The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Roger F Bone - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of polyethylene glycol modified biphenylsulfonyl thiophene Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Nalin Subasinghe, Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Roger F Bone, Richard M Soll, Carl Crysler, Kristi A. Leonard, Shelley K Ballentine, Nisha NinanAbstract:Complement C1s protease inhibitors have potential utility in the treatment of diseases associated with activation of the classical complement pathway such as humorally mediated graft rejection, ischemia-reperfusion injury (IRI), vascular leak syndrome, and acute respiratory distress syndrome (ARDS). The utility of biphenylsulfonyl-thiophene-Carboxamidine small-molecule C1s inhibitors are limited by their poor in vivo pharmacokinetic properties. Pegylation of a potent analog has provided compounds with good potency and good in vivo pharmacokinetic properties.
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biphenylsulfonyl thiophene Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2008Co-Authors: Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Joan Gushue, Kristi Leonard, Roger F Bone, Richard M Soll, Shelley K Ballentine, Hui Huang, Renee L DesjarlaisAbstract:Abstract Complement activation has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury, acute respiratory distress syndrome, and acute transplant rejection. Even though the complement cascade provides several protein targets for potential therapeutic intervention only two complement inhibitors have been approved so far for clinical use including anti-C5 antibodies for the treatment of paroxysmal nocturnal hemoglobinuria and purified C1-esterase inhibitor replacement therapy for the control of hereditary angioedema flares. In the present study, optimization of potency and physicochemical properties of a series of thiophene amidine-based C1s inhibitors with potential utility as intravenous agents for the inhibition of the classical pathway of complement is described.
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a novel series of arylsulfonylthiophene 2 Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2006Co-Authors: Nalin Subasinghe, Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Roger F Bone, Juan J Marugan, Shelley K Ballentine, Renee L Desjarlais, Hui Huang, Carl CryslerAbstract:Abstract Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia–reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-Carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a , thrombin, and plasmin.
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synthesis of thiophene 2 Carboxamidines containing 2 amino thiazoles and their biological evaluation as urokinase inhibitors
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Kenneth J Wilson, Roger F Bone, Nalin Subasinghe, Carl R Illig, James B Hoffman, Jonathan M Rudolph, Richard Soll, Christopher J Molloy, David Green, Troy RandallAbstract:The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-Carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.
Hakan Goker - One of the best experts on this subject based on the ideXlab platform.
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1h benzimidazole 5 Carboxamidine derivatives design synthesis molecular docking dft and antimicrobial studies
New Journal of Chemistry, 2020Co-Authors: Meryem Erol, Hakan Goker, Ismail Celik, Ozlem Temizarpaci, Fatma Kaynakonurdag, Suzan OktenAbstract:In this study, 15 new N-(cyclohexyl)-2-substituted-1H-benzimidazole-5-Carboxamidine derivatives that could be new antimicrobial agents were synthesized and their antimicrobial activities were determined using the microdilution method. Some of the derivatives showed significant efficacy against MRSA and VREF with an MIC value of 8 μg mL−1 compared to reference drugs. Molecular docking studies of the compounds against PBP4 and active and allosteric regions of PBP2a were performed and estimated ADME profiles were calculated. The nitrogens of the amidine group of M7, one of the most effective antimicrobial compounds compared to reference drugs, formed two separate hydrogen bonds with ASP275 (1.77 A) and ASP295 (1.83 A) in the allosteric region of PBP2a. Geometric optimization parameters, MEP analysis, and HUMO and LUMO quantum parameters of M7 were calculated using DFT/B3LYP theory and the 6-311G(d,p) basis set and the results are displayed.
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synthesis and potent antiprotozoal activity of mono di amidino 2 anilinobenzimidazoles versus plasmodium falciparum and trypanosoma brucei rhodesiense
Bioorganic & Medicinal Chemistry, 2016Co-Authors: Cigdem Karaaslan, Marcel Kaiser, Reto Brun, Hakan GokerAbstract:A series of mono and dicationic new 2-anilinobenzimidazole Carboxamidines were prepared in a four step process starting from 4-amino-3-nitrobenzonitrile and corresponding o-phenylenediamines. Their antiparasitic activity against Plasmodium falciparum (P. falciparum) and Trypanosoma brucei rhodesiense (T.b. rhodesiense) were evaluated in vitro. Some of the dicationic compounds (10,12,14) showed equal or very close activity against T.b. rhodesiense with melarsoprol and also showed promising activity against P. falciparum as compared to chloroquine. Among the monocationic derivatives compound 21 exhibited best inhibitory activity against P. falciparum.
