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  Subjects -> MEDICAL SCIENCES (Total: 7249 journals)
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MEDICAL SCIENCES (1802 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 3562 Journals sorted alphabetically
16 de Abril     Open Access  
AADE in Practice     Hybrid Journal   (Followers: 4)
ABCS Health Sciences     Open Access   (Followers: 1)
Abia State University Medical Students' Association Journal     Full-text available via subscription  
ACIMED     Open Access   (Followers: 1)
ACS Medicinal Chemistry Letters     Full-text available via subscription   (Followers: 39)
Acta Bio Medica     Full-text available via subscription   (Followers: 2)
Acta Bioethica     Open Access   (Followers: 1)
Acta Bioquimica Clinica Latinoamericana     Open Access   (Followers: 1)
Acta Facultatis Medicae Naissensis     Open Access  
Acta Informatica Medica     Open Access   (Followers: 1)
Acta Medica Bulgarica     Open Access  
Acta Medica Colombiana     Open Access   (Followers: 1)
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Acta Medica Indonesiana     Open Access  
Acta medica Lituanica     Open Access  
Acta Medica Marisiensis     Open Access  
Acta Medica Martiniana     Open Access  
Acta Medica Nagasakiensia     Open Access  
Acta Medica Peruana     Open Access   (Followers: 2)
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Acta Scientiarum. Health Sciences     Open Access  
Acupuncture & Electro-Therapeutics Research     Full-text available via subscription   (Followers: 2)
Addiction Science & Clinical Practice     Open Access   (Followers: 7)
Addictive Behaviors Reports     Open Access   (Followers: 6)
Advanced Health Care Technologies     Open Access   (Followers: 4)
Advanced Science, Engineering and Medicine     Partially Free   (Followers: 7)
Advances in Bioscience and Clinical Medicine     Open Access   (Followers: 5)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29)
Advances in Life Course Research     Hybrid Journal   (Followers: 8)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
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Advances in Molecular Oncology     Open Access   (Followers: 1)
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Advances in Parkinson's Disease     Open Access  
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Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20)
Advances in Therapy     Hybrid Journal   (Followers: 5)
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)
Advances in Wound Care     Hybrid Journal   (Followers: 10)
African Health Sciences     Open Access   (Followers: 2)
African Journal of Biomedical Research     Open Access  
African Journal of Clinical and Experimental Microbiology     Open Access   (Followers: 1)
African Journal of Laboratory Medicine     Open Access   (Followers: 2)
African Journal of Medical and Health Sciences     Open Access   (Followers: 2)
African Journal of Trauma     Open Access  
Afrimedic Journal     Open Access   (Followers: 2)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
AIDS Research and Human Retroviruses     Hybrid Journal   (Followers: 8)
AJOB Primary Research     Partially Free   (Followers: 3)
Aktuelle Ernährungsmedizin     Hybrid Journal   (Followers: 4)
Al-Azhar Assiut Medical Journal     Open Access  
Alexandria Journal of Medicine     Open Access   (Followers: 1)
Allgemeine Homöopathische Zeitung     Hybrid Journal   (Followers: 2)
Alpha Omegan     Full-text available via subscription  
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
American Journal of Biomedical Engineering     Open Access   (Followers: 11)
American Journal of Biomedical Research     Open Access   (Followers: 2)
American Journal of Biomedicine     Full-text available via subscription   (Followers: 6)
American Journal of Chinese Medicine, The     Hybrid Journal   (Followers: 5)
American Journal of Clinical Medicine Research     Open Access   (Followers: 5)
American Journal of Family Therapy     Hybrid Journal   (Followers: 11)
American Journal of Law & Medicine     Full-text available via subscription   (Followers: 12)
