JPH07503252A - Method for delaying HIV-induced AIDS by administration of substituted azasperane compounds - Google Patents
Method for delaying HIV-induced AIDS by administration of substituted azasperane compoundsInfo
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- JPH07503252A JPH07503252A JP5513407A JP51340793A JPH07503252A JP H07503252 A JPH07503252 A JP H07503252A JP 5513407 A JP5513407 A JP 5513407A JP 51340793 A JP51340793 A JP 51340793A JP H07503252 A JPH07503252 A JP H07503252A
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
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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
- A61K31/33—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
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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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
- A61K31/33—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
- A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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- 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
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- 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
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- 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
- A61P37/04—Immunostimulants
Abstract
(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。 (57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】 置換アザスペラン化合物投与によるHIV誘発エイズ遅延方法本発明は、ヒト免 疫不全ウィルス(HI V)血清陽性のヒトにおける後天性免疫不全症候群(エ イズ)の発症を予防または遅延する方法であって、有効量の置換アザスピランを かかるヒトに投与することからなる方法に関する。[Detailed description of the invention] Method for delaying HIV-induced AIDS by administration of substituted azasperane compounds The present invention provides Acquired immunodeficiency syndrome in HIV-seropositive humans A method for preventing or delaying the onset of cancer, comprising administering an effective amount of a substituted azaspiran. A method comprising administering to such a human.
発明の背景 免疫抑制/免疫調節剤の使用により、ウィルス複製が抑制されることが示されて いる。特に、免疫調節性CD8リンパ球は、末梢血単核細胞におけるHIV複製 を抑制することが示されており(ウォルタ−(falter)ら、サイエンス( Science)第234巻、1563〜1566頁(1986年))、活性化 CD8千T細胞は、無症候性HIV血清陽性個体由来のCDJ+細胞の培養にお いてHIVeI製を阻害することが示されている(ブリンチマン(Brinct ++*an)ら、CD8+T細胞、ジャーナル・オブ・イミュノロジー(J、 I+uuno1. )第144巻、3961〜2966頁(1990年))。さ らに、免疫抑制化合物シクロスポリンA(Cs A)は、数種の動物のウィルス 感染モデルにおいて防御効果を示した。とりわけ、LP−8M5ネズミ・白血病 ウィルスでの感染前および後におけるCsAでの慢性的症状の治療が、免疫不全 疾患の進行に対して有効であることがわかった(サー二一、エイ(Cerny、 ^、)ら、ヨーロピアン・ジャーナル・オブ・イミュノロジ−(Eur、 J、 Immunol、 )第21巻:1747〜1750頁(1991年))。Background of the invention The use of immunosuppressive/immunomodulatory agents has been shown to suppress viral replication. There is. In particular, immunoregulatory CD8 lymphocytes are involved in HIV replication in peripheral blood mononuclear cells. have been shown to inhibit (Falter et al., Science ( Science) Vol. 234, pp. 1563-1566 (1986)), Activation CD8,000 T cells are used in cultures of CDJ+ cells from asymptomatic HIV-seropositive individuals. has been shown to inhibit HIVeI production (Brinct). ++*an) et al., CD8+ T cells, Journal of Immunology (J, I+uuno1. ) Vol. 144, pp. 3961-2966 (1990)). difference Additionally, the immunosuppressive compound cyclosporine A (CsA) has been shown to be effective against several animal viruses. It showed protective effects in infection models. Among others, LP-8M5 murine leukemia Treatment of chronic symptoms with CsA before and after infection with the virus may lead to immunodeficiency. It was found to be effective against the progression of the disease (Cerny, ^, ) et al., European Journal of Immunology (Eur, J. Immunol, Volume 21: 1747-1750 (1991)).
CsAでのエイズおよびHIV−血清陽性非エイズ患者の治療がT4細胞を増加 させ、リンパ腺症を抑制するという証拠も報告されている(アンドリュー(^n drieu)ら、クリニカル・イミュノロジー・アンド・イミュノバソロジー( CIin、 Imn+uno1. and Immunopathol、)第4 6巻:181−198頁(1988年))。Treatment of AIDS and HIV-seropositive non-AIDS patients with CsA increases T4 cells There is also evidence that it suppresses lymphadenopathy (Andrew (^n drieu) et al., Clinical Immunology and Immunobathology ( CIin, Imn+uno1. and Immunopathol,) 4th 6:181-198 (1988)).
