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Publisher: Elsevier   (Total: 3044 journals)

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Showing 1 - 200 of 3044 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 22, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 21, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 84, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 23, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 29, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 343, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 214, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 23, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 3)
Acute Pain     Full-text available via subscription   (Followers: 13)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 134, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 25, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 25, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 5)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 41, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 40, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 48, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 35, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 15, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 61)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 2, SJR: 0.1, h-index: 2)
Advances in Space Research     Full-text available via subscription   (Followers: 348, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 7, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 317, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 8, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 408, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 39, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 54, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 8, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 47, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 48, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 45, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 39, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 16, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 24, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 46, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 192, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 56, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 4)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 24, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 26, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 34, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 55, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 9)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 166, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 156, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (Followers: 1, SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
Annales de Chirurgie Plastique Esthétique     Full-text available via subscription   (Followers: 2, SJR: 0.354, h-index: 22)
Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

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Journal Cover Advances in Medicinal Chemistry
  [5 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 1067-5698
   Published by Elsevier Homepage  [3044 journals]
  • List of contributors
    • Abstract: 2000
      Publication year: 2000
      Source:Advances in Medicinal Chemistry, Volume 5



      PubDate: 2012-12-17T08:20:51Z
       
  • Immunophilins The next generation
    • Abstract: 2000
      Publication year: 2000
      Source:Advances in Medicinal Chemistry, Volume 5



      PubDate: 2012-12-17T08:20:51Z
       
  • Discovery of ABT-594 and related neuronal nicotinic acetylcholine receptor
           modulators as analgesic agents Medicinal chemistry and biology
    • Abstract: 2000
      Publication year: 2000
      Source:Advances in Medicinal Chemistry, Volume 5

      ABT-594, a nicotinic acetylcholine receptor (nAChR) modulator that exhibits potent antinociceptive activity in animal models of pain, was discovered through optimization of a series of compounds that was first identified as part of a program directed toward the discovery of nAChR modulators for Alzheimer's disease. Structure-activity studies on ABT-594 indicate that both the azetidine ring and an appropriately substituted pyridine ring are key structural features contributing to its biological activity, which together with its favorable pharmacokinetic and safety profiles, has led to its advancement to clinical trials for treatment of pain in humans.

      PubDate: 2012-12-17T08:20:51Z
       
  • Discovery and preclinical evaluation of novel dopamine partial agonists as
           antipsychotic agents
    • Abstract: 2000
      Publication year: 2000
      Source:Advances in Medicinal Chemistry, Volume 5

      Antagonism of DA D2 receptors is thought to be the primary molecular mechanism for the efficacy of existing antipsychotic agents. This efficacy is believed to arise from blockade of DA D2 receptors in the mesolimbic and prefrontal brain regions. However blockade of DA D2 receptors in the striatum and caudate is thought to be responsible for the severe side effects associated with antipsychotic therapy including EPS and TD. Neurons that synthesize and release DA have DA autoreceptors on their presynpatic terminals and cell bodies. Stimulation of these autoreceptors by DA results in a negative feedback signal attenuating the synthesis and release of DA from these neurons. It has been hypothesized that partial agonists selective for DA autoreceptors could inhibit DA neurotransmission and therefore have antipsychotic efficacy. This review details the structure-activity relationships of DA partial agonists selective for DA D2 autoreceptors. Compounds having D2 and D3 affinity or D2 and 5-HT1A activity are also discussed. Compounds with the appropriate level of partial agonist activity were shown to have better efficacy/side effect profiles in primate models than standard DA D2 antagonists.

