Claims for Patent: 8,591,943
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Summary for Patent: 8,591,943
Title: | Pyrazolo[1,5-a]pyrimidine derivatives as mTOR inhibitors |
Abstract: | The present invention provides methods for inhibiting mTOR using pyrazolo[1,5-a]pyrimidine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with mTOR using such compounds. |
Inventor(s): | Deng; Yongqi (Newton, MA), Sun; Binyuan (Chestnut Hill, MA), Zeng; Hongbo (Westford, MA), Richards; Matthew (Somerville, MA), Shipps, Jr.; Gerald W. (Stoneham, MA), Cheng; Cliff C. (Cambridge, MA), Zhao; Yinyan (Rockville, MD), McRiner; Andrew (Melrose, MA), Meng; Zhaoyang (Lansdale, PA), Nan; Yang (Lansdale, PA), Patel; Mehul F. (Willow Grove, PA), Wrona; Iwona E. (Sharon, MA), Reddy; Panduranga Adulla (Walpole, MA), Eklov; Brian M. (Kalamazoo, MI), Tang; Shuyi (Belmont, MA), Liu; Duan (Arlington, MA), Mandal; Amit K. (Shrewsbury, MA), Zhao; Lianyun (Blue Bell, PA), Siddiqui; M. Arshad (Newton, MA) |
Assignee: | Merck Sharp & Dohme Corp. (Rahway, NJ) |
Application Number: | 13/263,193 |
Patent Claims: | 1. A method of treating a disease by inhibiting a mTOR, comprising administering to a patient in need of such treatment an amount of a first compound represented by the
structural Formula I: ##STR01967## or a pharmaceutically acceptable salt, or ester thereof, wherein: R is independently selected from the group consisting of halo, hydroxyl, amino, --CN, H, --(C.sub.1-C.sub.6)alkyl, alkoxy, --C(.dbd.O)alkyl, heteroaryl
and aryl, wherein each of said heteroaryl and aryl can be unsubstituted or substituted with one or more alkyl or halo; R.sup.1 is independently selected from the group consisting of heterocycloalkyl, spiroheterocycloalkyl, heterocyclenyl,
--NR.sup.3R.sup.4, cycloalkyl, heteroaryl, aryl, alkynyl, heterocyclenylalkyl, cycloalkylalkyl, heteroarylalkyl, heteroarylalkynyl, --N-heteroaryl, and arylalkyl, wherein each of said heterocycloalkyl, spiroheterocycloalkyl, heterocyclenyl, cycloalkyl,
heteroaryl, aryl, alkynyl, heterocyclenylalkyl, cycloalkylalkyl, heteroarylalkyl, heteroarylalkynyl, --N-heteroaryl and arylalkyl can be unsubstituted or substituted with one or moieties independently selected from the group X; X is alkoxyl, alkyl,
--C(O)alkyl, --C(O)-hydroxyalkyl, --C(O).sub.2alkyl, --C(O).sub.2H, hydroxyalkyl, --S(O).sub.2alkyl, hydroxyl, heterocycloalkyl, --NH-heterocycloalkyl, -trihaloalkyl, -dihaloalkyl, -monohaloalkyl, --N--S(O).sub.2-alkyl, --C(O)-heteroaryl,
-alkyl-C(O).sub.2H, -alkyl(CO)N(CH.sub.3)--O--CH.sub.3, -alkyl(CO)-heteroaryl, --C(O).sub.2-alkyl, -alkyl-C(O)--NH.sub.2, --NH.sub.2, heteroaryl, -alkyl-CN, --C(O).sub.2-arylalkyl, halo, carboxyesteralkyl, --C(O)--NH.sub.2, -alkyl-C(O).sub.2alkyl,
heteroarylalkyl, --C(O)-heteroaryl, --C(O)-alkyl-O-alkyl, -alkyl(CO)NS(O).sub.2-cycloalkyl, -alkyl(CO)N--S(O).sub.2--CF.sub.3, --N-alkyl, --SO.sub.2-cycloalkyl, -alkyl(CO)NS(O).sub.2-alkyl, -alkyl-C(O)--N(alkyl).sub.2, -alkyl-NS(O).sub.2-alkyl,
alkyl(CO)NS(O).sub.2-cycloalkyl, --CO--CO.sub.2H, --C(O).sub.2-alkyl-aryl, --SO.sub.2--CF.sub.3 or --C(O)H, wherein each of said heterocycloalkyl, heteroaryl or --C(O)-heteroaryl can be unsubstituted or substituted with one or more alkyl; R.sup.2 is
pyridyl optionally substituted with one or more moieties independently selected from the group consisting of alkyl, alkoxyl, --CN, aryloxyl, aryl, halo, hydroxyl, --C(CH.sub.3).sub.2CN, trifluoromethyl, difluoromethyl, monofluoromethyl, heterocycloalkyl,
and arylalkyl; R.sup.3 is cycloalkyl or heteroaryl, wherein each of said cycloalkyl or heteroaryl can be unsubstituted or substituted with one or more moieties independently selected from the group consisting of X; and R.sup.4 is H; and optionally an
amount of at least one second compound, said second compound being an anti-cancer agent; wherein the amounts of the first compound and said second compound result in a therapeutic effect.
