Bioorganic & Medicinal Chemistry Letters

article

D-Phe-Pro-p-Amidinobenzylamine: a potent and highly selective thrombin inhibitor

Michael R. Wiley, Nickolay Y. Chirgadze, David K. Clawson, Trelia J. Craft, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2387-2392

The design, synthesis, and enzyme inhibitory profile of D-Phe-Pro-p-Amidinobenzylamine are presented. This compound has inhibitory activity equivalent to D-Phe-Pro-Arg-H, two orders of magnitude more potent than D-Phe-Pro-Agmatine. The results indicate that binding energy provided by the covalent bond of a transition-state analog can be replaced with noncovalent interactions.

article

Concerning the thermolability of cholesta-5,8-dien-3β-ol, a sterol that accumulates in blood and tissues in a human genetic developmental disorder

B. Ruan, J. Pang, W. K. Wilson, G. J. Schroepfer

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2421-2424

Cholesta-5,8-dien-3β-ol, a sterol of current biomedical interest, undergoes facile thermal decomposition as its acetate and TMS derivatives to the corresponding derivatives of 19-norcholesta-5,7,9-trien-3β-ol. This finding may be relevant to the reported occurrence of the nortriene in blood of patients with Smith-Lemli-Opitz syndrome.

article

Isosteres of nucleoside triphosphates

Richard Weaver, Ian H. Gilbert, Naheed Mahmood, Jan Balzarini

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2405-2410

This paper describes the design and synthesis of lipophilic isosteres of nucleoside triphosphates as potential inhibitors of HIV reverse transcriptase. The isosteric replacement of the triphosphate group is a modification of the citrate group.

article

A rapid synthesis of some 5 -amino-nucleosides and nucleotides as potential antiviral compounds.

Christopher McGuigan, Stephen Turner, Naheed Mahmood, Alan J Hay

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2445-2448

We describe a convenient method for the synthesis of 5 -amino-3 -azido-3 -5 -dideoxythymidine, and its conversion to a 5 -blocked phosphate derivative. The compounds are evaluated as inhibitors of HIV-1 in vitro, but prove to be poorly effective by comparison to their 5 -oxygen analogues.

article

New antithrombotic RGD-mimetics with high bioavailability

Joachim Gante, Horst Juraszyk, Peter Raddatz, Hanns Wurziger, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2425-2430

A new class of antithrombotic RGD-mimetics with a novel oxazolidinonemethyl scaffold was synthesized. High oral activity and bioavailability was found in this series of compounds.

article

Inactivation of a prototypic zinc-containing protease with (S)-2-benzyl-2-(3-oxo-2-isoxazolidinyl)acetic acid

Kyung Joo Lee, Dong H. Kim

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2431-2436

(S)-2-Benzyl-2-(3-oxo-2-isoxazolidinyl)acetic acid was designed, synthesized, and kinetically proven to be a mechanism-based inactivator for carboxypeptidase A, a representative zinc-containing protease.

article

Synthesis and antibacterial activity of lipophilic carbapenems with anti-MRSA activity

Jean Claude Arnould, Ruth N Illingworth, Wright W Nichols, R. Geoffrey Wilson

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2449-2454

A series of sulphur-linked and carbon-linked lipophilic carbapenems has been prepared and evaluated for antibacterial activity in vitro and in vivo and for affinity for PBP2' of Staphyloccus aureus. Potent activity in vitro against methicillin-resistant S. aureus and methicillin-resistant coagulase negative staphylococci was observed despite IC ₅ ₀ values for PBP2' being higher than the...

article

Studies on the structural feature of S'1 subsite of neprilysin (EC.3.4.24.11) : stereochemical requirement for the enzyme-inhibitor docking process

Denis Danvy, Thierry Monteil, Jean-Christophe Plaquevent, Lucette Duhamel, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2437-2440

The preferred conformation of thiorphan during the inhibitor-neprilysin docking process was investigated. A series of achiral inhibitors were tested. This study led to the design of a potent inhibitor, in which the ethylenic bond bears the aryl residue of P'1.

article

Inhibition of HSV-1 protease by benzoxazinones

Richard L. Jarvest, Martin J. Parratt, Christine M. Debouck, Joselina G. Gorniak, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2463-2466

