JPS6140266A - Pyrazole derivative - Google Patents
Pyrazole derivativeInfo
- Publication number
- JPS6140266A JPS6140266A JP16332784A JP16332784A JPS6140266A JP S6140266 A JPS6140266 A JP S6140266A JP 16332784 A JP16332784 A JP 16332784A JP 16332784 A JP16332784 A JP 16332784A JP S6140266 A JPS6140266 A JP S6140266A
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- Prior art keywords
- phenyl
- pyrazole
- group
- formula
- alkyl
- Prior art date
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Abstract
Description
【発明の詳細な説明】
本発明は一般式
〔式中 R+は水素原子、低級アルキル基、低級アルキ
ルカルボン酸基、低級アルキルカルボン酸エステル基、
フェニル基、またはベンジル基、R2はカルボン酸基、
カルボン酸エステル基、Nに置換基を有するか若しくは
有しないカルバモイル基、または置換基を有するか若し
くは有しない低級アルキル基 R3は直鎖アルキル基、
またはベンゼン核の4位若しくはベンジル基のα位に置
換基を有するかあるいは有しないベンジル基を表わす〕
で示されるピラゾール誘導体CI)に関する。Detailed Description of the Invention The present invention is based on the general formula [wherein R+ is a hydrogen atom, a lower alkyl group, a lower alkyl carboxylic acid group, a lower alkyl carboxylic acid ester group,
Phenyl group or benzyl group, R2 is carboxylic acid group,
a carboxylic acid ester group, a carbamoyl group with or without a substituent on N, or a lower alkyl group with or without a substituent; R3 is a straight-chain alkyl group;
or a benzyl group with or without a substituent at the 4-position of the benzene nucleus or the α-position of the benzyl group]
Regarding the pyrazole derivative CI) represented by
上記CI)で示される本発明のピラゾール誘導体は、新
規化合物で優れた脂質低下作用、すなわち、高トリグリ
セライド血症う/トの血清脂質(トリグリセライド、ト
ータルコレステロール、リン脂質)を顕著に低下させる
作用を有し、かつHDL−コレステロールを顕著に上昇
させしかも低毒性の化合物であることより医薬品として
有用である。The pyrazole derivative of the present invention, represented by CI) above, is a novel compound that exhibits an excellent lipid-lowering effect, that is, an effect that significantly lowers serum lipids (triglycerides, total cholesterol, and phospholipids) in patients with hypertriglyceridemia. This compound is useful as a pharmaceutical because it significantly increases HDL-cholesterol and has low toxicity.
本発晶の花合物(’f、)は、種々の方法により製造す
ることができる。例えば、アセトフェノンをDMF中炭
酸カリウムの存在下、アルキル化またはベンジル化し、
ついでカルカリ存在下ジエチルシュウ酸をクライゼン縮
合させて得られる一般式(R5は上記と同じものを表わ
す)
で示されるエノラートナトリウム塩を、酢酸中、抱水ヒ
ドラジン、硫酸フェニルヒドラジンまたはメチルヒドラ
ジンで2〜6時間加熱還流することによって一般式(、
III)
〔式中、R1は水素原子、メチル基、またはフェニル基
、R5は直鎖アルキル基、またはベンゼン核の4位若し
くはベンジル基のα位に置換基を有するかあるいは有し
ないベンジル基を表わす〕で示されるピラゾール誘導体
を得る。The flower compound ('f,) of this crystallization can be produced by various methods. For example, acetophenone is alkylated or benzylated in the presence of potassium carbonate in DMF,
Then, the enolate sodium salt represented by the general formula (R5 represents the same as above) obtained by Claisen condensation of diethyloxalic acid in the presence of alkali was treated with hydrazine hydrate, phenylhydrazine sulfate, or methylhydrazine in acetic acid. By heating under reflux for 6 hours, the general formula (,
III) [In the formula, R1 represents a hydrogen atom, a methyl group, or a phenyl group, and R5 represents a straight-chain alkyl group, or a benzyl group with or without a substituent at the 4-position of the benzene nucleus or the α-position of the benzyl group. ] to obtain a pyrazole derivative.
