Stephen Hanessian

Summary

Country: Canada

Publications

  1. doi request reprint Design and synthesis of potential dual NK(1)/NK(3) receptor antagonists
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, Que H3C 3J7, Canada Electronic address
    Bioorg Med Chem Lett 24:510-4. 2014
  2. doi request reprint Concise and stereocontrolled synthesis of the tetracyclic core of daphniglaucin C
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, QC, H3C 3J7, Canada
    Org Lett 15:4134-7. 2013
  3. doi request reprint Probing functional diversity in pactamycin toward antibiotic, antitumor, and antiprotozoal activity
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, CP 6128, Montreal, QC, Canada H3C 3J7
    Bioorg Med Chem 21:1775-86. 2013
  4. doi request reprint Structure-based design of a highly constrained nucleic acid analogue: improved duplex stabilization by restricting sugar pucker and torsion angle γ
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, QC, Canada
    Angew Chem Int Ed Engl 51:11242-5. 2012
  5. doi request reprint The enterprise of synthesis: from concept to practice
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, succursale Centre Ville Montreal, Quebec H3C 3J7, Canada
    J Org Chem 77:6657-88. 2012
  6. doi request reprint A new approach to the synthesis of peptidomimetic renin inhibitors: palladium-catalyzed asymmetric allylation of acyclic alkyl aryl ketones
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Org Lett 14:3222-5. 2012
  7. ncbi request reprint Structure-based organic synthesis of a tricyclic N-malayamycin analogue
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Org Chem 71:9807-17. 2006
  8. ncbi request reprint 6-hydroxy to 6'''-amino tethered ring-to-ring macrocyclic aminoglycosides as probes for APH(3')-IIIa kinase
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    Bioorg Med Chem Lett 17:3221-5. 2007
  9. ncbi request reprint Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station, Centre Ville, Montreal, QC, Canada H3C 3J7
    Bioorg Med Chem Lett 17:3480-5. 2007
  10. ncbi request reprint Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, Montreal, Quebec, Canada
    Bioorg Med Chem Lett 17:6261-5. 2007

Detail Information

Publications84

  1. doi request reprint Design and synthesis of potential dual NK(1)/NK(3) receptor antagonists
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, Que H3C 3J7, Canada Electronic address
    Bioorg Med Chem Lett 24:510-4. 2014
    ..From this series emerged compounds with good NK1 receptor affinity, although only modest dual NK1/NK3 receptor affinity was observed with one of these analogs. ..
  2. doi request reprint Concise and stereocontrolled synthesis of the tetracyclic core of daphniglaucin C
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, QC, H3C 3J7, Canada
    Org Lett 15:4134-7. 2013
    ..7%. The key steps toward this core motif feature a reductive double bond transposition from an unactivated tertiary allylic alcohol, a Pd-catalyzed Stille coupling, and Dieckmann cyclizations. ..
  3. doi request reprint Probing functional diversity in pactamycin toward antibiotic, antitumor, and antiprotozoal activity
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, CP 6128, Montreal, QC, Canada H3C 3J7
    Bioorg Med Chem 21:1775-86. 2013
    ..The present study highlights the effects of changing the urea and aniline groups especially with regard to anticancer and antiprotozoal activities...
  4. doi request reprint Structure-based design of a highly constrained nucleic acid analogue: improved duplex stabilization by restricting sugar pucker and torsion angle γ
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, QC, Canada
    Angew Chem Int Ed Engl 51:11242-5. 2012
    ..This new modification increases the thermostability of an oligonucleotide duplex compared to using a single mode of constraint alone...
  5. doi request reprint The enterprise of synthesis: from concept to practice
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, succursale Centre Ville Montreal, Quebec H3C 3J7, Canada
    J Org Chem 77:6657-88. 2012
    ..Lessons learned and synthetic methods developed are discussed in the context of selected natural products covered in this Perspective...
  6. doi request reprint A new approach to the synthesis of peptidomimetic renin inhibitors: palladium-catalyzed asymmetric allylation of acyclic alkyl aryl ketones
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Org Lett 14:3222-5. 2012
    ..A beneficial effect of protic additives, such as BHT (2,6-di-tert-butyl-p-cresol), on the time and enantioselectivity of the reaction was discovered...
