andresderis
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The Medicinal Chemistry thread
hello to everybody , i ll be very pleasure to put here some selected medicinal chemistry papers and books .The idea is to get a systematic idea of
medicinal chemistry and his related branches (organic , biochemistry , pharmacology-physiology) , so here we go , the first three papers that IMO ,
you MUST to read and get a overall idea
Introduction To medicinal chemistry (Nature Drug Discovery reviews)
THE ROLE OF THE MEDICINAL
CHEMIST IN DRUG DISCOVERY —
THEN AND NOW
Joseph G. Lombardino* and John A. Lowe III‡
Abstract | The role of the medicinal chemist in drug discovery has undergone major changes
in the past 25 years, mainly because of the introduction of technologies such as combinatorial
chemistry and structure-based drug design. As medicinal chemists with more than 50 years of
combined experience spanning the past four decades, we discuss this changing role using
examples from our own and others’ experience. This historical perspective could provide insights
in to how to improve the current model for drug discovery by helping the medicinal chemist
regain the creative role that contributed to past successes.
http://rapidshare.de/files/17956670/intro_to_medicinal_chemistry__nature_reviews__01.pdf.html
QUANTITATIVE STRUCTURE--ACTIVITY RELATIONSHIPS (QSAR)
SEARCH FOR NEW DRUGS
USE OF QUANTITATIVE STRUCTURE--ACTIVITY RELATIONSHIPS (QSAR)
IN DRUG DESIGN (Review)*
C. Hansch UDC 615.015.11(048.8)
IMPORTANCE OF THE STRUCTURE--ACTIVITY PROBLEM
http://rapidshare.de/files/17752365/SearchForNewDrugs.pdf.html
ADME Approach in Drug Discovery (physicochemical parameters of drug action)
Experimental and computational approaches to estimate
solubility and permeability in drug discovery and development
q settings
* Christopher A. Lipinski , Franco Lombardo, Beryl W. Dominy, Paul J. Feeney
Central Research Division , Pfizer Inc ., Groton ,CT 06340,USA
http://rapidshare.de/files/17956833/sdarticle.pdf.html
enjoy it , and i will upload related papers soon as possible!!
go to ebooks section and download "fundamentals of medicinal chemistry" , so its very good reference in that field
best regards
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andresderis
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http://rapidshare.de/files/18885271/g24g431875352223_1_.pdf....
http://rapidshare.de/files/18885569/t0110410l4412vu4_1_.pdf....
[Edited on 25-4-2006 by andresderis]
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andresderis
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1: N Engl J Med. 1999 Dec 16;341(25):1865-73. Related Articles, Links
Comment in:
N Engl J Med. 1999 Dec 16;341(25):1925-6.
N Engl J Med. 2000 Apr 27;342(17):1290-1.
N Engl J Med. 2003 Dec 18;349(25):2460-1; author reply 2460-1.
Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1
infection in adults. Study 006 Team.
Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, Stryker R, Johnson P, Labriola DF, Farina D, Manion DJ, Ruiz
NM.
Klinikum der J.W. Goethe Universitat, Frankfurt, Germany.
BACKGROUND: Efavirenz is a nonnucleoside reverse-transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). We compared two regimens
containing efavirenz, one with a protease inhibitor and the other with two nucleoside reverse-transcriptase inhibitors, with a standard three-drug
regimen. METHODS: The study subjects were 450 patients who had not previously been treated with lamivudine or any nonnucleoside reverse-transcriptase
inhibitor or protease inhibitor. In this open-label study, patients were randomly assigned to one of three regimens: efavirenz (600 mg daily) plus
zidovudine (300 mg twice daily) and lamivudine (150 mg twice daily); the protease inhibitor indinavir (800 mg every eight hours) plus zidovudine and
lamivudine; or efavirenz plus indinavir (1000 mg every eight hours). RESULTS: Suppression of plasma HIV-1 RNA to undetectable levels was achieved in
more patients in the group given efavirenz plus nucleoside reverse-transcriptase inhibitors than in the group given indinavir plus nucleoside
reverse-transcriptase inhibitors (70 percent vs. 48 percent, P<0.001). The efficacy of the regimen of efavirenz plus indinavir was similar (53
percent) to that of the regimen of indinavir, zidovudine, and lamivudine. CD4 cell counts increased significantly with all combinations (range of
increases, 180 to 201 cells per cubic millimeter). More patients discontinued treatment because of adverse events in the group given indinavir and two
nucleoside reverse-transcriptase inhibitors than in the group given efavirenz and two nucleoside reverse-transcriptase inhibitors (43 percent vs. 27
percent, P=0.005). CONCLUSIONS: As antiretroviral therapy in HIV-1-infected adults, the combination of efavirenz, zidovudine, and lamivudine has
greater antiviral activity and is better tolerated than the combination of indinavir, zidovudine, and lamivudine.
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Antimicrob Agents Chemother. 1995 Dec;39(12):2602-5. Related Articles, Links
L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse
transcriptase.
Young SD, Britcher SF, Tran LO, Payne LS, Lumma WC, Lyle TA, Huff JR, Anderson PS, Olsen DB, Carroll SS, et al.
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
The clinical benefit of the human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) is limited by the
rapid selection of inhibitor-resistant viral variants. However, it may be possible to enhance the clinical utility of this inhibitor class by deriving
compounds that express both high levels of antiviral activity and an augmented pharmacokinetic profile. Accordingly, we developed a new class of
NNRTIs, the 1, 4-dihydro-2H-3, 1-benzoxazin-2-ones. L-743, 726 (DMP-266), a member of this class, was chosen for clinical evaluation because of its in
vitro properties. The compound was a potent inhibitor of the wild-type HIV-1 RT (Ki = 2.93 nM) and exhibited a 95% inhibitory concentration of 1.5 nM
for the inhibition of HIV-1 replicative spread in cell culture. In addition, L-7743, 7726 was found to be capable of inhibiting, with 95% inhibitory
concentrations of < or = 1.5 microM, a panel of NNRTI-resistant mutant viruses, each of which expressed a single RT amino acid substitution.
Derivation of virus with notably reduced susceptibility to the inhibitor required prolonged cell culture selection and was mediated by a combination
of at least two RT amino acid substitutions. Studies of L-743, 726 in rats, monkeys, and a chimpanzee demonstrated the compound's potential for good
oral bioavailability and pharmacokinetics in humans.
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download these two papers from here:
http://rapidshare.de/files/21911258/efavirenz02.zip.html
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