DOCSLIB.ORG

(10) Patent No.: US 8.476,225 B2 Casarez Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(10) Patent No.: US 8.476,225 B2 Casarez Et Al USOO8476225B2 (12) United States Patent (10) Patent No.: US 8.476,225 B2 Casarez et al. (45) Date of Patent: Jul. 2, 2013 (54) ANTIVIRAL COMPOUNDS (56) References Cited (75) Inventors: Anthony Casarez, Princeton, NJ (US); U.S. PATENT DOCUMENTS Mingzhe Ji, Union City, CA (US); 8,163,693 B2 4/2012 Chen et al. Choung U. Kim, San Carlos, CA (US); Xiaoning C. Sheng, Foster City, CA FOREIGN PATENT DOCUMENTS EP 2272858 A2 1, 2011 (US); Qiaoyin Wu, Foster City, CA (US) WO WO-2006O20276 A2 2, 2006 WO WO-2007OO9109 A2 1, 2007 (73) Assignee: Gilead Sciences, Inc., Foster City, CA WO WO-2008OO5565 A2 1, 2008 (US) WO WO-2009005.676 A2 1, 2009 WO WO-200900.5677 A2 1, 2009 (*) Notice: Subject to any disclaimer, the term of this OTHER PUBLICATIONS patent is extended or adjusted under 35 Ettmayer P. et al. J. Med. Chem. (2004) 47(10), pp. 2393-2404.* U.S.C. 154(b) by 211 days. Singh, Yashveeretal, “Recent Trends in Targeted Anticancer Prodrug and Conjugate.” DesignCurr MedChem. 2008; 15(18): 1802-1826.* (21) Appl. No.: 12/958,086 Muller, Christa E. "Prodrug Approaches for Enhancing the Bioavail ability of Drugs with Low Solubility.” Chemistry & Biodiversity, vol. (22) Filed: Dec. 1, 2010 6 (2009), pp. 2071-2083.* Beaumont, et, al"Design of Ester Prodrugs to Enhance Oral Absorp (65) Prior Publication Data tion of Poorly Permeable Compounds: Challenges to the Discovery Scientist.” Current Drug Metabolism, 2003, 4,461-485.* US 2011 FO1356O4A1 Jun. 9, 2011 Han, H.-K. AAPS Pharmsci. (2000) 2(1), Article 6, pp. 1-11.* Testa Prodrug research: futile or fertile? Biochemical Pharmacology (2004) 2097-2106.* Related U.S. Application Data (60) Provisional application No. 61/266,890, filed on Dec. * cited by examiner 4, 2009. Primary Examiner — Thomas Heard (51) Int. Cl. (57) ABSTRACT A6 IK38/00 (2006.01) The invention is related to anti-viral compounds, composi (52) U.S. Cl. tions containing such compounds, and therapeutic methods USPC ........................................................... S14/37 that include the administration of such compounds, as well as (58) Field of Classification Search to processes and intermediates useful for preparing Such com None pounds. See application file for complete search history. 45 Claims, No Drawings US 8,476,225 B2 1. 2 ANTIVIRAL COMPOUNDS R is optionally substituted C-Co cycloalkyl, optionally substituted aryl or optionally substituted heterocycle; This application is filed under 35 U.S.C. 111 (a) claiming m is 0, 1 or 2 the benefit under 35 U.S.C. 119(e) of U.S. provisional appli W is C-C alkylene, C-C alkenylene, or C-C alkynylene wherein the C-C alkylene, C-C alkenylene, or cation 61/266,890 filed Dec. 4, 2009 which is herein incor C-C alkynylene may be optionally substituted with porated by reference in its entirety for all purposes. C-C-alkyl, C-C-haloalkyl, cyano or halo; FIELD OF THE INVENTION R, is: 10 The invention relates generally to compounds with HCV Q O O O inhibitory activity. \/ -R 12 1n N n BACKGROUND OF THE INVENTION N R9. R or Hepatitis C is recognized as a chronic viral disease of the 15 Rs R11 O liver which is characterized by liver disease. Although drugs targeting the liver are in wide use and have shown effective ness, toxicity and other side effects have limited their useful -R ness. Inhibitors of HCV are useful to limit the establishment OR16 and progression of infection by HCV as well as in diagnostic Rs assays