  7. ncbi request reprint Structure-based organic synthesis of a tricyclic N-malayamycin analogue
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Org Chem 71:9807-17. 2006
    ..On the basis of this topological feature, we synthesized a tricyclic N-nucleoside analogue in which an ethano bridge linked the urea NH group with the ring junction of the bicyclic tetrahydrofuropyran unit...
  8. ncbi request reprint 6-hydroxy to 6'''-amino tethered ring-to-ring macrocyclic aminoglycosides as probes for APH(3')-IIIa kinase
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    Bioorg Med Chem Lett 17:3221-5. 2007
    ..Only one of two possible hydroxyl groups was phosphorylated by the kinase. The application of ring closure metathesis is presented for the first time to construct bridged macrocyclic analogues in the aminoglycoside series...
  9. ncbi request reprint Structure-based organic synthesis of unnatural aeruginosin hybrids as potent inhibitors of thrombin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station, Centre Ville, Montreal, QC, Canada H3C 3J7
    Bioorg Med Chem Lett 17:3480-5. 2007
    ..This is rationalized based on a better fit of the P(3) subunit in the hydrophobic S(3) enzyme site. Single digit nanomolar inhibition expressed as IC(50) was observed for several analogs...
  10. ncbi request reprint Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, Montreal, Quebec, Canada
    Bioorg Med Chem Lett 17:6261-5. 2007
    ..However, no significant difference in antiproliferative activity was observed between two enantiomers bearing the benzyl ether moiety...
  11. ncbi request reprint Self-assembly of noncyclic bis-D- and L-tripeptides into higher order tubular constructs: design, synthesis, and X-ray crystal superstructure
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, QC, H3C 3J7, Canada
    J Org Chem 73:1181-91. 2008
    ..Related bis-tripeptides with different amino acids showed extensive intramolecular H-bonding based on NMR titration and dilution experiments...
  12. ncbi request reprint Targeting ACE and ECE with dual acting inhibitors
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, QB, Canada
    Bioorg Med Chem Lett 18:1058-62. 2008
    ..Although excellent ACE and NEP inhibition was achieved, only modest ECE inhibition was observed with one analogue...
  13. ncbi request reprint Total synthesis and stereochemical confirmation of manassantin A, B, and B1
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Org Lett 8:5477-80. 2006
    ..Stereocontrolled total syntheses of manassantins A, B, and B1 and saucerneol are described for the first time based on a novel cycloetherification of end-differentiated benzylic alcohols as a common intermediate. [structure: see text]...
  14. ncbi request reprint Structure-based organic synthesis of drug prototypes: a personal odyssey
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, QC, H3C3J7, Canada
    ChemMedChem 1:1301-30. 2006
  15. ncbi request reprint Constrained azacyclic analogues of the immunomodulatory agent FTY720 as molecular probes for sphingosine 1-phosphate receptors
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, Que, Canada H3C 3J7
    Bioorg Med Chem Lett 17:491-4. 2007
    ..The phosphates may be useful to explore the biology and binding site of these receptors...
  16. ncbi request reprint Optimization of the catalytic asymmetric addition of nitroalkanes to cyclic enones with trans-4,5-methano-L-proline
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, QC H3C 3J7, Canada
    Org Lett 8:4787-90. 2006
    ..Proline hydroxamic acid and its trans-4,5-methano -l-proline hydroxamic acid are also effective organocatalysts in the addition of 2-nitropropane to 2-cyclohexenone (75% and 81% ee, respectively)...
  17. ncbi request reprint Synthesis and stereochemical confirmation of the secoiridoid glucosides nudiflosides D and A
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7 Canada
    Org Lett 8:4047-9. 2006
    ..We describe herein an efficient access to the highly substituted cyclopentane unit present in the Nudifloside secoiridoid family via crotyl phosphonamide anion mediated conjugate addition to cyclopentenone...
  18. ncbi request reprint Structure-based design, synthesis, and A-site rRNA cocrystal complexes of functionally novel aminoglycoside antibiotics: C2" ether analogues of paromomycin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada
    J Med Chem 50:2352-69. 2007
    ..Preliminary histopathological analysis of the kidney showed no overt signs of toxicity, while controls with neomycin and kanamycin were toxic at lower doses...
