CN1112109A - Novel arylglycinamide derivatives and preparative processes therefor - Google Patents
Novel arylglycinamide derivatives and preparative processes therefor Download PDFInfo
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- CN1112109A CN1112109A CN93109151A CN93109151A CN1112109A CN 1112109 A CN1112109 A CN 1112109A CN 93109151 A CN93109151 A CN 93109151A CN 93109151 A CN93109151 A CN 93109151A CN 1112109 A CN1112109 A CN 1112109A
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Abstract
Arylglycinamide derivatives represented by a general formula (1) (wherein Ar, R1, R2, R3, R4, R5 , R6, and m denotes the instruction), and their salts, which function as effective therapeutic drugs for the dysurias such as urinary incontinence and pollakiuria, and the preparative processes therefor are presented.
Description
Background technology
The present invention relates to new aryl glycinamide derivative and salt thereof as misnicturition such as the urinary incontinence and the effective therapeutical agent of frequent micturition.
The urinary incontinence and frequent micturition are brought soul pain to the patient, and they and society are isolated.The parafunctional characteristic of these neurogenic bladders is the detrusor hyperactivity hyperkinesia.
To adopting anticholinergic drug, comprise oxybutynin chloride and terodiline hydrochloride because of the unusual treatment of the hyperactive bladder function of detrusor.Clinically, the treatment of these medicines symptom that activity causes to bladder is effectively, but untoward reactions such as their normal generation drys, uroschesis.The partly cause that these untoward reactions occur is considered to by due to the non-selective cholinolytic effect of these medicines.Therefore, expect the new urinary incontinence and frequent micturition curative strongly, they do not produce such as serious adverse effects such as dry, renal shutdown and misnicturition.
With regard to aryl glycinamide derivatives, phenyl glycine esters (Yakugaku Zasshi with spasmolysis, 73,1327(1953)) and phenylglycollic acid fat derivative (J.Am.Chem.Soc., 70,4214(1948) existing report, but they are different with the new compound molecular structure among the present invention.In addition misnicturition such as the urinary incontinence and the medicative aryl glycinamide derivatives of frequent micturition then are not reported.
The invention provides the new drug of the treatment urinary incontinence and frequent micturition, they do not produce the untoward reaction of the conventional treatment urinary incontinences such as dry, renal shutdown and misnicturition, frequent micturition drug-induced.
The present invention's general introduction
The present inventor notices aryl glycinamide derivatives for above-mentioned purpose, the new aryl glycinamide derivatives that found that with general formula (1) expression diligent in one's studies
(wherein Ar represents to have 1-3 substituent phenyl that 1-3 substituent naphthyl, R maybe can be arranged
1And R
4Represent hydrogen atom identical or differently or have the low alkyl group of 1-3 carbon atom, R
2Expression have 1-6 carbon atom low alkyl group, have 3-6 carbon atom cycloalkyl, 1-4 carbon atom arranged and can have on the carbon atom and the individual substituent phenyl of 1-3 can maybe can be arranged, R with low alkyl group, norcamphyl, the adamantyl of the individual substituent phenyl of 1-3
3Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
2Form the ring that alkylidene group is formed together, R
5Expression has the low alkyl group of 1-6 carbon atom or the cycloalkyl of 5 or 6 carbon atoms, R is arranged
6Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
5Form the ring that alkylidene group is formed together, m represents 2 or 3) or its salt, they do not show the untoward reaction of existing medicine, and suppress bladder excessive activities, increase bladder capacity, thereby cause of the present invention finishing.
As " substituting group " of phenyl or naphthyl among the present invention, can mention halogen, low alkyl group, lower alkoxy, phenyl, hydroxyl etc." halogen " can be fluorine, chlorine and bromine." low alkyl group " can be the straight or branched alkyl of 1-6 carbon atom, as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl and the tertiary butyl." lower alkoxy " can be the alkoxyl group of 1-3 carbon atom, as methoxyl group, oxyethyl group and positive propoxy." cycloalkyl " can be the alicyclic hydrocarbon of 3-6 carbon atom, as cyclopentyl and cyclohexyl and similar group." alkylidene group " can be the alkylidene group of 3-6 carbon atom, as tetramethylene and pentamethylene.
