N-((phenyl, benzodioxinyl or N-heteroarylpiperazinyl)alkyl)-N-(N-heteroaryl)substituted carboxamides

• US 6,127,357 A
• Filed: 05/11/1995
• Issued: 10/03/2000
• Est. Priority Date: 05/02/1991
• Status: Expired due to Fees

• Current Assignee: John Wyeth & Brother Limited (Pfizer Inc.)
• Original Assignee: John Wyeth & Brother Limited (Pfizer Inc.)
• Inventors: Mansell, Howard Langham, Cliffe, Ian Anthony
• Primary Examiner(s): BERNHARDT, EMILY A
• Application Number:
  US08/438,812
• Time in Patent Office: 1,972 Days
• Field of Search: 544/360, 544/361, 544/363, 544/364, 544/367, 544/368, 544/377, 544/295, 544/238, 544/121, 544/357, 544/373, 544/376, 544/52, 544/105, 544/58.4, 540/598, 540/595, 514/210, 514/212, 514/235.8, 514/252-254, 514/224.2, 514/227.8, 514/230.5
• US Class Current: 514/210.2
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 215/38 Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 217/22 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
• CPC Class Codes: C07D 277/46 by carboxylic acids, or sulfur or nitrogen analogues thereof
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Piperazine derivatives of formula I ##STR1## and their pharmaceutically acceptable acid addition salts are 5-HT_1A binding agents, particularly 5-HT_1A antagonists and may be used, for example, as anxiolytics. In the formula A is C_2-4 alkylene chain optionally substituted by lower alkyl, Z is oxygen or sulphur, R is hydrogen or lower alkyl, R¹ is a mono or bicyclic aryl or heteroaryl radical, R² is a mono or bicyclic heteroaryl radical and R³ is hydrogen or a specified radical such as lower alkyl, cycloalkyl, aryl, heteroaryl or optionally substituted amino.

Claims

1. A compound of the formula ##STR13## or a pharmaceutically acceptable acid addition salt thereof, wherein A is an alkylene chain of 2 to 4 carbon atoms optionally substituted by one or more lower alkyl groups;

Z is oxygen or sulphur;

R is hydrogen or lower alkyl;

R¹ is aryl, tetrahydronaphthyl, heteroaryl, wherein aryl is phenyl or naphthyl each of which may be optionally substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, halogen, haloloweralkyl, nitro, nitrile, aminocarbonyl, loweralkoxycarbonyl, amino, loweralkylamino, or di-loweralkylamino, and heteroaryl is a monocyclic aromatic heterocyclic ring having 5 ring members and having as heteroatoms one or two N atoms or one N atom and one O or S atom, or a monocyclic aromatic heterocyclic ring having 6 ring members and having as heteroatoms one or two N atoms, or a bicyclic aromatic heterocyclic ring system having one such 5 or 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring, wherein such heteroaryl or tetrahydronaphthyl ring may be optionally substituted as for aryl,

or R¹ is a bicyclic oxygen-containing aryl radical of the formula ##STR14## wherein the heterocyclic oxygen-containing ring has 5 to 7 ring members, said heterocyclic ring being non-aromatic and optionally having one further hetero ring member selected from --O--, --S--, --SO₂ or NR⁷, wherein R⁷ is hydrogen or lower alkyl and wherein R⁸ and R⁹ represent hydrogen or one or more substituents independently selected from lower alkyl, halogen, hydroxy, loweralkoxy, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyloxy(loweralkyl), loweralkylcarbonyl, loweralkylcarbonyl(loweralkyl), amino, loweralkylamino or di-loweralkylamino,

or R¹ is an bicyclic oxygen-containing aryl radical of the formula ##STR15## wherein R⁸ and R⁹ are as defined above;

R² is a monocyclic aromatic heterocyclic ring having 6 members and having as heteroatoms one or two N atoms or a bicyclic aromatic heterocyclic ring system having one such 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring, which may be optionally substituted as for aryl, provided that, said bicyclic heterocyclic radical is connected to the amino nitrogen of formula I via such heterocyclic ring; and

R³ is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkyl(loweralkyl), aryl, aryl(loweralkyl), a group of formula --NR⁴ R⁵, or a group of formula OR⁶, in which R⁴ is hydrogen, lower alkyl, aryl or aryl(loweralkyl) and R⁵ is hydrogen, lower alkyl, --CO(loweralkyl), aryl, --COaryl, aryl(loweralkyl), cycloalkyl or cycloalkyl(loweralkyl), or R⁴ and R⁵ together with the nitrogen atom to which they are both attached represent azetidino, pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino which may be optionally substituted by lower alkyl, aryl or aryl(loweralkyl), and R⁶ is lower alkyl, cycloalkyl, cycloalkyl(loweralkyl), aryl, or aryl(loweralkyl),

wherein aryl is as defined for R¹ and cycloalkyl or cycloalkenyl is a mono-, bi-, tri-, or tetracyclic hydrocarbon group of 3 to 12 carbon atoms.

