JP6626831B2 - ベータ−クロロシクロペンタンの親水性エステルプロドラッグの使用による角膜中心肥厚の減少 - Google Patents
ベータ−クロロシクロペンタンの親水性エステルプロドラッグの使用による角膜中心肥厚の減少 Download PDFInfo
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- JP6626831B2 JP6626831B2 JP2016553327A JP2016553327A JP6626831B2 JP 6626831 B2 JP6626831 B2 JP 6626831B2 JP 2016553327 A JP2016553327 A JP 2016553327A JP 2016553327 A JP2016553327 A JP 2016553327A JP 6626831 B2 JP6626831 B2 JP 6626831B2
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本出願は、2012年8月27日に出願された米国特許仮出願シリアル番号61/693,437号の利益を主張する2013年8月23日出願された米国出願シリアル番号13/974,975号の一部継続出願であり、これらの全出願の全文が参照により本出願に組み入れられたものとする。
を有する化合物[式中、
Xは、CH2CH2、シス−CH=CH、インターアリレン(interaylene)、CH2S、CH2Oまたはアルキンであり、
Yは、C1−C3アルキル、O、S単結合、2重結合またはチオフェンであり、
Zは、インターアリレン(interarylene)、C1−C3アルキル、SCH2、 OCH2、単結合または2重結合であり、
Uは、O、Cl、H−CL、H−H、H−OH、H−Cl、H−FまたはH−CNであり、点線結合は単結合または2重結合を表し、
からなる群から独立して選択され、
R2は、H、C1−C6アルキル、C1−C6ヒドロキシアルキル、及び−OHからなる群から独立して選択され、
R3は、独立してH、C1−C6アルキル及びC1−C6ヒドロキシアルキル、−OH又はRであり、
nは、0〜8であり、
Y1は、C=Oまたは単結合であり、
Z1は、N、NH、NH2、CH2または−OHであり、
n1は、0〜2であり、
Rは、H、アルキル及びCH2OHであり、
Arは、モノ−、ジ−またはトリ−置換され、かつC1−C6アルキル、ヒドロキシアルキル、アリール、ハロゲン、OR、CF3、C(O)R4、COF3、SO2N(R4)2、SO2NH2、NO2及びCNからなる群から選択されて置換されるアリールまたはヘテロアリールであり、置換化合物は同じでも異なってもよく、
R4は、H、C1−C6アルキル及びアルキルアリールであり、またはH、C1−C6アルキル及びアルキルアリールから独立して選択される]。
本明細書で使用する略語は化学及び生物分野での通常の意味を有する。本明細書で記載する化学構造及び化学式は、化学分野で公知の化学原子価の標準規則に従って構成される。
下記の部分:
(A)−OH、−NH2、−SH、−CN、−CF3、−NO2、オキソ、ハロゲン、非置換アルキル、非置換ヘテロアルキル、非置換シクロアルキル、非置換ヘテロシクロアルキル、非置換アリール、非置換ヘテロアリール、並びに
(B)
(i)オキソ、−OH、−NH2、−SH、−CN、−CF3、−NO2、ハロゲン、非置換アルキル、非置換ヘテロアルキル、非置換シクロアルキル、非置換ヘテロシクロアルキル、非置換アリール、非置換ヘテロアリール、並びに
(ii)
(a)オキソ、−OH、−NH2、−SH、−CN、−CF3、−NO2、ハロゲン、非置換アルキル、非置換ヘテロアルキル、非置換シクロアルキル、非置換ヘテロシクロアルキル、非置換アリール、非置換ヘテロアリール、
並びに
(b)オキソ、−OH、−NH2、−SH、−CN、−CF3、−NO2、ハロゲン、非置換アルキル、非置換ヘテロアルキル、非置換シクロアルキル、非置換ヘテロシクロアルキル、非置換アリール、及び非置換ヘテロアリールから選択される少なくとも1つの置換基で置換されたアルキル、ヘテロアルキル、シクロアルキル、ヘテロシクロアルキル、アリールまたはヘテロアリール
から選択される少なくとも1つの置換基で置換されたアルキル、ヘテロアルキル、シクロアルキル、ヘテロシクロアルキル、アリール、及びヘテロアリール、
から選択される少なくとも1つの置換基で置換されたアルキル、ヘテロアルキル、シクロアルキル、ヘテロシクロアルキル、アリール及びヘテロアリール、
から選択される基を意味する。
本発明のいくつかの実施形態を次の段落で例示する。
1)式:
を有する化合物[式中、
Xは、CH2CH2、シス−CH=CH、インターアリレン(interaylene)、 CH2S、CH2Oまたはアルキンであり、
Yは、C1−C3アルキル、O、S単結合、2重結合またはチオフェンであり、
Zは、インターアリレン(interarylene)、C1−C3アルキル、SCH2、 OCH2、単結合または2重結合であり、
Uは、O、Cl、H−H、H−OH、H−Cl、H−FまたはH−CNであり、点線結合は単結合または2重結合を表し、
R1は、独立してH、C1―C6アルキル及びC1−C6ヒドロキシアルキル、−OH及び
R2は、H、C1−C6アルキル、C1−C6ヒドロキシアルキル、及び−OHからなる群から独立して選択され、
R3は、独立してH、C1−C6アルキル及びC1−C6ヒドロキシアルキル、−OH又はRであり、
nは、0〜8であり、
Y1は、C=Oまたは単結合であり、
Z1は、N、NH、NH2、CH2または−OHであり、
n1は、0〜2であり、
Rは、H、アルキル及びCH2OHであり、