Among the present invention, the compound of general formula (1) expression
(wherein, Ar, R
1, R
2, R
3, R
4, R
5, R
6The same with m) can be by compound shown in the general formula (3)
(wherein, R
4, R
5, R
6The same with m) with general formula (2) shown in compound
(wherein, Ar, R
1, R
2And R
3The same, X represents to eliminate group) reaction and make, the reaction in the presence of alkali, to carry out to good.
As " elimination group ", can mention halogen, aliphatic sulfonyloxy such as mesyloxy, aromatic series sulfonyloxy such as tosyloxy and similar group herein.
Reaction meets the requirements under the following conditions: 0-150 ℃; In organic solvent such as dimethyl formamide, methyl-sulphoxide, methylene dichloride, chloroform, benzene, toluene or dimethylbenzene; In the presence of mineral alkali, comprise alkali metal hydroxide such as sodium hydroxide or potassium hydroxide, alkaline carbonate such as yellow soda ash or salt of wormwood, alkali metal hydrocarbonate such as sodium bicarbonate or saleratus, alkaline earth metal hydroxides such as magnesium hydroxide or calcium hydroxide, metal hydride such as sodium hydride or its analogue, or in the presence of organic bases, comprise that tertiary amine such as pyridine or its analogue are as alkali.
And, in the present invention, compound shown in the general formula (4)
(wherein, Ar, R
1, R
2, R
3, R
4, R
5The same with m) can be by making compound shown in the general formula (6)
(wherein, R
5The same, p represents blocking group, and n represents 1 or 2) by compound shown in the general formula (5)
(wherein, Ar, R
1, R
2, R
3And R
4The same) 5 reduction aminations, remove the protecting group of gained compound (7) then
(wherein, Ar, R
1, R
2, R
3, R
4, R
5, m and p be the same) and make.
As blocking group, can mention carbamate groups such as ethoxycarbonyl and tertbutyloxycarbonyl herein.
Reduction amination is advisable under the following conditions: 0-100 ℃; In organic solvent such as methyl alcohol, ethanol, benzene and dimethyl formamide; Make reductive agent with noble metal catalyst such as palladium charcoal or platinum oxide, sodium borohydride, sodium cyanoborohydride or analogue.Protective reaction is at 0-100 ℃, under acidic conditions, reacts with trifluoroacetic acid, spirit of salt, Hydrogen bromide or class acidoid and to be advisable.
In addition, because aryl glycinamide derivatives of the present invention has unsymmetrical carbon at contiguous carbonyl place, therefore have optical isomer more than 2 kinds or 2 kinds at least, and these isomer and composition thereof include in the present invention.
By the acid of they and optical activity of substep recrystallization is as 10-camphorsulfonic acid, tartrate or O from suitable solvent, the salt that the O-dibenzoyl tartaric acid is become can obtain the optical isomer goods.Their also available stereoselectivity synthesis methods are prepared.Their also available chiral stationary phase chromatography technology are prepared.
And, by with physiology on available mineral acid example hydrochloric acid, sulfuric acid, Hydrogen bromide and phosphoric acid, or organic acid such as toxilic acid, fumaric acid, tartrate, oxalic acid, D-camphorsulfonic acid, D-(ten)-dibenzoyl tartaric acid etc. reacts by well-established law, can change novel cpd of the present invention into acid salt.
In addition, the administering mode of novel cpd of the present invention can mention with oral such as tablet, capsule, granule, pulvis, syrup or similar formulation, or with injection, suppository or similar formulation parenteral admin.
Below, will elaborate the present invention according to embodiment.
Reference example 1
N-cyclohexyl-α-bromophenyl ethanamide
Ice-cooled and stir under, through 10 minutes, in the mixture that encircles amine (10.9g), triethylamine (11.1g) and chloroform (200ml), drip α-bromophenyl Acetyl Chloride 98Min. (23.3g), with mixture backflow 10 hours.After the rotation cooling, use 0.5N hydrochloric acid (100ml), 0.5N aqueous sodium hydroxide solution (100ml) and saturated common salt solution (100ml) washing reaction mixture in succession, concentrate then.Residue is recrystallization from ethyl acetate-ethanol, gets 12.2g colourless crystallization title compound.Recrystallization mother liquor concentrates, residue column chromatography (developping agent: chloroform: ethanol=20: 1) purify, again 13.0g colourless crystallization title compound (total yield 85.4%).
