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Patrick T. Flaherty, Ph.D.

Associate Professor
Mylan School of Pharmacy
Medicinal Chemistry

445 A Mellon Hall
Phone: 412.396.1847

Education:

Ph.D., Medicinal Chemistry, University of Iowa, 1993
B.S., Chemistry, University of Pittsburgh, 1986
Research

The prime goal of the Flaherty lab is the development of new paradigms for addressing medicinal chemistry problems. The tools used to develop these approaches are molecular modeling, synthesis, and biochemical assays. An emphasis is placed on emerging biochemical targets relevant to human disease states, modern synthetic methodology, and iterative rounds of computational analysis, synthesis, then biochemical analysis. Practically most of what we do is synthesis.
Initial biological targets are CDK5, microtubules, DXR, and alpha-synuclein.
General therapeutic areas of focus are CNS agents and anti-cancer agents.

Specialties

Synthesis, molecular modeling, enzymology, protein purification.

Courses

Graduate courses:
GHPSC 257 Advanced Medicinal Chemistry II (3 Cr.)  The organic - mechanistic basis  of drug action and biological interaction.  This course is typically offered on alternating (odd) years or as required.  This follows a 3 credit introductory course GPHSC 257.

GPHSC 528 Heterocyclic Chemistry (3 Cr.)  Synthesis and properties of condensed heterocyclic systems from the late 1800's to the current time.  An emphasis is placed on physical properties and synthesis with a particular emphasis on drug design and drug development.  Modern organometallic and palladium coupling strategies are included.

GPHSC 623 Selected Topics in Medicinal Chemistry (3 Cr.)  An in-depth analysis of current medicinal chemistry topics selected by the instructor.  Prior topics: Current RNA topics, 5HT pharmacology and med chem , kinases pharmacology and med chem.

GPHSC 691/692 Graduate Student Seminar (1 Cr.)  This is a 1credit required graduate course for students in Medicinal Chemistry.

 Undergraduate (PharmD) courses:

PHBMS 350 and 351 Biochemistry (and associated lab)   (3 Cr. each)  A required course offered in the 3rd academic year (1st professional year) in the Doctor of Pharmacy professional program.  The focus of this course is fundamental biochemistry with selected topics emphasized that are of relevance to human health.

BMST 430 CNS Disorders II        (5 Cr.: team taught)  A required 4 credit course offered in the 4th  academic year (2nd  professional year) in the Doctor of Pharmacy professional program.  This course covers Central Nervous System active drugs from a pharmacological, medicinal chemistry, and therapeutics perspective. 

Publications

Identification of HIV Inhibitors Guided by Free Energy Perturbation Calculations, Orlando Acevedo, Zandrea Ambrose, Patrick T. Flaherty, Hadega Aamer, Prashi Jain, and Somisetti V. Sambasivarao

Current pharmaceutical design (2012), 18(9), 1199-216.

 

Peptidyl Prolyl Isomerase Inhibitors, Patrick T. Flaherty, Prashi Jain, Annual Reports in Medicinal Chemistry, Volume 46, Chapter 20, pp 337-349.

 

Design, Synthesis, and Testing of an 6-O-Linked Series of Benzimidazole Based Inhibitors of CDK5.

Patrick T. Flaherty, Prashi Jain, Shuyan Yi, Ishveen Chopra, Gwenyth Bleasdell, Josh Lipay, Yoan Ferandin, Laurent Meijer, Jeffry D. Madura, Bioorganic & Medicinal Chemistry (2011), pp. 359-373.

 

Suzuki-Miyaura cross coupling of potassium oraganoborate with 6-sulfonate benzimidazoles using microwave irradiation.  Prashi Jain, Shuyan Yi, Patrick T.  Flaherty (J. Het. Chem., Accepted 9/11/2011)

 

Structure Activity Relationships of Benzimidazole-Based Selective Inhibitors of the Mitogen Activated Kinase-5 signaling pathway, Flaherty, Patrick T.; Chopra, Ishveen; Jain, Prashi; Yi, Shuyan; Monlish, Darlene; Cavanaugh, Jane Cavanaugh, J. , (2010)   Bioorganic & Medicinal Chemistry. pp. 8054-8060.