Arは、モノ−、ジ−またはトリ−置換され、かつC1−C6アルキル、ヒドロキシアルキル、アリール、ハロゲン、OR、CF3、C(O)R4、COF3、SO2N(R4)2、SO2NH2、NO2及びCNからなる群から選択されて置換されるアリールまたはヘテロアリールであり、置換化合物は同じでも異なってもよく、
R4は、H、C1−C6アルキル及びアルキルアリールであり、またはH、C1−C6アルキル及びアルキルアリールから独立して選択される]。
を有する段落1に記載の化合物[式中、
Xは、CH2CH2またはシス−CH=CHであり、
Yは、単結合、2重結合、またはチオフェンであり、
Zは、C1−C3アルキル、SCH2、OCH2、単結合または2重結合であり、
Uは、ハロゲンまたはClであり、
R1は、H、−OHおよびC1−C3ヒドロキシアルキルからなる群から独立して選択され、
R2は、H、C1−C6アルキル、C1−C6ヒドロキシアルキル、及び−OHからなる群から独立して選択され、
R3は、H、C1−C6アルキル及びC1−C6ヒドロキシアルキル、−OHまたはRからなる群から独立して選択され、
nは、0〜3であり、
Y1は、C=Oまたは単結合であり、
Z1は、N、NH2、CH2または−OHであり、
n1は、0〜2であり、
Rは、H、アルキルおよびCH2OHであり、かつ
Arは、モノ−、ジ−またはトリ−置換され、かつハロゲン及びClからなる群から選択されて置換されるアリールまたはヘテロアリールである]。
を有する化合物[式中、
Xは、C1−C3アルキル、シス−CH=CH、インターアリレン(interarylene)、CH2S、CH2Oまたはアルキンであり、
Yは、C1−C3アルキル、O、S、単結合、2重結合またはチオフェンであり、
Zは、インターアリレン(interarylene)、C1−C3アルキル、SCH2、OCH2、単結合または2重結合であり、
Uは、O、H−H、H−OH、H−Cl、H−FまたはH−CNであり、点線結合は、単結合または2重結合を表し、
からなる群から独立して選択され、
R2は、H、C1−C6アルキル、C1−C6ヒドロキシアルキル、及び−OHからなる群から独立して選択され、
R3は、独立してH、C1−C6アルキル、C1−C6ヒドロキシアルキル、または−OHであり、
nは、0〜3であり、
Y1は、C=O、C1−C3ヒドロキシアルキルまたは単結合であり、
n1は、0〜2であり、
Arは、モノ−、ジ−またはトリ−置換され、かつC1−C6アルキル、ヒドロキシアルキル、アリール、ハロゲン、OR、CF3、C(O)R4、COF3、SO2N(R4)2、SO2NH2、NO2およびCNからなる群から選択されて置換されるアリールまたはヘテロアリールであり、置換化合物は同じでも異なってもよく、
R4は、H、C1−C6アルキル及びアルキルアリールであり、またはH、C1−C6アルキル及びアルキルアリールから独立して選択される]。
を有する、段落1又は35に記載の化合物[式中、
Xは、C1−C3アルキル及びCH2CH2CH2であり、
Yは、単結合、2重結合、またはチオフェンであり、
Zは、C1−C3アルキル、または単結合であり、
Uは、ハロゲンまたはH−Clであり、
る群から独立して選択され、
R2は、H、C1−C6アルキル、C1−C3ヒドロキシアルキル、または−OHからなる群から独立して選択され、
R3は、H、C1−C6アルキル及びC1−C6ヒドロキシアルキル、−OHまたはRからなる群から独立して選択され、
nは、0〜3であり、
Y1は、C=O、C1−C3ヒドロキシアルキル、CH2OHまたは単結合であり、
Z1は、N、NH、NH2、−OHであり、
n1は、0〜2であり、
Arは、モノ−、ジ−またはトリ−置換され、かつハロゲン及びClからなる群から選択されて置換されるアリールまたはヘテロアリールである]。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
の構造を有する。
を含む。
を含む。
を含む。
を有する。
別の態様では、本明細書で提供される化合物を含む眼病用の医薬組成物及びその実施形態(例えば、式I−XIVの化合物、またはそれらの誘導体、異性体若しくはエナンチオマー)が提供される。1実施形態では、化合物が式(I)の構造を有する。1実施形態では、化合物が式(III)の構造を有する。1実施形態では、化合物が式(IV)の構造を有する。1実施形態では、化合物が式(IVa)−(IVb)の1つの構造を有する。1実施形態では、化合物が式(V)の構造を有する。1実施形態では、化合物が式(Va)−(Vd)の1つの構造を有する。1実施形態では、化合物が式(X)の構造を有する。1実施形態では、化合物が式(Xa)−(Xc)の1つの構造を有する。1実施形態では、化合物が式(XI)の構造を有する。1実施形態では、化合物が式(VIIa)−(VIIp)、VIII、IX、X、XI、XII、XIII、XIVの1つの構造を有する。
本明細書で開示される化合物及び医薬組成物は、溶液、エマルション、ゲルまたはフォームを含む様々な形で調製して投与することができる。従って、本明細書で考察される医薬組成物は、薬剤的に許容される担体または賦形剤及び本明細書で記載される1つ以上の化合物を含む。「溶液」は、通常の意味で、化合物(例えば、本明細書で記載される化合物)が部分的に溶解し、好ましくは完全に溶解し、液体として投与され得る液体医薬組成物を指す。「エマルション」は、通常の意味で、1つの化合物(例えば、本明細書に記載されている化合物またはその溶液)が他の化合物(例えば、本明細書に記載されているような担体)を介して分散している2つまたはそれ以上の非混和性液の混合物を指す。「ゲル」は、通常の意味で、粘性のある半剛性液を生じる連続液相中の化合物の高粘度溶液、エマルションまたはコロイド懸濁を指す。「コロイド」は、通常の意味で、重力の影響下で沈降しない分散された小粒子が全体にある連続媒体を含む組成物を指す。「フォーム」は、通常の意味で、ガスが分散されている連続媒体(すなわち、溶液、エマルション、ゲル等)を含む組成物を指す。
