HK1072432A1 - Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands - Google Patents

Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands

Info

Publication number
HK1072432A1
HK1072432A1 HK05105957.5A HK05105957A HK1072432A1 HK 1072432 A1 HK1072432 A1 HK 1072432A1 HK 05105957 A HK05105957 A HK 05105957A HK 1072432 A1 HK1072432 A1 HK 1072432A1
Authority
HK
Hong Kong
Prior art keywords
thiadiazoleoxides
thiadiazoledioxides
cxc
chemokine receptor
receptor ligands
Prior art date
Application number
HK05105957.5A
Other languages
English (en)
Inventor
Arthur G Taveras
Cynthia J Aki
John J Baldwin
Ge Li
J Robert Merritt
Jianhua Chao
Younong Yu
Jay S Fine
Gaifa Lai
Minglang Wu
Purakkattle J Biju
William Hipkin
Evan A Hecker
Original Assignee
Pharmacopeia Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmacopeia Inc filed Critical Pharmacopeia Inc
Publication of HK1072432A1 publication Critical patent/HK1072432A1/xx

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/10—1,2,5-Thiadiazoles; Hydrogenated 1,2,5-thiadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/06—Antiabortive agents; Labour repressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
HK05105957.5A 2002-10-09 2005-07-13 Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands HK1072432A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41737102P 2002-10-09 2002-10-09
PCT/US2003/031707 WO2004033440A1 (en) 2002-10-09 2003-10-07 Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands

Publications (1)

Publication Number Publication Date
HK1072432A1 true HK1072432A1 (en) 2005-10-28

Family

ID=32094009

Family Applications (1)

Application Number Title Priority Date Filing Date
HK05105957.5A HK1072432A1 (en) 2002-10-09 2005-07-13 Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands

Country Status (16)