for HCV. There is a need for new HCV therapeutic agents. Rs is C-C alkyl, C-C alkenyl or C-C alkynyl wherein the SUMMARY OF THE INVENTION C-C alkyl, C-C alkenyl or C-C alkynyl may be 25 optionally substituted with halo or cyano; In one embodiment the invention provides a compound of Ro is Ro Ro NH- or Rio O formula 1 Ro is C-C alkyl, C-C, cycloalkyl or C-C cycloalkylalkyl wherein the C-C alkyl, C-C, cycloalkyl or C-C, cycloalkylalkyl may be optionally substituted with C-C- 30 alkyl, C-C-haloalkyl, cyano or halo: R is C-C alkyl, C-C, cycloalkyl or C-C cycloalkylalkyl wherein the C-C alkyl, C-C, cycloalkyl or C-C, N cycloalkylalkyl may be optionally substituted with C-C- alkyl, C-C-alkylthio, cyano or halo; 7 N 35 each R is independently H, C-C alkyl, C-C, cycloalkyl or N R C-C cycloalkylalkyl wherein the C-C alkyl, C-C, R e O cycloalkyl or C-C cycloalkylalkyl may be optionally Sub stituted with C-C-alkyl, C-C haloalkyl cyano or halo; O R3 R is H, OH, OR, C-C alkyl, C-C cycloalkyl, Ca-C 40 cycloalkylalkyl, aryl, arylalkyl, heterocycle or heterocy clylalkyl wherein the C-C alkyl, C-C cycloalkyl, or a racemate, enantiomer, Solvate, polymorph or salt thereof. C-C cycloalkylalkyl, aryl, arylalkyl, heterocycle or het wherein; erocyclylalkyl may be optionally substituted with C-C- R is R. , R. C(O)—, R O C(O)— or R. N(H) alkyl, C-C-haloalkyl cyano or halo; C(O)– 45 Ra is Rs Rs—C(O)—, Rs—O—C(O) s Ris O C R is optionally substituted C-Cs alkyl, optionally Substi (O)—X— tuted C-C cycloalkyl, optionally substituted C7-Ca Rs is C-C alkyl, C-C cycloalkyl, C7-C cycloalkylalkyl, cycloalkyl alkyl, optionally Substituted aryl, optionally aryl, arylalkyl, heterocycle, heterocyclylalkyl wherein the substituted arylalkyl, optionally substituted heterocycle or C-C alkyl, C-C, cycloalkyl, C7-C cycloalkylalkyl may optionally substituted heterocyclylalkyl: 50 be optionally Substituted with C-C2-alkyl, C-C-ha R is optionally substituted C-Cs alkyl, optionally Substi loalkyl, cyano or halo; tuted C-Co cycloalkyl, optionally Substituted C7-Ca X is C-C alkylene or C-C spiroalkylene; cycloalkylalkyl, optionally substituted heterocyclylalkyl, R is H. R. C(O)—, R-O-C(O) or R, O C or optionally substituted heterocycle, or R and Rs, along (O)—X—; with the atoms that connect them, form a 12 to 18 mem 55 each R, is independently H, C-C alkyl, C-C cycloalkyl or bered saturated, partially unsaturated or unsaturated het C-C cycloalkylalkyl wherein the C-C alkyl, C-C, erocycle wherein the 12 to 18 membered saturated, par cycloalkyl or C-C cycloalkylalkyl may be optionally Sub tially unsaturated or unsaturated heterocycle may be stituted with C-C2-alkyl, C-C-haloalkyl cyano or halo, optionally Substituted with C-C alkyl, C-C-haloalkyl, or two R, may, along with the carbon they are attached to, halo, oxo and cyano and wherein 0, 1, 2, or 3 carbon atoms 60 form a 3-6 membered spirocyclic carbocycle or hetero of R can be replaced by O, N, or S; cycle wherein any carbon of said carbocycle or heterocycle R is R. , R. Rs , R. W. , R. W. C(O)—, R. C may be substituted with C-C2-alkyl, C-C-haloalkyl, (O) , R. C(O)—W , R. W. O. C(O) , R. S cyano or halo and any nitrogen of said heterocycle may be (O), , R. W. S(O), , R. N(H)—C(O)—, R. N Substituted with C-C-alkyl, C-C-haloalkyl, C-Cs (H)—S(O), . Re-Rs S(O) - or R. N(H)—Rs—: 65 cycloalkyl or C-C acyl, or, taken together, two instances Rs is optionally substituted arylene or optionally substituted of R, together with the carbon they are attached to form a heteroarylene; carbonyl group; US 8,476,225 B2 3 4 In one embodiment of the invention R, is -continued N x N s n 4. 