WO 2014/018563 A2 30 January 2014 (30.01.2014)
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
(12) Patent Application Publication (10) Pub. No.: US 2012/0190743 A1 Bain Et Al
US 2012O190743A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0190743 A1 Bain et al. (43) Pub. Date: Jul. 26, 2012 (54) COMPOUNDS FOR TREATING DISORDERS Publication Classification OR DISEASES ASSOCATED WITH (51) Int. Cl NEUROKININ 2 RECEPTORACTIVITY A6II 3L/23 (2006.01) (75) Inventors: Jerald Bain, Toronto (CA); Joel CD7C 69/30 (2006.01) Sadavoy, Toronto (CA); Hao Chen, 39t. ii; C Columbia, MD (US); Xiaoyu Shen, ( .01) Columbia, MD (US) A6IPI/00 (2006.01) s A6IP 29/00 (2006.01) (73) Assignee: UNITED PARAGON A6IP II/00 (2006.01) ASSOCIATES INC., Guelph, ON A6IPI3/10 (2006.01) (CA) A6IP 5/00 (2006.01) A6IP 25/00 (2006.01) (21) Appl. No.: 13/394,067 A6IP 25/30 (2006.01) A6IP5/00 (2006.01) (22) PCT Filed: Sep. 7, 2010 A6IP3/00 (2006.01) CI2N 5/071 (2010.01) (86). PCT No.: PCT/US 10/48OO6 CD7C 69/33 (2006.01) S371 (c)(1) (52) U.S. Cl. .......................... 514/552; 554/227; 435/375 (2), (4) Date: Apr. 12, 2012 (57) ABSTRACT Related U.S. Application Data Compounds, pharmaceutical compositions and methods of (60) Provisional application No. 61/240,014, filed on Sep. treating a disorder or disease associated with neurokinin 2 4, 2009. (NK) receptor activity. Patent Application Publication Jul. 26, 2012 Sheet 1 of 12 US 2012/O190743 A1 LU 1750 15OO 1250 OOO 750 500 250 O O 20 3O 40 min SampleName: EM2OO617 Patent Application Publication Jul. 26, 2012 Sheet 2 of 12 US 2012/O190743 A1 kixto CFUgan <tro CFUgan FIG.2 Patent Application Publication Jul. -
Garden Mastery Tips March 2006 from Clark County Master Gardeners
Garden Mastery Tips March 2006 from Clark County Master Gardeners Flowering Quince Flowering quince is a group of three hardy, deciduous shrubs: Chaenomeles cathayensis, Chaenomeles japonica, and Chaenomeles speciosa. Native to eastern Asia, flowering quince is related to the orchard quince (Cydonia oblonga), which is grown for its edible fruit, and the Chinese quince (Pseudocydonia sinensis). Flowering quince is often referred to as Japanese quince (this name correctly refers only to C. japonica). Japonica is often used regardless of species, and flowering quince is still called Japonica by gardeners all over the world. The most commonly cultivated are the hybrid C. superba and C. speciosa, not C. japonica. Popular cultivars include ‘Texas Scarlet,’ a 3-foot-tall plant with red blooms; ‘Cameo,’ a double, pinkish shrub to five feet tall; and ‘Jet Trail,’ a white shrub to 3 feet tall. Flowering quince is hardy to USDA Zone 4 and is a popular ornamental shrub in both Europe and North America. It is grown primarily for its bright flowers, which may be red, pink, orange, or white. The flowers are 1 to 2 inches in diameter, with five petals, and bloom in late winter or early spring. The glossy dark green leaves appear soon after flowering and turn yellow or red in autumn. The edible quince fruit is yellowish-green with reddish blush and speckled with small dots. The fruit is 2 to 4 inches in diameter, fragrant, and ripens in fall. The Good The beautiful blossoms of flowering quince Flowering quince is an easy-to-grow, drought-tolerant shrub that does well in shady spots as well as sun (although more sunlight will produce better flowers). -
United States Patent (10) Patent No.: US 8,969,514 B2 Shailubhai (45) Date of Patent: Mar
