Carbazole compounds and therapeutic uses of the compounds

{
  "publication_number": "US9108916B2",
  "country": "US",
  "kind": "B2",
  "title": "Carbazole compounds and therapeutic uses of the compounds",
  "abstract": "Compounds of the general structural formula (I) and (II) and use of the compounds and salts and hydrates thereof, as therapeutic agents are disclosed. Treatable diseases and conditions include cancers, inflammatory diseases and conditions, and immunodeficiency diseases. (I), (II).",
  "claims": [
    "1. A method for treating a hematopoietic cancer, comprising administering to a patient in need thereof an effective amount of a compound of a structural formula: wherein R a is selected from the group consisting of C 1 - 6 alkyl, C 1 - 6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e, N(R e) 2, and SR e; alternatively, either R a and R 1 or NR e and R 1 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic or heterocyclic ring; R b is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e, N(R e) 2, and SR e, alternatively, either R b and R 6 or NR e and R 6 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic ring or a five or six-membered aliphatic carbocyclic or heterocyclic ring; R c is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e, or R c and R d are taken together to form a five, six, or seven-membered aliphatic ring, optionally containing an oxygen atom; R d is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e, or R d and R 7 together with the atoms to which they are attached form a five or six-membered aliphatic ring; R e, independently, is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or two R e groups taken together with a nitrogen to which they are attached to form a five or six-membered aliphatic ring; R 1, R 2, R 3, R 4, R 5, and R 6, independently, are selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, OR e, C(═O)R e, C(═O)OR e, OC(═O)R e, C(═O)N(R e) 2, C(═O)NR e SO 2 R e, N(R e) 2, NR e C(═O)R e, NR e C(═O)N(R e) 2, CN, NO 2, CF 3, OCF 3, SR e, SOR e, SO 2 N(Re) 2, and OSO 2 CF 3; R 7 is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and n is 1, 2, 3, 4, or 5, or a pharmaceutically acceptable salt or hydrate thereof.",
    "2. The method of claim 1, wherein the hematopoietic cancer is a leukemia or a lymphoma.",
    "3. The method of claim 2, wherein the leukemia or a lymphoma is one of acute lymphocytic leukemia, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, hairy cell leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, hairy cell lymphoma, histiocytic lymphoma, and Burkett's lymphoma.",
    "4. The method of claim 1, wherein the compound is",
    "5. A method for treating a tumor of the central and peripheral nervous system, comprising administering to a patient in need thereof an effective amount of a compound of a structural formula: wherein R a is selected from the group consisting of C 1 - 6 alkyl, C 1-6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e, N(R e) 2, and SR e; alternatively, either R a and R 1 or NR e and R 1 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic or heterocyclic ring; R b is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e, N(R e) 2, and SR e, alternatively, either R b and R 6 or NR e and R 6 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic ring or a five or six-membered aliphatic carbocyclic or heterocyclic ring; R c is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e, or R c and R d are taken together to form a five, six, or seven-membered aliphatic ring, optionally containing an oxygen atom; R d is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e, or R d and R 7 together with the atoms to which they are attached form a five or six-membered aliphatic ring; R e, independently, is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or two R e groups taken together with a nitrogen to which they are attached to form a five or six-membered aliphatic ring; R 1, R 2, R 3, R 4, R 5, and R 6, independently, are selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, OR e, C(═O)R e, C(═O)OR e, OC(═O)R e, C(═O)N(R e) 2, C(═O)NR e SO 2 R e, N(R e) 2, NR e C(═O)R e, NR e C(═O)N(R e) 2, CN, NO 2, CF 3, OCF 3, SR e, SOR e, SO 2 N(Re) 2, and OSO 2 CF 3; R 7 is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and n is 1, 2, 3, 4, or 5, or a pharmaceutically acceptable salt or hydrate thereof.",
    "6. The method of claim 5, wherein tumor of the central and peripheral nervous system is a glioblastoma or a neuroblastoma.",
    "7. The method of claim 5, wherein the compound is",
