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Building IP: CELG Patent Appl. re "SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS
SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH Provided herein are 4-aminoisoindoline-1,3-dione compounds having the following structure: ##STR00001## wherein R, Ring A, and n are as defined herein, compositions comprising an effective amount of a 4-aminoisoindoline-1,3-dione compound, and methods for treating or preventing disorders.
1. A compound of formula (I): ##STR00361## or a pharmaceutically acceptable salt, tautomer, isotopolog, or stereoisomer thereof, wherein: Ring A is an optionally substituted non-aromatic heterocyclyl; each R is independently substituted or unsubstituted C.sub.1-3 alkyl, or halogen; and n is 0, 1, 2, 3 or 4. 2. The compound of claim 1, wherein the compound is a compound of formula ##STR00362## or a pharmaceutically acceptable salt, tautomer, isotopolog, or stereoisomer thereof. 3. The compound of claim 1, wherein the compound is a compound of formula ##STR00363## or a pharmaceutically acceptable salt, tautomer, isotopolog, or stereoisomer thereof. 4. The compound of claim 1, wherein the compound is a compound of formula (IV): ##STR00364## or a pharmaceutically acceptable salt, tautomer, or isotopolog thereof. 5. The compound of claim 4, wherein the compound is a compound of formula (V): ##STR00365## or a pharmaceutically acceptable salt, tautomer, or isotopolog thereof. 6. The compound of claim 4, wherein the compound is a compound of formula (VI): ##STR00366## or a pharmaceutically acceptable salt, tautomer, or isotopolog thereof. 7. The compound of claim 1, wherein the compound is a compound of formula (VII): ##STR00367## or a pharmaceutically acceptable salt, tautomer, or isotopolog thereof. 8. The compound of claim 7, wherein the compound is a compound of formula (VIII): ##STR00368## or a pharmaceutically acceptable salt, tautomer, or isotopolog thereof. 9. The compound of claim 7, wherein the compound is a compound of formula (IX): ##STR00369## or a pharmaceutically acceptable salt, tautomer, or isotopolog thereof. 10. The compound of any one of claims 1-9, wherein Ring A is ##STR00370## wherein R.sup.a is H, and R.sup.b is C.sub.1-6 alkyl, non-aromatic heterocyclyl, aryl, heteroaryl, or O-aryl; or R.sup.a and R.sup.b together with the carbon to which they are attached form a 3-6 membered cycloalkyl, or a 4-6 membered non-aromatic heterocyclyl; wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted with one or more halogen, C.sub.1-3 alkyl, or CN. 11. The compound of any one of claims 1-9, wherein Ring A is ##STR00371## wherein RC is H, halogen, OH, or (C.sub.1-3 alkyl); and R.sup.d is optionally substituted (C.sub.1-3 alkyl), OR.sup.1, C(O)N(R.sup.2).sub.2, SO.sub.2(C.sub.1-4 alkyl), C.sub.3-7 cycloalkyl, non-aromatic heterocyclyl, aryl, heteroaryl, or O-heteroaryl; or RC and R.sup.d together with the carbon to which they are attached form a 3-6 membered cycloalkyl, or a 4-6 membered non-aromatic heterocyclyl; wherein R.sup.1 is H, optionally substituted C.sub.1-6 alkyl, or optionally substituted --(C.sub.0-3 alkyl)-(C.sub.3-7 cycloalkyl); each R.sup.2 is independently H, or C.sub.1-6 alkyl; and wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted with one or more halogen, C.sub.1-3 alkyl, or CN. 12. The compound of any one of claims 1-9, wherein Ring A is ##STR00372## wherein R.sup.e is C.sub.1-6 alkyl, SO.sub.2(C.sub.1-4 alkyl), --(C.sub.0-3 alkyl)-(C.sub.3-7 cycloalkyl), aryl, heteroaryl or CO-aryl; wherein the alkyl, cycloalkyl, aryl, or heteroaryl are optionally substituted. 