JPS5984868A

JPS5984868A - Ureidobenzamide

Info

Publication number: JPS5984868A
Application number: JP18748183A
Authority: JP
Inventors: Narimitsu Honda; 本田　成光; Hideaki Nagai; 秀明永井; Akiko Takishima; 滝島　章子; Akinori Kawamura; 河村　明典; Masuo Koizumi; 小泉　益男; Yasushi Murakami; 泰村上; Yoshikazu Hinohara; 日野原　好和
Original assignee: Chugai Pharmaceutical Co Ltd
Current assignee: Chugai Pharmaceutical Co Ltd
Priority date: 1982-10-07
Filing date: 1983-10-06
Publication date: 1984-05-16

Abstract

NEW MATERIAL:3-Ureido-N-(6-methyl-2-pyridyl)benzamide of formula. USE:Agent for depressing blood sugar level. PROCESS:The compound of formula can be prepared by (1) reacting 3-nitrobenzoyl chloride with 2-amino-6-methylpyridine in an inert solvent such as acetone, tetrahydrofuran, dioxane, etc. in the presence of a base such as triethylamine, pyridine, etc. at 0-30 deg.C for 1-5hr, (2) reducing the resultant 3-nitro-N-(6-methyl- 2-pyridyl)-benzamide to the corresponding 3-amino derivative by using a catalyst such as palladium-carbon, Raney-nickel, platinum dioxide, etc., (3) dissolving the derivative in an acidic solution acidified with hydrochloric acid, acetic acid, etc., and (4) reacting with an alkali metal cyanate at 0-100 deg.C for 1-5hr.

Description

【発明の詳細な説明】で表わされる新規なウレイドベンズアミド化合物に関す
る。DETAILED DESCRIPTION OF THE INVENTION This invention relates to a novel ureidobenzamide compound represented by:

本発明の化合物は、例えば３−二）０ベンゾイルクロラ
イドと２−アミノ−６−メチルピリジンとをアセトン、
テトラヒドロフラン、ジオキサン等の不活性溶媒中、ト
メエチルアミン、ピリジン等の塩基の存在下０〜３０℃
、１〜５時間反応させて得られる３−ニトロ−Ｎ−（６
−メチル−２−ピリジル）ベンズアミドをパラジウム−
炭素。For example, the compound of the present invention can be prepared by combining 3-2)0 benzoyl chloride and 2-amino-6-methylpyridine with acetone,
In an inert solvent such as tetrahydrofuran or dioxane, in the presence of a base such as tomethylamine or pyridine, at 0 to 30°C
, 3-nitro-N-(6
-Methyl-2-pyridyl)benzamide with palladium-
carbon.

ラネイニッケル、二酸化白金等の触媒を用いて還元して
対応する３−アミノ体とした後、これを塩酸。The corresponding 3-amino compound is reduced using a catalyst such as Raney nickel or platinum dioxide, and then converted to hydrochloric acid.

酢酸等の酸性水溶液に溶解しシアン酸アルカリを加えて
０〜１００℃、１〜５時間反応させることにより得られ
る。It is obtained by dissolving in an acidic aqueous solution such as acetic acid, adding an alkali cyanate, and reacting at 0 to 100°C for 1 to 5 hours.

かくして得ら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 thus obtained has an excellent hypoglycemic effect and is useful as a medicine.

