GB2129420A - Pyrazoline carboxylic acids - Google Patents

Pyrazoline carboxylic acids Download PDF

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Publication number
GB2129420A
GB2129420A GB08300874A GB8300874A GB2129420A GB 2129420 A GB2129420 A GB 2129420A GB 08300874 A GB08300874 A GB 08300874A GB 8300874 A GB8300874 A GB 8300874A GB 2129420 A GB2129420 A GB 2129420A
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GB
United Kingdom
Prior art keywords
compound
alkyl
general formula
represents hydrogen
hydrogen
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.)
Granted
Application number
GB08300874A
Other versions
GB2129420B (en
GB8300874D0 (en
Inventor
George Charles Rovnyak
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ER Squibb and Sons LLC
Original Assignee
ER Squibb and Sons LLC
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from US06/088,425 external-priority patent/US4254267A/en
Priority claimed from US06/140,355 external-priority patent/US4266065A/en
Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC
Publication of GB8300874D0 publication Critical patent/GB8300874D0/en
Publication of GB2129420A publication Critical patent/GB2129420A/en
Application granted granted Critical
Publication of GB2129420B publication Critical patent/GB2129420B/en
Expired legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Novel compounds have the general formula (I): - <IMAGE> wherein R1 represents hydrogen or alkyl and R2 represents hydrogen or alkyl.