パンジー? −(Badger)らの米国特許第4.963.557号(バッジ +−1)l:は、式 [式中、nは3〜7;mは1または2;R’およびR1は同じまたは異なり、水 素または直鎖あるいは分枝鎖アルキルから選択されるか(ただし、R1およびR 2に含まれる総炭素数は合わせて5〜10);またはR+およびR1は一緒にな って3〜7個の炭素原子を有する環式アルキル基を形成し、R1およびR4は同 じまたは異なり、水素または1〜3個の炭素原子を有する直鎖アルキルから選択 されるか;またはR3およびR4は窒素原子と一緒になって5〜8個の原子を有 する複素環を形成する] で示される化合物またはその医薬上許容される塩あるいは水和物もしくは溶媒和 物が開示されている。pansy? - (Badger) et al. U.S. Patent No. 4.963.557 (Badger) +-1) l: is the formula [where n is 3 to 7; m is 1 or 2; R' and R1 are the same or different, and water selected from plain or straight chain or branched alkyl (with the proviso that R1 and R The total number of carbon atoms contained in 2 is 5 to 10); or R+ and R1 are together form a cyclic alkyl group having 3 to 7 carbon atoms, and R1 and R4 are the same. same or different, selected from hydrogen or straight-chain alkyl having 1 to 3 carbon atoms or R3 and R4 together with the nitrogen atom have 5 to 8 atoms; ] A compound represented by or a pharmaceutically acceptable salt, hydrate or solvate thereof things are disclosed.
バラジャ−■には、式(1)の化合物が、サプレッサー細胞の活性を刺激するこ とにより特徴づけられる免疫調節効果を誘導する新規クラスの化合物として開示 されている。In Baraja-■, the compound of formula (1) stimulates the activity of suppressor cells. Disclosed as a novel class of compounds that induce immunomodulatory effects characterized by has been done.
バラジャ−■には、式(1)の化合物が、HIV血清陽性のヒトにおけるエイズ 発症を予防または遅延させるための薬剤としては記載されていない。Varaja-■ contains a compound of formula (1) that is effective against AIDS in HIV-seropositive humans. It is not listed as a drug to prevent or delay onset.
発明の概要 本発明は、ヒト免疫不全ウィルス(HIV)血清陽性のヒトにおけるエイズ発症 を予防または遅延する方法であって、有効量の式:[式中、nは3〜7; mは1または2: R1およびR1は同じまたは異なり、水素または直鎖あるいは分枝鎖アルキルか ら選択されるか(ただし、R1およびR1に含まれる総炭素数は合わせて5〜1 0);またはR+およびR1は一緒になって3〜7個の炭素原子を有する環式ア ルキル基を形成し; R3およびR4は同じまたは異なり、水素または1〜3個の炭素原子を有する直 鎖アルキルから選択されるか;またはR3およびR4は窒素原子と一緒になって 5〜8個の原子を有する複素環を形成する]で示される化合物またはその医薬上 許容される塩あるいは水和物もしくは溶媒和物をかかるヒトに投与することから なる方法に関する。Summary of the invention The present invention relates to the development of AIDS in human immunodeficiency virus (HIV) seropositive humans. A method for preventing or delaying an effective amount of the formula: [wherein n is 3 to 7; m is 1 or 2: R1 and R1 are the same or different and are hydrogen or straight or branched alkyl; (However, the total number of carbon atoms contained in R1 and R1 is 5 to 1 in total. 0); or R+ and R1 together represent a cyclic atom having 3 to 7 carbon atoms; forming a rukyl group; R3 and R4 are the same or different and are hydrogen or straight having 1 to 3 carbon atoms. chain alkyl; or R3 and R4 taken together with the nitrogen atom Forming a heterocycle having 5 to 8 atoms] or its pharmaceutical composition from administering an acceptable salt or hydrate or solvate to such a person. Concerning how to become.