13. The compound of any one of claims 1-9, wherein Ring A is an optionally substituted non-aromatic heterocyclyl selected from azetidyl; piperidyl; piperazinyl; morpholinyl; 5-azaspiro[2,3]hexyl; 2-azaspiro[3.3]heptyl; 2-oxa-6-azaspiro[3.3]heptyl; 2-azaspiro[3.4]octyl; 5-oxa-2-azaspiro[3.4]octyl; 6-oxa-2-azaspiro[3.4]octyl; 2-azaspiro[3.5]nonyl; 7-oxa-2-azaspiro[3.5]nonyl; octahydrocyclopenta[c]pyrrolyl; 1,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrolyl; 6-azaspiro[3.4]octyl; 2-oxa-6-azaspiro[3.4]octyl; 6-azaspiro[2.5]octyl; 7-azaspiro[3.5]nonyl; 1-oxa-8-azaspiro[4.5]decanyl; 2-oxa-8-azaspiro[4.5]decanyl; 2,8-diazaspiro[4.5]decan-1-onyl; 3-oxa-9-azaspiro[5.5]undecanyl; 1,4-oxazepanyl; 8-azabicyclo[3.2.1]octyl; and isoindolinyl. 14. The compound of claim 13, wherein Ring A is substituted with one or more substituents independently selected from halogen, C.sub.1-6 alkyl, OR.sup.1, CON(R.sup.2).sub.2, SO.sub.2(C.sub.1-4 alkyl), N(R.sup.2)SO.sub.2(C.sub.1-4 alkyl), --(C.sub.0-3 alkyl)-(C.sub.3-7 cycloalkyl), (non-aromatic heterocyclyl), aryl, heteroaryl, O-aryl, O-heteroaryl, and C(O)aryl; wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted; wherein R.sup.1 is H, optionally substituted C.sub.1-6 alkyl, or optionally substituted --(C.sub.0-3 alkyl)-(C.sub.3-7 cycloalkyl); and each R.sup.2 is independently H, or C.sub.1-6 alkyl. 15. The compound of claim 13, wherein Ring A is substituted with one or more substituents independently selected from F, Cl, Br, CH.sub.3, CH.sub.2CH.sub.3, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, CH.sub.2F, CHF.sub.2, CF.sub.3, CH.sub.2CH.sub.2F, CH.sub.2CHF.sub.2, CH.sub.2CF.sub.3, CH(CH.sub.3)CF.sub.3, CH.sub.2CH.sub.2CF.sub.3, OH, OCH.sub.3, OCH.sub.2CH.sub.3, O-isopropyl, O-n-propyl, O-n-butyl, O-isobutyl, O-t-butyl, OCF.sub.3, O-cyclopropyl, O-cyclobutyl, OCH.sub.2-cyclopropyl, OCH.sub.2-cyclobutyl, CONH.sub.2, CONH(CH.sub.3), CON(CH.sub.3).sub.2, SO.sub.2CH.sub.3, SO.sub.2CH.sub.2CH.sub.3, SO.sub.2-isopropyl, cyclopropyl, cyclobutyl, CH.sub.2-cyclopropyl, CH.sub.2-cyclobutyl; (non-aromatic heterocyclyl) selected from azetidyl, pyrrolidyl, pyrrolidonyl, isothiazolidyl, isothiazolidine 1,1-dioxidyl, piperidyl, piperazinyl, morpholinyl, 3-oxa-8-azabicyclo[3.2.1]octyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, wherein the heterocyclyl is optionally substituted with one or more substituents independently selected from CH.sub.3, CH.sub.2CH.sub.3, or CF.sub.3, phenyl, O-phenyl or C(O)-phenyl, wherein the phenyl is optionally substituted with one or more substituents independently selected from F, Cl, CH.sub.3, CN, or CONH.sub.2; heteroaryl selected from pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, or benzoisoxazolyl, wherein the heteroaryl is optionally substituted with one or more substituents independently selected from F, Cl, CF.sub.3, CN, CONH.sub.2, CONH(CH.sub.3).sub.2 or CON(CH.sub.3).sub.2; O-pyridyl, and O-pyrimidyl. 16. The compound of claim 13, wherein Ring A is substituted with one or more substituents independently selected from F, CH.sub.3, CH.sub.2CH.sub.3, isopropyl, t-butyl, CH.sub.2F, CF.sub.3, CH(CH.sub.3)CF.sub.3, OH, OCH.sub.3, OCH.sub.2CH.sub.3, O-isopropyl, O-n-propyl, O-isobutyl, O-t-butyl, OCF.sub.3, O-cyclobutyl, OCH.sub.2-cyclopropyl, CON(CH.sub.3).sub.2, SO.sub.2CH.sub.2CH.sub.3, SO.sub.2-isopropyl, cyclopropyl, cyclobutyl, CH.sub.2-cyclopropyl; (non-aromatic heterocyclyl) selected from pyrrolidyl, pyrrolidonyl, isothiazolidine 1,1-dioxidyl, morpholinyl, 3-oxa-8-azabicyclo[3.2.1]octyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, wherein the heterocyclyl is optionally substituted with one or more substituents independently selected from CH.sub.3, phenyl, O-phenyl or C(O)-phenyl, wherein the phenyl is optionally substituted with one or more substituents independently selected from F, Cl, CH.sub.3, CN, or CONH.sub.2; heteroaryl selected from pyrazolyl, oxazolyl, oxadiazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidyl or benzoisoxazolyl, wherein the heteroaryl is optionally substituted with one or more substituents independently selected from F, Cl, CF.sub.3, CN, CONH.sub.2, CON(CH.sub.3).sub.2; O-pyridyl, and O-pyrimidyl. 