Search Results - "Mazzola, Robert"

Generation of Leads for γ‑Secretase Modulation by Mandal, Mihirbaran, Buevich, Alexei, Caldwell, John P, Hyde, Lynn, Huang, Xianhai, Liu, Xiaoxiang, McKittrick, Brian, Mazzola, Robert D, Pissarnitski, Dmitri, Palani, Anandan, Zhang, Lili, Parker, Eric, Xiao, Li, Rindgen, Diane, Zhu, Zhaoning

“…Herein, we disclose three structurally differentiated γ-secretase modulators (GSMs) based on an oxadiazine scaffold. The analogues from series I potently…”
Get full text

Structure-Based Design of an Iminoheterocyclic β‑Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central Aβ in Nonhuman Primates by Mandal, Mihirbaran, Wu, Yusheng, Misiaszek, Jeffrey, Li, Guoqing, Buevich, Alexei, Caldwell, John P, Liu, Xiaoxiang, Mazzola, Robert D, Orth, Peter, Strickland, Corey, Voigt, Johannes, Wang, Hongwu, Zhu, Zhaoning, Chen, Xia, Grzelak, Michael, Hyde, Lynn A, Kuvelkar, Reshma, Leach, Prescott T, Terracina, Giuseppe, Zhang, Lili, Zhang, Qi, Michener, Maria S, Smith, Brad, Cox, Kathleen, Grotz, Diane, Favreau, Leonard, Mitra, Kaushik, Kazakevich, Irina, McKittrick, Brian A, Greenlee, William, Kennedy, Matthew E, Parker, Eric M, Cumming, Jared N, Stamford, Andrew W

“…We describe successful efforts to optimize the in vivo profile and address off-target liabilities of a series of BACE1 inhibitors represented by 6 that…”
Get full text

Overcoming Time-Dependent Inhibition (TDI) of Cytochrome P450 3A4 (CYP3A4) Resulting from Bioactivation of a Fluoropyrimidine Moiety by Mandal, Mihirbaran, Mitra, Kaushik, Grotz, Diane, Lin, Xinjie, Palamanda, Jairam, Kumari, Pramila, Buevich, Alexei, Caldwell, John P, Chen, Xia, Cox, Kathleen, Favreau, Leonard, Hyde, Lynn, Kennedy, Matthew E, Kuvelkar, Reshma, Liu, Xiaoxiang, Mazzola, Robert D, Parker, Eric, Rindgen, Diane, Sherer, Edward, Wang, Hongwu, Zhu, Zhaoning, Stamford, Andrew W, Cumming, Jared N

“…Herein we describe structure–activity relationship (SAR) and metabolite identification (Met-ID) studies that provided insight into the origin of time-dependent…”
Get full text

Design and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme‑1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation by Mandal, Mihirbaran, Zhu, Zhaoning, Cumming, Jared N, Liu, Xiaoxiang, Strickland, Corey, Mazzola, Robert D, Caldwell, John P, Leach, Prescott, Grzelak, Michael, Hyde, Lynn, Zhang, Qi, Terracina, Giuseppe, Zhang, Lili, Chen, Xia, Kuvelkar, Reshma, Kennedy, Matthew E, Favreau, Leonard, Cox, Kathleen, Orth, Peter, Buevich, Alexei, Voigt, Johannes, Wang, Hongwu, Kazakevich, Irina, McKittrick, Brian A, Greenlee, William, Parker, Eric M, Stamford, Andrew W

“…On the basis of our observation that the biaryl substituent of iminopyrimidinone 7 must be in a pseudoaxial conformation to occupy the contiguous S1–S3…”
Get full text

Discovery of potent iminoheterocycle BACE1 inhibitors by Caldwell, John P., Mazzola, Robert D., Durkin, James, Chen, Joseph, Chen, Xia, Favreau, Leonard, Kennedy, Matthew, Kuvelkar, Reshma, Lee, Julie, McHugh, Nansie, McKittrick, Brian, Orth, Peter, Stamford, Andrew, Strickland, Corey, Voigt, Johannes, Wang, Liyang, Zhang, Lili, Zhang, Qi, Zhu, Zhaoning

