Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-10-03
2001-09-11
Shah, Mukund J. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C544S251000, C544S252000
Reexamination Certificate
active
06288070
ABSTRACT:
TECHNICAL ART
The present invention relates to a novel triazolopurine derivative which exhibits an adenosine A3 receptor affinity, a pharmaceutical composition containing the derivative, an adenosine A3 receptor ligand, and a remedy for asthma.
BACKGROUND ART
J. Heterocyclic Chem., 31, 1171 (1994) discloses that 2-aryl-8-fluorobenzyl-1,2,4-triazolo[5,1-i]purine is useful as an adenosine A2 receptor ligand.
An object of the present invention is to provide a novel compound having an affinity to an adenosine A3 receptor.
DISCLOSURE OF THE INVENTION
The triazolopurine derivative of the present invention is represented by the general formula (1):
wherein R
1
represents an alkyl group, or a phenyl group which is optionally substituted with a lower alkyl group; R
2
represents a pyridyl group, a furyl group, a thienyl group, a lower alkyl group, a phenyl lower alkyl group which optionally has 1 to 3 lower alkoxy groups as a substituent, a styryl group which optionally has 1 to 3 lower alkoxy groups as a substituent, a naphthyl group which optionally has a hydroxy groups as a substituent, or a phenyl group which optionally has 1 to 3 groups selected from lower alkyl group, lower alkoxy group, nitro group, hydroxyl group, amino group, N-lower alkylamino group, N,N-di lower alkylamino group, N-phenyl lower alkylamino group, N,N-bisphenyl lower alkylamino group, phenyl group, phenoxy group, phenyl lower alkoxy group, halogen-substituted lower alkyl group, halogen-substituted lower alkoxy group, di lower alkylphosphorylmethyl group, lower alkylthio group, lower alkoxy lower alkyl group, phenyl lower alkoxy lower alkyl group and halogen atom as a substituent; and A represents a group:
wherein R
3
represents a lower alkyl group or a phenyl lower alkyl group.
The triazolopurine derivative of the present invention is a novel compound which has never been described in reference documents.
In the present invention, a triazolopurine derivative wherein A is a group:
is particularly preferable. In that case, R
2
is preferably a pyridyl group, a furyl group, a styryl group, a naphthyl group which optionally has a hydroxyl group as a substituent, a phenyl group which optionally has a group selected from lower alkyl group, N-lower alkylamino group, N,N-di lower alkylamino group, N-phenyl lower alkylamino group, N,N-bisphenyl lower alkylamino group, phenyl group, phenoxy group, phenyl lower alkoxy group, halogen-substituted lower alkyl group, halogen-substituted lower alkoxy group, di lower alkylphosphorylmethyl group, lower alkylthio group, hydroxyl group and halogen atom as a substituent, a phenyl group substituted with a hydroxyl group and a halogen atom, or a phenyl group having 1 to 3 lower alkoxy groups as a substituent.
Particularly preferable compound is a compound selected from the group of the following compounds (a), (b) and (c):
(a) compound wherein R
1
is an alkyl group or a lower alkyl-substituted phenyl group and R
2
is a phenyl group,
(b) compound wherein R
1
is a n-butyl group and R
2
is a pyridyl group, a furyl group, a styryl group, a naphthyl group which optionally has a hydroxy groups as a substituent, a phenyl group which optionally has a group selected from lower alkyl group, N-lower alkylamino group, N,N-di lower alkylamino group, N-phenyl lower alkylamino group, N,N-bisphenyl lower alkylamino group, phenyl group, phenoxy group, phenyl lower alkoxy group, halogen-substituted lower alkyl group, halogen-substituted lower alkoxy group, di lower alkylphosphorylmethyl group, lower alkylthio group, hydroxyl group and halogen atom as a substituent, a phenyl group substituted with a hydroxyl group and a halogen atom, or a phenyl group having 1 to 3 lower alkoxy groups as a substituent, and
(c) compound wherein R
1
is a phenyl group and R
2
is a phenyl group having 3 lower alkoxy groups.
