WO2010144759A1 - Iminosugars and methods of treating bunyaviral and togaviral diseases - Google Patents
Iminosugars and methods of treating bunyaviral and togaviral diseases Download PDFInfo
- Publication number
- WO2010144759A1 WO2010144759A1 PCT/US2010/038247 US2010038247W WO2010144759A1 WO 2010144759 A1 WO2010144759 A1 WO 2010144759A1 US 2010038247 W US2010038247 W US 2010038247W WO 2010144759 A1 WO2010144759 A1 WO 2010144759A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- virus
- substituted
- unsubstituted
- groups
- disease
- Prior art date
Links
- 0 CN*Nc1c(*)c(S)c(*)c(*)c1* Chemical compound CN*Nc1c(*)c(S)c(*)c(*)c1* 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present application relates to iminosugars and methods of treating viral diseases with iminosugars and, in particular, to the use of iminosugars for treatment and prevention of diseases caused by or associated with a virus that belongs to the Bunyaviridae or Togaviridae family.
- One embodiment provides a method of treating or preventing a disease or condition caused by or associated with a virus belonging to the Bunyaviridae family, the method comprising administering to a subject in need thereof a compound of the formula,
- R is either selected from substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted oxaalkyl groups; or wherein R is
- R 1 is a substituted or unsubstituted alkyl group
- X 1-5 are independently selected from H, NO 2 , N 3 , or NH 2 ;
- Y is absent or is a substituted or unsubstituted Ci-alkyl group, other than carbonyl; and Z is selected from a bond or NH; provided that when Z is a bond, Y is absent, and provided that when Z is NH, Y is a substituted or unsubstituted Ci-alkyl group, other than carbonyl; and wherein W 1-4 are independently selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted alkanoyl groups, substituted or unsubstituted aroyl groups, or substituted or unsubstituted haloalkanoyl groups.
- Another embodiment provides a method of treating or preventing a disease or condition caused by or associated with a virus belonging to the Togaviridae family, the method comprising administering to a subject in need thereof a compound of the formula,
- R is either selected from substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted oxaalkyl groups; or wherein R is
- R 1 is a substituted or unsubstituted alkyl group
- X 1-5 are independently selected from H, NO 2 , N 3 , or NH 2 ;
- Y is absent or is a substituted or unsubstituted Ci-alkyl group, other than carbonyl; and Z is selected from a bond or NH; provided that when Z is a bond, Y is absent, and provided that when Z is NH, Y is a substituted or unsubstituted Ci-alkyl group, other than carbonyl; and wherein W 1-4 are independently selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted alkanoyl groups, substituted or unsubstituted aroyl groups, or substituted or unsubstituted haloalkanoyl groups.
- Figures 1(A)-(E) present chemical formulas of the following iminosugars: A) TV- Butyl deoxynojirimycin (NB-DNJ or UV-I); B) N-Nonyl dexoynojirimycin (NN-DNJ or UV- 2); C) N-(7-Oxadecyl)deoxynojirimycin (N7-O-DNJ or UV-3); D) N-(9-Methoxynonyl) deoxynojirimycin (N9-DNJ or UV-4); E) 7V-(7V- ⁇ 4'-azido-2'-nitrophenyl ⁇ -6- aminohexyl)deoxynojirimycin (NAP-DNJ or UV-5).
- Figure 2 is a synthesis scheme for NN-DNJ.
- Figures 3A-D illustrate synthesis of N7-O-DNJ.
- Figure 3 A shows a sequence of reactions leading to N7-O-DNJ
- Figure 3B illustrates preparation of 6- propyloxy-1-hexanol
- Figure 3C illustrates preparation of 6-propyloxy-l-hexanal
- Figure 3D illustrates synthesis of N7-O-DNJ.
- Figures 4A-C relate to synthesis of 7V-(9-Methoxynonyl) deoxynojirimycin.
- Figure 4A illustrates preparation of 9-methoxy-l-nonanol
- Figure 4B illustrates preparation of 9-methoxy-l-nonanal
- Figure 4C illustrates synthesis of 7V-(9-Methoxynonyl) deoxynojirimycin.
- Figure 5 presents a table with in vitro IC50 ( ⁇ m) data for NB-DNJ; NN-DNJ; N7-O-
- FIG. 6 presents dose response curves for Rift Valley Fever virus (RVFV).
- Figure 7 presents dose response curves for Venezuelan equine encephalitis virus
- Figure 8 presents dose response curves for Chikingunya virus (CHIKV).