2 Os R3 10 F Br F Br In one embodiment of the invention R is Ro Ro NH Xsé, As4. or Rio O—: HCI, | | || In one embodiment of the invention R is Ro: 2 21 In one embodiment of the invention R is R O C 15 O O O (O) ; In one embodiment of the invention R is optionally sub stituted C-C alkyl, optionally Substituted C-Co cycloalkyl or optionally Substituted C7-C cycloalkylalkyl, In one embodiment of the invention each of R, is inde pendently H or substituted alkyl, In one embodiment of the invention R is 25 30 O O O 35 40 O, s O, 45 Halogen, s N N SAS s --F, --Cl, 50 21 2 2 >s so >s so >s so 55 N 60 HBr s s 21 65 US 8,476,225 B2 5 6 -continued -continued MeO N , MeO N N s n n N 21 N 2 F 15 h Ol F, CN 25 OMe, Alkoxy, 2y. 2/ 30 S N 35 40 O NH2 45 N ON 50 s e s es. 55 In one embodiment of the invention R is cyclopentyloxy carbonyl, t-butyloxycarbonyl, or 2.2.2-trifluoro-1,1-dimeth ylethyloxycarbonyl. C N OMe, MeS 60 In one embodiment of the invention R is cyclopentyl, t-butyl or 2.2.2-trifluoro-1,1-dimethylethyl. In one embodiment of the invention R is t-butyl. r In one embodiment of the invention R and Rs together form a C to Cs alkylene, wherein the alkylene may be option 65 ally unsaturated. In one embodiment of the invention R and Rs together form US 8,476,225 B2 8 In one embodiment of the invention R, is x-y O x-y R3 In one embodiment of the invention R is Re-alkylene-, 10 Re-alkylene-C(O)—, R.
Load more

Recommended publications
  • Current Therapies for Chronic Hepatitis C
    Southern Illinois University Edwardsville SPARK Pharmacy Faculty Research, Scholarship, and Creative Activity School of Pharmacy 1-2011 Current Therapies for Chronic Hepatitis C McKenzie C. Ferguson Southern Illinois University Edwardsville, [email protected] Follow this and additional works at: https://spark.siue.edu/pharmacy_fac Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Ferguson, McKenzie C., "Current Therapies for Chronic Hepatitis C" (2011). Pharmacy Faculty Research, Scholarship, and Creative Activity. 4. https://spark.siue.edu/pharmacy_fac/4 This Article is brought to you for free and open access by the School of Pharmacy at SPARK. It has been accepted for inclusion in Pharmacy Faculty Research, Scholarship, and Creative Activity by an authorized administrator of SPARK. For more information, please contact [email protected],[email protected]. Chronic Hepatitis C & Current Therapies 1 Review of Chronic Hepatitis C & Current Therapies Reviews of Therapeutics Pharmacotherapy McKenzie C. Ferguson, Pharm.D., BCPS From the School of Pharmacy, Southern Illinois University Edwardsville, Department of Pharmacy Practice, Edwardsville, Illinois. Address for reprint requests : Southern Illinois University Edwardsville School of Pharmacy 220 University Park Drive, Ste 1037 Edwardsville, IL 62026-2000 Email: [email protected] Keywords : hepatitis C, HCV, ribavirin, interferon, peginterferon alfa-2a, peginterferon alfa-2b, albinterferon, taribavirin, telaprevir, therapeutic efficacy, safety The author received no sources of support in the form of grants, equipment, or drugs. Chronic Hepatitis C & Current Therapies 2 ABSTRACT Hepatitis C virus affects more than 180 million people worldwide and as many as 4 million people in the United States. Given that most patients are asymptomatic until late in disease progression, diagnostic screening and evaluation of patients that display high-risk behaviors associated with acquisition of hepatitis C should be performed.