  19. ncbi request reprint Exploring alternative Zn-binding groups in the design of HDAC inhibitors: squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, Que, Canada H3C 3J7
    Bioorg Med Chem Lett 16:4784-7. 2006
    ..No inhibitory activity on HDAC was observed below 1.0 microM and no cytotoxic activity on different tumor cell lines was seen below 20.0 microM...
  20. ncbi request reprint Structure-based design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease beta-site amyloid precursor protein cleaving enzyme (BACE)
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Station Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Med Chem 49:4544-67. 2006
    ..Cocrystal structures of two synthetic analogues revealed interesting and unexpected binding interactions...
  21. doi request reprint Synthesis of chemically functionalized superparamagnetic nanoparticles as delivery vectors for chemotherapeutic drugs
    Stephen Hanessian
    Universite de Montreal, Department of Chemistry, PO Box 6128, Station, Centre Ville, Montreal, Que, Canada H3C 3J7
    Bioorg Med Chem 16:2921-31. 2008
    ..While the doxorubicin-SPIONs linked with a Gly-Phe-Leu-Gly tetrapeptide were cleaved by lysosomal enzymes, they exhibited poor uptake by human melanoma cells in culture...
  22. doi request reprint Design, synthesis, and thrombin-inhibitory activity of pyridin-2-ones as P2/P3 core motifs
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Que, Canada H3C 3J7
    Bioorg Med Chem Lett 18:1972-6. 2008
    ..Potent in vitro activity against thrombin, with excellent selectivity over trypsin was found for selected analogues...
  23. doi request reprint The practice of ring constraint in peptidomimetics using bicyclic and polycyclic amino acids
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Acc Chem Res 41:1241-51. 2008
    ..Specific applications as peptidomimetics of natural substrates for relevant enzymes, such as thrombin, were also pursued, resulting in highly active inhibitors in vitro...
  24. doi request reprint Hybrid aminoglycoside antibiotics via Tsuji palladium-catalyzed allylic deoxygenation
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, QC, Canada, H3C 3J7
    Org Lett 13:6476-9. 2011
    ..The neomycin-sisomicin hybrid exhibited superior in vitro antibacterial activity to the parent compound neomycin...
  25. doi request reprint Total synthesis of (+)-ent-cyclizidine: absolute configurational confirmation of antibiotic M146791
    Stephen Hanessian
    Department of Chemistry, Université de Montréal, Montreal, QC, Canada
    Org Lett 13:1048-51. 2011
    ..With this total synthesis, the absolute configuration of the natural product based on a redetermination of its X-ray structure has been confirmed...
  26. doi request reprint Applications of organocatalytic asymmetric synthesis to drug prototypes--dual action and selective inhibitors of n-nitric oxide synthase with activity against the 5-HT1D/1B subreceptors
    Stephen Hanessian
    Department of Chemistry, Université de Montréal, Montreal, QC, Canada
    Org Lett 13:840-3. 2011
    ..The scope and effect of the groups on nitrogen (R, R') has also been studied. The method has been applied to the concise synthesis of an advanced precursor to S-(+)-1, a drug prototype for the treatment of migraine headaches...
  27. doi request reprint Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Montreal, QC, Canada
    Bioorg Med Chem Lett 20:6925-8. 2010
    ..Several compounds displayed modest activity and good selectivity for Factor XIa. Within the series, a promising lead structure for developing novel macrocyclic inhibitors of thrombin was identified...
  28. doi request reprint Total synthesis of (+)-ambruticin S: probing the pharmacophoric subunit
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Canada H3C 3J7
    J Org Chem 75:5601-18. 2010
    ..Other key steps in the synthesis featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation...
  29. doi request reprint Total synthesis of jerangolid A
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, QC H3C 3J7, Canada
    Org Lett 12:3172-5. 2010
    ..Other key steps in the synthesis featured a novel application of a phosphonamide-anion based olefination and a Julia-Kocienski reaction...
  30. doi request reprint Substrate-controlled and organocatalytic asymmetric synthesis of carbocyclic amino acid dipeptide mimetics
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, QC H3C 3J7, Canada
    J Org Chem 75:2861-76. 2010
    ..The asymmetric synthesis of a carbocyclic delta-amino acid representing the P(2)/P(3) subunit of a nonpeptidic truncated peptidomimetic molecule is described relying on two independent approaches...
