Division of Medicinal Chemistry Abstracts-235th ACS National ...

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95A analog 2a,b with the essential functionalities sufficient for inhibition was derived. For further simplification the biaryl moiety was replaced with a nitro (3a) as well as an aniline (3b) biaryl ether macrocycle. Simultaneously we have optimised the amino acid sequence with the introduction of arginine residues targeting trypsin-like activity. X-ray crystallography as well as mass spectrometry gave evidence for the hydrolysis of this C-terminal amide. MEDI 25 Design and synthesis of polyketide-based affinity labels for acyl carrier protein domains Erick K. Leggans and Robert A. Fecik, Department of Medicinal Chemistry, University of Minnesota, 8-101 Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, legga001@umn.edu Polyketide synthases (PKSs) are a family of multienzyme complexes that biosynthesize natural products through the sequential condensation of simple two- or three-carbon building blocks. Polyketides have a wide range of biological and pharmacological activities and there has been much interest towards engineering PKSs systems for combinatorial biosynthesis in order to produce new drugs and novel molecules. However, an understanding of substrate stereospecificity and selectivity is unknown for nearly all of the PKS catalytic domains. The specific aim of this research is to design and synthesize polyketide-based affinity labels in order to understand this relationship. Here we present the design and synthesis of vinyl ketone affinity labels and their effective labeling of an acyl carrier protein which, with the aid of their crystal structures, will allow us to determine the stereochemical outcome of PKS activity. MEDI 26 2-Phenoxypyrimidine-5-carboxamide derivatives as a novel Prostaglandin D synthase inhibitor Keiko Yamane, Yoshiki Tanaka, Kazuhiko Shigeno, Toshiyuki Hosoya, Shin-ichi Inoue, Makoto Kitade, Takafumi Harada, Hiroki Aoyagi, Nao Miyoshi, Toshiharu Mutoh, Michinori Togawa, Mamoru Kiniwa, and Yasundo Yamasaki, Advanced Research Lab, Taiho Pharmaceutical Co., Ltd, 1-27, Misugidai, Hanno-shi 357-8527, Japan, Fax: +81-42-972-0034
Prostaglandin (PG) D 2 is an allergic and inflammatory mediator produced by mast cells and Th2 cells. Two distinct types of PGD synthase (PGDS) are known, lipocalin-type PGDS (L-PGDS) is localized in the central nervous system etc. and involved in the regulation of sleep and pain. The other hematopoietic PGDS (H-PGDS) is localized in mast cells, Th2 cells, microglia etc. and participates in allergic and inflammatory reactions. Therefore, selective H-PGDS inhibitors are expected for anti-allergic and anti-inflammatory drugs. We have found 2- phenoxypyrimidine-5-carboxamide (1) as a lead compound based on structure activities relationships. After the optimization of lead compound (1), we have developed orally available H-PGDS selective inhibitor 2. IC 50 value of 2 against H-PGDS is 0.28 mM, on the other hand, inhibitory activity of 2 against L-PGDS is 2% at 100 mM. The details of this work will be presented. MEDI 27 Cobalt(III) amine complexes as a potential antibacterial drugs Christa Simmers 1 , Eddie L. Chang 2 , and D. Andrew Knight 1 . (1) Department of Chemistry, Loyola University, 6363 St Charles Ave, New Orleans, LA 70118, csimmer@loyno.edu, (2) Center for Bio/Molecular Science and Engineering, Naval Research Laboratory, Washington, DC 20375-5438 The antibacterial effects of cobalt hexammine were investigated using E. coli model as a model. The ability of the cobalt hexammine to stop bacterial growth was determined from the absorbance of a sample of the bacteria and the cobalt hexammine complex. A possible magnesium ion channel blocking mechanism of cobalt hexammine was tested through the use of a TolC mutant strain of E. coli. MEDI 28 Acute osteomyelitis (OM): Nanometer-sized calcium phosphate (CP) particles as a carrier for bisphosphonate-ciprofloxacin (E41) antibiotic James C McPherson III 1 , Royce Runner 2 , Pal Herczegh 3 , and Thomas B Buxton 2 . (1) Dept. of Clinical Investigation, Dwight David Eisenhower Army Medical Center, Bldg 38705, Fort Gordon, GA 30905, Fax: 706-787-2730, james.mcpherson@amedd.army.mil, (2) The Geneva Foundation, Lakewood, WA 98405, (3) Dept. of Pharmaceutical Chemistry, University of Debrecen, Debrecen, Hungary
Page 1 and 2: Division of Medicinal Chemistry Abs
Page 3 and 4: discovery of S/GSK364735 was a resu
Page 5 and 6: compounds was then performed target
Page 7 and 8: MEDI 13 Potent, brain-penetrant, hy
Page 9 and 10: predominately in the liver, leads t
Page 11 and 12: Candidate Optimization Department,
Page 13: acceptor atoms as the core componen
Page 17 and 18: polymerization, as described, by pr
Page 19 and 20: MEDI 34 Pyrogallol and its analogs
Page 21 and 22: Nicos A. Petasis 1 , Jasim Uddin 1
Page 23 and 24: Yong-Gil Kim, Joon Heo, Mi-Kyung Ji
Page 25 and 26: A new class of potent NK1 receptor
Page 27 and 28: The significant antiviral propertie
Page 29 and 30: Laboratories, West Point, PA 19486,
Page 31 and 32: MEDI 58 Preparation and antiviral a
Page 33 and 34: MEDI 62 Caco-2 cell based assay dev
Page 35 and 36: FMS-like tyrosine kinase 3 (FLT3) r
Page 37 and 38: MEDI 70 Synthesis of bisphosphonate
Page 39 and 40: ing. These observations suggest a p
Page 41 and 42: MEDI 77 Probing the structure-activ
Page 43 and 44: B-Raf kinase plays a critical role
Page 45 and 46: Gal-CS was used to prepare nanopart
Page 47 and 48: MEDI 88 Trifluoromethyl substituted
Page 49 and 50: MEDI 92 Discovery of novel small mo