American Journal of Lifestyle Medicine     Hybrid Journal   (Followers: 5)
American Journal of Managed Care     Full-text available via subscription   (Followers: 11)
American Journal of Medical Case Reports     Open Access   (Followers: 1)
American Journal of Medical Sciences and Medicine     Open Access   (Followers: 1)
American Journal of Medicine     Hybrid Journal   (Followers: 46)
American Journal of Medicine and Medical Sciences     Open Access   (Followers: 1)
American Journal of Medicine Studies     Open Access  
American Journal of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American Journal of the Medical Sciences     Hybrid Journal   (Followers: 12)
American Journal on Addictions     Hybrid Journal   (Followers: 9)
American Medical Journal     Open Access   (Followers: 4)
American medical news     Free   (Followers: 3)
American Medical Writers Association Journal     Full-text available via subscription   (Followers: 2)
Amyloid: The Journal of Protein Folding Disorders     Hybrid Journal   (Followers: 4)
Anales de la Facultad de Medicina     Open Access  
Anales de la Facultad de Medicina, Universidad de la República, Uruguay     Open Access  
Anales del Sistema Sanitario de Navarra     Open Access   (Followers: 1)
Analgesia & Resuscitation : Current Research     Hybrid Journal   (Followers: 3)
Anatomical Science International     Hybrid Journal   (Followers: 2)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1)
Anatomy Research International     Open Access   (Followers: 2)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3)
Annales de Pathologie     Full-text available via subscription  
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annals of African Medicine     Open Access   (Followers: 1)
Annals of Anatomy - Anatomischer Anzeiger     Hybrid Journal   (Followers: 2)
Annals of Bioanthropology     Open Access   (Followers: 3)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 18)
Annals of Biomedical Sciences     Full-text available via subscription   (Followers: 3)
Annals of Clinical Microbiology and Antimicrobials     Open Access   (Followers: 8)
Annals of Family Medicine     Open Access   (Followers: 13)
Annals of Fundeni Hospital     Open Access   (Followers: 1)
Annals of Ibadan Postgraduate Medicine     Open Access  
Annals of Medical and Health Sciences Research     Open Access   (Followers: 7)
Annals of Medicine     Hybrid Journal   (Followers: 12)
Annals of Medicine and Surgery     Open Access   (Followers: 5)
Annals of Microbiology     Hybrid Journal   (Followers: 10)
Annals of Nigerian Medicine     Open Access   (Followers: 1)
Annals of Saudi Medicine     Open Access  
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5)
Annals of The Royal College of Surgeons of England     Full-text available via subscription   (Followers: 3)
Annual Reports in Medicinal Chemistry     Full-text available via subscription   (Followers: 7)
Annual Reports on NMR Spectroscopy     Full-text available via subscription   (Followers: 4)
Annual Review of Medicine     Full-text available via subscription   (Followers: 18)
Anthropological Review     Open Access   (Followers: 24)
Anthropologie et santé     Open Access   (Followers: 5)
Antibiotics     Open Access   (Followers: 9)
Antibodies     Open Access   (Followers: 2)
Antibody Technology Journal     Open Access   (Followers: 1)
Anuradhapura Medical Journal     Open Access  
Anwer Khan Modern Medical College Journal     Open Access   (Followers: 2)
Apmis     Hybrid Journal   (Followers: 1)
Apparence(s)     Open Access   (Followers: 1)
Applied Clinical Informatics     Hybrid Journal   (Followers: 2)
Applied Medical Informatics     Open Access   (Followers: 11)
Arab Journal of Nephrology and Transplantation     Open Access   (Followers: 1)
Arak Medical University Journal     Open Access  
Archive of Clinical Medicine     Open Access   (Followers: 1)
Archive of Community Health     Open Access  
Archives of Biomedical Sciences     Open Access   (Followers: 7)
Archives of Medical and Biomedical Research     Open Access   (Followers: 3)
Archives of Medical Laboratory Sciences     Open Access   (Followers: 1)
Archives of Medicine and Health Sciences     Open Access   (Followers: 3)
