Back to results
US 5,843,951 AGranted
Analgesic composition of pyrazolo(1,5-A) pyrimidines
AssigneeOtsuka Pharmaceutical Factory, Inc.
InventorsMakoto Inoue, Takashi Okamura, Yasuo Shoji, Kinji Hashimoto, Masayuki Ohara, Tsuneo Yasuda
Life of this patent
Estimating the term…
Abstract
The invention provides an analgesic composition containing as an active ingredient a specific pyrimidine derivative represented by one of the follwing formulas (1) to (3): ##STR1## wherein the substituents are as defined herein. This composition exhibits potent analgesic activity and is effective for alleviating various types of pain such as postoperative pain.
Claims11
An analgesic composition comprising as an active ingredient at least one compound selected from the group consisting of:
- pyrazolo1,5-a!pyrimidine derivatives of formula (1):
- ##STR110## wherein R.sup.11 represents hydrogen, lower alkyl, or phenyl optionally having lower alkyl or phenylthio as a substituent, R.sup.12 represents hydrogen, halogen, phenyl, phenyl having halogen, phenylthio or trifluoromethyl as a substituent, phenyl having trifluoromethyl and nitro as substituents, or phenyl having lower alkoxy and phenylthio as substituents, R.sup.13 represents hydrogen, lower alkyl optionally having oxo, ethylenedioxy, lower alkanoyloxy, lower alkoxy, lower alkylthio, carboxyl, halogen or thienyl as a substituent, lower alkenyl, cycloalkyl, or phenyl optionally having 1 to 3 substituents selected from the group consisting of lower alkyl, halogen and lower alkoxy, furyl or thienyl, R.sup.14 represents hydrogen, carboxyl, lower alkoxycarbonyl, nitro, halogen, or lower alkyl having lower alkoxycarbonyl or the residue of an alkali metal salt of carboxylic acid as a substituent;
- R.sup.13 and R.sup.14 may conjointly form lower alkylene, R.sup.15 represents hydrogen, alkali metal, lower alkyl, phenyl optionally having 1 to 3 substituents selected from the group consisting of lower alkyl and lower alkoxy, pyridyl optionally having lower alkyl or halogen as a substituent, quinolyl or isoquinolyl, and A represents a single bond or lower alkylene, with the proviso that the following compounds are excluded from formula (1):
- (A) when R.sup.11 is hydrogen, R.sup.12 is phenyl or phenyl having one or more substituents as defined, R.sup.13 is hydrogen, R.sup.14 is hydrogen, A is a single bond, and R.sup.15 is hydrogen or alkali metal, and
- (B) when R.sup.11 is hydrogen, R.sup.12 is hydrogen or halogen, R.sup.13 is hydrogen, lower alkyl or phenl, R.sup.14 is hydrogen or lower alkoxycarbonyl, and --A--R.sup.15 is defined as hydrogen or lower alkyl;
- 4. 7-dihydropyrazolo1,5-a!pyrimidine derivatives of formula (2):
- ##STR111## wherein R.sup.21 represents hydrogen or phenyl, R.sup.22 represents hydrogen, R.sup.23 represents hydrogen, lower alkyl or hydroxyl, R.sup.24 represents hydrogen or cyano, R.sup.23 and R.sup.24 may conjointly form lower alkylene or --C(NH.sub.2).dbd.N--N(CH.sub.3)--, R.sup.26 represents lower alkyl, lower alkoxycarbonyl, 4-phenylthiobenzyl, 2-propynyl, 2-piperidinocarbonylethyl or 5-dimethylaminocarbonylpentyl, provided that when R.sup.26 is lower alkyl, then R.sup.24 is cyano or R.sup.23 and R.sup.24 conjointly form lower alkylene or --C(NH.sub.2).dbd.N--N(CH.sub.3)--;
- and 4,5,6,7-tetrahydropyrazolo1,5-a!pyrimidine derivatives of formula (3):
- ##STR112## wherein R.sup.31 represents hydrogen or N-(lower)alkylpyrrolyl, R.sup.32 represents hydrogen, R.sup.33 represents lower alkyl, R.sup.34 represents cyano, R.sup.33 and R.sup.34 may conjointly form .dbd.C(NH.sub.2)--N(CH.sub.3)--N.dbd., and R.sup.36 represents hydrogen or lower alkyl;
- and also comprising a pharmaceutically acceptable non-toxic carrier.
7 more elements
An analgesic composition comprising as an active ingredient at least one pyrazolo1,5-a!pyrimidine derivative of formula (1):
- ##STR113## wherein R.sup.11 represents lower alkyl, R.sup.12 and R.sup.14 represent hydrogen, R.sup.13 represents lower alkyl, R.sup.15 represents pyridyl or phenyl having 3 lower alkoxy groups as substituents and A represents methylene, or wherein R.sup.12 represents halogen, R.sup.11 and R.sup.14 represent hydrogen, R.sup.13 represents lower alkyl, R.sup.15 represents pyridyl and A represents methylene;
- and also comprising a pharmaceutically acceptable non-toxic carrier.