2. A compound as claimed in claim 1 in which A is --(CH₂)₂ --, --(CH₂)₃ --, --(CH₂)₄ -- or --CH(CH₃).CH₂ --.

3. A compound as claimed in claim 1 in which R is hydrogen.

4. A compound as claimed in claim 1 in which R¹ is o-methoxyphenyl, o-isopropylphenyl, 4-fluoro-2-methoxyphenyl, 2,3-dihydro[1,4]-benzodioxan-5-yl, pyrimid-2-yl, 1-naphthyl, 3-(1,2-benzisothiazolyl), 1-(7-methoxynaphthyl) or 1-(5,6,7,8-tetrahydro)naphthyl.

6. A compound as claimed in claim 1 in which R³ is lower alkyl, cycloalkyl, cycloalkenyl, phenyl, piperidino or -NHcycloalkyl.

7. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

8. A compound as claimed in claim 1 which is N-cyclohexyl-N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl))ethyl)-N-(2-pyridinyl)urea or a pharmaceutically acceptable salt thereof.

9. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl)benzamide or a pharmaceutically acceptable salt thereof.

10. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridinyl)trimethylacetamide or a pharmaceutically acceptable salt thereof.

11. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-thiazolyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

12. A compound as claimed in claim 1 which is N-(2-(1-(4-(4-fluoro-2-methoxyphenyl)piperazinyl))-ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

13. A compound as claimed in claim 1 which is N-(2-(1-(4-(2,3-dihydro-1,4-benzodioxin-5-yl)-piperazinyl))ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

14. A compound as claimed in claim 1 which is N-[2-[1-[4-[3-(1,2-benzisothiazolyl)]]piperazinyl]-ethyl]-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

15. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(1-piperidinylcarbonyl)-2-aminopyridine or a pharmaceutically acceptable salt thereof.

16. A compound as claimed in claim 1 which is N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N-(pyridin-2-yl)-N'"'"'-cyclohexylthiourea or a pharmaceutically acceptable salt thereof.

17. A compound as claimed in claim 1 which is N-(2-(4-(2-hydroxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

18. A compound as claimed in claim 1 which is N-(2-(1-(4-(1-naphthyl))piperazinyl)ethyl)-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

19. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methylphenyl))piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

20. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-fluorophenyl))piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

21. A compound as claimed in claim 1 which is N-[2-[1-[4-(1-isoquinolinyl)]piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

22. A compound as claimed in claim 1 which is N-[2-[1-[4-[1-(7-methoxy)naphthyl]]piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

23. A compound as claimed in claim 1 which is N-(2-(1-(4-(2-methoxyphenyl)piperazinyl))ethyl)-N-(2-pyridyl)adamantane-1-carboxamide or a pharmaceutically acceptable salt thereof.

24. A compound as claimed in claim 1 which is N-[2-[1-[4-[1-(2-methoxy)naphthyl]]piperazinyl]ethyl]-N-[2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

25. A compound as claimed in claim 1 which is N-[2-[1-[4-[1-(5,6,7,8-tetrahydro)naphthyl]]-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

26. A compound as claimed in claim 1 which is (S)-N-(1-methyl-2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide or a pharmaceutically acceptable salt thereof.

27. A compound as claimed in claim 1 which is (R)-N-(1-methyl-2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane carboxamide or a pharmaceutically acceptable salt thereof.

28. A compound as claimed in claim 1 which is N-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]-N-(2-pyridinyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

29. A compound as claimed in claim 1 which is N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-quinolinyl)cyclohexane carboxamide or a pharmaceutically acceptable salt thereof.

30. A compound as claimed in claim 1 which is (Rac)-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)propyl)-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

31. A compound as claimed in claim 1 which is (S)-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)propyl)-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

32. A compound as claimed in claim 1 which is (R)-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)propyl-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

33. A compound as claimed in claim 1 which is N-(2-(4-phenyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

34. A compound as claimed in claim 1 which is N-(2-(4-(2-isopropylphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

35. A compound as claimed in claim 1 which is N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(4-pyridinyl)cyclohexane carboxamide or a pharmaceutically acceptable salt thereof.

36. A compound as claimed in claim 1 which is N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(3-pyridyl)cyclohexanecarboxamide or a pharmaceutically acceptable salt thereof.

37. A compound as claimed in claim 1 which is N-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-N-(2-pyridinyl)cyclohex-1-enecarboxamide or a pharmaceutically acceptable salt thereof.