 

Identification of benzimidazole-based inhibitors of the mitogen activated kinase-5 signaling pathway, Flaherty, Patrick T.; Chopra, Ishveen; Jain, Prashi; Yi, Shuyan; Allen, Erika; Cavanaugh, Jane Bioorganic & Medicinal Chemistry Letters (2010), 20(9), 2892-2896.

 

1-Isopropyl-4-nitro-6-methoxy-1H-benzimidazole,  Moore, Michael D.; Jain, Prashi; Flaherty, Patrick T.; Wildfong, Peter L. D., Crystallographica, Section E: Structure Reports Online (2008), E64(7), o1336-o1337, o1336/1-o1336/11.

 

 

2:  Previous Publications

 

Biphenyl/diphenyl ether renin inhibitors: filling the S1 pocket of renin via the S3 pocket Yuan Jing; Simpson Robert D; Zhao Wei; Tice Colin M; Xu Zhenrong; Cacatian Salvacion; Jia Lanqi; Flaherty Patrick T; Guo Joan; Ishchenko Alexey; et al. Bioorganic & Medicinal Chemistry Letters (2011), 21(16), 4836-43.

 

Optimization of orally bioavailable alkyl amine renin inhibitors, Xu, Zhenrong; Cacatian, Salvacion; Yuan, Jing; Simpson, Robert D.; Jia, Lanqi; Zhao, Wei; Tice, Colin M.; Flaherty, Patrick T.; Guo, Joan; Ishchenko, Alexey; et al. Bioorganic & Medicinal Chemistry Letters (2010), 20(2), 694-699.

 

Design and optimization of renin inhibitors: Orally bioavailable alkyl amines,  Tice, Colin M.; Xu, Zhenrong; Yuan, Jing; Simpson, Robert D.; Cacatian, Salvacion T.; Flaherty, Patrick T.; Zhao, Wei; Guo, Joan; Ishchenko, Alexey; Singh, Suresh B.;  et al.,  Bioorganic & Medicinal Chemistry Letters (2009), 19(13), 3541-3545.

 

Synthesis and Anti-Tubulin Activity of a 3'-(4-Azidophenyl)-3'-dephenylpaclitaxel Photoaffinity Probe, Spletstoser, Jared T.; Flaherty, Patrick T.; Himes, Richard H.; Georg, Gunda I. Journal of Medicinal Chemistry (2004), 47(26), 6459-6465.

 

Formal Total Synthesis of (+)-Salicylihalamides A and B: A Combined Chiral Pool and RCM Strategy, Yang, KyoungLang; Blackman, Burchelle; Diederich, Wibke; Flaherty, Patrick T.; Mossman, Craig J.; Roy, Subho; Ahn, Yu Mi; Georg, Gunda I., Journal of Organic Chemistry (2003), 68(26), 10030-10039.

 

Short and efficient chiral pool and RCM approach towards the synthesis of the macrocyclic core of the salicylihalamides, Georg, Gunda I.; Ahn, Yu Mi; Blackman, Burchelle; Farokhi, Faryar; Flaherty, Patrick T.; Mossman, Craig J.; Roy, Subho; Yang, KyoungLang , Chemical Communications (2001), (3), 255-256.

 

The non-mevalonate pathway for isoprenoid biosynthesis: new opportunities for drug design, Flaherty, Patrick T.; Georg, Gunda I. , Chemtracts (2000), 13(4), 237-244

 

Compatibility of Various Carbanion Nucleophiles with Heteroaromatic Nucleophilic Substitution by the SRN1 Mechanism, , Jim-Wah; Natalie, Kenneth J., Jr.; Nwokogu, Godson C.; Pisipati, Jyothi S.; Flaherty, Patrick T.; Greenwood, Thomas D.; Wolfe, James F., Journal of Organic Chemistry (1997), 62(18), 6152-6159.

 

 

Synthesis and Selective Monoamine Oxidase B-Inhibiting Properties of 1-Methyl-1,2,3,6-tetrahydropyrid-4-yl Carbamate Derivatives: Potential Prodrugs of (R)- and (S)-Nordeprenyl, Flaherty, Patrick; Castagnoli, Kay; Wang, You-Xiong; Castagnoli, Neal, Jr. Journal of Medicinal Chemistry (1996), 39(24), 4756-4761.