A method for treating pain comprising administering to a patient in need thereof an effective amount of an analgesic composition comprising as an active ingredient at least one compound selected from the group consisting of:
- pyrazolo1,5-a!pyrimidine derivatives of formula (1):
- ##STR114## wherein R.sup.11 represents hydrogen, lower alkyl, or phenyl optionally having lower alkyl or phenylthio as a substituent, R.sup.12 represents hydrogen, halogen, phenyl, phenyl having halogen, phenylthio or trifluoromethyl as a substituent, phenyl having trifluoromethyl and nitro as substituents, or phenyl having lower alkoxy and phenylthio as substituents, R.sup.13 represents hydrogen, lower alkyl optionally having oxo, ethylenedioxy, lower alkanoyloxy, lower alkoxy, lower alkylthio, carboxyl, halogen or thienyl as a substituent, lower alkenyl, cycloalkyl, or phenyl optionally having 1 to 3 substituents selected from the group consisting of lower alkyl, halogen and lower alkoxy, furyl or thienyl, R.sup.14 represents hydrogen, carboxyl, lower alkoxycarbonyl, nitro, halogen, or lower alkyl having lower alkoxycarbonyl or the residue of an alkali metal salt of carboxylic acid as a substituent;
- R.sup.13 and R.sup.14 may conjointly form lower alkylene, R.sup.15 represents hydrogen, alkali metal, lower alkyl, phenyl optionally having 1 to 3 substituents selected from the group consisting of lower alkyl and lower alkoxy, pyridyl optionally having lower alkyl or halogen as a substituent, quinolyl or isoguinolyl, and A represents a single bond or lower alkylene;
- 4. 7-dihydropyrazolo1,5-a!pyrimidine derivatives of formula (2):
- ##STR115## wherein R.sup.21 represents hydrogen or phenyl, R.sup.22 represents hydrogen, R.sup.23 represents hydrogen, lower alkyl or hydroxyl, R.sup.24 represents hydrogen or cyano, R.sup.23 and R.sup.24 may conjointly form lower alkylene or --C(NH.sub.2).dbd.N--N(CH.sub.3)--, R.sup.26 represents lower alkyl, lower alkoxycarbonyl, 4-phenylthiobenzyl, 2-propynyl, 2-piperidinocarbonylethyl or 5-dimethylaminocarbonylpentyl, provided that when R.sup.26 is lower alkyl, then R.sup.24 is cyano or R.sup.23 and R.sup.24 conjointly form lower alkylene or --C(NH.sub.2).dbd.N--N(CH.sub.3)--;
- and 4,5,6,7-tetrahydropyrazolo1,5-a!pyrimidine derivatives of formula (3):
- ##STR116## wherein R.sup.31 represents hydrogen or N-(lower)alkylpyrrolyl, R.sup.32 represents hydrogen, R.sup.33 represents lower alkyl, R.sup.34 represents cyano, R.sup.33 and R.sup.34 may conjointly form .dbd.C(NH.sub.2)--N(CH.sub.3)--N.dbd., and R.sup.36 represents hydrogen or lower alkyl;
- and also comprising a pharmaceutically acceptable non-toxic carrier.
5 more elements
A method for treating pain comprising administering to a patient in need thereof an effective amount of at least one compound selected from the group consisting of:
- pyrazolo1,5-a!pyrimidine derivatives of formula (1):
- ##STR117## wherein R.sup.11 represents hydrogen, lower alkyl, or phenyl optionally having lower alkyl or phenylthio as a substituent, R.sup.12 represents hydrogen, halogen, phenyl, phenyl having halogen, phenylthio or trifluoromethyl as a substituent, phenyl having trifluoromethyl and nitro as substituents, or phenyl having lower alkoxy and phenylthio as substituents, R.sup.13 represents hydrogen, lower alkyl optionally having oxo, ethylenedioxy, lower alkanoyloxy, lower alkoxy, lower alkylthio, carboxyl, halogen or thienyl as a substituent, lower alkenyl, cycloalkyl, or phenyl optionally having 1 to 3 substituents selected from the group consisting of lower alkyl, halogen and lower alkoxy, furyl or thienyl, R.sup.14 represents hydrogen, carboxyl, lower alkoxycarbonyl, nitro, halogen, or lower alkyl having lower alkoxycarbonyl or the residue of an alkali metal salt of carboxylic acid as a substituent;
- R.sup.13 and R.sup.14 may conjointly form lower alkylene, R.sup.15 represents hydrogen, alkali metal, lower alkyl, phenyl optionally having 1 to 3 substituents selected from the group consisting of lower alkyl and lower alkoxy, pyridyl optionally having lower alkyl or halogen as a substituent, quinolyl or isoquinolyl, and A represents a single bond or lower alkylene;
- 4. 7-dihydropyrazolo1,5-a!pyrimidine derivatives of formula (2):
- ##STR118## wherein R.sup.21 represents hydrogen or phenyl, R.sup.22 represents hydrogen, R.sup.23 represents hydrogen, lower alkyl or hydroxyl, R.sup.24 represents hydrogen or cyano, R.sup.23 and R.sup.24 may conjointly form lower alkylene or --C(NH.sub.2).dbd.N--N(CH.sub.3)--, R.sup.26 represents lower alkyl, lower alkoxycarbonyl, 4-phenylthiobenzyl, 2-propynyl, 2-piperidinocarbonylethyl or 5-dimethylaminocarbonylpentyl, provided that when R.sup.26 is lower alkyl, then R.sup.24 is cyano or R.sup.23 and R.sup.24 conjointly form lower alkylene or --C(NH.sub.2).dbd.N--N(CH.sub.3)--;
- and
- 4. 5,6,7-tetrahydropyrazolo1,5-a!pyrimidine derivatives of formula (3):
- ##STR119## wherein R.sup.31 represents hydrogen or N-(lower)alkylpyrrolyl, R.sup.32 represents hydrogen, R.sup.33 represents lower alkyl, R.sup.34 represents cyano, R.sup.33 and R.sup.34 may conjointly form .dbd.C(NH.sub.2)--N(CH.sub.3)--N.dbd., and R.sup.36 represents hydrogen or lower alkyl.
5 more elements
Dependencies are inferred from the claim text.