GB2034305A - Preparation of piperidine derivatives - Google Patents
Preparation of piperidine derivatives Download PDFInfo
- Publication number
- GB2034305A GB2034305A GB7936701A GB7936701A GB2034305A GB 2034305 A GB2034305 A GB 2034305A GB 7936701 A GB7936701 A GB 7936701A GB 7936701 A GB7936701 A GB 7936701A GB 2034305 A GB2034305 A GB 2034305A
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- United Kingdom
- Prior art keywords
- prepare
- urea
- piperid
- radical
- formula
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a new process for the preparation of compounds of value as pharmaceuticals or intermediates. The process comprises a process for preparing compounds of formula I <IMAGE> and acid addition salts thereof, wherein R is alkyl, cycloalkyl, aralkyl or aryl (including heteroaryl), R<1> is an organic radical, X is oxygen or sulphur and A is an alkylene, mono- or dioxo- or hydroxyalkylene radical of 1-5 carbon atoms, which process comprises reacting a compound of formula II <IMAGE> wherein R<1> and A are as defined above with an acylurea of formula H2NCXNHCOR wherein R is as defined above and X is oxygen or sulphur and if desired converting the product to an acid addition salt.
Description
SPECIFICATION
Preparation of piperidine derivatives
The invention relates to a new process for preparing acyl urea and thiourea derivatives.
In United Kingdom Patent Specifications 1 425 354 and 1 459 506 there are described novel piperidine derivatives which have a ureido or thioureido group, usually at the 4- position of the piperidine ring. One of the preferred substituents of this ureido orthioureido group is an acyl especially a benzoyl group. The preferred way of making the acyl ureido and thioureido compounds of the above mentioned specifications is to react the appropriate 4-amino-i -substituted-piperidine with an acylisocyanate or an acylisothiocyanate, for example benzoyl isocyanate.
This reaction can give variable yields. Also it is difficult to obtain good quality benzoylisocyanate which is an unstable compound which readily reacts with moisture in the atmosphere.
It has been known since 1954 that primary long chain amines can react with urea to give the corresponding alkylureas (see Erickson J.A.C.S.
1954, 3977). As described in this reference the reaction can give a variety of products namely alkylureas, 1,3-dialkylureas, l-alkyl-biurets, 1,3- dialkylbiurets and 1,5-dialkylbiurets.
It has now been found that acylureido or acylthioureido compounds of the above mentioned UK patent specification can be prepared in good yield by reacting the appropriate 4-amino-i -substituted-piperidine with an acylurea or acylthiourea, e.g. benzoylurea. This reaction may be used to prepare compounds of United
Kingdom Specifications 1 425 354 and 1 459 506 and also intermediates for these compounds such as 1-(1 -benzylpiperid-4-yl)-3- benzoylurea. The yields in the process of this invention are in general remarkably high.
Accordingly the invention provides a process for preparing compounds of formula I
and acid addition salts thereof wherein R is alkyl, cycloalkyl, aralkyl, or aryl (including heteroaryl), R' is an organic radical, X is oxygen or sulphur and A is an alkylene, mono- or dioxo- or hydroxyalkylene radical of 1-5 carbon atoms, which process comprises reacting a compound of formula II
wherein R' and A are as defined above with an acylurea of formula H2NCXNHCOR wherein R is as defined above and X is oxygen or sulphur and if desired converting the product to an acid addition salt.
The process of the invention may be performed in the absence of solvent but is usually carried out by heating the reactants in the presence of a suitable inert organic solvent, for example toluene, pyridine, xylene, chlorobenzene, dimethylformamide or dioxan. Pyridine is the preferred solvent. Often it is convenient to reflux the reactants in the solvent until the reaction is complete. High yields e.g. 80-90% can be obtained. Preferably the solvent has a boiling point greater than 1000C.
It is preferred to use equimolar amounts of the reactants.