 

Synthesis and evaluation of N-(phenylacetyl)trifluoromethanesulfonamides as anticonvulsant agents, Flaherty, Patrick T.; Greenwood, Thomas D.; Manheim, Amy L.; Wolfe, James F.,  Journal of Medicinal Chemistry (1996), 39(7), 1509-13.

 

A-Ring Ortho-Disubstituted Aporphine Derivatives as Potential Agonists or Antagonists at Serotonergic 5-HT1A Receptors, Cannon, Joseph G.; Flaherty, Patrick T.; Ozkutlu, Ugur; Long, John Paul,  Journal of Medicinal Chemistry (1995), 38(11), 1841-5.

Preparation of piperidine derivatives, especially amino acid and peptide piperidino amides, as renin inhibitors,  Baldwin, John J.; Cacatian, Salvacion; Claremon, David; Dillard, Lawrence W.; Flaherty, Patrick T.; Ghavimi-Alagha, Bahman; Ishchenko, Alexey V.; Ghirlanda, Damiano; Kallander, Lara S.; Lawhorn, Brian; et al.

PCT Int. Appl. (2009), WO 2009096996 A1 20090806.

 

Preparation of aminophenylpiperidinecarboxylate derivatives and analogs as renin inhibitors,  Baldwin, John J.; Cacatian, Salvacion; Claremon, David A.; Dillard, Lawrence W.; Flaherty, Patrick T.; Ishchenko, Alexey V.; Jia, Lanqi; McGeehan, Gerard; Simpson, Robert D.; Singh, Suresh B.;  et al. PCT Int. Appl. (2008), WO 2008156832 A2 20081224.

 

Preparation of phenyl[((amino)phenyl)methoxy]ethylcarbamate derivatives and analogs as renin inhibitors Baldwin, John J.; Cacatian, Salvacion; Claremon, David A.; Dillard, Lawrence W.; Flaherty, Patrick T.; Ishchenko, Alexey V.; Jia, Lanqi; McGeehan, Gerard; Simpson, Robert D.; Singh, Suresh B.;  et al. PCT Int. Appl. (2008), WO 2008156828 A2 20081224.

 

Preparation of phenyl[((amino)phenyl)methoxy]ethylcarbamate derivatives and analogs as renin inhibitors Baldwin, John J.; Cacatian, Salvacion; Claremon, David A.; Dillard, Lawrence W.; Flaherty, Patrick T.; Ischenko, Alexey V.; McGeehan, Gerard; Simpson, Robert D.; Singh, Suresh B.; Tice, Colin M.;  et al. PCT Int. Appl. (2008), WO 2008156817 A2 20081224.

 

Preparation of phenyloxooxatriazatridecanylcarbamate derivatives and analogs as renin inhibitors Baldwin, John J.; Cacatian, Salvacion; Claremon, David A.; Dillard, Lawrence W.; Flaherty, Patrick T.; Ishchenko, Alexey V.; Jia, Lanqi; McGeehan, Gerard; Simpson, Robert D.; Singh, Suresh B.;  et al. PCT Int. Appl. (2008), WO 2008156816 A2 20081224.

 

Preparation of aminobiphenylcyclopentanecarboxamide derivatives for use as renin inhibitors Baldwin, John J.; Cacatian, Salvacion; Claremon, David A.; Dillard, Lawrence W.; Flaherty, Patrick T.; Ishchenko, Alexey V.; Jia, Lanqi; McGeehan, Gerard; Simpson, Robert D.; Singh, Suresh B.;  et al. PCT Int. Appl. (2008), WO 2008156831 A2 20081224.

 

Preparation of substituted benzoylpiperidine derivatives and analogs as renin inhibitors Baldwin, John J.; Cacatian, Salvacion; Claremon, David; Dillard, Lawrence W.; Flaherty, Patrick T.; Ghavimi-Alagha, Bahman; Ghirlanda, Damiano; Ishchenko, Alexey V.; Kallander, Lara S.; Lawhorn, Brian;  et al. PCT Int. Appl. (2008), WO 2008124575 A1 20081016.