Fusing point: 126-127 ℃
H-NMR（CDCl
3）：δ：7.30-7.44（5H，m），6.56（1H，brs），5.42（1H，s），3.77-3.84（1H，m），1.94（2H，brs），1.72-1.74（2H，brs），1.57-1.64（1H，m），1.35-1.44（3H，m），1.20-1.29（5H，m）.
Embodiment 1
N-cyclohexyl-α-((2-(tert.-butoxy) ethyl) amino) phenylacetamide
The mixture of N-cyclohexyl-α-bromophenyl ethanamide (2.37g), N-tertiary butyl quadrol (2.00g), triethylamine (1.12ml) and toluene (30ml) was refluxed 18 hours.Reaction mixture is concentrated, and residue is white oily product through alumina column chromatography (developping agent: ethyl acetate) purify, reduced pressure distillation then gets 1.03g(38.9%) title compound.
Boiling point: 200 ℃ (2.0mmHg)
Ultimate analysis (%): with C
20H
33N
3The O meter
Calculated value C:72.46 H:10.03 N:12.68
Measured value C:72.33 H:10.19 N:12.61
Mass spectrum (m/z): 331(M
+), 245,205,149
H-NMR（CDCl
3）δ：7.27-7.38（5H，m），7.12（1H，s），4.12（1H，s），3.76-3.78（1H，m），2.65-2.69（4H，m），1.88（3H，m），1.58-1.68（3H，m），1.34-1.40（2H，m），1.16-1.23（2H，m），1.08（9H，s）.
Embodiment 2
N, N-diethyl-α-((uncle's 2-(fourth amino) ethyl) amino) phenylacetamide
Similar to Example 1, get 1.60g(26.2%) title compound, be yellow oil product.
Boiling point: 190 ℃ (0.5mmHg)
Ultimate analysis (%): with C
18H
31N
3O1/9H
2The O meter
Calculated value C:70.32 H:10.23 N:13.67
Measured value C:70.23 H:10.30 N:13.50
Mass spectrum (m/z): 305(M
+), 290,219
H-NMR（CDCl
3）δ：7.27-7.33（5H，m），4.44（1H，s），3.50-3.55（1H，m），3.24-3.33（2H，m），3.06-3.12（1H，m），2.52-2.73（4H，m），1.09-1.12（3H，t，J＝7.3Hz），1.08（9H，s），0.98-1.02（3H，t，J＝7.3Hz）.
Embodiment 3
The N-tertiary butyl-α-((2-(diethylin) ethyl) amino) phenylacetamide
Similar to Example 1, obtain 10.00g(65.5%) the colourless crystallization title compound
Fusing point: 50-52 ℃ (normal hexane)
Ultimate analysis (%): with C
18H
31N
3O1/10H
2The O meter
Calculated value C:70.78 H:10.23 N:13.76
Measured value C:70.44 H:10.31 N:13.74
Mass spectrum (m/z): 305(M
+), 205,163
H-NMR（CDCl
3）δ：7.26-7.34（5H，m），4.01（1H，s），2.63-2.65（2H，m），2.47-2.56（6H，m），1.35（9H，s），0.96-1.00（6H，t，J＝7.3Hz）.
Embodiment 4-45
Press the method for embodiment 1 and synthesize compound shown in the following general formula (1), see Table 1-8.
Table 2
＊1：mp89-92℃
Table 3
Table 4
＊2：mp79-81℃
Table 5
Table 6
＊3：mp103-105℃
Table 7
Table 8
＊4：mp71-72℃
Embodiment 46
N-cyclohexyl-α-((uncle's 2-(fourth amino) ethyl) amino) phenylacetamide one maleate
N-cyclohexyl-α-(((uncle's 2-(fourth amino) ethyl) amino) phenylacetamide (0.50g) is dissolved in ethyl acetate (15ml), after adding Maleic Acid, Anhydrous (0.17g) and ethanol (2ml) and the heating for dissolving, solution was placed in refrigerator two days.Filter and collect the crystallization of separating out, it in dry, is got 0.32g(47.3%) title compound.
