University of Pennsylvania

Other

University of California

Dana-farber-cancer Institute Inc.

Bryn Mawr College

Johns Hopkins University

Columbia University

University Patents, Inc.

Kosan Biosciences Incorporated

Monell Chemical Senses Center

Val-chum, Limited Partnership

Acidophil, LLC

Amos B Smith, Iii

Ralph F Hirschmann

Paul A Sprengeler

Thomas James Beauchamp

Carlo Ballatore

Matthew J LaMarche

David R Jones

Virginia Man-Yee Lee

John Q Trojanowski

Kurt R Brunden

Michael D Kaufman

Kaoru Kobayashi

Yuping Qiu

Adam T Hoye

Joseph G Sodroski

Navid Madani

Amy M Princiotto

Bruno Melillo

Judith M LaLonde

Hirokazu Arimoto

Xiaozhao Wang

David C Myles

Ernesto Freire

Joel R Courter

Simon James Shaw

Wayne A Hendrickson

Carol M Taylor

Won-Suk Kim

Hiroyuki Ikumura

Brian Scott Freeze

Tomoyasu Hirose

Matthew Le-Khac

Anne-Marie L Hogan

Hirokaza Arimoto

Takahiro Soeta

Akihisa Yokoyama

Kraig M Yager

Ryan C Holcomb

Francesco Piscitelli

Terence Keenan

Dionicio Martinez-Solorio

Rongbiao Tong

Minh Huu Nguyen

Mark Guzman

Luis Sanchez

John L Wood

Hu Liu

Peter D Kwong

John R Mascola

James William Leahy

Donna Mary Huryn

David Michael Jones

Zhuqing Liu

Paul Vincent Rucker

Young Do Kwon

Paul S Anderson

Barry S Cooperman

Jeffrey P Ciavarri

Joel Desharnais

Xueling Wu

Mark A Burlingame

Ming Xian

Kurt Frederick Sundermann

Angelo J Castellino

Danny Ng

Thomas M Razler

Alexander W Sun

Chengzao Sun

Gary K Beauchamp

Tadeusz F Molinski

Alison L Fisher

Bruce P Bryant

Wenqing Yao

Arne Schön

Tomoyasu Ishikawa

Ignació Brouard Martin

Thomas Nittoli

Killian Oukoloff

Sherrie Pietranico-Cole

William C Shakespeare

P Grant Spoors

Chihui An

Rachel D Van Rijn

Maria A Cichy-Knight

John Hynes, Jr

Toyoharu Kobayashi

Jongwoo Park

David A Favor

Andrew B Benowitz

Bari A Barwis

Setsuya Sasho

Paul Laub

Doralyn S Dalisay

Shrikumar Nair

Donna M Huym

Sugiyama Shimpei

Catherine Peyrot Des Gachons

Jeffrey B Sperry

Paul A S Breslin

Onur Atasoylu

Compounds and methods of treating HIV-1 in a human infected with HIV-1 or preventing HIV-1 infection in a human susceptible to infection with HIV-1 are provided. The compounds are of formula (I), (II), and (IA), wherein R-R, X, X', Y, Y′, Z, and n are defined herein, and the methods comprises administering therapeutically effective amounts of these compounds to the human.

Small molecules that sensitize HIV-1 infected cells to antibody dependent cellular cytotoxicity

The present disclosure provides compounds of formula (I) or (II) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Rx-R8 are defined herein. Also provided are compositions comprising a compound described herein and a pharmaceutically effective excipient, methods of stabilizing microtubules in a patient comprising administering to the patient a microtubule-stabilizing amount of a compound described herein, methods of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein, and methods of treating a neurodegenerative disease in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein. 

Substituted [1,2,4]triazolo[1,5-a]pyrimidines for stabilizing microtubules

The disclosure provides compositions and methods for sensitizing primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies, e.g., those directed against CD4-induced (CD4i) epitopes and the V3 region. In certain embodiments, the disclosure relates to the use of small molecules as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.