38. A compound as claimed in claim 1 which is N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexane thiocarboxamide or a pharmaceutically acceptable salt thereof.

43. A method for treating anxiety in a mammal which comprises administering to said mammal an effective amount of a compound claimed in claim 1.

5. A compound as claimed in claim l in which R² is pyridyl-2-yl, quinolin-2-yl or thiazol-2-yl.

39. A compound of the formula ##STR16## or a pharmaceutically acceptable acid addition salt thereof, wherein A is an alkylene chain of 2 to 4 carbon atoms optionally substituted by one or more lower alkyl groups;

Z is oxygen or sulphur,

R is hydrogen or lower alkyl;

R¹ is aryl, tetrahydronaphthyl, heteroaxyl, wherein aryl, is phenyl or naphthyl each of which may be optionally substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, halogen, haloloweralkyl, nitro, nitrile aminocarbonyl, loweralkoxycarbonyl, amino, loweralkylamino, or di-loweralkylamino, and heteroaryl is a monocyclic aromatic heterocyclic ring having 5 ring members and having as heteroatoms one or two N atoms or one N atom and one O or S atom, or a monocyclic aromatic heterocyclic ring having 6 ring members and having as heteroatoms one or two N atoms, or a bicyclic aromatic heterocyclic ring system having one such 5 or 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring,

R² is a monocyclic aromatic heterocyclic ring having 6 ring members and having as heteroatoms one or two N atoms or a bicyclic aromatic heterocyclic ring system having one such 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring, which may be optionally substituted as for aryl provided that, said bicyclic heterocyclic radical is connected to the amino nitrogen of formula I via such heterocyclic ring;

R³ is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkyl(loweralkyl), aryl, aryl(loweralkyl), a group of formula --NR⁴ R⁵, or a group of formula OR⁶, in which R⁴ is hydrogen, lower alkyl, aryl or aryl(loweralkyl) and R⁵ is hydrogen, lower alkyl, --CO(loweralkyl), aryl, --COaryl, aryl(loweralkyl), cycloalkyl or cycloalkyl(loweralkyl), or R⁴ and R⁵ together with the nitrogen atom to which they are both attached represent azetidino pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino which may be optionally substituted by lower alkyl, aryl or aryl(loweralkyl), and

R⁶ is lower alkyl cycloalkyl, cycloalkyl(loweralkyl), aryl or aryl(loweralkyl), wherein aryl is as defined for R¹ and cycloalkyl or cycloalkenyl is a mono-, bi-, tri-, or tetracyclic hydrocarbon group of 3 to 12 carbon atoms.

40. A compound of the formula ##STR17## or a pharmaceutically acceptable acid addition salt thereof, wherein A is an alkylene chain of 2 to 4 carbon atoms optionally substituted by one or more lower alkyl groups;

Z is oxygen or sulphur;

R is hydrogen or lower alkyl;

R¹ is a bicyclic oxygen-containing aryl radical of the formula ##STR18## wherein the heterocyclic oxygen-containing ring has 5 to 7 ring members, said heterocyclic ring being non-aromatic and optionally having one further hetero ring member selected from --O--, --S--, --SO₂ or NR⁷,

R² is a monocyclic aromatic heterocyclic ring having 6 ring members and having as heteroatoms one or two N atoms or a bicyclic aromatic heterocyclic ring system having one such 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring, which may be optionally substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, halogen, haloloweralkyl, nitro, nitrite, aminocarbonyl, loweralkoxycarbonyl, amino, loweralkylamino, or di-loweralkylamino, provided that, said bicyclic heterocyclic radical is connected to the amino nitrogen of formula I via such heterocyclic ring;

R³ is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkyl(loweralkyl), aryl, aryl(loweralkyl), a group of formula --NR⁴ R⁵, or a group of formula OR⁶, in which R⁴ is hydrogen, lower alkyl, aryl or aryl(loweralkyl)

R⁵ is hydrogen, lower alkyl, --CO(loweralkyl), aryl, --COaryl, aryl(loweralkyl), cycloalkyl or cycloalkyl(loweralkyl), or R⁴ and R⁵ together with the nitrogen atom to which they are both attached represent azetidino, pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino which may be optionally substituted by lower alkyl, aryl or aryl(loweralkyl),

R⁶ is lower alkyl cycloalkyl, cycloalkyl(loweralkyl), aryl, or aryl(loweralkyl), wherein aryl is as defined for R¹ and cycloalkyl or cycloalkenyl is a mono-, bi-, tri-, or tetracyclic hydrocarbon group of3 to 12 carbon atoms;

R⁷ is hydrogen or lower alkyl; and

R⁸ and R⁹ represent hydrogen or one or more substituents independently selected from lower alkyl, halogen, hydroxy, loweralkoxy, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyloxy(loweralkyl), loweralkylcarbonyl, loweralkylcarbonyl(loweralkyl), amino, loweralkylamino or di-loweralkylamino.