“…The synthesis of a series of iminoheterocycles and their structure–activity relationships (SAR) as inhibitors of the aspartyl protease BACE1 will be detailed…”
Get full text

Discovery of novel hydroxamates as highly potent tumor necrosis factor-α converting enzyme inhibitors. Part II: Optimization of the S3′ pocket by Mazzola, Robert D., Zhu, Zhaoning, Sinning, Lisa, McKittrick, Brian, Lavey, Brian, Spitler, James, Kozlowski, Joseph, Neng-Yang, Shih, Zhou, Guowei, Guo, Zhuyan, Orth, Peter, Madison, Vincent, Sun, Jing, Lundell, Daniel, Niu, Xiaoda

“…We herein disclose a novel series of cyclopropyl hydroxamates that are potent and selective TACE inhibitors with K i values in the picomolar range. A series of…”
Get full text

Iminoheterocycles as γ-secretase modulators by Caldwell, John P., Bennett, Chad E., McCracken, Troy M., Mazzola, Robert D., Bara, Thomas, Buevich, Alexei, Burnett, Duane A., Chu, Inhou, Cohen-Williams, Mary, Josein, Hubert, Hyde, Lynn, Lee, Julie, McKittrick, Brian, Song, Lixin, Terracina, Giuseppe, Voigt, Johannes, Zhang, Lili, Zhu, Zhaoning

“…The synthesis of a novel series of iminoheterocycles and their structure–activity relationship (SAR) as modulators of γ-secretase activity will be detailed…”
Get full text

Stereoselective Nazarov Cyclizations of Bridged Bicyclic Dienones by Mazzola, Robert D, White, Timothy D, Vollmer-Snarr, Heidi R, West, F. G

“…Bridged bicyclic dienones underwent silyl-directed Nazarov cyclization with generally very high diastereoselectivity. In most cases, a strong preference for…”
Get full text

Unexpected Participation of an Unconjugated Olefin during Nazarov Cyclization of Bridged Bicyclic Dienones by Giese, Sören, Mazzola Jr, Robert D., Amann, Clare M., Arif, Atta M., West, F. G.

“…Surprising rearrangements in a rigid system: A cyclopropyl ring is formed unexpectedly when a trienone substrate is subjected to the Nazarov cyclization (see…”
Get full text

Discovery of new SCH 39166 analogs as potent and selective dopamine D1 receptor antagonists by Qiang, Li, Sasikumar, T K, Burnett, Duane A, Su, Jing, Tang, Haiqun, Ye, Yuanzan, Mazzola, Jr, Robert D, Zhu, Zhaoning, McKittrick, Brian A, Greenlee, William J, Fawzi, Ahmad, Smith, Michelle, Zhang, Hongtao, Lachowicz, Jean E

“…A series of novel dopamine D(1) antagonists derived from functionalization of the D-ring of SCH 39166 were prepared. A number of these compounds displayed…”
Get full text

Mild Condition for the Deoxygenation of α‑Heteroaryl-Substituted Methanol Derivatives by Meng, Na, Yu, Wensheng, Suzuki, Takao, Chen, Maofen, Qi, Zhiqi, Hu, Bin, Bao, Jianming, Debenham, John S, Mazzola, Robert, Duffy, Joseph L

“…A mild condition via PPh3/I2/imidazole for the deoxygenation of substituted methanol derivatives has been identified. This metal-free process was found to…”
Get full text

Diversity & tractability revisited in collaborative small molecule phenotypic screening library design by Lahue, Brian R., Glick, Meir, Tudor, Matthew, Johnson, Scott Arne, Diratsouian, Janet, Wildey, Mary Jo, Burton, Marybeth, Mazzola, Robert, Wassermann, Anne Mai