17. The compound of claim 13, wherein Ring A is azetidyl, substituted with one or more substituents independently selected from C.sub.1-6 alkyl, (non-aromatic heterocyclyl), aryl, heteroaryl, O-aryl, and O-heteroaryl; wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted. 18. The compound of claim 13, wherein Ring A is azetidyl, substituted with one or more substituents independently selected from CH.sub.2CH.sub.3, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl; CF.sub.3; pyrrolidyl; pyrolidonyl; piperidyl; piperazinyl; morpholinyl, optionally substituted with one or more CH.sub.3; 3-oxa-8-azabicyclo[3.2.1]octyl; 8-oxa-3-azabicyclo[3.2.1]octyl; pyrazolyl; 2-pyridyl; 3-pyridyl; 4-pyridyl, phenyl; and O-phenyl; wherein the phenyl optionally is substituted with one or more substituents selected from F or CN. 19. The compound of claim 13, wherein Ring A is piperidyl, substituted with one or more substituents independently selected from halogen, C.sub.1-6 alkyl, OR.sup.1, CON(R.sup.2).sub.2, SO.sub.2(C.sub.1-4 alkyl), C.sub.3-7 cycloalkyl, non-aromatic heterocyclyl, aryl, heteroaryl and O-heteroaryl; wherein the alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl are optionally substituted; wherein R.sup.1 is H, optionally substituted C.sub.1-6 alkyl, or optionally substituted --(C.sub.0-3 alkyl)-(C.sub.3-7 cycloalkyl); and each R.sup.2 is independently H, or C.sub.1-6 alkyl. 20. The compound of claim 13, wherein Ring A is piperidyl, substituted with one or more substituents independently selected from F, Cl, CH.sub.3, CH.sub.2CH.sub.3, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, CH.sub.2F, CHF.sub.2, CF.sub.3, OH, OCH.sub.3, OCH.sub.2CH.sub.3, O-n-propyl, O-isopropyl, O-n-butyl, O-isobutyl, O-t-butyl, OCF.sub.3, O-cyclopropyl, O-cyclobutyl, OCH.sub.2-cyclopropyl, OCH.sub.2-cyclobutyl, CONH.sub.2, CONH(CH.sub.3), CON(CH.sub.3).sub.2, SO.sub.2CH.sub.3, SO.sub.2CH.sub.2CH.sub.3, SO.sub.2-isopropyl, cyclopropyl, cyclobutyl, pyrrolidonyl, isothiazolidine 1,1-dioxidyl, morpholinyl; tetrahydrofuranyl, tetrahydropyranyl, pyrazolyl; oxadiazolyl, optionally substituted with CH.sub.3; phenyl, optionally substituted with one or more F; 2-pyridyl, 3-pyridyl, 4-pyridyl, O-2-pyridyl, O-3-pyridyl, and O-4-pyridyl. 21. The compound of claim 13, wherein Ring A is piperidyl, substituted with one or more substituents independently selected from F, CH.sub.3, CH.sub.2CH.sub.3, isopropyl, t-butyl, CHF.sub.2, CF.sub.3, OH, OCH.sub.3, OCH.sub.2CH.sub.3, O-isopropyl, O-isobutyl, O-t-butyl, OCF.sub.3, O-cyclobutyl, OCH.sub.2-cyclopropyl, CON(CH.sub.3).sub.2, SO.sub.2CH.sub.2CH.sub.3, SO.sub.2-isopropyl, cyclopropyl, pyrrolidonyl, isothiazolidine 1,1-dioxidyl, morpholinyl; tetrahydropyranyl, pyrazolyl, oxadiazolyl, substituted with CH.sub.3; phenyl, substituted with one or more F; 2-pyridyl, and O-2-pyridyl. 22. The compound of claim 13, wherein Ring A is piperazinyl, substituted with one or more substituents independently selected from C.sub.1-6 alkyl, SO.sub.2(C.sub.1-4 alkyl), --(C.sub.0-3 (C.sub.3-7 cycloalkyl), aryl, heteroaryl and CO-aryl; wherein the alkyl, cycloalkyl, aryl, or heteroaryl are optionally substituted. 23. The compound of claim 13, wherein Ring A is piperazinyl, substituted with one or more substituents independently selected from CH.sub.3, CH.sub.2CH.sub.3, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, CF.sub.3, CH.sub.2CF.sub.3, CH(CH.sub.3)CF.sub.3, SO.sub.2CH.sub.3, SO.sub.2CH.sub.2CH.sub.3, SO.sub.2-isopropyl, cyclopropyl, cyclobutyl, (CH.sub.2)cyclopropyl, (CH.sub.2)cyclobutyl, phenyl, optionally substituted with one or more Cl, F, CN, CH.sub.3, CONH.sub.2; pyrazolyl, optionally substituted with CH.sub.3 or CH.sub.2CH.sub.3; oxazolyl, optionally substituted with CH.sub.3 or CH.sub.2CH.sub.3; oxadiazolyl, optionally substituted with CH.sub.3 or CH.sub.2CH.sub.3; thiadiazolyl, optionally substituted with CH.sub.3, CH.sub.2CH.sub.3, or CF.sub.3; 2-pyridyl, 3-pyridyl, or 4-pyridyl, each optionally substituted with Cl, F, CF.sub.3, CN, CONH.sub.2, CONH(CH.sub.3) or CON(CH.sub.3).sub.2; pyrazinyl, optionally substituted with CH.sub.3 or CH.sub.2CH.sub.3; pyrimidyl, optionally substituted with OCH.sub.3; benzoisoxazolyl; and CO(phenyl), wherein the phenyl is optionally fluorinated. 