DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2004/0229941A1 Hassman Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2004/0229941A1 Hassman Et Al US 2004O229941A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2004/0229941A1 HaSSman et al. (43) Pub. Date: Nov. 18, 2004 (54) ANALEPTIC AND ANTIDEPRESSANT Related U.S. Application Data COMBINATIONS (60) Provisional application No. 60/469,989, filed on May (75) Inventors: Howard A. Hassman, Moorestown, NJ 13, 2003. (US); Rodney J. Hughes, Kennett Square, PA (US) Publication Classification Correspondence Address: (51) Int. Cl." ...................... A61K 31/343; A61K 31/137 CEPHALON, INC. (52) U.S. Cl. ........................... 514/469; 514/617; 514/649 145 BRANDY WINE PARKWAY WEST CHESTER, PA 19380-4245 (US) (57) ABSTRACT (73) Assignee: Cephalon, Inc., West Chester, PA (21) Appl. No.: 10/844,134 Compositions and methods for the treatment of depressive disorders through the administration of modafinil with anti (22) Filed: May 12, 2004 depressants. US 2004/0229941 A1 Nov. 18, 2004 ANALEPTIC AND ANTIDEPRESSANT nocturnal Sleep. Pathological Somnolence, whether due to COMBINATIONS narcolepsy or other causes, is disabling and potentially dangerous. Causes of pathological Somnolence, other than BACKGROUND OF THE INVENTION narcolepsy, include chronic Sleep loSS; Sleep apnea; and other sleep disorders. Whether due to narcolepsy or other 0001) 1. Modafinil causes, pathological Somnolence produces episodes of unin 0002 Modafinil, CHNOS, also known as 2-(benzhy tended sleep, reduced attention, and performance errors. drylsulfinyl) acetamide, or 2-(diphenylmethyl) sulfinyl Consequently, it is linked to a variety of transportation and acetamide, is a Synthetic acetamide derivative with wake industrial accidents. A therapeutic agent that reduces or promoting activity, the Structure of which has been described eliminateS pathological Somnolence would have important in French Patent No. 78 05 510 and in U.S. Pat. No. implications not only for individual patients, but also for 4,177.290 (290), and which has been approved by the public health and Safety. United States Food and Drug Administration for use in the 0007. Other uses of modafinil have been presented. U.S. treatment of excessive daytime Sleepiness associated with Pat. No. 5,180,745 discloses the use of modafinil for pro narcolepsy. A method of preparation of a racemic mixture is Viding a neuroprotective effect in humans, and in particular described in the 290 patent and a method of preparation of for the therapy of Parkinson's disease. The levorotatory a levorotatory isomer is described in U.S. Pat. No. 4,927,855 form of modafinil, i.e., (-) benzhydrylsulfinyl-acetamide, (both incorporated herein by reference). The levorotatory may have potential benefit for therapy of depression, hyper isomer is reported to be useful for treatment of hyperSomnia, somnia and Alzheimer's disease (U.S. Pat. No. 4,927,855). depression, Alzheimer's disease and to have activity towards European Published Application 547952 discloses the use of the Symptoms of dementia and loSS of memory, especially in modafinil as an anti-ischemic agent. European Published the elderly. Application 594507 discloses the use of modafinil to treat 0003. The primary pharmacological activity of modafinil urinary incontinence. is to promote wakefulness. Modafinil promotes wakefulneSS 0008 U.S. Pat. No. RE37,516 discloses pharmaceutical in rats (Touret et al., 1995; Edgar and Seidel, 1997), cats compositions having a defined particle size, and in particular (Lin et al., 1992), canines (Shelton et al., 1995) and non compositions wherein 95% of the cumulative total of the human primates (Hernant et al., 1991) as well as in models effective amount of modafinil particles in the composition mimicking clinical situations, Such as sleep apnea (English have a diameter less than about 200 microns. bulldog sleep disordered breathing model) (Panckeri et al., 1996) and narcolepsy (narcoleptic canine) (Shelton et al., 0009 2. Antidepressants 1995). 0010 Antidepressants, including selective serotonin 0004 Modafinil has also been described as an agent with reuptake inhibitors (SSRIs) have become first choice thera activity in the central nervous System, and as a useful agent peutics in the therapy of depression, certain forms of anxiety in the treatment of Parkinson's disease (U.S. Pat. No. and Social phobias. In Some instances, SSRIs can be more 5,180,745); in the protection of cerebral tissue from favored because they are effective, well tolerated and have ischemia (U.S. Pat. No. 5,391,576); in the treatment of a favorable Safety profile compared to the classic tricyclic urinary and fecal incontinence (U.S. Pat. No. 5,401.776); antidepressants. and in the treatment of Sleep apneas and disorders of central 0011. However, there can be problems associated with