Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists.

21:38 EDT 22nd October 2014 | BioPortfolio

Summary of "Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists."

This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model.

Affiliation

Sunesis Pharmaceuticals, Inc., 395 Oyster Point Blvd., Suite 400, South San Francisco, CA 94080, USA.

Journal Details

This article was published in the following journal.

Name: Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Pages:

Links

PubMed Articles [6229 Associated PubMed Articles listed on BioPortfolio]

A PLK4 Inhibitor Has Single-Agent Activity in Preclinical Tumor Models.

CFI-400945 is a potent, selective, orally bioavailable PLK4 inhibitor with antitumor activity in vivo.

The discovery of potent, orally bioavailable pyrimidine-5-carbonitrile-6-alkyl CXCR2 receptor antagonists.

A hit-to-lead optimisation programme was carried out on the Novartis archive screening hit, pyrimidine 2-((2,6-dichlorobenzyl)thio)-5-isocyano-6-phenylpyrimidin-4-ol 4, resulting in the discovery of C...

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable stearoyl-CoA desaturase-1 (SCD1) inhibitors: Part 2. Pyridazine-based analogs.

Design, synthesis, and biological evaluation of pyridazine-based, 4-bicyclic heteroaryl-piperidine derivatives as potent stearoyl-CoA desaturase-1 (SCD1) inhibitors are described. In a chronic study o...

Synthesis, Antitubulin, and Antiproliferative SAR of C3/C1-Substituted Tetrahydroisoquinolines.

The syntheses and antiproliferative activities of novel substituted tetrahydroisoquinoline derivatives and their sulfamates are discussed. Biasing of conformational populations through substitution on...

Discovery of N-substituted Oseltamivir Derivatives as Potent and Selective Inhibitors of H5N1 Influenza Neuraminidase.

To discover Group-1-specific neuraminidase (NA) inhibitors that are especially involved in combating the H5N1 virus, two series of oseltamivir derivatives were designed and synthesized by targeting th...

Clinical Trials [824 Associated Clinical Trials listed on BioPortfolio]

A Phase 1 Dose Escalation Study of IPI-493

IPI-493 is a potent inhibitor of heat shock protein 90 (Hsp90) and is orally bioavailable via a novel formulation.

Alicaforsen (ISIS 2302) in Patients With Active Crohn's Disease

ISIS 2302 is an antisense oligonucleotide drug that reduces the production of a specific protein called intercellular adhesion molecule (ICAM-1), a substance that plays a significant role ...

Discovery Elbow Multi-Center Prospective Study

The purpose of this prospective clinical trial is to document the performance and clinical outcomes of Biomet Discovery Elbow.

Hydroxychloroquine and Gefitinib to Treat Lung Cancer

Non-small cell lung cancer (NSCLC) is the most common cause of cancer mortality in men and women in Singapore.Chemotherapy and biologically targeted agents can extend survival only modestl...

A Clinical Investigation of the Discovery™ Elbow System

The purpose of this study is to perform a five-year, multi-center prospective evaluation of the Discovery™ Elbow System for outcome and durability. Relief of pain and restoration of fun...

Medical and Biotech [MESH] Definitions

A long-acting beta-2-adrenergic receptor agonist. It is a potent bronchodilator that may be administered orally or by aerosol inhalation.

Morphine derivatives of the methanobenzazocine family that act as potent analgesics.

A toxic compound, isolated from the Spanish fly or blistering beetle (Lytta (Cantharis) vesicatoria) and other insects. It is a potent and specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.

Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.

A plant family of the order Cornales, subclass Rosidae, class Magnoliopsida, consisting of slow-growing evergreen trees common in tropical forests of south India and Burma. Members contain tetrahydroisoquinoline-monoterpene and iridoid glycosides.

Search BioPortfolio:
Loading
Advertisement

Relevant Topic

Antibodies
Latest News Clinical Trials Research Drugs Reports Corporate
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...

Advertisement