  31. doi request reprint Total synthesis of "aliskiren": the first Renin inhibitor in clinical practice for hypertension
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Org Lett 12:1816-9. 2010
    ....
  32. doi request reprint Biomimetic synthesis and structural refinement of the macrocyclic dimer aminoglycoside 66-40C--the remarkably selective self-condensation of a putative aldehyde intermediate in the submerged culture medium producing sisomicin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, QC, Canada H3C 3J7
    Chem Commun (Camb) 46:2013-5. 2010
    ....
  33. doi request reprint Structure-based design and synthesis of novel P2/P3 modified, non-peptidic beta-secretase (BACE-1) inhibitors
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Montreal, Canada
    Bioorg Med Chem Lett 20:1924-7. 2010
    ..Further optimization based on this structure resulted in highly potent BACE-1 inhibitors with selectivity over BACE-2 and cathepsin D...
  34. doi request reprint Total synthesis of oidiodendrolides and related norditerpene dilactones from a common precursor: metabolites CJ-14,445, LL-Z1271gamma, oidiolactones A, B, C, and D, and nagilactone F
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec, H3C 3J7, Canada
    Org Lett 11:4640-3. 2009
    ..Access to CJ-14,445, LL-Z1271gamma, oidiolactones A, B, C, and D, and nagilactone F was possible from a common intermediate. Structures and stereochemistry were determined by X-ray analysis...
  35. doi request reprint Total synthesis and structural revision of the presumed aeruginosins 205A and B
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    Org Lett 11:4232-5. 2009
    ..31 microM. The total synthesis of the presumed aeruginosin 205B shows that the alpha-d-xylopyranosyl unit carries a sulfate group at C-4' (and not at C-3'). Comparison of NMR data leads to the same revision of aeruginosin 205A...
  36. doi request reprint From natural products to achiral drug prototypes: potent thrombin inhibitors based on P2/P3 dihydropyrid-2-one core motifs
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    Bioorg Med Chem Lett 19:5429-32. 2009
    ..Moderate to low nanomolar inhibitory activities were obtained against thrombin and excellent selectivity against trypsin was observed...
  37. doi request reprint Synthesis and comparative antibacterial activity of verdamicin C2 and C2a. A new oxidation of primary allylic azides in dihydro[2H]pyrans
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada, H3C 3J7
    Org Lett 11:429-32. 2009
    ..Oxidation of allylic primary azides, ethers, and esters of 2-substituted dihydro[2H]pyrans with SeO(2) leads directly to the corresponding aldehydes...
  38. ncbi request reprint Design and synthesis of diversely substituted azacyclic inhibitors of endothelin converting enzyme
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    J Org Chem 71:2760-78. 2006
    ..Weak inhibitory activity was observed for one diastereomer in each series having the same relative orientation of substituents...
  39. ncbi request reprint Conformationally stable and constrained macrocarbocyclic pseudopeptide mimics of beta-hairpin structures
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, QC, Canada
    Chemistry 8:111-7. 2002
    ..NMR studies revealed the high conformational stability of these motifs...
  40. ncbi request reprint The N-acyloxyiminium ion aza-Prins route to octahydroindoles: total synthesis and structural confirmation of the antithrombotic marine natural product oscillarin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Station Centre Ville, Montreal, P Q, H3C 3J7 Canada
    J Am Chem Soc 126:6064-71. 2004
    ..X-ray crystal structures of products corroborate the expected stereochemistry...
  41. ncbi request reprint Total synthesis and structural confirmation of malayamycin A: a novel bicyclic C-nucleoside from Streptomyces malaysiensis
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Org Lett 5:4277-80. 2003
    ..reaction: see text] The stereocontrolled synthesis of malayamycin A, a novel naturally occurring bicyclic C-nucleoside of the perhydrofuropyran type, is described...
  42. ncbi request reprint Application of conformation design in acyclic stereoselection: total synthesis of borrelidin as the crystalline benzene solvate
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, P O Box 6128, Station Centre ville Montreal, Province of Quebec H3C 3J7, Canada
    J Am Chem Soc 125:13784-92. 2003
    ..A virtual diamond lattice was used as a visual tool to portray the low-energy conformations of the acyclic substrates, and corroborated by (1)H NMR homodecoupling studies...