USOO896.9514B2 (12) United States Patent (10) Patent No.: US 8,969,514 B2 Shailubhai (45) Date of Patent: Mar. 3, 2015 (54) AGONISTS OF GUANYLATECYCLASE 5,879.656 A 3, 1999 Waldman USEFUL FOR THE TREATMENT OF 36; A 6. 3: Watts tal HYPERCHOLESTEROLEMIA, 6,060,037- W - A 5, 2000 Waldmlegand et al. ATHEROSCLEROSIS, CORONARY HEART 6,235,782 B1 5/2001 NEW et al. DISEASE, GALLSTONE, OBESITY AND 7,041,786 B2 * 5/2006 Shailubhai et al. ........... 530.317 OTHER CARDOVASCULAR DISEASES 2002fOO78683 A1 6/2002 Katayama et al. 2002/O12817.6 A1 9/2002 Forssmann et al. (75) Inventor: Kunwar Shailubhai, Audubon, PA (US) 2003,2002/0143015 OO73628 A1 10/20024, 2003 ShaubhaiFryburg et al. 2005, OO16244 A1 1/2005 H 11 (73) Assignee: Synergy Pharmaceuticals, Inc., New 2005, OO32684 A1 2/2005 Syer York, NY (US) 2005/0267.197 A1 12/2005 Berlin 2006, OO86653 A1 4, 2006 St. Germain (*) Notice: Subject to any disclaimer, the term of this 299;s: A. 299; NS et al. patent is extended or adjusted under 35 2008/0137318 A1 6/2008 Rangarajetal.O U.S.C. 154(b) by 742 days. 2008. O151257 A1 6/2008 Yasuda et al. 2012/O196797 A1 8, 2012 Currie et al. (21) Appl. No.: 12/630,654 FOREIGN PATENT DOCUMENTS (22) Filed: Dec. 3, 2009 DE 19744O27 4f1999 (65) Prior Publication Data WO WO-8805306 T 1988 WO WO99,26567 A1 6, 1999 US 2010/O152118A1 Jun. 17, 2010 WO WO-0 125266 A1 4, 2001 WO WO-02062369 A2 8, 2002 Related U.S. -
Chaenomeles Speciosa) in the Naxi and Tibetan Highlands of NW Yunnan, China
Cultural and Ecosystem Services of Flowering Quince (Chaenomeles speciosa) in the Naxi and Tibetan Highlands of NW Yunnan, China. Authors: Lixin Yang, Selena Ahmed, John Richard Stepp, Yanqinag Zhao, Ma Jun Zeng, Shengji Pei, Dayuan Xue, and Gang Xu The final publication is available at Springer via https://dx.doi.org/10.1007/s12231-015-9318-7. Yang, Lixin, Selena Ahmed, John Richard Stepp, Yanqinag Zhao, Ma Jun Zeng, Shengji Pei, Dayuan Xue, and Gang Xu. “Cultural Uses, Ecosystem Services, and Nutrient Profile of Flowering Quince (Chaenomeles Speciosa) in the Highlands of Western Yunnan, China.” Economic Botany 69, no. 3 (September 2015): 273–283. doi:10.1007/s12231-015-9318-7. Made available through Montana State University’s ScholarWorks scholarworks.montana.edu Cultural Uses, Ecosystem Services, and Nutrient Profile Chaenomeles speciosa of Flowering Quince ( ) in the Highlands 1 of Western Yunnan, China 2,3 3,4 ,3,5 6 LIXIN YANG ,SELENA AHMED ,JOHN RICHARD STEPP* ,YANQINAG ZHAO , 7 2 ,3 2 MA JUN ZENG ,SHENGJI PEI ,DAYUAN XUE* , AND GANG XU 2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institutes of Botany, Chinese Academy of Sciences, Kunming, China 3College of Life and Environmental Science, Minzu University of China, Beijing, China 4Department of Health and Human Development, Montana State University, Bozeman, MT, USA 5Department of Anthropology, University of Florida, Gainesville, FL, USA 6College of Forestry and Vocational Technology in Yunnan, Kunming, China 7Southwest Forestry University, Bailongshi, Kunming, China *Corresponding author; e-mail: [email protected]; [email protected] Introduction ample light but is tolerant of partial shade. -
(19) United States (12) Patent Application Publication (10) Pub
US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist. -
Protocol/Amendment No.: 252-10 a Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Pembrolizumab (MK-3475) in Combin
Product: MK-3475 (SCH 900475), INCB024360 1 Protocol/Amendment No.: 252-10 (INCB 24360-301-10) / NCT02752074 THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK SHARP & DOHME CORP., A SUBSIDIARY OF MERCK & CO., INC., WHITEHOUSE STATION, NJ, U.S.A. This study is co-funded by Incyte and MSD. Execution of Trial: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. One Merck Drive P.O. Box 100 Whitehouse Station, New Jersey, 08889-0100, U.S.A. Protocol-specific Contact information can be found in the Investigator Trial File Binder (or equivalent). Global Sponsor of the Study: Incyte Corporation (Referenced herein as Sponsor) 1801 Augustine Cut-Off Wilmington, Delaware, 19803, U.S.A TITLE: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Pembrolizumab (MK- 3475) in Combination With Epacadostat or Placebo in Subjects with Unresectable or Metastatic Melanoma (KEYNOTE-252 / ECHO-301) IND NUMBER: 121,704 EudraCT NUMBER: 2015-004991-31 MK-3475-252-10 (INCB 24360-301-10) Final Protocol 18-May-2018 Confidential 04XN7M Product: MK-3475 (SCH 900475), INCB024360 2 Protocol/Amendment No.: 252-10 (INCB 24360-301-10) TABLE OF CONTENTS SUMMARY OF CHANGES.................................................................................................14 1.0 TRIAL SUMMARY...................................................................................................29 2.0 TRIAL DESIGN.........................................................................................................30 -
