RU2332999C2 - Therapeutic methods and applications of sapogenins and derivatives thereof - Google Patents

Therapeutic methods and applications of sapogenins and derivatives thereof Download PDF

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RU2332999C2
RU2332999C2 RU2004130281/15A RU2004130281A RU2332999C2 RU 2332999 C2 RU2332999 C2 RU 2332999C2 RU 2004130281/15 A RU2004130281/15 A RU 2004130281/15A RU 2004130281 A RU2004130281 A RU 2004130281A RU 2332999 C2 RU2332999 C2 RU 2332999C2
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pharmaceutically acceptable
acceptable salts
glucose
disease
smilagenin
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RU2004130281A (en
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Дарэл РИС
Фил Ганнинг
Антония Орси
Зонгкин Ксиа
Яар ХУ
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ФИТОФАРМ ПиЭлСи
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    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K31/655—Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
    • 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
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • 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
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • C07J71/0005—Oxygen-containing hetero ring
    • 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

Abstract

The invention discloses therapeutic methods and uses of certain steroidal sapogenins, related compounds and derivatives thereof, in the treatment of non-cognitive neurodegeneration, non-cognitive neuromuscular degeneration, motor-sensory neurodegeneration or receptor dysfunction or loss in the absence of cognitive, neural and neuromuscular impairment.

Description

Текст описания приведен в факсимильном виде.

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The text of the description is given in facsimile form.
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Claims (3)