Country Link
US (2) US20040186142A1 (de)
EP (1) EP1551818B1 (de)
JP (2) JP4664074B2 (de)
CN (1) CN1720240B (de)
AR (1) AR043052A1 (de)
AT (1) ATE422203T1 (de)
AU (1) AU2003288922A1 (de)
CA (1) CA2501535A1 (de)
DE (1) DE60326080D1 (de)
ES (1) ES2321186T3 (de)
HK (1) HK1072432A1 (de)
MX (1) MXPA05003867A (de)
MY (1) MY139601A (de)
PE (1) PE20040570A1 (de)
TW (1) TW200413342A (de)
WO (1) WO2004033440A1 (de)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040106794A1 (en) * 2001-04-16 2004-06-03 Schering Corporation 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
BR0308739A (pt) * 2002-03-18 2005-01-11 Schering Corp Tratamentos em combinação para doenças mediadas por quimiocina
ATE422203T1 (de) * 2002-10-09 2009-02-15 Schering Corp Thiadiazoldioxide und thiadiazoloxide als cxc- und cc-chemokinrezeptor liganden
US20060004088A1 (en) * 2002-10-22 2006-01-05 Oct Inc. Furan derivatives for preventing and curing osteoporosis and pharmaceutical compositions containing the same
AR047759A1 (es) * 2003-09-26 2006-02-22 Vertex Pharma Derivados de fenil - piperazina como moduladores de receptores muscarnicos
US7338968B2 (en) * 2003-12-19 2008-03-04 Schering Corporation Thiadiazoles AS CXC- and CC- chemokine receptor ligands
CA2550540A1 (en) * 2003-12-22 2005-07-28 Schering Corporation Isothiazole dioxides as cxc- and cc- chemokine receptor ligands
EP1745032B1 (de) 2004-05-12 2013-07-31 Merck Sharp & Dohme Corp. CXCR1- und CXCR2-Chemokin-Antagonisten
AR049384A1 (es) * 2004-05-24 2006-07-26 Glaxo Group Ltd Derivados de purina
JP2008500372A (ja) * 2004-05-26 2008-01-10 カリフォルニア インスティテュート オブ テクノロジー ニューロン成長の低分子刺激物質
BRPI0512535A (pt) 2004-06-24 2008-03-25 Incyte Corp compostos de piperidinas n-substituìdas, suas composições e métodos de modulações
GB0510140D0 (en) 2005-05-18 2005-06-22 Addex Pharmaceuticals Sa Novel compounds B2
JP2009500334A (ja) * 2005-06-29 2009-01-08 シェーリング コーポレイション Ｃｘｃ−ケモカインレセプターリガンドとしてのジ置換オキサジアゾール
ES2353401T3 (es) * 2005-06-29 2011-03-01 Schering Corporation Oxidiazolopirazinas y tiadiazolopirazinas 5,6-di-sustituidas como ligandos del receptor de cxc-quimiocina.
GB0514809D0 (en) 2005-07-19 2005-08-24 Glaxo Group Ltd Compounds
CA2657051A1 (en) * 2006-07-07 2008-01-10 Schering Corporation 3,4-di-substituted cyclobutene-1,2-diones as cxc-chemokine receptor ligands
EP2351743A4 (de) * 2008-10-27 2012-05-09 Takeda Pharmaceutical Bicyclische verbindung
WO2012007500A2 (de) 2010-07-15 2012-01-19 Bayer Cropscience Ag Neue heterocyclische verbindungen als schädlingsbekämpfungsmittel
WO2012148547A1 (en) * 2011-02-24 2012-11-01 The Schepens Eye Research Institute, Inc. Compositions and methods for treating inflammatory conditions of the ocular surface
US8865723B2 (en) 2012-10-25 2014-10-21 Tetra Discovery Partners Llc Selective PDE4 B inhibition and improvement in cognition in subjects with brain injury
US10227370B2 (en) 2013-08-02 2019-03-12 California Institute Of Technology Heparan sulfate/heparin mimetics with anti-chemokine and anti-inflammatory activity
US9770461B2 (en) 2013-08-02 2017-09-26 California Institute Of Technology Tailored glycopolymers as anticoagulant heparin mimetics
CN103724304B (zh) * 2013-12-24 2016-08-17 定陶县友帮化工有限公司 5-溴苯并呋喃的制备方法
CN103787956B (zh) * 2014-01-20 2016-03-30 上海医药工业研究院 用于制备泊马度胺的中间体的制备方法
US9763992B2 (en) 2014-02-13 2017-09-19 Father Flanagan's Boys' Home Treatment of noise induced hearing loss
WO2018073248A1 (en) 2016-10-17 2018-04-26 Icm (Institut Du Cerveau Et De La Moelle Épinière) Prognosis of demyelinating diseases patients and treatment thereof
WO2018106959A1 (en) 2016-12-07 2018-06-14 Progenity Inc. Gastrointestinal tract detection methods, devices and systems
WO2018112264A1 (en) 2016-12-14 2018-06-21 Progenity Inc. Treatment of a disease of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor
US11066488B2 (en) 2017-06-20 2021-07-20 Dow Global Technologies Llc Biaryl phenoxy group IV transition metal catalysts for olefin polymerization
GEP20237476B (en) * 2018-09-21 2023-03-27 Pfizer N-substituted-dioxocyclobutenylamino-3-hydroxypicolinamides useful as ccr6 inhibitors
WO2020106757A1 (en) 2018-11-19 2020-05-28 Progenity, Inc. Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
CN109970588B (zh) * 2019-03-14 2024-03-08 武汉南望环保技术研究有限责任公司 一种无毒耐久型防污涂料及其制备方法
US11707610B2 (en) 2019-12-13 2023-07-25 Biora Therapeutics, Inc. Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
BG113517A (bg) 2022-04-04 2023-10-16 "Мицар Иновейшън" ООД Пан-хемокинови антагонисти за използване при превенция и намаляване на ракови метастази