2. The method according to claim 1, wherein the one or more anti-cancer agents are selected from the group consisting of Adriamycin, Altretamine, Amidox, Aminoglutethimide, Amsacrine, Anastrazole, Antibodies to EGFR, 3-AP, Aphidicolon, Ara-C, Arsenic trioxide, L-Asparaginase, Bevacizumab, Bleomycin, BMS 214662, Bortezomib, Busulfan, Campath, Camptostar, Capecitabine, Carboplatin, Carmustine, Centrosome associated protein E ("CENP-E") inhibitors, Cetuximab, Cladribine, Chlorambucil, Chlormethine, Chlorotrianisene, Cisplatin, Clofarabine, cyclophosphamide, Cytarabine, a Cytostatic agent, Cytoxan, Dacarbazine, Dactinomycin, Daunorubicin, Dasatinib, Deforolimus, Deoxycoformycin, Didox, Diethylstilbestrol, Docetaxel, Doxorubicin, Dromostanolone, Droloxafine, Epirubicin, Epothilone, ERK inhibitors, Erlotinib, Etoposide, 17.alpha.-Ethinylestradiol, Estramustine, Exemestane, Floxuridine, Fludarabine, Fludarabine phosphate, 5-Fluorouracil, Fluoxymesterone, Flutamide, Fulvestrant, Gefitinib, Gemcitabine, Gemtuzumab ozogamcicin, Goserelin, GSK-923295, Hexamethylmelamine, Hydroxyprogesterone, Hydroxyurea, Ibritumomab Tiuxetan, Idarubicin, Ifosfamide, Imatinib mesylate, Intron, Irinotecan, ispinesib, KSP inhibitors, L778,123, Lapatinib, Leucovirin, Leuprolide, Lerozole, Letrazole, Levamisole, Liposomal Doxorubicin, Liposomal, Lomustine, Lonafarnib, Medroxyprogesteroneacetate, Megestrolacetate, Melphalan, 6-Mercaptopurine, Methoxtrexate, Methylprednisolone, Methyltestosterone, Mithramycin, Mitomycin-C, Mitotane, Mitoxantrone, Navelbene, Nilotinib, Oxaliplatin, Paclitaxel, Panitubimab, Pentostatin, Pipobroman, Porfimer, Prednisolone, Prednisone propionate, Procarbazine, Reloxafine, Rituximab, Satriplatin, SB-743921, Sml1, Sorafinib, Streptozocin, Sunitinib, Tamoxifen, Taxotere, Taxol, Temozolomide, Teniposide, Testolactone, Testosterone, Tezacitabine, 6-Thioguanine, Thiotepa, Tipifarnib, Topotecan, Toremifene, Tositumomab, Trastuzumab, Triamcinolone, Triapine, Triethylenemelamine, Triethylenethiophosphoramine, Trimidox, Uracil mustard, Vinblastine, Vincristine, Vindesine, and Vinorelbine. |
Details for Patent 8,591,943
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Recordati Rare Diseases, Inc. | ELSPAR | asparaginase | For Injection | 101063 | 01/10/1978 | ⤷ Try a Trial | 2039-02-26 |
Merck Sharp & Dohme Corp. | INTRON A | interferon alfa-2b | For Injection | 103132 | 06/04/1986 | ⤷ Try a Trial | 2039-02-26 |
Merck Sharp & Dohme Corp. | INTRON A | interferon alfa-2b | For Injection | 103132 | ⤷ Try a Trial | 2039-02-26 | |
Merck Sharp & Dohme Corp. | INTRON A | interferon alfa-2b | Injection | 103132 | ⤷ Try a Trial | 2039-02-26 | |
Genentech, Inc. | RITUXAN | rituximab | Injection | 103705 | 11/26/1997 | ⤷ Try a Trial | 2039-02-26 |
Idec Pharmaceuticals Corp. | RITUXAN | rituximab | Injection | 103737 | 02/19/2002 | ⤷ Try a Trial | 2039-02-26 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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