24. The compound of claim 13, wherein Ring A is piperazinyl, substituted with one or more substituents independently selected from CH.sub.3, isopropyl, t-butyl, CH(CH.sub.3)CF.sub.3, SO.sub.2CH.sub.2CH.sub.3, SO.sub.2-isopropyl, cyclopropyl, cyclobutyl, (CH.sub.2)cyclopropyl, phenyl, optionally substituted with one or more Cl, F, CN, CH.sub.3, CONH.sub.2; pyrazolyl, optionally substituted with CH.sub.3; oxazolyl, optionally substituted with CH.sub.3; oxadiazolyl, optionally substituted with CH.sub.2CH.sub.3; thiadiazolyl, optionally substituted with CH.sub.3, or CH.sub.2CH.sub.3; 2-pyridyl, optionally substituted with Cl, F, CF.sub.3, CN, or CONH.sub.2; 3-pyridyl, optionally substituted with CF.sub.3, CN, CONH.sub.2, or CON(CH.sub.3).sub.2; 4-pyridyl, optionally substituted with CONH.sub.2; pyrazinyl, optionally substituted with CH.sub.3; pyrimidyl, optionally substituted with OCH.sub.3; benzoisoxazolyl; and CO(phenyl), wherein the phenyl is optionally fluorinated. 25. The compound of claim 13, wherein Ring A is morpholinyl, and R is F or CH.sub.3, and n is 1. 26. The compound of claim 13, wherein Ring A is selected from 5-azaspiro[2,3]hexyl; 2-azaspiro[3.3]heptyl; 2-oxa-6-azaspiro[3.3]heptyl; 2-azaspiro[3.4]octyl; 5-oxa-2-azaspiro[3.4]octyl; 6-oxa-2-azaspiro[3.4]octyl; 2-azaspiro[3.5]nonyl; 7-oxa-2-azaspiro[3.5]nonyl; octahydrocyclopenta[c]pyrrolyl; 1,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrolyl; 6-azaspiro[3.4]octyl; 2-oxa-6-azaspiro[3.4]octyl; 6-azaspiro[2.5]octyl; 7-azaspiro[3.5]nonyl; 1-oxa-8-azaspiro[4.5]decanyl; 2-oxa-8-azaspiro[4.5]decanyl; 2,8-diazaspiro[4.5]decan-1-onyl; 3-oxa-9-azaspiro[5.5]undecanyl; 1,4-oxazepanyl; 8-azabicyclo[3.2.1]octyl; and isoindolinyl; each optionally substituted with one or more CH.sub.3 or F. 27. The compound of any one of claims 1-26, wherein R is F. 28. The compound of any one of claims 1-26, wherein R is CH.sub.3. 29. The compound of any one of claims 1-28, wherein n is 1. 30. The compound of claim 1, wherein the compound is selected from Table 1. 31. A pharmaceutical composition comprising an effective amount of a compound of any one of claims 1-30, or a pharmaceutically acceptable salt, tautomer, isotopologue, or stereoisomer thereof, and a pharmaceutically acceptable carrier, excipient or vehicle. 32. A method for the treatment of diffuse large B-cell lymphoma (DLBCL), comprising administering to a subject in need thereof an effective amount of a compound of any one of claims 1-30, or a pharmaceutical composition of claim 31. 33. The method of claim 32, wherein the DLBCL is relapsed or refractory DLBCL. 34. The method of claim 33, wherein the DLBCL is refractory to one or more of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, bendamustine, lenalidomide, or gemcitabine. 35. The method of claim 32, wherein the DLBCL is newly diagnosed DLBCL. 36. The method of any one of claims 32-35, further comprising administering one or more of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, bendamustine, lenalidomide, or gemcitabine. 37. A compound of any one of claims 1-30 or a pharmaceutical composition of claim 31 for use in a method for the treatment of diffuse large B-cell lymphoma (DLBCL), the method comprising administering to a subject in need thereof an effective amount of the compound or the pharmaceutical composition. 38. The compound or pharmaceutical composition for use of claim 37, wherein the DLBCL is relapsed or refractory DLBCL. 