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

More documents

Recommendations

Info

MEDI 56 Synthesis of 5,6-dihydropyran-2-ones as potential inhibitors of HIV-1 protease Jesse L. Nye and Levente Fabry-Asztalos, Department of Chemistry, Central Washington University, 400 East University Way, Ellensburg, WA 98926 HIV/AIDS has affected about 40 million people. One type of drug that is used to treat HIV/AIDS is a protease inhibitor. HIV-1 protease eventually becomes resistant to the inhibitors; therefore, new drugs are needed. This research builds on a previous research effort, in which structures for HIV-1 protease inhibitors were designed using molecular modeling methods and a Quantitative Structure-Activity Relationship (QSAR) study was performed using a fuzzy neural network to predict their biological activities. We hope that these inhibitors will possess better inhibitory properties, have increased bioavailability, and possibly have less toxicity than the inhibitors currently in use. These novel structures are currently being synthesized using known methodologies. Once synthesized their inhibitory values will be determined and then compared to inhibitory values predicted by the neural networks. We hope that these compounds will become lead compounds for further drug discovery for HIV/AIDS. MEDI 57 Synthesis and antiviral properties of 8-aza-7-deaza-Aristeromycin and Neplanocin Haisheng Wang, Yan Zhang, and Stewart W. Schneller, Department of Chemistry and Biochemistry, Auburn University, 179 chemistry building, Auburn, AL 36849, wangha2@auburn.edu Our laboratory has an ongoing interest in the design and synthesis of adenine-derived carbocyclic nucleosides as a consequence of their anticipated antiviral properties arising from inhibition of viral mRNA processing. Prominent compounds in this series area are aristeromycin (1) and neplanocin (2). To vary these structural prototypes, the 8-aza-7-deaza analogues 3 and 4 became target compounds. The synthesis of 3 and 4 and their antiviral properties will be reported. This research was supported by funds from the Department of Health and Human Services (AI 56540).
MEDI 58 Preparation and antiviral activity of N-1 / N-2 methyl-4-deazacarbaformycin Yan Zhang, Haisheng Wang, and Stewart W. Schneller, Department of Chemistry and Biochemistry, Auburn University, 179 chemistry building, Auburn, AL 36849, yzz0001@auburn.edu The medicinal potential of the naturally occurring C-nucleoside formycin (1) is limited by its metabolism by adenosine deaminase to formycin B (2). In our pursuit of the carbocyclic nucleoside congener of 1 (that is, 3) we sought the 4-deaza analog 4 with the possibility it would not be a substrate for the deaminase by analogy to 3-deazaadenosine. As part of that program, the N-1 and N-2 methyl derivatives of 4 (5 and 6) arose as relevant because of the established biological properties for the corresponding formycin methylated compounds. Our investigations of 5 and 6 will be presented. This research was supported by funds from the Department of Health and Human Services (AI 56540). MEDI 59 Early screening for PXR- and CAR-mediated ADME-Tox liabilities: New fluorescencebased ligand binding and coregulator recruitment assays William J. Frazee, Upinder Singh, Bryan D. Marks, Hildegard C. Eliason, Deborah K. Stafslien, Jill K. Wolken, and Kurt W. Vogel, Invitrogen Discovery Sciences, 501 Charmany Drive, Madison, WI 53719, Fax: 608-204-5200, jack.frazee@invitrogen.com Pregnane X receptor (PXR or SXR) and constitutive androstane receptor (CAR) are major regulators of drug metabolizing enzymes and transporters, playing key roles in the clinical efficacy and toxicity of drug candidates, including drug interactions. Like other nuclear receptors, the activities of PXR and CAR are modulated both by (endogenous or exogenous) ligands and by endogenous protein coregulators. We have developed a new competitive binding assay for PXR and a new coregulator recruitment assay for CAR. Ligand binding to PXR is detected by displacement of a fluorescent PXR ligand (tracer) from the receptor, resulting in loss of the FRET signal between the tracer and a terbium-labeled antibody to a GST tag on PXR. Modulation of coregulator peptide binding is detected by changes in the FRET signal between a terbium-labeled antibody to a GST tag on CAR and a fluorescein-labeled coregulator peptide. These assays enable the rapid evaluation of compounds for potential PXR- and CARmediated liabilities.