一般式〔■〕において、R1が低級アルキル基、低級ア
ルキルカルボン酸基、低級アルキルカルボン酸エステル
基、またはベンジル基の場合は、対応するハロゲン化物
と一般式〔■〕のR1が尿素原子である化合物を、DM
F中、炭酸カリウムの存在下、アルキル化またはベンジ
ル化することによって製造することができる。In the general formula [■], when R1 is a lower alkyl group, a lower alkylcarboxylic acid group, a lower alkylcarboxylic acid ester group, or a benzyl group, the corresponding halide and R1 in the general formula [■] are a urea atom. Compound, DM
It can be produced by alkylation or benzylation in F in the presence of potassium carbonate.
また一般式〔■〕においてR2がカルボン酸基の製造は
、上記で合成した対応するエステルを低級アルカノール
水溶液中、約80°Cで水酸化ナトリウムと反応させる
ことによって製造される。In the general formula [■], R2 is a carboxylic acid group, which is produced by reacting the corresponding ester synthesized above with sodium hydroxide in an aqueous lower alkanol solution at about 80°C.
また一般式〔I〕において、R2がカルバモイル基の化
合物の場合は、上記製法によって得られるカルボン酸を
、酸塩化物に変換したのち、ルイス塩基存在下、種々の
アミン類と反応させることによって製造される。In addition, in the case of a compound in which R2 is a carbamoyl group in general formula [I], the carboxylic acid obtained by the above production method is converted into an acid chloride, and then the compound is reacted with various amines in the presence of a Lewis base. be done.
また一般式CI)において R2がカルボン酸エステル
のうち、エチルエステル以外のものについては、上記製
法によって得られる酸塩化物にベンゼン中、種々のアル
コールを反′応させることによって製造される。Among the carboxylic acid esters in the general formula CI), those in which R2 is a carboxylic acid ester other than ethyl ester are produced by reacting the acid chloride obtained by the above production method with various alcohols in benzene.
つぎに、実施例を挙げて本発明の詳細な説明する。Next, the present invention will be explained in detail by giving examples.
実施例1
エチル5−L:4−(4−クロロベンジロキシ)フェニ
ル〕ピラゾール−6−カルボキシレートナトリウム1−
エトキシカルボニル−6−(4−クロロベンジロキシ)
フェニル−6−オキツブロバネート2142をエタノー
ル+0[]amに溶解し、抱水ヒドラジンろろノを室温
攪拌下滴下する。Example 1 Ethyl 5-L: 4-(4-chlorobenzyloxy)phenyl]pyrazole-6-carboxylate sodium 1-
Ethoxycarbonyl-6-(4-chlorobenzyloxy)
Phenyl-6-oxitubrovanate 2142 is dissolved in ethanol + 0 [am], and hydrazine hydrate is added dropwise under stirring at room temperature.
滴下終了後、攪拌下1時間加熱還流する。冷接、反応液
を減圧下濃縮乾固し、得られる残渣固形物にクロロホル
ムと水を加え、有機層を充分水洗いする。有機層を芒硝
で乾燥した後、減圧下濃縮乾固し、得られる粗結晶をT
HFより再結すると融点+98−200°Cを示す白色
針状晶の目的物14y(収率70%)を得る。After completion of the dropwise addition, the mixture was heated under reflux for 1 hour while stirring. The reaction solution is concentrated to dryness under reduced pressure, chloroform and water are added to the resulting solid residue, and the organic layer is thoroughly washed with water. After drying the organic layer with Glauber's salt, it was concentrated to dryness under reduced pressure, and the resulting crude crystals were
When recrystallized from HF, the desired product 14y (yield: 70%) is obtained as white needle-like crystals having a melting point of +98-200°C.
工RJ/nuj0’ am ’ : ’3270(
NH)、+695(c=o)。ENGRJ/nuj0'am': '3270(
NH), +695 (c=o).
NMR(DMSO−R6)δ:ピラゾール環の4位水素
。NMR (DMSO-R6) δ: hydrogen at position 4 of pyrazole ring.
7.13(iHs singlet)。7.13 (iHs singlet).