    "8. A method for treating a solid tumor, comprising administering to a patient in need thereof an effective amount of a compound of a structural formula: wherein R a is selected from the group consisting of C 1 - 6 alkyl, C 1 - 6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e, N(R e) 2, and SR e; alternatively, either R a and R 1 or NR e and R 1 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic or heterocyclic ring; R b is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR e, N(R e) 2, and SR e, alternatively, either R b and R 6 or NR e and R 6 together with the carbon atoms to which they are attached form a five or six-membered aliphatic carbocyclic ring or a five or six-membered aliphatic carbocyclic or heterocyclic ring; R c is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e, or R c and R d are taken together to form a five, six, or seven-membered aliphatic ring, optionally containing an oxygen atom; R d is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and C(═O)R e, or R d and R 7 together with the atoms to which they are attached form a five or six-membered aliphatic ring; R e, independently, is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or two R e groups taken together with a nitrogen to which they are attached to form a five or six-membered aliphatic ring; R 1, R 2, R 3, R 4, R 5, and R 6, independently, are selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, halo, OR e, C(═O)R e, C(═O)OR e, OC(═O)R e, C(═O)N(R e) 2, C(═O)NR e SO 2 R e, N(R e) 2, NR e C(═O)R e, NR e C(═O)N(R e) 2, CN, NO 2, CF 3, OCF 3, SR e, SOR e, SO 2 N(Re) 2, and OSO 2 CF 3; R 7 is selected from the group consisting of hydrogen, C 1-6 alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and n is 1, 2, 3, 4, or 5, or a pharmaceutically acceptable salt or hydrate thereof.",
    "9. The method of claim 5, wherein the solid tumor is one or more of a colorectal cancer, renal cancer, pancreatic cancer, head and neck cancer, prostate cancer, melanoma, and a lung cancer.",
    "10. The method of claim 8, wherein the compound is"
  ],
  "description_excerpt": "This invention relates to carbazole compounds, to methods of preparing the compounds, to pharmaceutical compositions containing the compounds, and to their use as therapeutic agents. In particular, the invention relates to carbazole compounds and their use in a variety of therapeutic areas, including the treatment of cancers.\n\nThe frequency of cancer in humans has increased in the developed world as the population has aged. For some types of cancers and the stage of disease at diagnosis, morbidity and mortality rates have not improved significantly in recent years despite extensive research. Induction of cell death is one of the most attractive cancer treatment strategies. There is a significant need to identify agents that are capable of inducing cell death in tumor cells and/or that potentiate chemotherapeutic and radiation therapies.\n\nThe present invention is directed to compounds and compositions that induce cell death, and to therapeutic uses of the compounds in the treatment of a cancer and other conditions in individuals in need of such treatment. The present invention also is directed to methods of preparing the therapeutic compounds. More particularly, the present invention is directed to compounds and methods of treating diseases and conditions such as cancers, inflammatory diseases, microbial infections, viral infections, and protozoan infections. The compounds are useful in a method comprising administering a therapeutically effective amount of a compound of structural formula (I) to an individual in need thereof.",
  "cpc": [
    "C07D 209/86",
    "A47C 13/005",
    "A47C 15/002",
    "A47C 17/045",
    "A47C 31/003",
    "A47C 4/028",
    "A47C 7/18",
    "A47C 7/20",
    "A61K 31/403",
    "A61K 31/439",
    "A61K 31/454",
    "A61K 31/506",
    "A61K 31/5377",
    "A61K 31/55",
    "A61K 9/0019",
    "A61P 17/00",
    "A61P 17/02",
    "A61P 17/06",
    "A61P 19/02",
    "A61P 19/10",
    "A61P 29/00",
    "A61P 31/00",
    "A61P 33/00",
    "A61P 33/02",
    "A61P 33/06",
    "A61P 35/00",
    "A61P 35/02",
    "A61P 35/04",
    "A61P 9/10",
    "C07D 209/88",
    "C07D 401/04",
    "C07D 487/04",
    "F16B 1/00",
    "F16B 12/00",
    "F16B 2200/81",
    "F16B 2200/83",
    "Y02A 50/30",
    "Y10T 29/49826",
    "Y10T 403/7164",
    "Y10T 403/7176"
  ],
  "ipc": [
    "A61K 31/4025",
    "A61K 31/403",
    "A61K 31/407",
    "A61K 31/4439",
    "A61K 31/454",
    "A61K 31/55",
    "C07D 209/82",
    "C07D 209/86",
    "C07D 209/88",
    "C07D 401/04",
    "C07D 403/06",
    "C07D 487/02",
    "C07D 487/04"
  ],
  "assignees": [
    "INCURON LLC"
  ],
  "inventors": [
    "TUCKER JOHN",
    "SVIRIDOV SERGEY",
    "BRODSKY LEONID",
    "BURKHART CATHERINE",
    "PURMAL ANDREI",
    "GUROVA KATERINA",
    "GUDKOV ANDREI"
  ],
  "filing_date": "2014-04-01",
  "publication_date": "2015-08-18",
  "grant_date": "2015-08-18",
  "priority_date": "2008-10-06",
  "application_number": "US-201414231841-A",
  "family_id": "41503680",
  "citations": [
    "DE2715680A1",
    "US2005143442A1",
    "US2015045406A1",
    "US7169802B2",
    "WO2004035580A1",
    "WO2008008155A2"
  ]
}