  43. ncbi request reprint Synthesis of functionally diverse and conformationally constrained polycyclic analogues of proline and prolinol
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    J Org Chem 68:7204-18. 2003
    ..Functional diversity was introduced via further manipulation of pendant groups on the original proline motif as well as on the aromatic moiety...
  44. ncbi request reprint Functionalized glycomers as growth inhibitors and inducers of apoptosis in human glioblastoma cells
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Province of Quebec, Canada, H3C 3J7
    J Med Chem 46:3600-11. 2003
    ..Thus, functionalized aryl beta-D-glycopyranosides represent a new class of molecules potentially able to control the progression of brain tumors...
  45. ncbi request reprint The power of visual imagery in drug design. Isopavines as a new class of morphinomimetics and their human opioid receptor binding activity
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Succersale Centre Ville, Montreal, Quebec, Canada
    J Med Chem 46:34-48. 2003
    ..Agonist-like activity is indicated in a functional assay for one of the analogues originally derived from d-alanine as a precursor. X-ray crystal structures of several compounds corroborate stereochemistries and overall topologies...
  46. ncbi request reprint Design, synthesis, and neuraminidase inhibitory activity of GS-4071 analogues that utilize a novel hydrophobic paradigm
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, QC, Canada
    Bioorg Med Chem Lett 12:3425-9. 2002
    ..An X-ray co-crystal structure of the new inhibitor (K(i)=45 nM) bound to the active site shows that the vinyl group occupies the same subsite as the amino group in GS-4071...
  47. ncbi request reprint Total synthesis and structural confirmation of the marine natural product Dysinosin A: a novel inhibitor of thrombin and Factor VIIa
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Quebec H3C 3J7 Canada
    J Am Chem Soc 124:13342-3. 2002
    ..The Grubbs olefin metathesis carbocyclization reaction was utilized to prepare two intermediates...
  48. ncbi request reprint Targeting thrombin and factor VIIa: design, synthesis, and inhibitory activity of functionally relevant indolizidinones
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, QC, Canada
    Bioorg Med Chem Lett 12:2907-11. 2002
    ....
  49. ncbi request reprint The power of visual imagery in synthesis planning. Stereocontrolled approaches to CGP-60536B, a potent renin inhibitor
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Quebec H3C 3J7, Canada
    J Org Chem 67:4261-74. 2002
    ..X-ray crystallography was used to corroborate the structures and stereochemistries of several intermediates...
  50. ncbi request reprint Design and synthesis of a novel class of constrained tricyclic pyrrolizidinone carboxylic acids as carbapenem mimics
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Org Chem 67:3387-97. 2002
    ..However, the antibacterial activity of ceftazidine was enhanced in the presence of the tricyclic analogues...
  51. ncbi request reprint Synthesis of a potent antagonist of E-selectin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7 Canada
    J Org Chem 67:3346-54. 2002
    ..Stereocontrolled glycosylations rely on the anomeric activation of 2-pyridylthio carbonate as leaving group for the attachment of beta-D-galactopyranosyl and alpha-L-fucopyranosyl units on a common 1,5-anhydro D-glucitol scaffold...
  52. doi request reprint Structure-based design, synthesis and A-site rRNA co-crystal complexes of novel amphiphilic aminoglycoside antibiotics with new binding modes: a synergistic hydrophobic effect against resistant bacteria
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Montreal, Canada
    Bioorg Med Chem Lett 20:7097-101. 2010
    ..Incorporation of an hydrophobic (phenethylamino)ethyl ether at C2″ of N1-(HABA)-3',4'-dideoxyparomomycin led to a novel analog with an excellent antibacterial profile against a host of resistant bacteria...
  53. ncbi request reprint Total synthesis of A-315675: a potent inhibitor of influenza neuraminidase
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Am Chem Soc 124:4716-21. 2002
    ..8% overall yield over 22 steps. Several crystalline intermediates were suitable for single-crystal X-ray analysis...
  54. ncbi request reprint A comparative docking study and the design of potentially selective MMP inhibitors
    S Hanessian
    Department of Chemistry, Universite de Montreal, QC, Canada
    J Comput Aided Mol Des 15:873-81. 2001
    ..AutoDock proved to be highly reliable, efficient and predictive for a set of inhibitors with less than six atom types...