- viral infection describes a diseased state, in which a virus invades a healthy cell, uses the cell's reproductive machinery to multiply or replicate and ultimately lyse the cell resulting in cell death, release of viral particles and the infection of other cells by the newly produced progeny viruses. Latent infection by certain viruses is also a possible result of viral infection.
- the present inventors discovered that certain iminosugars, such as deoxynojirimycin derivatives, can be effective against viruses that belong to the Bunyaviridae or Togaviridae family and, thus, these iminosugars can be useful for treating or preventing a disease or condition caused by or associated with a virus that belongs to the Bunyaviridae or
- the family Bunyaviridae contains the following genera: Genus Hantavirus; Genus
- Genus Orthobunyavirus Genus Phlebovirus
- Genus Tospovirus Genus
- Tenuivirus Of these genera, all can infect vertebrates except Tospoviruses, which can only infect arthropods and plants.
- Genus Hantavirus includes the following viruses: Andes virus (ANDV); Bayou virus (BAYV); Black Creek Canal Virus (BCCV); Cano Delgadito virus (CADV); Choclo virus (CHOV); Dobrava-Belgrade virus (DOBV); Hantaan virus (HNTV); IsIa Vista virus
- MULV New York virus
- PDV Prospect Hill Virus
- PMV Puumala virus
- Genus Nairovirus includes the following viruses: Crimean-Congo hemorrhagic fever virus; Dugbe Virus; Qalyub Virus; Sakhalin Virus; Dera Ghazi Khan; Thiafora Virus; and Hughes Virus.
- Genus Orthobunyavirus includes La Crosse virus; California encephalitis virus and
- Genus Phlebovirus includes Alenquer virus, Chandiru virus, Chagres virus, Sandfly
- HFRS hemorrhagic fever with renal syndrome
- HCPS Hantavirus cardiopulmonary syndrome
- Genus such as Sin Nombre virus, Andes virus, New York virus, Bayou virus, and Black
- the Togabiridae family includes Genus Alphavirus and Genus Rubivirus.
- Genus Alphavirus includes the following viruses: Sindbis virus; Semliki Forest virus; O'nyong'nyong virus; Chikungunya virus; Mayaro virus; Ross River virus; Barmah Forest virus; Eastern equine encephalitis virus; Western equine encephalitis virus; and Venezuelan equine encephalitis virus.
- Genus Rubivirus includes Rubella viruses.
- the iminosugar can be a compound of the following formula:
- W 1-4 are independently selected from hydrogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted haloalkyl groups, substituted or unsubstituted alkanoyl groups, substituted or unsubstituted aroyl groups, or substituted or unsubstituted haloalkanoyl groups.
- R can be selected from substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted aryl groups, or substituted or unsubstituted oxaalkyl groups.
- R can be substituted or unsubstituted alkyl groups and/or substituted or unsubstituted oxaalkyl groups comprise from 1 to 16 carbon atoms, from 4 to
- oxaalkyl refers to an alkyl derivative, which can contain from 1 to 5 or from 1 to 3 or from 1 to 2 oxygen atoms.
- oxaalkyl includes hydroxyterminated and methoxyterminated alkyl derivatives.
- R may be an branched or unbranched, substituted or unsubstituted alkyl group.
- the alkyl group may be a long chain alkyl group, which may be C6-C20 alkyl group; C8-C16 alkyl group; or C8-C10 alkyl group.
- R can have the following formula
- X 1-5 are independently selected from H, NO 2 , N 3 , or NH 2 ;
- Y is absent or is a substituted or unsubstituted Ci-alkyl group, other than carbonyl; and Z is selected from a bond or NH; provided that when Z is a bond, Y is absent, and provided that when Z is NH, Y is a substituted or unsubstituted Ci-alkyl group, other than carbonyl.
- Z is NH and R 1 -Y is a substituted or unsubstituted alkyl group, such as C2-C20 alkyl group or C4-C12 alkyl group or C4-C10 alkyl group.
- X 1 is NO 2 and X 3 is N 3 .
- each of X 2 , X 4 and X 5 is hydrogen.
- the iminosugar is a DNJ derivative disclosed in U.S. Patent application publication no. 2007/0275998, which is incorporated herein by reference.
- the deoxynojirimycin derivative can be one of the compounds presented in Figure 1.
- the iminosugar can be in a form of a salt derived from an inorganic or organic acid.