origin (U.S. Pat. No. 5,612,379). U.S. Pat. No. 5,618,845 any anti-depressant. Current antidepressant therapy can describes modafinil preparations of a defined particle size exhibit a delayed onset and modest proportion in achieving less than about 200 microns. In addition, modafinil may be response or remission. For example, the response at 6 weeks used in the treatment of eating disorders, or to promote to the selective serotonin reuptake inhibitor (SSRI) fluox weight gain or stimulate appetite in humans or animals (U.S. etine is about 50%. Remission rates with SSRIs at 8 weeks Pat. No. 6,455,588, incorporated herein by reference), or in are about 35%. Delayed, incomplete and lack of response of the treatment of attention deficit hyperactivity disorder a major depressive disorder to antidepressant therapy can be (ADHD) (U.S. Pat. No. 6,346,548, incorporated herein by problematic for numerous reasons, including premature reference), or fatigue, especially fatigue associated with treatment discontinuation. Sometimes Symptoms even multiple sclerosis (U.S. Pat. No. 6,488,164, incorporated worsen during the first weeks of therapy. In other cases, herein by reference). non-compliance can be related to Side effects, including 0005) Modafinil has been shown to be effective in treat Sexual dysfunction. ing narcolepsy, sleepiness, excessive sleepiness (e.g., sleepi 0012 Fatigue and excessive sleepiness are among the ness associated with disorders of Sleep and wakefulness), Symptoms of a major depressive disorder, and can be excessive daytime SleepineSS associated with narcolepsy, adverse experiences associated with antidepressant therapy Parkinson's disease, urinary incontinence, multiple Sclerosis and are often residual Symptoms inadequately treated with fatigue, ADHD, Alzheimer's disorder, Sleep apnea, obstruc SSRI antidepressant therapy. tive sleep apnea, depression, and ischemia. 0013 In addition, patients sometimes suffer side effects 0006 Narcolepsy is a chronic disorder characterized by asSociated with antidepressant therapy and withdrawal of intermittent Sleep attacks, persistent, excessive daytime antidepressant therapy. sleepiness and abnormal rapid eye movement (“REM”) Sleep manifestations, Such as sleep-onset REM periods, 0014. Because residual symptoms to antidepressant cataplexy, Sleep paralysis and hypnagogic hallucinations, or therapy predisposes patients with depression to a greater risk both. Most patients with narcolepsy also have disrupted of relapse and greater probability of recurrence, rapid US 2004/0229941 A1 Nov. 18, 2004 achievement of remission is an important consideration in tyline hydrochloride, iprindole, isocarboxazid; ketipramine choosing the most appropriate treatment Strategy. fumarate; lofepramine hydrochloride, lortalamine; mapro tiline; maprotiline hydrochloride; melitracen hydrochloride; 0.015 New therapies that address one or more of these millacemide hydrochloride; minaprine hydrochloride; mir problems are needed. tazapine; moclobemide; modaline Sulfate, napacitadine hydrochloride; napameZole hydrochloride; nefazodone SUMMARY OF THE INVENTION hydrochloride; nisoxetine, nitrafudam hydrochloride; 0016. In one embodiment, the present invention includes nomifensine maleate, nortriptyline hydrochloride; octrip a method of enhancing the activity of an antidepressant in an tyline phosphate, opipramol hydrochloride; Oxaprotiline animal Subject, preferably a human. The method includes hydrochloride; oxypertine, paroxetine; phenelZine Sulfate; the Step of pre-treating the Subject with an effective amount pirandamine hydrochloride, pizotyline; pridefine hydrochlo of one or more analeptics, including but not limited to ride, prolintane hydrochloride; protriptyline hydrochloride; modafinil and/or co-administering an effective amount of quipazine maleate, rolicyprine; Seproxetine hydrochloride; one or more analeptics, including but not limited to modafi Sertraline hydrochloride; Sibutramine hydrochloride; nil, with an antidepressant. Sulpiride, SuritoZole; tametraline hydrochloride; tampramine fumarate; tandamine hydrochloride; thiaZeSim hydrochlo DETAILED DESCRIPTION OF THE ride; thozalinone; tomoxetine hydrochloride; traZOdone INVENTION hydrochloride; trebenzomine hydrochloride; trimipramine; trimipramine maleate; Venlafaxine hydrochloride, Vilox 0.017. 1. Analeptic Agents azine hydrochloride, Zimeldine hydrochloride, Zometapine. 0.018 Analeptics are drugs that principally act as or are 0022. In certain embodiments, the antidepressant used as a central nervous System Stimulant. Preferred for use includes citalipram, fluoxetine, fluoxetine hydrochloride, in the practice of the invention are analeptics that operate on paroxetine, paroxetine hydrochloride, and/or clomipramine the sleep-wake centers of the brain and that lack the phar
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.
