JPH0753666B2 - Anti-inflammatory agent consisting of substituted diphenylthiazole derivative - Google Patents
Anti-inflammatory agent consisting of substituted diphenylthiazole derivativeInfo
- Publication number
- JPH0753666B2 JPH0753666B2 JP62230074A JP23007487A JPH0753666B2 JP H0753666 B2 JPH0753666 B2 JP H0753666B2 JP 62230074 A JP62230074 A JP 62230074A JP 23007487 A JP23007487 A JP 23007487A JP H0753666 B2 JPH0753666 B2 JP H0753666B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- substituted
- alkyl group
- diphenylthiazole
- inflammatory agent
- 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.)
- Expired - Lifetime
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- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】 産業上の利用分野 本発明は、優れた抗炎症作用を有する医薬品として有用
な置換ジフェニルチアゾール誘導体からなる抗炎症剤に
関するものである。TECHNICAL FIELD The present invention relates to an anti-inflammatory agent comprising a substituted diphenylthiazole derivative useful as a drug having an excellent anti-inflammatory effect.
従来の技術 置換ジフェニルチアゾール誘導体に関しては、特開昭50
−121269に、血小板凝集抑制作用を有する２−モルホリ
ノ−4,5−ジフェニルチアゾール等が例示されている。
また特開昭54−160369には２−フェネチルアミノ−4,5
−ジフェニルチアゾール臭酸塩等が、抗炎症作用及び免
疫調節作用を有することが例示されている。しかしなが
ら本発明の置換ジフェニルチアゾール誘導体に関しては
全く開示がなく、それを示唆する記載もない。2. Description of the Related Art Regarding substituted diphenylthiazole derivatives, Japanese Patent Application Laid-Open No.
-121269 exemplifies 2-morpholino-4,5-diphenylthiazole having a platelet aggregation inhibitory action.
Further, JP-A-54-160369 discloses 2-phenethylamino-4,5.
-Diphenylthiazole hydrobromide and the like are illustrated to have anti-inflammatory and immunomodulatory effects. However, there is no disclosure regarding the substituted diphenylthiazole derivative of the present invention, and no description suggesting it.
発明が解決しようとする問題点 非ステロイド性抗炎症薬は、一般に酸性系と塩基性系と
に分類されている。酸性系薬剤は、一般に急性炎症抑制
及び鎮痛作用を有し、慢性炎症（例えばリウマチのよう
な自己免疫性疾患など）に対しても抑制効果を有するも
のがあるといわれている。塩基性系薬剤は、鎮痛作用が
比較的強く、また急性炎症抑制も有しているといわれる
が、そのほとんどについて慢性炎症に対する効果はあま
り期待できないのが現状である。副作用は主として塩基
性系よりも酸性系にかなり強い胃腸管障害が認められる
傾向にある。Problems to be Solved by the Invention Nonsteroidal anti-inflammatory drugs are generally classified into acidic systems and basic systems. It is said that some acidic drugs generally have an acute inflammation-suppressing and analgesic action and also have an inhibitory effect on chronic inflammation (for example, autoimmune diseases such as rheumatism). It is said that basic drugs have a relatively strong analgesic effect and also have acute inflammation suppression, but most of them cannot be expected to have an effect on chronic inflammation at present. The side effects tend to be gastrointestinal tract disorders that are considerably stronger mainly in the acidic system than in the basic system.
従って、本発明の目的はより副作用の少ないしかも急性
炎症抑制や鎮痛作用だけでなく、慢性炎症に対して効果
を有す塩基性系薬剤として有用な置換ジフェニルチアゾ
ール誘導体からなる抗炎症剤を提供することにある。Therefore, an object of the present invention is to provide an anti-inflammatory agent comprising a substituted diphenylthiazole derivative which has less side effects and is effective as a basic drug having not only acute inflammation suppression and analgesic effects but also chronic inflammation. Especially.