- Pharmaceutically acceptable salts and methods for preparing salt forms are disclosed, for example, in Berge et al. (J. Pharm. ScL 66:1-18, 1977).
- salts include but are not limited to the following salts: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, cyclopentanepropionate, dodecylsulfate, ethanesulfonate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, nicotinate, 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate,
- the iminosugar may also used in a form of a prodrug.
- Prodrugs of DNJ derivatives such as the 6-phosphorylated DNJ derivatives, are disclosed in U.S. Patents nos. 5,043,273 and 5,103,008.
- the iminosugar may be used as a part of a composition, which further comprises a pharmaceutically acceptable carrier and/ or a component useful for delivering the composition to an animal.
- a pharmaceutically acceptable carrier useful for delivering the compositions to a human and components useful for delivering the composition to other animals such as cattle are known in the art. Addition of such carriers and components to the composition of the invention is well within the level of ordinary skill in the art.
- the iminosugar may be used in a liposome composition, such as those disclosed in US publication 2008/0138351; US application No. 12/410,750 filed March 25, 2009 and US provisional application No. 61/202,699 filed March 27, 2009.
- the iminosugar such as a DNJ derivative, can be administered to a cell or an animal affected by a virus.
- the iminosugar can inhibit morphogenesis of the virus, or it can treat the animal. The treatment can reduce, abate, or diminish the virus infection in the animal.
- Animals that can be infected with a virus that belongs to the Bunyaviridae or Togaviridae family include vertebrates, such as birds and mammals including primates, humans, rodents, livestock animals, such as sheep and goats, and equines such as horses, zebras and donkeys, as well as invertebrates.
- vertebrates such as birds and mammals including primates, humans, rodents, livestock animals, such as sheep and goats, and equines such as horses, zebras and donkeys, as well as invertebrates.
- the amount of iminosugar administered to a cell, or an animal can be an amount effective to inhibit the morphogenesis of a virus, that belongs to the Bunyaviridae or Togaviridae family.
- the term "inhibit” as used herein can refer to the detectable reduction and/or elimination of a biological activity exhibited in the absence of the iminosugar.
- the term "effective amount” can refer to that amount of the iminosugar necessary to achieve the indicated effect.
- treatment can refer to reducing or alleviating symptoms in a subject, preventing symptoms from worsening or progressing, inhibition or elimination of the causative agent, or prevention of the infection or disorder related to the virus that belongs to the Bunyaviridae or Togaviridae family in a subject who is free therefrom.
- treatment of the disease caused by or associated with a virus can include destruction of the infecting agent, inhibition of or interference with its growth or maturation, and neutralization of its pathological effects.
- the amount of the iminosugar which can be administered to the cell or animal is preferably an amount that does not induce any toxic effects which outweigh the advantages which accompany its administration.
- Actual dosage levels of active ingredients in the pharmaceutical compositions may vary so as to administer an amount of the active compound(s) that is effective to achieve the desired therapeutic response for a particular patient.
- the selected dose level can depend on the activity of the iminosugar, the route of administration, the severity of the condition being treated, and the condition and prior medical history of the patient being treated. However, it is within the skill of the art to start doses of the compound(s) at levels lower than required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose may be divided into multiple doses for purposes of administration, for example, two to four doses per day. It will be understood, however, that the specific dose level for any particular patient can depend on a variety of factors, including the body weight, general health, diet, time and route of administration and combination with other therapeutic agents and the severity of the condition or disease being treated.
- the adult human daily dosage may range from between about one microgram to about one gram, or from between about 10 mg and 100 mg, of the iminosugar per 10 kilogram body weight.
- the amount of the iminosugar which should be administered to a cell or animal can depend upon numerous factors well understood by one of skill in the art, such as the molecular weight of the iminosugar and the route of administration.
- Pharmaceutical compositions that are useful in the methods of the invention may be administered systemically in oral solid formulations, ophthalmic, suppository, aerosol, topical or other similar formulations. For example, it may be in the physical form of a powder, tablet, capsule, lozenge, gel, solution, suspension, syrup, or the like.
- compositions may contain pharmaceutically-acceptable carriers and other ingredients known to enhance and facilitate drug administration.
- Other possible formulations such as nanoparticles, liposomes resealed erythrocytes, and immunologically based systems may also be used to administer the iminosugar.
- Such pharmaceutical compositions may be administered by a number of routes.
- parenteral used herein includes subcutaneous, intravenous, intraarterial, intrathecal, and injection and infusion techniques, without limitation.