Nalin Subasinghe - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of polyethylene glycol modified biphenylsulfonyl thiophene Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Nalin Subasinghe, Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Roger F Bone, Richard M Soll, Carl Crysler, Kristi A. Leonard, Shelley K Ballentine, Nisha NinanAbstract:Complement C1s protease inhibitors have potential utility in the treatment of diseases associated with activation of the classical complement pathway such as humorally mediated graft rejection, ischemia-reperfusion injury (IRI), vascular leak syndrome, and acute respiratory distress syndrome (ARDS). The utility of biphenylsulfonyl-thiophene-Carboxamidine small-molecule C1s inhibitors are limited by their poor in vivo pharmacokinetic properties. Pegylation of a potent analog has provided compounds with good potency and good in vivo pharmacokinetic properties.
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a novel series of arylsulfonylthiophene 2 Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2006Co-Authors: Nalin Subasinghe, Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Roger F Bone, Juan J Marugan, Shelley K Ballentine, Renee L Desjarlais, Hui Huang, Carl CryslerAbstract:Abstract Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia–reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-Carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a , thrombin, and plasmin.
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synthesis of thiophene 2 Carboxamidines containing 2 amino thiazoles and their biological evaluation as urokinase inhibitors
Bioorganic & Medicinal Chemistry Letters, 2001Co-Authors: Kenneth J Wilson, Roger F Bone, Nalin Subasinghe, Carl R Illig, James B Hoffman, Jonathan M Rudolph, Richard Soll, Christopher J Molloy, David Green, Troy RandallAbstract:The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-Carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.
Jeremy M Travins - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of polyethylene glycol modified biphenylsulfonyl thiophene Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2012Co-Authors: Nalin Subasinghe, Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Roger F Bone, Richard M Soll, Carl Crysler, Kristi A. Leonard, Shelley K Ballentine, Nisha NinanAbstract:Complement C1s protease inhibitors have potential utility in the treatment of diseases associated with activation of the classical complement pathway such as humorally mediated graft rejection, ischemia-reperfusion injury (IRI), vascular leak syndrome, and acute respiratory distress syndrome (ARDS). The utility of biphenylsulfonyl-thiophene-Carboxamidine small-molecule C1s inhibitors are limited by their poor in vivo pharmacokinetic properties. Pegylation of a potent analog has provided compounds with good potency and good in vivo pharmacokinetic properties.
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biphenylsulfonyl thiophene Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2008Co-Authors: Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Joan Gushue, Kristi Leonard, Roger F Bone, Richard M Soll, Shelley K Ballentine, Hui Huang, Renee L DesjarlaisAbstract:Abstract Complement activation has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury, acute respiratory distress syndrome, and acute transplant rejection. Even though the complement cascade provides several protein targets for potential therapeutic intervention only two complement inhibitors have been approved so far for clinical use including anti-C5 antibodies for the treatment of paroxysmal nocturnal hemoglobinuria and purified C1-esterase inhibitor replacement therapy for the control of hereditary angioedema flares. In the present study, optimization of potency and physicochemical properties of a series of thiophene amidine-based C1s inhibitors with potential utility as intravenous agents for the inhibition of the classical pathway of complement is described.
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a novel series of arylsulfonylthiophene 2 Carboxamidine inhibitors of the complement component c1s
Bioorganic & Medicinal Chemistry Letters, 2006Co-Authors: Nalin Subasinghe, Jeremy M Travins, Ehab Khalil, Heather Rae Hufnagel, Roger F Bone, Juan J Marugan, Shelley K Ballentine, Renee L Desjarlais, Hui Huang, Carl CryslerAbstract:Abstract Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia–reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-Carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a , thrombin, and plasmin.
Jeffrey R Spencer - One of the best experts on this subject based on the ideXlab platform.
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2 2 hydroxy 3 alkoxyphenyl 1h benzimidazole 5 Carboxamidine derivatives as potent and selective urokinase type plasminogen activator inhibitors
Bioorganic & Medicinal Chemistry Letters, 2002Co-Authors: Richard L Mackman, Bradley A Katz, Christine Luong, Arnold Martelli, Hon Chung Hui, Guy J Breitenbucher, Danny Mcgee, Kesavan Radika, Martin Sendzik, Jeffrey R SpencerAbstract:The development of potent and selective urokinase-type plasminogen activator (uPA) inhibitors based on the lead molecule 2-(2-hydroxy-3-ethoxyphenyl)-1H-benzimidazole-5-Carboxamidine (3a) is described.
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development of serine protease inhibitors displaying a multicentered short 2 3 a hydrogen bond binding mode inhibitors of urokinase type plasminogen activator and factor xa
Journal of Medicinal Chemistry, 2001Co-Authors: Erik Verner, Bradley A Katz, Jeffrey R Spencer, Darin Allen, Jason M Hataye, Witold N Hruzewicz, Aleksandr Kolesnikov, Yong Li, Christine Luong, Arnold MartelliAbstract:Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-Carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608−612).1 Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 A) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-Carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-Carboxamidine, 22f. Structure−activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho subst...