More preferable compound is a compound selected from the group of the following compounds (i) and (ii):
(i) compound wherein R
1
is a lower alkyl group and R
2
is a phenyl group, and
(ii) compound wherein R
1
is a n-butyl group and R
2
is a naphthyl group which optionally has a hydroxy group as a substituent, a phenyl group which optionally has a group selected from lower alkyl group, N,N-di lower alkylamino group, N-phenyl lower alkylamino group, phenyl group, phenoxy group, phenyl lower alkoxy group, halogen-substituted lower alkyl group, halogen-substituted lower alkoxy group, di lower alkylphosphorylmethyl group, lower alkylthio group and halogen atom as a substituent, a phenyl group substituted with a hydroxyl group and a halogen atom, or a phenyl group having 1 to 3 lower alkoxy groups as a substituent.
The compound of the present invention is preferably a compound selected from 5-n-butyl-8-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-(4-chlorophenyl)-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-(4-methoxyphenyl)-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-[4-(N,N-dimethylamino)phenyl]-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-(4-propoxyphenyl)-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-(4-ethoxyphenyl)-1H-1,2,4-triazolo[5,1-i]purine, 8-(4-biphenylyl)-5-n-butyl-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-(4-trifluoromethylphenyl)-1H-1,2,4-triazolo[5,1-i]purine and 5-n-pentyl-8-phenyl-1H-1,2,4-triazolo[5,1-i]purine, and is particularly preferably a compound selected from 5-n-butyl-8-(4-methoxyphenyl)-1H-1,2,4-triazolo[5,1-i]purine, 5-n-butyl-8-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazolo[5,1-i]purine and 8-(4-biphenylyl)-5-n-butyl-1H-1,2,4-triazolo[5,1-i]purine.
It is expected that the triazolopurine derivative of the present invention is applied to antihypertensive, antiallergic agent, anti-inflammatory agent, remedy for ischemic heart disease, remedy for leukemia, antipruritic, expectorant, cough medicine, remedy for asthma, and analgesic as a compound capable of binding with an adenosine A3 receptor because of its excellent affinity to an adenosine A3 receptor.
Accordingly, the present invention also provides a pharmaceutical composition comprising the triazolopurine derivative described above and a pharmaceutically acceptable carrier.
Specifically, the present invention provides an adenosine A3 receptor ligand comprising the triazolopurine derivative described above as an active ingredient, and a remedy for asthma, comprising triazolopurine derivative as an active ingredient.
BEST MODE FOR CARRYING OUT THE INVENTION
In the present invention, the lower alkyl group includes, for example, straight-chain or branched lower alkyl groups having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl.
The alkyl group includes, for example, alkyl groups having 7 to 8 carbon atoms, such as heptyl and octyl, in addition to the lower alkyl groups described above.
The lower alkoxy group includes, for example, straight-chain or branched lower alkoxy groups having 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy.
The halogen atom includes fluorine, chlorine, bromine, or iodine.
The pyridyl group includes 2-pyridyl, 3-pyridyl and 4-pyridyl.
The furyl group includes 2-furyl and 3-furyl.
The thienyl group includes 2-thienyl group and 3-thienyl group.
The naphthyl group which optionally has a hydroxyl group as a substituent includes, for example, 1-naphthyl, 2-naphthyl, 1-hydroxy-2-naphthyl, 3-hydroxy-2-naphthyl, 4-hydroxy-2-naphthyl, 5-hydroxy-2-naphthyl, 6-hydroxy-2-naphthyl, 7-hydroxy-2-naphthyl, 8-hydroxy-2-naphthyl, 2-hydroxy-1-naphthyl, 3-hydroxy-1-naphthyl, 4-hydroxy-1-naphthyl, 5-hydroxy-1-naphthyl, 6-hydroxy-1-naphthyl, 7-hydroxy-1-naphthyl, and 8-hydroxy-1-naphthyl.
The phenyl which optionally has a group selected from lower alkyl group, lower alkoxy group, nitro group, hydroxyl group, amino group, N-lower alkylamino group, N,N-di lower alkylamino group, N-phenyl lower alkylamino group, N,N-bisphenyl lower alkylamino group, phenyl gr
Kurogi Yasuhisa
Nishikawa Hiroshi
Okamura Takashi
Otsuka Pharmaceutical Factory Inc.
Shah Mukund J.
Sughrue Mion Zinn Macpeak & Seas, PLLC
Truong Tamthom N.
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