- the pharmaceutical compositions may be administered orally, topically, parenterally, systemically, or by a pulmonary route.
- compositions may be administered in a single dose or in multiple doses which are administered at different times. Because the inhibitory effect of the composition upon a virus, that belongs to the Bunyaviridae or Togaviridae family, may persist, the dosing regimen may be adjusted such that virus propagation is retarded while the host cell is minimally effected.
- an animal may be administered a dose of the composition of the invention once per week, whereby virus propagation is retarded for the entire week, while host cell functions are inhibited only for a short period once per week.
- Embodiments described herein are further illustrated by, though in no way limited to, the following working examples.
- the filtrate was concentrated in vacuo to get the crude product.
- the crude product was dissolved in dichloromethane and washed with water, and then brine, dried over sodium sulfate. The organic layer was concentrated in vacuo to get the crude product.
- the crude product was purified by column chromatography using 230-400 mesh silica gel. A solvent gradient of ethyl acetate in hexanes (10-45%) was used to elute the product from the column. All fractions containing the desired pure product were combined and concentrated in vacuo to give pure 6-propyloxy-l-hexanol (lot D-1029-048, 1.9 g, 25%) Completion of the reaction was monitored by thin layer chromatography (TLC); (eluent: 60% ethyl acetate in hexanes).
- TLC thin layer chromatography
- the filtrate was concentrated in vacuo to get a crude product.
- the crude product was purified by column chromatography using 250-400 mesh silica gel (20 g). A solvent gradient of methanol in ethyl acetate (5- 25%) was used to elute the product from the column. All fractions containing the desired pure product were combined, and concentrated in vacuo to give an off white solid. The solid was triturated in ethyl acetate (20 mL), filtered and dried in high vacuum to give a white solid [lot: D-1027-158 (165.3 mg, 28.1%). Completion of the reaction was monitored by thin layer chromatography (TLC) using a thin layer silica gel plate; eluent: 50% methanol in dichloromethane .
- TLC thin layer chromatography
- Figure 5 presents a table with in vitro IC50 ( ⁇ m) data for NB-DNJ; NN-DNJ; N7-O- DNJ; N9-DNJ and NAP-DNJ against Rift Valley Fever virus (RVFV)), which is a Bunyavirus, and Venezuelan equine encephalitis virus (VEEV)) and Chikingunya virus (CHIKV), which are Togaviruses.
- RVV Rift Valley Fever virus
- VEEV Venezuelan equine encephalitis virus
- CHIKV Chikingunya virus
- Base stocks of the following compounds were prepared in dimethylsulfoxide (DMSO) to a final maximal DMSO concentration of 0.5%: NB-DNJ, NN- DNJ, N7-O-DNJ, N9-DNJ, and NAP-DNJ. All compounds were diluted from the base stocks to their experimental concentrations.
- DMSO dimethylsulfoxide
- Viruses The compounds were screened for inhibition against Rift Valley Fever Virus (Bunyavirus) MP 12 strain, Chikungunya (Togaviridae) 181/25 strain, and the Venezuelan Equine Encephalitis (Togaviridae) TC-83 strain.
- Viral stocks were made by propagation in Vero cells using modified Eagle medium (MEM, Sigma), supplemented with 2% fetal bovine serum, 2 mM L-glutamine, 100 U/ml penicillin, 100 ug/ml streptomycin and titered using the standard plaque assay (method presented below). Viral stocks were stored at -80 0 C until used.
- MEM modified Eagle medium
- virus Yield Reduction Assay The virus yield assay were performed by standard plaque assay on supernatant samples generated from virus-infected cells incubated with different concentrations of the UV compound. 24-well cell culture plates were seeded with cells in ImL MEM with 10% fetal bovine serum Vero cells (ATCC, Mannassas, VA; ATCC number CCL-81) in MEM with Earl's salts (Sigma, St Louis, MO) supplemented with 2mM L-glutamine, 100U/mL penicillin/streptomycin, and 2% heat-inactivated fetal bovine serum and incubated at 37°C for 24 hours or until -80% confiuency.
- Viral supernatant were diluted from 10 "3 to 10 "8 and added (10OuL) to the cells and incubated at 37°C for 1 hour with shaking every 5- 10 minutes.
- Viral infection medium (10OuL) were aspirated and replace with ImL pre- warmed 2% low-melt agarose mixed 1:1 with 2X MEM (5% fetal calf serum) and incubated at 37°C, 5% CO 2 for 6 days followed by plaque visualization by neutral red staining.