Fusing point: 152-154 ℃
Ultimate analysis (%): with C
20H
33N
3OC
4H
4O
4Meter
Calculated value C:64.39 H:8.34 N:9.39
Measured value C:64.37 H:8.36 N:9.38
Embodiment 47
N, N-diethyl-α-((uncle's 2-(fourth amino) ethyl) amino) phenylacetamide one maleate
Similar with embodiment 46, obtain 0.50g(72.5%) the colourless crystallization title compound.
Fusing point: 107-110 ℃
Ultimate analysis (%): with C
18H
31N
3OC
4H
4O
4Meter
Calculated value C:62.69 H:8.37 N:9.97
Measured value C:62.57 H:8.44 N:9.80
Embodiment 48
The N-tertiary butyl-α-((2-(diethylin) ethyl) amino) phenylacetamide one maleate
Similar with embodiment 46, obtain 0.45g(67.2%) the colourless crystallization title compound.
Fusing point: 89-91 ℃
Ultimate analysis (%): with C
18H
31N
3OC
4H
4O
4Meter
Calculated value C:62.69 H:8.37 N:9.97
Measured value C:62.63 H:8.48 N:9.90
Embodiment 49-53
Press the method for embodiment 46, compound shown in the synthetic following general formula (8) sees Table 9,10.
Table 9
* 1 with 1/2H
2The O meter
* 2 with 1/3H
2The O meter
* 3 with 1/6H
2The O meter
* 4 decomposition points
Reference example 2
N-tertbutyloxycarbonyl-N-tertiary butyl glycinal
Under ice-cooled and stirring, in the 500ml round-bottomed flask that N-tertbutyloxycarbonyl-N-tertiary butyl thanomin (7.24g), triethylamine (13.5g) and methylene dichloride (150ml) are housed, once add sulphur trioxide-pyridine mixture (15.9g) solution that is dissolved in 150ml DMSO.After at room temperature stirring 10 minutes, in 1 liter of saturated common salt solution of reaction mixture impouring.After telling dichloromethane layer, the water layer ether extraction merges institute's organic layer, with anhydrous sodium sulfate drying and concentrated.(chloroform: ethanol=20: 1) purify, get 6.80g purpose product, be a light yellow oily product to residue through silica gel column chromatography.Yield 94.8%.
Embodiment 54
(S)-and N, the amino ethylamino of N-diethyl-uncle's 2-(2-fourth)-2-phenylacetamide one maleate
Be used for the 100ml reaction flask of middle pressure catalytic reduction, (the S)-2-phenylglycocoll diethylamide (0.90g) of packing into, N-tertbutyloxycarbonyl-N-tertiary butyl glycinal(1.80g), 10% palladium charcoal (1.06g), molecular sieve 4A activation powder (9.03g) and ethanol (50.0ml), at room temperature, at 3.6kg/cm
2Under the initial pressure, carry out 10 hours hydrogenation reactions.Filter insolubles, use washing with alcohol, then filtrate is concentrated.Under ice-cooled, in residue, add the 30.0ml trifluoroacetic acid.After mixture at room temperature stirs 1 hour, the excessive trifluoroacetic acid of pressure reducing and steaming.In residue, add 100ml water and 40.0ml28% ammoniacal liquor, use CHCl
3Extract.Organic layer also concentrates with anhydrous sodium sulfate drying.Residue is purified through alumina column chromatography (ethyl acetate), handles with toxilic acid, thereby obtains 730mg(yield 39.6%) (S)-diethyl-uncle's 2-(2-fourth amino-ethyl)-2-phenylacetamide one maleate, be colourless crystallization shape powder.
Fusing point: 111-113 ℃ (ethyl acetate)
〔α〕
20 D＝+60.88°（C＝0.722，EtOH）
Ultimate analysis (%): with C
18H
31N
3OC
4H
4O
4Meter
Calculated value C:62.69 H:8.37 N:9.97
Measured value C:62.38 H:8.17 N:9.92
NMR（400MHz，d
6DMSO，δ）7.34-7.40（m，5H），6.04（S，2H），4.76（m，1H），3.22-3.37（m，4H），2.95-2.96（m，2H），2.65（m，2H），1.25（S，9H），0.99-1.02（t，3H，J＝6.8Hz），0.84-0.88（t，3H，J＝6.8Hz）.
Through using the HPLC(post of chiral column: chirality cel OD-R) analyze, the optical purity of gained optically active substance is 99.8%e.e.