      PubDate: 2012-12-17T08:20:51Z
       
  • Nonpeptide inhibitors of HIV protease
    • Abstract: 2000
      Publication year: 2000
      Source:Advances in Medicinal Chemistry, Volume 5

      Mass screening of our compound collection, utilizing the Amersham SPA technology, afforded pyrone and coumarin non-peptide templates as initial lead structures. X-ray cocrystallization and structure-based design were utilized to assist in the design of more potent inhibitors. These efforts resulted in the design of the 5,6-dihydropyrones, which afforded a more flexible template from which to fill the internal pockets of the enzyme. Optimization of the dihydropyrone series afforded a potent antiviral agent, PD 178390 (EC50=0.20 μM, TD50=>100 μM). PD 178390 retained antiviral potency in the presence of serum proteins with a modest three-to fivefold drop in antiviral activity in the presence of 40% human serum. The antiviral activity, in PBMCs, was unchanged against clinical strains of resistant HIV virus. In addition, PD 178390 showed excellent bioavailability in mice, rats, and dogs as well as a low level of P450 inhibition in microsomal assays. This combination of good antiviral efficacy, good pharmacokinetics, and low P450 inhibition make PD 178390 a promising agent for the treatment of HIV infection.

      PubDate: 2012-12-17T08:20:51Z
       
  • List of contributors
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4



      PubDate: 2012-12-17T08:20:51Z
       
  • Novel peptide mimetic building blocks and strategies for efficient lead
           finding
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4



      PubDate: 2012-12-17T08:20:51Z
       
  • Recent advances in the medicinal chemistry of taxoid anticancer agents
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4

      Taxol® (paclitaxel) and Taxotère® (docetaxel) are currently considered to be the most promising leads in cancer chemotherapy. Both paciltaxel and docetaxel exhibit significant antitumor activity against various cancers, especially breast and ovarian cancers, which have not been effectively treated by existing chemotherapeutic drugs. The anticancer activity of these drugs is ascribed to their unique mechanism of action, i.e. causing mitotic arrest in cancer cells leading to apoptosis through inhibition of the depolymerization of microtubules. Although both paclitaxel and docetaxel possess potent antitumor activity, treatment with these drugs often results in a number of undesired side effects as well as multidrug resistance (MDR). Therefore, it has become essential to develop new anticancer agents with fewer side effects, superior pharmacological properties, and improved activity against various classes of tumors. This chapter describes the accounts of our research on the chemistry of paclitaxel and taxoid anticancer agents at the biomedical interface including: (i) the development of a highly efficient method for the semisynthesis of paclitaxel and a variety of taxoids by means of the β-Lactam Synthon Method (β-LSM), (ii) the structure-activity relationship (SAR) study of taxoids for their activities against human cancer cell lines, (iii) the discovery and development of “second-generation” taxoid anticancer agents that possess exceptional activities against drug-resistant cancer cells expressing the MDR phenotype as well as solid tumors (human cancer xenografts in mice), (iv) the development of fluorine-containing taxoids as a series of the second-generation taxoid anticancer agents and as excellent probes for the identification of bioactive conformation(s) of paclitaxel and taxoids by means of 19F NMR in solution as well as in solid state for the microtubule-taxoid complex, (v) the development of radiolabeled photoreactive analogues of paclitaxel for photoaffinity labeling and mapping of the drug-binding domain on microtubules as well as P-glycoprotein that is responsible for MDR, and (vi) an SAR study of taxoids on their activities for inducing NO and tumor necrosis factor (TNF) through macrophage activation, which may be operative as an alternative mechanism of action. Thus, this chapter covers a wide range of issues associated with these powerful taxoid anticancer agents, discussing current status and future prospects.

      PubDate: 2012-12-17T08:20:51Z
       
  • Synthesis and structure-activity relationships of peroxidic antimalarials
           based on artemisinin
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4



      PubDate: 2012-12-17T08:20:51Z
       
  • Design of compound libraries for detecting and pursuing novel small
           molecule leads
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4

      The selection of compounds for synthesis in high-throughput synthesis experiments and for use in high-throughput biological assays is of prime importance in the detection of exploitable biological properties in novel small molecule leads. We discuss factors associated with the design of compound libraries for use in such high-throughput methods, and how these impact both on finding new leads and on following up on them. Specifically four key design elements are discussed, viz. the relevance of the compounds to lead discovery, the collective diversity of the library, the “uniqueness” of individual compounds, and their synthetic accessibility. The design of the Optiverse library is discussed as an example and a comparison is made of the structural similarities between Optiverse, a database of recent therapeutic patents, and a database of commercial reagents.

