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1
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Identification of a hydroxylamine glucuronide metabolite of an oral hypoglycemic agent

Miller, Randall R ; Doss, George A ; Stearns, Ralph A

Drug metabolism and disposition: the biological fate of chemicals, February 2004, Vol.32(2), pp.178-85 [Peer Reviewed Journal]

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Conversion of the 2,2,6,6-tetramethylpiperidine moiety to a 2,2-dimethylpyrrolidine by cytochrome P450: evidence for a mechanism involving nitroxide radicals and heme iron

Yin, Wenji ; Mitra, Kaushik ; Stearns, Ralph A ; Baillie, Thomas A ; Kumar, Sanjeev

Biochemistry, 11 May 2004, Vol.43(18), pp.5455-66 [Peer Reviewed Journal]

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Cytochrome P450 3A4-mediated oxidative conversion of a cyano to an amide group in the metabolism of pinacidil

Zhang, Zhoupeng ; Li, Ying ; Stearns, Ralph A ; Ortiz De Montellano, Paul R ; Baillie, Thomas A ; Tang, Wei

Biochemistry, 26 February 2002, Vol.41(8), pp.2712-8 [Peer Reviewed Journal]

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Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide

Kumar, Sanjeev ; Samuel, Koppara ; Subramanian, Ramaswamy ; Braun, Matthew P ; Stearns, Ralph A ; Chiu, Shuet-Hing Lee ; Evans, David C ; Baillie, Thomas A

The Journal of pharmacology and experimental therapeutics, December 2002, Vol.303(3), pp.969-78 [Peer Reviewed Journal]

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5
Mechanism-Based Inhibition of Human Steroid 5α-Reductase by Finasteride:  Enzyme-Catalyzed Formation of NADP−Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor
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Mechanism-Based Inhibition of Human Steroid 5α-Reductase by Finasteride:  Enzyme-Catalyzed Formation of NADP−Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor

Bull, Herbert G. ; Garcia-Calvo, Margarita ; Andersson, Stefan ; Baginsky, Walter F. ; Chan, H. Karen ; Ellsworth, Dina E. ; Miller, Randall R. ; Stearns, Ralph A. ; Bakshi, Raman K. ; Rasmusson, Gary H. ; Tolman, Richard L. ; Myers, Robert W. ; Kozarich, John W. ; Harris, Georgianna S.

Journal of the American Chemical Society, 01/1996, Vol.118(10), pp.2359-2365 [Peer Reviewed Journal]

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6
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Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist

Hong, Qingmei ; Bakshi, Raman K ; Palucki, Brenda L ; Park, Min K ; Ye, Zhixiong ; He, Shuwen ; Pollard, Patrick G ; Sebhat, Iyassu K ; Liu, Jian ; Guo, Liangqin ; Cashen, Doreen E ; Martin, William J ; Weinberg, David H ; Macneil, Tanya ; Tang, Rui ; Tamvakopoulos, Constantin ; Peng, Qianping ; Miller, Randy R ; Stearns, Ralph A ; Chen, Howard Y

Bioorganic & Medicinal Chemistry Letters, 2011, Vol.21(8), pp.2330-2334 [Peer Reviewed Journal]

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7
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N-acetylation of the glutamate residue of intact glutathione conjugates in rats: a novel pathway for the metabolic processing of thiol adducts of xenobiotics

Yin, Wenji ; Doss, George A ; Stearns, Ralph A ; Kumar, Sanjeev

Drug metabolism and disposition: the biological fate of chemicals, January 2004, Vol.32(1), pp.43-8 [Peer Reviewed Journal]

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8
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Effect of quinidine on the 10-hydroxylation of R-warfarin: species differences and clearance projection

Chen, Qing ; Tan, Eugene ; Strauss, John R ; Zhang, Zhoupeng ; Fenyk-Melody, Judith E ; Booth-Genthe, Catherine ; Rushmore, Thomas H ; Stearns, Ralph A ; Evans, David C ; Baillie, Thomas A ; Tang, Wei

