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James C. Barrow

James C. Barrow
Department Affiliation: Primary: Pharmacology and Molecular Sciences;
Lieber Institute for Brain Development 
Degree: Ph.D., Harvard University
Rank: Associate Professor
Telephone Number : 410-955-0894
Fax Number: 410-955-3023
E-mail address: jbarrow@jhmi.edu
School of Medicine Address: Room 336, John G. Rangos, Sr., Building, 855 N. Wolfe Street, Baltimore, MD  21205
 

Drug discovery for disorders of neurodevelopment.

The research group is a laboratory focused on medicinal chemistry, primarily addressing diseases of neurodevelopment such as schizophrenia. Biological activity and structure-based drug design are used to drive chemistry target selection, and we are developing synthetic methods to efficiently prepare those targets. These efforts are tightly coupled with in vitro and in vivo testing and analysis, in collaboration with other research groups and core facilities at Johns Hopkins University or externally. At the core, the lab is engaged in the design and synthesis of molecules for a given biological target, analysis of in vitro and in vivo results, as well as further refinement through multiple cycles of synthesis and testing. Advances in reaction methodology, reagent availability, parallel synthesis, and purification technology now allow preparation of compounds in an efficient manner so that we can quickly drive structure-activity relationship studies and identify advanced leads. These advanced leads will have good potency and selectivity for the target of interest, and will be used to test biological hypotheses both in vitro and in vivo to determine if modulating the target is indeed a viable therapeutic strategy. By executing on medicinal chemistry programs, we will drive translational science from target and pathway discovery to novel medicines for patients.
 

Representative Publications:  

  • Barrow, J.C., Stauffer, S.R., Rittle, K.E.,  Ngo, P.L., Yang, Z., Selnick, H.G., Graham, S.L., Munshi, S., McGaughey, G.B.,  Holloway, M.K., Simon, A.J., Price, E.A., Sankaranarayanan, S.,  Colussi, D.,  Tugusheva, K., Lai, M.T., Espeseth, A.S., Xu, M., Huang, Q., Wolfe, A., Pietrak, B., Zuck, P., Levorse, D.A., Hazuda, D., Vacca, J.P.  Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of beta-Secretase. J. Med. Chem. 51: 6259-6262, 2008.  Pub Med Reference 

  • Uebele, V.N., Gotter, A.L., Nuss, C.E., Kraus, R.L., Doran, S.M., Garson, S.L., Reiss, D.R., Li, Y., Barrow, J.C., Reger, T.S., Yang, Z.Q., Ballard, J.E., Tang, C., Metzger, J.M., Wang, S.P., Koblan, K.S., Renger, J.J. T-type Calcium Channel Antagonism Inhibits High Fat Diet-Induced Weight Gain. J. Clin. Invest.  19: 1659-1667, 2009.   Pub Med Reference

  • Yang, F.V., Shipe, W.D., Bunda, J.L., Nolt, M.B., Wisnoski, D.D., Zhao, Z., Barrow, J.C., Ray, W.J., Ma, L., Whitmann, M., Seager, M.A., Koeplinger, K.A., Hartman, G.D., Lindsley, C.W.  Parallel Synthesis of N-Biaryl Quinoline Carboxylic Acids as Selective M1 Positive Allosteric Modulators. Bioorg. Med. Chem. Lett.  20: 531-536, 2010.  Pub Med Reference

  • Barrow, J.C., Rittle, K.E., Reger, T.S., Yang, Z.Q., Bondiskey, P., McGaughey, G.B., Bock, M.G., Hartman, G.D., Tang, C., Ballard, J.E., Kuo, Y., Prueksaritanont, T., Nuss, C.E., Doran, S.M., Fox, S.V., Garson, S.L., Kraus, R.L., Li, Y., Marino, M.J.,  Kuzmick, Graufelds V.,  Uebele, V.N., Renger, J.J.  Discovery of 4,4-Disubstituted Quinazolin-2-ones as T-Type Calcium Channel Antagonists. ACS Med. Chem. Lett. 1: 75-, 2010.  Pub Med Reference not available.