式(1)のすべての化合物およびその医薬上許容される塩、水和物および溶媒和 物の製造が、米国特許第4.963,557号に開示されており、その全開示を 出典明示により本明細書に一体化させる。All compounds of formula (1) and their pharmaceutically acceptable salts, hydrates and solvates The manufacture of products is disclosed in U.S. Pat. No. 4,963,557, the full disclosure of which It is incorporated herein by reference.
当該新規方法に用いる好ましい化合物は、R1およびR2がプロピル、R3およ びR4がメチル、mが1、rlが3である式(I)の化合物の2塩酸塩(N、N −ジメチル−8,8−ジプロピル−2−アザスピロ[4,5]デカン−2−プロ パンアミン2塩酸塩)である。Preferred compounds for use in the new method are those in which R1 and R2 are propyl, R3 and and R4 is methyl, m is 1 and rl is 3, dihydrochloride (N, N -dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2-pro panamine dihydrochloride).
該新規方法に用いる好ましい化合物は、R1およびR2がプロピル、R3および R4がエチル、mが1、nが3である式(1)の化合物(N、N−ノエチル−8 ゜8−ジプロピル−2−アザスピロ[4,5]デカン−2−プロパンアミン)お よびその塩である。Preferred compounds for use in the new method are those in which R1 and R2 are propyl, R3 and A compound of formula (1) in which R4 is ethyl, m is 1, and n is 3 (N,N-noethyl-8 ゜8-dipropyl-2-azaspiro[4,5]decane-2-propanamine) and its salt.
本発明は、式(1)の化合物およびその医薬上許容される塩あるいは水和物もし くは溶媒和物を、HIV血清陽性のヒトにおけるエイズ発症予防または遅延に有 用なものとして開示する。The present invention provides compounds of formula (1) and pharmaceutically acceptable salts or hydrates thereof. or solvates may be useful in preventing or delaying the onset of AIDS in HIV-seropositive humans. Disclosed as useful.
本発明は、HTV血清陽性のヒトに、有効量の式([)の化合物またはその医薬 上許容される塩あるいは水和物もしくは溶媒和物を投与することからなる、エイ ズ発症遅延または予防力に関する。式(I)の化合物またはその医薬上許容され る塩あるいは水和物もしくは溶媒和物を慣用的な医薬上許容される担体または希 釈剤と既知の方法(例えばバージー(I)、米国特許第4,963.557号記 載の方法)にしたがって混合することにより製造される慣用的服用形態として、 かかるヒトに式(1)の化合物またはその医薬上許容される塩あるいは水和物も しくは溶媒和物を投与することができる。The present invention provides for administering an effective amount of a compound of formula ([) or a pharmaceutical thereof to HTV seropositive humans. the administration of an acceptable salt or hydrate or solvate. Regarding the delay in the onset of cancer or the ability to prevent it. A compound of formula (I) or a pharmaceutically acceptable compound thereof salts or hydrates or solvates in conventional pharmaceutically acceptable carriers or diluted carriers. diluents and known methods (e.g. Virgie (I), U.S. Pat. No. 4,963,557). As a conventional dosage form prepared by mixing according to the method described in The compound of formula (1) or a pharmaceutically acceptable salt or hydrate thereof may also be administered to such humans. Alternatively, solvates can be administered.
医薬上許容される担体または希釈剤の形態および性質は、それが混合される活性 成分の量、投与経路およびよ(知られた池の変数により決定されることが当業者 筒より理解されよう。式(1)の化合物またはその医薬上許容される塩あるいは 水和物もしくは溶媒和物の十分量をHIV血清陽性のヒトに投与してエイズ発症 を予防または遅延する。The form and nature of the pharmaceutically acceptable carrier or diluent will dictate the activity with which it is mixed. Those skilled in the art will determine the amount of ingredients, route of administration, and other known variables. It will be better understood than the tube. A compound of formula (1) or a pharmaceutically acceptable salt thereof or Administering sufficient amounts of hydrates or solvates to HIV-seropositive humans to develop AIDS. prevent or delay
式(1)の化合物の投与経路は厳密なものではないが、通常は、経口または非経 口、好ましくは経口である。Although the route of administration of the compound of formula (1) is not critical, it is usually administered orally or parenterally. Orally, preferably orally.