- IC50 was determined as concentration of compound resulting in 50% virus inhibition.
- FIG. 6 presents dose response curves for Rift Valley Fever virus (RVFV).
- RVFV MP 12 virus inhibition was found for compounds UV-2 (NN-DNJ), -3 (N7-O-DNJ), and -5 (NAP-DNJ) with EC50s of 58, 218, and 49 ⁇ M.
- UV-2 was toxic to cells at the highest concentration (250 ⁇ M).
- Compounds UV-I (NB-DNJ) and -4 (N9-DNJ) all have EC50s over 250 ⁇ M.
- Figure 7 presents dose response curves for Venezuelan equine encephalitis virus (VEEV). The virus yield assay were performed as disclosed above for Figure 5.
- VEEV Venezuelan equine encephalitis virus
- VEE virus inhibition was found for compounds UV-I (NB-DNJ), -2 (NN-DNJ), and -5 (NAP-DNJ) with EC50s of 156, 12, and 2 ⁇ M.
- UV-2 was toxic at the highest concentration (250 ⁇ M).
- Figure 8 presents dose response curves for Chikingunya virus (CHIKV). The virus yield assay were performed as in Figure 5.
- Chikungunya virus inhibition was found for compounds UV-5 (NAP-DNJ) with an EC50 of 22 ⁇ M.
- UV-2 (NN-DNJ) showed protection with an EC50 of 56 ⁇ M.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2012515167A JP5634510B2 (en) | 2009-06-12 | 2010-06-11 | Methods for treating iminosugars and bunyavirus and togavirus diseases |
EP10786885.3A EP2440205B1 (en) | 2009-06-12 | 2010-06-11 | Iminosugars for use in the treatment of bunyaviral and togaviral diseases |
ES10786885.3T ES2524361T3 (en) | 2009-06-12 | 2010-06-11 | Iminoazúcares for use in the treatment of bunyavirus and togavirus diseases |
CA2765086A CA2765086C (en) | 2009-06-12 | 2010-06-11 | Iminosugars and methods of treating bunyaviral and togaviral diseases |
KR1020127000433A KR101463661B1 (en) | 2009-06-12 | 2010-06-11 | Iminosugars and methods of treating bunyaviral and togaviral diseases |
CN201080033499.6A CN102639133B (en) | 2009-06-12 | 2010-06-11 | Iminosugars and methods of treating bunyaviral and togaviral diseases |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18661409P | 2009-06-12 | 2009-06-12 | |
US61/186,614 | 2009-06-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2010144759A1 true WO2010144759A1 (en) | 2010-12-16 |
Family
ID=43306958
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2010/038247 WO2010144759A1 (en) | 2009-06-12 | 2010-06-11 | Iminosugars and methods of treating bunyaviral and togaviral diseases |
Country Status (8)
Country | Link |
---|---|
US (2) | US8426445B2 (en) |
EP (1) | EP2440205B1 (en) |
JP (1) | JP5634510B2 (en) |
KR (1) | KR101463661B1 (en) |
CN (1) | CN102639133B (en) |
CA (1) | CA2765086C (en) |
ES (1) | ES2524361T3 (en) |
WO (1) | WO2010144759A1 (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102875450A (en) * | 2012-10-25 | 2013-01-16 | 上海丝绸集团股份有限公司 | Technological method for extracting 1-deoxynojirimycin from mulberry leaf |
WO2016073652A1 (en) * | 2014-11-05 | 2016-05-12 | Unither Virology, Llc | Iminosugars useful for the treatment of viral diseases |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20120042716A (en) | 2009-02-23 | 2012-05-03 | 유나이티드 세러퓨틱스 코오포레이션 | Iminosugars and methods of treating viral diseases |
CA2765086C (en) * | 2009-06-12 | 2015-12-15 | United Therapeutics Corporation | Iminosugars and methods of treating bunyaviral and togaviral diseases |
EP2858642A4 (en) | 2012-06-06 | 2015-12-02 | Unither Virology Llc | Novel iminosugars and their applications |
US9623016B2 (en) | 2013-03-15 | 2017-04-18 | Emergent Virology Llc | Antibacterial compounds |
CA2924026C (en) | 2013-09-16 | 2021-12-28 | Emergent Virology Llc | Deoxynojirimycin derivatives and methods of their using |
CN104357583B (en) * | 2014-10-31 | 2016-11-09 | 中国检验检疫科学研究院 | The real-time fluorescent RT-PCR detection reagent box of Ba Maha forest virus and method |
