NZ248043A - 1-(4-hydroxy-3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methy l-5-benzenesulphonyl-1,3-pentadiene derivatives; methods of preparation - Google Patents
1-(4-hydroxy-3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methy l-5-benzenesulphonyl-1,3-pentadiene derivatives; methods of preparationInfo
- Publication number
- NZ248043A NZ248043A NZ248043A NZ24804391A NZ248043A NZ 248043 A NZ248043 A NZ 248043A NZ 248043 A NZ248043 A NZ 248043A NZ 24804391 A NZ24804391 A NZ 24804391A NZ 248043 A NZ248043 A NZ 248043A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- cyclohexen
- trimethyl
- oxo
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 3
- IWRZNIQIZTYBGU-UHFFFAOYSA-N 3-[5-(benzenesulfonyl)-3-methylpenta-1,3-dienyl]-6-hydroxy-2,4,4-trimethylcyclohex-2-en-1-one Chemical class CC=1C(=O)C(O)CC(C)(C)C=1C=CC(C)=CCS(=O)(=O)C1=CC=CC=C1 IWRZNIQIZTYBGU-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 229910052736 halogen Chemical group 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical group COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 claims description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 4
- 229940022405 astaxanthin Drugs 0.000 description 4
- 235000013793 astaxanthin Nutrition 0.000 description 4
- 239000001168 astaxanthin Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 229940073584 methylene chloride Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- APEWRHVWMCBRAQ-UHFFFAOYSA-N 3,3-bis(benzenesulfonyl)oxaziridine Chemical compound C1(=CC=CC=C1)S(=O)(=O)C1(NO1)S(=O)(=O)C1=CC=CC=C1 APEWRHVWMCBRAQ-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical group 0.000 description 1
- JEHKKBHWRAXMCH-UHFFFAOYSA-N benzenesulfinic acid Chemical compound O[S@@](=O)C1=CC=CC=C1 JEHKKBHWRAXMCH-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- -1 camphorylsulfonyl-oxaziridine Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- SJGALSBBFTYSBA-UHFFFAOYSA-N oxaziridine Chemical compound C1NO1 SJGALSBBFTYSBA-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- CHLCPTJLUJHDBO-UHFFFAOYSA-M sodium;benzenesulfinate Chemical compound [Na+].[O-]S(=O)C1=CC=CC=C1 CHLCPTJLUJHDBO-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000005389 trialkylsiloxy group Chemical group 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
New Zealand Paient Spedficaiion for Paient Number £48043
248043
Patents Form 5
Priority Dciie{s): . 5l9l
Complete Specifics-tion Filed:
Class:
'"J' '2 5 MAR'TO
Publication Date:
P.O. Journal, No: ....ISO
Under the provisions of RoflW-
lation 23 (1) the
Coysfi£j;&
Specification has been ante-dated to...s£l 19 31
A
N.Z. No.
(Divided out of New Zealand NEW ZEALAND Patent Specification No. 240765)
Patents Act 1953
COMPLETE SPECIFICATION
NOVEL COMPOUNDS
We, NEUROSEARCH A/S, a Danish company of Smedeland 26, DK-2600 Glostrup, Denmark do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: -
- 1 - (Followed by 1A)
248043
1A
The present invention provides a compound of the following formula
wherein R1 is alkyl, alkoxy, N02, NH2 or halogen.
In a further aspect the present invention provides a method for the preparation of a compound having the formula wherein R' is alkyl, alkoxy, "NO,, NH, or halogen, which method comprises the step of reacting a compound having the formula
12 3* OSiR R R
wherein R1, R2 and R3 independently are C^- alkyl which may be branched or phenyl with a compound having the formula wherein R' is alkyl, alkoxy, NO,, NH2 or halogen.
2
248043
Background of "the invention
USP 4,585,885 discloses a compound having the formula wherein R2 is an trialkylsiloxy group or an ether group, which is oxidized with, a percarboxylic acid to form a compound having the formula wherein R2 is as above.
