Author
W. L. Whitter
Other affiliations: Merck & Co.
Bio: W. L. Whitter is an academic researcher from United States Military Academy. The author has contributed to research in topics: Diastereomer & Receptor. The author has an hindex of 5, co-authored 7 publications receiving 1437 citations. Previous affiliations of W. L. Whitter include Merck & Co..
Topics: Diastereomer, Receptor, Cholecystokinin, Amide, Drug discovery
Papers
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TL;DR: 3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.
Abstract: 3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.
1,311 citations
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TL;DR: In this article, 3.3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described.
Abstract: 3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.
178 citations
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TL;DR: In this paper, a new method for the resolution of amines and its application to 3-aminobenzodiazepines was described, which involves the synthesis and separation of a pair of phenylalanyl amide diastereomers followed by removal of phenYLalanine via the Edman degradation to give the individual enantiomers of 1 with high chiral purities.
30 citations
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6 citations
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TL;DR: Coupling of the benzophenones (I) with D-tryptophan methyl ester hydrochloride (II) gives the benzodiazepinones (III) as mentioned in this paper.
Abstract: Coupling of the benzophenones (I) with D-tryptophan methyl ester hydrochloride (II) gives the benzodiazepinones (III).
5 citations
Cited by
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TL;DR: Privileged substructures are believed to achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns.
Abstract: Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.
2,620 citations
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TL;DR: This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases and effective drug development depends on multidisciplinary collaborations.
2,272 citations
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TL;DR: Recent technological advances that help to address issues such as the lack of compatibility of traditional natural-product extract libraries with high-throughput screening and unrealized expectations from current lead-generation strategies have led to a renewed interest in natural products in drug discovery.
Abstract: Natural products and their derivatives have historically been invaluable as a source of therapeutic agents. However, in the past decade, research into natural products in the pharmaceutical industry has declined, owing to issues such as the lack of compatibility of traditional natural-product extract libraries with high-throughput screening. However, as discussed in this review, recent technological advances that help to address these issues, coupled with unrealized expectations from current lead-generation strategies, have led to a renewed interest in natural products in drug discovery.
2,254 citations
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1,777 citations
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TL;DR: 3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.
Abstract: 3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.
1,311 citations