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K. G. Messenger, Kathleen Gibberd Educational Correspondent of The Sunday Times, Peter Brinson, (Monsignor) Derek Worlock Private Secretary to Cardinal Godfrey, Clarence Elliott, Richard Buckle, Elizabeth Nicholas, Harold Hobson, Dr. Sabin, Ian Peebles, John Collier, Mr. K. S. Peacock, A. A., Maurice Edelman, Antony Terry, C. V. Hancock, Gavin Lyall, Moira Keenan, Richard Kellett, Lella Smee, Rt. Hon. Edward Heath M. P., Ian Coulter The Sunday Times Industrial Correspondent, Henry Brandon, John Russell, Henry Brandon Washington Correspondent of The Sunday Times, Hugh Wynn, Arthur Jenkins, Robert Lindley, Derek Prouse, Patrick Campbell, Vivian Jenkins, Wm. Corbishley, James Stuart, Tom Margerison, Robert Targett, Peter Willett, Geoff Whitten, C. V. Wedgwood, Robin Marlar, Rev. G. W. Butterworth Litt. D., Hugh Somerville, Cyril Connolly, (Mrs.) Geryke Young, Ian Goulter Industrial Correspondent of The Sunday Times, Alwyne Wheeler, Virginia Chapman, Raymond Mortimer, Joan Vickers, Maxwell Boyd, Elizabeth, Evelyn Irons, Peter Clifton, Maurice Colbourne, Admiral Sir Michael Denny, J. H. Plumb, Susan Noel, Arthur C. Taylor, Alan Houghton Brodrick, Roger Mortimer, Ronald Hingley, John Raymond, Ernestine Carter, John Holloway, R. E. Peierls, Desmond Shawe-Taylor, Stephen Coulter, Elizabeth Longford, Michael Campbell, Bill Sowerbutts, R. C. Robertson-Glasgow, Margaret Lane, Dilys Powell, Mary Dorkenoo, Gerald Pawle, George M. Fullard, Richard Hughes, Felix Aprahamian, Tom Stacey, Jack Fingleton, Margaret Costa, Robert Robinson, Henry Williamson, Henry Longhurst, Sandra Marrs, Brian Glanville, Iain Lang, Contango, Auriel Limbert, Papas, C. H. O'd. Alexander, George Schwartz, John Bowen, Atticus, Maurice Wiggin, J. R. Astbury, Ralph W. G. Robinson City Councillor, Geoffrey Tillotson, Gordon Ross, D. S. T., James Evans, Laurence Lerner, (Miss) Terry Workman, Richard Strout, Susan Cooper, Rev. C. J. Parsons, Christopher Mayhew M. P., F. Rodgers, Kenneth Konstam, William Rees-Mogg The Sunday Times City Editor, David Attenborough,

... Human Brotherhood On Human Unity. By E. E. Hirschmann. (Gollancz. 25s) Laymen and the Law The Services ...

1961 - Gale Group | Sunday Times HA GDA

Artigo Revisado por pares

Amos B. Smith, Andrew B. Benowitz, Mark C. Guzman, Paul A. Sprengeler, Ralph Hirschmann, Edwin J. Schweiger, David Bolin, Zoltán Á. Nagy, Robert M. Campbell, Donald C. Çox, Gary L. Olson,

... B. Benowitz, Mark C. Guzman, Paul A. Sprengeler, Ralph Hirschmann, Edwin J. Schweiger, David R. Bolin, Zoltan Nagy, ...

Tópico(s): Monoclonal and Polyclonal Antibodies Research

1998 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

Amos B. Smith, Ralph Hirschmann, Alexander Pasternak, Wenyan Yao, Paul A. Sprengeler, M. Katharine Holloway, Lawrence C. Kuo, Zhongguo Chen, Paul L. Darke, William A. Schleif,

... Crystal Structure of the Enzyme ComplexAmos B. Smith, Ralph Hirschmann, Alexander Pasternak, Wenquing Yao, Paul A. Sprengeler, M. ...

Tópico(s): HIV/AIDS drug development and treatment

1997 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Amos B. Smith, Ralph Hirschmann, Alexander Pasternak, Mark C. Guzman, Akihisa Yokoyama, Paul A. Sprengeler, Paul L. Darke, Emilio A. Emini, William A. Schleif,

... Activity: Evidence for Improved TransportAmos B Smith . III, Ralph Hirschmann, Alexander Pasternak, Mark C. Guzman, Akihisa Yokoyama, Paul ...

Tópico(s): Click Chemistry and Applications

1995 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

Amos B. Smith, Ralph Hirschmann, Alexander Pasternak, Ryouichi Akaishi, Mark C. Guzman, David Jones, Terence P. Keenan, Paul A. Sprengeler, Paul L. Darke,

... renin. Evidence for improved transportAmos B. Smith III, Ralph Hirschmann, Alexander Pasternak, Ryouichi Akaishi, Mark C. Guzman, David ...

