US4831013A
Expired / Lapsed
US
⏱️ 0.0 years remaining
2-substituted-e-fused-[1,2,4]triazolo[1,5-c]pyrimidines, pharmaceutical compositions, and uses thereof
Assignee: Novartis Corp
•
Filing: 1987-02-27
•
Granted: 1989-05-16
•
Expires: 2007-02-27
Abstract
Abstract Compounds of the formula ##STR1## wherein R 1 is optionally substituted phenyl, pyridyl, thienyl, furyl, pyrrolyl, thiazolyl, or ribofuranosyl; X is oxygen, NR, or sulfur; R is hydrogen, lower alkyl, lower alkenyl, or lower alkynyl; and ring A is (a) an optionally substituted 5-8 membered monocycloalken-1,2-diyl; (b) an optionally substituted carbobicyclic ring of the formula ##STR2## wherein n and m are each independently one or two; or (c) an optionally substituted 5-6 membered heterocycle having one or two heteroatoms, the atoms of which are selected from carbon, oxygen, nitrogen, and sulfur. Also disclosed are tautomers of the above and pharmaceutically acceptable salts; compositions thereof; and methods of using the compounds, tautomer, or salts.
Inventors
- 👤 John E. Francis
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 07:40
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/12; C07D471/14; C07D487/00; C07D487/02; C07D487/04; C07D487/12; C07D487/14; C07D491/00; C07D491/12; C07D491/14; C07D495/00; C07D495/12; C07D495/14; C07H; C07H17/00; C07H17/02
Claims Analysis
Total Claims: 48
Claim 1
Independent Claim
120 words
A 2-substituted-e-fused[1,2,4]-triazolo[1,5-c]pyrimidine compound of the formula ##STR35## a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer, wherein X is oxygen; R 1 is selected from (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, or halogen; (b) furyl, thienyl, pyridyl, pyrrolyl, and thiazolyl, each of which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, hydroxy-lower alkyl, halogen, or amino; and (c) β-D-ribofuranosyl; ring A being selected from cyclohexene, cycloheptene, pyridine, tetrahydropyridine, pyrazine, pyrimidine and imidazole, each ring A being unsubstituted or substituted by a substituent selected from lower alkyl, lower alkoxy, hydroxy, halogen, halo-lower alkyl, nitro, amino, carbamoyl, lower alkoxy-carbamoyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, phenyl-lower alkyl, and benzoyl.
Claim 2
Dependent Claim
120 words
A 2-substituted-e-fused[1,2,4]-triazolo[1,5-c]pyrimidine compound of the formula ##STR35## a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer, wherein X is oxygen; R 1 is selected from (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, or halogen; (b) furyl, thienyl, pyridyl, pyrrolyl, and thiazolyl, each of which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, hydroxy-lower alkyl, halogen, or amino; and (c) β-D-ribofuranosyl; ring A being selected from cyclohexene, cycloheptene, pyridine, tetrahydropyridine, pyrazine, pyrimidine and imidazole, each ring A being unsubstituted or substituted by a substituent selected from lower alkyl, lower alkoxy, hydroxy, halogen, halo-lower alkyl, nitro, amino, carbamoyl, lower alkoxy-carbamoyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, phenyl-lower alkyl, and benzoyl.
Claim 3
Dependent Claim
62 words
The compound of claim 1 wherein R 1 is (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, or halogen; or (b) furyl, pyridyl, pyrrolyl, or thiazolyl which is mono or disubstituted by lower alkyl, lower alkoxy, hydroxy, hydroxy lower alkyl, halogen, or amino; or (c) β-D-ribofuranosyl; a tautomer thereof or a salt of said compound or said tautomer.
Claim 4
Dependent Claim
32 words
The compound of claim 1 wherein R 1 is selected from phenyl, halophenyl, furyl, pyridyl, pyrrolyl, and β-D-ribofuranosyl; a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 5
Dependent Claim
31 words
The compound of claim 3 wherein R 1 is selected from 2-chlorophenyl, 2-fluorophenyl, 2-pyridyl, 2-pyrrolyl, and 2-furyl; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 6
Dependent Claim
14 words
The methane sulfonate salt of a compound of claim 1 or a tautomer thereof.