Family Cites Families (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3115496A (en) * 1963-05-13 1963-12-24 Upjohn Co Certain 3, 4-disubstituted-1, 2, 5-thiadiazole-1, 1-dioxides and their preparation
US3115495A (en) * 1963-05-13 1963-12-24 Upjohn Co Certain 3, 4-diaryl-delta2-1, 2, 5-thiadiazoline-1, 1-dioxides and their preparation
DE1669798A1 (de) 1966-07-28 1971-08-26 Huels Chemische Werke Ag Verfahren zum Stabilisieren markomolekularer Polyacetale
CS214745B2 (en) * 1976-08-28 1982-05-28 Huels Chemische Werke Ag Shaped and non-shaped products from plastic materials
NL189197C (nl) 1979-09-04 1993-02-01 Bristol Myers Squibb Co 3,4-digesubstitueerde-1,2,5-thiadiazool-1-oxiden en 1,1-dioxiden, bereiding daarvan alsmede farmaceutische preparaten.
DE3175201D1 (en) 1980-04-30 1986-10-02 Merck & Co Inc Aminothiadiazoles as gastric secretion inhibitors
US4394508A (en) * 1980-06-07 1983-07-19 Bristol-Myers Company Chemical compounds
US4510309A (en) * 1981-03-03 1985-04-09 Bristol-Myers Company Histamine H2 -antagonists
IE53068B1 (en) 1981-06-15 1988-05-25 Merck & Co Inc Diamino isothiazole-1-oxides and -1,1-dioxides as gastic secretion inhibitors
BE897247A (fr) 1982-07-08 1984-01-09 Glaxo Group Ltd Nouveau composes heterocycliques
FI832519L (fi) * 1982-07-12 1984-01-13 Bristol Myers Co Farmaceutiska foerfaranden och sammansaettningar
AU2222083A (en) * 1982-12-14 1984-06-21 Smith Kline & French Laboratories Limited Pyridine derivatives
US4863936A (en) * 1982-12-14 1989-09-05 Smith Kline & French Laboratories Limited 3,5-Substituted-2-pyridyl-alkylaminocyclobutenediones having histamine h1 -antagonist activity
DE3374007D1 (en) * 1982-12-23 1987-11-12 Smith Kline French Lab Pyridine derivatives
DE3309655A1 (de) * 1983-03-17 1984-09-20 Bayer Ag, 5090 Leverkusen 1,2,5-thiadiazol-1-oxide und 1,1-dioxide, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
US4497810A (en) * 1983-10-14 1985-02-05 Merck & Co., Inc. Thiatriazine dioxides as gastric anti-secretory agents
US4562184A (en) * 1984-04-02 1985-12-31 Merck & Co., Inc. Substituted-aminohydroxypropoxy-thiadiazoles, β-blocking compositions and use
JPS60255756A (ja) * 1984-06-01 1985-12-17 Ikeda Mohandou:Kk アミノアルキルフエノキシ誘導体
GB8501535D0 (en) * 1985-01-22 1985-02-20 Smith Kline French Lab Chemical compounds
HU198696B (en) 1987-01-20 1989-11-28 Nissan Chemical Ind Ltd Process for producing 3/2h/-pyridazinon derivatives and pharmaceutical compositions containing them as active components
JPH02256668A (ja) 1988-12-20 1990-10-17 Nissan Chem Ind Ltd ピリダジノン誘導体
US5206252A (en) * 1992-05-08 1993-04-27 American Home Products Corporation Thiadiazolyl-amino derivatives of benzopyrans and indanes
GB9312210D0 (en) 1993-06-14 1993-07-28 Smithkline Beecham Plc Chemical compounds
US5506252A (en) * 1993-11-17 1996-04-09 American Home Products Corporation Substituted N-heteroaryl and N-aryl-1,2-diaminocyclobutene-3,4-diones
US5354763A (en) * 1993-11-17 1994-10-11 American Home Products Corporation Substituted N-heteroaryl and N-aryl-1,2-diaminocyclobutene-3,4-diones
US5550139A (en) * 1994-01-03 1996-08-27 The Wichita State University Serine protease inhibitors
US5466712A (en) * 1994-11-04 1995-11-14 American Home Products Corporation Substituted n-aryl-1,2-diaminocyclobutene-3,4-diones
ATE176223T1 (de) 1994-11-16 1999-02-15 American Home Prod Diaminocyclobuten-3,4-dione
US5494925A (en) * 1994-12-02 1996-02-27 Sterling Winthrop Inc. 2-heterocyclyloxymethyl and 2-heterocyclylthiomethyl-1,2,5-thiadiazolidin-3-one 1,1-dioxides and compositions and method of use thereof
US5958957A (en) * 1996-04-19 1999-09-28 Novo Nordisk A/S Modulators of molecules with phosphotyrosine recognition units
HUP0001943A3 (en) * 1997-01-23 2002-12-28 Smithkline Beecham Corp Benzimidazole and benzotriazole derivatives, their use, process for their preparation and pharmaceutical compositions containing them
US5840764A (en) * 1997-01-30 1998-11-24 American Home Products Corporation Substituted hydroxy-anilino derivatives of cyclobutene-3,4-diones