問題を解決するための手段 本発明は下記一般式（Ｉ） （式中、X,Yは同一または異なってもよく、水素原子、
ハロゲン原子または低級アルキル基を、ｎは０〜７の整
数を、R1は水素原子またはアシル基を、R2は長鎖アルキ
ル基、シクロアルキル基、低級アルコキシ基、無置換ま
たは置換フェノキシ基、複素環基または環状アミノ基を
意味する）で表わされる置換ジフェニルチアゾール誘導
体及びその医薬として有用な酸付加塩（但し、Ｘ及びＹ
が４−OMeの場合は−（CH2）ｎ−R2炭素数11以上のアル
キル基であり、また、ｎが１又は２の場合R2が低級アル
キル基又はハロゲンで置換されてもよいチエニル基又は
フリル基である場合を除く）からなる抗炎症剤に関す
る。Means for Solving the Problems The present invention provides the following general formula (I). (In the formula, X and Y may be the same or different, a hydrogen atom,
A halogen atom or a lower alkyl group, n is an integer of 0 to 7, R 1 is a hydrogen atom or an acyl group, R 2 is a long-chain alkyl group, a cycloalkyl group, a lower alkoxy group, an unsubstituted or substituted phenoxy group, A substituted diphenylthiazole derivative represented by a heterocyclic group or a cyclic amino group) and a pharmaceutically useful acid addition salt thereof (provided that X and Y
If is 4-OMe - (CH 2) a n-R 2 an alkyl group having 11 or more carbon atoms, also, n is optionally substituted by 1 or 2 when R 2 is a lower alkyl group or a halogen thienyl Group, except when it is a group or a furyl group).
上記一般式（Ｉ）について具体的に説明する。ハロゲン
原子とは弗素、塩素、臭素、沃素を、低級アルコキシ基
とはメトキシ基、エトキシ基、ｎ−プロポキシ基、iso
−プロポキシ基、ｎ−ブトキシ基、iso−ブトキシ基、t
ert.−ブトキシ基等の炭素数２〜６個程度のアルカノイ
ル基、ベンゾイル基及びトリフルオロメチルカルボニル
基等を、長鎖アルキル基とはデシル基、ウンデシル基、
ドデシル基等の炭素数10個以上のアルキル基を、シクロ
アルキル基とはシクロプロピル基、シクロペンチル基、
シクロヘキシル基、シクロヘプチル基等の炭素数３〜７
個のシクロアルキル基を、置換フェノキシ基の置換基と
はメチル基、エチル基、ｎ−プロピル基、iso−プロピ
ル基、ｎ−ブチル基、ｎ−ペンチル基、iso−ペンチル
基等の炭素数１〜６個の低級アルキル基（さらにこの低
級アルキル基は置換分としてモノまたはジＣ１〜６アル
キルアミノ基も含む）を、複素環基とは２−ピリジル
基、２−ピリミジル基、２−チアゾリル基、２−チアゾ
リン−２−イル基、２−チアゾリジニル基等を、環状ア
ミノ基とはピペリジノ基、ピロリジノ基、モルホリノ
基、ピペラジノ基、ピペコリノ基等の窒素原子または酸
素原子を含有してもよい５または６員の環状アミノ基
（さらにメチル基、エチル基等の炭素数１〜４個のアル
キル基、ベンジル基等のフェニルＣ１〜４アルキル基、
アセチル基、プロピオニル基等の炭素数２〜６個のアル
カノイル基などによって置換されていてもよい）を意味
する。The general formula (I) will be specifically described. Halogen atom is fluorine, chlorine, bromine, iodine, and lower alkoxy group is methoxy group, ethoxy group, n-propoxy group, iso.