Inhibitors of HIV-1 entry and methods of use thereof

The present disclosure pertains to the field peptide stapling and/or macrocyclization, where a structural motif is used to improve the properties of amino acid sequences (e.g. protease resistance, cellular penetration, biological activity). Also within the scope of the disclosure are methods for unstapling the S,S-tetrazine-containing amino acid sequence. The disclosure is also directed to methods for the reductive removal of thiocyanates from an amino acid sequence with cysteine to recycle back to the native amino acid sequence.

Methods of stapling and unstapling peptides and proteins

Compositions and methods using silicon-based cross-coupling agents in the formation of carbon-carbon and carbon-nitrogen bonds are described.

Silicon-based cross coupling agents and methods of their use

The invention provides for compounds of formula I: wherein Z is absent or (CRR)W; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHR, NRR, SH, S(O)R; or (iii) Rand Rtogether form C(O); W is absent, C(O), C(O)O, C(O)NRR, O, S(O), or NRR; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NRR; wherein Rand Rare each independently H, alkyl or aryl; Xis selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each Ris independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof. 

Small molecule CD4 mimetics and uses thereof

The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.

Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies

The present invention is directed to compounds of formula I: wherein A is n is 0, 1, or 2; m is 0 or 1; Ris H or Calkyl and Ris H, Calkyl, Calkaryl, aryl, or heteroaryl; and X is O or NH. Tautomers, enantiomers, and diastereomers, as well as pharmaceutically acceptable salt forms, of compounds of formula I are also within the scope of the invention. Methods of preparing and using the compounds of formula I are also described.  

Cycloalkyl-dione derivatives and methods of their use

The present invention is directed to irciniastatin analogs. Uses of these analogs also described.

Irciniastatin analogues

Described herein are small-molecule mimics of CD4, which both enter the Phe43 cavity and target Asp368 of gp120, the HIV-1 envelope protein. Also described herein are methods of using these compounds to inhibit the transmission or progression of HIV infection. These compounds exhibit antiviral potency greater than that of a known antiviral, NBD-556, with 100% breadth against clade B and C viruses. Importantly, the compounds do not activate HIV infection of CD4-negative, CCR5-positive cells, in contrast to NBD-556.

CD4-mimetic inhibitors of HIV-1 entry and methods of use thereof

The present invention is directed to hemi phorboxazole A: and its stereoisomers, as well as derivatives of hemi phorboxazole A of formula I: wherein ring A is aryl or a 5- or 6-membered heteroaryl optionally substituted with one or more of halogen, &#x2014;OH, or &#x2014;Calkyl; and R is &#x2014;CN, a 5- or 6-membered heteroaryl, or halogen; and the pharmaceutically acceptable salt forms thereof, in addition to methods of using these compounds. 

Hemi-phorboxazole A derivatives and methods of their use

The present invention relates to novel TP receptor antagonists, which optionally cross the blood-brain barrier of a mammal. The invention also provides methods for treating a disorder related to activation of TP receptor utilizing the compounds of the invention.

Thromboxane A2 (TP) receptor antagonists

The invention provides oleocanthal analogs and methods of using oleocanthals in various formulations including, food additives; pharmaceuticals; cosmetics; animal repellants; and discovery tools for mammalian irritation receptor genes, gene products, alleles, splice variants, alternate transcripts and the like.

Use of the irritating principal oleocanthal in olive oil, as well as structurally and functionally similar compounds

The present invention is directed to carboxylic acid-containing pharmaceutical compounds where the carboxylic acid moieties have been substituted with cycloalkyl-dione derivatives, as well as tautomers and pharmaceutically acceptable salt forms thereof. These bioisosteric replacements improve the compound's ability to effectively cross the blood brain barrier and result in improved pharmacokinetic, toxicological, and/or safety profiles.

Growing community of inventors

Merion, PA, United States of America

Amos B Smith, Iii