Telik, Inc.

Cv Therapeutics, Inc.

Verrica Pharmaceuticals Inc.

Other

Leland Stanford Junior University

Steven R Schow

Robert T Lum

Michael M Wick

Michael R Kozlowski

Songyuan Shi

Louise Robinson

Prasad V V S V Manchem

Alison Joly

Richard L Mackman

Suresh Kerwar

Pavel E Zhichkin

Wayne R Spevak

Matthew Gene Davidson

R Jason Herr

Cheri Lynn Blum

Marek G Nelson

Harold Meckler

Hugo O Villar

William Allen Boulanger

Natalia Aurrecoechea

Reyna J Simon

Lisa Wang

Dennis L Edie

Robert W Macsata

Ronan Y Guevel

Pedro E Hernandez Abad

Jeff A Zablocki

Prabha N Ibrahim

Steven James Collier

Richard Neil Zare

Lawrence M Kauvar

Stephan D Parent

Jurg R Pfister

Robert J Greenhouse

George Frederic Schreiner

Jeffery A Zablocki

Matthew H Lyttle

Garry Southan

Robert Moore

Kevin T Weber

Brian T Peterson

Fanying Meng

Wenli Ma

Dean W Felsher

Peter Wuts

Andrew B Kelson

Thomas Redelmeier

David R Allen

Brad Melvin Loertscher

Anthony J Sanchez

Nicholas M Santiago

Chunsheng Qiao

Stephen A Eastham

Prabbha Ibrahim

Nicolas Cairns

Hans J Kjaersgaard

Micheal M Wick

Robert E Polomski

Jeong Weon Park

Steven Richards

David Loughhead

Katherine Margulis

Feng Jin

Arvin Gouw

Brian Matthew Eklov

Steven J Collier

Pedro E Hernández Abad

Jason R Herr

Pavel Zhichkin

The invention provides synthetic methods for the preparation of cantharidin and analogs thereof. In one aspect, the invention provides an improved Diels-Alder cycloaddition to generate a key intermediate en route to cantharidin and analogs thereof. In certain embodiments, the new Diels-Alder reaction involves reacting Compound (2) in the presence of furan, and in the absence of acid or increased pressure, in an aprotic polar solvent with slight warming, to yield Compound (1) in favorable yield and exo-endo ratio. In another aspect, the invention also provides a new Diels-Alder reaction between compounds of Formula (III) and furan to yield compounds of Formula (IV), which can then be transformed into cantharidin or analogs thereof. In yet another aspect, the invention describes a new palladium-mediated carbonylation providing another key intermediate en route to cantharidin and analogs thereof. In addition to synthetic methods, present invention also provides compounds (i.e., intermediates) useful in the synthesis of cantharidin and analogs thereof. Compounds provided herein may have biological activity, and therefore may be used in the treatment of diseases or conditions (e.g., infectious diseases and skin conditions).

Synthesis of cantharidin

Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome and hyperlipidemia.

Inhibitors of phospholipid synthesis and methods of use

The present disclosure provides methods for purifying a solution comprising cantharidin and cantharidin-associated impurities. A method to purify the solution can comprise recrystallization or sublimation, for example. The purified cantharidin can be analyzed using a detection method comprising a stationary phase and one or more mobile phases.

Quantification and preparation of pharmaceutical grade cantharidin

The present disclosure provides methods for synthesizing cantharidin and cantharidin derivatives.

Commercially viable synthesis of cantharidin and bioactive cantharidin derivatives

Disclosed herein are tablets comprising ezatiostat hydrochloride wherein the ezatiostat hydrochloride comprises from about 75 to about 82 percent by weight of the tablet.

Tablet formulation of ezatiostat

A process for and intermediates in the preparation of canfosfamide and its salts. Some of the intermediates have anticancer activity.

Process for and intermediates in the preparation of canfosfamide and its salts

Sulfonylethyl and thioethyl phosphorodiamidates, their preparation and intermediates in their preparation, formulations containing them, and their pharmaceutical use. The compounds are useful for treating cancer, alone and in combination with other anticancer therapies.

Sulfonylethyl phosphorodiamidates

Tripeptide and tetrapeptide sulfones, pharmaceutical compositions containing them, their pharmaceutical use, and their preparation, are disclosed. The compounds are useful in potentiating the cytotoxic effects of chemotherapeutic agents in tumor cells, selectively exerting toxicity in tumor cells, elevating the production of GM progenitors in bone marrow cells, stimulating the differentiation of bone marrow, mitigating the myelosuppressive effects of chemotherapeutic agents, and modulating hematopoiesis in bone marrow.

Tripeptide and tetrapeptide sulfones

Tripeptide and tetrapeptide thioethers, pharmaceutical compositions containing them, their pharmaceutical use, and their preparation. The compounds are useful in potentiating the cytotoxic effects of chemotherapeutic agents in tumor cells, selectively exerting toxicity in tumor cells, elevating the production of GM progenitors in bone marrow, stimulating the differentiation of bone marrow, mitigating the myelosuppressive effects of chemotherapeutic agents, and modulating hematopoiesis in bone marrow.

Tripeptide and tetrapeptide thioethers

Compounds of the following formula are provided: In the Formula (I), Ris &#x2014;X&#x2014;R'; in which R&#x2032; is optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocyclyl, and X is &#x2014;NH&#x2014;. Ris lower alkyl optionally substituted with one, two or three groups chosen from hydroxy, lower alkoxy, and halogen. And Ris &#x2014;NRR; in which Ris hydrogen and Ris lower alkyl substituted with amino; or (ii) Rand Rare both lower alkyl optionally substituted with one, two or three groups chosen from hydroxy and amino. It is to be understood that R&#x2032; is not cyclohexylmethyl, phenyl, substituted phenyl, benzyl, phenylethyl, or m-hydroxybenzyl. The compounds inhibit CDK-2 activity and are useful for treating disorders characterized by undesirable cell proliferation.

Purine inhibitors of cyclin dependent kinase 2 and I&#x3ba;B-&#x3b1;

Compounds of formula I are useful for treating conditions associated with hyperglycemia, especially Type II diabetes. These compounds are useful in stimulating the kinase activity of the insulin receptor, activating the insulin receptor, and stimulating the uptake of glucose. Pharmaceutical compositions comprising the antidiabetic compounds are also disclosed.

Naphthalene ureas as glucose uptake enhancers

Pharmaceutical compositions and methods of using them. Lipid formulations of a glutathione analog and methods of manufacturing them. Their use to stimulate hematopoiesis, protect hematopoietic cells from damage caused by radiation or chemotherapy, or potentiate the stimulatory action of one or a combination of cytokines on colony formation by hematopoietic progenitor cells, protect a subject from a destructive effect of a chemotherapeutic agent or irradiation, or to potentiate the effect of a chemotherapeutic agent.

Therapeutic compositions containing glutathione analogs

Purine inhibitors of cyclin dependent kinase 2 & ikappabalpha

Growing community of inventors

Redwood City, CA, United States of America

Steven R Schow