DOCSLIB.ORG

(12) United States Patent Ly

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent Ly US008147852B2 (12) United States Patent (10) Patent No.: US 8,147,852 B2 Borgers et al. (45) Date of Patent: Apr. 3, 2012 (54) MODIFIED AZOLE COMPOUNDSAS (56) References Cited ANTIFUNGALAND ANTIBACTERIAL AGENTS U.S. PATENT DOCUMENTS 4,911,432 A 3/1990 Walden ......................... 424,642 5,061,700 A * 10/1991 Dow et al. ...... ... 514,169 (75) Inventors: Marcel Borgers, Knokke (BE); 6,001,864 A 12/1999 Akashi et al. ................. 514,399 Maarten van Geffen, Beerse (BE); Jannie Ausma, Goirle (NL) FOREIGN PATENT DOCUMENTS WO WO 98.43673 10, 1998 (73) Assignee: Barrier Therapeutics, Inc., Princeton, OTHER PUBLICATIONS NJ (US) Zhang et al. “Structure and generation mechanism of a novel degra dation product formed by oxidatively induced coupling of (*) Notice: Subject to any disclaimer, the term of this miconazole nitrate with butylated hydroxytoluene in a topical oint patent is extended or adjusted under 35 ment studied by HPLC-ESI-MS and organic synthesis' J. Pharma U.S.C. 154(b) by 514 days. ceutical Sciences 93(2):300-309 (2004). * cited by examiner Appl. No.: 12/108,262 (21) Primary Examiner — Shengjun Wang (74) Attorney, Agent, or Firm — The Nath Law Group; (22) Filed: Apr. 23, 2008 Joshua B. Goldberg (65) Prior Publication Data (57) ABSTRACT The present invention relates to the compounds of formula (I), US 2008/O213398 A1 Sep. 4, 2008 their preparation and use as antifungal and/or antibacterial agents. Related U.S. Application Data (63) Continuation of application No. 1 1/591,609, filed on (I) Nov. 2, 2006. ORI (60) Provisional application No. 60/835,085, filed on Aug. 3, 2006. (51) Int. C. A6 IK9/00 (2006.01) A6 IK3 L/45 (2006.01) A6 IK3I/065 (2006.01) (52) U.S. Cl. ......................... 424/400: 514/396; 514/726 (58) Field of Classification Search .................. 424/400; where the values for R', R. R. R. Rand A are as defined 514/396, 728 herein. See application file for complete search history. 18 Claims, 3 Drawing Sheets o No. ly c scs css C -- s T miconazole nitrate | sty c ly e NO roSN B-tricanszole aduct U.S. Patent Apr. 3, 2012 Sheet 1 of 3 US 8,147,852 B2 y OH C (H3C)3C C(CH3) C -- O C CH C BHT miconazole nitrate O (H3CsC CCH) -- ww. fyN \ O NO C N C O C C BHT-miconazole adduct Figure 1 U.S. Patent Apr. 3, 2012 Sheet 2 of 3 US 8,147,852 B2 O (C) CCs Cis o O (CC CC) thC) CCs (CC CCs awww.& O > Disproportionalion C Chis C s e O d (c)3C C(CH) (HCC C(CHs HC 2 - - 3. NO N C l| \ C N O C C HNO C 2 O C C 1. Figure 2 U.S. Patent Apr. 3, 2012 Sheet 3 of 3 US 8,147,852 B2 Antifungal effect with and without Mico-BHT Expressed as number of colonies grown 140 12O 1 OO 80 60 40 2O i O PEG 0.6 mg/ml 1.25 2.5 mg/ml 5 mg/ml 10 mg/ml control mg/ml Figure 3 US 8,147,852 B2 1. MODIFIED AZOLE COMPOUNDS AS ANTIFUNGALAND ANTIBACTERIAL (I) AGENTS RELATED APPLICATIONS This is a continuation application of U.S. application Ser. No. 1 1/591,609 (filed Nov. 2, 2006), which claims the benefit of U.S. Provisional Application No. 60/835,085 (filed Aug. 3, 10 2006), both of which are herein incorporated by reference in their entireties. wherein R'= H, alkyl, -C(O)R. —C(O)OR or FIELD OF THE INVENTION 15 —S(O).R. R. R. RandR independently= H or alkyl: Aanazole; R-alkyl, aryl or heteroaryl; and n=1 or 2, or a The present invention relates to various modified azole pharmaceutically acceptable salt thereof. compounds and their preparation and use as antifungal and/or Another aspect of the invention is a method of treating antibacterial agents. fungal and/or bacterial disorders comprising systemically or topically administering to a recipient in need of Such treat ment an effective amount of a compound or a pharmaceuti BACKGROUND OF THE INVENTION cally acceptable salt of the compound formed by the combi nation of di-tert-butyl-4-methylphenol (BHT) with an azole. The increasing global incidence of systemic fungal infec Another aspect of the invention is a pharmaceutical com tions may largely be attributed to advances in medical tech 25 position comprising a compound of the formula (I) nology and organ transplantation, an increase in the preva lence of cytotoxic chemotherapeutic interventions, the (I) widespread use of broad spectrum antimicrobials and an ORI increasing number of immunocompromised patients. 