Description

1
GB 2 129 420 A 1
SPECIFICATION Amino acids
The present invention relates to a compound of the general formula I,
a
I
HN-
(i)
c-oh
R2 0
5 wherein R, represents hydrogen or alkyl and Rz represents hydrogen or alkyl. 5
These compounds are useful in the preparation of certain mercaptoacyldihydropyrazole carboxylic acid derivatives which form the subject of our copending application No, 8034001, from which the present application is divided.
The term "aryl", as used herein, either by itself or as a part of a larger group, refers to phenyl or 10 phenyl substituted with one, two or three halogen, alkyl, alkoxy, alkanoyl, nitro, amino, alkylamino, 10 dialkylamino, trifluoromethyl, cyano or carboxyl groups. Phenyl is the preferred aryl group.
The term "alkanoyl", as used herein, either by itself or as a part of a larger group, refers to groups having 2 to 9 carbon atoms.
The terms "alkyl" and "alkoxy" as used herein, either individually or as part of a larger group, refer 15 to groups having 1 to 8 carbon atoms. Alkyl and alkoxy groups having 1 to 3 carbon atoms are 15
preferred.
The term "halogen", as used herein, either by itself or as part of a larger group, refers to fluorine, chlorine, bromine and iodine. The preferred halogen groups are chlorine and bromine except in the case of "haloalkyl" where fluorine is the preferred "halo" group. Trifluoromethyl is the preferred haloalkyl 20 group. 20
A first aspect of the invention provides a compound of the general formula I:
n
I
hn-
(I)
c-oh r2 0
wherein R, represents hydrogen or alkyl and R2 represents hydrogen or alkyl.
A second aspect of the invention provides a method of preparing a compound of the general 25 formula (la):
25
N I
hn
X
c-oh
(la)
r2 o wherein R, is hydrogen or alkyl and R2 is alkyl, which method comprises tautomerising and hydrolysing a compound of the general formula (II):
1
r^
II
0
II
■c-0R3
(II)
alkyi
30 wherein R3 represents hydrogen, alkyl or arylalkyl.
30
2
GB 2 129 420 A 2
Preferably the compound of the general formula II:
N
II
N-
X
o ii
-c-or3
alkyl is prepared by cycloaddition of a diazoalkane of the general formula (III):
R,—CHN2
5 and an acrylic ester of the general formula (IV):
CH2
II
alkyl—C—C—ORg.
II
0
(ID
(III)
(IV)
A third aspect of the invention provides a method of preparing a compound of the general formula (lb):
X
hn-
c-oh
(lb)
f?2 0
10 wherein R, represents hydrogen or alkyl and R2 is hydrogen, comprising the step of treating a compound of the general formula (V):
10
X
(V)
^alkyl C02 alkyl.
with gaseous hydrogen chloride in ether, followed by heating the resulting 2-pyrazoline hydrochloride salt to from 60°C to 80°C in hydrochloric acid.
1 5 Preferably the compound of the general formula V is prepared by reacting a compound of the 15
general formula (VI):
CH2=C(C02alkyl)2 (VI)
with a diazoalkane of the general formula (III):
R—CHN2. (Ill)
20 Those amino acids of formula I wherein R2 is alkyl can be prepared by a two step process. The 20 cycloaddition of a diazoalkane having the formula
R,—CHN2 (III)
and an acrylic ester having the formula
3
GB 2 129 420 A 3
CH,
alkyl—C—C—OR3,
II
0
yields a 1-pyrazolirte derivative having the formula
(IV)
r
1
II
0
II
■c-or
3
alkyl
Tautomerization and hydrolysis of a compound of formula II to a 2-pyrazoline derivative having the 5 formula
Jl hh-
c-oh
(VII)
alkyl can be accomplished by first treating the 1-pyrazoline derivative with gaseous hydrogen chloride in ether followed by treatment with hydrochloric acid.
Amino acids of formula I wherein R2 is hydrogen can be prepared by reacting a compound having 10 the formula 10
CH2=C(C02alkyi)z with a diazoalkane of formula III to obtain a compound having the formula
(VI)
X
^alkyl C02 alkyl.
(V)
Treatment of a compound of formula V with gaseous hydrogen chloride in ether, followed by heating 15 the resulting 2-pyrazoline hydrochloride salt to about 60—80°C in hydrochloric acid yields a 2-pyrazoline derivative having the formula
15
co2h
The invention will be further described by way of example.
(VIII)
20
Example 1
4,5-Dihydro-1 W-pyrazole-5-carboxylic acid A) Diethyl-3,4-dihydro-5W-pyrazole-5,5-dicarboxylic acid
A solution of 29.3 g of diethyl ethylenemalonate in 300 ml of ether is treated with ethereal diazomethane until a slight yellow colour persists. Excess diazomethane is removed on a steam bath, and the solution is then concentrated in vacuo to give 32.5 g of the title compound as an oil.
20
25
Analysis calc'd for C9H14N204: C, 50.45; H, 6.58; N, 13.08 Found: C, 50.34; H, 6.61; N, 12.90
25
4
GB 2 129 420 A 4
B) Diethyl-4,5-dihydro-1//-pyrazole-5,5-dicarboxylic acid, hydrochloride salt
A cold solution of 32,5 g of diethyl-3,4-dihydro-5W-pyrazole-5,5-dicarboxylic acid in 250 ml of ether is treated with a slight excess of gaseous hydrogen chloride. The product appears as an oil, and slowly crystallizes on standing at room temperature for several hours to give 31.2 g of the title 5 hydrochloride salt, melting point 90—94°C. 5
Analysis calc'd for C9H14N204 . HCI: C, 43.12; H, 6.03 N, 11.17
Found: C, 43.17; H, 6.08; N, 11.21
C) 4,5-Dihydro-1W-pyrazole-5-carboxylic acid
A solution of 18.5 g of diethyl-4,5-dihydro-1 W-pyrazole-5,5-dicarboxylic acid, hydrochloride salt 10 in 72 ml of 1.07 N hydrochloric acid is stirred and heated at 70—75°C (oil bath) until evolution of 10
carbon dioxide ceases (6 hours). The solution is cooled, and the water evaporated in vacuo to give 12.0 g of a viscous residue.
To remove the HCI from the above crude product, an aqueous solution is slowly passed through a column of 100 ml of 20—50 mesh Dowex 50W-X8 resin (H+). The strongly acidic initial fractions are 15 set aside for later purification over regenerated resin. The neutral column is treated with 3N NH40H. 15 Evaporation of the eluate gives 4.8 g of impure amino acid. An additional 1.5 g of similar material is obtained from the acidic fractions described above (the initial acidic fractions can be significantly reduced in volume by an extended batch slurry of a portion of the resin with the aqueous hydrochloride before placing the resin in the column).
20 A solution of this material in a small amount of methanol is placed on seven preparative plates 20 (Merck 2 mm) and developed in methanol (6 hours). Of the three UV absorbing areas detected, the center portion contains the desired product, which is obtained by methanol extraction to give 3.45 g of the title compound as an oil.
Examples 2 to 4
25 Following the procedure of Example 1, but substituting the compound listed in column I for 25
diazomethane, yields the compound listed in column II.
Example I //
2 diazoethane 4,5-dihydro-3-methyl-1#-pyrazole-
5-carboxylic acid
30 3 1-diazopropane 4,5-dihydro-3-ethyl-1W-pyrazole- 30
5-carboxylic acid 4 1-diazobutane 4,5-dihydro-3-(/7-propyl)-1 H-
pyrazole-5-carboxylic acid
Example 5
35 4,5-Dihydro-5-methyI-1//-pyrazole-5-carboxylic acid 35
A) Methyl-3,4-dihydro-5-methyl-5A/-pyrazole-5-carboxylic acid
A solution of 10 g of methyl methacrylate in 100 ml of ether is treated with an excess of ethereal diazomethane for about 16 hours. The ether is removed in vacuo to give 12.5 g of the title compound as an oil. Examination of the oil on thin layer chromatography silica gel plates using 40% ethyl 40 acetate/hexane shows a single spot at Rf=0.34, visualized with phosphomolybdic acid plus heat. The 40 oil has the following spectral characteristics: NMR (13C, CDCI3 ppm), 170.9 (C-1), 94.1 (C-2), 28.0 (C-3), 77.1 (C-4), 21.1 (C-5), 52.3 (C-6), IR (neat), 5.78 /u (C02CH3), 6.5 /x (N=N).
" 2
H -
■cd2CH3
ch3
B) Methyl-4,5-dihydro-5-methyl-1W-pyrazole-5-carboxylic acid
45 A solution of 0.5 g of methyl-3,4-dihydro-5-methyl-5W-pyrazole-5-carboxylic acid in 10 ml of 45 ether is treated with gaseous hydrogen chloride, rapidly forming an amorphous precipitate. After cooling for about 16 hours at 5°C, ether is decanted and the residue is washed several times with ether. The residue is dissolved in water, made basic with saturated sodium bicarbonate and extracted with ether. The ether extracts are washed with saturated brine, dried over anhydrous magnesium 50 sulfate and concentrated to give 60 mg of product as an oil. 50
5
GB 2 129 420 A 5
The original ether washes are washed with saturated sodium bicarbonate and saturated brine, dried over anhydrous magnesium sulfate and concentrated to give 260 mg of product identical to the 60 mg obtained above. Examination of the combined product on thin layer chromatography silica gel plates using 40% ethyl acetate/hexane shows a single spot at Rf=0.34, visualized with phosphomolybdic acid plus heat. The product has the following spectral characteristics: NMR (13C, CDCI3, ppm), 175.2 (C-1), 66.4 (C-2), 43.6 (C-3), 142.7 (C-4), 23.5 (C-5), 52.3 (C-6).
||^3l
I
HN
CH
■C09CHq 1 L 6 J
3
C) 4,5-Dihydro-5-methyl-1W-pyrazole-5-carboxylic acid
A solution of methyl-4,5-dihydro-5-methyl-1 W-pyrazole-5-carboxylic acid in chloroform is stirred 10 with 1N sodium hydroxide at room temperature for 5 hours. The aqueous layer is separated, acidified with 1.5 equivalents of hydrochloric acid and placed on a column of AG50W-X8 (H+ form) ion exchange resin. The column is washed with water until neutral and the product is then eluted with 3N ammonium hydroxide. Evaporation in vacuo yields the title compound.
10
15

