JPH01132542A - Method for optically resolving gossypol racemic modification - Google Patents
Method for optically resolving gossypol racemic modificationInfo
- Publication number
- JPH01132542A JPH01132542A JP29049687A JP29049687A JPH01132542A JP H01132542 A JPH01132542 A JP H01132542A JP 29049687 A JP29049687 A JP 29049687A JP 29049687 A JP29049687 A JP 29049687A JP H01132542 A JPH01132542 A JP H01132542A
- Authority
- JP
- Japan
- Prior art keywords
- gossypol
- phenylalaninol
- racemic modification
- separated
- gotssypol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- QBKSWRVVCFFDOT-UHFFFAOYSA-N gossypol Chemical compound CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(C=3C(O)=C4C(C=O)=C(O)C(O)=C(C4=CC=3C)C(C)C)=C(C)C=C21 QBKSWRVVCFFDOT-UHFFFAOYSA-N 0.000 title claims abstract description 24
- QHOPXUFELLHKAS-UHFFFAOYSA-N Thespesin Natural products CC(C)c1c(O)c(O)c2C(O)Oc3c(c(C)cc1c23)-c1c2OC(O)c3c(O)c(O)c(C(C)C)c(cc1C)c23 QHOPXUFELLHKAS-UHFFFAOYSA-N 0.000 title claims abstract description 9
- 229950005277 gossypol Drugs 0.000 title claims abstract description 9
- 229930000755 gossypol Natural products 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 11
- 238000012986 modification Methods 0.000 title abstract 4
- 230000004048 modification Effects 0.000 title abstract 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000004811 liquid chromatography Methods 0.000 claims abstract description 10
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 230000003287 optical effect Effects 0.000 claims description 12
- 239000000203 mixture Substances 0.000 abstract description 5
- 239000002246 antineoplastic agent Substances 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000003480 eluent Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical group 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、ゴツシポールラセミ体の光学分割法に関し、
詳しくはゴツシポールラセミ体から（＋または−）−ゴ
ツシポールを高純度かつ高収率で簡便に分離するゴツシ
ポールラセミ体の光学分割法に関する。[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a method for optical resolution of racemic Gotsusypol,
More specifically, the present invention relates to an optical resolution method for racemic gossypol that easily separates (+ or -)-gossypol from racemic gossypol with high purity and high yield.
［従来技術］
ワタの種子の内部等に含まれるゴツシポール（ｇｏｓｓ
ｙｐｏｌ）には、“「ケミストリイ イン プリテン（
Ｃｈｅｓｌｓｔｒｙ ｉｎ Ｂｒ１ｔａ１ｎ） Ｊ 、
１９８４年１１月、第９７０頁”によれば（＋）、
（−）の光学異性体があることが知られている。また、
綿の一種であるＴ ｈｅｓｐｅｓｉａ ｐｏｐｕｌｎｅ
ａより採れるゴツシポールは、（＋）−ゴツシポールの
みだが、（−）−ゴツシポールのみをつくる種は見つか
っていない。[Prior art] Gossipol, which is contained inside cotton seeds, etc.
ypol), “Chemistry in Printen (
Cheslstry in Br1taln) J,
According to “November 1984, page 970” (+),
It is known that there is a (-) optical isomer. Also,
T hespesia populne, a type of cotton
The only type of gotssypol that can be obtained from A. a., is (+)-gotssypol, but no species that produces only (-)-gotssypol has been found.
このゴツシポールは、精子抑制作用を有することが知ら
れているが、副作用が生じることが確認されている。Gotsusipol is known to have a sperm suppressive effect, but it has been confirmed that it causes side effects.
すなわち、ハムスターによる動物実験において、ゴツシ
ポールのラセミ体である（±）−ゴツシポールは、精子
抑制作用を有するものの、副作用として食欲不振を生じ
る。一方、（＋）−ゴツシポールのみでは、このような
精子抑制作用は生じず、また（−）−ゴツシポールのみ
を用いた場合には、精子抑制作用を顕著に有し、副作用
が生じずに、ハムスターは体重増を示している。That is, in animal experiments using hamsters, (±)-gotssipol, which is a racemic form of gotssipol, has a sperm suppressive effect, but causes anorexia as a side effect. On the other hand, (+)-Gotsusipol alone does not have such a sperm-inhibitory effect, and (-)-Gotsusipol alone has a marked sperm-inhibitory effect and can be used in hamsters without any side effects. indicates weight gain.
また、精子抑制作用は、抗ガン作用と共通点を有してい
るので、この（−）−ゴツシポールは、抗ガン剤として
も期待されている。Furthermore, since the sperm suppression effect has something in common with the anticancer effect, this (-)-gotssypol is also expected to be used as an anticancer agent.
