http://rdf.ncbi.nlm.nih.gov/pubchem/patent/GB-1215812-A
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_c8cbc6261d883f27c8339ffb4b4cfeaa |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D499-00 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D499-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D499-68 |
| filingDate | 1967-09-29-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_43971dc77b8e0b61d82e4198cc6198ae http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_fca1cbe1a498b2049d4d9c73e5f6f5c8 |
| publicationDate | 1970-12-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | GB-1215812-A |
| titleOfInvention | Esters of penicillanic acids |
| abstract | 1,215,812. α-Aminobenzylpenicillanic esters. LOVENS KEMISKE FABRIK PRODUKTIONS A.S. 27 Sept., 1968 [29 Sept., 1967; 5 Oct., 1967; 23 Oct., 1967; 10 Nov., 1967; 6 Dec., 1967; 3 Jan., 1968; 22 March, 1968; 29 March, 1968], Nos. 44535/67, 45600/67, 48127/67, 51358/67; 55489/67, 499/68, 14041/68 and 15312/68. Headings C2A and C2C. Novel esters of α-aminobenzylpenicillin of the general Formula I wherein n is an integer of 0 to 5, A is a substituted or unsubstituted aliphatic, alicyclic, aromatic or heterocyclic radical, and * indicates an asymmetric carbon atom, and the individual epimers and non-toxic salts thereof, are prepared by (a) reaction an α-substituted benzylpenicillin derivative of Formula II with a compound of Formula III or (b) reacting an α-substituted phenylacetic acid derivative of Formula V with a 6 - aminopenicillic ester or derivative thereof of Formula VI in each case to give a compound of Formula IV in which formulµ n and A are as above, R is an amino group, a substituted amino group, or a group convertible to an amino group (e.g. azido, halo or nitro) and in (a) -COOY and X-CH 2 -, and in (b) -COY<SP>1</SP> and X<SP>1</SP>NH, represent radicals capable of reacting together to eliminate XY or Y<SP>1</SP>X<SP>1</SP> with formation respectively of an ester or amide linkage, whereafter if necessary R is converted to an amino group. If individual epimers are required, the corresponding epimeric penicillin starting material is employed. The compounds may be isolated as their acid addition salts, e.g. the hydrochloride, phosphate, acetate or phenoxymethylpenicillinate. Reactions (a) and (b) may be effected at ambient or elevated temperatures in an organic or aqueous-organic solvent. In reaction (a) Y may be hydrogen, alkali metal or tertiary amino, and X may be halogen, C 1 -C 16 acyloxy, alkylsulphonyloxy or arylsulphonyloxy. In reaction (b) -COY<SP>1</SP> may be a radical of an acid halide, anhydride, or mixed anhydride with an alkyl-carbonic acid, a carboxylic acid radical, an inorganic acid or sulphonic acid group, or a radical derived from reacting the α-substituted phenylacetic acid with a carbodiimide or N,N<SP>1</SP>- carbonyldiimidazole; X<SP>1</SP> may be hydrogen or a tri-C 1 to C 5 alkyl-silyl group. The compounds of Formula IV wherein R is other than -NH 2 are novel intermediates. When R is substituted amino, i.e. Z-NH-, Z may be a benzyloxycarbonyl-; p-halo-, p-nitro- or p-methoxybenzyloxycarbonyl-; #,#,#-trichloroethyloxycarbonyl, or allyloxy carbonyl radical; or a sulphur-containing radical such as tritylsulphenyl, arylsulphenyl, or o-nitrophenylsulphenyl; a triphenylmethyl- or tert. butoxycarbonyl group; or a radical obtained by reacting the free -NH 2 group with a #- dicarbonyl compound, e.g. acetylacetone, acetoacetic ester or benzoyl acetone, to form an enamine or Schiff base. Alternatively R may be halo, especially Br, nitro or azido. Conversion of such R groups into -NH 2 is effected by an appropriate known procedure, e.g. catalytic hydrogenation, reduction with Zn/HAc or by electrolysis, mild acid hydrolysis (when Z is S- containing or an enamine or Schiff base), reaction with Na or Kiodide, thiosulphate, hydrogen sulphide, dithionite or thiocyanate (when Z is sulphonamido), or amination with hexamethylenetetramine when Z is halo. The compounds of Formula VI are also novel intermediates. They may be prepared by esterifying a salt of 6-aminopenicillanic acid with a methyl ester of Formula VII wherein A and n are as above and R 2 is halogen, methanesulphonyloxy- or toluenesulphonyloxy-, if necessary after protection of the 6-amino group. Alternatively an acylaminopenicillin may be correspondingly esterified, and the acyl group subsequently removed by reaction with an acid halide (e.g. PCl 5 ) in the presence of an acid-binding agent (e.g. quinoline or pyridine), followed by treatment of the resulting imino halide with a primary alcohol to form the imino ether, which is alcoholysed or hydrolysed to the required 6-amino penicillanic ester. These esters may be isolated as their salts, e.g. the toluenesulphonate, sulphate, phosphate, hydrochloride, acetate, maleate or tartrate. Pivaloyloxymethyl p-toluenesulphonate is prepared by reacting silver p-toluenesulphonate with chloromethyl pivalate in dry acetonitrile. Pharmaceutical compositions comprise the inventive ester of Formula I or an epimer or non-toxic salt thereof together with an oral, parenteral or topical pharmaceutically acceptable carrier. The preferred epimer is the D(-) form. |
| isCitedBy | http://rdf.ncbi.nlm.nih.gov/pubchem/patent/JP-S4826792-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-4389408-A |
| priorityDate | 1967-09-29-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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