Tópico(s): Click Chemistry and Applications

1994 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Ruth F. Nutt, Frederick W. Holly, CARL G. HOMNICK, Ralph Hirschmann, Daniel F. Veber, Byron H. Arison,

... effectsRuth F. Nutt, Frederick W. Holly, Carl Homnick, Ralph Hirschmann, Daniel F. Veber, and Byron H. ArisonCite this: ...

Tópico(s): Thyroid Disorders and Treatments

1981 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

John J. Baldwin, William C. Lumma, G. F. Lundell, G. S. PONTICELLO, A. W. RAAB, Edward L. Engelhardt, Ralph Hirschmann, Charles S. Sweet, Alexander Scriabine,

... S. Ponticello, Andrew W. Raab, Edward L. Engelhardt, Ralph Hirschmann, Charles S. Sweet, and Alexander ScriabineCite this: J. ...

Tópico(s): Chemistry and Chemical Engineering

1979 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Roger Freidinger, Ralph Hirschmann, Daniel F. Veber,

... nitroarginyl peptides: synthesis of arginine vasotocinRoger M. Freidinger, Ralph Hirschmann, and Daniel F. VeberCite this: J. Org. Chem. ...

Tópico(s): Chemical Synthesis and Reactions

1978 - American Chemical Society | The Journal of Organic Chemistry

Artigo Revisado por pares

Walfred S. Saari, Mark B. Freedman, Richard D. Hartman, Stella W. King, A. W. RAAB, William C. Randall, Edward L. Engelhardt, Ralph Hirschmann, Avery Rosegay,

... W. Raab, William C. Randall, Edward L. Engelhardt, Ralph Hirschmann, Avery Rosegay, and Cite this: J. Med. Chem. ...

Tópico(s): Eicosanoids and Hypertension Pharmacology

1978 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Stephen F. Brady, Ralph Hirschmann, Daniel F. Veber,

... novel, acid-labile amine protecting groupsStephen F. Brady, Ralph Hirschmann, and Daniel F. VeberCite this: J. Org. Chem. ...

Tópico(s): Synthesis and Biological Evaluation

1977 - American Chemical Society | The Journal of Organic Chemistry

Artigo Revisado por pares

Daniel F. Veber, R. G. Strachan, Susan J. Bergstrand, Frederick W. Holly, Carl F. Homnick, Ralph Hirschmann, Mary Lou Torchiana, Richard Saperstein,

... J. Bergstrand, Frederick W. Holly, Carl F. Homnick, Ralph Hirschmann, Mary L. Torchiana, and Richard SapersteinCite this: J. ...

Tópico(s): Pituitary Gland Disorders and Treatments

1976 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

Daniel F. Veber, Sándor Varga, John D. Milkowski, H Joshua, John B. Conn, Ralph Hirschmann, Robert G. Denkewalter,

... John D. Milkowski, H. Joshua, John B. Conn, Ralph Hirschmann, and Robert G. DenkewalterCite this: J. Am. Chem. ...

Tópico(s): Analytical Chemistry and Chromatography

1969 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

Daniel F. Veber, Ralph Hirschmann, Robert G. Denkewalter,

... unsymmetrical cystine peptide fragment of insulinDaniel F. Veber, Ralph Hirschmann, and Robert G. DenkewalterCite this: J. Org. Chem. ...

Tópico(s): Ferrocene Chemistry and Applications

1969 - American Chemical Society | The Journal of Organic Chemistry

Artigo Revisado por pares

John H. Fried, Helmut Mrozik, Glen E. Arth, T. S. Bry, N. G. Steinberg, Max Tishler, Ralph Hirschmann, S. L. Steelman,

... T. S. Bry, N. G. Steinberg, M. Tishler, Ralph. Hirschmann, and S. L. SteelmanCite this: J. Am. Chem. ...

Tópico(s): Phytochemical Studies and Bioactivities

1963 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

B. G. CHRISTENSEN, R. G. Strachan, Nelson R. Trenner, Byron H. Arison, Ralph Hirschmann, J. M. Chemerda,

... G. Strachan, N. R. Trenner, B. H. Arison, Ralph Hirschmann, and J. M. ChemerdaCite this: J. Am. Chem. ...

Tópico(s): Pharmacogenetics and Drug Metabolism

1960 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

C. F. Hiskey, Ralph Hirschmann, N. L. Wendler,

... 17a)-C-NOR/D-HOMO-STEROIDClaude F. Hiskey, Ralph Hirschmann, and N. L. WendlerCite this: J. Am. Chem. ...

