Back to results
US 2003/0171584 A1Published application
6-Substituted pyrido-pyrimidines
AssigneeSyntex (U.S.A.) Inc.
InventorsJian Jeffrey Chen, James Patrick Dunn, David Michael Goldstein, Christoph Martin Stahl
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of the Formula I and II: 1 wherein R1, R3, W, Z, X1, X2, Ar1, R8 and R9 are as defined herein, and methods and intermediates for their preparation and uses thereof.
Claims59
A compound of the Formula I or II
- 421
- or pharmaceutically acceptable salts thereof,
- wherein:
- Z is N or CH;
- W is NR2;
- X1 is O, NR4 (where R4 is hydrogen or alkyl), S, or CR5R6 (where R5 and R6 are independently hydrogen or alkyl) or C═O;
- X is O or NR;
- Ar1 is aryl or heteroaryl;
- R2 is hydrogen alkyl, acyl, alkoxycarbonyl, aryloxycarbonyl, heteroalkylcarbonyl, heteroalkyloxycarbonyl or —R21—R22 where R21 is alkylene or —C(═O)— and R22 is alkyl or alkoxy;
- R1 is hydrogen, alkyl, haloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, cycloalkyl, cycloalkylalkyl, heteroalkylsubstituted cycloalkyl, heterosubstituted cycloalkyl, heteroalkyl, cyanoalkyl, heterocyclyl, heterocyclylalkyl, R12—SO2-heterocycloamino (where R12 is haloalkyl, aryl, aryalkyl, heteroaryl or heteroaralkyl), —Y1—C(O)—Y2—R11 (where Y1 and Y2 are independently either absent or an alkylene group and R11 is hydrogen, alkyl, haloalkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino), (heterocyclyl)(cycloalkyl)alkyl or (heterocyclyl)(heteroaryl)alkyl;
- R3 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, haloalkyl, heteroalkyl, cyanoalkyl, alkylene-C(O)—R31 (where R31 is hydrogen, alkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino), amino, monoalkylamino, dialkylamino or NR32—Y3—R33 (where Y3 is —C(O), —C(O)O—, —C(O)NR34, S(O)2 or S(O)2NR3;
- R32, R34 and R35 are independently hydrogen or alkyl;
- and R33 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl or optionally substituted phenyl) or acyl;
- R7 is hydrogen or alkyl;
- and
- R8 and R9 are independently hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, alkylsulfonyl, arylsulfonyl, —C(O)—R81 (where R81is alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, alkoxy, aryloxy, amino, mono- or di-alkylamino, arylamino or aryl(alkyl)amino) or R8 and R9 together form ═CR82R83 (where R82 and R83 are independently hydrogen, alkyl, cycloalkyl, cycloalkylalkyl or optionally substituted phenyl).
- or pharmaceutically acceptable salts thereof,
14 more elements
The compound of claim 35, wherein Ar1 is 2-chlorophenyl, 2-fluorophenyl, 2-methylphenyl, 2-fluoro-4-methylphenyl or 2,4-difluorophenyl.
A method for preparing a sulfide compound of the formula:
- 422
- wherein:
- Z is N or CH;
- X1 is O, NR4 (where R4 is hydrogen or alkyl), S, CR5R6 (where R5 and R6 are independently hydrogen or alkyl) or C═O;
- X2 is O;
- Ar1 is aryl or heteroaryl;
- R is alkyl or aryl;
- R3 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, haloalkyl, heteroalkyl, cyanoalkyl, acyl, alkylene-C(O)—R31 (where R31 is hydrogen, alkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino), amino, monoalkylamino, dialkylamino or NR32—Y31—R33 (where Y3 is —C(O), —C(O)O—, —C(O)NR34, S(O)2 or S(O)2NR35;
- R32, R34 and R35 are independently hydrogen or alkyl;
- and R33 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl or optionally substituted phenyl);
- said method comprising the steps of:
- contacting an aldehyde of the formula:
- 423
- with an aryl compound of the formula:
- 424
- wherein
- X3 is —C(═O)—OR′ and R′ is alkyl,
- under conditions sufficient to produce said sulfide compound.
15 more elements
A compound of Formula I′ or II″
- 427
- wherein:
- Z is N or CH;
- W is S, S(O), S(O)2 or O;
- X1 is O, NR4 (where R4 is hydrogen or alkyl), S, or CR5R6 (where R5 and R6 are independently hydrogen or alkyl) or C═O;
- X2 is O or NR7;
- Ar1 is aryl or heteroaryl;
- R10 is alkyl, aryl, aralkyl, cycloalkyl or cycloalkylalkyl, or R10W together form a leaving group or hydroxy;
- R3 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, haloalkyl, heteroalkyl, cyanoalkyl, alkylene-C(O)—R31 (where R31 is hydrogen, alkyl, hydroxy, alkoxy, amino, monoalkylamino or dialkylamino), amino, monoalkylamino, dialkylamino or NR32—Y3—R33 (where Y3 is —C(O), —C(O)O—, —C(O)NR34, S(O)2, or S(O)2NR35;
- R32, R34 and R35 are independently hydrogen or alkyl;
- and R33 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl or optionally substituted phenyl) or acyl;
- R7 is hydrogen or alkyl;
- and
- R8 and R9 are independently hydrogen, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, alkylsulfonyl, arylsulfonyl, —C(O)—R81 (where R81is alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, alkoxy, aryloxy, amino, mono- and di-alkylamino, arylamino or aryl(alkyl)amino) or R8 and R9 together form ═CR82R83 (where R82 and R83 are independently hydrogen, alkyl, cycloalkyl, cycloalkylalkyl or optionally substituted phenyl).
11 more elements
Dependencies are inferred from the claim text.