When group R is an alkyl radical it is preferably lower alkyl of 1 to 6 carbon e.g. methyl, ethyl, npropyl, isopropyl, n-butyl or isobutyl, pentyl or hexyl. When R is aryl it may be carbocyclic aryl or heterocyclic aryl. Preferred aryl groups are phenyl which may be substituted e.g. by halogen or lower alkoxy. The preferred heteroaryl group is thenyl.
The preferred cycloalkyl groups are those having from 5 to 7 carbon atoms e.g. cyclohexyl.
The group R' may be an aryl group especially phenyl or substituted phenyl, for example as described in United Kingdom Specification 1 459 506. The substituents include halogen, e.g.
fluorine or chlorine, lower alkoxy, e.g. methoxy, aryl lower alkoxy, e.g. benzyloxy, hydroxy, lower alkyl e.g. methyl, alkylenedioxy, e.g.
methylenedioxy, or trihalo lower alkyl, e.g.
trifluoromethyl.
The term "lowef' in relation to alkyl and alkoxy radicals used herein means that the radical contains from 1 to 6 carbon atoms. Usually such radicals containing from 1 to 4 carbon atoms are preferred.
R' may be an indolyl radical such as described in United Kingdom Patent Specification 1,425,354. The indolyl radical-may have the formula Ill
Wherein R2 represents hydrogen, lower alkyl, or
aryi, R3 represents hydrogen, halogen, lower alkoxy, aryl lower alkoxy, hydroxy or lower alkyl and R4 represents hydrogen, lower alkyl, aryl lower alkyl or arnyl.
The process of this invention may also be used to prepare compounds wherein R' is a 1,4benzodioxan-2-yl group such as those described in
United Kingdom Patent Application No. 51 781/76 and cognate 45142/77.
The 1 ,4-benzodioxan-2-yl group may have the formula
wherein R5 represents, hydrogen, halogen, lower alkyl, or lower alkoxy.
Furthermore the process of the invention may be used to prepare compounds wherein R' is of formula V
wherein R6 is hydrogen or lower alkyl, and R7 is hydrogen, halogen, lower alkyl or lower alkoxy.
Compounds of this type are described in United
Kingdom Patent Application 51781/76 and cognate 45142/77.
The alkylene radical A may be a straight chain or branched and when A is branched it is preferably a straight chain alkylene containing up to 4 carbon atoms in the chain and carrying one methyl substituent. Examples for the alkylene chain A are described in U.K. Patent Specification
No. 1 425 354. When R1 is of formula V then A preferably has formula CHOHCH2 or COCH2.
The products of the process of the invention are generally pharmaceuticals as described in U.K.
Patent Specification 1 425 354, 1 459 506 or 1 494 805 or United Kingdom Patent Applications
Serial Nos.51781/76 and 45142/77.
However, certain products are intermediates e.g. those in which R' is a phenyl and A is -CH2-. These compounds can be hydrogenolysed to remove the benzyl group giving a piperidine which is an intermediate for preparing compounds of United Kingdom specifications 1 425 354 or 1 459 506 by routes described in these Specifications.
The acid addition salts include those formed from organic and inorganic acids e.g. sulphates, hydrochlorides, hydrobromides, hydroiodides, nitrates, phosphates, sulphonates (e.g. methane and p-toluene sulphonates), acetates, maleates, fu ma rates, ta rtrates, and formats.
The invention is illustrated by the following examples.
EXAMPLE 1
Preparation of I-II -Benzylpiperid-4-yll-3- benzoylurea
A solution of benzoylurea (0.82 g, 5 mmol) and 4-amino-1-benzylpiperidine (0.95 g, 5 mmol) in pyridine (4 cm3) was heated under reflux for 2.5 hours. The solution was then poured into water and the precipitated product collected by filtration, washed well with water, and dried to give the title compound 1.55 g (92%) m.p. 180-810C.This product is an intermediate for 1 -(piperid-4-yl)-3benzoyl urea.