The Journal of pharmacology and experimental therapeutics, October 2004, Vol.311(1), pp.307-14 [Peer Reviewed Journal]

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9
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Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity

He, Shuwen ; Ye, Zhixiong ; Dobbelaar, Peter H ; Sebhat, Iyassu K ; Guo, Liangqin ; Liu, Jian ; Jian, Tianying ; Lai, Yingjie ; Franklin, Christopher L ; Bakshi, Raman K ; Dellureficio, James P ; Hong, Qingmei ; Weinberg, David H ; Macneil, Tanya ; Tang, Rui ; Strack, Alison M ; Tamvakopoulos, Constantin ; Peng, Qianping ; Miller, Randy R ; Stearns, Ralph A

Bioorganic & Medicinal Chemistry Letters, 01 August 2010, Vol.20(15), pp.4399-4405 [Peer Reviewed Journal]

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10
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Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity

He, Shuwen ; Ye, Zhixiong ; Dobbelaar, Peter H ; Bakshi, Raman K ; Hong, Qingmei ; Dellureficio, James P ; Sebhat, Iyassu K ; Guo, Liangqin ; Liu, Jian ; Jian, Tianying ; Lai, Yingjie ; Franklin, Christopher L ; Reibarkh, Mikhail ; Holmes, Mark A ; Weinberg, David H ; Macneil, Tanya ; Tang, Rui ; Tamvakopoulos, Constantin ; Peng, Qianping ; Miller, Randy R

Bioorganic & Medicinal Chemistry Letters, 2010, Vol.20(22), pp.6524-6532 [Peer Reviewed Journal]

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11
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Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands

Hong, Qingmei ; Bakshi, Raman K ; Dellureficio, James ; He, Shuwen ; Ye, Zhixiong ; Dobbelaar, Peter H ; Sebhat, Iyassu K ; Guo, Liangqin ; Liu, Jian ; Jian, Tianying ; Tang, Rui ; Kalyani, Rubana N ; Macneil, Tanya ; Vongs, Aurawan ; Rosenblum, Charles I ; Weinberg, David H ; Peng, Qingping ; Tamvakopoulos, Constantin ; Miller, Randy R ; Stearns, Ralph A

Bioorganic & Medicinal Chemistry Letters, 01 August 2010, Vol.20(15), pp.4483-4486 [Peer Reviewed Journal]

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12
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Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist

He, Shuwen ; Ye, Zhixiong ; Dobbelaar, Peter H ; Sebhat, Iyassu K ; Guo, Liangqin ; Liu, Jian ; Jian, Tianying ; Lai, Yingjie ; Franklin, Christopher L ; Bakshi, Raman K ; Dellureficio, James P ; Hong, Qingmei ; Tsou, Nancy N ; Ball, Richard G ; Cashen, Doreen E ; Martin, William J ; Weinberg, David H ; Macneil, Tanya ; Tang, Rui ; Tamvakopoulos, Constantin

Bioorganic & Medicinal Chemistry Letters, 2010, Vol.20(7), pp.2106-2110 [Peer Reviewed Journal]

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13
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Characterization of two cyclic metabolites of sitagliptin

Liu, David Q ; Arison, Byron H ; Stearns, Ralph A ; Kim, Dooseop ; Vincent, Stella H

Drug metabolism and disposition: the biological fate of chemicals, April 2007, Vol.35(4), pp.521-4 [Peer Reviewed Journal]

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14
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Design and pharmacology of N-(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl-(1R)-1-(4-chlorobenzyl)- 2-4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist

Sebhat, Iyassu K ; Martin, William J ; Ye, Zhixiong ; Barakat, Khaled ; Mosley, Ralph T ; Johnston, David B R ; Bakshi, Raman ; Palucki, Brenda ; Weinberg, David H ; Macneil, Tanya ; Kalyani, Rubana N ; Tang, Rui ; Stearns, Ralph A ; Miller, Randy R ; Tamvakopoulos, Constantin ; Strack, Alison M ; Mcgowan, Erin ; Cashen, Doreen E ; Drisko, Jennifer E ; Hom

Journal of medicinal chemistry, 10 October 2002, Vol.45(21), pp.4589-93 [Peer Reviewed Journal]

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15
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A novel P450-catalyzed transformation of the 2,2,6,6-tetramethyl piperidine moiety to a 2,2-dimethyl pyrrolidine in human liver microsomes: characterization by high resolution quadrupole-time-of-flight mass spectrometry and 1H-NMR

Yin, Wenji ; Doss, George A ; Stearns, Ralph A ; Chaudhary, Ashok G ; Hop, Cornelis E ; Franklin, Ronald B ; Kumar, Sanjeev

Drug metabolism and disposition: the biological fate of chemicals, February 2003, Vol.31(2), pp.215-23 [Peer Reviewed Journal]

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16
Discovery of a Potent, Orally Bioavailable β 3 Adrenergic Receptor Agonist, ( R )- N -[4-[2-[[2-Hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide
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Discovery of a Potent, Orally Bioavailable β 3 Adrenergic Receptor Agonist, ( R )- N -[4-[2-[[2-Hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide

Mathvink, Robert J. ; Tolman, J. Samuel ; Chitty, Dawn ; Candelore, Mari R. ; Cascieri, Margaret A. ; Colwell, Lawrence F. ; Deng, Liping ; Feeney, William P. ; Forrest, Michael J. ; Hom, Gary J. ; Macintyre, D. Euan ; Miller, Randall R. ; Stearns, Ralph A. ; Tota, Laurie ; Wyvratt, Matthew J. ; Fisher, Michael H. ; Weber, Ann E.

Journal of Medicinal Chemistry, 10/2000, Vol.43(21), pp.3832-3836 [Peer Reviewed Journal]

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17
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In vivo covalent binding of [ 14C]trinitrotoluene to proteins in the rat

Liu, Yu-Ying ; Lu, Anthony Y.H ; Stearns, Ralph A ; Chiu, Shuet-Hing Lee

Chemico-Biological Interactions, 1992, Vol.82(1), pp.1-19 [Peer Reviewed Journal]

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18
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In vitro metabolic activation of lumiracoxib in rat and human liver preparations

Li, Ying ; Slatter, J Greg ; Zhang, Zhoupeng ; Li, Yan ; Doss, George A ; Braun, Matthew P ; Stearns, Ralph A ; Dean, Dennis C ; Baillie, Thomas A ; Tang, Wei

Drug metabolism and disposition: the biological fate of chemicals, February 2008, Vol.36(2), pp.469-73 [Peer Reviewed Journal]

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19
Roles of Human Hepatic Cytochrome P450s 2C9 and 3A4 in the Metabolic Activation of Diclofenac †
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Roles of Human Hepatic Cytochrome P450s 2C9 and 3A4 in the Metabolic Activation of Diclofenac †

Tang, Wei ; Stearns, Ralph A. ; Wang, Regina W. ; Chiu, Shuet-Hing L. ; Baillie, Thomas A.

Chemical Research in Toxicology, 02/1999, Vol.12(2), pp.192-199 [Peer Reviewed Journal]

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20
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Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes

Xu, Shiyao ; Zhu, Bing ; Teffera, Yohannes ; Pan, Deborah E ; Caldwell, Charles G ; Doss, George ; Stearns, Ralph A ; Evans, David C ; Beconi, Maria G

Drug metabolism and disposition: the biological fate of chemicals, January 2005, Vol.33(1), pp.121-30 [Peer Reviewed Journal]

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21
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Metabolism of a thiazole benzenesulfonamide derivative, a potent and elective agonist of the human beta3-adrenergic receptor, in rats: identification of a novel isethionic acid conjugate