特に、（−）−ゴツシポールに例えば官能基を導入する
ことによって、これらの作用がさらに向上する可能性が
ある。In particular, these effects may be further improved by introducing, for example, a functional group into (-)-gossypol.
［発明が解決しようとする問題点］
そこで、ゴツシポールのラセミ体である（±）−ゴツシ
ポールから（＋）−ゴツシポールと（−）−ゴツシポー
ルとを有効に分離することが望まれているが、高純度、
高収率で（＋または−）−ゴツシポールを簡便に分離す
る方法は未だ得られていない。[Problems to be Solved by the Invention] Therefore, it is desired to effectively separate (+)-gotssypol and (-)-gotssypol from (±)-gotssypol, which is the racemic form of gotssypol. purity,
A method for easily separating (+ or -)-gotsusipol in high yield has not yet been obtained.
本発明は、かかる見地からなされたもので、ゴツシポー
ルのラセミ体から（＋または−）−ゴツシポールが高純
度、高収率で、しかも簡便に得られるゴツシポールラセ
ミ体の光学分割法を提供することを目的とする。The present invention has been made from such a viewpoint, and provides an optical resolution method for racemic gossypol that allows (+ or -)-gossypol to be obtained easily with high purity and high yield from the racemic form of gotsussypol. The purpose is to
［問題点を解決するための手段］
本発明の上記目的は、（−）−フェニルアラニノールを
用いた次に示す光学分割法により達成される。[Means for Solving the Problems] The above objects of the present invention are achieved by the following optical resolution method using (-)-phenylalaninol.
すなわち本発明は、ゴツシポールのラセミ体を（−）−
フェニルアラニノールと溶媒中で反応させ、得られたジ
アスレオマー塩を液体クロマトグラフィーで分離するこ
とを特徴とするゴツシポールラセミ体の光学分割法にあ
る。That is, the present invention provides a racemic form of gotssypol (-)-
A method for optical resolution of racemic gotsusypol, which is characterized by reacting with phenylalaninol in a solvent and separating the obtained diathreomer salt by liquid chromatography.
本発明では、先ずラセミ体である下記構造式を有する（
±）−ゴツシポール（Ｃ３０Ｈ３００８）と下記構造式
を有する（−）−フェニルアラニノール
を溶媒、例えばメタノール中で反応させ、シッフ塩基で
あるジアステレオマー塩を製造する。得られるジアステ
レオマー異性体の混合物は、（＋）−ゴツシポール／（
−）−フェニルアラニノールと（−）−ゴツシポール／
（−）−フェニルアラニノールである。In the present invention, first, it has the following structural formula which is a racemic body (
±)-Gotsusipol (C30H3008) and (-)-phenylalaninol having the following structural formula are reacted in a solvent such as methanol to produce a diastereomeric salt that is a Schiff base. The resulting mixture of diastereoisomers is composed of (+)-gotssypol/(
-)-Phenylalaninol and (-)-Gotsusipol/
(-)-phenylalaninol.
このものを液体クロマトグラフィーを用いて（＋）−ゴ
ツシポール／（−）−フェニルアラニノールと（−）−
ゴツシポール／（−）−フェニルアラニノールに分離す
る。この液体クロマトグラフィーとしては、例えば充填
剤としてＯＤＳ。This product was separated into (+)-gotsusipol/(-)-phenylalaninol and (-)- using liquid chromatography.
Separate into gotsusipol/(-)-phenylalaninol. For this liquid chromatography, for example, ODS is used as a packing material.
Ｃ−８等の逆相系充填剤、溶離液としてメタノール−水
、エタノール−水等のアルコール−水の混合溶液を用い
る。このアルコール−水の混合比は、任意に選択される
。A reverse phase packing material such as C-8 and a mixed solution of alcohol and water such as methanol-water and ethanol-water are used as the eluent. This alcohol-water mixing ratio is arbitrarily selected.
このようにして得られた（＋）−ゴツシポール／（−）
−フェニルアラニノールと（−）−ゴツシポール／（−
）−フェニルアラニノールをジメトキシエタンと水とを
、例えば８０：２０の混合容量比で混合した混合溶液に
溶解し、少量の濃硫酸の存在下に加熱、加水分解する。Thus obtained (+)-gotssypol/(-)
-phenylalaninol and (-)-gotsusipol/(-
)-Phenylalaninol is dissolved in a mixed solution of dimethoxyethane and water in a mixing volume ratio of 80:20, for example, and heated and hydrolyzed in the presence of a small amount of concentrated sulfuric acid.