本明細書に用いる非経口なる語は、静脈内、筋肉内、皮下、鼻腔内、直腸内、経 皮、膣内投与を包含する。非経口投与のうち皮下および筋肉内が一般的に好まし い。毎日の非経口投与規則は、好ましくは、約0.01mg/kg体重ないし約 10mg/kg体重であり、最も好ましくは約0.1mg/kg体重ないし約1 mg/kg体重である。好ましくは、個々の非経口服用単位は約0.1mgない し約100mgの量の活性成分を含有する。As used herein, the term parenteral refers to intravenous, intramuscular, subcutaneous, intranasal, intrarectal, intrarectal, Includes dermal and intravaginal administration. Of parenteral administration, subcutaneous and intramuscular are generally preferred. stomach. The daily parenteral administration regimen is preferably about 0.01 mg/kg body weight to about 10 mg/kg body weight, most preferably about 0.1 mg/kg body weight to about 1 mg/kg body weight. Preferably, each parenteral dosage unit is no more than about 0.1 mg. It contains an amount of active ingredient of about 100 mg.
経口的に投与した場合に活性のある式(1)の化合物を、液剤(例えばスシロッ プ、懸濁液またはエマルジョン)、錠剤、カプセル剤およびトローチ剤として処 方することができる。A compound of formula (1) which is active when administered orally can be administered in a liquid form (e.g. sushiro). tablets, capsules and lozenges); You can do it either way.
液剤処方は、一般的には、例えば、懸濁化剤、保存料、香料または着色剤を伴っ たエタノール、グリセリン、非水溶媒(例えばポリエチレングリコール)、油脂 、または水のごとき適当な液状担体中の該化合物または医薬上許容される塩の懸 濁液または溶液からなる。Liquid formulations typically include, for example, suspending agents, preservatives, flavoring or coloring agents. ethanol, glycerin, non-aqueous solvents (e.g. polyethylene glycol), fats and oils , or suspension of the compound or a pharmaceutically acceptable salt in a suitable liquid carrier such as water. Consists of a suspension or solution.
錠剤形態の組成物を、固形処方を製造するのに用いられるいがなる適当な担体を 用いても製造することができる。カプセル形態の組成物を、通常のカプセル被覆 法を用いて製造することができる。例えば、活性成分を含有する小丸薬を、標準 的な担体を用いて製造し、ついで、硬ゼラチンカプセルに充填することができる 。別法として、分散物または懸濁液を、いかなる適当な医薬上許容される担体( 例えば水性ガム、セルロース、シリケートまたは油脂)を用いても製造すること ができ、ついで、得られた分散物または懸濁液を軟ゼラチンカプセルに充填する こともできる。Compositions in tablet form can be prepared using any suitable carrier used to produce solid formulations. It can also be manufactured using The composition in capsule form is coated with a conventional capsule. It can be manufactured using a method. For example, small pills containing the active ingredient can be can be prepared using standard carriers and then filled into hard gelatin capsules. . Alternatively, the dispersion or suspension may be prepared in any suitable pharmaceutically acceptable carrier ( (e.g., water-based gums, cellulose, silicates, or fats and oils) The resulting dispersion or suspension is then filled into soft gelatin capsules. You can also do that.
毎日の経口服用規則は、好ましくは、約0.01mg/kg体重ないし約10m g/kg体重である。好ましくは、個々の経口服用単位は、約0.1mgないし 約100mgの量の活性成分を含有する。The daily oral dosing rule is preferably about 0.01 mg/kg body weight to about 10 m g/kg body weight. Preferably, each oral dosage unit contains between about 0.1 mg and Contains an amount of active ingredient of approximately 100 mg.
活性成分のみを投与することが可能であるが、医薬処方として提供するのが好ま しい。Although it is possible to administer the active ingredient alone, it is preferable to present it as a pharmaceutical formulation. Yes.