Tang, Wei ; Stearns, Ralph A ; Miller, Randall R ; Ngui, Jason S ; Mathvink, Robert J ; Weber, Ann E ; Kwei, Gloria Y ; Strauss, John R ; Keohane, Carol A ; Doss, George A ; Chiu, Shuet-Hing L ; Baillie, Thomas A

Drug metabolism and disposition: the biological fate of chemicals, July 2002, Vol.30(7), pp.778-87 [Peer Reviewed Journal]

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22
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Addressing the metabolic activation potential of new leads in drug discovery: a case study using ion trap mass spectrometry and tritium labeling techniques

Samuel, Koppara ; Yin, Wenji ; Stearns, Ralph A. ; Tang, Yui S. ; Chaudhary, Ashok G. ; Jewell, James P. ; Lanza, Thomas ; Lin, Linus S. ; Hagmann, William K. ; Evans, David C. ; Kumar, Sanjeev

Journal of Mass Spectrometry, February 2003, Vol.38(2), pp.211-221 [Peer Reviewed Journal]

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23
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Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation

Chen, Qing ; Ngui, Jason S ; Doss, George A ; Wang, Regina W ; Cai, Xiaoxin ; Dininno, Frank P ; Blizzard, Timothy A ; Hammond, Milton L ; Stearns, Ralph A ; Evans, David C ; Baillie, Thomas A ; Tang, Wei

Chemical research in toxicology, July 2002, Vol.15(7), pp.907-14 [Peer Reviewed Journal]

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24
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Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs

Beconi, Maria G ; Reed, James R ; Teffera, Yohannes ; Xia, Yuan-Qing ; Kochansky, Christopher J ; Liu, David Q ; Xu, Shiyao ; Elmore, Charles S ; Ciccotto, Suzanne ; Hora, Donald F ; Stearns, Ralph A ; Vincent, Stella H

Drug metabolism and disposition: the biological fate of chemicals, April 2007, Vol.35(4), pp.525-32 [Peer Reviewed Journal]

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25
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Evidence for the bioactivation of zomepirac and tolmetin by an oxidative pathway: identification of glutathione adducts in vitro in human liver microsomes and in vivo in rats

Chen, Qing ; Doss, George A ; Tung, Elaine C ; Liu, Wensheng ; Tang, Yui S ; Braun, Matthew P ; Didolkar, Varsha ; Strauss, John R ; Wang, Regina W ; Stearns, Ralph A ; Evans, David C ; Baillie, Thomas A ; Tang, Wei

Drug metabolism and disposition: the biological fate of chemicals, January 2006, Vol.34(1), pp.145-51 [Peer Reviewed Journal]

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26
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In vitro bioactivation of dihydrobenzoxathiin selective estrogen receptor modulators by cytochrome P450 3A4 in human liver microsomes: formation of reactive iminium and quinone type metabolites

Zhang, Zhoupeng ; Chen, Qing ; Li, Ying ; Doss, George A ; Dean, Brian J ; Ngui, Jason S ; Silva Elipe, Maria ; Kim, Seongkon ; Wu, Jane Y ; Dininno, Frank ; Hammond, Milton L ; Stearns, Ralph A ; Evans, David C ; Baillie, Thomas A ; Tang, Wei

Chemical research in toxicology, April 2005, Vol.18(4), pp.675-85 [Peer Reviewed Journal]

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27
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2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists

Palucki, Brenda L ; Park, Min K ; Nargund, Ravi P ; Tang, Rui ; Macneil, Tanya ; Weinberg, David H ; Vongs, Aurawan ; Rosenblum, Charles I ; Doss, George A ; Miller, Randall R ; Stearns, Ralph A ; Peng, Qianping ; Tamvakopoulos, Constantin ; Van Der Ploeg, Lex H.T ; Patchett, Arthur A

