JPS59181257A - Ureidobenzamide derivative - Google Patents
Ureidobenzamide derivativeInfo
- Publication number
- JPS59181257A JPS59181257A JP5380383A JP5380383A JPS59181257A JP S59181257 A JPS59181257 A JP S59181257A JP 5380383 A JP5380383 A JP 5380383A JP 5380383 A JP5380383 A JP 5380383A JP S59181257 A JPS59181257 A JP S59181257A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- derivative
- ureidobenzamide
- give
- 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
- CXGQKYNRBWUOMP-UHFFFAOYSA-N 2-(carbamoylamino)benzamide Chemical class NC(=O)NC1=CC=CC=C1C(N)=O CXGQKYNRBWUOMP-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical group [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 16
- 150000001412 amines Chemical class 0.000 abstract description 6
- 239000012948 isocyanate Substances 0.000 abstract description 3
- 150000002513 isocyanates Chemical class 0.000 abstract description 3
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 239000008280 blood Substances 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract description 2
- -1 nitrobenzoyl halide Chemical class 0.000 abstract description 2
- KLGQWSOYKYFBTR-UHFFFAOYSA-N 2-nitrobenzamide Chemical class NC(=O)C1=CC=CC=C1[N+]([O-])=O KLGQWSOYKYFBTR-UHFFFAOYSA-N 0.000 abstract 1
- 150000008065 acid anhydrides Chemical class 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- QUXLCYFNVNNRBE-UHFFFAOYSA-N 6-methylpyridin-2-amine Chemical compound CC1=CC=CC(N)=N1 QUXLCYFNVNNRBE-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FKBYDGHOPOEEEP-UHFFFAOYSA-N 2-pyridin-2-ylbenzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC=CC=N1 FKBYDGHOPOEEEP-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000005755 formation reaction Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は次の一般式
〔式中Ｒ１は水素原子又は１〜２個の低級アルキル基を
示し、Ｙは２位又は４位に結合する基−ＮＨ０ＯＮＨＲ
２（ここで８２は水素原子、低級アルキル基又は核に置
換基を有し得るアリール基を意味する）を示し、ｎは０
又は１を示す〕
で表わされるウレイドベンズアミド誘導体に関する。Detailed Description of the Invention The present invention is based on the following general formula [wherein R1 represents a hydrogen atom or 1 to 2 lower alkyl groups, and Y is a group bonded to the 2- or 4-position -NH0ONHR]
2 (here, 82 means a hydrogen atom, a lower alkyl group, or an aryl group that may have a substituent on the nucleus), and n is 0.
or 1] The present invention relates to a ureidobenzamide derivative represented by:
上式（１）で表わされる本発明の化合物は優れた血糖降
下作用を有し医薬として有用である。The compound of the present invention represented by the above formula (1) has an excellent hypoglycemic effect and is useful as a medicine.
本発明の化合物は例えば以下に示すようにニトロベンゾ
イルハライドとアミン類とを塩基の存在下反応させ二）
ｏベンズアミド誘導体とし、次いで常法により還元して
アミノベンズアミド誘導体とした後、インシアナート類
と反応させることに゛、より得ることができる。また２
−ウレイドベンズアミド誘導体の場合は、無水イサトン
酸とアミン類とを反応させ２−了ミノベンズアミド誘導
体とし、次いでイソシアナー）類と反応させることによ
っても得ることができる。The compound of the present invention can be prepared by reacting nitrobenzoyl halide with an amine in the presence of a base, for example, as shown below.
It can be obtained by making an o-benzamide derivative, then reducing it by a conventional method to make an aminobenzamide derivative, and then reacting it with an incyanate. Also 2
-Ureidobenzamide derivatives can also be obtained by reacting isatonic anhydride with amines to obtain 2-ureidobenzamide derivatives, and then reacting with isocyaners.
これを式示ずれば以下のとおりである。尚、式中Ｘはハ
ロゲン原子を意味し、その他の記号もま前記と同一の意
味を有する。The formula for this is as follows. In the formula, X means a halogen atom, and the other symbols have the same meanings as above.
〔■〕Ｃｍ）
［）１
化合物（Ｕ）とアミン類との反応は通常の酸アミド形成
反応条件により行なわれ、例えば、アセトン、テトラヒ
ドロフラン、ジオキサン等の不活性溶媒中、好ましくは
、トリエチルアミン、ビ１）ジン等の塩基の存在下Ｏ〜
３０℃、１〜５時間で行なわれる。[■]Cm) [)1 The reaction between compound (U) and amines is carried out under normal acid amide forming reaction conditions, for example, in an inert solvent such as acetone, tetrahydrofuran, dioxane, etc., preferably in triethylamine, dioxane, etc. 1) O in the presence of a base such as gin
It is carried out at 30°C for 1 to 5 hours.
