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US 2003/0114467 A1Published application
Novel pyrazolo- and pyrrolo-pyrimidines and uses thereof
OwnerWilliam C. Shakespeare, Tomi K. Sawyer +4inventors
InventorsWilliam C. Shakespeare, Tomi K. Sawyer, Chester A. Metcalf III, Yihan Wang, Regine Bohacek, Rajeswari Sundaramoorthi
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Abstract
The invention relates to compounds of the general formula: 1 in which RA-RC and W are as defined herein, and to their preparation and use.
Claims31
A compound having the formula (and pharmaceutically acceptable derivatives thereof):
- 140
- wherein RA is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- RB is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, halogen, —CN, —S(O)nRJ, —NO2, —CORJ, —CO2RJ, —NRJCORJ, —NRJ(CO)NRJRJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, or -ZRJ, wherein Z is —O—, —S—, or NRK, wherein each occurrence of RJ and RK is independently hydrogen, —CORJ, —CO2RJ, —CONRJRJ, —CO(NORJ)RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and n is 1 or 2;
- RC is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- W is —CRD— or —N—;
- is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, halogen, —CN, —S(O)nRJ, —NO2, —CORJ, —CO2RJ, —NRJCORJ, —NRJ(CO)NRJRJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, or -ZRJ, wherein Z is —O—, —S—, or NRK, wherein each occurrence of RJ and RK is independently hydrogen, —CORJ, —CO2RJ, —CONRJRJ, —CO(NORJ)RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of RA, RB, RC, or RD as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula where RA is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl group AR:
- 153
- wherein AR is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- wherein RB is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, halogen, —CN, —S(O)nRJ, —NO2, —CORJ, —CO2RJ, —NRJCORJ, —NRJ(CO)NRJRJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)R, or -ZRJ, wherein Z is —O—, —S—, or NRK, wherein each occurrence of RJ and RK is independently hydrogen, —CORJ, —CO2RJ, —CONRJRJ, —CO(NORJ)RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and n is 1 or 2;
- RC is hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- W is —CRD— or —N—;
- RD is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, halogen, —CN, —S(O)nRJ, —NO2, —CORJ, —CO2RJ, —NRJCORJ, —NRJ(CO)NRJRJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, or -ZRJ, wherein Z is —O—, —S—, or NRK, wherein each occurrence of RJ and RK is independently hydrogen, —CORJ, —CO2RJ, —CONRJRJ, —CO(NORJ)RJ, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of AR, RB, RC, or RD as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula in which RA is a substituted or unsubstituted aliphatic or heteroaliphatic moiety AL:
- 154
- wherein RB is hydrogen, halogen, —CN, CORJ, CO2R3, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NR1, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- RC is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- AL is a substituted or unsubstituted, cyclic or acyclic, linear or branched aliphatic or heteroaliphatic moiety;
- W is —CRD— of —N—;
- RD is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of AL, RB, RC, or RD as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula:
- 155
- wherein RA is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- RC is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- AR is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- W is —CRD— of —N—;
- RD is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCOJR, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of RA, RC, RD, or AR as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula:
- 156
- wherein RA is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- RC is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- AL is a substituted or unsubstituted, cyclic or acyclic, linear or branched aliphatic or heteroaliphatic moiety;
- W is —CRD— of —N—;
- RD is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of AL, RA, RC, or RD as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula:
- 157
- wherein RA is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- RB is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- AR is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- W is —CRD— of —N—;
- RD is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2R, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of RA, RB, RD, or AR as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula where RC is a substituted or unsubstituted aliphatic or heteroaliphatic moiety AL:
- 158
- wherein RA is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- RB is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- AL is a substituted or unsubstituted, cyclic or acyclic, linear or branched aliphatic or heteroaliphatic moiety;
- Z is —CRD— of —N—;
- RD is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RW is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of AL, RA, RC, or RD as defined above, comprises a phosphorus-containing moiety.
6 more elements
A compound having the formula:
- 159
- wherein RA is hydrogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- RB, independently for each occurrence, is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- RC is hydrogen, halogen, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;
- W is —CRD— of —N—;
- RD is hydrogen, halogen, —CN, CORJ, CO2RJ, —NRJCORJ, —NRJCO2RJ, —CONRJRJ, —CO(NORJ)RJ, an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety, or -ZRE, wherein Z is —O—, —S—, or —NRF, wherein each occurrence of RE, RF, and RJ is independently hydrogen, or an aliphatic, heteroaliphatic, aryl, heteroaryl, alkylaryl, or alkylheteroaryl, and n is 1 or 2;
- wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;
- and
- at least one of RA, R3, RC, or RD as defined above, comprises a phosphorus-containing moiety.
6 more elements
A pharmaceutical composition comprising any one of the compounds of claims 1 and 17-24, or a pharmaceutically acceptable derivative thereof;
- and
- a pharmaceutically acceptable carrier or diluent,
- said composition optionally further comprising an additional therapeutic agent.
A method for treating a bone-related disorder comprising administering a therapeutically effective amount of any one of compounds 1 and 17-24, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof,
- and optionally further comprising administering an additional therapeutic agent.
A method for treating a proliferative disorder comprising administering a therapeutically effective amount of any one of compounds 1 and 17-24, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof,
- and optionally further comprising administering an additional therapeutic agent.
Dependencies are inferred from the claim text.