Ma8s m/e : 556(M )−元素分析値(
C+9H+7CIN206として)理論値(%l):
c、 63.96;H,4,80;IJ、 7.85実
測値((イ): C,64,13プH,4,76; N
、 7.99゜実施例2
エチル1−フェニル−5−C1−(4−クロロベンジロ
キシ)フェニル〕ピラゾール−6−カルボキシレート
ナトリウム1−エトキシカルボニル−6−(4−クロロ
ベンジロキシ)フェニル−3−オキソプロバネ−)10
.7yをエタノール+00+++j’、濃塩酸2−の混
合液中に溶解し、フェニルヒドラジン・硫酸塩6yを室
温攪拌下滴下する。滴下終了後、攪拌下6時間加熱還流
する。冷接、反応液を減圧下濃縮乾固し、得られる残渣
固形物にクロロホルムと水を加え、有機層を充分水洗い
する。有機層を芒硝で乾燥した後、減圧下濃縮乾固し、
得られる粗結晶をクロロホルム−メタノールの混合浴I
Kで再結すると融点+42−141°Cを示す白色針状
晶の目的物91y(収率75%)を得る。Ma8s m/e: 556 (M) - elemental analysis value (
C+9H+7CIN206) Theoretical value (%l):
c, 63.96; H, 4,80; IJ, 7.85 actual measurement value ((a): C, 64,13p H, 4,76; N
, 7.99゜Example 2 Ethyl 1-phenyl-5-C1-(4-chlorobenzyloxy)phenyl]pyrazole-6-carboxylate sodium 1-ethoxycarbonyl-6-(4-chlorobenzyloxy)phenyl-3 -Oxoprobane-)10
.. 7y was dissolved in a mixture of ethanol +00+++j' and concentrated hydrochloric acid 2-, and phenylhydrazine sulfate 6y was added dropwise with stirring at room temperature. After completion of the dropwise addition, the mixture was heated under reflux for 6 hours while stirring. The reaction solution is concentrated to dryness under reduced pressure, chloroform and water are added to the resulting solid residue, and the organic layer is thoroughly washed with water. After drying the organic layer with Glauber's salt, it was concentrated to dryness under reduced pressure.
The obtained crude crystals were placed in a chloroform-methanol mixed bath I.
Recrystallization with K gives the desired product 91y (75% yield) as white needles with a melting point of +42-141°C.
工RyW巴01cm ’ : +710(C!=O)。Engineering RyW Tomoe 01cm’: +710 (C!=O).
NMR(DMSO−C6)li :ビラゾール環の4位
水素。NMR (DMSO-C6)li: Hydrogen at the 4-position of the virazole ring.
716 (I H,singlet )。716 (IH, singlet).
Mass m/e : 452(M”)。Mass m/e: 452 (M”).
元素分析値(025H2I CIN2O3として)理論
値(%) : C,69,ろ6:H,4,87iN、
6.47実測値((6): c、 69.02;H,4
,59;N、 6.67゜実施例ろ
5−[:’4−(4−クロロベンジロキシ)フェニル〕
ピラゾールー6−カルボン酸
実施例1により合成したエチル5−(:、4−(クロロ
ベンジロキシ)フェニル〕ピラゾールーローカルボキシ
レート10yを4%水酸化ナトリウム−エタノール溶液
50meに溶解し、攪拌下2時間加熱還流する。冷接、
反応液を酢酸で酸性にし、減圧上濃縮乾固する。得られ
る粗結晶をDMF=−水の混合溶媒で再結すると融点2
6ろ一265°Cを示す白色板状晶の目的物8.52(
収率89%)を得る。Elemental analysis value (as 025H2I CIN2O3) Theoretical value (%): C, 69, Ro6:H, 4,87iN,
6.47 Actual value ((6): c, 69.02; H, 4
,59;N, 6.67゜Example 5-[:'4-(4-chlorobenzyloxy)phenyl]
Pyrazole-6-carboxylic acid Ethyl 5-(:,4-(chlorobenzyloxy)phenyl)pyrazole-local boxylate 10y synthesized according to Example 1 was dissolved in 50me of 4% sodium hydroxide-ethanol solution and stirred for 2 hours. Heating to reflux.Cold welding,
The reaction solution was made acidic with acetic acid and concentrated to dryness under reduced pressure. When the obtained crude crystals are recrystallized with a mixed solvent of DMF=-water, the melting point is 2.
Object 8.52 (white plate-like crystals exhibiting a temperature of 265°C)
Yield: 89%).
nujol −1。nujol -1.
工Rνmax Cm 、3+80(NH)、+
610(c=o)。Engineering Rνmax Cm, 3+80 (NH), +
610 (c=o).
NMR(DMSO−C6)δ:ビラゾール環の4位水素
。NMR (DMSO-C6) δ: hydrogen at the 4-position of the virazole ring.
6.82 (I HXsinglet ) 。6.82 (I HXsinglet).