化合物帽〕は常法により、例えば、ノぐラジウム−炭素
、ラネイニッケル等の触媒を用いる還元反応により化合
物（Ｖ）に導くことができる。The compound (V) can be introduced into the compound (V) by a conventional method, for example, by a reduction reaction using a catalyst such as noradium-carbon or Raney nickel.
一方、無水イサトン［１２（ＩＶ）とアミン類との反応
は無浴媒、あるいは、ジオキサン、トルエン、キシレン
等の溶媒中、攪拌下５０〜１８０℃、１〜５時間で行な
われ化合物（Ｖ） （２−置換体）を得ることができる
。On the other hand, the reaction between anhydrous isatone [12(IV) and amines is carried out without bath or in a solvent such as dioxane, toluene, xylene, etc., at 50 to 180°C for 1 to 5 hours with stirring, resulting in compound (V). (2-substituted product) can be obtained.
化合物〔■〕とイソシアナート類との反応（ま通常の尿
素形成反応条件により行なわれ、例えばＲ２〆Ｈのとき
は、ベンゼン、トルエン、アセトン、テトラヒト占フラ
ン、ジオキサン等の不活性溶媒中、好ましくはトリエチ
ルアミン、ピリジン等の塩基の存在下２０〜１０α１〜
４８時間で行なわれる。また、Ｒ２＝Ｈのときは、化合
物〔■〕を塩酸。Reaction of compound [■] with isocyanates (carried out under normal urea formation reaction conditions; for example, in the case of R2H, reaction is preferably carried out in an inert solvent such as benzene, toluene, acetone, tetrahydrofuran, dioxane, etc.) is 20~10α1~ in the presence of a base such as triethylamine or pyridine.
It will be done in 48 hours. Moreover, when R2=H, the compound [■] is hydrochloric acid.
酢酸等の酸性水溶液に溶解し、次いでシアン酸アルカリ
水溶液を攪拌下加え、０〜１００℃、１〜５時間で行な
われる。It is dissolved in an acidic aqueous solution such as acetic acid, then an alkali cyanate aqueous solution is added under stirring, and the reaction is carried out at 0 to 100°C for 1 to 5 hours.
実施例１゜
無水イサトン酸２５９．２−アミノ−６−メチルビリジ
ン１６．６ ｒを蕪溶媒攪拌下１００℃に加熱する。し
ばらくして発泡が始まるが、さらに同湿度で４時間攪拌
を続ける。冷後反応混合物をクロロホルムに溶解後シリ
カゲルクロマトグラフィーに付しクロロホルム流出部よ
り、２−アミノ−Ｎ−６−メチル−２−ピリジルベンズ
アミド１３２を得た（無色プリズム晶、ｎ−ヘキサン、
ベンゼン混合溶媒から再結晶）。収率３７％、融点８６
〜８７℃。Example 1: 259.2-amino-6-methylpyridine isatonic anhydride and 16.6 r of 2-amino-6-methylpyridine are heated to 100 DEG C. with stirring in a solvent. Foaming begins after a while, but stirring is continued for another 4 hours at the same humidity. After cooling, the reaction mixture was dissolved in chloroform and subjected to silica gel chromatography, and 2-amino-N-6-methyl-2-pyridylbenzamide 132 was obtained from the chloroform outflow (colorless prism crystals, n-hexane,
(recrystallized from benzene mixed solvent). Yield 37%, melting point 86
~87℃.
この２．３ｆを５％塩酸溶液１５ｍ１に溶解し、室温（
ひ拌下、過剰の１０％シアン酸カリウム水浴液を加えて
アルカリ性とし、同温度で２時間攪拌を続ける。析出し
た結晶を＼炉取し、水洗後メタノールから再結晶して、
無色針状晶の２−ウレイド−Ｎ−６−メチル−２−ピリ
ジルベンズアミド（化合物１ ） ２．１９を得た。This 2.3f was dissolved in 15ml of 5% hydrochloric acid solution, and room temperature (
While stirring, add an excess of 10% potassium cyanate aqueous solution to make alkaline, and continue stirring at the same temperature for 2 hours. The precipitated crystals were collected in a furnace, washed with water, and then recrystallized from methanol.
2.19 of 2-ureido-N-6-methyl-2-pyridylbenzamide (compound 1) was obtained as colorless needle-like crystals.
収率７７％、融点１８０〜１８１℃。Yield 77%, melting point 180-181°C.