  55. pmc Total synthesis of the cytotoxic cyclodepsipeptide (-)-doliculide: the "ester" effect in acyclic 1,3-induction of deoxypropionates
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, QC, Canada H3C 3J7
    Proc Natl Acad Sci U S A 101:11996-2001. 2004
    ..The 1-methyl-1-cyclopentyl ester group was found to confer the best syn selectivity to the cuprate addition products, especially in seven-carbon enoates...
  56. ncbi request reprint Synthesis of 3 10-helix-inducing constrained analogues of L-proline
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, Quebec, Canada H3C 3J7
    J Org Chem 69:4891-9. 2004
    ..Variable-temperature NMR, DMSO titration, CD spectra, and X-ray structure analyses, in conjunction with molecular modeling, confirmed the existence of 3(10)-helical motifs with di- and tetrapeptides of l-Ala...
  57. ncbi request reprint Total synthesis and structural confirmation of (+)-longicin
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Org Lett 7:3989-92. 2005
    ..The use of Grubbs' RCM reaction as a novel "chain elongation" strategy for the synthesis of acetogenin-type structures and a new protocol for butenolide incorporation are also described. [structure: see text]..
  58. ncbi request reprint Man, machine and visual imagery in strategic synthesis planning: computer-perceived precursors for drug candidates
    Stephen Hanessian
    Universite de Montreal, Department of Chemistry, CP 6128, Succursale Centre Ville, Montreal, Canada
    Curr Opin Drug Discov Devel 8:798-819. 2005
    ..Applications to strategic syntheses of drug candidates are demonstrated...
  59. ncbi request reprint Phenolic P2/P3 core motif as thrombin inhibitors--design, synthesis, and X-ray co-crystal structure
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, PQ, Canada H3C 3J7
    Bioorg Med Chem Lett 16:1032-6. 2006
    ..Prototypical thrombin inhibitors were synthesized based on a trisubstituted phenol as a core motif. A naphthylsulfonamide analogue showed excellent antithrombin activity. An X-ray co-crystal structure showed the expected interactions...
  60. ncbi request reprint Probing the "additive effect" in the proline and proline hydroxamic acid catalyzed asymmetric addition of nitroalkanes to cyclic enones
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, Canada
    Chirality 17:540-3. 2005
    ..Proline hydroxamic acid is shown for the first time to be an effective organocatalyst in the same Michael reaction...
  61. ncbi request reprint Stereoselective synthesis of constrained azacyclic hydroxyethylene isosteres as aspartic protease inhibitors: dipolar cycloaddition and related methodologies toward branched pyrrolidine and pyrrolidinone carboxylic acids
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    J Org Chem 70:6746-56. 2005
    ..Low nanomolar inhibition of BACE1, an enzyme implicated in the cascade of events leading to plaque formation in Alzheimer's disease, was found with a pyrrolidinone analogue...
  62. ncbi request reprint Stereoselective synthesis of constrained oxacyclic hydroxyethylene isosteres of aspartic protease inhibitors: aldol and Mukaiyama aldol methodologies for branched tetrahydrofuran 2-carboxylic acids
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    J Org Chem 70:6735-45. 2005
    ..This was used as a constrained THF subunit in the synthesis of a peptidomimetic intended as an inhibitor of the enzyme BACE1, which is implicated in the cascade of events leading to plaque formation in Alzheimer's disease...
  63. ncbi request reprint Total synthesis of N-malayamycin A and related bicyclic purine and pyrimidine nucleosides
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succ Centre Ville, Montreal, P Q, Canada H3C 3J7
    J Org Chem 70:6721-34. 2005
    ..Ring closure metathesis was used in two approaches to build the bicyclic dioxa heterocycle. Another approach relied on the use of a sugar precursor and cyclization to the bicyclic thioglycoside...
  64. ncbi request reprint Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Province Quebec, Canada H3C 3J7
    J Med Chem 48:5175-90. 2005
    ..X-ray cocrystal structures of two analogues 5 and 45 revealed excellent convergence with the original inhibitor 1 structure while providing new insights into other interactions which could be exploited for future modifications...
  65. ncbi request reprint 3-N,N-Dimethylamino-3-deoxy lincomycin: a structure-based hybrid between lincomycin and the desosamine unit of erythromycin
    Stephen Hanessian
    PO Box 6128, Department of Chemistry, University of Montreal, Montreal, QC, Canada H3C 3J7
    Bioorg Med Chem 13:5283-8. 2005
    ..The synthesis in eight steps from lincomycin, involving a trans-diequatorial opening of an intermediate epoxide as the key step, is described...