別の態様では、ヒトの眼疾患の治療方法が提供される。前記方法は、治療的有効量の本明細書で提供される化合物及びその実施形態(例えば、式I−XIVの化合物、またはそれらの誘導体、異性体若しくはエナンチオマー)を、それを必要とする対象に投与することを含む。1実施形態では、投与は局所投与である。1実施形態では、疾患は黄斑部変性である。1実施形態では、疾患は眼圧に起因する。1実施形態では、疾患は緑内障である。
本明細書で使用する略語は化学技術分野における通常の意味を有する。具体的な略語としては、以下のTBDMSO:(tert-ブチルジメチルシリル)オキシ;DMF:ジメチルホルムアミド;EDC:1−エチル−3−[3−ジメチルアミノプロピル]カルボジイミド塩酸塩;DMAP:4−ジメチルアミノピリジン;THF:テトラヒドロフラン;Bu4NF:フッ化テトラブチルアンモニウムが挙げられる。
(R)−2,3−ジヒドロキシプロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物3)の合成。
スキーム1:
((S)−2,2−ジメチル−1,3−ジオキソラン−4−イル)メチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物4)の合成。
(S)−2,3−ジヒドロキシプロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物5)の合成。
((4R,5R)−5−(ヒドロキシメチル)−2,2−ジメチル−1,3−ジオキソラン−4−イル)メチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物6)の合成。
(2R,3R)−2,3,4−トリヒドロキシブチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物7)の合成。
((4S,5S)−5−(ヒドロキシメチル)−2,2−ジメチル−1,3−ジオキソラン−4−イル)メチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物8)の合成。
(2S,3S)−2,3,4−トリヒドロキシブチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物9)の合成。
((4R,4′S,5R)−2,2,2′2′−テトラメチル−[4,4′−ビ(1,3−ジオキソラン)]−5−イル)メチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物10)の合成。
(2R,3R,4S)−2,3,4,5−テトラヒドロキシペンチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(11)の合成。
(S)−2−ヒドロキシ−2−((4R,4′R,5R)−2,2,2′,2′−テトラメチル−[4、4′−ビ(1,3−ジオキソラン)]−5−イル)エチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物12)の合成。
2,3,4,5,6−ペンタヒドロキシヘキシル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物13)の合成。
3−ヒドロキシ−2−(ヒドロキシメチル)プロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物14)の合成。
3−ヒドロキシ−2−(ヒドロキシメチル)−2−メチルプロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物15)の合成。
(5−(ヒドロキシメチル)−1,3−ジオキサン−5-イル)メチル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物16)の合成。
3−(ビス(2−((テトラヒドロ−2H−ピラン−2−イル)オキシ)エチル)アミノ)−3−オキソプロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物17)の合成。
3−(ビス(2−ヒドロキシエチル)アミノ)−3−オキソプロピル5−(3−((1R、2R、3R、5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物18)の合成。
3−((1,3−ビス((テトラヒドロ−2H−ピラン−2−イル)オキシ)プロパン−2−イル)アミノ)−3−オキソプロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)−プロピル)チオフェン−2−カルボキシラート(化合物19)の合成。
3−((1,3−ジヒドロキシプロパン−2−イル)アミノ)−3−オキソプロピル5−(3−((1R,2R,3R,5R)−5−クロロ−2−(3,5−ジクロロフェネチル)−3−ヒドロキシシクロペンチル)プロピル)チオフェン−2−カルボキシラート(化合物20)の合成。
Claims (4)
- 以下からなる群から選択される化合物:
- 請求項1に記載の化合物を含み及び任意に医薬的に許容可能な担体を含んでも良い医薬組成物。
- ヒトにおける眼性疾患の治療の為の請求項2に記載の医薬組成物。