分解物は液体クロマトグラフィーで分離、精製し、（−
）−ゴツシポールおよび（＋）−ゴツシポールをそれぞ
れ得る。この液体クロマトグラフィ、−も、例えば充填
剤としてＯＤＳ、Ｃ−８等の逆相系充填剤、溶離液とし
てメタノール−水、エタノール−水等のアルコール−水
を任意の割合で混合した混合溶液が用いられる。The decomposition products were separated and purified by liquid chromatography, and (-
)-Gotssypol and (+)-Gotssypol are obtained, respectively. This liquid chromatography also uses, for example, a reverse-phase packing material such as ODS or C-8 as a packing material, and a mixed solution of an alcohol-water mixture such as methanol-water, ethanol-water, etc. in an arbitrary ratio as an eluent. It will be done.
［実施例］ 以下、実施例に基づき本発明を具体的に説明する。[Example] Hereinafter, the present invention will be specifically explained based on Examples.
実施例
ゴツシポールのラセミ体である（±）−ゴツシポール１
００ＯＩＩＩＳＦ （１，９３０１ｏｌｅ ）および（
−）−フェニルアラニノール７０８Ｎ （４，８７５ｍ
ｍｏｌｅ ）をメタノール３０ｄに溶解し、室温（約２
０℃）で１０時間撹拌し、次いでメタノールを減圧留去
後、得られた反応物を下記の条件で液体クロマトグラフ
ィーを用いて分離した。Example Gotsusipol racemic (±)-Gotsusipol 1
00OIIISF (1,9301ole) and (
-)-Phenylalaninol 708N (4,875m
mole ) in 30 d of methanol and heated to room temperature (approximately 2
After stirring at 0° C. for 10 hours, methanol was then distilled off under reduced pressure, and the resulting reaction product was separated using liquid chromatography under the following conditions.
（分離条件）
カラム：築山科学製ガラスカラム ４５φｘ４９０ｇ充
填剤：野村化学製Ｄ ｅｖｅｌｏｓｉｌ ＯＤ Ｓ
３０−５０溶離液：メタノール−水−９５： ５
（容ｆｆｉ比）流速： ７．Ｏｍ／ｗｉｎ
１フラクション： ２４．５ｄ
この結果、フラクション１２〜１７から（−）−ゴツシ
ポール／（−）−フェニルアラニノール６４９ｍ９ （
収率４２，９％）とフラクション２１〜３２から（＋）
−ゴツシポール／（−）−フェニルアラニノールＧ４０
／７１５Ｆ （収率４２，３％）を得た。(Separation conditions) Column: Glass column manufactured by Tsukiyama Scientific Co., Ltd. 45φ x 490g Packing material: Develosil OD S manufactured by Nomura Chemical Co., Ltd.
30-50 eluent: methanol-water-95:5
(Volume ffi ratio) Flow rate: 7. Om/win 1 fraction: 24.5d As a result, (-)-Gotsusypol/(-)-phenylalaninol 649m9 (
yield 42.9%) and from fractions 21-32 (+)
-Gotsusipol/(-)-phenylalaninol G40
/715F (yield 42.3%) was obtained.
次に、得られた（−）−ゴツシポール／（−）−フェニ
ルアラニノール２２５ｍ９．８０％ジメトキシエタン溶
液ＬＯＩｎｌ、 Ｃ−Ｈ２Ｓ ０４１０滴の混合物を窒
素雰囲気下、６０℃で３時間加熱・撹拌した。冷却後、
ジクロロメタン（ＣＨ２Ｃ）、２） ５０７を加え、初
めに水ついで飽和食塩水で洗浄し、硫酸ナトリウムで乾
燥した。濾過後、濾液を減圧濃縮し、得られた濃縮物を
下記条件で液体クロマトグラフィーを用いて分離した。Next, the resulting mixture of (-)-gotsusypol/(-)-phenylalaninol (225 m), 9.80% dimethoxyethane solution LOInl, and 10 drops of C-H2S was heated and stirred at 60°C for 3 hours under a nitrogen atmosphere. After cooling,
Dichloromethane (CH2C), 2) 507 was added, first washed with water and then with saturated brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting concentrate was separated using liquid chromatography under the following conditions.
