Yale University

Harvard College

Seth Herzon

Maung Kyaw Moe Tun

Andrew G Myers

Peter M Glazer

Christina Woo

Jeremy Earle Wulff

Jakub Svenda

Alan Healy

Romain Siegrist

Matthew Allen Zajac

Maung Kyaw Tun

Maung Kway Moe Tun

The invention provides (1) processes for making substantially-pure (−) huperzine A and substantially-pure (−) huperzine A derivatives; (2) compositions useful in making substantially-pure (−) huperzine A and substantially-pure (−) huperzine A derivatives; and (3) methods of treating or preventing neurological disorders using substantially-pure (−) huperzine A and substantially-pure (−) huperzine A derivatives.

(−)-huperzine A processes and related compositions and methods of treatment

The invention provides (1) processes for making substantially-pure (&#x2212;) huperzine A and substantially-pure (&#x2212;) huperzine A derivatives; (2) compositions useful in making substantially-pure (&#x2212;) huperzine A and substantially-pure (&#x2212;) huperzine A derivatives; and (3) methods of treating or preventing neurological disorders using substantially-pure (&#x2212;) huperzine A and substantially-pure (&#x2212;) huperzine A derivatives.

(&#x2212;)-huperzine A processes and related compositions and methods of treatment

The present invention is directed to novel anticancer compounds which show excellent activity as anticancer agents. The present invention is also directed to pharmaceutical compositions based upon these compounds and methods of treating cancer, including drug resistant, multiple drug resistant, metastatic and recurrent cancer.

Compounds and methods for treating cancer

(&#x2212;)-Huperzine A processes and related compositions and methods of treatment

The present invention is directed to novel anti-cancer compounds and methods of treating and/or inhibiting cancer in patients, including metastatic cancer, recurrent cancer and drug resistant cancers, including multiple drug resistant cancers. Compounds according to the present invention provide anti-cancer activity, at least in part, by virtue of their nucleotide intercalating activity through the use of analogs of (&#x2212;)lomaiviticin A, a potent anticancer agent which exhibits cytotoxicity through its principal mechanism of cleavage and to a lesser extent, its intercalation of cellular polynucleotides, especially DNA. In additional embodiments, compounds according to the present invention are also conjugated and/or linked to other bioactive agents, especially agents which selectively target cancer cells (cancer cell targeting moiety or CCTM) to target and increase the delivery of the anticancer agent to the cancer cell. These targeting agents include folate receptor-targeted moieties, other cancer binding moieties such as PMSA binding moieties as otherwise described herein and antibodies, including single chain variable fragment antibodies (scFv antibodies). Pharmaceutical compositions based upon these novel compounds are also disclosed pursuant to the present invention. Methods of treating, inhibiting and/or reducing the likelihood of cancer, including metastatic and recurrent cancer and drug resistant, including multiple drug resistant cancer in a patient are also disclosed.

Anti-cancer compounds and methods for treating cancer

The syntheses of the natural products, avrainvillamide and stephacidin B, are provided. The &#x3b1;,&#x3b2;-unsaturated nitrone functionality of avrainvillamide and its 3-alkylidene-3H-indole 1-oxide core is shown to covalently and reversibly bond to heteroatom-based nucleophiles. This capability may allow these molecules to bind active site nucleophiles and may provide the basis for designing potent and selective enzyme inhibitors. Both avrainvillamide and its dimer stephacidin B have been reported to exhibit antiproliferative activity, and avrainvillamide has been reported to exhibit antimicrobial activity against multi-drug resistant bacteria. Avrainvillamide has been found to target cytoskeleton-linking membrane protein (CLIMP-63) thereby preventing cells from undergoing mitosis. The invention provides syntheses of these natural products as well as analogs of these natural products and their functional cores. The compounds of the invention may be used in the treatment of diseases such as cancer, autoimmune diseases, and bacterial infection.

Synthesis of avrainvillamide, strephacidin B, and analogues thereof

Growing community of inventors

New Haven, CT, United States of America

Seth Herzon