-Propoxy group, n-butoxy group, iso-butoxy group, t
ert.-Butoxy group and the like alkanoyl group having about 2 to 6 carbon atoms, benzoyl group and trifluoromethylcarbonyl group, etc., and long-chain alkyl group as decyl group, undecyl group,
An alkyl group having 10 or more carbon atoms such as a dodecyl group, a cycloalkyl group is a cyclopropyl group, a cyclopentyl group,
3 to 7 carbon atoms such as cyclohexyl group and cycloheptyl group
1 cycloalkyl group is a substituted phenoxy group having a carbon number of 1 such as methyl group, ethyl group, n-propyl group, iso-propyl group, n-butyl group, n-pentyl group and iso-pentyl group. To 6 lower alkyl groups (further, the lower alkyl group also includes a mono- or di-C 1-6 alkylamino group as a substituent), and the heterocyclic group means 2-pyridyl group, 2-pyrimidyl group, 2-thiazolyl group. Group, 2-thiazolin-2-yl group, 2-thiazolidinyl group, etc., and cyclic amino group may contain a nitrogen atom or oxygen atom such as piperidino group, pyrrolidino group, morpholino group, piperazino group, pipecolino group. 5- or 6-membered cyclic amino group (further, alkyl group having 1 to 4 carbon atoms such as methyl group and ethyl group, phenyl C 1-4 alkyl group such as benzyl group,
It may be substituted with an alkanoyl group having 2 to 6 carbon atoms such as an acetyl group and a propionyl group).
また医薬として許容される酸の付加塩は１あるいは２当
量の酸からなるものである。適した酸はこれらに限定さ
れるものではないが塩酸、硫酸、硝酸、リン酸等の無機
酸およびマレイン酸、フマル酸、シュウ酸、コハク酸、
マロン酸、乳酸、クエン酸等の有機酸である。Further, the pharmaceutically acceptable acid addition salt is composed of 1 or 2 equivalents of the acid. Suitable acids include, but are not limited to, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid and maleic acid, fumaric acid, oxalic acid, succinic acid,
Organic acids such as malonic acid, lactic acid and citric acid.
一般式（Ｉ）で示される化合物やその酸付加塩を医薬と
して用いる場合は、そのままもしくは公知の賦形剤等と
共に錠剤、散剤、カプセル剤、注射剤、坐剤などの適宜
の剤形として経口的または非経口的に安定に投与するこ
とができる。投与量は症状、投与対象の年齢、性別等を
考慮して個々の場合に応じて適宜決定されるが、通常成
人に対して経口投与する場合、化合物（Ｉ）またはそれ
らの酸付加塩を１回量１〜300mg程度、１日約１〜３回
程度投与するのが好都合である。When the compound represented by the general formula (I) or an acid addition salt thereof is used as a medicine, it is orally used as an appropriate dosage form such as tablets, powders, capsules, injections and suppositories together with known excipients and the like. It can be administered stably or parenterally. The dose is appropriately determined depending on the individual case in consideration of the symptoms, age of the subject to be administered, sex and the like, but when orally administered to an adult, usually, the compound (I) or an acid addition salt thereof is It is convenient to administer a dose of about 1 to 300 mg, about 1 to 3 times a day.
次に本発明の成分となる化合物の製造法について述べ
る。本発明の成分となる化合物は下記に記載する方法に
よって収率よく得ることができるが、本発明の範囲はこ
れらに限定されるものではない。なお、一般式（II）、
（III）で表わされる出発原料は一般的に知られた公知
の方法〔例えば、Aust.J.Chem.,8,385（1955）,Russian
Chemical Reviews,42（７）,587（1973）〕によって容
易に合成することができる。Next, a method for producing the compound as a component of the present invention will be described. The compound as the component of the present invention can be obtained in good yield by the method described below, but the scope of the present invention is not limited thereto. In addition, general formula (II),
The starting material represented by (III) is a generally known and known method [eg, Aust. J. Chem., 8,385 (1955), Russian.
Chemical Reviews, 42 (7), 587 (1973)].
製造法 （式中、Ｘ、Ｙ、ｎ、R1、R2は前記と同じ意味を有し、
H1はハロゲン原子を意味する） 一般式（II）で表わされる化合物と一般式（III）で表
わされる化合物を、メタノール、エタノール、アセト
ン、ジメチルホルムアミド等の有機溶媒中、20〜120℃
にて１〜48時間反応させることにより（Ｉ）を得ること
ができる。Manufacturing method (In the formula, X, Y, n, R 1 and R 2 have the same meanings as described above,
H1 means a halogen atom) The compound represented by the general formula (II) and the compound represented by the general formula (III) are placed in an organic solvent such as methanol, ethanol, acetone or dimethylformamide at 20 to 120 ° C.
