James C. Barrow

Image of Dr. James Barrow

James C. Barrow

Associate Professor
Primary Appointment: 
Pharmacology and Molecular Sciences
Lieber Institute for Brain Development
Office: 410-955-0894
Lab: 410-955-3023

855 N. Wolfe Street
Rangos Bldg., Room 336
Baltimore MD 21205

Research topic: 

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.

Selected Publications: 

Coleman, P.J. and Barrow, J.C. Challenges and Opportunities in Neuroscience Research. ChemMedChem 7: 339-341, 2012. (Editorial)

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.

Harrison, S.T., Mulhearn, J., Wolkenberg, S.E., Miller, P.J., O'Malley, 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.

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.

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.

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.

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

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.

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.

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.

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.

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.