Embodiment 55-66
With the method same with embodiment 54, synthetic below compound shown in the general formula (1), see Table 11,12.
Table 11
Experimental example 1
Cholinolytic effect on the isolated guinea pig ileum sample
(the about 2cm of length) is suspended among the 10ml organ bath that Tyrode liquid is housed with male guinea pig ileum sample.Tyrode liquid constantly fills with 95%O
2+ 5%CO
2, be incubated 37 ℃.Through isotonic transducer, record shrinks on pen-ink recorder.
Vagusstoff accumulation is added in the bath, to obtain the constant dose-response curve, before studying the different concns test-compound then and handling and handle after 5 minutes influence the dose-response curve of vagusstoff.Its contraction intensity is expressed as the ratio of vagusstoff maximum collapse intensity when not adding test-compound.The pA that test-compound is obtained by the Schild graphing method the avidity of poisonous weeds alkali acceptor
2Value is converted into concentration and records.The results are shown in Table 13.
Experimental example 2
Restraining effect to the rhythmicity bladder contracts
Male rat is faced upward the position fix under halothane anesthesia, open belly, expose bladder, make a little otch at its top, will insert bladder with the conduit of rubber ball through this otch, and make purse wire and sew up along center line.Conduit is drawn the epigastrium of stitching, be connected in stop,threeway, connect syringe, connect pressure transmitter at the other end, to measure intravesical pressure at an end of stop,threeway.The water of about 0.1-0.3ml is injected ball to cause the rhythmicity bladder contracts, after reaching constant rhythmicity bladder contracts amplitude, give test-compound through duodenum.Reduce to record retarding effect by the bladder contracts amplitude.
Experimental example 3
Restraining effect to the sialisterium salivation
Under urethane anesthesia, make a little otch at male rat epigastrium, give test-compound through duodenum.After 30 minutes, subcutaneous injection 1mg/kg pilocarpine.After giving pilocarpine to 1.5 hour, collected saliva with the absorbent cotton that places mouth in per 30 minutes.Minimizing by absorbent cotton weight records the secretion inhibitor effect.
The The compounds of this invention demonstration is better than the bladder selectivity of control drug terodiline hydrochloride and oxybutynin chloride (to the restraining effect (ID of salivation
30)/to the restraining effect (ED of rhythmicity bladder contracts
30)).Their cholinolytic effect is the 1/5000-1/8 of control drug, and to the restraining effect of bladder be 1/5-4 doubly.Particularly, embodiment 1,6 and 7 compound almost equate with oxybutynin chloride the restraining effect of bladder, but its restraining effect to salivation (one of untoward reaction) only is the latter's 1/6-1/10.
Table 13
Anticholinergic activity and bladder selectivity
As mentioned above, new compound aryl glycinamide derivatives of the present invention shows can have therapeutic action to misnicturition such as the urinary incontinence and frequent micturition, and does not produce untoward reaction such as dry, renal shutdown and the misnicturition of the conventional urinary incontinence, frequent micturition medicine.
Claims (4)
1, the aryl glycinamide derivatives and the salt thereof of general formula (1) expression
Wherein Ar represents to have 1-3 substituent phenyl that 1-3 substituent naphthyl, R maybe can be arranged
1And R
4Represent hydrogen atom identical or differently or have the low alkyl group of 1-3 carbon atom, R
2Expression have 1-6 carbon atom low alkyl group, have 3-6 carbon atom cycloalkyl, 1-4 carbon atom arranged and can have on the carbon atom and the individual substituent phenyl of 1-3 can maybe can be arranged, R with low alkyl group, norcamphyl, the adamantyl of the individual substituent phenyl of 1-3
3Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
2Form the ring that alkylidene group is formed together, R
5Expression has the low alkyl group of 1-6 carbon atom or the cycloalkyl of 5 or 6 carbon atoms, R is arranged
6Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
5Form the ring that alkylidene group is formed together, m represents 2 or 3.
