http://rdf.ncbi.nlm.nih.gov/pubchem/patent/EP-0106541-A2
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_1965c83ab73b95e6e6903d4345464fb9 http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_29e74a5ec161f84d563fbffcbaff9038 http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_000463bbced4dfad468b9fb8254b8370 http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_624f5768b3bbc21a2a5c0a7c5a3360b7 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D233-64 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P27-06 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D233-64 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P27-06 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D233-54 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P27-02 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-415 |
| filingDate | 1983-09-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_206a6f1ef3aa18bf2518bd8c5e572470 |
| publicationDate | 1984-04-25-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | EP-0106541-A2 |
| titleOfInvention | Pilocarpine prodrugs |
| abstract | Compounds are disclosed of the general formula In wherein R, is a group of the formula IIn wherein R 3 is alkyl phenyl; phenyl substituted with halogen, lower alkyl, hydroxy, lower alkoxy, or phenoxy; phenyl-lower alkyl in which the phenyl group may be substituted with halogen, lower alkyl, hydroxy, lower alkoxy, or phenoxy; phenyl-lower alkenyl in which the phenyl group may be substituted with halogen, lower alkyl, hydroxy, lower alkoxy or phenoxy; and X is oxygen or sulfur; or R, is a group of the formula IIIn wherein R 4 has the same meaning as R 3 as defined above; or R 4 is a group of the formula IVn wherein R 7 has the same meaning as R 3 as defined above; or R 7 is an aromatic 5- or 6-membered heterocyclic ring containing one or two heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; and wherein R 5 and R 6 are the same or different and each represent hydrogen or have the same meaning as R 3 as defined above; n or R, is a group of the formula Vn wherein R 5 and R 6 are as defined above and R s is polyhalogenated lower alkyl or a group of the formula VIn wherein R 3 is as defined above; or R, is a group of the formula VIIn wherein R 10 and R 11 together with the adjacent nitrogen atom form a 5- or 6-membered heterocyclic ring, which in addition to the nitrogen may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur; or R, is a group of the formula VIIIn wherein R 13 is a group of the formula II, wherein R 3 and X are as defined above; or R 13 is a group of the formula VIIan wherein R 16 and R 17 are the same or different and each represent hydrogen or have the same meaning as R 3 as defined above; or R, 3 is a group of the formula VII, wherein R 10 and R 11 are as defined above; or R, is a group of the formula IXn wherein R 13 is as defined above; and R 2 is hydrogen or a group of the formula IV, wherein R 7 is as defined above; or R 2 is a group of the formula VI, wherein R 3 is as defined above; and salts thereof. n In the formula I, R, is preferably phenyl-lower alkoxy, in which the phenyl group is optionally substituted, such as benzyloxy, 2-phenylethyloxy, 4-chlorobenzyloxy, 4-methylbenzyloxy, and 4-tert.butylbenzyloxy, and R 2 is preferably hydrogen, acetyl, propionyl, butyryl, or benzoyl, and salts thereof. n Specially preferred compounds are such in which R, is benzyloxy, 2-phenylethyloxy, 4-chlorobenzyloxy, 4-tert butylbenzyloxy, or 4-methylbenzyloxy, and R 2 is acetyl, propionyl, butyryl, or benzoyl, and salts thereof. n Also disclosed are substantially pure salts of pilocarpic acid, which are prepared by hydrolyzing pilocarpine with a strong base, such as an alkaline metal or alkaline earth metal hydroxide in an aqueous medium at a temperature around 0°C. n The compounds of the formula I may be prepared by various methods, among which a preferred method is reacting a salt of pilocarpic acid such as a metal salt, or a compound of the formula X, or a salt thereofn in which R' 2 is a group R 2 as defined above or a protection group, with a compound of the formula XIn wherein R 14 is the same as R 3 as defined above, or R 14 is a group of the formula XIIn wherein R 4 , R s , and R 6 are as defined above, or R 14 is a group of the formula XIIIn wherein R 5 , R 6 , and R 8 are as defined above, and Z is hydroxy or a leaving group. n The compounds of the formula I are prodrugs of pilocarpine. When administered ophthatmically to a warm-blooded animal, such as a human, compounds of formula I, due to their high lipophilicity, will penetrate the cornea in an extent greater than pilocarpine itself, and will thereafter be converted into pilocarpine in a slow and controlled manner (Figures 3 and 4), thus obviating the need for frequent administration and the consequent side effects, such as induced myopia and miosis, that characterizes the use of pilocarpine. |
| isCitedBy | http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-4742073-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-5436350-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/WO-9209583-A1 http://rdf.ncbi.nlm.nih.gov/pubchem/patent/LT-3081-B http://rdf.ncbi.nlm.nih.gov/pubchem/patent/LT-3532-B http://rdf.ncbi.nlm.nih.gov/pubchem/patent/WO-9324466-A1 http://rdf.ncbi.nlm.nih.gov/pubchem/patent/US-5073641-A http://rdf.ncbi.nlm.nih.gov/pubchem/patent/WO-8801615-A1 |
| priorityDate | 1982-09-17-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
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