    [Show full text]
  • Design and Evaluation of 5•²-O-Dicarboxylic And
    University of Rhode Island DigitalCommons@URI Open Access Master's Theses 2014 DESIGN AND EVALUATION OF 5′-O-DICARBOXYLIC AND POLYARGININE FATTY ACYL DERIVATIVES OF ANTI-HIV NUCLEOSIDES Bhanu Priya Pemmaraju Venkata University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation Pemmaraju Venkata, Bhanu Priya, "DESIGN AND EVALUATION OF 5′-O-DICARBOXYLIC AND POLYARGININE FATTY ACYL DERIVATIVES OF ANTI-HIV NUCLEOSIDES" (2014). Open Access Master's Theses. Paper 474. https://digitalcommons.uri.edu/theses/474 This Thesis is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. DESIGN AND EVALUATION OF 5′-O- DICARBOXYLIC AND POLYARGININE FATTY ACYL DERIVATIVES OF ANTI-HIV NUCLEOSIDES BY BHANU PRIYA, PEMMARAJU VENKATA A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE MASTER’S DEGREE IN BIOMEDICAL AND PHARMACEUTICAL SCIENCES UNIVERSITY OF RHODE ISLAND 2014 MASTER OF SCIENCE THESIS OF BHANU PRIYA, PEMMARAJU VENKATA APPROVED: Thesis Committee: Major Professor Keykavous Parang Roberta King Stephen Kogut Geoffrey D. Bothun Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL UNIVERSITY OF RHODE ISLAND 2014 ABSTRACT 2′,3′-Dideoxynucleoside (ddNs) analogs are the most widely used anti-HIV drugs in the market. Even though these drugs display very potent activities, they have a number of limitations when are used as therapeutic agents. The primary problem associated with ddNs is significant toxicity, such as neuropathy and bone marrow suppression.
    [Show full text]
  • Taribavirin.Pdf
    Virologic Response Rates of Weight-Based Taribavirin Versus Ribavirin in Treatment-Naive Patients with Genotype 1 Chronic Hepatitis C Fred Poordad,1 Eric Lawitz,2 Mitchell L. Shiffman,3 Tarek Hassanein,4 Andrew J. Muir,5 Bruce R. Bacon,6 Jamie Heise,7 Deanine Halliman,7 Eric Chun,7 and Janet Hammond7 Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C. The study aimed to determine if weight-based dosing of taribavirin (TBV), an oral prodrug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previ- ously demonstrated anemia advantage with fixed dose administration. A U.S. phase 2b randomized, open-label, active-controlled, parallel-group study was conducted in 278 treatment-naive patients infected with genotype 1 who were stratified by body weight and baseline viral load. Patients were randomized 1:1:1:1 to receive TBV (20, 25, or 30 mg/kg/ day) or RBV (800-1400 mg/day) with pegylated interferon alfa-2b for 48 weeks. The SVR rates in this difficult-to-cure patient demographics (mean age, 49 years; 61% male; 30% African American or Latino; high viral load; advanced fibrosis; and mean weight, 82 kg) were 28.4%, 24.3%, 20.6%, and 21.4% in the 20, 25, and 30 mg/kg TBV groups and the RBV group, respectively. There were no statistical differences in the efficacy analyses. Ane- mia rates were significantly lower (P < 0.05) in the 20 and 25 mg/kg/day TBV treatment groups (13.4% and 15.7%, respectively) compared to RBV (32.9%).