Claims (1)

  1. Claims
    1. A compound of tho general formula (I):
    15
    N I
    HH-
    a
    (i)
    20
    25
    C-OH If
    R2 0
    wherein R, represents hydrogen or alkyl and R2 represents hydrogen or alkyl.
    2. A compound as claimed in claim 1, containing an alkyl group having from 1 to 8 carbon atoms.
    3. A compound as claimed in claim 2, wherein the alkyl group has from 1 to 3 carbon atoms.
    4. A compound as claimed in any one of claims 1 to 3 wherein R, represents hydrogen.
    5. A compound as claimed in any one of claims 1 to 3 wherein R2 represents hydrogen.
    6. A compound as claimed in any one of claims 1 to 3, wherein R, represents alkyl.
    7. A compound as claimed in any one of claims 1 to 3, wherein R2 represent alkyl.
    8. 4,5-Dihydro-1 W-pyrazole-5-carboxylic acid.
    9. A method of preparing a compound of the general formula (la):
    20
    25
    N I
    HN-
    (la)
    C-OH
    R2 0
    wherein R, is hydrogen or alkyl and R2 is alkyl, which method comprises tautomerising and hydrolysing a compound of the general formula (II):
    R
    1
    ii
    0
    II
    •C-0R3
    (ii)
    alkyl
    30 wherein R3 represents hydrogen, alkyl or arylalkyl.
    30
    GB 2 129 420 A
    10. A method as claimed in claim 9, wherein the tautomerisation and hydrolysis are carried out by treatment with gaseous hydrogen chloride in ether followed by treatment with hydrochloric acid.
    11. A method as claimed in claim 9 or 10 wherein the compound of the general formula (II)
    1
    II
    0
    II
    ■c-0R3
    (II)
    alkyl
    5 is prepared by cycloaddition of a diazoalkane of the general formula (111):
    R,—CHN2
    and an acrylic ester of the general formula (IV):
    CH2
    II
    alkyl—C—C—0R3,
    il
    0
    12. A method of preparing a compound of the general formula (lb):
    (III)
    (IV)
    X
    10
    I
    HH-
    C-OH
    (lb)
    10
    R2 0
    wherein R, represents hydrogen or alkyl and R2 is hydrogen, comprising the step of treating a compound of the general formula (V).
    X
    C02alkyl C02 alkyl
    (V)
    with gaseous hydrogen chloride in ether, followed by heating the resulting 2-pyrazoline hydrochloride 15 salt to from 60°C to 80°C in hydrochloric acid.
    13. A method as claimed in claim 12, wherein the compound of the general formula (V) is prepared by reacting a compound of the general formula (VI):
    15
    20
    CH2=C(C02alkyl)2 with a diazoalkane of the general formula (III):
    R1—CHN2
    (VI)
    (III)
    20
    14. A method of preparing a compound as claimed in claim 1, substantially as hereinbefore described with reference to any one of the Examples 1 to 5.
    15. A compound as claimed in claim 1, when prepared by a method as claimed in any one of claims 9 to 13.
    Printed for Her Majesty's Stationery Office by the Courier Press, Leamington Spa, 1984. Published by the Patent Office, 25 Southampton Buildings, London, WC2A 1 AY, from which copies may be obtained.
GB08300874A 1979-10-25 1983-01-13 Pyrazoline carboxylic acids Expired GB2129420B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US06/088,425 US4254267A (en) 1979-10-25 1979-10-25 Mercaptoacyldihydropyrazole carboxylic acid derivatives
US06/140,355 US4266065A (en) 1980-04-14 1980-04-14 Mercaptoacyldihydropyrazole carboxylic acid derivatives