Page 51 and 52: MEDI 96 Synthesis and antiprolifera
Page 53 and 54: MEDI 99 Development of novel antica
Page 55 and 56: MEDI 103 Discovery of N-aryl-9-oxo-
Page 57 and 58: Compounds that interfere with micro
Page 59 and 60: Carbonyl reductase (CR) has been im
Page 61 and 62: Apoptosis is a process of cell deat
Page 63 and 64: MEDI 120 Novel purine based "atypic
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MEDI 124 Efficient removal of ruthe
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library approach using technology-e
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MEDI 131 Synthesis and biological e
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MEDI 135 Identification of AT-1002
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Spectroscopic evidence was used to
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MEDI 142 Molecular basis for irreve
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MEDI 146 Effect of fluorine on subs
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MEDI 151 Overview of newer approach
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MEDI 156 Defining structure-activit
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MEDI 160 Bivalent inhibitors of P-g
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MEDI 164 Molecular basis for effica
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MEDI 167 Discovery of the highly po
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highly asymmetric, closely packed d
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4/WP14-3, Sumneytown Pike, West Poi
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MEDI 179 Design, synthesis, and eva
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MEDI 182 Substituted-pyrrole 2-amin
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MEDI 186 Discovery and optimization
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phosphatase SHIP. Bioassay guided f
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epibatidine for nicotinic channels.
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derivative with striking solubility
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MEDI 203 Core-modified mannopeptimy
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MEDI 207 Enhancing the kinetic prof
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hydroxyphenyl)piperazin-1-yl)butyl)
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migration of people from these area
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Schistosomiasis is, after malaria,
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-Ketoacyl-ACP-synthase III (FabH) h
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MEDI 225 Synthesis of the analog of
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MEDI 229 Structure-based virtual sc
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MEDI 234 TG100801: A prodrug for th
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In the past, large collections of c
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approach to the treatment of autoim
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logPe values. The residual mean squ
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Oligo-chitosan (OCS) which is a kin
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characterization of novel muscarini
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MEDI 257 Rigid analogs of 4,4-diary
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MEDI 261 Strategies toward improvin
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disease. It is generally accepted t
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(BBB). Our preliminary in vitro dat
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It is well-documented that androgen
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MEDI 276 Investigating the manipula
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were screened by FACS sarin labeled
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MEDI 285 Design, synthesis and biol
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equipment set-up and large scale ma
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Significant effort has been directe
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esearch was supported by funds from
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synthesized a series of carbamoylch
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proceeded more rapidly by switching
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genes. With the understanding of th
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MEDI 310 Optimized methods for the
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Coupled with crystallographic data,
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MEDI 317 Design and synthesis of hy
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MEDI 320 Synthesis and antibacteria
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DTPA. Incorporation of the nitro fu
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MEDI 328 The mechanism of bioreduct
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esistance, there is an urgent need
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Giving the Rule-of-5 a more accurat
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MEDI 338 Structure guided design of
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MEDI 342 Synthesis of peptide-amilo
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MEDI 346 Design, synthesis, and ant
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