Benzoxazinones have been discovered which are mechanism based inhibitors of HSV-1 protease with micromolar IC ₅ ₀ values. Formation of a monoadduct consistent with the acyl-enzyme complex was detected by mass spectroscopy. A parallel array synthesis was developed to explore 2-heteroatom substituted SAR.

article

7,10-bis(2-mercapto-2-methyl)propyl-7,10-diazapalmitic acid: a novel, N ₂ S ₂ ligand for technetium-99m

G. S. Jones, D. R. Elmaleh, H. W. Strauss, A. J. Fischman

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2399-2404

7,10-Bis(2-mercapto-2-methyl)propyl-7,10-diazapalmitic acid (7) was synthesized and evaluated as a new ligand for technetium-99m ( ⁹ ⁹ ^m Tc). The title fatty acid analog, an achiral, bis(aminoethanethiol) derivative in which the amines are tertiary, gave a stable complex with ⁹ ⁹ ^m Tc. The biodistribution of ⁹ ⁹ ^m Tc-labeled 7 in rats is reported.

article

Synthesis and biological activity of 4 -azido- and 4 -trifluoracetamido-3 -chloro-3 -deamino-4 -deoxydaunorubicin.

Nectarios Aligiannis, Nicole Pouli, Panagiotis Marakos, Alexios-Leandros Skaltsounis, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2473-2476

The syntheses of 1-O-acetyl-4-azido-3-chloro-L-lyxo-hexopyranose and 1-O-acetyl-3-chloro-4-trifluoracetamido-L-lyxo-hexopyranose are described. These aminosugars were successfully employed for the synthesis of 4 -azido- 3 -chloro-3 -deamino-4 -deoxydaunorubicin and 3 -chloro-3 -deamino-4 -deoxy-4 -trifluoroacetamidodaunorubicin. The cytotoxicity of the above-mentioned compounds is discussed.

article

Palladium-catalysed synthesis of some biologically active 5,6-disubstituted uracils

Palas Das, C.P. Spears, A. H. Shahinian, Swapan K. Dasgupta, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2477-2480

Synthesis of some 5-halo-[E]-6(2-p-toluoylvinyl)uracils and some 5-alkynyl-[E]-6-(2-p-toluoylvinyl)uracils through palladium-catalysed procedure and cytotoxicities of the former and [E]-6-(2-p-toluoylvinyl)uracils are reported.

article

Adenosine deaminase inhibitors. Synthesis and biological evaluation of chain modified analogs of (+)-EHNA.

Palle V. P. Pragnacharyulu, Lu Pei-Jung, Elie Abushanab

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2417-2420

Unsaturated chain modified analogs of (+)-EHNA have been prepared and evaluated as inhibitors of adenosine deaminase. The geometry appears to play a role in binding to the enzyme.

article

Synthesis and cytotoxic activity of phenyl-hexahydropyrrolo[3,4-c]carbazoles

Esther Caballero, Francine García, Dolores Gª Grávalos, Manuel Medarde, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2459-2462

A synthetic methodology for the preparation of fused carbazole derivatives has been developed. The presence of a trimethoxyphenyl substituent and the hexahydropyrrolo[3,4-c]carbazole system produced a new family of compounds, that display cytotoxic activity.

article

Syntheses of Trans-3'-substituted-CCG-IV Analogs and Their Characterization to Ionotropic Glutamate Receptors

Keiko Shimamoto, Yasushi Shigeri, Terumi Nakajima, Noboru Yumoto, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2381-2386

Trans-3'-substituted-CCG-IV analogs (2 and 3) were efficiently synthesized via an intramolecular cycloaddition of diazoacetamide 4a using a chiral rhodium catalyst. These analogs evoked marked depolarization through ionotropic glutamate receptors on the spinal motoneurons or the kainate-sensitive dorsal root C-fiber of new born rats even though their binding affinities for the receptors on rat brain...

article

Synthesis and antifungal activity of new azole derivatives containing an oxathiane ring

Hiroshi Miyauchi, Tomoharu Tanio, Naohito Ohashi

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2377-2380

A series of azole derivatives containing an oxathiane ring, which were designed to simulate the D ring of lanosterol, were synthesized and evaluated for their antifungal activity. 3,3-Dimethyl derivatives showed potent activity against murine systemic candidosis and aspergillosis, whereas (2R ^* ,3R ^* )-3-monomethyl derivatives showed only weak activity in both in vitro and in vivo.