Hass m/e : 329(M+)。Hass m/e: 329 (M+).
元素分析値(C17H15CIN205として)理論値
((6): C) 62.+0;H,5,99;N%
8.52実側値(@: C,、6189;H,4,13
iN、 886゜実施例4
5−(4−(4−クロロベンジロキシ)フェニル〕ピラ
ゾールー6−カルパマイド
実施例乙により合成した5−111:1−(4−クロロ
ベンジロキシ)フェニル〕ピラゾールー6−カルボン酸
33yをベンゼンI 5ome、 DMF + 0rn
eの混合溶媒中に懸濁させ、塩化チオニル15.62を
室温攪拌上滴下する。滴下終了後、80°Cで4時間加
熱攪拌する。冷接、反応液を減圧上濃縮乾固すると、淡
黄色の油状物である5−C4−(4−クロロベンジロキ
シ)フェニル〕ピラゾール−6−カルポイルクロライド
を2 e、6y (収率82%)得る。ついで、5−C
4−C4−クロロベンジロキシ)フェニル〕ピラゾール
−6−カルポイルクロライド279yをジクロルエタン
200meに溶解する。室温攪拌下、トリエチルアミン
162y加えたのち、アンモニアガスを1時間吹き込む
。吹き込み終了後、反応液を減圧上濃縮乾固し、得られ
る粗結晶をDMFより再結すると融点289°C(de
comp、 )を示す白色板状晶の目的物75y(収率
29%)を得る。Elemental analysis value (as C17H15CIN205) Theoretical value ((6): C) 62. +0;H,5,99;N%
8.52 real value (@: C,, 6189; H, 4, 13
iN, 886° Example 4 5-(4-(4-chlorobenzyloxy)phenyl]pyrazole-6-carpamide 5-111:1-(4-chlorobenzyloxy)phenyl]pyrazole-6-carvone synthesized according to Example B Acid 33y to benzene I 5ome, DMF + 0rn
15.62 of thionyl chloride was added dropwise while stirring at room temperature. After completion of the dropwise addition, the mixture was heated and stirred at 80°C for 4 hours. After cold welding, the reaction solution was concentrated to dryness under reduced pressure to obtain 5-C4-(4-chlorobenzyloxy)phenyl]pyrazole-6-carpoyl chloride as a pale yellow oil (2e,6y (yield: 82%) )obtain. Next, 5-C
4-C4-chlorobenzyloxy)phenyl]pyrazole-6-carpoyl chloride 279y is dissolved in dichloroethane 200me. After adding 162 y of triethylamine while stirring at room temperature, ammonia gas was blown in for 1 hour. After blowing, the reaction solution was concentrated to dryness under reduced pressure, and the resulting crude crystals were re-crystallized from DMF to give a melting point of 289°C (de
The desired product 75y (yield 29%) is obtained as white plate-like crystals exhibiting comp, ).
IRv品’:、尖010m ’ : 3280(NH)
、1610(c=o)。IRv product':, Tip 010m': 3280 (NH)
, 1610 (c=o).
NMR(DMSO−d6 )δ:ピラゾール環の4位水
素。NMR (DMSO-d6) δ: hydrogen at position 4 of pyrazole ring.
7.08 (I H,s inglet ) 。7.08 (IH,s inlet).
1Vlass m/e : 327(M )−元素分析
値(C17H14CIN303として)理論値(%)
: c、 62.29 ;H,4,3+ ;N、 +2
.82実測値(%): 0M6211;H,4,26+
Ni2.61゜実施例5
シクロヘキシル5−C4−(4−クロロベンジロキシ)
フェニル〕ピラゾールー5−カルボキシレート
実施例4により中間体として合成したら−〔4−(4−
10ロベンジロキシ)フェニル〕ビラソールーローカル
ボイルクロライド5gをベンゼン100yneに懸濁さ
せ、シクロヘキサノール46yを室温攪拌上滴下する。1Vlass m/e: 327 (M) - Elemental analysis value (as C17H14CIN303) Theoretical value (%)
: c, 62.29; H, 4, 3+; N, +2
.. 82 Actual value (%): 0M6211; H, 4,26+
Ni2.61゜Example 5 Cyclohexyl 5-C4-(4-chlorobenzyloxy)
Phenyl]pyrazole-5-carboxylate When synthesized as an intermediate according to Example 4, -[4-(4-
5 g of 10 lobenzyloxy) phenyl] virazole-local boil chloride is suspended in 100 yne of benzene, and 46 y of cyclohexanol is added dropwise while stirring at room temperature.