1. Применение активного средства, которое выбирают из соединений общей формулы Ia:1. The use of an active agent that is selected from compounds of general formula Ia:
Figure 00000049
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 где группу R выбирают из атома водорода, алкилкарбонил-, алкоксикарбонил-, алкилкарбамоил- или арилкарбонилгруппы или сульфогруппы (HO3S); фосфоногруппы ((НО)2Р(О)-); или моно-, ди- или трисахарида, где алкилгруппу возможно замещают арил-, амино-, моно- или диалкиламиногруппой, остатком карбоновой кислоты (-СООН) или комбинацией их; иwhere the R group is selected from a hydrogen atom, an alkylcarbonyl, alkoxycarbonyl, alkylcarbamoyl or arylcarbonyl group or sulfo group (HO 3 S); phosphono groups ((HO) 2 P (O) -); or a mono-, di- or trisaccharide, wherein the alkyl group is optionally substituted with an aryl, amino, mono- or dialkylamino group, a carboxylic acid residue (—COOH), or a combination thereof; and всех их рацемических смесей, всех их фармацевтически приемлемых солей и всех их смесей и комбинацийall their racemic mixtures, all their pharmaceutically acceptable salts and all their mixtures and combinations в качестве активного компонента композиции для лечения какой-либо из следующих болезней у людей и животных, страдающих от или восприимчивых к депрессии, шизофрении, мышечной дистрофии, включая плечелопаточно-лицевую миопатию (FSH), мышечную дистрофию Дюшенна, мышечную дистрофию Беккера и мышечную дистрофию Бруца, дистрофию Фука, миотоническую дистрофию, корнеальную дистрофию, рефлекторный синдром симпатической дистрофии (reflex sympathetic dystrophy syndrome, RSDSA), нейроваскулярную дистрофию, болезнь Хантингтона; мотонейронному заболеванию, включая боковой амиотрофической склероз (amyotrophic lateral sclerosis, ALS), травматической нейродегенерации, например последующий удар или последующую травму (например, травматическое повреждение головы или повреждение спинного мозга), болезнь Баттена, синдром Коккейна, синдром Дауна, кортикобазальную ганглионарную дегенерацию, множественную системную атрофию, церебральную атрофию, множественную системную атрофию, церебральную атрофию, оливопонтоцеребеллярную атрофию, дентаторубральную атрофию, паллидолуизианскую атрофию, спинобульбарную атрофию; ретробульбарному невриту, подострому склерозирующему панэнцефалиту (sclerosing panencephalitis, SSPE), расстройству недостаточности внимания, поствирусному энцефалиту, постполиомиелитному синдрому, синдрому Фара, синдрому Юберта, синдрому Гийена-Барре, лиссэнцефалии, болезни Моямоа, нейронным миграционным расстройствам, полиглутаминовой болезни, болезни Ниманна-Пика, прогрессирующей многоочаговой лейкодистрофии, ложной опухоли мозжечка, болезни Рефсума, синдрому Целлвегера, супрануклеарному параличу, наследственной атаксии Фридрейха, спиромозжечковой атаксии 2 типа, синдрому Ретта, синдрому Шая-Дрейджера, туберозному склерозу, болезни Пика, заболеванию нервной системы, включая наследственное заболевание нервной системы, диабетическую нейропатию и митотическую нейропатию, "prion-based" нейродегенерации, включая болезнь Крейтцфельдта-Якоба (Creutzfeldt-Jakob, CJD), вариант CJD, новый вариант CJD, бычью губкообразную энцефалопатию (bovine spongiform encephalopathy, BSE), GSS, FFI, куру и синдром Адлера; болезни Джозефа, острому рассеянному энцефаломиелиту, арахноидиту, сосудистым поражениям центральной нервной системы, потери нейронной функции конечности, болезни Шарко-Мари-Тута, восприимчивости к сердечной недостаточности и дегенерации желтого пятна.as an active component of a composition for treating any of the following diseases in humans and animals suffering from or susceptible to depression, schizophrenia, muscular dystrophy, including shoulder-facial-myopathy (FSH), Duchenne muscular dystrophy, Becker muscular dystrophy, and Bruz muscular dystrophy Fook's dystrophy, myotonic dystrophy, corneal dystrophy, reflex sympathetic dystrophy syndrome (RSDSA), neurovascular dystrophy, Huntington's disease; motor neuronal disease, including amyotrophic lateral sclerosis (ALS), traumatic neurodegeneration, for example a subsequent stroke or subsequent trauma (for example, traumatic head injury or spinal cord injury), Butten's disease, Cockney syndrome, Down syndrome, corticobasal ganglion degeneration systemic atrophy, cerebral atrophy, multiple systemic atrophy, cerebral atrophy, olivopontocerebellar atrophy, dentorothoracic atrophy, pallidoloisian trophy, spinobulbar atrophy; retrobulbar neuritis, subacute sclerosing panencephalitis (SSPE), attention deficit disorder, post-viral encephalitis, post-poliomyelitis syndrome, Farah syndrome, Hubert syndrome, Guillain-Barré syndrome, lissencephaloma, polymorrhea disease, Moylamo disease, Moyoma disease , progressive multifocal leukodystrophy, a cerebellar pseudotumor, Refsum disease, Zellweger syndrome, supranuclear palsy, hereditary Friedreich ataxia, spirochromism type 2 ataxia, Rett syndrome, Shay-Drager syndrome, tuberous sclerosis, Peak disease, nervous system disease, including hereditary nervous system disease, diabetic neuropathy and mitotic neuropathy, "prion-based" neurodegeneration, including Creutzfeldt-Jakob Creut disease Jakob, CJD), variant CJD, new variant CJD, bovine spongiform encephalopathy (bovine spongiform encephalopathy, BSE), GSS, FFI, Kuru and Adler's syndrome; Joseph's disease, acute disseminated encephalomyelitis, arachnoiditis, vascular lesions of the central nervous system, loss of neural function of the limb, Charcot-Marie-Tooth disease, susceptibility to heart failure and macular degeneration. 