30 The most common causes of these infections are due to Candida spp., of which C. albicans accounts for approxi mately 50% and filamentous fungi such as Aspergillus spp. (Kremery and Barnes, 2002). Mortality associated with inva sive Candida ranges from around 40% (Edmond et al., 1999), 35 while mortality associated with invasive Aspergillus approaches 100% in Solid organ transplant recipients (Minari et al., 2002). Given the lack of readily available fungal vaccines, the 40 wherein R'= H, alkyl, -C(O)R. —C(O)OR or only clinical resource available to combat fungal infections is —S(O).R. R. R. RandR independently= H or alkyl: antifungal therapeutics (antimycotics). The antimycotics cur Aanazole; R-alkyl aryl or heteroaryl; and n=1 or 2, or a pharmaceutically acceptable salt thereof. rently in clinical use are limited either by their general inef Yet another aspect of the invention is a pharmaceutical fectiveness and inadequate pharmacological profile, includ 45 composition comprising an adduct of BHT or a compound of ing undesired drug-drug interactions and narrow activity formula (I) otheran BHT with anazole-containing compound spectrum, their fungistatic nature, or by their high overall selected from the group consisting of miconazole, clotrima cytotoxicity (White et al., 1998). Accordingly, there is a criti Zole, econazole, fluconazole, itraconazole, ketoconazole, cal need for new antifungal compounds that could overcome 50 pramiconazole, Sertaconazole, butoconazole, raVuconazole, these disadvantages. Voriconazole, posaconazole, luliconazole and pharmaceuti Zhang et al. recently reported the formation of a 1:1 adduct cally acceptable salts thereof. of the antifungal azole compound miconazole nitrate with Another aspect of the invention is compound of formula (I) 2,6-di-tert-butyl-4-methylphenol (BHT) (Zhanget al., 2004). The present invention relates in part to the unexpectedly 55 enhanced antifungal activity exhibited by this adduct as well (I) as by adducts of BHT with other azole compounds and adducts of compounds of formula (I) other than BHT with miconazole nitrate and other azole compounds. 60 SUMMARY OF THE INVENTION An aspect of the invention is a method of treating fungal and/or bacterial disorders comprising systemically or topi 65 cally administering to a recipient in need of Such treatment an effective amount of a compound of the formula (I) US 8,147,852 B2 3 4 wherein R = H, alkyl, -C(O)R. —C(O)OR or butyl)-phenyl-amine, including pharmaceutically accept —S(O).R. R. R. R* and R independently= H or alkyl: able salts thereof. The chemical structure of rambazole is Aanazole; R-alkyl, aryl or heteroaryl; and n=1 or 2, or a indicated below: pharmaceutically acceptable salt thereof, with the proviso that R' is not–Hwhen RandR are tert-butyl, RandR are —H, and A is miconazole. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 depicts an exemplary embodiment of a compound 10 y-si-)--O of formula (I), which is the adduct miconazole nitrate and BHT. FIG. 2 depicts a proposed reaction mechanism between As defined herein, the term “alkyl.” by itself or as part of miconazole nitrate (i.e., an exemplary azole) and BHT (i.e., 15 another Substituent refers to, unless otherwise Stated, a an exemplary compound of formula II) to form the micona straight or branched chain, or cyclic hydrocarbon radical, or Zole nitrate—BHT adduct as a salt (i.e., an exemplary com combination thereof, which may be fully saturated, mono- or pound of formula I). polyunsaturated and can include di- and multivalent radicals, FIG. 3 depicts a comparison of the antifungal effect of having the number of carbon atoms designated (i.e. C-Co miconazole nitrate () with the compound representing the means one to ten carbons). Examples of Saturated hydrocar adduct of miconazole nitrate with BHT (0). bon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl. n-butyl, t-butyl, isobutyl, DETAILED DESCRIPTION OF THE INVENTION sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylm ethyl, methylene, ethylene and homologs and isomers of for Definitions 25 example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group is one having one or more double Unless defined otherwise, all technical and scientific terms bonds or triple bonds. Examples of unsaturated alkyl groups used herein generally have the same meaning as commonly include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-iso understood by one of ordinary skill in the art to which this pentenyl, 2-(butadienyl), 2.4-pentadienyl, 3-(1,4-pentadi invention belongs. 30 As defined herein, “effective amount’ or “an amount effec enyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher tive to” or a “therapeutically effective amount” or any gram homologs and isomers. The term “alkyl, unless otherwise matically equivalent term refers to the amount that, when noted, is also meant to include those derivatives of alkyl administered to an animal for treating a disease or condition, defined in more detail below, such as "heteroalkyl.