(I) can be obtained by reacting at 1 to 48 hours.
実施例 以下に実施例を示し、本発明を更に具体的に説明する。
勿論、本発明はこれら実施例のみに限定されものではな
い。Examples The present invention will be described in more detail below with reference to Examples.
Of course, the present invention is not limited to these examples.
実施例１ α−クロロデオキシベンゾイン3.45g及びＮ−（２−モ
ルホリノエチル）チオ尿素2.85gをエタノールに加え、
次いで24時間還流を行った。その後エタノールを減圧留
去し、残渣を0.1NHClに溶解させ、酢酸エチルで洗浄し
た。次いで５％NaOHでアルカリ性にし、酢酸エチルで抽
出した後乾燥させ、さらに酢酸エチルを減圧留去する
と、4,5−ジフェニル−２−（２−モルホリノエチル）
アミノチアゾール3.8gを得た。Example 1 3.45 g of α-chlorodeoxybenzoin and 2.85 g of N- (2-morpholinoethyl) thiourea were added to ethanol,
Then, the mixture was refluxed for 24 hours. After that, ethanol was distilled off under reduced pressure, the residue was dissolved in 0.1N HCl, and washed with ethyl acetate. Then it was made alkaline with 5% NaOH, extracted with ethyl acetate, dried, and ethyl acetate was distilled off under reduced pressure to give 4,5-diphenyl-2- (2-morpholinoethyl).
3.8 g of aminothiazole was obtained.
この物質の融点及び元素分析値は下記の通りであった。The melting point and elemental analysis values of this substance were as follows.
融 点 116〜118℃ 元素分析値 C21H23N3OSとして 計 算 値 N:69.01 H:6.34 N:11.50 実 測 値 N:69.11 H:6.33 N:11.72 実施例２ α−ブロモ−4,4′−ジフルオロデオキシベンゾイン2.3
4g及びＮ−（２−ピリジル）チオ尿素1.22gをエタノー
ル30mlに加え、次いで１時間還流を行った。さらに24時
間室温で撹拌した後析出した4,5−ビス（４−フルオロ
フェニル）−２−（２−ピリジル）アミノチアゾール臭
酸塩をろ取した。次いでその結晶に５％NaOH水20ml加え
て、酢酸エチルで抽出した後、乾燥させ、さらに酢酸エ
チルを減圧留去すると、4,5−ビス（４−フルオロフェ
ニル）−２−（２−ピリジル）アミノチアゾール1.2gを
得た。Melting point 116 to 118 ° C Elemental analysis value C 21 H 23 N 3 Calculated value as OS N: 69.01 H: 6.34 N: 11.50 Actual value N: 69.11 H: 6.33 N: 11.72 Example 2 α-bromo-4, 4'-difluorodeoxybenzoin 2.3
4 g and 1.22 g of N- (2-pyridyl) thiourea were added to 30 ml of ethanol and then refluxed for 1 hour. After further stirring at room temperature for 24 hours, the precipitated 4,5-bis (4-fluorophenyl) -2- (2-pyridyl) aminothiazole hydrobromide was collected by filtration. Then, 20% of 5% NaOH water was added to the crystals, extracted with ethyl acetate, dried, and ethyl acetate was distilled off under reduced pressure to give 4,5-bis (4-fluorophenyl) -2- (2-pyridyl). 1.2 g of aminothiazole was obtained.
この物質の融点及び元素分析値は下記の通りであった。The melting point and elemental analysis values of this substance were as follows.