    [Show full text]
  • Strategies for Managing Sexual Dysfunction Induced by Antidepressant Medication
    King’s Research Portal DOI: 10.1002/14651858.CD003382.pub3 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA): Taylor, M. J., Rudkin, L., Bullemor-Day, P., Lubin, J., Chukwujekwu, C., & Hawton, K. (2013). Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews, (5). https://doi.org/10.1002/14651858.CD003382.pub3 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • Efficient Synthesis of Pyrazolopyridines Containing a Chromane Backbone Through Domino Reaction
    Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction Razieh Navari1, Saeed Balalaie*1,2, Saber Mehrparvar1, Fatemeh Darvish1, Frank Rominger3, Fatima Hamdan1 and Sattar Mirzaie1 Full Research Paper Open Access Address: Beilstein J. Org. Chem. 2019, 15, 874–880. 1Peptide Chemistry Research Center, K. N. Toosi University of doi:10.3762/bjoc.15.85 Technology, P. O. Box 15875-4416, Tehran, Iran, Tel: +98-21-23064226, Fax: +98-21-22889403, 2Medical Biology Received: 07 February 2019 Research Center, Kermanshah University of Medical Sciences, Accepted: 29 March 2019 Kermanshah, Iran and 3Organisch-Chemisches Institut der Published: 11 April 2019 Universitaet Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany Associate Editor: T. J. J. Müller Email: © 2019 Navari et al.; licensee Beilstein-Institut. Saeed Balalaie* - [email protected] License and terms: see end of document. * Corresponding author Keywords: chromane; domino reaction; fused heterocyclic skeletons; pyrazolopyridines Abstract An efficient approach for the synthesis of pyrazolopyridines containing the aminochromane motif through a base-catalyzed cycliza- tion reaction is reported. The synthesis was carried out through a three-component reaction of (arylhydrazono)methyl-4H-chromen- 4-one, malononitrile, primary amines in the presence of Et3N at room temperature. However, carrying out the reaction under the same conditions without base led to a fused chromanyl-cyanopyridine. High selectivity, high atom economy, and good to high yields in addition to mild reaction conditions are the advantages of this approach. Introduction The synthesis of new fused heterocyclic backbones has always Chromone derivatives have been found to exhibit a broad range been a major challenge in the field of organic synthesis [1-3].
    [Show full text]
  • Crystal Structure Analysis of Ethyl 6-(4-Methoxyphenyl)-1-Methyl-4-Methyl- Sulfanyl-3-Phenyl-1H-Pyrazolo[3,4-B]Pyridine-5-Carboxylate
    research communications Crystal structure analysis of ethyl 6-(4-methoxy- phenyl)-1-methyl-4-methylsulfanyl-3-phenyl-1H- pyrazolo[3,4-b]pyridine-5-carboxylate ISSN 2056-9890 H. Surya Prakash Rao,a,b* Ramalingam Gunasundarib and Jayaraman Muthukumaranc‡ Received 4 June 2020 aDepartment of Chemistry and Biochemistry, School of Basic Sciences and Research, Sharda University, Greater Noida Accepted 30 June 2020 201306, India, bDepartment of Chemistry, Pondicherry University, Puducherry 605 014, India, and cDepartment of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201306, India. *Correspon- dence e-mail: [email protected] Edited by D. Chopra, Indian Institute of Science Education and Research Bhopal, India In the title compound, C24H23N3O3S, the dihedral angle between the fused ‡ Additional correspondence author, e-mail: pyrazole and pyridine rings is 1.76 (7) . The benzene and methoxy phenyl rings [email protected]. make dihedral angles of 44.8 (5) and 63.86 (5) , respectively, with the pyrazolo[3,4-b] pyridine moiety. An intramolecular short SÁÁÁO contact Keywords: crystal structure; pyrazolopyridine; [3.215 (2) A˚ ] is observed. The crystal packing features C—HÁÁÁ interactions. pyrazolo[3,4-b]pyridine; C—HÁÁÁ interactions. CCDC reference: 2005976 Supporting information: this article has 1. Chemical context supporting information at journals.iucr.org/e Pyrazolopyridines, in which a group of three nitrogen atoms is incorporated into a bicyclic heterocycle, are privileged medicinal scaffolds, often utilized in drug design and discovery regimes (Kumar et al., 2019). Owing to the possibilities of the easy synthesis of a literally unlimited number of a combina- torial library of small organic molecules with a pyrazolo- pyridine scaffold, there has been enormous interest in these molecules among medicinal chemists (Kumar et al.
