Abstract: Novel spermicidal compounds which are organometallic cyclopentadienyl metal complexes, particularly vanadium IV complexes, are described including corresponding contraceptive and therapeutic compositions and method for providing contraception and selective killing of testicular germ cells. Included among the vanadium complexes are vanadocene dichloride, vanadocene dibromide, bis (methyl cyclopentadienyl) vanadium dichloride, vanadocene diiodide, vanadocene di-pseudohalides, and others. Most active found was vanadocene diselenocyanate.
Type:
Application
Filed:
September 29, 2003
Publication date:
September 1, 2005
Applicant:
Parker Hughes Institute
Inventors:
Osmond D'Cruz, Phalguni Ghosh, Fatih Uckun
Abstract: Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. Thes novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-1). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzyloxopyrimidine (DABO), and of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes. The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.
Abstract: Novel compounds that are potent inhibitors of HIV reverse transcriptase (RT) are described in the invention. Thes novel compounds also inhibit replication of a retrovirus, such as human immunodeficiency virus-1 (HIV-1). The novel compounds of the invention include analogs and derivatives of phenethylthiazolylthiourea (PETT), of dihydroalkoxybenzyloxopyrimidine (DABO), and of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). The invention additionally provides a composite HIV reverse-transcriptase (RT) nonnucleoside inhibitor (NNI) binding pocket constructed from a composite of multiple NNI-RT complexes The composite RT-NNI binding pocket provides a unique and useful tool for designing and identifying novel, potent inhibitors of reverse transcriptase.
Abstract: Methods for increasing the elimination half-life of key metabolites such as d4T by administering an aryl phosphate derivative of d4T having an electron withdrawing substituent on the aryl group and an amino acid substituent on the phosphate group are described. A preferred aryl phosphate derivative of d4T is HI-113 (d4T-5?-[p-bromophenyl methoxyalaninyl phosphate]). The administration of HI-113 results in more prolonged systemic exposure to the key metabolites, Ala-d4T-MP and d4T, than administration of an equimolar dose of either metabolite. Each metabolite has a significantly longer elimination half life when formed in vivo from the administration of HI-113 than when the metabolite is administered directly.
Type:
Application
Filed:
October 26, 2004
Publication date:
June 30, 2005
Applicant:
Parker Hughes Institute
Inventors:
Fatih Uckun, Chun-Lin Chen, Taracad Venkatachalam, Zhoa-Hai Zhu
Abstract: Synthetic Phorboxazole A and derivatives thereof for the treatment of cancer, including inhibition of cancer cell growth, induction of apoptosis, and inhibition of metastises.
Type:
Application
Filed:
September 28, 2004
Publication date:
June 2, 2005
Applicants:
Parker Hughes Institute, Regents of the University of Minnesota
Inventors:
Fatih Uckun, Rama Narla, Craig Forsyth, Chi Lee, Feryan Ahmed, Russell Cink
Abstract: This invention provides combinatorial chemistry libraries containing thiourea and urea compounds. In addition, the invention relates to methods for constructing combinatorial chemistry libraries containing thiourea and urea compounds. Furthermore, this invention relates to methods for the identification of bioactive thiourea and urea compounds as well as compositions and therapeutic methods for treating cancer.
Type:
Application
Filed:
September 21, 2004
Publication date:
May 5, 2005
Applicant:
Parker Hughes Institute
Inventors:
Zhaohai Zhu, Chen Mao, Rama Narla, Fatih Uckun
Abstract: Novel compounds and pharmaceutical compositions useful as EGFR tyrosine kinase inhibitors. Methods of the invention include administration of the EGFR TK inhibitors to treat diseases characterized by enhanced expression of EGF, including cancers, particularly breast cancer. Additionally, a homology model representing the structure of EGFR kinase domain is provided, which model is useful for the rationally design and screening of compounds predicted to bind favorably to EGFR and to inhibit EGFR TK.
Type:
Grant
Filed:
September 5, 2001
Date of Patent:
March 8, 2005
Assignee:
Parker Hughes Institute
Inventors:
Fatih M. Uckun, Yaguo Zheng, Sutapa Ghosh
Abstract: Methods for increasing the elimination half-life of key metabolites such as d4T by administering an aryl phosphate derivative of d4T having an electron withdrawing substituent on the aryl group and an amino acid substituent on the phosphate group are described. A preferred aryl phosphate derivative of d4T is HI-113 (d4T-5′-[p-bromophenyl methoxyalaninyl phosphate]). The administration of HI-113 results in more prolonged systemic exposure to the key metabolites, Ala-d4T-MP and d4T, than administration of an equimolar dose of either metabolite. Each metabolite has a significantly longer elimination half life when formed in vivo from the administration of HI-113 than when the metabolite is administered directly.