Publications (3)

Publication Number Publication Date
GB8300874D0 GB8300874D0 (en) 1983-02-16
GB2129420A true GB2129420A (en) 1984-05-16
GB2129420B GB2129420B (en) 1984-10-31

Family

ID=26778642

Family Applications (2)

Application Number Title Priority Date Filing Date
GB8034001A Expired GB2061934B (en) 1979-10-25 1980-10-22 Mercaptoacyldihydropyrazole carboxylic acid derivatives
GB08300874A Expired GB2129420B (en) 1979-10-25 1983-01-13 Pyrazoline carboxylic acids

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Application Number Title Priority Date Filing Date
GB8034001A Expired GB2061934B (en) 1979-10-25 1980-10-22 Mercaptoacyldihydropyrazole carboxylic acid derivatives

Country Status (5)

Country Link
CA (1) CA1156236A (en)
DE (1) DE3040258A1 (en)
FR (2) FR2482099A1 (en)
GB (2) GB2061934B (en)
IT (1) IT1134037B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1179503B (en) * 1984-07-20 1987-09-16 Roussel Maestretti Spa New 4-furyl-4-oxo-butenoic acid derivs.
SE454355B (en) * 1983-01-24 1988-04-25 Roussel Uclaf ACRYLIC ACID DERIVATIVES CONTAINING A FURYL, PYRANYL, BENZOFURANYL, OXAZOLYL OR ISOXAZOLYL GROUP, PROCEDURES FOR PREPARING THEREOF, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEMSELVES

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3013015A (en) * 1959-09-29 1961-12-12 Gen Aniline & Film Corp 1-substituted-2-pyrazoline-3-carbox-aldehyde dye intermediates
US3666772A (en) * 1970-02-26 1972-05-30 Carlisle Chemical Works Preparation of pyrazolines by cyclization of an azine
US4105776A (en) * 1976-06-21 1978-08-08 E. R. Squibb & Sons, Inc. Proline derivatives and related compounds
US4211786A (en) * 1979-03-08 1980-07-08 E. R. Squibb & Sons, Inc. Mercaptoacyldihydropyrazole carboxylic acid derivatives
US4288368A (en) * 1979-07-30 1981-09-08 E. R. Squibb & Sons, Inc. Dithioacylproline derivatives

Also Published As

Publication number Publication date
FR2482099A1 (en) 1981-11-13
FR2474494A1 (en) 1981-07-31
FR2474494B1 (en) 1983-06-17
CA1156236A (en) 1983-11-01
FR2482099B1 (en) 1983-09-30
DE3040258A1 (en) 1981-05-21
GB2129420B (en) 1984-10-31
IT8025575A0 (en) 1980-10-24
GB8300874D0 (en) 1983-02-16
IT1134037B (en) 1986-07-24
GB2061934B (en) 1984-06-06
GB2061934A (en) 1981-05-20

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