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 and 14: acceptor atoms as the core componen
Page 15 and 16: Prostaglandin (PG) D 2 is an allerg
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: Laboratories, West Point, PA 19486,
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
Page 65 and 66: MEDI 124 Efficient removal of ruthe
Page 67 and 68: library approach using technology-e
Page 69 and 70: MEDI 131 Synthesis and biological e
Page 71 and 72: MEDI 135 Identification of AT-1002
Page 73 and 74: Spectroscopic evidence was used to
Page 75 and 76: MEDI 142 Molecular basis for irreve
Page 77 and 78: MEDI 146 Effect of fluorine on subs
Page 79 and 80: MEDI 151 Overview of newer approach
Page 81 and 82:
MEDI 156 Defining structure-activit
Page 83 and 84:
MEDI 160 Bivalent inhibitors of P-g
Page 85 and 86:
MEDI 164 Molecular basis for effica
Page 87 and 88:
MEDI 167 Discovery of the highly po
Page 89 and 90:
highly asymmetric, closely packed d
Page 91 and 92:
4/WP14-3, Sumneytown Pike, West Poi
Page 93 and 94:
MEDI 179 Design, synthesis, and eva
Page 95 and 96:
MEDI 182 Substituted-pyrrole 2-amin
Page 97 and 98:
MEDI 186 Discovery and optimization
Page 99 and 100:
phosphatase SHIP. Bioassay guided f
Page 101 and 102:
epibatidine for nicotinic channels.
Page 103 and 104:
derivative with striking solubility
Page 105 and 106:
MEDI 203 Core-modified mannopeptimy
Page 107 and 108:
MEDI 207 Enhancing the kinetic prof
Page 109 and 110:
hydroxyphenyl)piperazin-1-yl)butyl)
Page 111 and 112:
migration of people from these area
Page 113 and 114:
Schistosomiasis is, after malaria,
Page 115 and 116:
-Ketoacyl-ACP-synthase III (FabH) h
Page 117 and 118:
MEDI 225 Synthesis of the analog of
Page 119 and 120:
MEDI 229 Structure-based virtual sc
Page 121 and 122:
MEDI 234 TG100801: A prodrug for th
Page 123 and 124:
In the past, large collections of c
Page 125 and 126:
approach to the treatment of autoim
Page 127 and 128:
logPe values. The residual mean squ
Page 129 and 130:
Oligo-chitosan (OCS) which is a kin
Page 131 and 132:
characterization of novel muscarini
Page 133 and 134:
MEDI 257 Rigid analogs of 4,4-diary
Page 135 and 136:
MEDI 261 Strategies toward improvin
Page 137 and 138:
disease. It is generally accepted t
Page 139 and 140:
(BBB). Our preliminary in vitro dat
Page 141 and 142:
It is well-documented that androgen
Page 143 and 144:
MEDI 276 Investigating the manipula
Page 145 and 146:
were screened by FACS sarin labeled
Page 147 and 148:
MEDI 285 Design, synthesis and biol
Page 149 and 150:
equipment set-up and large scale ma
Page 151 and 152:
Significant effort has been directe
Page 153 and 154:
esearch was supported by funds from
Page 155 and 156:
synthesized a series of carbamoylch
Page 157 and 158:
proceeded more rapidly by switching
Page 159 and 160:
genes. With the understanding of th
Page 161 and 162:
MEDI 310 Optimized methods for the
Page 163 and 164:
Coupled with crystallographic data,
Page 165 and 166:
MEDI 317 Design and synthesis of hy
Page 167 and 168:
MEDI 320 Synthesis and antibacteria
Page 169 and 170:
DTPA. Incorporation of the nitro fu
Page 171 and 172:
MEDI 328 The mechanism of bioreduct
Page 173 and 174:
esistance, there is an urgent need
Page 175 and 176:
Giving the Rule-of-5 a more accurat
Page 177 and 178:
MEDI 338 Structure guided design of
Page 179 and 180:
MEDI 342 Synthesis of peptide-amilo
Page 181:
MEDI 346 Design, synthesis, and ant
show all

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

Create successful ePaper yourself

Delete template?

Save as template?