2. Применение по п.1, в котором одно или несколько соединений выбирают из:2. The use according to claim 1, in which one or more compounds are selected from: сарсасапогенина;sarsasapogenin; сарсасапогенина катилата;sarsasapogenin catilate; сарсасапогенина ацетата;sarsasapogenin acetate; сарсасапогенина сукцината и его фармацевтически приемлемых солей;sarsasapogenin succinate and its pharmaceutically acceptable salts; сарсасапогенина глицината и его фармацевтически приемлемых солей;sarsasapogenin glycinate and its pharmaceutically acceptable salts; сарсасапогенина аланината и его фармацевтически приемлемых солей;sarsasapogenin alaninate and its pharmaceutically acceptable salts; сарсасапогенина валината и его фармацевтически приемлемых солей;sarsasapogenin valinate and its pharmaceutically acceptable salts; сарсасапогенина фенилаланината и его фармацевтически приемлемых солей;sarsasapogenin phenylalaninate and its pharmaceutically acceptable salts; сарсасапогенина изолейцината и его фармацевтически приемлемых солей;sarsasapogenin isoleucine and its pharmaceutically acceptable salts; сарсасапогенина метионината и его фармацевтически приемлемых солей;sarsasapogenin methioninate and its pharmaceutically acceptable salts; эписарсасапогенина;episarsasapogenin; эписарсасапогенина катилата;episarsasapogenin catilate; эписарсасапогенина ацетата;episarsasapogenin acetate; эписарсасапогенина сукцината и его фармацевтически приемлемых солей;episarsasapogenin succinate and its pharmaceutically acceptable salts; эписарсасапогенина глицината и его фармацевтически приемлемых солей;Epiparsasapogenin glycinate and its pharmaceutically acceptable salts; эписарсасапогенина аланината и его фармацевтически приемлемых солей;episarsasapogenin alaninate and its pharmaceutically acceptable salts; эписарсасапогенина валината и его фармацевтически приемлемых солей;episarsasapogenin valinate and its pharmaceutically acceptable salts; эписарсасапогенина фенилаланината и его фармацевтически приемлемых солей;episarsasapogenin phenylalaninate and its pharmaceutically acceptable salts; эписарсасапогенина изолейцината и его фармацевтически приемлемых солей;episarsasapogenin isoleucine and its pharmaceutically acceptable salts; эписарсасапогенина метионината и его фармацевтически приемлемых солей;episarsasapogenin methioninate and its pharmaceutically acceptable salts; смилагенина;smilagenin; смилагенина катилата;smilagenin catylate; смилагенина ацетата;smilagenin acetate; смилагенина сукцината и его фармацевтически приемлемых солей;smilagenin succinate and its pharmaceutically acceptable salts; смилагенина глицината и его фармацевтически приемлемых солей;smilagenin glycinate and its pharmaceutically acceptable salts; смилагенина аланината и его фармацевтически приемлемых солей;smilagenin alaninate and its pharmaceutically acceptable salts; смилагенина валината и его фармацевтически приемлемых солей;smilagenin valinate and its pharmaceutically acceptable salts; смилагенина фенилаланината и его фармацевтически приемлемых солей;smilagenin phenylalaninate and its pharmaceutically acceptable salts; смилагенина изолейцината и его фармацевтически приемлемых солей;smilagenin isoleucinate and its pharmaceutically acceptable salts; смилагенина метионината и его фармацевтически приемлемых солей;smilagenin methioninate and its pharmaceutically acceptable salts; эписмилагенина;epismilagenin; эписмилагенина катилата;Epismilagenin Catylate; эписмилагенина ацетата;epismilagenin acetate; эписмилагенина сукцината и его фармацевтически приемлемых солей;Epismilagenin Succinate and its pharmaceutically acceptable salts; эписмилагенина глицината и его фармацевтически приемлемых солей;epismilagenin glycinate and its pharmaceutically acceptable salts; эписмилагенина аланината и его фармацевтически приемлемых солей;epismilagenin alaninate and its pharmaceutically acceptable salts; эписмилагенина валината и его фармацевтически приемлемых солей;Epismilagenin Valinate and its pharmaceutically acceptable salts; эписмилагенина фенилаланината и его фармацевтически приемлемых солей;epismilagenin phenylalaninate and its pharmaceutically acceptable salts; эписмилагенина изолейцината и его фармацевтически приемлемых солей;epismilagenin isoleucinate and its pharmaceutically acceptable salts; эписмилагенина метионината и его фармацевтически приемлемых солей;epismilagenin methioninate and its pharmaceutically acceptable salts; сапониновых производных сарсасапогенина, эписарсасапогенина, смилагенина и эписмилагенина, в которых в каждом случае атом углерода в 3-м положении содержит О-углеводный остаток, где углеводный остаток выбирают из глюкозы, маннозы, фруктозы, галактозы, мальтозы, целлобиозы, сахарозы, рамнозы, ксилозы, арабинозы, фукозы, хиновозы, апиозы, лактозы, галактозы-глюкозы, глюкозы-арабинозы, фукозы-глюкозы, рамнозы-глюкозы, глюкозы-глюкозы-глюкозы, глюкозы-рамнозы, маннозы-глюкозы, глюкозы-(рамнозы)-глюкозы, глюкозы-(рамнозы)-рамнозы, глюкозы-(глюкозы)-глюкозы, галактозы-(рамнозы)-галактозы;saponin derivatives of sarsasapapogenin, episarsasapogenin, smilagenin and epismilagenin, in which in each case the carbon atom in the 3rd position contains an O-carbohydrate residue, where the carbohydrate residue is selected from glucose, mannose, fructose, galactose, maltose, cellobiose, sucrose, ramnose, k , arabinose, fucose, quinose, apiosis, lactose, galactose-glucose, glucose-arabinose, fucose-glucose, rhamnose-glucose, glucose-glucose-glucose, glucose-rhamnose, mannose-glucose, glucose- (rhamnose) -glucose, glucose - (ramnose) -ramnose, glucose- (glucose ) -glucose, galactose- (ramnose) -galactose; и их фармацевтически приемлемых солей.and their pharmaceutically acceptable salts. 3. Применение по п.2, в котором одно или несколько соединений выбирают из сарсасапогенина и смилагенина.3. The use according to claim 2, in which one or more compounds is selected from sarsasapogenin and smilagenin.
RU2004130281/15A 2002-03-27 2003-03-27 Therapeutic methods and applications of sapogenins and derivatives thereof RU2332999C2 (en)

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Application Number Priority Date Filing Date Title
ARP020101170 2002-03-27
ARP020101170A AR033079A1 (en) 2001-03-28 2002-03-27 SAPOGENINE DERIVATIVES, SYNTHESIS AND USE, AND METHODS BASED ON USE
US36817802P 2002-03-28 2002-03-28
US60/368178 2002-03-28
GBPCT/GB02/01578 2002-03-28
PCT/GB2002/001578 WO2002079221A2 (en) 2001-03-28 2002-03-28 Sapogenin derivatives, their synthesis and use

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