滴下終了後、攪拌下1時間加熱還流する。冷接、反応液
を減圧上濃縮乾固し、得られる粗結晶をメタノールより
再結すると融点215−217°Cを示ず白色板状晶の
目的物28y(収率48%)を得る。After completion of the dropwise addition, the mixture was heated under reflux for 1 hour while stirring. After cooling, the reaction solution was concentrated to dryness under reduced pressure, and the resulting crude crystals were recrystallized from methanol to obtain the desired product 28y (yield: 48%) in the form of white plate-like crystals with a melting point of 215-217°C.
工R,nuJO1+ 。Engineering R, nuJO1+.
max Crrl 、3215(NH)、+66
5(c=o)。max Crrl, 3215 (NH), +66
5 (c=o).
NMR(DMS 0−C6)δ:ビラゾール環の4位水
素。NMR (DMS 0-C6) δ: Hydrogen at the 4-position of the virazole ring.
7.12 (1HXsinglet )。7.12 (1HXsinglet).
Mass m/e : 409(M )。Mass m/e: 409 (M).
元素分析値(C25H22CIN2貼として)理論値(
%) : c、 67.40 ; H,5,37; N
、 6.84実測値(%): C,67、+2;H,5
,39iN、 6.72゜実施例6
エチル1−ベンジル−5−C4−(4−クロロベンジロ
キシ)フェニル〕ビラゾールー6−カルボキシレート
実施例乙により合成した5−〔4,(4−クロロベンジ
ロキシ)フェニル〕ピラゾールー3−カルボン酸10y
をDMF300ml!に溶解し、室温攪拌下炭酸カリウ
ム58yを加える。40°Cで加熱攪拌下、ベンジルブ
ロマイド6ii7を滴下する。Elemental analysis value (as C25H22CIN2 paste) theoretical value (
%): c, 67.40; H, 5,37; N
, 6.84 Actual value (%): C, 67, +2; H, 5
, 39iN, 6.72° Example 6 Ethyl 1-benzyl-5-C4-(4-chlorobenzyloxy)phenyl]virazole-6-carboxylate 5-[4,(4-chlorobenzyloxy) synthesized according to Example B ) phenyl]pyrazole-3-carboxylic acid 10y
300ml of DMF! and add 58y of potassium carbonate while stirring at room temperature. While heating and stirring at 40°C, benzyl bromide 6ii7 is added dropwise.
滴下終了後、反応液を5時間加熱攪拌する。冷接、反応
液を減圧下濃縮乾固し、得られる粗結晶をクロロホルム
−メタノールの混合溶媒で再結すると融点126−12
7°Cを示す白色板状晶の目的物552(収率44%)
を得る。After the dropwise addition is completed, the reaction solution is heated and stirred for 5 hours. Cold welding, the reaction solution was concentrated to dryness under reduced pressure, and the resulting crude crystals were reconsolidated with a mixed solvent of chloroform-methanol to give a melting point of 126-12.
Target product 552 (yield 44%) as white plate crystals showing 7°C
get.
IRvnuJolam ’ : +700(C=0)
−NMR(DMSO−d6)δ:ピラゾール環の4位水
素。IRvnuJolam': +700 (C=0)
-NMR (DMSO-d6) δ: hydrogen at the 4-position of the pyrazole ring.
7ろI (I HXsing]、et )。7ro I (I HXsing), etc.
Mass m/e : 446(M )。Mass m/e: 446 (M).
元素分析値(C26H2sC1,N2O3として)理論
値(%) : C,69,87; H,519; N、
627実測値(@: c、 70.16 ; H,5
28; N、 6.03゜実施例7〜ろ0
上記実施例1〜6に準拠して、反応および後処理を行な
うことにより第1表に記載したピラゾール誘導体を得る
。Elemental analysis value (as C26H2sC1, N2O3) Theoretical value (%): C, 69,87; H, 519; N,
627 actual measurement value (@: c, 70.16; H, 5
28; N, 6.03° Examples 7 to 0 The pyrazole derivatives listed in Table 1 are obtained by performing the reaction and post-treatment according to Examples 1 to 6 above.