  • Rajapakse, H.A., Nantermet, P.G., Selnick, H.G., Barrow, J.C., McGaughey, G.B., Munshi, S., Lindsley, S.R., Young, M.B., Ngo, P.L., Holloway, M.K., Lai, M.T., Espeseth, A.S., Shi, X.P., Colussi, D., Pietrak, B., Crouthamel, M.C., Tugusheva, K., Huang, Q., Xu, M., Simon, A.J., Kuo, L., Hazuda, D.J., Graham, S.L., Vacca, J.P. SAR of tertiary carbinamine derived BACE1 inhibitors: Role of aspartate ligand amine pKa in enzyme inhibition. Bioorg. Med. Chem. Lett.  2010; 20: 1885-1889, 2010.  Pub Med Reference

  • Barrow, J.C., Duffy, J.L. Voltage-Gated Calcium Channel Antagonists for the Central Nervous System. Ann. Rept. Med. Chem. 45:3, 2010.  Link to Ann. Rept. Med. Chem.

  • Kraus, R.L., Li, Y., Gregan, Y., Gotter, A.L., Uebele,V.N., Fox, S.V., Doran, S.M., Barrow, J.C., Yang, Z.Q., Reger, T.S., Koblan, K.S., Renger, J.J.  In Vitro Characterization of T-type Calcium Channel Antagonist TTA-A2 and In Vivo Effects on Arousal in Mice. JPET,  335:409-417, 2010.  Pub Med Reference

  • Wolkenberg, S.E., Zhao, Z., Mulhearn, J.J., Harrison, S.T., Sanders, J.M., Cato, M.J., Jovanovska, A., Panigel, J., Cook, S.P., Henze, D.A., Kane, S.A., Hartman, G.D., Barrow, J.C.  High concentration electrophysiology-based fragment screen: discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors.  Bioorg. Med. Chem. Lett. 21(9):2646-9, 2011.  Pub Med Reference

  • Reger, T.S., Yang, Z.Q., Schlegel, K.A.S., Shu, Y., Mattern, C., Cube, R., Rittle, K.E., McGaughey, G.B., Hartman, G.D., Tang, C., Ballard, J., Kuo, Y., Prueksaritanont, T., Nuss, C.E., Doran, S.M., Fox, S.V., Garson, S.L., Li, Y., Kraus, R.L., Uebele, V.N., Renger, J.J., Barrow, J.C.  Pyridyl amides as potent inhibitors of T-type calcium channels.  Bioorg. Med. Chem. Lett. 21(6):1692-6, 2011.  Pub Med Reference

  • Uslaner, J.M., Smith, S.M., Huszar, S.L., Pachmerhiwala, R., Hinchliffe, R.M., Vardigan, J.D., Nguyen, S.J., Surles, N.O., Yao, L., Barrow, J.C., Uebele, V.N., Renger, J.J., Clark, J., Hutson, P.H.  T-type calcium channel antagonism produces antipsychotic-like effects and reduces stimulant-induced glutamate release in the nucleus accumbens of rats.  Neuropharmacology.  Epub ahead of print.  Pub Med Reference

  • Harrison, S.T., Mulhearn, J., Wolkenberg, S.E., Miller, P.J., O'Malley, S.S., Zeng, Z., Williams, D.L., Hostetler, E.D., Sanabria-Bohrquez, S., Gammage, L., Fan, H., Sur, C., Culberson, J.C., Hargreaves, R.J., Cook, J.J., Hartman, G.D., Barrow, J.C.  Synthesis and evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as ß-Amyloid PET ligands and indentification of MK-3328.  ACS Med. Chem. Lett. 2(7):498-502, 2011.  Link to ACS Med. Chem. Lett.
  • Coleman, P.J. and Barrow, J.C. Challenges and Opportunities in Neuroscience Research.  ChemMedChem 7: 339-341, 2012.  (Editorial)  Pub Med Reference not available.


Other graduate programs in which Dr. Barrow participates: None

 
 
 
 
 
 

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