Load more

Recommended publications
  • Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix
    United States International Trade Commission Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix USITC Publication 4208 December 2010 U.S. International Trade Commission COMMISSIONERS Deanna Tanner Okun, Chairman Irving A. Williamson, Vice Chairman Charlotte R. Lane Daniel R. Pearson Shara L. Aranoff Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix Publication 4208 December 2010 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 15, 2010, set forth at the end of this publication, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the United States International Trade Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement changes to the Pharmaceutical Appendix, effective on January 1, 2011. Table 1 International Nonproprietary Name (INN) products proposed for addition to the Pharmaceutical Appendix to the Harmonized Tariff Schedule INN CAS Number Abagovomab 792921-10-9 Aclidinium Bromide 320345-99-1 Aderbasib 791828-58-5 Adipiplon 840486-93-3 Adoprazine 222551-17-9 Afimoxifene 68392-35-8 Aflibercept 862111-32-8 Agatolimod
    [Show full text]
  • WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT (51) International Patent Classification: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, C07K 7/60 (2006.01) G01N 33/53 (2006.01) EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, CI2Q 1/18 (2006.01) MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (21) International Application Number: KM, ML, MR, NE, SN, TD, TG). PCT/US2017/063696 (22) International Filing Date: Published: 29 November 201 7 (29. 11.201 7) — with international search report (Art. 21(3)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/427,507 29 November 2016 (29. 11.2016) US 62/484,696 12 April 2017 (12.04.2017) US 62/53 1,767 12 July 2017 (12.07.2017) US 62/541,474 04 August 2017 (04.08.2017) US 62/566,947 02 October 2017 (02.10.2017) US 62/578,877 30 October 2017 (30.10.2017) US (71) Applicant: CIDARA THERAPEUTICS, INC [US/US]; 63 10 Nancy Ridge Drive, Suite 101, San Diego, CA 92121 (US). (72) Inventors: BARTIZAL, Kenneth; 7520 Draper Avenue, Unit 5, La Jolla, CA 92037 (US). DARUWALA, Paul; 1141 Luneta Drive, Del Mar, CA 92014 (US). FORREST, Kevin; 13864 Boquita Drive, Del Mar, CA 92014 (US).
    [Show full text]
  • Seborrheic Dermatitis More Than Meets the Eye
    SEBORRHEIC DERMATITIS More than meets the eye Martijn Gerard Hendrik Sanders Financial support for the printing of this thesis was kindly provided by: La Roche-Posay UCB Chipsoft LEO Pharma Louis Widmer L’Oréal Lilly Merz Pharma Van der Bend B.V. Olmed ISBN: 978-94-6361-558-7 Cover illustration by Sara van der Linde Cover design, lay-out and printing by Optima Grafische Communicatie Copyright © M.G.H. Sanders, Rotterdam 2021 All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system or transmitted in any form by any means without permission from the author, or when appropriate, of the publisher of the publication. Seborrheic Dermatitis More than meets the eye Seborroïsch eczeem Niet alles is wat het lijkt Proefschrift ter verkrijging van de graad van doctor aan de Erasmus Universiteit Rotterdam op gezag van de rector magnificus Prof.dr. F.A. van der Duijn Schouten en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatvinden op donderdag 24 juni 2012 om 10:30 uur Door Martijn Gerard Hendrik Sanders geboren te Almelo PROMOTIECOMMISSIE Promotor: prof. dr. T.E.C. Nijsten Overige leden: prof. dr. E.P. Prens prof. dr. A.G. Uitterlinden prof. dr. J.L.W. Lambert Copromotor: dr. L.M. Pardo Cortes CONTENTS Chapter 1 General introduction 7 Chapter 2 Dermatological screening of a middle-aged and elderly population: 19 the Rotterdam Study Chapter 3 3.1 Prevalence and determinants of seborrheic dermatitis in a middle 29 aged and elderly population: the Rotterdam Study 3.2 Association between