Archives of Trauma Research     Open Access   (Followers: 2)
Archivos de Medicina (Manizales)     Open Access  
ArgoSpine News & Journal     Hybrid Journal  
Arquivos Brasileiros de Oftalmologia     Open Access  
Arquivos de Ciências da Saúde     Open Access  
Arquivos de Medicina     Open Access  
ARS Medica Tomitana     Open Access   (Followers: 1)
Art Therapy: Journal of the American Art Therapy Association     Full-text available via subscription   (Followers: 10)
Arterial Hypertension     Open Access  
Artificial Intelligence in Medicine     Hybrid Journal   (Followers: 12)
Artificial Organs     Hybrid Journal   (Followers: 1)
Asia Pacific Family Medicine     Open Access  
Asia Pacific Journal of Clinical Nutrition     Full-text available via subscription   (Followers: 9)
Asia Pacific Journal of Clinical Trials : Nervous System Diseases     Open Access  
Asian Bioethics Review     Full-text available via subscription   (Followers: 2)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Health     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 2)
Asian Journal of Medical and Pharmaceutical Researches     Open Access   (Followers: 1)
Asian Journal of Medical Sciences     Open Access   (Followers: 1)
Asian Journal of Scientific Research     Open Access   (Followers: 2)
Asian Journal of Transfusion Science     Open Access   (Followers: 2)
Asian Medicine     Hybrid Journal   (Followers: 4)
ASPIRATOR : Journal of Vector-borne Disease Studies     Open Access  
Astrocyte     Open Access  
Atención Familiar     Open Access  
Atención Primaria     Open Access   (Followers: 1)
Audiology - Communication Research     Open Access   (Followers: 8)
Auris Nasus Larynx     Full-text available via subscription  
Australian Coeliac     Full-text available via subscription   (Followers: 2)
Australian Family Physician     Full-text available via subscription   (Followers: 3)
Australian Journal of Medical Science     Full-text available via subscription   (Followers: 1)
Autopsy and Case Reports     Open Access  
Aviation, Space, and Environmental Medicine     Full-text available via subscription   (Followers: 10)
Avicenna     Open Access   (Followers: 2)
Avicenna Journal of Medicine     Open Access   (Followers: 1)
Bangabandhu Sheikh Mujib Medical University Journal     Open Access   (Followers: 1)
Bangladesh Journal of Anatomy     Open Access   (Followers: 1)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 3)
Bangladesh Journal of Medical Education     Open Access   (Followers: 2)
Bangladesh Journal of Medical Microbiology     Open Access   (Followers: 3)
Bangladesh Journal of Medical Physics     Open Access  
Bangladesh Journal of Medical Science     Open Access  
Bangladesh Journal of Medicine     Open Access   (Followers: 1)
Bangladesh Journal of Physiology and Pharmacology     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 2)
Bangladesh Medical Journal     Open Access  
Bangladesh Medical Journal Khulna     Open Access  
Bangladesh Medical Research Council Bulletin     Open Access  
Basal Ganglia     Hybrid Journal  
Basic Sciences of Medicine     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BC Medical Journal     Free  
Benha Medical Journal     Open Access  
Bijblijven     Hybrid Journal  
Bijzijn     Hybrid Journal   (Followers: 2)
Bijzijn XL     Hybrid Journal   (Followers: 1)
Bio-Algorithms and Med-Systems     Hybrid Journal   (Followers: 1)
BioDiscovery     Open Access   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 1)
Bioengineering & Translational Medicine     Open Access  
Bioethics     Hybrid Journal   (Followers: 14)
Bioethics Research Notes     Full-text available via subscription   (Followers: 14)
Biologics in Therapy     Open Access  
Biology of Sex Differences     Open Access   (Followers: 3)

        1 2 3 4 5 6 7 8 | Last

Journal Cover Advances in Medicinal Chemistry
  [5 followers]  Follow
    
   Full-text available via subscription Subscription journal
   ISSN (Print) 1067-5698
   Published by Elsevier Homepage  [3049 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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