CN109771432B (en) * | 2019-03-13 | 2022-04-19 | 中国人民解放军军事科学院军事医学研究院 | Application of glucosamine and derivatives thereof as antiviral drugs |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4246345A (en) | 1978-08-03 | 1981-01-20 | Bayer Aktiengesellschaft | Process for the production of 6-amino-6-deoxy-L-sorbose |
US4266025A (en) | 1978-12-12 | 1981-05-05 | Bayer Aktiengesellschaft | Production of N-substituted derivatives of 1-desoxy-nojirimycin |
US4405714A (en) | 1980-10-15 | 1983-09-20 | Bayer Aktiengesellschaft | Production of N-substituted derivatives of 1-desoxynojirimicin |
US4806650A (en) | 1986-04-09 | 1989-02-21 | Bayer Aktiengesellschaft | Process for preparing 1-deoxynojirimycin and N-derivatives thereof |
US4994572A (en) | 1989-10-12 | 1991-02-19 | Monsanto Company | Synthesis of nojirimycin derivatives |
US5043273A (en) | 1989-08-17 | 1991-08-27 | Monsanto Company | Phosphorylated glycosidase inhibitor prodrugs |
US5103008A (en) | 1989-08-17 | 1992-04-07 | Monsanto Company | Compound, N-butyl-deoxynojirimycin-6-phosphate |
US5200523A (en) | 1990-10-10 | 1993-04-06 | Monsanto Company | Synthesis of nojirimycin derivatives |
US5622972A (en) | 1994-02-25 | 1997-04-22 | G. D. Searle & Co. | Method for treating a mammal infected with respiratory syncytial virus |
WO2006077427A2 (en) | 2005-01-21 | 2006-07-27 | Mnl Pharma Limited | Antiviral drug combinations |
US20070275998A1 (en) | 2006-05-24 | 2007-11-29 | Butters Terry D | Deoxynojirimycin and d-arabinitol analogs and methods of using |
US20080138351A1 (en) | 2006-08-02 | 2008-06-12 | United Therapeutics Corporation | Liposome treatment of viral infections |
Family Cites Families (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1555654A (en) * | 1977-06-25 | 1979-11-14 | Exxon Research Engineering Co | Agricultural burner apparatus |
NO154918C (en) * | 1977-08-27 | 1987-01-14 | Bayer Ag | ANALOGUE PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE DERIVATIVES OF 3,4,5-TRIHYDROXYPIPERIDINE. |
DE2839309A1 (en) * | 1978-09-09 | 1980-03-27 | Bayer Ag | 3,4,5-TRIHYDROXYPIPERIDINE DERIVATIVES |
US5030638A (en) * | 1990-02-26 | 1991-07-09 | G. D. Searle & Co. | Method of antiviral enhancement |
US5206251A (en) * | 1992-04-01 | 1993-04-27 | G. D. Searle & Co. | 2- and 3- amino and azido derivatives of 1,5-iminosugars |
US5399567A (en) * | 1993-05-13 | 1995-03-21 | Monsanto Company | Method of treating cholera |
US6465487B1 (en) * | 1997-12-11 | 2002-10-15 | Synergy Pharmaceuticals, Inc. | Inhibition of membrane-associated viral replication |
US6809083B1 (en) | 1998-02-12 | 2004-10-26 | Richard A. Mueller | Use of N-substituted-1, 5-dideoxy-1, 5-imino-D-glucitol compounds for treating hepatitis virus infections |
EP1714676A3 (en) | 1998-02-12 | 2006-11-15 | G.D. Searle LLC. | Use of N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds for treating hepatitis virus infections |
US6689759B1 (en) * | 1998-02-12 | 2004-02-10 | G. D. Searle & Co. | Methods of Treating hepatitis virus infections with N-substituted-1,5-dideoxy-1,5-imino-d-glucitol compounds in combination therapy |
US6610703B1 (en) | 1998-12-10 | 2003-08-26 | G.D. Searle & Co. | Method for treatment of glycolipid storage diseases |
GB9828474D0 (en) * | 1998-12-24 | 1999-02-17 | British Aerospace | Surface topology inspection |
US6545021B1 (en) * | 1999-02-12 | 2003-04-08 | G.D. Searle & Co. | Use of substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds for treating hepatitis virus infections |
GB0100889D0 (en) * | 2001-01-12 | 2001-02-21 | Oxford Glycosciences Uk Ltd | Compounds |