EXAMPLE 2 7 -(1 -Benzylpiperid-4-ylJ-3-(3- methoxybenzoyl)urea
A solution of m-methoxybenzoylurea (9.7 g, 0.05 mol) and 4-amino-1 -benzylpiperidine (9.5 g, 0.05 mol) in pyridine (40 cm3) was heated under reflux for 3 hours. The solution was then poured into water (100 cm3), cooled in ice, and the precipitated product collected by filtration, washed with water, and dried to give the title compound (17.7 g, 94%). A sample crystallised from ethanol gave m.p. 1 49-500C. The product is an intermediate for 1-(piperid-4-ly)-3-(3- methoxybenzoyl)urea.
EXAMPLE 3 1 -Benzoyl-3-( 1 -[2-(indoi-3-yI)ethyllpiperid-4- yi)urea A solution of 4-amino-1 -(2 [indol3-yl]ethyl)- piperidine (1.21 g, 5 mmol) and benzoylurea (0.82 g, 5 mmol) in pyridine (4 cm3) was heated under reflux for 3 hours. The solution was then diluted with water and the precipitated product collected by filtration washed with water and dried to give the title compound (1.6 9,87%). The base was suspended in hot ethanol (30 cm3) and acidified with ethanolic hydrogen chloride to precipitate the hydrochloride. Recrystallisation from aqueous methanol (80% methanol) gave 1.07 g (50.5%) m.p. 260-61 OC.
EXAMPLE 4
1 -Benzoyl-3-( 1 -[4-oxo-4-phenylbutylipiperid-4- vi) urea Reaction of 4 amino-1 -(4-oxo-phenylbutyl)piperidine (1.5 g, 5 mmol) with benzoylurea (0.82 g, 5 mmol) following the procedure of example 3 gave (1.7 g, 91%) of the title compound.
Conversion to the hydrochloride and recrystallisation as in example 3 gave 1.47 g (68.5%) m.p209-1 10C.
EXAMPLE 5 1 -Benzo yi-3-( 1 -[indol-3-ylmethylipiperid-4- yl)urea
Reaction of 4-amino-1-(indol-3-ylmethyl)- piperidine. (1.14 g, 5 mmol) with benzoylurea (0.82 g, 5 mmol) following the procedure of example 3 gave (1.5 9,79%) of the title compound. Conversion to the hydrochloride with ethanolic hydrogen chloride gave 0.55 (37.5%) m.p. 260--62 OC.
EXAMPLE 6 1 -(1 -Benzylpiperid-4-yl)-3-benzoylurea A solution of benzoylurea (0.82 g, 5 mmol) and 4-amino-l -benzylpiperidine (0.95 g, 5 mmol) in
toluene (20 cm3) was heated under reflux for 7
hours to give a clear solution. (The reaction was
shown to be complete by t.l.c.). The solution was
cooled in ice and the precipitated title compound
collected by filtration 1.35 g (80%).
EXAMPLE 7 1 -Benzoyl-3-[(2-(indol-3- -(2-(indoA3W)-ethWfpIpefld-4-
yl]thiourea A solution of 4-amino-l -(2-[indol-3-yl]- ethyl)piperidine (1 mol) and benzoylthiourea (1
mol) in xylene is heated under reflux for several
hours. The solution is cooled in ice and the title
compound filtered off.
EXAMPLE 8
1 -(2-Thenoyi)-3-[1 -r2-[3-indolyl]ethyl)piperid- 4-yllurea
A solution of 4-a mino-l -(2-[indol-3
yl]ethyl)piperidine (1 mol) and thenoylurea (1 mol)
in dimethylformamide is heated under reflux for
several hours until formation of the title compound
is complete as shown by t.l.c. The solution is
cooled, poured into water and the title compound
is filtered off and dried.
EXAMPLE 9
1 -Cyclohexanecarbonyl-3-[1 -(2-[3 indolyllethyl)piperid-4-yl]urea.
A solution of 4-amino-1 -(2-[indol-3
yl]ethyl)piperidine (1 mol) and cyclohexanecarbonylurea (1 mol) in pyridine is
heated under reflux until formation of the title
compound is complete. The solution is cooled,
poured into water and the title compound is filtered off and dried.