融 点 221〜223℃ 元素分析値 C20H13F2N3Sとして 計 算 値 N:65.74 H:3.59 N:11.50 実 測 値 N:65.65 H:3.59 N:11.32 実施例３〜36 実施例1,2の方法に準じて次表の本発明化合物を合成し
た。Melting point 221 to 223 ℃ Elemental analysis value Calculated as C 20 H 13 F 2 N 3 S N: 65.74 H: 3.59 N: 11.50 Actual value N: 65.65 H: 3.59 N: 11.32 Examples 3 to 36 Examples The compounds of the present invention shown in the following table were synthesized according to the methods 1 and 2.
作用 試験例１ 抗炎症作用試験 試験法 体重140g〜160gのウィスター系雄性ラットを１群８匹と
して実験に使用した。試験化合物はいずれも0.5％トラ
ガント水溶液に懸濁し、0.5ml/100g,B.W.の割合で経口
投与した。対照群には同量の0.5％トラガント水溶液を
同様に投与した。試験化合物投与１時間％に１鵜ラムダ
カラゲニン−生理食塩水0.1mlを右後肢足蹠に皮下注射
し、浮腫を惹起させた。以後経時的に足蹠容積を測定し
た。結果は反応惹起３時間目の対照群に抑制率で示し
た。 Action Test Example 1 Anti-inflammatory Action Test Test Method A group of 8 Wistar male rats weighing 140 g to 160 g was used for the experiment. All test compounds were suspended in 0.5% tragacanth aqueous solution and orally administered at a rate of 0.5 ml / 100 g, BW. The same amount of 0.5% tragacanth aqueous solution was similarly administered to the control group. Edema was induced by subcutaneously injecting 1 ml of cormorant lambda carrageenin-physiological saline 0.1 ml into the footpad of the right hind leg for 1 hour after administration of the test compound. Thereafter, the footpad volume was measured over time. The results are shown as the inhibition rate in the control group 3 hours after the reaction was induced.
上記試験結果から明らかなように、この発明の目的化合
物はラットにおける顕著な足浮腫抑制を示し、抗炎症作
用を有することが判明した。 As is clear from the above test results, it was found that the object compound of the present invention exhibited a remarkable inhibition of paw edema in rats and an anti-inflammatory effect.
発明の効果 本発明は顕著な抗炎症作用を有する抗炎症剤を提供し、
他に鎮痛作用，解熱作用，抗リウマチ作用を有するた
め、優れた抗炎症剤としてのみならず、鎮痛剤、解熱
剤、抗リウマチ剤等の医薬品として有用である。Effect of the Invention The present invention provides an anti-inflammatory agent having a remarkable anti-inflammatory effect,
Since it also has analgesic action, antipyretic action and antirheumatic action, it is useful not only as an excellent anti-inflammatory drug but also as a drug such as an analgesic drug, antipyretic drug and antirheumatic drug.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 出口 芳樹 佐賀県鳥栖市田代大官町774―１ (72)発明者 野田 寛治 福岡県筑紫野市大字常松320―93 (56)参考文献 特開 昭54−160369（ＪＰ，Ａ) 特開 昭54−55566（ＪＰ，Ａ) 特開 昭63−243080（ＪＰ，Ａ) 特開 昭58−216186（ＪＰ，Ａ) 特開 昭50−121269（ＪＰ，Ａ) 特開 昭57−118574（ＪＰ，Ａ) 米国特許4307106（ＵＳ，Ａ) 米国特許3458526（ＵＳ，Ａ) Ｃｈｅｍｉｃａｌ Ａｂｓｔｒａｃｔｓ 106：102309ｇ（1987) Ｊ．Ｈｅｔｅｒｏｃｙｃｌ．Ｃｈｅｍ. Ｖｏｌ．16 Ｎｏ．７（1979）Ｐ．1377− 1383 Ｉｎｄｉａｎ．Ｊ．Ｃｈｅｍ．Ｓｅｃ ｔ．Ｂ 17 Ｂ（1979）Ｐ．22−24 Ｊ．Ｈｅｔｅｒｏｃｙｃｌ．Ｃｈｅｍ. Ｖｏｌ．13 Ｎｏ．４（1976）Ｐ．873− 876 Ｊ．Ｈｅｔｅｒｏｃｙｃｌ．Ｃｈｅｍ. Ｖｏｌ．11 Ｎｏ．１（1974）Ｐ．