    [Show full text]
  • Current Options in Antifungal Pharmacotherapy
    Current Options in Antifungal Pharmacotherapy John Mohr, Pharm.D., Melissa Johnson, Pharm.D., Travis Cooper, Pharm.D., James S. Lewis, II, Pharm.D., and Luis Ostrosky-Zeichner, M.D. Infections caused by yeasts and molds continue to be associated with high rates of morbidity and mortality in both immunocompromised and immuno- competent patients. Many antifungal drugs have been developed over the past 15 years to aid in the management of these infections. However, treatment is still not optimal, as the epidemiology of the fungal infections continues to change and the available antifungal agents have varying toxicities and drug- interaction potential. Several investigational antifungal drugs, as well as nonantifungal drugs, show promise for the management of these infections. Key Words: antifungal drugs, invasive fungal infection, amphotericin B, polyenes, invasive aspergillosis, liposomal amphotericin B, L-AmB. (Pharmacotherapy 2008;28(5):614–645) OUTLINE Icofungipen Polyenes Conclusion Mechanism of Action Invasive fungal infections continue to be asso- Clinical Efficacy ciated with high rates of morbidity and mortality Safety in both immunocompromised and immuno- Azoles competent hosts. Amphotericin B deoxycholate Mechanism of Action (AmBd) has been the cornerstone for treatment Clinical Efficacy of invasive fungal infections since the early Safety 1950s. However, new agents have emerged to Echinocandins manage these infections over the past 15 years Mechanism of Action (Figure 1). Although Candida species remain the Clinical Efficacy most common pathogens associated with fungal Safety disease, infections caused by Aspergillus and Investigational Antifungal Drugs and Other Cryptococcus sp, Zygomycetes, and the endemic Nonantifungal Agents fungi (Histoplasma, Blastomyces, and Coccidioides Monoclonal Antibody Against Heat Shock Protein 90 sp) also account for many fungal infections.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8.404,751 B2 Birnbaum Et Al
    USOO8404751B2 (12) United States Patent (10) Patent No.: US 8.404,751 B2 Birnbaum et al. (45) Date of Patent: Mar. 26, 2013 (54) SUBUNGUICIDE, AND METHOD FOR 5,696,105 A * 12/1997 Hackler ........................ 514f172 TREATING ONYCHOMYCOSIS 5,894,020 A 4, 1999 Concha 6,008,173 A * 12/1999 Chopra et al. ................ 51Of 152 6,043,063 A 3/2000 Kurdikar et al. (75) Inventors: Jay E. Birnbaum, Montville, NJ (US); 6,143,794. A 11/2000 Chaudhuri et al. Keith A. Johnson, Durham, NC (US) 6,162,420 A 12/2000 Bohn et al. 6,207,142 B1 3/2001 Oddset al. (73) Assignee: Hallux, Inc., Santa Ana, CA (US) 6,221,903 B1 4/2001 Courchesne 6,224,887 B1 5, 2001 Samour et al. (*)c Notice:- r Subject to any disclaimer, the term of this 6,264,9276,231,840 B1 7/20015, 2001 MonahanBuck patent is extended or adjusted under 35 6.361,785 B1 3/2002 Nair et al. U.S.C. 154(b) by 233 days. 6,733,751 B2 5, 2004 Farmer 6,846,837 B2 1/2005 Maibach et al. (21) Appl. No.: 12/606,324 6,878,365 B2 * 4/2005 Brehove .......................... 424,61 7,074,392 B1 7/2006 Friedman et al. 2002/017343.6 A1 11/2002 Sonnenberg et al. (22) Filed: Oct. 27, 2009 2002/0183387 A1 12/2002 Bogart 2003/OOOT939 A1 1/2003 Murad (65) Prior Publication Data 2003/0207971 A1* 11/2003 Stuartet al. ................... 524, 274 2004.0062733 A1 4/2004 Birnbaum US 201O/OO48724 A1 Feb.