Tópico(s): Organic Chemistry Cycloaddition Reactions

1953 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

F. A. Cutler, J. P. Conbere, Robert M. Lukes, J. F. Fisher, Holly E. Mertel, Ralph Hirschmann, J. M. Chemerda, Lewis H. Sarett, K. Pfister,

... M. Lukes, J. F. Fisher, H. E. Mertel, Ralph Hirschmann, J. M. Chemerda, L. H. Sarett, and K. ...

Tópico(s): Cancer Treatment and Pharmacology

1958 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

Michael T. Hirschmann, Ralph Mayer, A Kentsch, Niklaus F. Friederich,

Tópico(s): Total Knee Arthroplasty Outcomes

2009 - Springer Science+Business Media | Knee Surgery Sports Traumatology Arthroscopy

Artigo Revisado por pares

William S. Johnson, C. David Gutsche, Ralph Hirschmann, V. L. Stromberg,

... Equilenin Synthesis1,2William S. Johnson, C. David Gutsche, Ralph Hirschmann, and Verner L. StrombergCite this: J. Am. Chem. ...

Tópico(s): Cholinesterase and Neurodegenerative Diseases

1951 - American Chemical Society | Journal of the American Chemical Society

Artigo Revisado por pares

R. G. Strachan, M. A. P. Meisinger, W. V. Ruyle, Ralph Hirschmann, T. Y. Shen,

... Strachan, M. A. P. Meisinger, W. V. Ruyle, Ralph Hirschmann, and T. Y. ShenCite this: J. Med. Chem. ...

Tópico(s): Pharmacogenetics and Drug Metabolism

1964 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Acesso aberto Revisado por pares

Amos B. Smith, Adam K. Charnley, Ralph Hirschmann,

Peptides and proteins, evolved by nature to perform vital biological functions, would constitute ideal candidates for therapeutic intervention were it not for their generally poor pharmacokinetic profiles. Nonpeptide peptidomimetics have thus been pursued because they might overcome these limitations while maintaining both the potency and selectivity of the parent peptide or protein. Since the late 1980s, we have sought to design, synthesize, and evaluate a novel, proteolytically stable nonpeptide ...

Tópico(s): Click Chemistry and Applications

2010 - American Chemical Society | Accounts of Chemical Research

Revisão Acesso aberto Revisado por pares

Ralph Hirschmann, K. C. Nicolaou, Angie R. Angeles, Jason S. Chen, Amos B. Smith,

Activity and selectivity are typically the first considerations when designing a drug. However, absorption, distribution, metabolism, excretion, and toxicity (ADMET) are equally important considerations. Peptides can provide a combination of potent binding and exquisite selectivity, as evidenced by their pervasive use as enzymes, hormones, and signaling agents within living systems. In particular, peptidic turn motifs are key elements of molecular recognition. They may be found at the exposed surfaces ...

Tópico(s): Protein Structure and Dynamics

2009 - American Chemical Society | Accounts of Chemical Research

Artigo Revisado por pares

Amos B. Smith, Adam K. Charnley, Hironori Harada, Jason J. Beiger, Louis‐David Cantin, Craig S. Kenesky, Ralph Hirschmann, Sanjeev Munshi, David B. Olsen, Mark W. Stahlhut, William A. Schleif, Lawrence C. Kuo,

A series of monopyrrolinone-based HIV-1 protease inhibitors possessing rationally designed P2' side chains have been synthesized and evaluated for activity against wild-type HIV-1 protease. The most potent inhibitor displays subnanomolar potency in vitro for the wild-type HIV-1 protease. Additionally, the monopyrrolinone inhibitors retain potency in cellular assays against clinically significant mutant forms of the virus. X-ray structures of these inhibitors bound in the wild-type enzyme reveal ...

Tópico(s): Click Chemistry and Applications

2005 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters

Artigo Revisado por pares

Amos B. Smith, Adam K. Charnley, Eugen F. Mesaros, Osamu Kikuchi, Wenyong Wang, Andrew B. Benowitz, C.T. Chu, Jin-Jye Feng, Kuo-Hsin Chen, Atsui Lin, Fong‐Chi Cheng, Laurie L. Taylor, Ralph Hirschmann,

Tetrapyrrolinone somatostatin (SRIF) mimetics (cf. 1), based on a heterochiral (d,l-mixed) pyrrolinone scaffold, were designed, synthesized, and evaluated for biological activity. The iterative synthetic sequence, incorporating the requisite functionalized coded and noncoded amino acid side chains, comprised a longest linear synthetic sequence of 23 steps. Binding affinities at two somatostatin receptor subtypes (hsst 4 and 5) reveal micromolar activity, demonstrating that the d,l-mixed pyrrolinone ...