    [Show full text]
  • Emtricitabine/Rilpivirine/Tenofovir Alafenamide Fixed-Dose Combination (Ftc/Rpv/Taf [F/R/Taf] Fdc)
    SECTION 2.6.—NONCLINICAL SUMMARY SECTION 2.6.1—INTRODUCTION EMTRICITABINE/RILPIVIRINE/TENOFOVIR ALAFENAMIDE FIXED-DOSE COMBINATION (FTC/RPV/TAF [F/R/TAF] FDC) Gilead Sciences 11 May 2015 CONFIDENTIAL AND PROPRIETARY INFORMATION FTC/RPV/Tenofovir alafenamide 2.6.1 Introduction Final TABLE OF CONTENTS SECTION 2.6.1—INTRODUCTION ...........................................................................................................................1 TABLE OF CONTENTS ..............................................................................................................................................2 GLOSSARY OF ABBREVIATIONS AND DEFINITION OF TERMS......................................................................3 NOTE TO REVIEWER.................................................................................................................................................4 1. NONCLINICAL SUMMARY..............................................................................................................................6 1.1. Introduction..............................................................................................................................................6 1.1.1. Emtricitabine ..........................................................................................................................6 1.1.2. Rilpivirine ..............................................................................................................................7 1.1.3. Tenofovir Alafenamide ..........................................................................................................7
    [Show full text]
  • EUROPEAN PHARMACOPOEIA 10.0 Index 1. General Notices
    EUROPEAN PHARMACOPOEIA 10.0 Index 1. General notices......................................................................... 3 2.2.66. Detection and measurement of radioactivity........... 119 2.1. Apparatus ............................................................................. 15 2.2.7. Optical rotation................................................................ 26 2.1.1. Droppers ........................................................................... 15 2.2.8. Viscosity ............................................................................ 27 2.1.2. Comparative table of porosity of sintered-glass filters.. 15 2.2.9. Capillary viscometer method ......................................... 27 2.1.3. Ultraviolet ray lamps for analytical purposes............... 15 2.3. Identification...................................................................... 129 2.1.4. Sieves ................................................................................. 16 2.3.1. Identification reactions of ions and functional 2.1.5. Tubes for comparative tests ............................................ 17 groups ...................................................................................... 129 2.1.6. Gas detector tubes............................................................ 17 2.3.2. Identification of fatty oils by thin-layer 2.2. Physical and physico-chemical methods.......................... 21 chromatography...................................................................... 132 2.2.1. Clarity and degree of opalescence of
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,871,799 B2 Adonato Et Al
    USOO8871799B2 (12) United States Patent (10) Patent No.: US 8,871,799 B2 adonato et al. (45) Date of Patent: Oct. 28, 2014 (54) IMINOCHROMENE ANTI-VIRAL the action of nucleophilic reagents. 5. Interactions of COMPOUNDS 2-Iminocoumarin-3-carboxamide with anthranilic acid and its derivatives. (2000) Chemistry of Heterocyclic COmpounds, vol. 36. (75) Inventors: Shawn P. Ladonato, Seattle, WA (US); pp. 1026-1031.* Kristin Bedard, Seattle, WA (US) Banerjee, S., et al. (2008) Multi-targeted therapy of cancer by genistein, Cancer Lett 269, 226-242. (73) Assignee: Kineta, Inc., Seattle, WA (US) Barnard, D. L. (2009) Animal models for the study of influenza pathogenesis and therapy, Antiviral Res 82, Al 10-122. (*) Notice: Subject to any disclaimer, the term of this Blight, J.J. et al., (2002) Highly Permissive Cell Lines for patent is extended or adjusted under 35 Subgenomic and Genomic Hepatitis C Virus RNA Replication, J. U.S.C. 154(b) by 55 days. Virology 76:13001-13014. Dafis, S., et al. (2008) Toll-like receptor 3 has a protective role (21) Appl. No.: 13/642,823 against West Nile virus infection, JVirol 82, 10349-10358. Horsmans, Y, et al. (2005) Isatoribine, an agonist of TLR7, reduces (22) PCT Filed: Apr. 20, 2011 plasma virus concentration in chronic hepatitis C infection, Hepatol ogy 42, 724-731. (86). PCT No.: PCT/US2011/033309 Johnson, C. L., and Gale, M., Jr. (2006) CARD games between virus S371 (c)(1), and host get a new player, Trends Immunol 27, 1-4. (2), (4) Date: Oct. 22, 2012 Kato, H., et al.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • EASL - Beyond Protease Inhibitors Hep C Pipeline Filling Up