“…To create your abstract, type over the instructions in the template box below. Fonts or abstract dimensions should not be changed or altered. [Display omitted]…”
Get full text

Discovery of [11C]MK-6884: A Positron Emission Tomography (PET) Imaging Agent for the Study of M4Muscarinic Receptor Positive Allosteric Modulators (PAMs) in Neurodegenerative Diseases by Tong, Ling, Li, Wenping, Lo, Michael Man-Chu, Gao, Xiaolei, Wai, Jenny Miu-Chen, Rudd, Michael, Tellers, David, Joshi, Aniket, Zeng, Zhizhen, Miller, Patricia, Salinas, Cristian, Riffel, Kerry, Haley, Hyking, Purcell, Mona, Holahan, Marie, Gantert, Liza, Schubert, Jeffrey W, Jones, Kristen, Mulhearn, James, Egbertson, Melissa, Meng, Zhaoyang, Hanney, Barbara, Gomez, Robert, Harrison, Scott T, McQuade, Paul, Bueters, Tjerk, Uslaner, Jason, Morrow, John, Thomson, Fiona, Kong, Jongrock, Liao, Jing, Selyutin, Oleg, Bao, Jianming, Hastings, Nicholas B, Agrawal, Sony, Magliaro, Brian C, Monsma, Frederick J, Smith, Michelle D, Risso, Stefania, Hesk, David, Hostetler, Eric, Mazzola, Robert

“…The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed…”
Get full text

Unprecedented Reversal of Regioselectivity during Methanolysis and an Interception of Curtius Rearrangement by Mandal, Mihirbaran, Buevich, Alexei V., Wang, Hongwu, Brunskill, Andrew, Orth, Peter, Caldwell, John P., Liu, Xiaoxiang, Mazzola, Robert, Cumming, Jared, McKittrick, Brian, Zhu, Zhaoning, Stamford, Andrew

“…Unprecedented reversal in regioselectivity during methanolysis of anhydrides due to the change in substitution pattern of fluorine in the phenyl moiety, and…”
Get full text

Discovery of Ruzasvir (MK-8408): A Potent, Pan-Genotype HCV NS5A Inhibitor with Optimized Activity against Common Resistance-Associated Polymorphisms by Tong, Ling, Yu, Wensheng, Chen, Lei, Selyutin, Oleg, Dwyer, Michael P, Nair, Anilkumar G, Mazzola, Robert, Kim, Jae-Hun, Sha, Deyou, Yin, Jingjun, Ruck, Rebecca T, Davies, Ian W, Hu, Bin, Zhong, Bin, Hao, Jinglai, Ji, Tao, Zan, Shuai, Liu, Rong, Agrawal, Sony, Xia, Ellen, Curry, Stephanie, McMonagle, Patricia, Bystol, Karin, Lahser, Frederick, Carr, Donna, Rokosz, Laura, Ingravallo, Paul, Chen, Shiying, Feng, Kung-I, Cartwright, Mark, Asante-Appiah, Ernest, Kozlowski, Joseph A

“…We describe the research that led to the discovery of compound 40 (ruzasvir, MK-8408), a pan-genotypic HCV nonstructural protein 5A (NS5A) inhibitor with a…”
Get full text

Antinociceptive effects of potent, selective and brain penetrant muscarinic M 4 positive allosteric modulators in rodent pain models by Grauer, Steven M, Sanoja, Raul, Poulin, Dominic, Rashid, Harunor, Jochnowitz, Nina, Calhoun, Michael, Zwilling, Daniel, Varty, Geoffrey B, Rosahl, Thomas W, Meziane, Hamid, Mittlelhaeuser, Christopher, Mazzola, Robert, Morrow, John, Smith, Sean M, Henze, Darrell, Marcus, Jacob