2, the preparation method of compound and salt thereof shown in the general formula (1)
Wherein Ar represents to have 1-3 substituent phenyl that 1-3 substituent naphthyl, R maybe can be arranged
1And R
4Represent hydrogen atom identical or differently or have the low alkyl group of 1-3 carbon atom, R
2Expression have 1-6 carbon atom low alkyl group, have 3-6 carbon atom cycloalkyl, 1-4 carbon atom arranged and can have on the carbon atom and the individual substituent phenyl of 1-3 can maybe can be arranged, R with low alkyl group, norcamphyl, the adamantyl of the individual substituent phenyl of 1-3
3Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
2Form the ring that alkylidene group is formed together, R
5Expression has the low alkyl group of 1-6 carbon atom or the cycloalkyl of 5 or 6 carbon atoms, R is arranged
6Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
5Form the ring that alkylidene group is formed together, m represents 2 or 3, the method is characterized in that: with compound shown in the general formula (3)
(wherein, R
4, R
5, R
6The same with m) with general formula (2) shown in compound
(wherein, Ar, R
1, R
2And R
3The same, X represents to eliminate group) react.
3, the preparation method of compound and salt thereof shown in the general formula (4)
Wherein Ar represents to have 1-3 substituent phenyl that 1-3 substituent naphthyl, R maybe can be arranged
1And R
4Represent hydrogen atom identical or differently or have the low alkyl group of 1-3 carbon atom, R
2Expression have 1-6 carbon atom low alkyl group, have 3-6 carbon atom cycloalkyl, 1-4 carbon atom arranged and can have on the carbon atom and the individual substituent phenyl of 1-3 can maybe can be arranged, R with low alkyl group, norcamphyl, the adamantyl of the individual substituent phenyl of 1-3
3Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
2Form the ring that alkylidene group is formed together, R
5Expression has the low alkyl group of 1-6 carbon atom or the cycloalkyl of 5 or 6 carbon atoms is arranged, and m represents that 2 or 3 the method is characterized in that: with compound shown in the general formula (6)
(R wherein
5The same, p represents blocking group, and n represents 1 or 2) with compound shown in reductive agent and the general formula (5)
(wherein, Ar, R
1, R
2, R
3, R
4The same) react, remove the protecting group of gained compound (7) then
(wherein, Ar, R
1, R
2, R
3, R
4, R
5, m and p be the same).
4, dysuric medicine, it is characterized in that containing aryl glycinamide shown in one or more general formulas (1) and salt thereof is effective constituent
Wherein Ar represents to have 1-3 substituent phenyl that 1-3 substituent naphthyl, R maybe can be arranged
1And R
4Represent hydrogen atom identical or differently or have the low alkyl group of 1-3 carbon atom, R
2Expression have 1-6 carbon atom low alkyl group, have 3-6 carbon atom cycloalkyl, 1-4 carbon atom arranged and can have on the carbon atom and the individual substituent phenyl of 1-3 can maybe can be arranged, R with low alkyl group, norcamphyl, the adamantyl of the individual substituent phenyl of 1-3
3Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
2Form the ring that alkylidene group is formed together, R
5Expression has the low alkyl group of 1-6 carbon atom or the cycloalkyl of 5 or 6 carbon atoms, R is arranged
6Expression hydrogen atom or the low alkyl group or and the R of 1-6 carbon atom are arranged
5Form the ring that alkylidene group is formed together, m represents 2 or 3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP219699/92 | 1992-07-27 | ||
| JP21969992 | 1992-07-27 |
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| Publication Number | Publication Date |
|---|---|
| CN1112109A true CN1112109A (en) | 1995-11-22 |
| CN1042728C CN1042728C (en) | 1999-03-31 |
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ID=16739583
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|---|---|---|---|
| CN93109151A Expired - Fee Related CN1042728C (en) | 1992-07-27 | 1993-07-27 | Novel arylglycinamide derivatives and preparative processes therefor |
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| Country | Link |
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| CN (1) | CN1042728C (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5153226A (en) * | 1989-08-31 | 1992-10-06 | Warner-Lambert Company | Acat inhibitors for treating hypocholesterolemia |
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Correction item: Priority Correct: [32]1992.07.27 [33]JP [31]219699/1992 [32]1993.07.14 [33]JP [31]196882/1993 False: [32]1992.07.27 [33]JP [31]219699/92 Number: 13 Page: The title page Volume: 15 |
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Free format text: CORRECT: PRIORITY; FROM: [32]1992.7.27[33]JP[31]219699/92 TO: [32]1992.7.27[33]JP[31]219699/1992 [32]1993.7.14[33]JP[31]196882/1993 |
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