    April 04, 2011 EASL - Beyond protease inhibitors hep C pipeline filling up Amy Brown With the development of hepatitis C protease inhibitors boceprevir and telaprevir all but concluded, specialists in treating the liver disease now are looking beyond the two first-in-class drugs (see tables below). Research is focusing on a combination of molecules or even a single agent that can reduce the burden of treatment, combat a wider spectrum of virus genotypes, dodge viral resistance and succeed in more patients, particularly those who have not seen relief with existing therapies. A top priority among experts gathered at the EASL International Liver Congress is developing an interferon-free regimen, to eliminate the flu-like symptoms and other side effects common with the immunostimulant, a goal that seems tantalysingly just out of reach for patients and physicians. “The real success will probably be in five or six years when we’re able to combine different oral agents, different small molecules with different modes of action and maybe get rid of interferon,” says Antonio Craxi, professor of gastroenterology and internal medicine at the University of Palermo. Viral breakthrough For now, viral breakthrough has haunted therapies that have attempted trial arms without peginterferon-alfa and ribavirin, the antiviral that makes up the other half of the current standard of care. For example, viral breakthrough forced Vertex Pharmaceuticals to cancel an arm of its phase II trial of telaprevir and VX-222 that did not include a background standard of care therapy. The trial continues in the quadruple-therapy arm, with positive interim results presented at the conference.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr
    US008158152B2 (12) United States Patent (10) Patent No.: US 8,158,152 B2 Palepu (45) Date of Patent: Apr. 17, 2012 (54) LYOPHILIZATION PROCESS AND 6,884,422 B1 4/2005 Liu et al. PRODUCTS OBTANED THEREBY 6,900, 184 B2 5/2005 Cohen et al. 2002fOO 10357 A1 1/2002 Stogniew etal. 2002/009 1270 A1 7, 2002 Wu et al. (75) Inventor: Nageswara R. Palepu. Mill Creek, WA 2002/0143038 A1 10/2002 Bandyopadhyay et al. (US) 2002fO155097 A1 10, 2002 Te 2003, OO68416 A1 4/2003 Burgess et al. 2003/0077321 A1 4/2003 Kiel et al. (73) Assignee: SciDose LLC, Amherst, MA (US) 2003, OO82236 A1 5/2003 Mathiowitz et al. 2003/0096378 A1 5/2003 Qiu et al. (*) Notice: Subject to any disclaimer, the term of this 2003/OO96797 A1 5/2003 Stogniew et al. patent is extended or adjusted under 35 2003.01.1331.6 A1 6/2003 Kaisheva et al. U.S.C. 154(b) by 1560 days. 2003. O191157 A1 10, 2003 Doen 2003/0202978 A1 10, 2003 Maa et al. 2003/0211042 A1 11/2003 Evans (21) Appl. No.: 11/282,507 2003/0229027 A1 12/2003 Eissens et al. 2004.0005351 A1 1/2004 Kwon (22) Filed: Nov. 18, 2005 2004/0042971 A1 3/2004 Truong-Le et al. 2004/0042972 A1 3/2004 Truong-Le et al. (65) Prior Publication Data 2004.0043042 A1 3/2004 Johnson et al. 2004/OO57927 A1 3/2004 Warne et al. US 2007/O116729 A1 May 24, 2007 2004, OO63792 A1 4/2004 Khera et al.
    [Show full text]
  • Hepatitis C Virus Management: Potential Impact of Nanotechnology Mostafa H
    Elberry et al. Virology Journal (2017) 14:88 DOI 10.1186/s12985-017-0753-1 REVIEW Open Access Hepatitis C virus management: potential impact of nanotechnology Mostafa H. Elberry1,2, Noureldien H. E. Darwish1,3 and Shaker A. Mousa1* Abstract Around 170–200 million individuals have hepatitis C virus (HCV), which represents ~ 3% of the world population, including ~ 3–5 million people in the USA. According to the WHO regional office in the Middle East, Egypt has the highest prevalence in the world, with 7% prevalence in adults. There had been no effective vaccine for HCV; a combination of PEG-Interferon and ribavirin for at least 48 weeks was the standard therapy, but it failed in more than 40% of the patients and has a high cost and serious side effects. The recent introduction of direct-acting antivirals (DAA) resulted in major advances toward the cure of HCV. However, relapse and reduced antiviral efficacy in fibrotic, cirrhotic HCV patients in addition to some undesired effects restrain the full potential of these combinations. There is a need for new approaches for the combinations of different DAA and their targeted delivery using novel nanotechnology approaches. In this review, the role of nanoparticles as a carrier for HCV vaccines, anti-HCV combinations, and their targeted delivery are discussed. Keywords: Hepatitis C virus, Drug delivery system, HCV genotypes, Nanoparticles Background Until 2011, the standard treatment was a blend of From the time of its discovery in 1989, hepatitis C virus subcutaneous pegylated interferon (PEG-IFN) in (HCV) has been known globally as the primary reason addition to oral ribavirin (RBV), administered for 24 or for chronic liver disease [1].