CA2378776A1 (en) * | 1999-07-26 | 2001-02-01 | G.D. Searle & Co. | Use of long-chain n-alkyl derivatives of deoxynojirimycin and a glucocerebrosidase enzyme for the manufacture of medicament for the treatment of glycolipid storage diseases |
US7256005B2 (en) * | 1999-08-10 | 2007-08-14 | The Chancellor, Masters And Scholars Of The University Of Oxford | Methods for identifying iminosugar derivatives that inhibit HCV p7 ion channel activity |
PT2441467E (en) * | 2003-01-31 | 2015-10-12 | Sinai School Medicine | Combination therapy for treating protein deficiency disorders |
US7446098B2 (en) * | 2003-02-18 | 2008-11-04 | Mount Sinai School Of Medicine Of New York University | Combination therapy for treating protein deficiencies |
US7135575B2 (en) * | 2003-03-03 | 2006-11-14 | Array Biopharma, Inc. | P38 inhibitors and methods of use thereof |
US20060211752A1 (en) | 2004-03-16 | 2006-09-21 | Kohn Leonard D | Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression |
US20050256168A1 (en) * | 2004-04-28 | 2005-11-17 | Block Timothy M | Compositions for oral administration for the treatment of interferon-responsive disorders |
US7524829B2 (en) * | 2004-11-01 | 2009-04-28 | Avi Biopharma, Inc. | Antisense antiviral compounds and methods for treating a filovirus infection |
EP2058004A1 (en) * | 2005-03-16 | 2009-05-13 | University of Oxford | Mannose immunogens for HIV-1 |
EP3441090A1 (en) * | 2005-05-17 | 2019-02-13 | Amicus Therapeutics, Inc. | A method for the treatment of pompe disease using 1-deoxynojirimycin and derivatives |
EP1909812A4 (en) * | 2005-07-27 | 2009-11-25 | Univ Florida | Small compounds that correct protein misfolding and uses thereof |
NZ565954A (en) * | 2005-07-27 | 2012-03-30 | Univ Florida | Use of heat shock inducing compound and an agent that increases stem cell mobilization int he manufacture of a medicament to treat ocular disease |
US20070244184A1 (en) * | 2006-01-09 | 2007-10-18 | Simon Fraser University | Glycosidase inhibitors and methods of synthesizing same |
EP2010551B1 (en) * | 2006-04-24 | 2010-09-01 | Academisch Medisch Centrum | Improved treatment of cystic fibrosis |
JP2010510171A (en) * | 2006-08-21 | 2010-04-02 | ユナイテッド セラピューティクス コーポレーション | Combination therapy for the treatment of viral infections |
WO2008068548A1 (en) | 2006-12-08 | 2008-06-12 | Institut Necker | Use of inhibitors of the glycosylation process for the prevention and treatment of genetic diseases |
KR20100127842A (en) * | 2008-03-26 | 2010-12-06 | 유니버시티 오브 옥스퍼드 | Endoplasmic reticulum targeting liposomes |
WO2010027996A1 (en) * | 2008-09-02 | 2010-03-11 | Institute For Hepatitis And Virus Research | Novel imino sugar derivatives demonstrate potent antiviral activity and reduced toxicity |
EP2410989A2 (en) * | 2009-03-27 | 2012-02-01 | The Chancellor, Masters and Scholars of the University of Oxford | Cholesterol level lowering liposomes |
CA2765086C (en) * | 2009-06-12 | 2015-12-15 | United Therapeutics Corporation | Iminosugars and methods of treating bunyaviral and togaviral diseases |
-
2010
- 2010-06-11 CA CA2765086A patent/CA2765086C/en not_active Expired - Fee Related
- 2010-06-11 KR KR1020127000433A patent/KR101463661B1/en not_active IP Right Cessation
- 2010-06-11 JP JP2012515167A patent/JP5634510B2/en not_active Expired - Fee Related
- 2010-06-11 WO PCT/US2010/038247 patent/WO2010144759A1/en active Application Filing
- 2010-06-11 ES ES10786885.3T patent/ES2524361T3/en active Active
- 2010-06-11 US US12/813,882 patent/US8426445B2/en not_active Expired - Fee Related
- 2010-06-11 CN CN201080033499.6A patent/CN102639133B/en not_active Expired - Fee Related
- 2010-06-11 EP EP10786885.3A patent/EP2440205B1/en not_active Not-in-force
-
2013
- 2013-02-07 US US13/761,583 patent/US8748460B2/en not_active Expired - Fee Related