- 角膜肥厚の低減の為の、請求項2に記載の医薬組成物。
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KR (1) | KR20160124835A (ja) |
CN (1) | CN106029643A (ja) |
AU (1) | AU2015259752B2 (ja) |
CA (1) | CA2939569A1 (ja) |
DK (1) | DK3107906T3 (ja) |
ES (1) | ES2717481T3 (ja) |
TR (1) | TR201902864T4 (ja) |
WO (1) | WO2015175075A1 (ja) |
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CA2962766A1 (en) | 2014-10-02 | 2016-04-07 | Allergan, Inc. | Ester prodrugs of gamma-lactams and their use |
JP7197880B2 (ja) * | 2017-10-19 | 2022-12-28 | 学校法人 名城大学 | エステル化剤及びその利用 |
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US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
ATE141502T1 (de) | 1991-01-15 | 1996-09-15 | Alcon Lab Inc | Verwendung von karrageenan in topischen ophthalmologischen zusammensetzungen |
US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
US6309853B1 (en) | 1994-08-17 | 2001-10-30 | The Rockfeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
WO2008008718A2 (en) * | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Cyclopentane derivatives as antiglaucoma agents |
US20080015219A1 (en) * | 2006-07-11 | 2008-01-17 | Allergan, Inc. | Therapeutic compounds |
US7947732B2 (en) * | 2007-07-13 | 2011-05-24 | Allergan, Inc. | Therapeutic substituted chlorocyclopentanols |
US7732443B2 (en) * | 2008-03-18 | 2010-06-08 | Yariv Donde | Therapeutic substituted cyclopentanes |
US7960378B2 (en) * | 2008-03-18 | 2011-06-14 | Allergan, Inc. | Therapeutic compounds |
US7737140B2 (en) * | 2008-04-24 | 2010-06-15 | Allergan, Inc. | Therapeutic compounds |
US20120322882A1 (en) | 2009-11-09 | 2012-12-20 | Allergan, Inc. | Compositions And Methods For Stimulating Hair Growth |
US20110136872A1 (en) * | 2009-12-09 | 2011-06-09 | Burk Robert M | Stable aqueous compositions of prostglandin agonist prodrugs and methods for use thereof |
DK2888239T3 (en) * | 2012-08-27 | 2019-03-04 | Allergan Inc | REDUCED CENTRAL CORCHET THICKENING USING HYDROFILE ESTER PRODUGS OF BETA-CHLORCYCLOPENTANE |
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EP3107906A1 (en) | 2016-12-28 |
KR20160124835A (ko) | 2016-10-28 |
JP2017509610A (ja) | 2017-04-06 |
AU2015259752B2 (en) | 2019-06-20 |
CA2939569A1 (en) | 2015-11-19 |
WO2015175075A1 (en) | 2015-11-19 |
TR201902864T4 (tr) | 2019-03-21 |
ES2717481T3 (es) | 2019-06-21 |
DK3107906T3 (en) | 2019-03-18 |
AU2015259752A1 (en) | 2016-09-01 |
EP3107906B1 (en) | 2018-12-05 |
CN106029643A (zh) | 2016-10-12 |
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