元素分析値 分子式０１４Ｈ１４Ｎ４０２としてＯＨＮ
理論値（財） ６２．２１ ５．２２ ２０．７３実
測値（至） ６２．２４ ５．２５ ２０．７６実施
例２゜
２−アミ／−Ｎ−６−メチル−２−ピリジルベンズアミ
ド２．３ｆお上びアセトン２０ｍ／の混合溶液に室温攪
拌下メチルイソシアナート０．６９および触媒量のトリ
エチルアミンを加える。２４時間攪拌後、析出する結晶
を炉腹し、水洗後アセトンから再結晶して無色針状晶の
２−（３−メチルウレイド）−Ｎ−６−メチル−２−ピ
リジルベンズアミド（化合物２）２．５ｆを得た。Elemental analysis value OHN as molecular formula 014H14N402 Theoretical value (Foundation) 62.21 5.22 20.73 Actual value (To) 62.24 5.25 20.76 Example 2゜2-Ami/-N-6-Methyl- To a mixed solution of 2.3 f of 2-pyridylbenzamide and 20 m of acetone, 0.69 g of methyl isocyanate and a catalytic amount of triethylamine are added while stirring at room temperature. After stirring for 24 hours, the precipitated crystals were crushed, washed with water, and recrystallized from acetone to obtain colorless needle-like crystals of 2-(3-methylureido)-N-6-methyl-2-pyridylbenzamide (compound 2). .5f was obtained.
収率８７％、融点１３５〜１３６℃。Yield 87%, melting point 135-136°C.
元素分析値 分子式０１５ ＨＩ３ Ｎ４０２としてＯ
ＨＮ
理論値（６） ６３．３６ ５．６７ １９．７１”実
測値（財） ６３．３２ ５．６４ １９．７４実施
例３゜
２−アミノ−６−メチルピリジン１４．６ｆ、）リエチ
ルアミン２５ ｒｉｌおよびアセトン３００ｄの混合溶
液に、水冷攪拌下、４−ニトロベンゾイルクロライド２
５２を徐々に加える。同温度で３０分、次いで室温で１
時間投拌後、反応溶液を１．５１の水に注ぎ、析出する
結晶を炉腹し、水洗後メタノールから再結晶して無色針
状晶の４−ニトロ−Ｎ−６−メチル−２−ピリジルベン
ズアミド２０Ｖを得た。収率５８％、融点２３１〜２３
２℃。Elemental analysis value Molecular formula 015 HI3 N402 as O
HN Theoretical value (6) 63.36 5.67 19.71" Actual value (foundation) 63.32 5.64 19.74 Example 3゜2-amino-6-methylpyridine 14.6f,) ethylamine 25 4-nitrobenzoyl chloride 2 was added to a mixed solution of 300 d of ril and acetone under water cooling and stirring.
52 gradually. 30 minutes at the same temperature, then 1 hour at room temperature.
After stirring for an hour, the reaction solution was poured into 1.51 g of water, and the precipitated crystals were filtered, washed with water, and recrystallized from methanol to form colorless needle-like crystals of 4-nitro-N-6-methyl-2-pyridyl. Benzamide 20V was obtained. Yield 58%, melting point 231-23
2℃.
この２（１’、１０％パラジウム−炭素１．５２および
エタノール３００ｍ１の混液に水素を通じ、常法により
接触還元する。計ｎ量の水素を吸収後触媒を除去し、反
応液を減圧濃縮し、残渣をｎ−ヘキサン、ベンゼンの混
合浴媒から再結晶して無色プリズム晶の４−アミノ−Ｎ
−６−メチル−２−ピリジルベンズアミドｌ ５．７
ｆを得た。Hydrogen is passed through a mixture of 2(1', 1.52 ml of 10% palladium-carbon and 300 ml of ethanol, and catalytic reduction is carried out by a conventional method. After absorbing a total of n amount of hydrogen, the catalyst is removed, and the reaction liquid is concentrated under reduced pressure. The residue was recrystallized from a mixed bath medium of n-hexane and benzene to obtain colorless prismatic crystals of 4-amino-N.
-6-Methyl-2-pyridylbenzamide l 5.7
I got f.
収率８９％、融点１３６〜１３７℃。Yield 89%, melting point 136-137°C.