  66. ncbi request reprint Sulfonamide-based acyclic and conformationally constrained MMP inhibitors: from computer-assisted design to nanomolar compounds
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    Curr Top Med Chem 4:1269-87. 2004
    ..This ultimately led to compounds exhibiting inhibitory activities in the nanomolar range. Interestingly, the qualitative ranking prediction was found to be in good agreement with the observed activities...
  67. ncbi request reprint Total synthesis and structural confirmation of chlorodysinosin A
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Station Centre Ville, Montreal, P Q, H3C 3J7 Canada
    J Am Chem Soc 128:10491-5. 2006
    ....
  68. ncbi request reprint A method for induced-fit docking, scoring, and ranking of flexible ligands. Application to peptidic and pseudopeptidic beta-secretase (BACE 1) inhibitors
    Nicolas Moitessier
    Department of Chemistry, McGill University, 801 Sherbrooke Street W, Montreal, Quebec H3A 2K6, Canada
    J Med Chem 49:5885-94. 2006
    ..The significant enrichment at the top of the ranking list in active compounds demonstrated the ability of the docking and scoring protocol to rank the compounds relative to their activities...
  69. ncbi request reprint Alternative and expedient asymmetric syntheses of L-(+)-noviose
    Stephen Hanessian
    Department of Chemistry, Universite de Montreal, PO Box 6128, Station Centre Ville, Montreal, QC, H3C 3J7 Canada
    Org Lett 10:261-4. 2008
    ....
  70. ncbi request reprint Asymmetric synthesis of functionalized carbocycles and heterocycles
    S Hanessian
    Department of Chemistry, Universite de Montreal, Succursale Centreville, Montreal, Quebec, Canada
    Chirality 12:342-5. 2000
    ..Addition to imines is also possible. The adducts can be transformed into enantiopure or enriched carbocyclic and heterocyclic compounds bearing useable functionality...
  71. ncbi request reprint Pyrrolidine as a cogwheel-like scaffold for the deployment of diverse functionality through cycloaddition reactions of metallo-1,3-dipoles in aqueous media
    S Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, QC, Canada
    Bioorg Med Chem Lett 10:427-31. 2000
    ..The reaction of glycinatocopper complexes with cinnamaldehydes under mildy basic aqueous conditions, affords polysubstituted prolines, which can be systematically modified in a number of chemoselective transformations...
  72. ncbi request reprint Design and synthesis of mimics of S-adenosyl-L-homocysteine as potential inhibitors of erythromycin methyltransferases
    S Hanessian
    Department of Chemistry, Universite de Montreal, Station Centre Ville, QC, Canada
    Bioorg Med Chem Lett 10:433-7. 2000
    ..A carbocyclic analogue derived from quinic acid was also synthesized and tested...
  73. ncbi request reprint Design and synthesis of matrix metalloproteinase inhibitors guided by molecular modeling. Picking the S(1) pocket using conformationally constrained inhibitors
    S Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, P Q H3C 3J7, Canada
    J Med Chem 44:3074-82. 2001
    ..Biological evaluation showed low nanomolar activity and modest selectivity toward different MMP subclasses, delineating the importance of binding to the S(1) pocket for both activity and selectivity...
  74. ncbi request reprint Design and synthesis of functionalized glycomers as non-peptidic ligands for SH2 binding and as inhibitors of A-431 human epidermoid and HT-29 colon carcinoma cell lines
    S Hanessian
    Department of Chemistry, Universite de Montreal, CP 6128, Succursale Centre Ville, PQ, Canada
    Bioorg Med Chem Lett 10:439-42. 2000
    ..A set of O-substituted aryl beta-D-glucopyranosides were prepared and found to have inhibitory activity on the growth of two carcinoma cell lines...
  75. ncbi request reprint N-Aryl sulfonyl homocysteine hydroxamate inhibitors of matrix metalloproteinases: further probing of the S(1), S(1)', and S(2)' pockets
    S Hanessian
    Department of Chemistry, Universite de Montreal, C P 6128, Succursale Centre Ville, Montreal, Quebec H3C 3J7, Canada
    J Med Chem 44:3066-73. 2001
    ..A series of N-arylsulfonyl S-alkyl homocysteine hydroxamic acids were synthesized with variations in three subsites corresponding to P(1), P(1)', and P(2)'. Enzyme assays with a variety of MMPs revealed activity at the low nanomolar level...
