-positions, R² means a hydrogen atom or a lower alkyl, aralkyl in which alkyl is C₁ -C₄ and aryl is C₆ -C₈, cyano or formyl group, R³ denotes a hydrogen atom or a lower alkoxycarbonyl or phenyl group, R⁴ is a hydrogen atom or a lower alkyl, lower cycloalkyl, hydroxy-substituted lower alkyl, lower alkoxy-substituted lower alkyl, phenyl or aralkyl in which alkyl is C₁ -C₄ and aryl is phenyl and X stands for an oxygen or sulfur atom.

6. The compound as claimed in claim 2, wherein Het is represented by the formula III in which either single or double bond is formed between the 2- and 3-positions, and R⁵ means a hydrogen atom or a lower alkyl group.

7. The compound as claimed in claim 2, wherein Het is represented by the formula IV in which R⁶ and R⁷ mean individually a hydrogen atom or a lower alkyl group.

8. The compound as claimed in claim 2, wherein Het is represented by the formula V in which R⁸ and R⁹ mean individually a hydrogen atom or a lower alkyl group.

9. The compound as claimed in claim 2, wherein Het is represented by the formula VI in which m stands for 2 or 3, and R¹⁰ means a hydrogen atom or a lower alkyl group.

10. The compound as claimed in claim 2, wherein Het is represented by the formula VIII in which R¹¹, R¹² and R¹³ mean individually a hydrogen atom or a lower alkyl group.

11. The compound as claimed in claim 2, wherein Het is represented by the formula X in which R¹⁶ means a lower alkyl group.

12. The compound as claimed in claim 2, wherein Het is represented by the formula XIV in which R²⁵ means a C₅ -C₈ alkyl, C₄ -C₇ cycloalkyl, hydroxy-substituted lower alkyl group, lower alkoxy-substituted lower alkyl, di(lower alkylamino)-substituted lower alkyl or aralkyl in which alkyl is C₁ -C⁴ and aryl is phenyl.

14. An antihypertensive preparation comprising, as an active component, an effective amount of a quinazoline compound according to claim 2, and a pharmaceutically acceptable carrier therefor.

3. A quinazoline compound represented by the following formula I" or a pharmacologically acceptable salt thereof:

##STR241## wherein Het is represented by the following formula;

##STR242## where R²⁵ means a C₅ -C₈ alkyl, C₄ -C₇ cycloalkyl, hydroxy-substituted lower alkyl group, lower alkoxy-substituted lower alkyl, di(lower alkylamino)-substituted lower alkyl or aralkyl in which alkyl is C₁ -C₄, alkyl and aryl is phenyl.

15. An antihypertensive preparation comprising, as an active component, an effective amount of a quinazoline compound according to claim 3 and a pharmacologically acceptable carrier therefor.

4. A quinazoline conpound represented by the following formula I or a pharmacologically acceptable salt thereof:

##STR243## wherein R²⁰⁰ and R³⁰⁰ mean individually a hydrogen atom or lower alkoxy group, and R⁴ denotes a lower alkyl group.

16. An antihypertensive preparation comprising, as an active component, a quinazoline compound represented by the following formula I or a pharmacologically acceptable salt thereof:

##STR244## wherein R²⁰⁰ and R³⁰⁰ mean individually a hydrogen atom or lower alkoxy group, and R⁴ denotes a lower alkyl group.