Patent Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4246345A (en) | 1978-08-03 | 1981-01-20 | Bayer Aktiengesellschaft | Process for the production of 6-amino-6-deoxy-L-sorbose |
US4266025A (en) | 1978-12-12 | 1981-05-05 | Bayer Aktiengesellschaft | Production of N-substituted derivatives of 1-desoxy-nojirimycin |
US4405714A (en) | 1980-10-15 | 1983-09-20 | Bayer Aktiengesellschaft | Production of N-substituted derivatives of 1-desoxynojirimicin |
US4806650A (en) | 1986-04-09 | 1989-02-21 | Bayer Aktiengesellschaft | Process for preparing 1-deoxynojirimycin and N-derivatives thereof |
US5043273A (en) | 1989-08-17 | 1991-08-27 | Monsanto Company | Phosphorylated glycosidase inhibitor prodrugs |
US5103008A (en) | 1989-08-17 | 1992-04-07 | Monsanto Company | Compound, N-butyl-deoxynojirimycin-6-phosphate |
US4994572A (en) | 1989-10-12 | 1991-02-19 | Monsanto Company | Synthesis of nojirimycin derivatives |
US5200523A (en) | 1990-10-10 | 1993-04-06 | Monsanto Company | Synthesis of nojirimycin derivatives |
US5622972A (en) | 1994-02-25 | 1997-04-22 | G. D. Searle & Co. | Method for treating a mammal infected with respiratory syncytial virus |
WO2006077427A2 (en) | 2005-01-21 | 2006-07-27 | Mnl Pharma Limited | Antiviral drug combinations |
US20070275998A1 (en) | 2006-05-24 | 2007-11-29 | Butters Terry D | Deoxynojirimycin and d-arabinitol analogs and methods of using |
US20080138351A1 (en) | 2006-08-02 | 2008-06-12 | United Therapeutics Corporation | Liposome treatment of viral infections |
Non-Patent Citations (2)
Title |
---|
BERGE ET AL., J. PHARM. SCI., vol. 66, 1977, pages 1 - 18 |
See also references of EP2440205A4 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102875450A (en) * | 2012-10-25 | 2013-01-16 | 上海丝绸集团股份有限公司 | Technological method for extracting 1-deoxynojirimycin from mulberry leaf |
WO2016073652A1 (en) * | 2014-11-05 | 2016-05-12 | Unither Virology, Llc | Iminosugars useful for the treatment of viral diseases |
US10428022B2 (en) | 2014-11-05 | 2019-10-01 | Emergent Virology Llc | Iminosugars useful for the treatment of viral diseases |
Also Published As
Publication number | Publication date |
---|---|
US8748460B2 (en) | 2014-06-10 |
CA2765086A1 (en) | 2010-12-16 |
KR20120038960A (en) | 2012-04-24 |
US20130150405A1 (en) | 2013-06-13 |
US8426445B2 (en) | 2013-04-23 |
KR101463661B1 (en) | 2014-11-19 |
JP2012530061A (en) | 2012-11-29 |
ES2524361T3 (en) | 2014-12-05 |
EP2440205A1 (en) | 2012-04-18 |
CN102639133A (en) | 2012-08-15 |
EP2440205B1 (en) | 2014-08-27 |
US20100317696A1 (en) | 2010-12-16 |
CA2765086C (en) | 2015-12-15 |
EP2440205A4 (en) | 2013-04-24 |
CN102639133B (en) | 2015-03-11 |
JP5634510B2 (en) | 2014-12-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2765086C (en) | Iminosugars and methods of treating bunyaviral and togaviral diseases | |
EP2473046B1 (en) | Iminosugars for their use in the treatment of filoviral diseases | |
US9943532B2 (en) | Iminosugars and methods of treating viral diseases | |
EP2400843B1 (en) | Iminosugars and methods of treating arenaviral infections | |
CA2772875A1 (en) | Methods of treating orthomyxoviral infections |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 201080033499.6 Country of ref document: CN |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 10786885 Country of ref document: EP Kind code of ref document: A1 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2765086 Country of ref document: CA Ref document number: 2012515167 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2010786885 Country of ref document: EP |
|
ENP | Entry into the national phase |
Ref document number: 20127000433 Country of ref document: KR Kind code of ref document: A |