Marnett Research Laboratory

Md Jashim Uddin, Ph.D.,
Research Assistant Professor

Md Jashim Uddin received his B.Sc. (Honors) degree in 1991 in Chemistry and M.S. in 1993 in Organic Chemistry at Dhaka University, Bangladesh. In 1997 he was awarded the Japanese Government (Monbusho) scholarship for his doctoral study with Dr. Iwao Yamamoto in Japan and received his Ph.D. degree in Organic Chemistry at Shinshu University, Japan in 2001. It’s a constant challenge for the organic chemists to control the stereoselectivity of the carbon-carbon or carbon-heteroatom bond forming reactions, where either a single or a group of chiral center originates in a single laboratory operation. In this regard, to control the stereoselectivity of the asymmetric cycloaddition reactions, he developed an isoxazolidine based new chiral controller, which induced a high level of diastereoselectivity in intermolecular dipole-olefin cycloaddition reactions. This discovery is highly significant in modern asymmetric synthesis. In 2002, he was awarded the Alberta Heritage Foundation for Medical Research (AHFMR) scholarship for his postdoctoral training in medicinal chemistry to design COX-2 inhibitors with Dr. Edward Knaus at the University of Alberta, Canada, where he acquired an extensive structure-activity relationship study in selective COX-2 inhibition, from which a number of new drug design concepts, pertaining to COX-2 novel hitherto unknown pharmacophores, such as, azido and sulfonyl azido moieties, were developed. The acyclic (Z)- and (E)-olefinic COX-2 inhibitors that he designed are now at the leading edge of drug design worldwide. For further training in the area of medicinal and biological chemistry, he accepted a postdoctoral position at Marnett laboratory in October 2004. In July 2005, he was promoted to the faculty position and appointed as a Research Assistant Professor of Biochemistry. His current research interest is focused on the design and discovery of fluorescent COX-2 inhibitors as molecular targeting agents for diagnosis of early stage human esophageal cancer.

Patent:

1. Marnett, L. J., Uddin, M. J., Crews, B. C.
“Methods and Composition for Diagnostic and therapeutic targeting of COX-2.”
United States Patent Appl. 2006 (Submitted).

Papers:

14. Anning, P. B.; Coles, B.; Morton, J.; Wang, H.; Uddin, M. J.; Morrow, J. D.; Dey, S. K.; Marnett, L. J.; O'donnell, V. B. “Nitric oxide deficiency promotes vascular side effects of cyclooxygenase inhibitors.” Blood2006, 13, 4059.

13. Uddin, M. J.; Rao, P. N. P.; McDonald, R.; Knaus, E. E.“Design and Synthesis of (E)-1,1,2-triarylethenes: Novel Inhibitors of the Cyclooxygenase-2 (COX-2) Isozyme.”Bioorganic & Medicinal Chemistry Letters 2005, 15, 439.

12. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design and Synthesis of (Z)-1,2-Diphenyl-1-(4-methanesulfonamidophenyl-2-alk-1-enes and (Z)-1-(4-azidophenyl)-1,2-diphenyl-2-alk-1-enes: Novel Inhibitors of Cyclooxygenase-2 (COX-2) with Antiinflammatory and Analgesic Activity.”Bioorganic & Medicinal Chemistry 2005, 13, 417.

11. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design and Synthesis of Acyclic Triaryl (Z)-Olefins: A Novel Class of Cyclooxygenase-2 (COX-2) Inhibitors.”Bioorganic & Medicinal Chemistry 2004, 12, 5929.

10. Uddin, M. J.; Rao, P. N. P.; McDonald, R.; Knaus, E. E.“A New Class of Acyclic 2-alkyl-1,1,2-Triaryl (Z)-Olefins as Selective Cyclooxygenase-2 (COX-2) inhibitors.”Journal of Medicinal Chemistry 2004, 47, 6108.

9. Uddin, M. J.; Rao, P. N. P.; Rahim, M. A.; McDonald, R.; Knaus, E. E.“A New Class of Acyclic 2-alkyl-1,2-diaryl (E)-Olefins as Selective Cyclooxygenase-2 (COX-2) inhibitors”. Bioorganic & Medicinal Chemistry Letters2004, 14, 4911

.8. Rao, P. N. P.; Uddin, M. J.; Knaus, E. E.“Design, Synthesis and Structure-Activity Relationship (SAR) Studies of 3,4,6-Triphenylpyran-2-ones as Selective Cyclooxygenase-2 (COX-2) Inhibitors.”Journal of Medicinal Chemistry 2004, 47, 3972

7. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Methylsulfonyl and Hydroxyl Substituents Induce (Z)-Stereocontrol in the McMurry Olefination Reaction” Synlett 2004, 1513.

6. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design of Acyclic Triaryl Olefins: A New Class of Potent and Selective Cyclooxygenase-2 (COX-2) Inhibitors.”Bioorganic & Medicinal Chemistry Letters2004, 14, 1953.

5. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design, Synthesis and Biological Evaluation of Novel Rofecoxib Analogs as Potential Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Methylsulfonyl Pharmacophore by a Sulfonylazide Bioisostre.”Journal of Heterocyclic Chemistry, 2003, 40, 861.

4. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design, Synthesis and Biological Evaluation of Novel Celecoxib Analogs as Selective Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Sulfonamide Pharmacophore by a Sulfonylazide Bioisostre.”Bioorganic & Medicinal Chemistry,2003, 11, 5273.

3. Uddin, M. J.; Shinooka, A.; Fujimoto, T.; Shirai, H.; Yamamoto, I. “Isoxazolidine Based New Chral Auxiliary for Asymmetric Synthesis.”Heterocyclic Communications, 2000, 6, 505.

2. Uddin, M. J.; Fujimoto, T.; Kakehi, A.; Shirai, H.; Yamamoto, I. “Diastereoselective Synthesis of Bridgehead Heterocyclic Spiro Compounds Derived from Tandem Michael Intramolecular 1,3-Dipolar Cycloaddition of Nitrones.”Heterocyclic Communications, 2000, 6, 113.

1. Uddin, M. J.; Kikuchi, M.; Takedatsu, K.; Arai, K.-I.; Fujimoto, T.; Motoyoshiya, J.; Kakehi, A.; Iriue, R.; Shirai, H.; Yamamoto, I. “Synthesis and Structure of Condensed Heterocycles Derived from Intramolecular 1,3-Dipolar Cycloaddition of Transient and Enantiomerically Pure a-Allylamino Nitrones and Nitrile Oxides in a High Level of Diastereoselectivity.” Synthesis, 2000, 365.•

Proceedings:

7. Uddin, M. J.; Brenda C. Crews; Marnett, L. J.“COX-2 targeted Molecular Imaging Agents” 2nd Vanderbilt Institute of Chemical Biology (VICB) Retreat, Vanderbilt University, Tennessee, U.S.A. 2006.

6. Uddin, M. J.; Brenda C. Crews; Marnett, L. J.“Fluorescent Derivatives of Indomethacin as Selective Inhibitor of Cyclooxygenase-2.” U54 Network in Translational Research in Optical Imaging Retreat, Stanford University, California 2005.

5. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E. “Design of Selective Cyclooxygenase-2 Inhibitors.” Drug Discovery 2004 Lecture Series, University of Alberta Canada 2004.

4. Knaus, E. E. Uddin, M. J.; Rao, P. N. P.“Design of Acyclic Triaryl Olefins: A New Class of Highly Potent and Selective Cyclooxygenase-2 (COX-2) Inhibitors.” 7th Annual Symposium of Canadian Society for Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada 2004.

3. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design and Synthesis of Acyclic Triaryl Olefins: A New Class of Highly Potent and Selective Cyclooxygenase-2 (COX-2) Inhibitors.”12th Symposium on Organo-Metallic Chemistry Directed Toward Organic Synthesis (OMCOS 12),Toronto University, Toronto, Canada2003, 45.

2. Uddin, M. J.; Rao, P. N. P.; Knaus, E. E.“Design, Synthesis and Biological Evaluation of Novel Celecoxib and Rofecoxib Analogs as Selective Cyclooxygenase-2 (COX-2) Inhibitors: Replacement of Sulfonamide and Methylsulfonyl Pharmacophore by a Sulfonylazide Bioisostre.” 5th Annual Symposium of Canadian Society for Pharmaceutical Sciences, Banff Center, Alberta, Canada 2002, 54.

1. Uddin, M. J.; Kikuchi, M.; Takedatsu, K.; Arai, K.-I.; Fujimoto, T.; Yamamoto, I.“Synthesis of Isoxazolidine fused Heterocycles from Diastereoselective Intramolecular 1,3-Dipolar Cycloaddition of Nitrones.” 76th Annual Conference of the Chemical Society of Japan, Kanagawa, Japan1999, 76 (II), 1029.