式(1)化合物またはその医薬上許容される塩あるいは水和物もしくは溶媒和物 の1回ごとの投薬の最適量および投薬間隔を、治療すべき症状の性質および程度 、投与の形態、経路および部位、そして治療すべき個々の患者により決定し、か かる最適量を慣用的方法により決定することができることが、当業者により理解 されよう。最適な治療コース(すなわち式(1)化合物またはその医薬上許容さ れる塩あるいは水和物もしくは溶媒和物の1日の投薬回数)および治療期間を、 慣用的な治療決定試験のコースを用いて当業者により決定されうろことも、当業 者により理解されよう。Compound of formula (1) or a pharmaceutically acceptable salt, hydrate or solvate thereof The optimal dose and interval for each dose of , the form, route and site of administration, and the individual patient being treated; It will be appreciated by those skilled in the art that such optimal amounts can be determined by conventional methods. It will be. the optimal course of treatment (i.e. the compound of formula (1) or its pharmaceutically acceptable the number of daily doses of the salt or hydrate or solvate) and the duration of treatment. Scales that can be determined by one of ordinary skill in the art using a routine course of treatment-determining tests are also within the skill of the art. be understood by those who
さらに、本発明化合物を、レトロウィルスのごときHIV血清陽性のヒトにおけ るエイズ発症の予防または遅延をすることが知られている他の既知化合物(商品 名シトプシン(以前はアジドチミンン(A Z T)と呼ばれた))のようなさ らなる活性成分と同時投与してもよい。。Additionally, the compounds of the present invention may be used in humans who are seropositive for HIV, such as retroviruses. other known compounds (commercial products) known to prevent or delay the onset of AIDS. Cytopsin (formerly known as azidothymine (AZT)) It may also be co-administered with other active ingredients. .
さらなる努力をすることなく、当業者は、以下の記載を用いて、本発明を最大限 に利用することができると確信する。それゆえ、以下の実施例は、単に説明的な ものであって、本発明の範囲をを同等限定するものではない。Without further elaboration, one skilled in the art can, using the following description, utilize the present invention to its fullest extent. I am confident that it can be used for Therefore, the following examples are merely illustrative. However, they are not intended to limit the scope of the present invention in the same way.
実施例1−カプセル組成物 標準的な2ピース硬ゼラチンカプセルに下表1に示す配合成分を充填することに より式(1)の化合物を投与するための軽口服用形態を製造した。Example 1 - Capsule composition A standard two-piece hard gelatin capsule is filled with the ingredients shown in Table 1 below. A light dosage form for administering the compound of formula (1) was prepared.
N、N−ジメチル−8,8−ジプロピル−2−25mgアザスピロ[4,5]デ カン−2−プロパンアミン2塩酸塩ラクトース 55mg タルク 16mg ステアリン酸マグネシウム 4mg 実施例2−注射可能な非経口組成物 ゛水中10重量%のプロピレングリコール 中で1.5重量%のN、N−ジメチル−8,8−ジプロピル−2−アザスピロ[ 4,5]デカン−2−プロパンアミン2塩酸塩を撹拌することにより式(1)の 化合物を投与するための注射可能な形態を製造した。N,N-dimethyl-8,8-dipropyl-2-25mg azaspiro[4,5]de Can-2-propanamine dihydrochloride lactose 55mg Talc 16mg Magnesium stearate 4mg Example 2 - Injectable parenteral composition 10% by weight propylene glycol in water 1.5% by weight of N,N-dimethyl-8,8-dipropyl-2-azaspiro[ By stirring 4,5]decane-2-propanamine dihydrochloride, the formula (1) can be obtained. An injectable form was prepared for administering the compound.
実施例3−錠剤組成物 下表IIに示すスクロース、硫酸カルシウム2水和物および式(1)の化合物を 10%ゼラチン溶液と混合し、ついで、顆粒化した。湿顆粒をふるいにかけ、圧 縮して錠剤にした。Example 3 - Tablet composition Sucrose, calcium sulfate dihydrate and the compound of formula (1) shown in Table II below were Mixed with 10% gelatin solution and then granulated. Sift the wet granules and press It was compressed and made into tablets.
