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United States Patent 6,037,340
Castelhano, et. al. Mar. 14, 2000
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Synthesis and use of thiophene- and pyrrole-based heteroaromatic compounds
Abstract
Methods for preparing thiophene and pyrrole-based heterocyclic compounds are disclosed. Also disclosed are libraries of thiophene and pyrrole-based heterocyclic compounds, methods for preparing the libraries of thiophene and pyrrole-based heterocyclic compounds, and methods for using the thiophene and pyrrole-based heterocyclic compounds and compound libraries of the invention. The compounds of the invention have biological activity including anti-cancer activity.
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Inventors: Castelhano; Arlindo L. (New City, NY); McKibben; Bryan (White Plains, NY).
Assignee: Cadus Pharmaceutical Corporation (Tarrytown, NY).
Appl. No.: 864,240
Filed: May 28, 1997
Intl. Cl. : A61K 31/38, A61K 31/40, A61K 31/435, C07D 205/02
Current U.S. Cl.: 514/183; 514/342; 514/422; 514/443; 514/447; 540/480; 540/596; 546/280.4; 548/527; 548/950; 548/962; 549/50; 549/68; 549/69
Field of Search: 514/443, 447; 549/68, 69, 50
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References Cited | [Referenced By]
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U.S. Patent Documents
1,642,462 Sept., 1927 Reach 473/290
3,732,212 May, 1973 Carabateas 260/239.3
3,904,603 Sept., 1975 Kim 260/239
3,925,361 Dec., 1975 Kim 260/239
3,947,408 Mar., 1976 Wright, Jr. 260/239.3
3,984,103 Oct., 1976 Nix 473/291
4,147,349 Apr., 1979 Jeghers 473/291
4,256,878 Mar., 1981 Klaus et al. 542/412
4,346,161 Aug., 1982 Krutak et al. 430/223
5,228,688 Jul., 1993 Davis 473/290
5,565,324 Oct., 1996 Still et al. 435/6
Foreign Patent Documents
0006154 Jan., 1980 EP
0207345 Jan., 1987 EP
0364598 Apr., 1990 EP
0399814 Nov., 1990 EP
2513337 Oct., 1976 DE
2724445 Dec., 1977 DE
4029771 Mar., 1992 DE
4119767 Dec., 1992 DE
1394366 May, 1975 GB
WO 93/08197 Apr., 1993 WO
WO 9408051 Apr., 1994 WO
Other References
Combinatorial Synthesis of Small Organic Molecules, F. Balkenhol et al., Angew. Chem. Int. Ed. Engl. (1996), 35, 2288-2337.
Certified English Translation of K. Gewald et al. Chem. Ber., pp. 1-10, 1996, vol. 99, 94.
Carabateas, P.M. et al. "Analgesic Antagonists. I. 4-Substituted 1-Acyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepines" J. Med. Chem. 9:6-10 (1966).
DeGrado, W.F. et al. "Polymer-Bound Oxime Esters as Supports for Solid-Phase Peptide Synthesis. Preparation of Protected Peptide Fragments" J. Org. Chem. 45:1295-1300 (1980).
DeWitt, S.H. et al "Diversomers: An Approach to Nonpeptide, Nonoligomeric Chemical Diversity" Proc. Natl. Acad. Sci. USA 90:6909-6913 (1993).
Errede, L.A. et al. "Acylanthranils.3. The Influence of Ring Substituents on Reactivity and Selectivity in the Reaction of Acylanthranils with Amines" J. Org. Chem. 42(1):12-18 (1977).
Foster, C.H. et al. "Novel One-Pot Synthesis of 4-Aminoquinazolines" J. Org. Chem. 41(15) :2646-2647 (1976).
Gewald, K. et al. "2-Amino-thiopene aus methylenaktiven Nitrilen, Carbonylverbindungen und Schwefel" Chem. Ber. 99:94-100 (1966).
Gordon, E.M. et al. "Applications of Combinatorial Technologies to Drug Discovery. 2. Combinatorial Organic Synthesis, Library Screening Strategies, and Future Directions" Journal of Medical Chemistry 37(10):1385-1401 (1994).
Houghten, R.A. et al. "Generation and Use of Synthetic Peptide Cominatorial Libraries for Basis Research and Drug Discovery" Naturem 354:84-86 (1991).
Kim, D.H. "Improved Synthesis of 1,4-Benzodiazepine-2,5-diones" J. Heterocyclic Chem.12:1323-1324 (1975).
Mayer, J.P. et al. "Solid Phase Synthesis of 1,4-Benzodiazepine-2,5-diones" Tetrahedron Letters 37(45):8081-8084 (1996).
Mitscher, L.A. et al. "Quinolone Antimicrobial Agents. 1. Versatile New Synthesis of 1-Alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic Acids" Journal of Medical Chemistry 21(5):485-489 (1978).
Molina, P. et al. "Heterocyclic Synthesis via a Tandem Aza-wittig Reaction/Heterocumulene-mediated Annulation reaction. New Methodology for the Preparation of Quinazoline Derivatives" Tetrahedron Letters 29(31):3849-3852 (1988).
Muller, C.E. et al. "Chiral Pyrrolo[2,3-d]pyrimidine and Pyrimido[4,5-b]indole Derivatives: Structure-Activity Relationships of Potent, Highly Stereoselective A(1) -Adenosine Receptor Antagonists" J. Med. Chem. 39:2482-2491 (1996).
Roth, H.J. et al. "Synthese von 2-Amino-3-cyano-pyrrolen" Arch. Pharmaz. 308(75):179-185 (1975).
Sampson, N.S. et al. "Attempted de Novo Design, Synthesis, and Evaluation of a Ligand for the Allosteric Site of Phosphofructokinase" J. Org. Chem. 56:7179-7183 (1991).
Takashi, M. et al. Nippon Kaguku Kaishi 8:1259 (1972).
Primary Examiner: Richter; Johann
Assistant Examiner: Solola; Taofiq A.
Attorney, Agent or Firm: Lahive & Cockfield, LLPDeConti, Jr. Esq.; Giulio A., Lauro, Esq.; Peter C.
64 Claims, No Drawings
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