91−92 ＣＡ 75：88538ｐ，ＣＡ 74：108592 ｍ ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yoshiki Deguchi 774-1 Tashiro Daikancho, Tosu City, Saga Prefecture (72) Inventor Kanji Noda 320-93, Tsunematsu, Chikushino City, Fukuoka Prefecture (56) References JP 54 -160369 (JP, A) JP 54-55566 (JP, A) JP 63-243080 (JP, A) JP 58-216186 (JP, A) JP 50-121269 (JP, A) ) JP 57-118574 (JP, A) U.S. Pat. No. 4307106 (US, A) U.S. Pat. No. 3458526 (US, A) Chemical Abstracts 106: 102309 g (1987) J. Am. Heterocycl. Chem. Vol. 16 No. 7 (1979) P. 1377-1383 Indian. J. Chem. Sec t. B 17 B (1979) P. 22-24 J. Heterocycl. Chem. Vol. 13 No. 4 (1976) P. 873-876 J. Heterocycl. Chem. Vol. 11 No. 1 (1974) p. 91-92 CA 75: 88538p, CA 74: 108592m
Claims (1)
ハロゲン原子または低級アルキル基を、ｎは０〜７の整
数を、R1は水素原子またはアシル基を、R2は長鎖アルキ
ル基、シクロアルキル基、低級アルコキシ基、無置換ま
たは置換フェノキシ基、複素環基または環状アミノ基を
意味する） で表わされる置換ジフェニルチアゾール誘導体及びその
医薬として有用な酸付加塩（但し、R2が低級アルキル基
又はハロゲンで置換されてもよいチエニル基又はフリル
基である場合を除く、また、Ｘ及びＹが４−OMeの場合
はR2が長鎖アルキル基である場合を除く）からなる抗炎
症剤。1. A general formula (In the formula, X and Y may be the same or different, a hydrogen atom,
A halogen atom or a lower alkyl group, n is an integer of 0 to 7, R 1 is a hydrogen atom or an acyl group, R 2 is a long-chain alkyl group, a cycloalkyl group, a lower alkoxy group, an unsubstituted or substituted phenoxy group, A heterocyclic group or a cyclic amino group) and a pharmaceutically useful acid addition salt thereof, provided that R 2 is a lower alkyl group or a thienyl group or a furyl group optionally substituted with halogen. Except in certain cases, and when X and Y are 4-OMe, R 2 is a long chain alkyl group).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62230074A JPH0753666B2 (en) | 1987-09-14 | 1987-09-14 | Anti-inflammatory agent consisting of substituted diphenylthiazole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62230074A JPH0753666B2 (en) | 1987-09-14 | 1987-09-14 | Anti-inflammatory agent consisting of substituted diphenylthiazole derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6475475A JPS6475475A (en) | 1989-03-22 |
| JPH0753666B2 true JPH0753666B2 (en) | 1995-06-07 |
Family
ID=16902136
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62230074A Expired - Lifetime JPH0753666B2 (en) | 1987-09-14 | 1987-09-14 | Anti-inflammatory agent consisting of substituted diphenylthiazole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0753666B2 (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5145860A (en) * | 1989-01-05 | 1992-09-08 | Fujisawa Pharmaceutical Co., Ltd. | Thiazole compounds and pharmaceutical composition comprising the same |
| AU654125B2 (en) * | 1991-03-07 | 1994-10-27 | Hisamitsu Pharmaceutical Co., Inc. | Novel diphenylthyazole derivative |
| BR0013899A (en) | 1999-09-10 | 2003-07-08 | Merck & Co Inc | A compound, pharmaceutical composition, processes for treating or preventing cancer, a disease in which angiogenesis is implicated, retinal vascularization, diabetic retinopathy, age-related macular degeneration, inflammatory diseases, tyrosine-dependent disease or conditions. kinase, bone-associated pathologies, and processes for producing a pharmaceutical composition, and for reducing or preventing tissue damage following a cerebral ischemic event |
