The Johns Hopkins University

Guilford Pharmaceuticals, Inc.

ÚStav Organické Chemie A Biochemie Av {Hacek Over (c)}r, V.v.i.

Institute of Organic Chemistry and Biochemistry Ascr, V.v.i.

Ustav Organicke Chemie a Biochemie Av Cr, V.v.i.

Dracen Pharmaceuticals, Inc.

Sequoia Pharmaceuticals, Inc.

Ustav Organicke Chemie a Biochemie Akademie Ved Cr, V.v.i.

Ustav Makromolekularni Chemie Av Cr, V.v.i.

Univerzita Karlova V Praze, Prirodovedecka Fakulta

Institute of Organic Chemistry & Biochemistry

Inst of Organic Chem. and Biochemistry As Cr V.v.i

ÚStav Organické Chemie A Biochemie Av {Hacek Over (c)}{hacek Over ( )}R, V.v.i.

Pavel Majer

Barbara S Slusher

Rana Rais

Andrej Jancarik

Lukas Tenora

Tomas Tichy

Takashi Tsukamoto

Doris Stoermer

Marcela Krecmerova

Jan Vavra

Jonathan David Powell

Jan Konvalinka

Yiyang Shao

Pavel Sacha

Jiri Schimer

Jon Philip Lawson

Judson Englert

Vaclav Navratil

Robert Christian Wild

Jinxiao Chu

Jinchao Weng

Katerina Novotna

Robert Leone

Paul F Jackson

Keith M Maclin

Michael Eissenstat

Eric Yanjun Wang

Gregory J Riggins

Weizheng Xu

Rena S Lapidus

Qun Liu

Petr Cigler

Karel Ulbrich

Jiri Strohalm

Tomas Knedlik

Vladimir Subr

Rongjuan Lu

Peter Michael Hudlicky

Brian Grella

Bunda Hin

Kvido Strisovsky

Jesse Alt

Martin Hadzima

Jan Tykvart

Lukáš Tenora

Ivan Šnajdr

Stanco Stancev

Frantisek Sedlak

Anezka Ticha

Andrei Jancarik

Jonathan Powell

The present disclosure provides methods of preparing a compound of Formula (I): wherein R, R, and Rare as defined as set forth in the application. In one embodiment, a compound of Formula (I) is prepared in >95% chemical purity and >95% enantiomeric excess.

Method of preparing a DON prodrug from L-glutamic acid

Glutamine antagonists and their use for treating oncological, immunological, and neurological diseases are disclosed. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder, the method comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof. Also disclosed are methods of enhancing the effects of an immune checkpoint inhibitor, enabling a subject to respond to an immune checkpoint inhibitor, or enabling the toxicity or the dose or number of treatments with an immune checkpoint inhibitor to be reduced, comprising administering to a subject in need of treatment thereof a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof, and an immune checkpoint inhibitor. Also disclosed are methods for treating an oncological, immunological, infectious or neurological disease or disorder that is refractory to checkpoint inhibitor therapy, the method comprising administering to a subject in need thereof, and having the refractory disease or disorder, a therapeutically effective amount of a glutamine antagonist of the disclosure or the pharmaceutical composition thereof.

Glutamine antagonists and uses thereof

Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA.

Prodrugs of prostate specific membrane antigen (PSMA) inhibitor

The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R, R, R′, and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Prodrugs of glutamine analogs

Prodrugs of hydroxamate-based GCPII inhibitors and methods of their use for treating a disease or condition are disclosed.

Prodrugs of hydroxamate-based GCPII inhibitors

The present disclosure provides a method of preparing a compound of Formula I, wherein Ris C-Calkyl; Ris C1-C4 alkyl; and Ris selected from the group consisting of C-Calkyl, (aryl)alkyl, and (heteroaryl)alkyl in &#x3e;95% chemical purity and &#x3e;95% enantiomeric excess.

Method of preparing a DON prodrug from L-pyroglutamic acid

The disclosure provides methods of treating cancer in a subject or preventing a relapse or reducing the incidence of relapse of cancer in a subject in remission, comprising administering to the subject: (a) a therapeutically effective amount of an immunotherapeutic agent, e.g., an immune checkpoint blockade therapy, an adoptive cellular therapy, a marrow-infiltrating lymphocytes, an adenosine A2aR inhibitor, or an antibody; and (b) a compound having formula (I): and the pharmaceutically acceptable salts thereof, wherein R, R, R', and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON).

Methods for cancer and immunotherapy using prodrugs of glutamine analogs

Prodrugs of mebendazole and methods for their use in treating a disease, disorder, or disorder, including cancer, are disclosed.

Mebendazole prodrugs with enhanced solubility and oral bioavailability

Prodrugs of glutamine analogs, such as prodrugs of acivicin, are disclosed.

Prodrug compositions and utility of hydroxamate-based GCPII inhibitors

The disclosure provides compounds having formula (I): and the pharmaceutically acceptable salts thereof, wherein R, R, R', and X are as defined as set forth in the specification. Compounds having formula (I) are prodrugs that release glutamine analogs, e.g., 6-diazo-5-oxo-L-norleucine (DON). The disclosure also provides compounds having formula (I) for use in treating cancer.

Compounds useful for the treatment of malaria, cancer, Parkinson's disease, diabetes, and bacterial infection.

Peptidyl ketoamides as inhibitors of rhomboid proteases

Growing community of inventors

Sykesville, MD, United States of America

Pavel Majer