この２．３ｆを５％塩酸浴液１５ｍＪに溶解し、室温攪
拌下、過剰の１０％シアン酸カリウム水溶液を加えてア
ルカリ性とし、同温度で２時間攪拌を続ける。析出した
結晶を炉取し水洗後メタ７−ルから再結晶して無色針状
晶の４−ウレイド−Ｎ−６−メチル−２−ピリジルベン
ズアミド（化合物３ ）１．９を得た。This 2.3f is dissolved in 15 mJ of a 5% hydrochloric acid bath solution, and while stirring at room temperature, an excess of 10% potassium cyanate aqueous solution is added to make it alkaline, and stirring is continued at the same temperature for 2 hours. The precipitated crystals were collected in a furnace, washed with water, and then recrystallized from methanol to obtain 1.9 g of 4-ureido-N-6-methyl-2-pyridylbenzamide (compound 3) as colorless needle-like crystals.
収率６９％、融点２２５〜２２７℃。Yield 69%, melting point 225-227°C.
元素分析値 分子式〇１４ ＨＩ３ Ｎ４０２として０
、 ＨＮ
理論値（財） ６２，２１ ５．２２ ２０．７３実測
値（至） ６２．２３ ５．２６ ２０．７１実施例４
゜
４−アミノ−Ｎ−６−メチル−２−ピリジルベンズアミ
ド２．３１およびアセトン２０ｒｒｔｌの混合溶液に室
温攪拌下、メチルイソシアナート０．６２および触媒ｉ
ｔのトリエチルアミンを加える。２４時間攪拌後、析出
する結晶を炉取し水洗後、アセトンから再結晶して無色
針状晶の４−（３−メチルウレイド）−Ｎ−６−メチル
−２−ピリジルベンズアミド（化合物４）２．４９を得
た。収率８３％、融点２００〜２０２℃。Elemental analysis value Molecular formula 〇14 HI3 0 as N402
, HN Theoretical value (goods) 62.21 5.22 20.73 Actual value (to) 62.23 5.26 20.71 Example 4
゜Methyl isocyanate 0.62 and catalyst i were added to a mixed solution of 2.31 4-amino-N-6-methyl-2-pyridylbenzamide and 20 rrtl of acetone with stirring at room temperature.
Add t of triethylamine. After stirring for 24 hours, the precipitated crystals were collected in a furnace, washed with water, and then recrystallized from acetone to obtain colorless needle-like crystals of 4-(3-methylureido)-N-6-methyl-2-pyridylbenzamide (compound 4) 2 I got .49. Yield 83%, melting point 200-202°C.
元素分析値 分子式ｃｔｓ ）（ｔａ Ｎ４０２として
０ ）（Ｎ
理論値（至） ６３．３６ ５．６７ １９．７１
実測値（至） ６３．３２ ５．６１ １９．７６
実施例４６゜
１群５匹の５迎令ＤＤＹ系マウス（雄９体重２５〜３０
ｆ）を１６時間絶食後、アルキサン７５ｍｇ／Ｈを静脈
内に投与し、４８時間後に、本発明化合物（２００ｍ！
ｉ’／Ｍｆ）の水溶液又はけん濁液を経口投与し、１５
０分後に心煕から採血し、グルなお、表中の化合物番号
は、前記実施例の化合物番号に対応している。Elemental analysis value Molecular formula cts ) (ta 0 as N402) (N Theoretical value (to) 63.36 5.67 19.71
Actual value (to) 63.32 5.61 19.76
Example 46゜Group: 5 mice of the 5-year-old DDY strain (9 males weighing 25-30
f) After fasting for 16 hours, 75 mg/H of alkane was administered intravenously, and 48 hours later, the compound of the present invention (200 m!) was administered intravenously.
Orally administer an aqueous solution or suspension of i'/Mf),
After 0 minutes, blood was collected from Shin Hee.The compound numbers in the table correspond to the compound numbers in the above examples.