39. The compound or pharmaceutical composition for use of claim 38, wherein the DLBCL is refractory to one or more of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, bendamustine, lenalidomide, or gemcitabine. 40. The compound or pharmaceutical composition for use of claim 37, wherein the DLBCL is newly diagnosed DLBCL. 41. The compound or pharmaceutical composition for use of any one of claims 37-40, further comprising administering one or more of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide, bendamustine, lenalidomide, or gemcitabine. 42. A method for preparing a compound of formula (I): ##STR00373## the method comprising contacting a compound of formula (Ia): ##STR00374## in the presence of a base, in a solvent, under conditions suitable to provide a compound of formula (I), wherein Ring A is an optionally substituted non-aromatic heterocyclyl; each R is independently substituted or unsubstituted C.sub.1-3 alkyl, or halogen; n is 0, 1, 2, 3 or 4; and LG is OMs, OTs, or halogen. [0001] This application is a divisional application of U.S. patent application Ser. No. 16/390,815, filed Apr. 22, 2019, which claims priority to U.S. Provisional Application No. 62/661,525, filed Apr. 23, 2018, the entirety of each of which is incorporated herein by reference. FIELD [0002] Provided herein are certain 4-aminoisoindoline-1,3-dione compounds, compositions comprising an effective amount of such compounds, and methods for treating or preventing Diffuse Large B-Cell Lymphoma (DLBCL), comprising administering an effective amount of such 4-aminoisoindoline-1,3-dione compounds to a subject in need thereof. BACKGROUND [0003] Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, or lymphatic or blood-borne spread of malignant cells to regional lymph nodes and metastasis. Clinical data and molecular biologic studies indicate that cancer is a multistep process that begins with minor preneoplastic changes, which may under certain conditions progress to neoplasia. The neoplastic lesion may evolve clonally and develop an increasing capacity for invasion, growth, metastasis, and heterogeneity, especially under conditions in which the neoplastic cells escape the host's immune surveillance. Current cancer therapy may involve surgery, chemotherapy, hormonal therapy and/or radiation treatment to eradicate neoplastic cells in a patient. Recent advances in cancer therapeutics are discussed by Rajkumar et al. in Nature Reviews Clinical Oncology 11, 628-630 (2014). [0004] All of the current cancer therapy approaches pose significant drawbacks for the patient. Surgery, for example, may be contraindicated due to the health of a patient or may be unacceptable to the patient. Additionally, surgery may not completely remove neoplastic tissue. Radiation therapy is only effective when the neoplastic tissue exhibits a higher sensitivity to radiation than normal tissue. Radiation therapy can also often elicit serious side effects. Hormonal therapy is rarely given as a single agent. Although hormonal therapy can be effective, it is often used to prevent or delay recurrence of cancer after other treatments have removed the majority of cancer cells. [0005] With respect to chemotherapy, there are a variety of chemotherapeutic agents available for treatment of cancer. A majority of cancer chemotherapeutics act by inhibiting DNA synthesis, either directly or indirectly by inhibiting the biosynthesis of deoxyribonucleotide triphosphate precursors, to prevent DNA replication and concomitant cell division. Gilman et al., Goodman and Gilman's: The Pharmacological Basis of Therapeutics, Tenth Ed. (McGraw Hill, New York). [0006] Despite availability of a variety of chemotherapeutic agents, chemotherapy has many drawbacks. Stockdale, Medicine, vol. 3, Rubenstein and Federman, eds., ch. 12, sect. 10, 1998. Almost all chemotherapeutic agents are toxic, and chemotherapy causes significant, and often dangerous side effects including severe nausea, bone marrow