    [Show full text]
  • Effect of Pramiconazole on Signs and Symptoms of Tinea Cruris/Corporis
    Open Label Phase IIa Trials to Evaluate the Effects of Short Term Oral Pramiconazole in Tinea Pedis and Tinea Cruris/Corporis 1Jacques Decroix, 2Jannie Ausma, 2Luc Wouters, 2Marcel Borgers, 2Lieve Vandeplassche 1Avenue du Parc 39, Mouscron, Belgium and 2Barrier Therapeutics, Geel, Belgium Introduction Efficacy Results Tinea Pedis Efficacy Results Tinea Cruris/Corporis Table 3: Effect of pramiconazole on signs and symptoms of tinea Pramiconazole, previously referred to as R126638, is a broad spectrum antifungal Table 1: Effect of pramiconazole on signs and symptoms of tinea pedis belonging to the class of triazoles. It has excellent potential for oral and topical cruris/corporis treatment of fungal infections of skin, hair, nails, oral and genital mucosa. In vitro data Day All Patients Cohort I Cohort II Day All Patients Cohort I Cohort II demonstrated its activity against dermatophytes (Trichophyton spp., Microsporum (3 & 5 days) (3 days) (5 days) (3 & 5 days) (3 days) (5 days) canis, Epidermophyton floccosum), yeasts and many other fungi. Furthermore, Total Signs & 1 9.9 (3-14) 10.2 (8-12) 9.5 (3-14) Total Signs & 1 5.8 (4-9) 6.1 (8-12) 5.6 (3-14) efficacy studies in animals provided evidence for a potent therapeutic effect of Symptoms 4/6 7.2 (2-11) <.001 7.8 (6-11) 0.004 6.6 (2-11) 0.002 Symptoms 4/6 4.8 (3-7) <.001 5.0 (6-11) 0.063 4.6 (2-11) 0.031 R126638 that proved to be 3- to 8-fold superior over that of itraconazole, especially Score** 14 3.4 (1-6) <.001 3.3 (2-5) 0.002 3.5 (1-6) 0.002 Score** 14 2.8 (2-4) <.001 2.9 (2-5) 0.004 2.7 (1-6) 0.004 for superficial fungal infections.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • Primary Target Prediction of Bioactive Molecules from Chemical Structure
    bioRxiv preprint doi: https://doi.org/10.1101/413237; this version posted September 10, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Primary Target Prediction of Bioactive Molecules from Chemical Structure Abed Forouzesh1, Sadegh Samadi Foroushani1,*, Fatemeh Forouzesh2, and Eskandar Zand1 1Iranian Research Institute of Plant Protection, Agricultural Research Education and Extension Organization (AREEO), Tehran, Iran 2Department of Medicine, Tehran Medical Branch, Islamic Azad University, Tehran, Iran *To whom correspondence should be addressed. Tel: (+9821) 22400080; Fax: (+9821) 22400568; Email: [email protected] ABSTRACT There are various tools for computational target prediction of bioactive molecules from a chemical structure in a machine-readable material but these tools can’t distinguish a primary target from other targets. Also, due to the complex nature of bioactive molecules, there has not been a method to predict a target and or a primary target from a chemical structure in a non-digital material (for example printed or hand-written documents) yet. In this study, an attempt to simplify primary target prediction from a chemical structure was resulted in developing an innovative method based on the minimum structure which can be used in both formats of non-digital and machine-readable materials. A minimum structure does not represent a real molecule or a real association of functional groups, but is a part of a molecular structure which is necessary to ensure the primary target prediction of bioactive molecules.
    [Show full text]
  • Correlation of Malassezia Species with Clinical Characteristics of Pityriasis Versicolor
    Dissertation zum Erwerb des Doctor of Philosophy (Ph.D.) an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München Doctoral Thesis for the awarding of a Doctor of Philosophy (Ph.D.) at the Medical Faculty of Ludwig-Maximilians-Universität, Munich vorgelegt von submitted by Perpetua Ibekwe ____________________________________ aus (Geburtsort) born in (place of birth) Enugu, Nigeria ____________________________________ am (Tag an dem die Dissertation abgeschlossen wurde) submitted on (day of finalization of the thesis) 24 April 2014 __________________ Supervisors LMU: Title, first name, last name: Prof. dr. med. dr. Thomas Ruzicka Habilitated Supervisor ______________________________ Dr. dr. med. Miklós Sárdy Direct Supervisor ______________________________ Reviewing Experts: st 1 Reviewer Prof. Dr. Thomas Ruzicka nd 2 Reviewer Dr. Miklós Sárdy Dean: Prof. Dr. med. Dr. h. c. M. Reiser, FACR, FRCR Date of Oral Defence: 15 September 2014 Correlation of Malassezia species with clinical characteristics of pityriasis versicolor Affidavit Ibekwe, Perpetua Surname, first name University of Abuja Teaching Hospital Gwagwalada Street PMB 228, Abuja Zip code, town Nigeria Country I hereby declare, that the submitted thesis entitled Correlation of Malassezia species with clinical characteristics of pityriasis versicolor Thesis Title Thesis Title (cont.) Thesis Title (cont.) is my own work. I have only used the sources indicated and have not made unauthorised use of services of a third party. Where the work of others has been quoted or reproduced, the source is always given. The submitted thesis or parts thereof have not been presented as part of an examination degree to any other university. I further declare that the electronic version of the submitted thesis is congruent with the printed version both in content and format.