“…Analgesic properties of orthosteric agonists of the muscarinic M receptor subtype have been documented in literature reports, with evidence from…”
Get full text

Antinociceptive effects of potent, selective and brain penetrant muscarinic M4 positive allosteric modulators in rodent pain models by Grauer, Steven M., Sanoja, Raul, Poulin, Dominic, Rashid, Harunor, Jochnowitz, Nina, Calhoun, Michael, Zwilling, Daniel, Varty, Geoffrey B., Rosahl, Thomas W., Meziane, Hamid, Mittlelhaeuser, Christopher, Mazzola, Robert, Morrow, John, Smith, Sean M., Henze, Darrell, Marcus, Jacob

“…•Two novel M4 PAMs were characterized in rodent models of acute pain.•Compounds reduced nociceptive behaviors in mouse formalin and tail flick models.•KO…”
Get full text

MK-8325: A silyl proline-containing NS5A inhibitor with pan-genotype activity for treatment of HCV by Nair, Anilkumar G., Zeng, Qingbei, Selyutin, Oleg, Rosenblum, Stuart B., Jiang, Yueheng, Yang, De-Yi, Keertikar, Kerry, Zhou, Guowei, Dwyer, Michael, Kim, Seong Heon, Shankar, Bandarpalle, Yu, Wensheng, Tong, Ling, Chen, Lei, Mazzola, Robert, Caldwell, John, Tang, Haiqun, Agrawal, Sony, Liu, Rong, Kong, Rong, Ingravallo, Paul, Xia, Ellen, Zhai, Ying, Nomeir, Amin, Asante-Appiah, Ernest, Kozlowski, Joseph A.

“…HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral…”
Get full text

Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development by Nair, Anilkumar G., Zeng, Qingbei, Selyutin, Oleg, Rosenblum, Stuart B., Jiang, Yueheng, Yang, De-Yi, Keertikar, Kerry, Zhou, Guowei, Dwyer, Michael P., Kim, Seong Heon, Shankar, Bandarpalle, Yu, Wensheng, Tong, Ling, Chen, Lei, Mazzola, Robert, Caldwell, John, Tang, Haiqun, Allard, Melissa L., Buckle, Ronald N., Gauuan, Polivina Jolicia F., Holst, Christian L., Martin, Gregory S., Naicker, Kannan P., Vellekoop, Samuel, Agrawal, Sony, Liu, Rong, Kong, Rong, Ingravallo, Paul, Xia, Ellen, Zhai, Ying, Nomeir, Amin, Kozlowski, Joseph A.

“…HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral…”
Get full text

Cyclic Hydroxyamidines as Amide Isosteres: Discovery of Oxadiazolines and Oxadiazines as Potent and Highly Efficacious γ-Secretase Modulators in Vivo by Sun, Zhong-Yue, Asberom, Theodros, Bara, Thomas, Bennett, Chad, Burnett, Duane, Chu, Inhou, Clader, John, Cohen-Williams, Mary, Cole, David, Czarniecki, Michael, Durkin, James, Gallo, Gioconda, Greenlee, William, Josien, Hubert, Huang, Xianhai, Hyde, Lynn, Jones, Nicholas, Kazakevich, Irina, Li, Hongmei, Liu, Xiaoxiang, Lee, Julie, MacCoss, Malcolm, Mandal, Mihir B, McCracken, Troy, Nomeir, Amin, Mazzola, Robert, Palani, Anandan, Parker, Eric M, Pissarnitski, Dmitri A, Qin, Jun, Song, Lixin, Terracina, Giuseppe, Vicarel, Monica, Voigt, Johannes, Xu, Ruo, Zhang, Lili, Zhang, Qi, Zhao, Zhiqiang, Zhu, Xiaohong, Zhu, Zhaoning

“…Cyclic hydroxyamidines were designed and validated as isosteric replacements of the amide functionality. Compounds with these structural motifs were found to…”
Get full text