This compound is then transformed into a compound having the formula wherein R3 is an alkylether or an hydroxy group.
This compound is then transformed into a Wittig compound which upon reaction with a compound having the formula will yield astaxanthin.
24 8 0 4 3
3
Detailed Description
The novel process of the present invention is carried out much more convenient, in that it avoids the use of peracids and allows a much more direct approach to the production of astaxanthin.
The novel process and the novel intermediates of the invention are illustrated in the below scheme
1
well known compound of USP 4; 098,827
0
Step 1
TMSC1 (trimethylsilyl chloride) in triethylamine, methylenechloride
2
0
1) NaHMDS (in THF)
Ph0
Step 2
2) 1Z_^N
Novel Process
3) HOAc
3
HO
Novel Compound
0
4
24 8 0 4 J
Step 3
Ph^ NsO~Na+
(in HOAc) Novel Process
Novel Compound
Step 4
1) NaOCH,
2) Br.
(in THF)
SOnPh
S02Ph
Step 5
1) KOt-Bu (in hexane)
Astaxanthin
24 8 04 3
The above scheme illustrate preferred reagents, solvents, " acids and bases of the processes of the invention.
However the NaHMDS (sodiumhexamethyldisilazane) of step 2 above may easily be substituted for other bases as for example KHMDS, LiHMDS, LDA (lithium diisopropyl amide), sodium-hydride, potassium t-butylat as well as several others.
The oxidizing agent of ^_step 2, trans-2-(phenylsulfonyl)-3-phenyloxaziridine (Ph-£-N-S02Ph), is a key element.of step 2. However, this oxidizing agent may be any oxaziridine having the below formula
•so2R'
wherein R1 is phenyl, phenyl substituted with a substituent which is stable under the conditions of reaction, C3_7-cyclo-alkyl, and wherein R2 independently signifies hydrogen or the same radical as R1, or wherein R1 and R2 together form a cyclic or bicyclic radical as for example camphorylsulfonyl-oxaziridine.
The acid of step 2 used to quench the reaction mixture may be any proton donor. Any protic compounds such as water, alcohols, and hydrogen-donating acids may be employed, however, it preferred that the quenching proton donor is at least slightly acidic in order to avoid the formation of strong base during the quenching step.
The phenylsulphinate employed in step 3 above may be substituted for any substituted derivative thereof. For example the phenyl group may be substituted with alkyl, alkoxy, NOz, and halogen. The acetic acid employed in this step 3 may be sub-
24 BB4J5
6
stituted by any organic acid, or any neutral organic solvent with addition of an acid, for example ethanol added hydrogen chloride may conveniently be employed instead.
Step 4 and 5 above illustrate the utility of the novel intermediates of the invention produced by the novel processes of the invention for the production os astaxanthin.
Step 4 and step 5 above may conveniently be effected by use of the reagents indicated above. The principles of the processes are described in more detail in examples 5 and 6 of USP 4,049,718.
Examples
The invention will now be described in greater detail with reference to the following examples, which are given by way of illustration only and are not to be construed as limiting.
l-(3-oxo-2,6, 6-trimethyl-l-cyclohexen-l-yl )-3-methyl-3-trimethylsiloxy-1,4-pentadiene
A solution of l-(3-oxo-2, 6, 6-trimethyl-l-cyclohexen-l-yl )-3-methyl-l,4-pentadiene-3-ol (2.34 g, 10 mmoles)(prepared as described in J. Org. Chem. 47, 2130-2134 (1982)) in methylenechloride is added triethylamine (2.08 ml, 15 mmoles), trimethylchlorosilane (1.9 ml, 15 mmoles), and N,N-dimethyl-4-aminopyridine (5 nig, catalytic amount). The mixture is stirred at room temperature for four hours, followed by concentration in vacuo and trituration with dry diethyl-ether. The suspension is filtered and the filtrate is concentrated in vacuo yielding the title compound as a slightly yellow oil.