Tópico(s): Neuroendocrine Tumor Research Advances

2005 - American Chemical Society | Organic Letters

Artigo Revisado por pares

Santhosh Neelamkavil, Byron H. Arison, Elizabeth T. Birzin, Jin-Jye Feng, Kuo-Hsin Chen, Atsui Lin, Fong‐Chi Cheng, Laurie L. Taylor, Edward R. Thornton, Amos B. Smith, Ralph Hirschmann,

An alanine scan performed in the 1970s suggested that Phe6 and Phe11 are required for the binding of somatostatin (SRIF-14). Molecular modeling studies and replacement of Phe6 and Phe11 with a cystine bridge affording ligands with the retention of high biological activity, however, led to the alternate conclusion that Phe6 and Phe11 stabilize the bioactive conformation of SRIF-14. Subsequent studies revealed that Phe11 shields Phe6 in a "herringbone" arrangement. More recently, a report from this ...

Tópico(s): Monoclonal and Polyclonal Antibodies Research

2005 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Vidya Prasad, Elizabeth T. Birzin, Cheryl T. McVaugh, Rachel D. van Rijn, Susan P. Rohrer, Gary G. Chicchi, Dennis Underwood, Edward R. Thornton, Amos B. Smith, Ralph Hirschmann,

In our continuing program exploring glucose-based peptidomimetics of somatostatin (SRIF-14), we sought to improve the water solubility of our glycosides. This led to insights into the nature of the ligand binding sites at the SRIF receptor. Replacement of the C4 benzyl substituent in glucoside (+)-2 with pyridinylmethyl or pyrazin-2-ylmethyl congeners increased water solubility and enhanced affinity for the human SRIF subtype receptor 4 (sst4). We attribute this effect to hydrogen bond formation. The ...

Tópico(s): Chemical Synthesis and Analysis

2003 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Amos B. Smith, Young Shin Cho, George R. Pettit, Ralph Hirschmann,

Cryptophycins, depsipeptides isolated from terrestrial blue–green algae, show potent activity against a variety of tumor cell lines. Given the potential of the cryptophycins for cancer therapy, we developed a new class of non-peptide peptidomimetic, designed to replace the 16-membered macrolide ring with a 7-membered azepine ring for attachment of the cryptophycin side chains with the required spatial orientation to mimic the conformation of the relevant region of the natural product. Monte Carlo ...

Tópico(s): Biochemical and Structural Characterization

2003 - Elsevier BV | Tetrahedron

Artigo Revisado por pares

Leïla Abrous, Patrick A. Jokiel, Sarah R. Friedrich, John Hynes, Amos B. Smith, Ralph Hirschmann,

New molecular platforms which are hybrids of two scaffoldsnamely, β-d-glucose and benzodiazepine, each able to bind several proteinswere designed, synthesized and functionalized to serve as probes for broad biological screening. Herein, we describe the syntheses and chemical properties of these novel chimeric scaffolds. Attempted cyclization of the functionalized analogues (−)-96 and (−)-97 afforded the corresponding dimers (−)-98 and (−)-99, respectively, under a variety of reaction conditions, even at concentrations ...

Tópico(s): Asymmetric Synthesis and Catalysis

2003 - American Chemical Society | The Journal of Organic Chemistry

Artigo Revisado por pares

Amos B. Smith, Louis‐David Cantin, Alexander Pasternak, Lisa Guise-Zawacki, Wenquin Yao, Adam K. Charnley, Joseph Barbosa, Paul A. Sprengeler, Ralph Hirschmann, Sanjeev Munshi, David B. Olsen, William A. Schleif, Lawrence C. Kuo,

The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors [(−)-6, (−)-7, (−)-23, (+)-24] based upon the 3,5,5-trisubstituted pyrrolin-4-one scaffold is described. Use of a monopyrrolinone scaffold leads to inhibitors with improved cellular transport properties relative to the earlier inhibitors based on bispyrrolinones and their peptide counterparts. The most potent inhibitor (−)-7 displayed 13% oral bioavailability in dogs. X-ray structure analysis of the monopyrrolinone compounds cocrystallized ...

Tópico(s): HIV/AIDS Research and Interventions

2003 - American Chemical Society | Journal of Medicinal Chemistry

Artigo Revisado por pares

Leïla Abrous, John Hynes, Sarah R. Friedrich, Amos B. Smith, Ralph Hirschmann,

We describe the syntheses of novel tricyclic scaffolds that incorporate a fusion of a substituted pyranose ring with the seven-membered rings of 1,2,3,4-tetrahydrobenzo[e][1,4]diazepin-5-one and the corresponding oxazepine and pyridyldiazepine to generate the benzodiazepines, and the related heterocycles. In each instance, the pyranose rings contain three protected hydroxyls, suitable for selective derivatization.

Tópico(s): Cancer therapeutics and mechanisms

2001 - American Chemical Society | Organic Letters