      PubDate: 2012-12-17T08:20:51Z
       
  • A theoretical model of the human thrombin receptor (PAR-1), the first
           known protease-activated g-protein-coupled receptor
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4

      A three-dimensional molecular model of the human thrombin receptor (TR; PAR-1), a member of the seven-transmembrane G-protein-coupled receptor (GPCR) superfamily of glycoproteins and the first GPCR to have a tethered-peptide ligand (ref. 7), was constructed by using de novo computer-based modeling techniques. Because of numerous short comings associated with the use of the bacteriorhodopsin template for building GPCR models, we employed an alternative modeling strategy involving GPCR alignment and topological properties, as first described by Moereels (ref. 10). To initiate assembly of the seven-helix bundle for PAR-1, we relied on specific, conserved residues in the transmembrane (TM) domains, which in this instance are Asn-120 in TM1, Asp-148 in TM2, and Asp-367 in TM7. The side chains of these residues then comprise a hydrogen-bonding network that orients the three helices so that they are properly positioned to interact with each other. The energy-minimized three-helix bundle (TM1-TM2-TM7) served as a cornerstone for assembly of the complete seven-helix bundle, through systematic addition of TM3 through TM6 involving suitable orientation followed by limited translation, rotation, and tilting. The three extracellular (EC) loops were added to the energy-minimized, seven-helix construct via loop-search routines, and the disulfide bridge between two GPCR-conserved cysteines on loops EC1 and EC2 was formed using the protein manipulation software program SCULPT. Finally, part of the extracellular N-terminus, from Tyr-95 (at the extracellular end of TM1) to Asn-75, was attached to the receptor. The known structure-activity relationship surrounding the thrombin receptor agonist peptide motif SFLLRN, coupled with the results from our receptor-based, site-directed mutagenesis, were used to define and enhance our computer-generated, energy-minimized models of the ligand-bound thrombin receptor. We examined the acidic residues in the three extracellular loops (seven total: D167 and E173 in EC1; E241, D256, E260, and E264 in EC2; and E347 in EC3) to identify electrostatic interactions that could account for the ammonium N-terminus and/or the Arg residue of SFLLRN. When both EC1 acidic residues were mutated to Ala, there was no change in receptor functional responses. However, when all four acid residues in EC2 were mutated to Ala, there was a significant reduction in receptor activation in the presence of thrombin or agonist peptide. When the single acidic residue in EC3 was mutated to Ala, reduced functional activity was also observed. Comtrary to published observations (refs. 20 and 24), we were unable to find an important role for Glu-260 (E260A mutant TR), whereas replacement of Asp-256 (D256A mutant TR) had a significant effect on receptor function, especially in response to the TR-agonist peptide SFLLRNP-NH2 (TRAP-7). Our mutagenesis work also confirmed the importance of the peptide triad Asn-120/Asp-148/Asp-367 (viz. refs. 10 and 18) and the C-175/C-254 disulfide bridge (viz. ref. 25) in receptor function. On the basis of our studies, we suggest that the ammonium group at the N-terminus of the peptide ligand interacts with the carboxylic acid side chain of Glu-347, at the extracellular surface of TM7, and that the aromatic ring of the ligand's critical Phe residue binds within a hydrophobic pocket on the receptor defined by the side chains of Phe-182, Leu-340, Tyr-337, and Phe-339.

      PubDate: 2012-12-17T08:20:51Z
       
  • Farnesyl transferase inhibitors Design of a new class of cancer
           chemotherapeutic agents
    • Abstract: 1999
      Publication year: 1999
      Source:Advances in Medicinal Chemistry, Volume 4

      This review chronicles the strategies and hurdles encountered in farnesyl transferase inhibitor drug discovery programs, with the major focus on substrate-based inhibitor design. Recently reported enzyme structure studies and their potential impact on drug design are also discussed. The anti-proliferative effect that FTIs exhibit in both genetically engineered and human tumor cell lines suggest that this type of drug may be efficacious in treating certain cancers.