 

Preparation of substituted carbonylpiperidine derivatives as renin inhibitors Baldwin, John J.; Cacatian, Salvacion; Claremon, David; Dillard, Lawrence W.; Flaherty, Patrick T.; Ghavimi-Alagha, Bahman; Ghirlanda, Damiano; Hou, Xiaoping; Ishchenko, Alexey V.; Kallander, Lara S.;  et al. PCT Int. Appl. (2008), WO 2008124582 A1 20081016.

 

Preparation of substituted carbonylpiperidine derivatives as renin inhibitors, John J.; Cacatian, Salvacion; Claremon, David; Dillard, Lawrence W.; Flaherty, Patrick T.; Ghavimi-Alagha, Bahman; Gleason, John; Ishchenko, Alexey V.; Lawhorn, Brian; McGeehan, Gerard;  et al. PCT Int. Appl. (2008), WO 2008124577 A1 20081016.

 

Preparation of piperidine derivatives as renin inhibitors Baldwin, John J.; Claremon, David A.; Tice, Colin M.; Cacatian, Salvacion; Dillard, Lawrence W.; Ishchenko, Alexey V.; Yuan, Jing; Xu, Zhenrong; McGeehan, Gerard; Zhao, Wei;  et al. PCT Int. Appl. (2008), WO 2008036247 A1 20080327.

 

Preparation of piperidine derivatives as renin inhibitors Baldwin, John J.; Claremon, David A.; Tice, Colin M.; Cacatian, Salvacion; Dillard, Lawrence W.; Ishchenko, Alexey V.; Yuan, Jing; Xu, Zhenrong; McGeehan, Gerard; Zhao, Wei;  et al. PCT Int. Appl. (2008), WO 2008036216 A1 20080327.

 

Acylpiperidine compounds as renin inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases associated with aspartic protease activity Baldwin, John J.; Claremon, David A.; Tice, Colin M.; Cacatian, Salvacion; Dillard, Lawrence W.; Ishchenko, Alexey V.; Yuan, Jing; Xu, Zhenrong; Mcgeehan, Gerard; Zhao, Wei;  et al. PCT Int. Appl. (2007), WO 2007117482 A2 20071018.

 

Diaminopropanol derivatives as renin inhibitors and their preparation, pharmaceutical compositions and use in the treatment of diseases Baldwin, John J.; Claremon, David A.; Tice, Colin M.; Cacatian, Salvacion; Dillard, Lawrence W.; Ishchenko, Alexey V.; Yuan, Jing; Xu, Zhenrong; Mcgeehan, Gerard; Zhao, Wei;  et al. PCT Int. Appl. (2007), WO 2007117557 A2 20071018.

 

Piperidine derivatives as aspartic protease inhibitors and their preparation, pharmaceutical compositions and use in the treatment of aspartic protease mediated diseases Baldwin, John J.; Claremon, David A.; Tice, Colin; Cacatian, Salvation; Dillard, Lawrence W.; Ishchenko, Alexey V.; Yuan, Jing; Xu, Zhenrong; McGeehan, Gerard; Simpson, Robert D.;  et al. PCT Int. Appl. (2007), WO 2007070201 A1 20070621.

 

Preparation of diaminoalkanes, particularly N-(1-aminopropan-2-yl)piperidine-1-carboxamides, as aspartic protease inhibitors Baldwin, John J.; Claremon, David A.; Tice, Colin; Cacatian, Salvation; Dillard, Lawrence W.; Ishchenko, Alexey V.; Yuan, Jing; Xu, Zhenrong; McGeehan, Gerard; Zhao, Wei;  et al. PCT Int. Appl. (2006), WO 2006042150 A1 20060420.

 

Prodrugs for the selective inhibition of monoamine oxidase-B Castagnoli, Neal, Jr.; Flaherty, Patrick; Castagnoli, Kay; Wang, You-Xiong PCT Int. Appl. (1998), WO 9822110 A1 19980528.

Grants/Contracts

Current funding:

Synthesis and Testing of Rigid CDK5 inhibitors.

September 30, 2008 to September 29, 2012

National Institutes of Health (NINDS)

$150,000 direct costs

 Synthesis and analysis of small molecule probes for analysis of glycerophosphoinositol (GPI) interacting proteins.

April 2010 to April 2013

Faculty Development fund (Duquesne University)

$ 5,000 direct costs