Claim 7
Dependent Claim
44 words
The compound of claim 1 wherein said phenyl of R 1 is phenyl which is substituted by one to three groups selected from lower alkyl, lower alkoxy, hydroxy, and halogen; a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 8
Dependent Claim
70 words
The compound of claim 1 wherein said R 1 furyl is 2-furyl or 3-furyl; said R 1 thienyl is 2-thienyl or 3-thienyl; said R 1 pyridyl is 2-pyridyl, 3-pyridyl, or 4-pyridyl; said R 1 pyrrolyl is 2-pyrrolyl or 3-pyrrolyl; each of the foregoing R 1 groups being unsubstituted or substituted by lower alkyl, hydroxy, or halogen; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 9
Dependent Claim
37 words
The compound of claim 1 wherein said R 1 phenyl is unsubstituted or substituted in the ortho or meta position by fluorine or chlorine; a tautomer thereof or a pharmaceutically accetable salt thereof or of said tautomer.
Claim 10
Dependent Claim
22 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 1 wherein said ring A substituent is selected from phenyl-lower alkyl and carbamoyl.
Claim 11
Dependent Claim
27 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 9 wherein said ring A is unsubstituted or substituted by a substituent selected from benzyl, 1-phenethyl, and carbamoyl.
Claim 12
Dependent Claim
33 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 1 wherein ring A is selected from pyridine, pyrazine, pyrimidine, tetrahydropyridine, and imidazole, each of which is unsubstituted or substituted as in claim 1.
Claim 13
Dependent Claim
26 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 11 ring A is tetrahydropyridine piperideine, or pyridine which is unsubstituted or substituted as in claim 11.
Claim 14
Dependent Claim
49 words
The compound, tautomer or pharmaceutically acceptable salt of claim 12 wherein ring A is 1,2,5,6- or 1,2,3,6-tetrahydropyridine or pyridine fused to the pyrimidine ring of formula A at the b, c, d, or e face of said pyridine ring A, which is unsubstituted or substituted as in claim 12.
Claim 15
Dependent Claim
48 words
The compound, tautomer or pharmaceutically acceptable salt of claim 13 wherein said ring A is 1,2,5,6-tetrohydropyridine or pyridine fused to the pyrimidine ring of formula A at the c or d face of said pyridine ring A, each of which is unsubstituted or substituted as in claim 13.
Claim 16
Dependent Claim
54 words
The compound of claim 1 wherein (a) R 1 is o-fluorophenyl and ring A is cycloheptene-1,2-diyl; (b) R 1 is phenyl, 2-halophenyl, 2-pyridyl, 2-pyrrolyl, 2-furyl, and ring A is N-benzyl-(1,2,5,6 or 1,2,3,6)-tetrahydropyridin-3,4-dioyl or b, c, d, or e fused pyridine; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 17
Dependent Claim
27 words
A compound of claim 1 selected from 9-benzyl-2-(2-chlorophenyl)-7,8,9.10-tetrahydropyrido-[3,4-e][1,2,4]triazolo[1,5-c]pyrimidine-5(6H)-one; 9-benzyl-2-(2-pyridyl)-7,8,9,10-tetrahydropyrido[3,4-e] [1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one; 2-(2-furyl)-pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one; 2-(2-fluorophenyl)-pyrido[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one; and 2-(2-furyl)-pyrido[3,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5(6H)-one; a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer.
Claim 18
Dependent Claim
29 words
The compound of claim 1 wherein R 1 is o-fluorophenyl and ring A is cyclohepten-1,2-diyl, a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 19
Dependent Claim
113 words
A compound of the formula ##STR36## a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer wherein R 1 is selected from (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, or halogen; (b) furyl, thienyl, pyridyl, pyrrolyl, and thiazolyl, each of which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, hydroxy-lower alkyl, halogen, or amino; and (c) β-D-ribofuranosyl; ring A being selected from tetrahydropyridine, pyridine, pyrazine, pyrimidine, and imidazole, each of which is unsubstituted or substituted by a substituent from lower alkyl, lower alkoxy, hydroxy, halogen, halo-lower alkyl, nitro, amino, carbamoyl, lower alkoxycarbonyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, phenyl-lower alkyl, and benzoyl.
Claim 20
Dependent Claim
113 words
A compound of the formula ##STR36## a tautomer thereof or a pharmaceutically acceptable salt of said compound or tautomer wherein R 1 is selected from (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, or halogen; (b) furyl, thienyl, pyridyl, pyrrolyl, and thiazolyl, each of which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, hydroxy-lower alkyl, halogen, or amino; and (c) β-D-ribofuranosyl; ring A being selected from tetrahydropyridine, pyridine, pyrazine, pyrimidine, and imidazole, each of which is unsubstituted or substituted by a substituent from lower alkyl, lower alkoxy, hydroxy, halogen, halo-lower alkyl, nitro, amino, carbamoyl, lower alkoxycarbonyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, phenyl-lower alkyl, and benzoyl.