    [Show full text]
  • Longitudinal Analysis of the Utility of Liver Biochemistry in Hospitalised COVID-19 Patients As Prognostic Markers
    medRxiv preprint doi: https://doi.org/10.1101/2020.09.15.20194985; this version posted September 18, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Longitudinal analysis of the utility of liver biochemistry in hospitalised COVID-19 patients as prognostic markers. Authors: Tingyan Wang1,2*, David A Smith1,3*, Cori Campbell1,2*, Steve Harris1,4, Hizni Salih1, Kinga A Várnai1,3, Kerrie Woods1,3, Theresa Noble1,3, Oliver Freeman1, Zuzana Moysova1,3, Thomas Marjot5, Gwilym J Webb6, Jim Davies1,4, Eleanor Barnes2,3*, Philippa C Matthews3,7*. Affiliations: 1. NIHR Oxford Biomedical Research Centre, Big Data Institute, University of Oxford 2. Nuffield Department of Medicine, University of Oxford 3. Oxford University Hospitals NHS Foundation Trust 4. Department of Computer Science, University of Oxford 5. Oxford Liver Unit, Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford University Hospitals 6. Cambridge Liver Unit, Addenbrooke's Hospital, Cambridge 7. Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust *Equal Contributions Corresponding Author: Professor Eleanor Barnes, The Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK. Telephone: 01865 281547. Email: [email protected] Author Contributions: T.W, D.A.S, C.C., P.C.M and E.B contributed equally to this work. T.W, D.A.S and C.C performed the data analysis and wrote the manuscript and were supervised by E.B, P.C.M and J.D.
    [Show full text]
  • A Computational Approach to Aid Clinicians in Selecting Anti-Viral
    www.nature.com/scientificreports OPEN A computational approach to aid clinicians in selecting anti‑viral drugs for COVID‑19 trials Aanchal Mongia1, Sanjay Kr. Saha2, Emilie Chouzenoux3* & Angshul Majumdar1* The year 2020 witnessed a heavy death toll due to COVID‑19, calling for a global emergency. The continuous ongoing research and clinical trials paved the way for vaccines. But, the vaccine efcacy in the long run is still questionable due to the mutating coronavirus, which makes drug re‑positioning a reasonable alternative. COVID‑19 has hence fast‑paced drug re‑positioning for the treatment of COVID‑19 and its symptoms. This work builds computational models using matrix completion techniques to predict drug‑virus association for drug re‑positioning. The aim is to assist clinicians with a tool for selecting prospective antiviral treatments. Since the virus is known to mutate fast, the tool is likely to help clinicians in selecting the right set of antivirals for the mutated isolate. The main contribution of this work is a manually curated database publicly shared, comprising of existing associations between viruses and their corresponding antivirals. The database gathers similarity information using the chemical structure of drugs and the genomic structure of viruses. Along with this database, we make available a set of state‑of‑the‑art computational drug re‑positioning tools based on matrix completion. The tools are frst analysed on a standard set of experimental protocols for drug target interactions. The best performing ones are applied for the task of re‑positioning antivirals for COVID‑19. These tools select six drugs out of which four are currently under various stages of trial, namely Remdesivir (as a cure), Ribavarin (in combination with others for cure), Umifenovir (as a prophylactic and cure) and Sofosbuvir (as a cure).
    [Show full text]