Type:
Grant
Filed:
October 19, 2001
Date of Patent:
November 30, 2004
Assignee:
Parker Hughes Institute
Inventors:
Fatih Uckun, Chun-Lin Chen, Taracad K. Venkatachalam, Zhoa-Hai Zhu
Abstract: The invention provides methods for treating cancer and compounds that are useful for the treatment of tumors, as well as pharmaceutical compositions comprising the compounds, and synthetic methods and intermediates useful for preparing the compounds.
Type:
Application
Filed:
May 28, 2004
Publication date:
November 25, 2004
Applicant:
Parker Hughes Institute
Inventors:
Faith M. Uckun, Yanhong Dong, Phalguni Gosh
Abstract: Compounds are described that bind to tubulin causing tubulin depolymerization and inhibiting tubulin polymerization. The compounds of the invention are therapeutically effective to inhibit cellular proliferation, for example, as effective anti-cancer agents. The compounds can also induce cytotoxicity in cells such as leukemia cells. The chemical structure of the compounds includes a furan, thiophene, thiazole, oxazole, or imidazole group at one end of the molecule (head) and a hydrophobic, aliphatic chain at the other end of the molecule (tail).
Abstract: The invention provides a method for inhibiting c-jun activation in mammalian or avian cells comprising contacting the cells with a substance that inhibits the activity of Janus family kinase 3 (JAK-3). The invention also provides a therapeutic method for preventing or treating a pathological condition in a mammal wherein c-jun activation is implicated and inhibition of its activation is desired comprising administering to a mammal in need of such therapy, an effective amount of a substance that inhibits the activity of JAK-3. Novel compounds that are JAK-3 inhibitors, as well as pharmaceutical compositions comprising the compounds are also provided.
Abstract: The invention provides novel JAK-3 inhibitors that are useful for treating leukemia and lymphoma. The compounds are also useful to treat or prevent skin cancer, as well as sunburn and UVB-induced skin inflammation. In addition, the compounds of the present invention prevent the immunosuppressive effects of UVB radiation, and are useful to treat or prevent autoimmune diseases, inflammation, and transplant rejection. The invention also provides pharmaceutical compositions comprising compounds of the invention, as well as therapeutic methods for their use.
Type:
Application
Filed:
November 17, 2003
Publication date:
September 30, 2004
Applicant:
Parker Hughes Institute
Inventors:
Fatih M. Uckun, Elise A. Sudbeck, Marina Cetkovic, Ravi Malaviya, Xing-Ping Liu
Abstract: Synthetic Phorboxazole A and derivatives thereof for the treatment of cancer, including inhibition of cancer cell growth, induction of apoptosis, and inhibition of metastises.
Type:
Grant
Filed:
May 14, 2002
Date of Patent:
September 28, 2004
Assignees:
Parker Hughes Institute, Regents of the University of Minnesota
Inventors:
Fatih M. Uckun, Rama K. Narla, Craig Forsyth, Chi Sing Lee, Feryan Ahmed, Russell Drew Cink
Abstract: This invention provides combinatorial chemistry libraries containing thiourea and urea compounds. In addition, the invention relates to methods for constructing combinatorial chemistry libraries containing thiourea and urea compounds. Furthermore, this invention relates to methods for the identification of bioactive thiourea and urea compounds as well as compositions and therapeutic methods for treating cancer.
Type:
Grant
Filed:
September 19, 2001
Date of Patent:
September 21, 2004
Assignee:
Parker Hughes Institute
Inventors:
Zhaohai Zhu, Chen Mao, Rama K. Narla, Fatih M. Uckun
Abstract: Aryl phosphate derivatives of d4T with para-bromo substitution on the aryl group show markedly increased potency as anti-HIV agents without undesirable levels of cytotoxic activity. In particular, these derivatives are potent inhibitors of HIV reverse transcriptase. In a preferred aspect of the present invention, the phosphorus of the aryl phosphate group is further substituted with an amino acid residue that may be esterified or substituted, such as a methoxy alaninyl group.
Abstract: Contraceptive activity as well as anti-microbial, particularly anti-viral protection is provided by contraceptive compositions containing a thiourea compound of the invention exhibiting spermicidal or sperm-immobilizing activity. Preferred compounds of the invention are cyclohexenyl-substituted thiourea compounds.