      PubDate: 2012-12-17T08:20:51Z
       
  • List of contributors
    • Abstract: 1995
      Publication year: 1995
      Source:Advances in Medicinal Chemistry, Volume 3



      PubDate: 2012-12-17T08:20:51Z
       
  • Novel antipsychotics with unique D2/5-HT1A affinity and minimal
           extrapyramidal side effect liability
    • Abstract: 1995
      Publication year: 1995
      Source:Advances in Medicinal Chemistry, Volume 3



      PubDate: 2012-12-17T08:20:51Z
       
  • Antiplatelet and antithrombotic agents From viper venom proteins, to
           peptides and peptidomimetics, to small organic molecules
    • Abstract: 1995
      Publication year: 1995
      Source:Advances in Medicinal Chemistry, Volume 3

      The importance of developing thrombolytics for the treatment of myocardial infarction and other major coronary diseases cannot be disputed. The continued mortality and morbidity associated with cardiovascular disease justify the continued pursuit of newer and better therapies. As examples, Glycomed's Astenose was recently reported to cut restenosis 50-75% in baboons receiving injuries from balloon angioplasty, 175 Gensia's Protara (formerly arasine) is currently under review by the FDA prior to its approval for the prevention of myocardial infarction, and for use in coronary artery bypass surgery, 176 and the comparison of currently approved thrombolytic agents continues (i.e., streptokinase vs Activase (tPA), 3 and Activase (tPA) vs Eminase 177 ). Furthermore, in a report recently published in the Annals of Emergency Medicine, a government panel recently concluded that not enough heart attack patients are being treated with thrombolytic drugs, and further recommended that “clotbusting” agents (Activase, tPA, Genentech; Eminase, SmithKline- Beecham; and streptokinase, Astra Pharmaceutical Products) should be kept in hospital emergency rooms, rather than hospital formularies, to save time. 178 Several synthetic peptides are in various stages of development as antithrombotics. Searle is pursuing the preclinical development of a pseudopeptide, 8-guanidino-octanoyl-Asp-Phe 179 ; Telios' cyclic peptide TP-9201 is currently being evaluated clinically 27 ; and Biogen is set to announce the results of TIMI-7 (thrombolysis in myocardial infarction) with its synthetic peptide thrombin inhibitor Hirulog. 20,180 COR Therapeutics will announce further results of Phase II studies with its synthetic peptide Integrelin, specifically on the issue raised in a recent study, in which it was found that the use of the drug produced an increase in the number of bleeding events over placebo. 180 The potency of the cyclic RGD peptides that have thus far been prepared have proved a boon to computational and synthetic chemists pursuing small molecule antagonists of GpllblIIa/Fg. Regardless of the actual conformation of R-G-D present in many of the natural proteins and cyclic peptides synthesized and studied, and the uncertainty surrounding the conformation of this critical epitope, the rigid constraint of RGD in these contexts provides a much clearer departure point for the design of molecules that can mimic RGD in this critical (though not necessarily native) conformation and good evidence of the power of "rational design." Other evidence of the expediency of rational design is beginning to surface in the literature, 181–183 perhaps proving that RGD is not unique in providing just such a design opportunity. As for the pursuit of small organic molecules as therapeutics, the best affirmation of the potential success that might be achieved is with the clinical development of argatroban by Houston Biotechnology Corporation. 21,184 Merck 185 and Roche 186 are currently pursuing preclinical and clinical studies of their small molecule antiplatelet GplIblIia antagonists. Certainly, the United States Pharmacopeia is replete with small organic molecules approved for use as drugs; small molecules can be used for oral administration, can be modified to improve absorption and/or clearance and minimize side effects, and are certainly more cost-effective to produce.

      PubDate: 2012-12-17T08:20:51Z
       
  • Discovery and preclinical development of the serotonin reuptake inhibitor
           sertraline
    • Abstract: 1995
      Publication year: 1995
      Source:Advances in Medicinal Chemistry, Volume 3



      PubDate: 2012-12-17T08:20:51Z
       
  • Boronic acid inhibitors of dipeptidyl peptidase IV A new class of
           immunosuppressive agents
    • Abstract: 1995
      Publication year: 1995
      Source:Advances in Medicinal Chemistry, Volume 3



      PubDate: 2012-12-17T08:20:51Z
       
 
 
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