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US 2003/0144307 A1Published application
7-oxo-pyridopyrimidines (II)
AssigneeSyntex (U.S.A.) Inc.
InventorsHumberto Bartolome Arzeno, Jian Jeffrey Chen, James Patrick Dunn, David Michael Goldstein, Julie Anne Lim
Life of this patent
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Abstract
The present invention provides compounds of the formula: 1 a prodrug or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3 and Ar1 are those defined herein, and methods for preparation and uses thereof.
Claims20
A compound of the formula:
- 79
- a prodrug or a salt thereof,
- wherein:
- R1 is hydrogen or alkyl;
- R2 is —CR′R″—Ra (where R′ and R″ are hydrogen, hydroxyalkyl or alkyl with at least one being alkyl or hydroxyalkyl and Ra is hydroxyalkyl), Rx—S—Ry— (where Rx is alkyl and Ry is alkylene), alkoxy-substituted alkyl, heterocyclylalkyl or C4-C5 cycloalkyl, wherein each of the hydroxy group present in R2 can be independently in the form of an ester, a carbamate, a carbonate, or a sulfonate derivative;
- or
- R1 and R2 together with the nitrogen atom to which they are attached form a heterocyclyl group;
- R3 is hydrogen, alkyl, amino, monoalkylamino, dialkylamino, cycloalkyl, aryl, aralkyl, haloalkyl, heteroalkyl, cyanoalkyl, alkylene-C(O)—R (where R is hydrogen, alkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino) or acyl;
- and
- Ar1 is aryl.
7 more elements
A composition comprising:
- (a) an excipient;
- and
- (b) a compound of the formula:
- 81
- a prodrug or a pharmaceutically acceptable salt thereof,
- wherein
- R1 is hydrogen or alkyl;
- R2 is —CR′R″—Ra (where R′ and R″ are hydrogen, hydroxyalkyl or alkyl with at least one being alkyl or hydroxyalklyl and Ra is hydroxyalkyl), Rx—S—Ry— (where Rx is alkyl and Ry is alkylene), alkoxy-substituted alkyl, heterocyclylalkyl or C4-C5 cycloalkyl, wherein each of the hydroxy group present in R2 can be independently in the form of an ester, a carbamate, a carbonate, or a sulfonate derivative;
- or
- R1 and R2 together with the nitrogen atom to which they are attached form a heterocyclyl group;
- R3 is hydrogen, alkyl, amino, monoalkylamino, dialkylamino, cycloalkyl, aryl, aralkyl, haloalkyl, heteroalkyl, cyanoalkyl, alkylene-C(O)—R (where R is hydrogen, alkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino) or acyl;
- and
- Ar1 is aryl.
10 more elements
A process for producing a pyrimidine of the formula:
- 84
- comprising:
- (a) contacting an acetal of the formula NC—CH2—C(ORa)2, with an alkyl formate of the formula HCO2R in the presence of a condensation base under conditions sufficient to produce a condensed product;
- and
- (b) contacting said condensed product with thiourea in the presence of a cyclization base under conditions sufficient to produce said pyrimidine of Formula II-c, wherein each of R and Ra is independently alkyl.
2 more elements
A process for producing a pyridopyrimidine of the formula:
- 85
- comprising:
- (a) contacting a pyrimidine of the formula:
- 86
- with an alkylating agent of the formula R—X1 in the presence of an alkylating base under conditions sufficient to produce an alkylated pyrimidine of the formula:
- 87
- and
- (b) contacting said alkylated pyrimidine of Formula II-d with an aryl acetate of the formula Ar1—CH2—CO2R in the presence of a cyclization base under conditions sufficient to produce said pyridopyrimidine of Formula II-e
- or
- (a) contacting said pyrimidine of Formula II-c with said aryl acetate of the formula Ar1—CH2—CO2R in the presence of a cyclization base under conditions sufficient to produce a thiol pyridopyrimidine of the formula:
- 88
- and
- (b) contacting said thiol pyridopyrimidine of Formula III with said alkylating agent of the formula R—X1 in the presence of an alkylating base under conditions sufficient to produce said pyridopyrimidine of Formula II,
- wherein
- X1 is a leaving group;
- each R is independently alkyl;
- Ar1 is aryl;
14 more elements
Dependencies are inferred from the claim text.