YTN Ci Y COOCH3 --Al-E- F 7.1% F 5 6
USOO5853696A United States Patent (19) 11 Patent Number: 5,853,696 Elmaleh et al. (45) Date of Patent: Dec. 29, 1998 54 SUBSTITUTED 2-CARBOXYALKYL-3 Carroll et al., “Synthesis, Ligand Binding, QSAR, and (FLUOROPHENYL)-8-(3-HALOPROPEN-2- CoMFA Study . , Journal of Medicinal Chemistry YL) NORTROPANES AND THEIR USE AS 34:2719-2725, 1991. IMAGING AGENTS FOR Madras et al., “N-Modified Fluorophenyltropane Analogs. NEURODEGENERATIVE DISORDERS ... ", Pharmcology, Biochemistry & Behavior 35:949–953, 1990. 75 Inventors: David R. Elmaleh; Bertha K. Madras, Milius et al., “Synthesis and Receptor Binding of N-Sub both of Newton; Peter Meltzer, stituted Tropane Derivatives . , Journal of Medicinal Lexington; Robert N. Hanson, Newton, Chemistry 34:1728-1731, 1991. all of Mass. Boja et al. “New, Potent Cocaine Analogs: Ligand Binding 73 Assignees: Organix, Inc., Woburn; The General and Transport Studies in Rat Striatum' European J. of Hospital Corporation, Boston; The Pharmacology, 184:329–332 (1990). President and Fellows of Harvard Brownell et al. *Use of C-11 College, Cambridge; Northeastern 2B-Carbomethoxy-3B-4-Fluorophenyl Tropane (C-11 University, Boston, all of Mass. CFT) in Studying Dopamine Fiber Loss in a Primate Model of Parkinsonism” J. Nuclear Med. Abs., 33:946 (1992). 21 Appl. No.: 605,332 Canfield et al. “Autoradiographic Localization of Cocaine Binding Sites by HICFT (I HIWIN 35,428) in the 22 Filed: Feb. 20, 1996 Monkey Brain” Synapse, 6:189-195 (1990). Carroll et al. “Probes for the Cocaine Receptor. Potentially Related U.S. Application Data Irreversible Ligands for the Dopamine Transporter” J. Med. 62 Division of Ser. No. 142.584, Oct. -
)&F1y3x PHARMACEUTICAL APPENDIX to THE
)&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE -
Inhibition of Monoamine Oxidase in 5
Br. J. Pharmac. (1985), 85, 683-690 Inhibition ofmonoamine oxidase in 5- hydroxytryptaminergic neurones by substitutedp- aminophenylalkylamines Anna-Lena Ask, Ingrid Fagervall, L. Florvall, S.B. Ross1 & Susanne Ytterborn Research Laboratories, Astra Likemedel AB, S-151 85 Si3dertilje, Sweden 1 A series ofsubstituted p-aminophenethylamines and some related compounds were examined with regards to the inhibition ofmonoamine oxidase (MAO) in vivo inside and outside 5-hydroxytryptamin- ergic neurones in the rat hypothalamus. This was recorded as the protection against the irreversible inhibition of MAO produced by phenelzine by determining the remaining deaminating activity in the absence and presence ofcitalopram using a low (0.1 yIM) concentration of ['4CJ-5-hydroxytryptamine (5-HT) as substrate. 2 Some ofthe phenethylamines were much more potent inside than outside the 5-hydroxytryptamin- ergic neurones. This neuronal selectivity was antagonized by pretreatment of the rats with norzimeldine, a 5-HT uptake inhibitor, which indicates that these compounds are accumulated in the 5-HT nerve terminals by the 5-HT pump. 3 Selectivity was obtained for compounds with dimethyl, monomethyl or unsubstituted p-amino groups. An isopropyl group appears to substitute for the dimethylamino group but with considerably lower potency. Compounds with 2-substitution showed selectivity for aminergic neurones and this effect decreased with increased size of the substituent. The 2,6-dichloro derivative FLA 365 had, however, no neuronal selective action but was a potent MAO inhibitor. Substitutions in the 3- and 5- positions decreased both potency and selectivity. 4 Prolongation ofthe side chain with one methylene group abolished the preference for the MAO in 5-hydroxytryptaminergic neurones although the MAO inhibitory potency remained. -
