Advertisement

Topics

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

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

DeepDyve research library

PubMed Articles [6352 Associated PubMed Articles listed on BioPortfolio]

Discovery of 2-((R)-4-(2-Fluoro-4-(methylsulfonyl)phenyl)-2-methylpiperazin-1-yl)-N-((1R,2s,3S,5S,7S)-5-hydroxyadamantan-2-yl)pyrimidine-4-carboxamide (SKI2852): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1).

A series of picolinamide- and pyrimidine-4-carboxamide-based inhibitors of 11β-hydroxysteroid dehydrogenase type 1 was synthesized and evaluated to optimize the lead compound 9. The combination of th...

Tetrahydroisoquinolines in therapeutics: A patent review (2010-2015).

1,2,3,4-Tetrahydroisoquinoline (THIQ) is one of the "privileged scaffolds", commonly found in nature. Initially, this class of compounds was known for its neurotoxicity. Later on, 1-methyl-1,2,3,4-tet...

Discovery and Optimization of Quinazolinone-pyrrolopyrrolones as Potent and Orally Bioavailable pan-Pim Kinase Inhibitors.

The high expression of proviral insertion site of Moloney murine leukemia virus kinases (Pim-1, -2, and -3) in cancers, particularly the hematopoietic malignancies, is believed to play a role in promo...

Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo4,5-bpyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor.

The work in this paper describes the optimization of the 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine chemical series as potent, selective allosteric inhibitors of AKT kinases, leading to...

Discovery of S3-truncated, C-6 heteroaryl substituted aminothiazine β-site APP cleaving enzyme-1 (BACE1) inhibitors.

Truncation of the S3 substituent of the biaryl aminothiazine 2, a potent BACE1 inhibitor, led to a low molecular weight aminothiazine 5 with moderate activity. Despite its moderate activity, compound ...

Clinical Trials [1351 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 ...

Oral ONC201 in Relapsed/Refractory Multiple Myeloma

ONC201 is an orally bioavailable first-in-class small molecule with demonstrated antitumor activity in preclinical models of difficult-to-treat solid and liquid tumors without imparting si...

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...

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.

Quick Search
Advertisement
 


DeepDyve research library

Relevant Topics

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Antibodies
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...


Searches Linking to this Article