（分離条件）
カラム：築山科学製ガラスカラム ２４φｘ３６０ｍｍ
充填剤：野村化学製Ｄ ｅｖｅｌｏｓｌｌ ＯＤ Ｓ
３０−５０溶離液：メタノール−水−９０： １０
（容量比）流速： １．Ｏｍ／ｍｉｎ
■フラクション；７．０戴
この結果、（−）−ゴツシポール９７７７１ｇ（収率６
５．５％）を得た。また、比旋光度［α］ｏ＝−４２３
° （Ｃ−１，９９、ベンゼン）であった。(Separation conditions) Column: Tsukiyama Kagaku glass column 24φx360mm
Filler: D evelosll OD S manufactured by Nomura Chemical
30-50 eluent: methanol-water-90:10
(Capacity ratio) Flow rate: 1. Om/min ■ Fraction; 7.0 As a result, (-)-gotsusipol 97771 g (yield 6
5.5%). Also, specific optical rotation [α]o=-423
° (C-1,99, benzene).
（＋）−ゴツシポール／（−）−フェニルアラニノール
についても上記同様な分離を行なった。The same separation as above was also performed for (+)-gotsusipol/(-)-phenylalaninol.
すなわち、（＋）−ゴツシポール／（−）−フェニルア
ラニノール２００１１１９．８０％ジメトキシエタン溶
液１０ｍ５ＣＨ２Ｓ ０４１０ｍノ混合物を上記と同様
にして分離を行なった。That is, a mixture of (+)-gotssypol/(-)-phenylalaninol 20011119.80% dimethoxyethane solution (10m5CH2S0410m) was separated in the same manner as above.
この結果、（＋）−ゴツシポール８２＃Ｉｇ（収率６２
．１％）を得た。また、比旋光度［α］ｏ＝＋４１６°
（Ｃ−１，８４、ベンゼン）であった。As a result, (+)-gotssypol 82#Ig (yield 62
．． 1%). Also, specific optical rotation [α] o = +416°
(C-1,84, benzene).
［発明の効果］
以上説明したように、本発明の光学分割法によって、ゴ
ツシポールのラセミ体から、（＋または−）−ゴツシポ
ールが高純度、高収率で、簡便に得られる。[Effects of the Invention] As explained above, by the optical resolution method of the present invention, (+ or -)-gossypol can be easily obtained with high purity and high yield from the racemic form of gossypol.
このようにして得られた（＋または−）−ゴツシポール
、特に（−）−ゴツシポールは、精子抑制作用を有し、
抗ガン作用も期待され、さらに官能基を導入することに
よって、これらの作用がさらに上昇する可能性が高いこ
とから、本発明の光学分割法は、医学、薬学等の分野に
適用可能である。The (+ or -)-gotssipol obtained in this way, especially (-)-gotssipol, has a sperm-inhibitory effect,
It is also expected to have anticancer effects, and these effects are likely to be further enhanced by introducing a functional group, so the optical resolution method of the present invention is applicable to fields such as medicine and pharmacy.
Claims (1)
ノールと溶媒中で反応させ、得られたジアスレオマー塩
を液体クロマトグラフィーで分離することを特徴とする
ゴッシポールラセミ体の光学分割法。 ２、前記溶媒がメタノールである特許請求の範囲第１項
記載のゴッシポールラセミ体の光学分割法。[Claims] 1. A racemic form of gossypol, which is characterized in that the racemic form of gossypol is reacted with (-)-phenylalaninol in a solvent, and the resulting diathreomer salt is separated by liquid chromatography. Optical resolution method. 2. The method for optical resolution of racemic gossypol according to claim 1, wherein the solvent is methanol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29049687A JPH01132542A (en) | 1987-11-19 | 1987-11-19 | Method for optically resolving gossypol racemic modification |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP29049687A JPH01132542A (en) | 1987-11-19 | 1987-11-19 | Method for optically resolving gossypol racemic modification |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH01132542A true JPH01132542A (en) | 1989-05-25 |
Family
ID=17756775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP29049687A Pending JPH01132542A (en) | 1987-11-19 | 1987-11-19 | Method for optically resolving gossypol racemic modification |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH01132542A (en) |
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01290635A (en) * | 1988-05-18 | 1989-11-22 | Daicel Chem Ind Ltd | Optical resolution process |
| WO1994002108A1 (en) * | 1992-07-24 | 1994-02-03 | The Johns Hopkins University | Chemotherapy for cancer |
| US5614551A (en) * | 1994-01-24 | 1997-03-25 | The Johns Hopkins University | Inhibitors of fatty acid synthesis as antimicrobial agents |
| US5665874A (en) * | 1989-01-17 | 1997-09-09 | John Hopkins University | Cancer related antigen |
| US5759837A (en) * | 1989-01-17 | 1998-06-02 | John Hopkins University | Chemotherapy for cancer by inhibiting the fatty acid biosynthetic pathway |
| US5846489A (en) * | 1994-04-09 | 1998-12-08 | Boehringer Mannheim Gmbh | System for opening closures of vessels and for the contamination-free operation of reaction sequences |