Bioorganic & Medicinal Chemistry Letters, 2005, Vol.15(8), pp.1993-1996 [Peer Reviewed Journal]

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28
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Metabolic activation of a 1,3-disubstituted piperazine derivative: evidence for a novel ring contraction to an imidazoline

Doss, George A ; Miller, Randall R ; Zhang, Zhoupeng ; Teffera, Yohannes ; Nargund, Ravi P ; Palucki, Brenda ; Park, Min K ; Tang, Yui S ; Evans, David C ; Baillie, Thomas A ; Stearns, Ralph A

Chemical research in toxicology, February 2005, Vol.18(2), pp.271-6 [Peer Reviewed Journal]

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29
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The pharmacokinetics of a thiazole benzenesulfonamide beta 3-adrenergic receptor agonist and its analogs in rats, dogs, and monkeys: improving oral bioavailability

Stearns, Ralph A ; Miller, Randy R ; Tang, Wei ; Kwei, Gloria Y ; Tang, Frank S ; Mathvink, Robert J ; Naylor, Elizabeth M ; Chitty, Dawn ; Colandrea, Vincent J ; Weber, Ann E ; Colletti, Adria E ; Strauss, John R ; Keohane, Carol Ann ; Feeney, William P ; Iliff, Susan A ; Chiu, Shuet-Hing Lee

Drug metabolism and disposition: the biological fate of chemicals, July 2002, Vol.30(7), pp.771-7 [Peer Reviewed Journal]

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30
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Discovery of an orally bioavailable alkyl oxadiazole β 3 adrenergic receptor agonist

Feng, Danqing D ; Biftu, Tesfaye ; Candelore, Mari R ; Cascieri, Margaret A ; Colwell, Lawrence F ; Deng, Liping ; Feeney, William P ; Forrest, Michael J ; Hom, Gary J ; Macintyre, D.Euan ; Miller, Randall R ; Stearns, Ralph A ; Strader, Catherine D ; Tota, Laurie ; Wyvratt, Matthew J ; Fisher, Michael H ; Weber, Ann E

Bioorganic & Medicinal Chemistry Letters, 2000, Vol.10(13), pp.1427-1429 [Peer Reviewed Journal]

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31
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1-Amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid as a Tic mimetic: Application in the synthesis of potent human melanocortin-4 receptor selective agonists

Bakshi, Raman K ; Hong, Qingmei ; Olson, J.T ; Ye, Zhixiong ; Sebhat, Iyassue K ; Weinberg, David H ; Macneil, Tanya ; Kalyani, Rubana N ; Tang, Rui ; Martin, William J ; Strack, Alison ; Mcgowan, Erin ; Tamvakopoulos, Constantin ; Miller, Randy R ; Stearns, Ralph A ; Tang, Wei ; Maclntyre, D. Euan ; van Der Ploeg, Lex H.T ; Patchett, Arthur A ; Nargund, Ravi P

Bioorganic & Medicinal Chemistry Letters, 2005, Vol.15(14), pp.3430-3433 [Peer Reviewed Journal]

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32
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Discovery of (2 S)- N-[(1 R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist

Palucki, Brenda L ; Park, Min K ; Nargund, Ravi P ; Ye, Zhixiong ; Sebhat, Iyassu K ; Pollard, Patrick G ; Kalyani, Rubana N ; Tang, Rui ; Macneil, Tanya ; Weinberg, David H ; Vongs, Aurawan ; Rosenblum, Charles I ; Doss, George A ; Miller, Randall R ; Stearns, Ralph A ; Peng, Qianping ; Tamvakopoulos, Constantin ; Mcgowan, Erin ; Martin, William J ; Metzger, Joseph M

Bioorganic & Medicinal Chemistry Letters, 2005, Vol.15(1), pp.171-175 [Peer Reviewed Journal]

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33
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Human β3 adrenergic receptor agonists containing cyclic ureidobenzenesulfonamides