EXAMPLE 10
1 -(4-Chiorohenzoyi)-3-( 1 -[indol-3- ylmethylipiperid-4-yl)urea A mixture of 4-amino-i(indol-3- ylmethyl)piperidine (1.5 g, 6.5 mmol), 4
chlorobenzoylurea (1 g, 5 mmol) and pyridine (4 cm3) was heated under reflux for 3 hours. The
mixture was then poured into water and the
precipitated product collected by filtration washed
with water and dried to give the title compound as the free base. The base was then suspended in warm ethanol and acidified with ethanolic hydrogen chloride to give a clear solution which
crystallised after ice cooling to give the
hydrochloride. This was recrystallised twice from
methanol to give the hydrochloride mp 269-271 0C.
Analysis: Found: C, 58.74; H, 5.65; N, 12.68% C22H23CIN402.Hcl requires C, 59.07; H,5.18; N, 12.52%.
EXAMPLE 11
1 -Benzoyl-3-/ 1 -(2-( I ,4-benzodioxan-2- yi)- oxoethyi]piperid-4- yllurea.
A mixture of benzoylurea (1 mol) and 4-amino1 -(2-( 1 ,4-benzodioxan-2-yl)2-oxoethyl)piperidine (1 mol) in dimethylformamide is heated under reflux for several hours. Water is added, the title compound precipitates and is filtered off and dried.
EXAMPLE 12 1 -Renzoyl-3-[1 -K2-hydroxy-3-[2- methoxyphenoxylpropyl)-piperid-4-yl]urea.
A mixture of benzoylurea (1 mol) and 4-amino
1 -(2-hydroxy-3-[methoxyphenoxy| propyl)piperidine (1 mol) in pyridine is refluxed for several hours until formation of the title compound is complete as shown by t.l.c. The resulting solution is poured into water and the title compound filtered off and dried.
Claims (31)
1. A process for preparing compounds of formula I
and acid addition salts thereof, wherein R is alkyl, cycloalkyl, aralkyl or aryl (including heteroaryl), R1 is an organic radical, X is oxygen or sulphur and A is an alkylene, mono- or dioxo- or hydroxyalkylene radical of 1-5 carbon atoms, which process comprises reacting a compound of formula II
wherein R' and A are as defined above with an acylurea of formula H2NCXNHCOR wherein R is as defined above and X is oxygen or sulphur and if desired converting the product to an acid addition salt.
2. A process as claimed in Claim 1, wherein R1 is an indolyl radical.
3. A process as claimed in Claim 2, wherein the indolyl radical has the formula Ill
wherein R2 represents hydrogen, lower alkyl, or aryl, R3 represents hydrogen, halogen, lower alkoxy, aryl lower alkoxy, hydroxy or lower alkyl and R4 represents hydrogen, lower alkyl, aryl lower alkyl or aroyl.
4. A process as claimed in Claim 1, wherein R1 represents a carbocyclic aryl radical.
5. A process as claimed in Claim 4 wherein R1 represents a substituted or unsubstituted phenyl radical.
6. A process as claimed in Claim 5, wherein R1 represents phenyl substituted by halogen, lower alkoxy, aryllower alkoxy, hydroxy, lower alkyl, alkylenedioxy or trihalo-lower alkyl.
7. A process as claimed in Claim 1, wherein R1 represents a 1 ,4-benzodioxan-2-yl radical.
8. A process as claimed in Claim 7, wherein the 1 ,4-benzodioxan-2-yl radical has the formula (lV)
wherein R5 represents hydrogen, halogen, lower alkyl or lower alkoxy.
9. A process as claimed in Claim 1, wherein R1 represents a radical of formula V.
wherein R5 is hydrogen or lower alkyl, and R7 is hydrogen, halogen, lower alkyl or lower alkoxy.