実施例１゜２−アミノ−６−メチルピリジン３２．５ｆ、）リエチ
ルアミン４５ｍＪ及びアセトン６００罰の混合溶液に、
水冷攪拌下、３−ニトロベンゾイルク四ライド５５．８
ｆを徐々に加える。同温度で３０分、次いで室温で１時
間攪拌後、反応溶液を３Ｉｔの水に注ぎ、析出する結晶
を炉取し、水洗後メタノールより再結晶して無色針状晶
の３−二トローＮ−（６−メチ／Ｉ／−２−ピリジル）
ベンズアミド６９、６　ｆを得た。収率９０％、融点１
４５〜１４７℃。この１７．４Ｆ、１０％パラジウム−
炭素１．５１及びエタノール３００ｄの混液に水素を通
じ、常法により接触還元する。計算量の水素を吸収後触
媒を除去し、反応液を減圧濃縮し、残渣をエタノールよ
り再結晶して無色針状晶の３−アミノ−Ｎ−（６−メチ
ル−２−ピリジル）ベンズアミド１１．５ｆを得た。収
率７５Ｘ、融点１１７〜１１８℃。この６．８ｆを５％
塩塩溶溶液５０ゴ溶解し、室温攪拌下、過剰のＩＯＸシ
アン酸カリウム水麹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３−ウレイド−
Ｎ−（６−メチル−２−ピリジル）ベンズアミド６．７
ｆ番得た。収率７５％、融点２０５〜２０７℃０元素分析値　分子式０１４Ｈ１４Ｎ４０２としてＯＨＮ理論値（至）　６２．２１　５．２２　２０．７３実測
値（至）　６２．１９　５．２５　２０．７０実施例２１群５匹の５退会ＤＤＹ系マウス（雄１体重２５〜３０
ｆ）を１６時間絶食後、ア胃キサン７５り／＃を静脈内
に投与し、４８時間後に、本発明化合物（２００り／＃
）の本番会灸棲けん濁液を経口投与し、１５０分後に心
臓から採血し、グルコースオキシダーゼ法により血中糖
量を測定したところ、本発明の化合物の代りに生理食塩
水を投与した対照群が５３６±２５■／ｄであったのに
対し本発明化合物投与群は３４１±３３〜／６（Ｐ　＜
　０．００．１　）と優れた血糖降下を示した。Example 1 In a mixed solution of 32.5 f of 2-amino-6-methylpyridine, 45 mJ of ethylamine and 600 g of acetone,
Under stirring with water cooling, 3-nitrobenzoyl tetralide 55.8
Add f gradually. After stirring at the same temperature for 30 minutes and then at room temperature for 1 hour, the reaction solution was poured into 3It of water, the precipitated crystals were collected in a furnace, washed with water, and then recrystallized from methanol to form colorless needle-like crystals of 3-nitro-N- (6-methy/I/-2-pyridyl)
Benzamide 69,6f was obtained. Yield 90%, melting point 1
45-147°C. This 17.4F, 10% palladium-
Hydrogen is passed through a mixture of 1.51 d of carbon and 300 d of ethanol, and catalytic reduction is carried out by a conventional method. After absorbing the calculated amount of hydrogen, the catalyst was removed, the reaction solution was concentrated under reduced pressure, and the residue was recrystallized from ethanol to give colorless needle-like crystals of 3-amino-N-(6-methyl-2-pyridyl)benzamide 11. I got 5f. Yield 75X, melting point 117-118°C. 5% of this 6.8f
Dissolve 50 g of the salt solution, make it alkaline by adding excess IOX potassium cyanate water koji solution under stirring at room temperature, 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 to obtain colorless needle-shaped 3-ureido.
N-(6-methyl-2-pyridyl)benzamide 6.7
I got number f. Yield 75%, melting point 205-207℃0 Elemental analysis value OHN as molecular formula 014H14N402 Theoretical value (to) 62.21 5.22 20.73 Actual value (to) 62.19 5.25 20.70 Example 2 1 Group of 5 mice with 5 withdrawn DDY mice (1 male weighing 25-30
f) After fasting for 16 hours, 75 l/# of agastric xane was administered intravenously, and 48 hours later, the compound of the present invention (200 l/#
) was orally administered, blood was collected from the heart after 150 minutes, and the blood sugar level was measured using the glucose oxidase method. was 536 ± 25 /d, while in the group administered with the compound of the present invention it was 341 ± 33 - /6 (P <
0.00.1), which showed an excellent blood sugar lowering.

出願人　　中外製薬株式会社第１頁の続き ′０発　明　者　日野原好和東京都豊島区高田三丁目４１番８号中外製薬株式会社内Applicant: Chugai Pharmaceutical Co., Ltd. Continuation of page 1 '0 shot clear person Yoshikazu Hinohara 3-41-8 Takada, Toshima-ku, Tokyo Inside Chugai Pharmaceutical Co., Ltd.

Claims

[Claims]

Ureidobenzamide represented by 0