| JP2004535437A (en) | 2001-06-22 | 2004-11-25 | メルク エンド カムパニー インコーポレーテッド | Tyrosine kinase inhibitor |
| US6872724B2 (en) | 2002-07-24 | 2005-03-29 | Merck & Co., Inc. | Polymorphs with tyrosine kinase activity |
| BRPI0706621A2 (en) | 2006-01-18 | 2011-04-05 | Amgen Inc | compound, pharmaceutical composition, methods for treating a kinase-mediated disorder in a mammal and for treating a proliferation-related disorder in a mammal, and, use of the compound |
| AU2008276521B2 (en) | 2007-07-17 | 2011-11-03 | Amgen Inc. | Heterocyclic modulators of PKB |
| US7919504B2 (en) | 2007-07-17 | 2011-04-05 | Amgen Inc. | Thiadiazole modulators of PKB |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3458526A (en) | 1966-09-26 | 1969-07-29 | Upjohn Co | Certain 2-amino-4,5-bis(p-methoxyphenyl)thiazoles |
| US4307106A (en) | 1978-06-02 | 1981-12-22 | Pfizer Inc. | Aminothiazoles |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH587836A5 (en) * | 1974-01-31 | 1977-05-13 | Serono Lab | |
| US4168315A (en) * | 1977-09-28 | 1979-09-18 | The Upjohn Company | Dianisyl thiazole compound, compositions and method of antithrombotic treatment |
| DK150068C (en) * | 1978-06-02 | 1987-06-29 | Pfizer | METHOD OF ANALOGUE FOR THE PREPARATION OF AMINOTHIAZOLES |
| JPS57118574A (en) * | 1981-01-13 | 1982-07-23 | Mitsui Toatsu Chem Inc | N-(4-phenylthiazol-2-yl)carbamate derivative, its preparation and medicinal composition containing the same |
| DE3220118A1 (en) * | 1982-05-28 | 1983-12-01 | Bayer Ag, 5090 Leverkusen | ALKYLENE-BRIDGED GUANIDINOTHIAZOLE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICINAL PRODUCTS |
| FR2612187B1 (en) * | 1987-03-12 | 1989-07-21 | Sanofi Sa | THIAZOLE DERIVATIVES ACTIVE IN THE CHOLINERGIC SYSTEM, THEIR PREPARATION METHOD AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
-
1987
- 1987-09-14 JP JP62230074A patent/JPH0753666B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3458526A (en) | 1966-09-26 | 1969-07-29 | Upjohn Co | Certain 2-amino-4,5-bis(p-methoxyphenyl)thiazoles |
| US4307106A (en) | 1978-06-02 | 1981-12-22 | Pfizer Inc. | Aminothiazoles |
Non-Patent Citations (6)
| Title |
|---|
| ＣＡ７５：８８５３８ｐ，ＣＡ７４：１０８５９２ｍ |
| ＣｈｅｍｉｃａｌＡｂｓｔｒａｃｔｓ１０６：１０２３０９ｇ（１９８７） |
| Ｉｎｄｉａｎ．Ｊ．Ｃｈｅｍ．Ｓｅｃｔ．Ｂ１７Ｂ（１９７９）Ｐ．２２−２４ |
| Ｊ．Ｈｅｔｅｒｏｃｙｃｌ．Ｃｈｅｍ．Ｖｏｌ．１１Ｎｏ．１（１９７４）Ｐ．９１−９２ |
| Ｊ．Ｈｅｔｅｒｏｃｙｃｌ．Ｃｈｅｍ．Ｖｏｌ．１３Ｎｏ．４（１９７６）Ｐ．８７３−８７６ |
| Ｊ．Ｈｅｔｅｒｏｃｙｃｌ．Ｃｈｅｍ．Ｖｏｌ．１６Ｎｏ．７（１９７９）Ｐ．１３７７−１３８３ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6475475A (en) | 1989-03-22 |
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