10. A process as claimed in any one of claims 1 to 6 wherein A is -CH2-.
11. A process as claimed in Claim 7, 8 or 9, wherein A is CHOHCH2- or -COCH2-.
12. A process as claimed in any one of the preceding claims wherein R is phenyl, halophenyl or lower alkoxyphenyl.
13. A process as claimed in any one of Claims 111, wherein R isthenyl.
14. A process as claimed in any one of Claims 1-11, wherein R is cyclohexyl.
15. A process as claimed in Claim 1 when used to prepare 1 -(1 -benzylpiperid-4-yl)-3-benzoylurea.
1 6. A process as claimed in Claim 1, when used to prepare 1 -(1 -benzylpiperid-4-yl)-3-(3methoxybenzyl)urea.
1 7. A process as claimed in Claim 1, when used to prepare 1 -benzoyl-3-(1 -[2-(indol-3 yl)ethyl]piperid-4-yl)urea.
1 8. A process as claimed in Claim 1, when used to prepare 1 -benzoyl-3-( 1 -[4-oxo-4phenylbutyl]piperid-4-yl)urea.
1 9. A process as claimed in Claim 1, when used to prepare 1 -benzoyl-3-(1 -[indol-3 ylmethyl]piperid-4-yI)urea.
20. A process as claimed in Claim 1, when used to prepare 1 -benzoyl-3-[1 -(2-indol-3-yl- ethyl)piperid-4-yl]thiourea.
21. A process as claimed in Claim 1, when used to prepare 1-(2-thenoyl)-3-[1-(2 [indolyl]ethyl)piperid-4-yl] urea.
22. A process as claimed in Claim 1, when used to prepare 1-cyclohexane carbonyl-3-[1-(2-[3indolyl]ethyl)piperid-4-yl]urea.
23. A process as claimed in Claim 1, when used to prepare 1-(4-chlorobenzoyl)-3-(1-[indol-3- ylmethyl]piperid-4-yl)urea.
24. A process as claimed in Claim 1, when used to prepare 1 -benzoyl-3-[1 -(2-( 1 ,4-benzodioxan-2- yl)-2-oxoethyl] piperid-4-yl] urea.
25. A process as claimed in Claim 1, when used to prepare 1 -benzoyl-3-[1 -(2-hydroxy-3-[2- methoxyphenoxy]propyl)-piperid-4-yl] urea.
26. A process as claimed in any one of the preceding claims when carried out by heating the reactants in an inert organic solvent which has a boiling point above 1 0O0C.
27. A process as claimed in Claim 26, wherein the solvent is pyridine.
28. A process as claimed in Claim 26, wherein the solvent is toluene.
29. A process as claimed in any one of claims 26 to 28, when carried out under reflux.
30. A process as claimed in Claim 1, substantially as herein before described in any one of Examples 1 to 12.
31. A compound of formula I whenever prepared by a process as claimed in any one of the preceding claims.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE2100/78A IE47461B1 (en) | 1977-12-01 | 1978-10-24 | Indole derivatives, their preparation and use in pharmaceutical compositions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB2034305A true GB2034305A (en) | 1980-06-04 |
| GB2034305B GB2034305B (en) | 1982-12-22 |
Family
ID=11032790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB7936701A Expired GB2034305B (en) | 1978-10-24 | 1979-10-23 | Preparation of piperidine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2034305B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0035374A2 (en) * | 1980-03-01 | 1981-09-09 | JOHN WYETH & BROTHER LIMITED | Piperidyl - urea, - thiourea and - guanidine derivatives, and intermediates therefor, processes for preparing them and pharmaceutical compositions containing the derivatives |
| WO1983004022A1 (en) * | 1982-05-18 | 1983-11-24 | Bouchara, Emile | New phenyloxoalkyl piperidines, methods for obtaining them and pharmaceutical compositions containing them |