article

Trifluoromethyl Alcohol and Ketone Inhibitors of Metallo-β-Lactamases

Magnus W. Walter, Antonio Felici, Moreno Galleni, Raquel Paul Soto, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2455-2458

α-Amido trifluoromethyl alcohols and ketones were synthesised via two independent routes using Ruppert's Reagent (TMS-CF ₃ ) and shown to be the first reported synthetic inhibitors of metallo-β-lactamases.

article

Synthesis of a highly functionalized rigid template by solid phase azomethine ylide cycloaddition

Andrew J. Bicknell, Nicholas W. Hird

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2441-2444

A series of 1,5-diazabicyclo[3.3.0]octane-2-carboxylic acids have been synthesized in good yields and purities via cycloaddition of maleimides to polymer supported azomethine ylides. N-Acylation of the resulting cycloadduct enables the synthesis of diverse molecules based on a highly functionalized rigid template.

article

Lipophilic bioisosteres of nucleoside triphosphates

Alastair O. Goldring, Ian H. Gilbert, Naheed Mahmood, Jan Balzarini

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2411-2416

This paper describes the design and synthesis of lipophilic bioisosteres of nucleoside triphosphates as potential inhibitors of HIV reverse transcriptase. The bioisostere is designed to mimic the conformation of the nucleoside triphosphate when complexed to a metal ion such as magnesium.

article

Halogen substitution at the isoxazole ring enhances the activity of n-(isoxazolyl)sulfonamide endothelin antagonists

Fai Chan Ming, B. Raju, Adam Kois, Rosario S. Castillo, more

Bioorganic & Medicinal Chemistry Letters > 1996 > 6 > 20 > 2393-2398

Replacement of the 4-methyl group in a series of N-(3,4-dimethylisoxazolyl)benzenesulfonamide endothelin antagonists with a bromine or chlorine atom resulted in a three- to ten-fold increase in the binding affinity for both the ET _A and ET _B receptors. This potentiation in activities was also observed for naphthalene and biphenylsulfonamide endothelin antagonists.

INFONA - science communication portal

Bioorganic & Medicinal Chemistry Letters

D-Phe-Pro-p-Amidinobenzylamine: a potent and highly selective thrombin inhibitor

Concerning the thermolability of cholesta-5,8-dien-3β-ol, a sterol that accumulates in blood and tissues in a human genetic developmental disorder

Isosteres of nucleoside triphosphates

A rapid synthesis of some 5 -amino-nucleosides and nucleotides as potential antiviral compounds.

New antithrombotic RGD-mimetics with high bioavailability

Inactivation of a prototypic zinc-containing protease with (S)-2-benzyl-2-(3-oxo-2-isoxazolidinyl)acetic acid

Synthesis and antibacterial activity of lipophilic carbapenems with anti-MRSA activity

Studies on the structural feature of S'1 subsite of neprilysin (EC.3.4.24.11) : stereochemical requirement for the enzyme-inhibitor docking process

Inhibition of HSV-1 protease by benzoxazinones

7,10-bis(2-mercapto-2-methyl)propyl-7,10-diazapalmitic acid: a novel, N ₂ S ₂ ligand for technetium-99m

Synthesis and biological activity of 4 -azido- and 4 -trifluoracetamido-3 -chloro-3 -deamino-4 -deoxydaunorubicin.

Palladium-catalysed synthesis of some biologically active 5,6-disubstituted uracils

Adenosine deaminase inhibitors. Synthesis and biological evaluation of chain modified analogs of (+)-EHNA.

Synthesis and cytotoxic activity of phenyl-hexahydropyrrolo[3,4-c]carbazoles

Syntheses of Trans-3'-substituted-CCG-IV Analogs and Their Characterization to Ionotropic Glutamate Receptors

Synthesis and antifungal activity of new azole derivatives containing an oxathiane ring

Trifluoromethyl Alcohol and Ketone Inhibitors of Metallo-β-Lactamases

Synthesis of a highly functionalized rigid template by solid phase azomethine ylide cycloaddition

Lipophilic bioisosteres of nucleoside triphosphates

Halogen substitution at the isoxazole ring enhances the activity of n-(isoxazolyl)sulfonamide endothelin antagonists

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