AU6250298A (en) 1997-01-30 1998-08-25 American Home Products Corporation Substituted hydroxy-anilino derivatives of cyclobutene-3,4-diones
AR015425A1 (es) * 1997-09-05 2001-05-02 Smithkline Beecham Corp Compuestos de benzotiazol, composicion farmaceutica que los contiene, su uso en la manufactura de un medicamento, procedimiento para su preparacion,compuestos intermediarios y procedimiento para su preparacion
DE69903053T2 (de) 1998-10-02 2003-05-22 Neurosearch As Ballerup Diaminocyclobuten-3,4-dionderivate, deren herstellung und deren verwendung
ATE284387T1 (de) 1998-10-08 2004-12-15 Smithkline Beecham Plc 3-(3-chloro-4-hydroxyphenylamino)-4-(2- nitrophenyl)-1h-pyrrol-2,5-dion als glykogen synthase kinase-3 inhibitor (gsk-3)
US6376555B1 (en) * 1998-12-04 2002-04-23 American Home Products Corporation 4-substituted-3-substituted-amino-cyclobut-3-ene-1,2-diones and analogs thereof as novel potassium channel openers
EP1140792A1 (de) 1998-12-14 2001-10-10 American Home Products Corporation 3,4-diamino-3-cyclobutene-1,2-dione derivate welche leukocytenadhesion verursacht von vla-4 inhibieren
US6420396B1 (en) * 1998-12-16 2002-07-16 Beiersdorf Ag Biphenyl and biphenyl-analogous compounds as integrin antagonists
EE200100317A (et) 1998-12-16 2002-08-15 Bayer Aktiengesellschaft Uued bifenüül- ja bifenüülanaloogsed ühendid kui integriini antagonistid
US6518283B1 (en) 1999-05-28 2003-02-11 Celltech R&D Limited Squaric acid derivatives
CO5190696A1 (es) 1999-06-16 2002-08-29 Smithkline Beecham Corp Antagonistas de los receptores il-8
AU1201101A (en) 1999-10-15 2001-04-30 Du Pont Pharmaceuticals Company Bicyclic and tricyclic amines as modulators of chemokine receptor activity
EP1220836A2 (de) 1999-10-15 2002-07-10 Bristol-Myers Squibb Pharma Company Benzylcyklohexylamine als modulatoren der chemokin-rezeptor-aktivität
EP1265905A4 (de) 2000-03-01 2003-03-12 Smithkline Beecham Corp Il-2 receptor antagonisten
AR033803A1 (es) * 2000-03-01 2004-01-07 Smithkline Beecham Corp Compuestos de dianilino escuarano, composiciones farmaceuticas que los comprenden, y el uso de los mismos en la fabricacion de medicamentos para tratar enfermedades mediadas por quimioquinas
EP1274415A4 (de) 2000-03-14 2005-09-07 Smithkline Beecham Corp Il-8 rezeptorantagonisten
IL152775A0 (en) * 2000-05-30 2003-06-24 Smithkline Beecham Corp Il-8 receptor antagonists
US6395762B1 (en) * 2000-07-17 2002-05-28 American Home Products Corporation Phenyl amino squarate and thiadiazole dioxide beta-3 adrenergic receptor agonists
EP1357909B1 (de) * 2001-01-16 2009-01-07 Smithkline Beecham Corporation Il-8-rezeptor-antagonisten
DE60216229T2 (de) * 2001-01-16 2007-10-04 Smithkline Beecham Corp. Il-8-rezeptorantagonisten
US20030204085A1 (en) * 2001-02-02 2003-10-30 Taveras Arthur G. 3, 4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor antagonists
JP2004529911A (ja) * 2001-02-02 2004-09-30 シェーリング　コーポレイション Ｃｘｃケモカインレセプターアンタゴニストとしての３，４−二置換シクロブテン−１，２−ジオン
US7132445B2 (en) * 2001-04-16 2006-11-07 Schering Corporation 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
ATE365154T1 (de) 2001-04-16 2007-07-15 Schering Corp 3,4-disubstituierte cyclobuten-1,2-dione als cxc- chemokinrezeptorliganden
JP2005505595A (ja) * 2001-10-12 2005-02-24 シェーリング　コーポレイション Ｃｘｃ−ケモカインレセプターアンタゴニストとしての３，４−二置換マレイミド化合物
US6878709B2 (en) * 2002-01-04 2005-04-12 Schering Corporation 3,4-di-substituted pyridazinediones as CXC chemokine receptor antagonists
BR0308739A (pt) 2002-03-18 2005-01-11 Schering Corp Tratamentos em combinação para doenças mediadas por quimiocina
ATE422203T1 (de) 2002-10-09 2009-02-15 Schering Corp Thiadiazoldioxide und thiadiazoloxide als cxc- und cc-chemokinrezeptor liganden
US7338968B2 (en) * 2003-12-19 2008-03-04 Schering Corporation Thiadiazoles AS CXC- and CC- chemokine receptor ligands
CA2550540A1 (en) * 2003-12-22 2005-07-28 Schering Corporation Isothiazole dioxides as cxc- and cc- chemokine receptor ligands