depression, and immunosuppression. Additionally, even with administration of combinations of chemotherapeutic agents, many tumor cells are resistant or develop resistance to the chemotherapeutic agents. In fact, those cells resistant to the particular chemotherapeutic agents used in the treatment protocol often prove to be resistant to other drugs, even if those agents act by different mechanism from those of the drugs used in the specific treatment. This phenomenon is referred to as pleiotropic drug or multidrug resistance. Because of the drug resistance, many cancers prove or become refractory to standard chemotherapeutic treatment protocols. [0007] Diffuse large B-cell lymphoma (DLBCL) accounts for approximately one-third of non-Hodgkin's lymphoma (NHL). NHL is the fifth most common cancer for both men and women in the United States. An estimated 385,700 patients worldwide were diagnosed with NHL in 2012 and approximately 199,700 patients died as a result of the disease. (Torre, L. A. et al. Global cancer statistics, 2012; CA Cancer J. Clin. 65, 87-108 (2015)). DLBCL, the most common form of B-cell NHL, had an estimated 27,650 new cases in the USA in 2016, accounting for approximately 26% of all mature B-cell NHL neoplasms diagnosed. (Teras, L. R. et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes; CA Cancer J. Clin. 66, 443-459 (2016)). While some DLBCL patients are cured with traditional chemotherapy, the remainder die from the disease. [0008] There remains a significant need for safe and effective methods of treating, preventing and managing DLBCL, particularly for DLBCL that is refractory to standard treatments, such as surgery, radiation therapy, chemotherapy and hormonal therapy, while reducing or avoiding the toxicities and/or side effects associated with conventional therapies. [0009] Citation or identification of any reference in this section of this application is not to be construed as an admission that the reference is prior art to the present application. SUMMARY [0010] Provided herein are compounds having the following formula (I): ##STR00002## [0011] or a pharmaceutically acceptable salt, tautomer, isotopolog, or stereoisomer thereof, wherein R, Ring A and n are as defined herein. [0012] A compound of formula (I) or a pharmaceutically acceptable salt, tautomer, isotopolog, or stereoisomer thereof (each being referred to herein as an "Isoindolinedione Compound") is useful for treating or preventing DLBCL. [0013] In one aspect, provided herein are Isoindolinedione Compounds as described in the instant disclosure, such as, for example, in Table 1. [0014] In one aspect, provided herein are pharmaceutical compositions comprising an effective amount of an Isoindolinedione Compound as described herein, and a pharmaceutically acceptable carrier, excipient or vehicle. In some embodiments the pharmaceutical composition is suitable for oral, parenteral, mucosal, transdermal or topical administration. [0015] In one aspect, provided herein are methods for treating or preventing DLBCL, comprising administering to a subject in need thereof an effective amount of an Isoindolinedione Compound as described herein. In another aspect, provided herein are methods for treating or preventing DLBCL, comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition described herein. In another aspect, provided herein are Isoindolinedione Compounds as described herein for use in the treatment of DLBCL. In another aspect, provided herein are pharmaceutical compositions as described herein for use in the treatment of DLBCL. [0016] In another aspect provided herein are methods for preparing Isoindolinedione Compounds as described herein. [0017] The present embodiments can be understood more fully by reference to the detailed description and examples, which are intended to exemplify non-limiting embodiments. |
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