Claim 21
Dependent Claim
141 words
A compound of the formula ##STR37## a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer wherein R 1 is selected from (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, or halogen; and (b) furyl, thienyl, pyridyl, pyrrolyl, or thiazolyl, each of which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, hydroxy-lower alkyl, halogen, or amino; and (c) β-D-ribofuranosyl; ring A being selected from tetrahydropyridine, pyridine, pyrazine, pyrimidine, and imidazole; each ring A being unsubstituted or substituted by a substituent selected from lower alkyl, lower alkoxy, hydroxy, halogen, halo-lower alkyl, nitro, amino, carbamoyl, lower alkoxy carbonyl, lower alkyl thio, lower alkyl sulfinyl, lower alkyl sulfonyl, aryl lower alkyl, and aryl carbonyl,; wherein said aryl portion is phenyl; R 3 is selected from hydrogen, lower alkyl, lower alkenyl, and lower alkynyl.
Claim 22
Dependent Claim
141 words
A compound of the formula ##STR37## a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer wherein R 1 is selected from (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, or halogen; and (b) furyl, thienyl, pyridyl, pyrrolyl, or thiazolyl, each of which is unsubstituted or substituted by lower alkyl, lower alkoxy, hydroxy, hydroxy-lower alkyl, halogen, or amino; and (c) β-D-ribofuranosyl; ring A being selected from tetrahydropyridine, pyridine, pyrazine, pyrimidine, and imidazole; each ring A being unsubstituted or substituted by a substituent selected from lower alkyl, lower alkoxy, hydroxy, halogen, halo-lower alkyl, nitro, amino, carbamoyl, lower alkoxy carbonyl, lower alkyl thio, lower alkyl sulfinyl, lower alkyl sulfonyl, aryl lower alkyl, and aryl carbonyl,; wherein said aryl portion is phenyl; R 3 is selected from hydrogen, lower alkyl, lower alkenyl, and lower alkynyl.
Claim 23
Dependent Claim
62 words
The compound of claim 19 wherein R 1 is (a) phenyl which is unsubstituted or substituted by lower alkyl, lower alkoxy, or halogen; or (b) furyl, pyridyl, pyrrolyl, or thiazolyl which is mono or disubstituted by lower alkyl, lower alkoxy, hydroxy, hydroxy lower alkyl, halogen, or amino; or (c) β-D-ribofuranosyl; a tautomer thereof or a salt of said compound or said tautomer.
Claim 24
Dependent Claim
32 words
The compound of claim 19 wherein R 1 is selected from phenyl, halophenyl, furyl, pyridyl, pyrrolyl, and β-D-ribofuranosyl; a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 25
Dependent Claim
31 words
The compound of claim 21 wherein R 1 is selected from 2-chlorophenyl, 2-fluorophenyl, 2-pyridyl, 2-pyrrolyl, and 2-furyl; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 26
Dependent Claim
14 words
The methane sulfonate salt of a compound of claim 19 or a tautomer thereof.
Claim 27
Dependent Claim
44 words
The compound of claim 19 wherein said phenyl of R 1 is phenyl which is substituted by one to three groups selected from lower alkyl, lower alkoxy, hydroxy, and halogen; a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 28
Dependent Claim
72 words
The compound of claim 19 wherein said R 1 furyl is 2-furyl or 3-furyl; said R 1 is thienyl is 2-thienyl or 3-thienyl; said R 1 pyridyl is 2-pyridyl, 3-pyridyl, or 4-pyridyl; said R 1 is pyrrolyl is 2-pyrrolyl or 3-pyrrolyl; each of the foregoing R 1 groups being unsubstituted or substituted by lower alkyl, hydroxy, or halogen; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 29
Dependent Claim
37 words
The compound of claim 19 wherein said R 1 phenyl is unsubstituted or substituted in the ortho or meta position by fluorine or chlorine; a tautomer thereof or a pharmaceutically acceptable salt thereof or of said tautomer.
Claim 30
Dependent Claim
32 words
The compound, tautomer or pharmaceutically acceptable salt of claim 19 wherein said ring A substituent is selected from, aryl lower alkyl, carboxy lower alkyl, and carbamoyl, in which said aryl is phenyl.
Claim 31
Dependent Claim
27 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 27 wherein said ring A is unsubstituted or substituted by a substituent selected from benzyl, 1-phenethyl, and carbamoyl.