Also Published As

Publication number Publication date
MXPA05003867A (es) 2005-11-23
US20070264230A1 (en) 2007-11-15
ATE422203T1 (de) 2009-02-15
DE60326080D1 (en) 2009-03-19
WO2004033440A1 (en) 2004-04-22
WO2004033440A8 (en) 2005-06-02
JP4664074B2 (ja) 2011-04-06
AU2003288922A1 (en) 2004-05-04
CA2501535A1 (en) 2004-04-22
EP1551818A1 (de) 2005-07-13
CN1720240A (zh) 2006-01-11
MY139601A (en) 2009-10-30
PE20040570A1 (es) 2004-08-30
US20040186142A1 (en) 2004-09-23
ES2321186T3 (es) 2009-06-03
AR043052A1 (es) 2005-07-13
TW200413342A (en) 2004-08-01
US7691856B2 (en) 2010-04-06
EP1551818B1 (de) 2009-02-04
JP2006508079A (ja) 2006-03-09
CN1720240B (zh) 2010-10-27
JP2010270151A (ja) 2010-12-02

Similar Documents

Publication Publication Date Title
HK1072432A1 (en) Thiadiazoledioxides and thiadiazoleoxides as cxc- and cc-chemokine receptor ligands
HK1087711A1 (en) Thiadiazoles as cxc and cc- chemokine receptor ligands
EP1547488A4 (de) Sitz
EP1522237A4 (de) Matte
AU2003276494A8 (en) Functional sites
ZA200507350B (en) Cannabinoid receptor ligands and uses thereof
IL172026A0 (en) Cannabinoid receptor ligands and uses thereof
EP1552981A4 (de) Sitzkonstruktion
AU2003272511A8 (en) Cd44-binding ligands
DE60323213D1 (en) Brenner
IL173265A0 (en) Imidazo-pyrimidines and triazolo-pyrimidines: benzodiazcpine receptor ligands
GB0220922D0 (en) Improved mat
IL173337A0 (en) Receptor
AU2003283562A8 (en) Ligands
GB0230202D0 (en) Ligand
GB2389525B (en) Mat
AU2003226764A8 (en) Novel glucocorticoid receptor ligands
GB0215389D0 (en) Receptor
GB2389526B (en) Mat
SI1648899T1 (sl) Imidazo-pirimidini in triazolo-pirimidini: benzodiazepinski receptorski ligandi
GB0211204D0 (en) Receptor and its ligand
GB0211205D0 (en) Receptor and ligand
GB0321998D0 (en) Receptor
GB0321391D0 (en) Flexi-facial plus
ZA200400707B (en) Mixer

Legal Events

Date Code Title Description
PC Patent ceased (i.e. patent has lapsed due to the failure to pay the renewal fee)

Effective date: 20121007