| WO1985001288A1 (en) * | 1983-09-19 | 1985-03-28 | Bouchara, Emile | New substituted piperidinoguanidines, preparation process and pharmaceutical compositions containing them |
| EP0228795A1 (en) * | 1985-11-15 | 1987-07-15 | JOHN WYETH & BROTHER LIMITED | Piperidine derivatives having a psychotropic activity |
| EP0234098A1 (en) * | 1985-11-15 | 1987-09-02 | JOHN WYETH & BROTHER LIMITED | N-[piperidylaminocarbonyl]quinolinecarboxamide derivatives having psychotropic activity |
| US4806552A (en) * | 1980-03-01 | 1989-02-21 | John Wyeth & Brother, Limited | Pyridyl- and/or pyridoyl-(piperid-4-yl) ureas and analogues thereof |
| WO2005000826A1 (en) * | 2003-06-23 | 2005-01-06 | Cv Therapeutics, Inc. | Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors |
| WO2005061470A1 (en) * | 2003-12-18 | 2005-07-07 | Cv Therapeutics, Inc. | 1-akan-2-ol substituted piperazine and piperidine compounds |
-
1979
- 1979-10-23 GB GB7936701A patent/GB2034305B/en not_active Expired
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4806552A (en) * | 1980-03-01 | 1989-02-21 | John Wyeth & Brother, Limited | Pyridyl- and/or pyridoyl-(piperid-4-yl) ureas and analogues thereof |
| EP0035374A3 (en) * | 1980-03-01 | 1981-11-11 | John Wyeth & Brother Limited | Piperidyl - urea, - thiourea and - guanidine derivatives, and intermediates therefor, processes for preparing them and pharmaceutical compositions containing the derivatives |
| EP0035374A2 (en) * | 1980-03-01 | 1981-09-09 | JOHN WYETH & BROTHER LIMITED | Piperidyl - urea, - thiourea and - guanidine derivatives, and intermediates therefor, processes for preparing them and pharmaceutical compositions containing the derivatives |
| US5212179A (en) * | 1980-03-01 | 1993-05-18 | John Wyeth And Brother Limited | Piperidine derivatives |
| US4985438A (en) * | 1980-03-01 | 1991-01-15 | John Wyeth & Brother, Limited | Pyridyl-and/or pyridoyl-(piperid-4-yl) ureas and analogues thereof |
| WO1983004022A1 (en) * | 1982-05-18 | 1983-11-24 | Bouchara, Emile | New phenyloxoalkyl piperidines, methods for obtaining them and pharmaceutical compositions containing them |
| WO1985001288A1 (en) * | 1983-09-19 | 1985-03-28 | Bouchara, Emile | New substituted piperidinoguanidines, preparation process and pharmaceutical compositions containing them |
| US4778802A (en) * | 1985-11-15 | 1988-10-18 | John Wyeth & Brother, Ltd. | Heterocyclic compounds |
| EP0234098A1 (en) * | 1985-11-15 | 1987-09-02 | JOHN WYETH & BROTHER LIMITED | N-[piperidylaminocarbonyl]quinolinecarboxamide derivatives having psychotropic activity |
| EP0228795A1 (en) * | 1985-11-15 | 1987-07-15 | JOHN WYETH & BROTHER LIMITED | Piperidine derivatives having a psychotropic activity |
| WO2005000826A1 (en) * | 2003-06-23 | 2005-01-06 | Cv Therapeutics, Inc. | Urea derivatives of piperazines and piperidines as fatty acid oxidation inhibitors |
| US7208496B2 (en) | 2003-06-23 | 2007-04-24 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
| JP2007518677A (en) * | 2003-06-23 | 2007-07-12 | シーブイ・セラピューティクス・インコーポレイテッド | Piperazine and urea derivatives of piperidine as fatty acid oxidation inhibitors |
| WO2005061470A1 (en) * | 2003-12-18 | 2005-07-07 | Cv Therapeutics, Inc. | 1-akan-2-ol substituted piperazine and piperidine compounds |
| US7115610B2 (en) | 2003-12-18 | 2006-10-03 | Cv Therapeutics, Inc. | Substituted heterocyclic compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2034305B (en) | 1982-12-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19951023 |