Parmee, Emma R ; Naylor, Elizabeth M ; Perkins, Leroy ; Colandrea, Vincent J ; Ok, Hyun O ; Candelore, Mari R ; Cascieri, Margaret A ; Deng, Liping ; Feeney, William P ; Forrest, Michael J ; Hom, Gary J ; Macintyre, D.Euan ; Miller, Randall R ; Stearns, Ralph A ; Strader, Catherine D ; Tota, Laurie ; Wyvratt, Matthew J ; Fisher, Michael H ; Weber, Ann E

Bioorganic & Medicinal Chemistry Letters, 1999, Vol.9(5), pp.749-754 [Peer Reviewed Journal]

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34
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Synthesis and SAR of benzyl and phenoxymethylene oxadiazole benzenesulfonamides as selective β 3 adrenergic receptor agonist antiobesity agents

Biftu, Tesfaye ; Feng, Dennis D ; Liang, Gui-Bai ; Kuo, Howard ; Qian, Xiaoxia ; Naylor, Elizabeth M ; Colandrea, Vincent J ; Candelore, Mari R ; Cascieri, Margaret A ; Colwell, Lawrence F ; Forrest, Michael J ; Hom, Gary J ; Macintyre, D.Euan ; Stearns, Ralph A ; Strader, Catherine D ; Wyvratt, Matthew J ; Fisher, Michael H ; Weber, Ann E

Bioorganic & Medicinal Chemistry Letters, 2000, Vol.10(13), pp.1431-1434 [Peer Reviewed Journal]

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35
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L-770,644: A potent and selective human β3 adrenergic receptor agonist with improved oral bioavailability

Shih, Thomas L ; Candelore, Mari R ; Cascieri, Margaret A ; Chiu, Shuet-Hing L ; Colwell, Lawrence F ; Deng, Liping ; Feeney, William P ; Forrest, Michael J ; Hom, Gary J ; Macintyre, D.Euan ; Miller, Randall R ; Stearns, Ralph A ; Strader, Catherine D ; Tota, Laurie ; Wyvratt, Matthew J ; Fisher, Michael H ; Weber, Ann E

Bioorganic & Medicinal Chemistry Letters, 1999, Vol.9(9), pp.1251-1254 [Peer Reviewed Journal]

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36
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Discovery and activity of (1 R,4 S,6 R)- N-[(1 R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist

Ye, Zhixiong ; Guo, Liangqin ; Barakat, Khaled J ; Pollard, Patrick G ; Palucki, Brenda L ; Sebhat, Iyassu K ; Bakshi, Raman K ; Tang, Rui ; Kalyani, Rubana N ; Vongs, Aurawan ; Chen, Airu S ; Chen, Howard Y ; Rosenblum, Charles I ; Macneil, Tanya ; Weinberg, David H ; Peng, Qianping ; Tamvakopoulos, Constantin ; Miller, Randy R ; Stearns, Ralph A ; Cashen, Doreen E

Bioorganic & Medicinal Chemistry Letters, 2005, Vol.15(15), pp.3501-3505 [Peer Reviewed Journal]

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37
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3-Pyridyloxypropanolamine agonists of the β3 adrenergic receptor with improved pharmacokinetic properties

Weber, Ann E ; Ok, Hyun O ; Alvaro, Raul F ; Candelore, Mari R ; Cascieri, Margaret A ; Chiu, Shuet-Hing L ; Deng, Liping ; Forrest, Michael J ; Hom, Gary J ; Hutchins, Jennifer E ; Kao, John ; Macintyre, D.Euan ; Mathvink, Robert J ; Mcloughlin, Debra ; Miller, Randall R ; Newbold, Ronald C ; Olah, Timothy V ; Parmee, Emma R ; Perkins, Leroy ; Stearns, Ralph A

Bioorganic & Medicinal Chemistry Letters, 1998, Vol.8(16), pp.2111-2116 [Peer Reviewed Journal]

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