Designing Inhibitors Via Molecular Modelling Methods for Monoamine Oxidase Isozymes a and B Filiz Varnali Kadir Has Universit
DESIGNING INHIBITORS VIA MOLECULAR MODELLING METHODS FOR MONOAMINE OXIDASE ISOZYMES A AND B FİLİZ VARNALI KADİR HAS UNIVERSITY 2012 DESIGNING INHIBITORS VIA MOLECULAR MODELLING METHODS FOR MONOAMINE OXIDASE ISOZYMES A AND B FİLİZ VARNALI M.S. in Computational Biology and Bioinformatics, Kadir Has University, 2012 Submitted to the Graduate School of Science and Engineering in partial fulfilment of the requirements for the degree of Master of Science in Computational Biology and Bioinformatics KADİR HAS UNIVERSITY 2012 DESIGNING INHIBITORS VIA MOLECULAR MODELING METHODS FOR MONOAMINE OXIDASE ISOZYMES A AND B Abstract In drug development studies, a large number of new drug candidates (leads) have to be synthesized and optimized by changing several moieties of the leads in order to increase efficacies and decrease toxicities. Each synthesis of these new drug candidates include multi-steps procedures. Overall, discovering a new drug is a very time-consuming and very costly works. The development of molecular modelling programs and their applications in pharmaceutical research have been formalized as a field of study known computer assisted drug design (CADD) or computer assisted molecular design (CAMD). In this study, using the above techniques, Monoamine Oxidase isozymes, which play an essential role in the oxidative deamination of the biogenic amines, were studied. Compounds that inhibit these isozymes were shown to have therapeutic value in a variety of conditions including several psychiatric and neurological as well as neurodegenerative diseases. First, a series of new pyrazoline derivatives were screened using molecular modelling and docking methods and promising lead compounds were selected, and proposed for synthesis as novel selective MAO-A or –B inhibitors. -
Treatment of Social Phobia with Antidepressants
Antidepressants for Social Phobia Treatment of Social Phobia With Antidepressants Franklin R. Schneier, M.D. This article reviews evidence for the utility of antidepressant medications in the treatment of social phobia. Monoamine oxidase inhibitors (MAOIs) were the first antidepressants shown to be effective © Copyrightfor social phobia, but 2001dietary restrictions Physicians and a relatively Postgraduate high rate of adverse effects Press, often relegate Inc. MAOIs to use after other treatments have been found ineffective. Reversible inhibitors of monoamine oxidase (RIMAs) hold promise as safer alternatives to MAOIs, but RIMAs may be less effective and are currently unavailable in the United States. Selective serotonin reuptake inhibitors (SSRIs), of which paroxetine has been the best studied in social phobia to date, have recently emerged as a first- line treatment for the generalized subtype of social phobia. The SSRIs are well tolerated and consis- tently have been shown to be efficacious in controlled trials. (J Clin Psychiatry 2001;62[suppl 1]:43–48) arly evidence that antidepressantsOne might personal have utility copy maypressant be printed treatment of other anxiety disorders, such as panic E in the treatment of social phobia emerged in the disorder and obsessive-compulsive disorder. In particular, 1970s when studies found efficacy for monoamine oxidase the high rate of comorbidity of anxiety disorders with de- inhibitors (MAOIs) in patient samples that included both pression3 makes treatment with antidepressants an efficient -
PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.