AMP deaminase inhibitors. 3. SAR of 3-(carboxyarylalkyl)coformycin aglycon analogues

Journal of Medicinal Chemistry

Volumn 43, Issue 8, 2000, Pages 1508-1518

  Kasibhatla, Srinivas Rao ^a   Bookser, Brett C ^a   Probst, Gary ^a   Appleman, James R ^a   Erion, Mark D ^a  

^a Metabasis Therapeutics Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (5 CARBOXYPENTYL) 3,6,7,8 TETRAHYDROIMIDAZO[4,5 D][1,3]DIAZEPIN 8 OL; 3 [2 (3 CARBOXY 5 ETHYLPHENYL)ETHYL] 3,6,7,8 TETRAHYDROIMIDAZO[4,5 D][1,3]DIAZEPIN 8 OL; 3 [2 (3 CARBOXY 6 METHYLPHENYL)ETHYL]COFORMYCIN AGLYCON; ADENOSINE MONOPHOSPHATE DEAMINASE; ADENOSINE MONOPHOSPHATE DEAMINASE INHIBITOR; COFORMYCIN; ENZYME INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; BRAIN PROTECTION; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; HEART PROTECTION; STRUCTURE ACTIVITY RELATION;

AMP DEAMINASE; AZEPINES; COFORMYCIN; ENZYME INHIBITORS; IMIDAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034692173     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990448e     Document Type: Article

References (17)

1. Adenosine as cardio- and neuroprotective agent, see references: (a) Winn, H. R.; Welsh, J. E.; Rubio, R.; Berne, R. M. Changes in Brain Adenosine during Bicuculline-Induced Seizure in Rats. Circ. Res. 1980, 47, 568-577.
2. (b) Gruber, H. E.; Hoffer, M. E.; McAllister, D. R.; Laikind, P. K.; Lane, T. A.; Schmid-Schoenbein, G. W.; Engler, R. L. Increased Adenosine Concentration in Blood from Ischemic Myocardium by AICA Riboside. Circulation 1989, 80, 1400.
3. (c) Erion, M. D. Adenosine Receptors as Pharmacological Targets. Annu. Rep. Med. Chem. 1993, 28, 295-304.
4. Erion, M. D.; Kasibhatla, S. R.; Bookser, B. C.; van Poelje, P. D.; Reddy, M. R.; Gruber, H. E.; Appleman, J. R. Discovery of AMP Mimetics that Exhibit High Inhibitory Potency and Specificity for AMP Deaminase. J. Am. Chem. Soc. 1999, 121, 308-319.
5. Bookser, B. C.; Kasibhatla, S. R.; Appleman, J. R.; Erion, M. D. AMP Deaminase Inhibitors. 2. Initial Discovery of a Non-Nucleotide Transition-State Inhibitor Series. J. Med. Chem. 2000, 43, 1495-1507.
6. Chan, E.; Putt, S. R.; Showalter, H. D.; Baker, D. C. Total Synthesis of (8R)-3-(2-Deoxy-β-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazolo[4, 5-d][1,3]diazepine-8-ol (Pentostatin), the Potent Inhibitor of Adenosine Deaminase. J. Org. Chem. 1982, 47, 3457-3464.
7. For more details about the regioisomer distribution, see ref 3.
8. Palladium-catalyzed reactions: (a) McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Still, J. K. Synthesis of Functionalized Styrenes via Palladium-Catalyzed Coupling of Aryl Bromides with Vinyl Tin Reagents. J. Org. Chem. 1987, 5, 422-424.
9. (b) Echavarren, A. M.; Still, J. K. Palladium-Catalyzed Coupling of Aryl Triflates with Organostannanes. J. Am. Chem. Soc. 1987, 109, 5478-5486.
10. (c) Miyaura, M.; Yanagi, T.; Suzuki, A. The Palladium-Catalyzed Cross-Coupling Reaction of Phenylboronic Acid with Haloarens in the Presence of Base. Synth. Commun. 1981, 11, 513-519.
11. (d) Alo, B. I.; Kandil, A.; Patil, P. A.; Siddiqui, M. A.; Snieckus, V. Sequential Directed Ortho Metalation-Boronic Acid Cross-Coupling Reactions. A General Regiospecific Route to Oxygenated Dibenzo[b,d] pyran-6-one Related to Ellagic Acid. J. Org. Chem. 1991, 56, 3763-3768.
12. (e) Schoenberg, A.; Bartoletti, I.; Heck, R. F. Palladium-Catalyzed Caboalkoxylation of Aryl, Benzyl, and Vinylic Halides. J. Org. Chem. 1974, 39, 3318-3326.
13. (f) Sonogashira, K.; Tohda, Y.; Hagihara, N. A Convenient Synthesis of Acetylenes: Catalytic Substitutions of Acetylenic Hydrogen with Bromoalkenes, Idoarenes, and Bromopyridines. Tetrahedron Lett. 1975, 4467-4470.
14. Figuly, G. D.; Loop, C. K.; Martin, J. C.; Directed Ortho-Lithiation of Lithium Thiophenolate. New Methodology for the Preparation of Ortho-Substituted Thiophenols and Related Compounds. J. Am. Chem. Soc. 1989, 111, 654-658.
15. For enzyme assay methods, see ref 2.
16. A detailed optimization study will be published later. Bookser, B. C.; Kasibhatla, S. R.; Cottrell, M.; Probst, G.; Appleman, J. R.; Erion, M. D. Unpublished results.
17. i = 6.3 μM).