来Ｐ：＜０．０５ 未来： Ｐ＜０．０１ 来米米
：Ｐ＜０．００１表４Coming to the United States: P<0.05 Future: P<0.01 Coming to the United States: P<0.001 Table 4
Claims (1)
示し、Ｙは２位又は４位に結合する基−ＮＨ００Ｎ Ｈ
Ｒ，２（ここでＲ１２は水素原子、低級アルキル基又は
核に置換基を有し得る了り−ル基を意味する）を示し、
ｎはＯ又は１を示す〕 で表わされるウレイドベンズアミド誘導体。[Claims] General formula [In the formula, R1 represents a hydrogen atom or 1 to 2 lower alkyl groups, and Y is a group bonded to the 2- or 4-position -NH00NH
R, 2 (here, R12 means a hydrogen atom, a lower alkyl group, or an atomyl group which may have a substituent on the nucleus),
n represents O or 1] A ureidobenzamide derivative represented by:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5380383A JPS59181257A (en) | 1983-03-31 | 1983-03-31 | Ureidobenzamide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5380383A JPS59181257A (en) | 1983-03-31 | 1983-03-31 | Ureidobenzamide derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS59181257A true JPS59181257A (en) | 1984-10-15 |
Family
ID=12952963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5380383A Pending JPS59181257A (en) | 1983-03-31 | 1983-03-31 | Ureidobenzamide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59181257A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996034856A1 (en) * | 1995-05-05 | 1996-11-07 | Grelan Pharmaceutical Co. Ltd. | 2-ureido-benzamide derivatives |
| US6376515B2 (en) | 2000-02-29 | 2002-04-23 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor Xa |
| WO2002062295A3 (en) * | 2001-02-02 | 2003-07-03 | Icagen Inc | Pyridine-substituted benzanilides as potassium ion channel openers |
| US6737422B2 (en) | 1999-08-04 | 2004-05-18 | Icagen, Inc. | Benzanilides as potassium channel openers |
| US6844367B1 (en) | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| WO2006052722A1 (en) * | 2004-11-09 | 2006-05-18 | Smithkline Beecham Corporation | Glycogen phosphorylase inhibitor compounds and pharmaceutical compositions thereof |
| AU2002238023B2 (en) * | 1999-08-04 | 2008-03-13 | Icagen, Inc | Pyridine-substituted benzanilides as potassium ion channel openers |
| US8524907B2 (en) | 2006-11-02 | 2013-09-03 | Millennium Pharmaceuticals, Inc. | Methods of synthesizing pharmaceutical salts of a factor Xa inhibitor |
-
1983
- 1983-03-31 JP JP5380383A patent/JPS59181257A/en active Pending
Cited By (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0742208A1 (en) * | 1995-05-05 | 1996-11-13 | Grelan Pharmaceutical Co., Ltd. | 2-Ureido-benzamide derivatives |
| US5872115A (en) * | 1995-05-05 | 1999-02-16 | Grelan Pharmaceutical Co. Ltd. | 2-ureido-benzamide derivatives |
| WO1996034856A1 (en) * | 1995-05-05 | 1996-11-07 | Grelan Pharmaceutical Co. Ltd. | 2-ureido-benzamide derivatives |
| US6989398B2 (en) | 1999-08-04 | 2006-01-24 | Icagen, Inc. | Benzanilides as potassium channel openers |
| AU2002238023B2 (en) * | 1999-08-04 | 2008-03-13 | Icagen, Inc | Pyridine-substituted benzanilides as potassium ion channel openers |
| US6737422B2 (en) | 1999-08-04 | 2004-05-18 | Icagen, Inc. | Benzanilides as potassium channel openers |
| US7285565B2 (en) | 1999-09-17 | 2007-10-23 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US6844367B1 (en) | 1999-09-17 | 2005-01-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US7342013B2 (en) | 2000-02-29 | 2008-03-11 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US8691847B2 (en) | 2000-02-29 | 2014-04-08 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US6835739B2 (en) | 2000-02-29 | 2004-12-28 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US7314874B2 (en) | 2000-02-29 | 2008-01-01 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US10179124B2 (en) | 2000-02-29 | 2019-01-15 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US6376515B2 (en) | 2000-02-29 | 2002-04-23 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor Xa |
| US9629831B2 (en) | 2000-02-29 | 2017-04-25 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor XA |
| US7727982B2 (en) | 2000-02-29 | 2010-06-01 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US7727981B2 (en) | 2000-02-29 | 2010-06-01 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US8063036B2 (en) | 2000-02-29 | 2011-11-22 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| US9108922B2 (en) | 2000-02-29 | 2015-08-18 | Millennium Pharmaceuticals, Inc. | Benzamides and related inhibitors of factor Xa |
| WO2002062295A3 (en) * | 2001-02-02 | 2003-07-03 | Icagen Inc | Pyridine-substituted benzanilides as potassium ion channel openers |
| JP2008519761A (en) * | 2004-11-09 | 2008-06-12 | スミスクライン ビーチャム コーポレーション | Glycogen phosphorylase inhibiting compound and pharmaceutical composition thereof |
| WO2006052722A1 (en) * | 2004-11-09 | 2006-05-18 | Smithkline Beecham Corporation | Glycogen phosphorylase inhibitor compounds and pharmaceutical compositions thereof |
| US8524907B2 (en) | 2006-11-02 | 2013-09-03 | Millennium Pharmaceuticals, Inc. | Methods of synthesizing pharmaceutical salts of a factor Xa inhibitor |
| US9221758B2 (en) | 2006-11-02 | 2015-12-29 | Millennium Pharmaceuticals, Inc. | Methods of synthesizing pharmaceutical salts of a factor Xa inhibitor |
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