  76. ncbi request reprint Exploring the chiral space within the active site of alpha-thrombin with a constrained mimic of D-Phe-Pro-Arg--design, synthesis, inhibitory activity, and X-ray structure of an enzyme-inhibitor complex
    S Hanessian
    Department of Chemistry, Universite de Montreal, Quebec, Canada
    Bioorg Med Chem Lett 10:243-7. 2000
    ..An X-ray crystal structure of the inhibitor with alpha-thrombin shows the expected interactions with key amino acids within the active site and some notable changes in positions...
  77. ncbi request reprint Docking of aminoglycosides to hydrated and flexible RNA
    Nicolas Moitessier
    Department of Chemistry, McGill University, 801 Sherbrooke Street W, Montreal, Quebec H3A 2K6, Canada
    J Med Chem 49:1023-33. 2006
    ..As an application, a set of 11 aminoglycosides was docked with an average root-mean-square deviation (RMSD) of 1.41 A to be compared with an average RMSD of 3.25 A when the original AutoDock protocol was used...
  78. ncbi request reprint Chemistry and biology of the aeruginosin family of serine protease inhibitors
    Karolina Ersmark
    Department of Chemistry, Universite de Montreal, C P 6128, Station Centre Ville, Montreal, PQ, H3C 3J7, Canada
    Angew Chem Int Ed Engl 47:1202-23. 2008
    ..In this article, we provide the first comprehensive review on the chemistry and biology of the aeruginosins, with an emphasis on their sources, structural revisions, and total syntheses...
  79. ncbi request reprint Total synthesis of bafilomycin A(1) relying on iterative 1,2-induction in acyclic precursors
    S Hanessian
    Department of Chemistry, , C.P. 6128, Succursale Centre-Ville, , , Canada
    J Am Chem Soc 123:10200-6. 2001
    ..The resulting seco-ester was further manipulated to provide crystalline bafilomycin A(1) via a conventional carbodiimide-mediated Keck-type macrolactonization...
  80. ncbi request reprint Antibacterial aminoglycosides with a modified mode of binding to the ribosomal-RNA decoding site
    Boris François
    Institut de biologie moléculaire et cellulaire UPR9002 CNRS, Universite Louis Pasteur, 15 rue Rene Descartes, 67084 Strasbourg Cedex, France
    Angew Chem Int Ed Engl 43:6735-8. 2004
  81. ncbi request reprint Ring-modified analogues and molecular dynamics studies to probe the requirements for fungicidal activities of malayamycin A and its N-nucleoside variants
    Olivier Loiseleur
    Syngenta, Crop Protection Research, Schwarzwaldallee 215, CH 4002 Basel, Switzerland
    J Org Chem 72:6353-63. 2007
    ..Molecular dynamics studies on malayamycin A and analogues were performed to highlight the importance of properly orientating the urea and methyl ether groups...
  82. ncbi request reprint Crystal structure of the bacterial ribosomal decoding site complexed with a synthetic doubly functionalized paromomycin derivative: a new specific binding mode to an a-minor motif enhances in vitro antibacterial activity
    Jiro Kondo
    Architecture et Reactivite de l ARN, Universite Louis Pasteur, Institut de Biologie Moleculaire et Cellulaire, CNRS, 15 rue Rene Descartes, 67084 Strasbourg, France
    ChemMedChem 2:1631-8. 2007
    ....
  83. ncbi request reprint Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins
    Crystel Ogier
    Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 6184 Université de la Méditerranée, Faculte de Medecine de Marseille, IFR Jean Roche, Pierre Dramard 13916, Marseille Cedex 20, France
    Glia 54:272-84. 2006
    ....
  84. ncbi request reprint Neuronal activity-dependent increase of net matrix metalloproteinase activity is associated with MMP-9 neurotoxicity after kainate
    Jerome Jourquin
    Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS FRE 2533 IFR Jean Roche Université de la Méditerranée Faculté de Médecine de Marseille, 27 Bd Jean Moulin 13385, Marseille Cedex 05, France
    Eur J Neurosci 18:1507-17. 2003
    ....