Claims (1)
キルカルボン酸基、低級アルキルカルボン酸エステル基
、フエニル基、またはベンジル基、R^2はカルボン酸
基、カルボン酸エステル基、Nに置換基を有するか若し
くは有しないカルバモイル基、または置換基を有するか
若しくは有しない低級アルキル基、R^3は直鎖アルキ
ル基、またはベンゼン核の4位若しくはベンジル基のα
位に置換基を有するかあるいは有しないベンジル基を表
わす〕で示されるピラゾール誘導体。(1) General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. R^2 is a carboxylic acid group, a carboxylic acid ester group, a carbamoyl group with or without a substituent on N, or a lower alkyl group with or without a substituent, R^3 is a linear alkyl group, or benzene α of the 4-position of the nucleus or the benzyl group
A pyrazole derivative represented by a benzyl group with or without a substituent at that position.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP16332784A JPS6140266A (en) | 1984-08-01 | 1984-08-01 | Pyrazole derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP16332784A JPS6140266A (en) | 1984-08-01 | 1984-08-01 | Pyrazole derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS6140266A true JPS6140266A (en) | 1986-02-26 |
Family
ID=15771739
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP16332784A Pending JPS6140266A (en) | 1984-08-01 | 1984-08-01 | Pyrazole derivative |
Country Status (1)
Country | Link |
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JP (1) | JPS6140266A (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5134142A (en) * | 1989-09-22 | 1992-07-28 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives, and pharmaceutical composition comprising the same |
US5550147A (en) * | 1992-02-05 | 1996-08-27 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives, processes for preparation thereof and pharmaceutical composition comprising the same |
EP0854142A1 (en) * | 1997-01-16 | 1998-07-22 | Bayer Ag | Process for the preparation of 1-alkylpyrazole-5-carboxylic esters |
US6297386B1 (en) | 1998-07-02 | 2001-10-02 | Bayer Aktiengesellschaft | Method of preparing 1-alkyl-pyrazol-5-carboxylic acid esters |
JP2005520858A (en) * | 2002-03-20 | 2005-07-14 | メタボレックス, インコーポレイテッド | Substituted phenylacetic acid |
US7622471B2 (en) | 2003-02-07 | 2009-11-24 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives having a pyridazine and pyridine functionality |
US7977358B2 (en) | 2007-07-26 | 2011-07-12 | Hoffmann-La Roche Inc. | Pyrazol derivatives |
CN109422690A (en) * | 2017-08-31 | 2019-03-05 | 浙江省化工研究院有限公司 | A method of preparing 1- alkyl -3- alkyl pyrazole -5- formic acid esters |
-
1984
- 1984-08-01 JP JP16332784A patent/JPS6140266A/en active Pending
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5134142A (en) * | 1989-09-22 | 1992-07-28 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives, and pharmaceutical composition comprising the same |
US5550147A (en) * | 1992-02-05 | 1996-08-27 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazole derivatives, processes for preparation thereof and pharmaceutical composition comprising the same |
EP0854142A1 (en) * | 1997-01-16 | 1998-07-22 | Bayer Ag | Process for the preparation of 1-alkylpyrazole-5-carboxylic esters |
US6297386B1 (en) | 1998-07-02 | 2001-10-02 | Bayer Aktiengesellschaft | Method of preparing 1-alkyl-pyrazol-5-carboxylic acid esters |
WO2000001673A3 (en) * | 1998-07-02 | 2002-09-26 | Bayer Ag | Method for preparing 1-alkyl-pyrazol-5-carboxylic acid esters |
JP2003513004A (en) * | 1998-07-02 | 2003-04-08 | バイエル アクチェンゲゼルシャフト | Method for producing 1-alkyl-pyrazole-5-carboxylic acid ester |
JP2005520858A (en) * | 2002-03-20 | 2005-07-14 | メタボレックス, インコーポレイテッド | Substituted phenylacetic acid |
EP1487843A4 (en) * | 2002-03-20 | 2010-03-10 | Metabolex Inc | Substituted phenylacetic acids |
US7622471B2 (en) | 2003-02-07 | 2009-11-24 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives having a pyridazine and pyridine functionality |
US7977358B2 (en) | 2007-07-26 | 2011-07-12 | Hoffmann-La Roche Inc. | Pyrazol derivatives |
CN109422690A (en) * | 2017-08-31 | 2019-03-05 | 浙江省化工研究院有限公司 | A method of preparing 1- alkyl -3- alkyl pyrazole -5- formic acid esters |
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