    [Show full text]
  • (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.
    [Show full text]
  • 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
    [Show full text]
  • Customs Tariff - Schedule
    CUSTOMS TARIFF - SCHEDULE 99 - i Chapter 99 SPECIAL CLASSIFICATION PROVISIONS - COMMERCIAL Notes. 1. The provisions of this Chapter are not subject to the rule of specificity in General Interpretative Rule 3 (a). 2. Goods which may be classified under the provisions of Chapter 99, if also eligible for classification under the provisions of Chapter 98, shall be classified in Chapter 98. 3. Goods may be classified under a tariff item in this Chapter and be entitled to the Most-Favoured-Nation Tariff or a preferential tariff rate of customs duty under this Chapter that applies to those goods according to the tariff treatment applicable to their country of origin only after classification under a tariff item in Chapters 1 to 97 has been determined and the conditions of any Chapter 99 provision and any applicable regulations or orders in relation thereto have been met. 4. The words and expressions used in this Chapter have the same meaning as in Chapters 1 to 97. Issued January 1, 2020 99 - 1 CUSTOMS TARIFF - SCHEDULE Tariff Unit of MFN Applicable SS Description of Goods Item Meas. Tariff Preferential Tariffs 9901.00.00 Articles and materials for use in the manufacture or repair of the Free CCCT, LDCT, GPT, UST, following to be employed in commercial fishing or the commercial MT, MUST, CIAT, CT, harvesting of marine plants: CRT, IT, NT, SLT, PT, COLT, JT, PAT, HNT, Artificial bait; KRT, CEUT, UAT, CPTPT: Free Carapace measures; Cordage, fishing lines (including marlines), rope and twine, of a circumference not exceeding 38 mm; Devices for keeping nets open; Fish hooks; Fishing nets and netting; Jiggers; Line floats; Lobster traps; Lures; Marker buoys of any material excluding wood; Net floats; Scallop drag nets; Spat collectors and collector holders; Swivels.
    [Show full text]
  • )&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
    [Show full text]
  • 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.
    [Show full text]
  • A Synthetic Overview of New Molecules with 5-HT1A Binding Affinities
    77 A Synthetic Overview of New Molecules with 5-HT1A Binding Affinities Hernán Pessoa-Mahana* 1 ; Ramiro Araya-Maturana1 , Claudio Saitz, B.1 and C. David Pessoa-Mahana2 1Departamento de Química Orgánica y Fisicoquímica. Facultad de Ciencias Químicas y Farmacéuticas. Universidad de Chile. Olivos 1007.Casilla 233. Santiago 1. Chile 2Departamento de Farmacia. Facultad de Química. Pontificia Universidad Católica de Chile. Vicuña Mackenna 4860-Casilla 306, Correo 22 Santiago-Chile Abstract: The present review discusses the synthetic strategies of new ligands exhibiting mainly 5-HT1A binding affinities. Specifically we focused our attention in the synthesis of compounds structurally related to arylpiperazine, 2-aminotetralin, and benzopyran derivatives. Keywords: serotonin, 5-HT1A ligands, arylpiperazines, aminotetralins, benzopyrans. INTRODUCTION During the last 15 years, seven distinct families of 5-HT receptors have been identified (5-HT1–5-HT7), and at least Depression is one of the most common illnesses, 15 subpopulations have been described for several of these affecting up to one-third of all people at the same time. [4,5]. The 5-HT1A receptors represent a major target for Depressive disorders encompass a variety of conditions neurobiological research and drug developments. A study on including two major forms of unipolar depression (i.e. major distribution of 5-HT1A receptors in the brains of various depression and dysthymia), adjustment disorders, animal species indicates that the highest densities are located subsyndromal depression (minor depression), seasonal in the hippocampus, septum, amygdale, and cortical limbic affective disorder (SAD), premenstrual dysphoric disorder areas. The 5-HT1A receptors located in the raphe nuclei are (PMDD), postpartum depression, atypical depression and known as somatodendritic autoreceptors.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]