表II 成分 量 N、N−ジエチルー8.8−ジプロピル−2−20mgアザスピロ[4,5]デ カン−2−プロパンアミン2塩酸塩硫酸カルシウム2水和物 30mg スクロース 4mg 澱粉 2mg タルク 1mg ステアリン酸 Q、5mg 上の記載および実施例により、本発明およびその好ましい具体例が十分に説明さ れるが、本発明は、以下の請求の範囲に包含される開示された特別な具体例に限 定されないことが理解される。Table II Ingredient amount N,N-diethyl-8,8-dipropyl-2-20mg azaspiro[4,5]de Can-2-propanamine dihydrochloride calcium sulfate dihydrate 30mg Sucrose 4mg Starch 2mg Talc 1mg Stearic acid Q, 5mg The above description and examples fully illustrate the invention and its preferred embodiments. However, the invention is limited to the particular embodiments disclosed that fall within the scope of the following claims. It is understood that this is not specified.
PCT/lJs93100730PCT/lJs93100730
Claims (18)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9201803.5 | 1992-01-28 | ||
GB929201803A GB9201803D0 (en) | 1992-01-28 | 1992-01-28 | Methods |
PCT/US1993/000730 WO1993014760A2 (en) | 1992-01-28 | 1993-01-27 | Methods |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH07503252A true JPH07503252A (en) | 1995-04-06 |
Family
ID=10709398
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP5513407A Pending JPH07503252A (en) | 1992-01-28 | 1993-01-27 | Method for delaying HIV-induced AIDS by administration of substituted azasperane compounds |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0624089A4 (en) |
JP (1) | JPH07503252A (en) |
KR (1) | KR950700068A (en) |
AU (1) | AU666175B2 (en) |
CA (1) | CA2128535A1 (en) |
GB (1) | GB9201803D0 (en) |
WO (1) | WO1993014760A2 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007537251A (en) * | 2004-05-12 | 2007-12-20 | ブリストル−マイヤーズ スクイブ カンパニー | HIV integrase inhibitor: cyclic pyrimidinone compound |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9315351D0 (en) * | 1993-07-23 | 1993-09-08 | Smithkline Beecham Corp | Methods |
GB9315340D0 (en) * | 1993-07-23 | 1993-09-08 | Smithkline Beecham Corp | Methods |
GB9315306D0 (en) * | 1993-07-23 | 1993-09-08 | Smithkline Beecham Corp | Methods |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US181704A (en) * | 1876-08-29 | Improvement in flour-dressing machines | ||
US4963557A (en) * | 1987-09-28 | 1990-10-16 | Smithkline Beecham Corporation | Immunomodulatory azaspiranes |
EP0550595A4 (en) * | 1990-09-24 | 1993-09-08 | Smithkline Beecham Corporation | Methods |
ZA921120B (en) * | 1991-02-19 | 1993-01-27 | Smithkline Beecham Corp | Cytokine inhibitors |
-
1992
- 1992-01-28 GB GB929201803A patent/GB9201803D0/en active Pending
-
1993
- 1993-01-27 AU AU35951/93A patent/AU666175B2/en not_active Ceased
- 1993-01-27 CA CA002128535A patent/CA2128535A1/en not_active Abandoned
- 1993-01-27 KR KR1019940702596A patent/KR950700068A/en not_active Application Discontinuation
- 1993-01-27 EP EP93904671A patent/EP0624089A4/en not_active Withdrawn
- 1993-01-27 WO PCT/US1993/000730 patent/WO1993014760A2/en not_active Application Discontinuation
- 1993-01-27 JP JP5513407A patent/JPH07503252A/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007537251A (en) * | 2004-05-12 | 2007-12-20 | ブリストル−マイヤーズ スクイブ カンパニー | HIV integrase inhibitor: cyclic pyrimidinone compound |
Also Published As
Publication number | Publication date |
---|---|
WO1993014760A3 (en) | 1993-09-02 |
EP0624089A1 (en) | 1994-11-17 |
WO1993014760A2 (en) | 1993-08-05 |
EP0624089A4 (en) | 1994-12-14 |
AU3595193A (en) | 1993-09-01 |
KR950700068A (en) | 1995-01-16 |
CA2128535A1 (en) | 1993-08-05 |
AU666175B2 (en) | 1996-02-01 |
GB9201803D0 (en) | 1992-03-11 |
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