41. A compound of the formula ##STR19## or a pharmaceutically acceptable acid addition salt thereof, wherein A is an alkylene chain of 2 to 4 carbon atoms optionally substituted by one or more lower alkyl groups;

Z is oxygen or sulphur;

R is hydrogen or lower alkyl;

R¹ is a bicyclic oxygen-containing aryl radical of the formula ##STR20## R² is a monocyclic aromatic heterocyclic ring having 6 ring members and having as heteroatoms one or two N atoms or a bicyclic aromatic heterocyclic ring system having one such 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring, which may be optionally substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, halogen, haloloweralkyl, nitro, nitrile, aminocarbonyl, loweralkoxycarbonyl, amino, loweralkylamino, or di-loweralkylamino, provided that, said bicyclic heterocyclic radical is connected to the amino nitrogen of formula I via such heterocyclic ring;

R³ is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkyl(loweralkyl), aryl, aryl(loweralkyl), a group of formula --NR⁴ R⁵, or a group of formula OR⁶, in which R⁴ is hydrogen, lower alkyl, aryl or aryl(loweralkyl) and R⁵ is hydrogen, lower alkyl, --CO(loweralkyl), aryl, --COaryl, aryl(loweralkyl), cycloalkyl or cycloalkyl(loweralkyl), or R⁴ and R⁵ together with the nitrogen atom to which they are both attached represent azetidino, pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino which may be optionally substituted by lower alkyl, aryl or aryl(loweralkyl);

R⁶ is lower alkyl, cycloalkyl, cycloalkyl(loweralkyl), aryl, or aryl(loweralkyl), wherein aryl is as defined for R¹ and cycloalkyl or cycloalkenyl is a mono-, bi-, tri-, or tetracyclic hydrocarbon group of 3 to 12 carbon atoms; and

R⁸ and R⁹ represent hydrogen or one or more substituents independently selected from lower alkyl, halogen, hydroxy, loweralkoxy, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyloxy(loweralkyl), loweralkylcarbonyl, loweralkylcarbonyl(loweralkyl), amino, loweralkylamino or di-loweralkylamino.

42. A compound of the formula ##STR21## or a pharmaceutically acceptable acid addition salt thereof, wherein A is an alkylene chain of 2 to 4 carbon atoms optionally substituted by one or more lower alkyl groups,

Z is oxygen or sulphur;

R is hydrogen or lower alkyl;

R¹ is a bicyclic oxygen-containing aryl radical selected from the group consisting of;

##STR22## R² is a monocyclic aromatic heterocyclic ring having 6 ring members and having as heteroatoms one or two N atoms or a bicyclic aromatic heterocyclic ring system having one such 6 membered monocyclic aromatic heterocyclic ring fused to a benzene ring, which may be optionally substituted by one or more substituents independently selected from lower alkyl, lower alkoxy, halogen, haloloweralkyl, nitro, nitrile, aminocarbonyl, loweralkoxycarbonyl, amino, loweralkylamino, or di-loweralkylamino, provided that, said bicyclic heterocyclic radical is connected to the amino nitrogen of formula I via such heterocyclic ring;

R³ is hydrogen, lower alkyl, cycloalkyl, cycloalkenyl, cycloalkyl(loweralkyl), aryl, aryl(loweralkyl), a group of formula --NR⁴ R⁵, or a group of formula OR⁶, in which R⁴ is hydrogen, lower alkyl, aryl or aryl(loweralkyl)

R⁵ is hydrogen, lower alkyl, --CO(loweralkyl), aryl, --COaryl, aryl(loweralkyl), cycloalkyl or cycloalkyl(loweralkyl), or R⁴ and R⁵ together with the nitrogen atom to which they are both attached represent azetidino, pyrrolidino, piperidino, hexahydroazepino, morpholino or piperazino which may be optionally substituted by lower alkyl, aryl or aryl(loweralkyl),

R⁶ is lower alkyl, cycloalkyl, cycloalkyl(loweralkyl), aryl, or aryl(loweralkyl), wherein aryl is as defined for R¹ and cycloalkyl or cycloalkenyl is a mono-, bi-, tri-, or tetracyclic hydrocarbon group of 3 to 12 carbon atoms; and

R⁸ and R⁹ represent hydrogen or one or more substituents independently selected from lower alkyl, halogen, hydroxy, loweralkoxy, hydroxyloweralkyl, loweralkoxyloweralkyl, loweralkanoyloxy(loweralkyl), loweralkylcarbonyl, loweralkylcarbonyl(loweralkyl), amino, loweralkylamino or di-loweralkylamino.