piperidines and laquinimod

Inflammatory bowel diseases (IBDs) are immune-mediated chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is not yet fully understood. Despite the advent of biological agents, there are still unmet needs for IBD patients, due to suboptimal rate of sustained remission achieved. Small molecule drugs (SMDs), the next generation of selective drugs in IBD, show promising results in ongoing trials.. We describe the pharmacodynamics and pharmacokinetic features of novel SMDs and their main differences with biologic agents.. Small molecule drugs are a promising class of drugs for the treatment of ulcerative colitis and Crohn's disease with good results in inducing and maintaining remission. Hence, over the next few years physicians will have numerous options of small molecule drugs for the treatment of patients with IBD. This group of drugs are potentially easier to use over biological agents due to pharmacokinetic features such as oral administration, short half-life, high volume of distribution, and lack of immunogenicity. On the other hand, drug-drug interactions can happen with small-molecule drugs, principally due to competitive metabolic and clearance mechanisms.

Topics: Acetates; Animals; Clinical Trials as Topic; Colitis, Ulcerative; Crohn Disease; Heterocyclic Compounds, 3-Ring; Humans; Indans; Indoles; Janus Kinase Inhibitors; Oxadiazoles; Piperidines; Pyridines; Pyrimidines; Quinolones; Sphingosine-1-Phosphate Receptors; Triazoles

Multiple sclerosis (MS) is a heterogeneous, chronic, debilitating immune-mediated disease of the central nervous system (CNS). There are four types of MS according to their relapsing or progressive pattern that include relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). There is no definite cure for MS, thus medications typically focus on slowing the progression of the disease, managing symptoms and improving the quality of life. There is no specific medication for the management of PPMS and thus these patients are often neglected. New medicines in this phase of the disease are needed. On the other hand injectable immunomodulatory medicines, which dominated the MS market for over the past two decades, raise the issues of adherence and tolerance while oral therapies do offer a step forward in convenience. This systematic review article discusses the emerging synthetic small molecule that administered orally for MS treatment. We searched PubMed, Web of Science and Google Scholar to summaries the present knowledge on mechanism of action, and completed and current clinical trial of laquinimod, masitinib and siponimod. Data were collected from 1985 to January 2015. The development of effective medicines for MS is critically dependent upon understanding the biological basis of this complex multifactorial disease. The current pharmacotherapeuetic options for its treatment are mainly immunomodulators which were developed on the basis that MS is an autoimmune disease. The new synthetic small molecule agents such as laquinimod, masitinib and siponimod with different mechanism of actions can be administered orally rather than by injection.

Topics: Benzamides; Humans; Immunologic Factors; Multiple Sclerosis; Piperidines; Pyridines; Quinolones; Small Molecule Libraries; Thiazoles

In recent years, many new agents have been evaluated for the treatment of inflammatory bowel disease. In this paper, we critically review recently published literature about these novel therapies, which have been the result of extensive research identifying molecular targets. Of the various biologicals and small molecules that have recently been tested in clinical trials, several demonstrated clinical efficacy with a tolerable safety profile. We discuss a number of them with specific focus on vedolizumab, a monoclonal antibody directed against the alpha4beta7 integrin on lymphocytes, ustekinumab, a monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23, and tofacitinib, a small molecule targeting Janus-activated kinase. Most likely, these three agents will find their way to the market and offer significant therapeutic alternatives for the management of Crohn's disease and/or ulcerative colitis.

Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cell Adhesion Molecules; Certolizumab Pegol; Colitis, Ulcerative; Crohn Disease; Humans; Immunoglobulin Fab Fragments; Infliximab; Natalizumab; Piperidines; Polyethylene Glycols; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quinolones; Tumor Necrosis Factor-alpha; Ustekinumab

Topics: Administration, Oral; Anti-Inflammatory Agents; Colitis, Ulcerative; Crohn Disease; Humans; Immunologic Factors; Indans; Inflammatory Bowel Diseases; Oxadiazoles; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quinolones; Randomized Controlled Trials as Topic; Treatment Outcome; Tumor Necrosis Factor-alpha