l-(4-hydroxy-3-oxo-2,6,6-trimethyl-l-cyclohexen-l-yl)-3-methyl-3-trimethylsiloxy-l, 4-pentadiene
248043
7
A solution of l-(3-oxo-2,6,6-trimethyl-l-cyclohexen-l-yl)-3-methyl-trimethylsiloxy-1,4-pentadiene (918 mg, 3 mmoles) in 10 ml absolute tetrahydrofurane at -20°C is slowly added sodium hexamethyldisilazane (4.5 ml 1M in THF, 4.5 mmoles) forming a violet solution of sodium-enolate. The mixture is stirred 30 minutes at -20°C, the temperature is lowered to -78°C and a solution of diphenyl-sulfonyloxaziridine (1.17 g, 4.5 mmoles) in 10 ml absolute tetrahydrofurane is added.
After stirring for 30 minutes glacial acetic acid (257 jil, 4.5 mmoles) is added and the mixture is concentrated in vacuo and the remanecens is subjected to column chromatography using methylenechloride/ethylacetate (95/5) as eluent. The fractions containing the product is concentrated in vacuo yielding the title compound as a yellow oil.
l-(4~hydroxy-3-oxo-2,6,6-trimethyl-l-cyclohexen-l-yl)-3-methyl-5-benzenesulfonyl-l,3-pentadiene
A solution of l-(4-hydroxy-3-oxo-2,6,6-trimethyl-l-cyclohexen-l-yl )-3-methyl-3-trimethylsiloxy-l, 4-pentadiene (200 mg, 0.62 mmol) in 1 ml glacial acetic acid is added benzene-sulfinic acid, sodium salt (153 mg, 0.93 mmoles) and the mixture is stirred overnight at ambient temperature. The mixture is concentrated in vacuo and the remanecens is taken up in 10 ml diethylether and 10 ml 1M sodium hydroxide. The aqueous layer is separated and extracted twice with 10 ml diethyl-, ether. The combined ether phases are dried and concentrated in vacuo yielding the title compound as a slightly yellow oil.
8
Claims (4)
1. A compound having the formula 24 8 04 3 o wherein R' is alkyl, alkoxy, N02, NH2 or halogen.
2. A method for the preparation of a compound having the formula wherein R' is alkyl, alkoxy, "N02, NH2 or halogen, which method comprises the step of reacting a compound having the formula wherein R1, R2 and R3 independently are C1.6-alkyl which may be branched or phenyl with a compound having the formula 0 II wherein R' is alkyl, alkoxy, N02, NH2 or halogen. 4 i 9 24 8 0 & T " - /
3. A compound according to claim 1 substantially as herein described or exemplified.
4. A method according to claim 2 substantially as herein described or exemplified. NEUROSEARCH A IS By Their Attorneys HENRY HUGHES LTD Per:
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/626,573 US5107010A (en) | 1990-12-12 | 1990-12-12 | Astaxanthin intermediates |
| NZ240765A NZ240765A (en) | 1990-12-12 | 1991-11-27 | Silicon-containing intermediates for the preparation of astaxanthin; methods of preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ248043A true NZ248043A (en) | 1994-03-25 |
Family
ID=26651030
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ248043A NZ248043A (en) | 1990-12-12 | 1991-11-27 | 1-(4-hydroxy-3-oxo-2,6,6-trimethyl-1-cyclohexen-1-yl)-3-methy l-5-benzenesulphonyl-1,3-pentadiene derivatives; methods of preparation |
Country Status (1)
| Country | Link |
|---|---|
| NZ (1) | NZ248043A (en) |
-
1991
- 1991-11-27 NZ NZ248043A patent/NZ248043A/en not_active IP Right Cessation
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|---|---|---|---|
| RENW | Renewal (renewal fees accepted) | ||
| EXPY | Patent expired |