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

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established presence of NK-2 in the CNS suggests potential anxiolytic/antidepressant properties for NK-2 receptor antagonists. Therefore, the objective of this early phase research program was to develop a selective, potent and orally - active Neurokinin 2- receptor antagonist for the treatment of depression. The design, synthesis and evaluation of potent NK-2 receptor antagonists for the treatment of depression are described. Substituted piperidinyl 3,4- dihydroisoquinoline amides 1 were formally derived by a combination of classic SAR and solution phase library synthesis. Some members of this chemical series showed significant selectivity and binding affinity for the cloned human NK-2 receptor. MEDI 41 Novel 5-HT2A/D2/Sigma receptor ligands: Psychiatric disorder treatment agents Yong-Gil Kim, Joon Heo, Seon-Min Dong, Yun-Hee Kim, and Byong-Sung Kwak, Drug Development Center, SK Holdings, 140-1, Wonchon-dong, Yuseong-gu, Daejeon 305-712, South Korea, Fax: 82-42-866-7702, yonggil.kim@sk.com, joon.heo@sk.com Agents potently acting on the sigma receptors may be useful in the therapy of CNS diseases. Also, creating a specific drug for sigma receptor interaction and finding the novel pharmacological effect are important for developing new types of drugs. In our research strategy for new CNS drugs, we designed a novel ligand for sigma receptors and 5-HT2A/D2 receptors, conventional mechanism of atypical antipsychotics, which has potent affinity for triple mechanism. Potential applications of triple mechanism ligands are the treatment of depression, psychosis, and so on. Through our research strategy, we discovered that members of this class compounds demonstrate to be effective for schizophrenia and depression. This poster will highlight the SAR and biological data of these compounds. MEDI 42 Synthesis and structure-activity relationship of a series of alpha-azole substituted phenyl alkyl amines as 5-HT2A/D2 receptor ligands: Potential psychosis treatment agents
Yong-Gil Kim, Joon Heo, Mi-Kyung Ji, Nahm-Ryune Cho, Man-Young Cha, and Byong-Sung Kwak, Drug Development Center, SK Holdings, 140-1, Wonchon-dong, Yuseong-gu, Daejeon 305-712, South Korea, Fax: 82-42-866-7702, yonggil.kim@sk.com, mikyung.ji@sk.com The discovery and development of MNRA (Mixed Neurotransmitter Receptor Antagonists) as potential anti-psychosis agents are an attractive approach since many antipsychotics are known as serotonin / dopamine antagonists. By applying our library, we have identified a series of alpha-azole substituted phenyl alkyl amines as a 5-HT2A/D2 ligands and psychosis disorder treatment agents. The synthesis and biological activity of these compounds will be presented. MEDI 43 Structure activity relationship and pharmacological evaluation of carbamic acid benzoyl piperidine analog: YKP1358, novel atypical antipsychotics Yong-Gil Kim, Joon Heo, Seon-Min Dong, Mi-Kyung Ji, and Byong-Sung Kwak, Drug Development Center, SK Holdings, 140-1, Wonchon-dong, Yuseong-gu, Daejeon 305-712, South Korea, Fax: 82-42-866-7702, yonggil.kim@sk.com The development of atypical antipsychotics was an important milestone in the history of psychiatry, because it brought effective treatment options with reduced risks for adverse events. Unfortunately, current atypical antipsychotics did not clearly solve the side effect issues such as extrapyramidal syndrome, metabolic disorder. These side effects were due to low selectivity to side effect inducing receptor binding affinity / target receptor binding affinity. A clean ligand for target receptor is required for medical unmet need satisfaction. As a result of intensive and thorough research, we have found that a novel atypical antipsychotics, YKP1358, is more potent in efficacy and shows cleaner side effect profile than current atypicals. The SAR, antipsychotic efficacy and side effect profile of this novel compound will be presented along with a comparison with atypical antipsychotics. MEDI 44 Synthesis and SAR of pyridinyl-pyrazole derivatives as selective 5HT 2A inverse-agonists for platelet aggregation Peter I. Dosa, Bradley R. Teegarden, Jarrod Davidson, Martin Casper, John Adams, Juan Ramirez, William Thomsen, and Diane Yuskin, Arena Pharmaceuticals, Inc, 6166 Nancy Ridge Drive, San Diego, CA 92121, pdosa@arenapharm.com Inverse-agonists of the 5-HT 2A -receptor subtype are known to alleviate negative symptoms in schizophrenia, influence sleep patterns, and reduce the aggregation of platelets. As part of our investigations on 5-HT 2A inverse-agonists, a series of pyridinyl-pyrazole derivatives was identified. Several compounds were determined to be potent in both a 5-HT 2A binding assay and a platelet aggregation assay and were inactive at both the 5-HT 2B and 5-HT 2C serotonin receptors. The synthesis and SAR of this series will be presented.
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: Nicos A. Petasis 1 , Jasim Uddin 1
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
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
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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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