| US5864011A (en) * | 1989-01-17 | 1999-01-26 | The Johns Hopkins University | Cancer related antigen |
| US5981575A (en) * | 1996-11-15 | 1999-11-09 | Johns Hopkins University, The | Inhibition of fatty acid synthase as a means to reduce adipocyte mass |
| WO2001094334A1 (en) * | 2000-06-02 | 2001-12-13 | Eli Lilly & Company | Methods for resolving chiral (2s) and (2r) chromanes |
| US7342046B2 (en) | 2004-03-25 | 2008-03-11 | The Regents Of The University Of Michigan | Gossypol co-crystals and the use thereof |
| US7354928B2 (en) | 2001-11-01 | 2008-04-08 | The Regents Of The University Of Michigan | Small molecule inhibitors targeted at Bcl-2 |
| US7427689B2 (en) | 2000-07-28 | 2008-09-23 | Georgetown University | ErbB-2 selective small molecule kinase inhibitors |
| US7432304B2 (en) | 2001-05-30 | 2008-10-07 | The Regents Of The University Of Michigan | Small molecule antagonists of Bcl-2 family proteins |
| USRE40862E1 (en) | 1990-07-12 | 2009-07-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gossypolone for the treatment of cancer |
| US7696372B2 (en) | 2007-10-01 | 2010-04-13 | Ascenta Therapeutics, Inc. | Process for preparing R-gossypol L-phenylalaninol dienamine |
-
1987
- 1987-11-19 JP JP29049687A patent/JPH01132542A/en active Pending
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01290635A (en) * | 1988-05-18 | 1989-11-22 | Daicel Chem Ind Ltd | Optical resolution process |
| US5665874A (en) * | 1989-01-17 | 1997-09-09 | John Hopkins University | Cancer related antigen |
| US5759837A (en) * | 1989-01-17 | 1998-06-02 | John Hopkins University | Chemotherapy for cancer by inhibiting the fatty acid biosynthetic pathway |
| US5864011A (en) * | 1989-01-17 | 1999-01-26 | The Johns Hopkins University | Cancer related antigen |
| US5872217A (en) * | 1989-01-17 | 1999-02-16 | The Johns Hopkins University | Antibodies which specifically bind a cancer related antigen |
| USRE40862E1 (en) | 1990-07-12 | 2009-07-21 | The United States Of America As Represented By The Department Of Health And Human Services | Gossypolone for the treatment of cancer |
| WO1994002108A1 (en) * | 1992-07-24 | 1994-02-03 | The Johns Hopkins University | Chemotherapy for cancer |
| US5614551A (en) * | 1994-01-24 | 1997-03-25 | The Johns Hopkins University | Inhibitors of fatty acid synthesis as antimicrobial agents |
| US5846489A (en) * | 1994-04-09 | 1998-12-08 | Boehringer Mannheim Gmbh | System for opening closures of vessels and for the contamination-free operation of reaction sequences |
| US5981575A (en) * | 1996-11-15 | 1999-11-09 | Johns Hopkins University, The | Inhibition of fatty acid synthase as a means to reduce adipocyte mass |
| WO2001094334A1 (en) * | 2000-06-02 | 2001-12-13 | Eli Lilly & Company | Methods for resolving chiral (2s) and (2r) chromanes |
| US7427689B2 (en) | 2000-07-28 | 2008-09-23 | Georgetown University | ErbB-2 selective small molecule kinase inhibitors |
| US7432304B2 (en) | 2001-05-30 | 2008-10-07 | The Regents Of The University Of Michigan | Small molecule antagonists of Bcl-2 family proteins |
| US8163805B2 (en) | 2001-05-30 | 2012-04-24 | The Regents Of The University Of Michigan | Small molecule antagonists of Bcl-2 family proteins |
| US7354928B2 (en) | 2001-11-01 | 2008-04-08 | The Regents Of The University Of Michigan | Small molecule inhibitors targeted at Bcl-2 |
| US7342046B2 (en) | 2004-03-25 | 2008-03-11 | The Regents Of The University Of Michigan | Gossypol co-crystals and the use thereof |
| US7432300B2 (en) | 2004-03-25 | 2008-10-07 | The Regents Of The University Of Michigan | Gossypol co-crystals and the use thereof |
| US7696372B2 (en) | 2007-10-01 | 2010-04-13 | Ascenta Therapeutics, Inc. | Process for preparing R-gossypol L-phenylalaninol dienamine |
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