Claim 32
Dependent Claim
66 words
The compound of claim 19 wherein R 1 is 2-furyl and ring A is (a) 2-, 3-, or 4-pyridyl, (b) the tetrahydro analogs of `a` in which the side fused to the pyrimidine ring is a double bond, or (c) imidazolyl each of which is unsubstituted or substituted as in claim 19; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 33
Dependent Claim
38 words
The compound of claim 29 wherein said ring A is 1,2,5,6-tetrahydropyridine, 2-pyridyl or imidazolyl, each of which is unsubstituted or substituted by lower alkyl; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 34
Dependent Claim
33 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 19 wherein ring A is selected from tetrahydropyridine pyridine, pyrazine, pyrimidine and imidazole, each of which is unsubstituted or substituted as in claim 19.
Claim 35
Dependent Claim
25 words
The compound, tautomer, or pharmaceutically acceptable salt of claim 31 ring A is tetrahydropyridine or pyridine which is unsubstituted or substituted as in claim 31.
Claim 36
Dependent Claim
47 words
The compound, tautomer or pharmaceutically acceptable salt of claim 32, wherein ring A is 1,2,5,6-tetrahydropyridine or pyridine fused to the pyrimidine ring of formula A at the b, c, d, or e face of said pyridine ring A, which is unsubstituted or substituted as in claim 32.
Claim 37
Dependent Claim
49 words
The compound, tautomer or pharmaceutically acceptable salt of claim 33 wherein said ring A is 1,2,5 6-tetrahydropyridine or pyridine fused to the pyrimidine ring of formula A at the c or d face of said pyridine ring A, each of which is unsubstituted or substituted as in claim 33.
Claim 38
Dependent Claim
32 words
The compound of claim 19 wherein R 1 is 2-furyl and ring A is cyclopenten-1,2-diyl, cyclohexen-1,2-diyl, or pyridyl, a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 39
Dependent Claim
25 words
The compound of claim 19 wherein R 3 is lower alkyl, a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 40
Dependent Claim
26 words
The compound of claim 19 selected from 2-(2-furyl)-5-imino-5,6,7,8,9,10-hexahydro-[1,2,4]triazolo-[1,5-c]-pyrimidine; 5,6-dihydro-2-(2-furyl)-5-imino-pyrido[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine; and 5,6-dihydro-2-(2-furyl)-5-imino-pyrido[4,3,-e][1,2,4]l triazolo[1,5-c]pyrimidine; a tautomer thereof or a pharmaceutically acceptable salt of said compound or said tautomer.
Claim 41
Dependent Claim
32 words
A method of counteracting the effects of a benzodiazepine comprising administering to a mammal in need of such administration a benzodiazepine antagonistically effective amount of a benzodiazepine antagonistic compound of claim 1.
Claim 42
Dependent Claim
26 words
A method of reducing anxiety comprising administering to a mammal in need of such administration an anxiolytically effective amount of an anxiolytic compound of claim 1.
Claim 43
Dependent Claim
31 words
A method of counteracting the effects of adenosine comprising administering to a mammal in need of such administration an adenosine antagonistically effective amount of an adenosine antagonistic compound of claim 19.
Claim 44
Dependent Claim
26 words
A method of treating asthma comprising administering to a mammal in need of such administration an anti-asthmatic effective amount of an antiasthmatic compound of claim 19.
Claim 45
Dependent Claim
28 words
A pharmaceutical composition for counteracting the effects of benzodiazepine comprising a benzodiazepine antagonistic effective amount of a benzodiazepine antagonistic compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 46
Dependent Claim
22 words
A pharmaceutical composition for treating anxiety comprising an antianxiety effective amount of anxiolytic compound of claim 1 and a pharmaceutically acceptable carrier.
Claim 47
Dependent Claim
28 words
A pharmaceutical composition for counteracting the effects of adenosine comprising an adenosine antagonistic effective amount of an adenosine antagonistic compound of claim 19 and a pharmaceutically acceptable carrier.
Claim 48
Dependent Claim
25 words
A pharmaceutical composition for the treatment of asthma comprising an anti-asthmatic effective amount of an anti-asthmatic compound of claim 19 and a pharmaceutically acceptable carrier.
References Cited (Backward Citations)
US3045015A
Cited
US3053844A
Cited
DE1670375A1
Cited
US4053600A
Cited
US3850932A
Cited
US4124764A
Cited
US4087423A
Cited
US4112096A
Cited
US4164578A
Cited
US4128644A
Cited
US4112098A
Cited
US4312870A
Cited
US4585772A
Cited
US4463007A
Cited
US4524146A
Cited
US4479955A
Cited
US4560689A
Cited
US4602014A
Cited
EP0181282A1
Cited
US4713383A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-05-15 | 1992-11-14 | 1993-05-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-05-15 | 1996-11-14 | 1997-05-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-05-15 | 2000-11-14 | 2001-05-16 | $7700.00 | Window Closed / Lapsed |