    [Show full text]
  • Paradigm Shift in the Management of Topical Tinea Infections Dr Hardik Pathak
    Review Article Luliconazole: Paradigm Shift in the Management of Topical Tinea Infections Dr Hardik Pathak Abstract Luliconazole is an imidazole topical antifungal agent with a unique structure. Pre-clinical studies have dem- onstrated excellent activity against dermatophytes. Although luliconazole belongs to the azole group, it has strong antifungal activities against Trichophyton spp. This may be attributed to a combination of strong in vi- tro antifungal activity and favourable pharmaco kinetic properties in the skin. Clinical trials have demonstrat- ed its superiority over placebo in dermatophytosis, and performed better than terbinafine. The frequency of application (once daily) and duration of treatment (one week for tinea corporis/cruris and 2 weeks for inter- digital tinea pedis) was favourable when compared to other topical regimens in treating tinea pedis. Such regimens include 2–4 weeks of twice-daily treatment with econazole, up to 4 weeks of twice-daily treatment with sertaconazole, 1–2 weeks of twice-daily treatment with terbinafine, 4 weeks of once-daily application of naftifine and 4–6 weeks of once-daily treatment with amorolfine. Luliconazole 1% cream was approved in Japan in 2005 for the treatment of tinea infections. Recently, the US Food and Drug Administration (USFDA) approved luliconazole for interdigital tinea pedis, tinea cruris, and tinea corporis treatment. Topical lulicon- azole has a favourable safety profile, with mild application-site reactions reported occasionally. Keywords: Luliconazole, Tinea pedis, Tinea corporis, Tinea cruris, once a daily Conflict Of Interest: Dr Hardik Pathak is a salaried employee of Dr. Reddy’s Laboratories Ltd, Hyderabad, Telangana, India. Dermatophytosis: A Global Burden (1) he prevalence of superficial mycotic infection is hair, and nails), Epidermophyton (skin and nails), and 20–25% worldwide; most common agents be- Microsporum (skin and hair).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,841,351 B2 Sawant (45) Date of Patent: *Sep
    USOO8841351B2 (12) United States Patent (10) Patent No.: US 8,841,351 B2 SaWant (45) Date of Patent: *Sep. 23, 2014 (54) POLYMERICTOPICAL COMPOSITIONS 4,938,964 A 7, 1990 Sakai et al. 4,940,579 A 7, 1990 Randen 4.954,332 A 9, 1990 Bissett et al. (71) Applicant: Stiefel Research Australia Pty Ltd., 5,081,157 A 1/1992 Pomerantz Rowville (AU) 5,082,656 A 1/1992 Hui et al. 5,304,368 A 4, 1994 Sherinov et al. (72) Inventor: Prashant Sawant, Rowville (AU) 5,436,241 A 7, 1995 Shin et al. 5,573,759 A 11/1996 Blank (73) Assignee: Stiefel Research Australia Pty Ltd., 5,658,559 A 8, 1997 Smith 5,674,912 A 10, 1997 Martin Rowville, Victoria (AU) 6,010,716 A 1/2000 Saunal et al. 6,017,520 A 1/2000 Synodis et al. (*) Notice: Subject to any disclaimer, the term of this 6,123,924 A 9/2000 Mistry et al. patent is extended or adjusted under 35 6,211,250 B1 4/2001 Tomlinson et al. U.S.C. 154(b) by 0 days. 6,582,683 B2 6/2003 Jezior 7,678,366 B2 3/2010 Friedman et al. This patent is Subject to a terminal dis 2005/0175641 A1 8, 2005 Deo et al. claimer. 2007/0196323 A1 8/2007 Zhang et al. 2007/0196325 A1 8/2007 Zhang et al. (21) Appl. No.: 13/910,158 2007/0219.171 A1 9, 2007 Lulla et al. 2008. O152603 A1 6/2008 Rudolph et al.
    [Show full text]