# US 4,391,816 A · N-(Naphthalenylthioxomethyl)aminoacid derivatives > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,391,816 A - Document ID: US4391816A - Status: Granted - Kind: A - Application number: 06/321,304 - Filed: 1981-11-13 - Granted: 1983-07-05 - Earliest claimed: 1981-11-02 - Assignees: Ayerst McKenna and Harrison Ltd. - Inventors: Kazimir Sestanj; Nedumparambil A. Abraham; Francesco Bellini; Adi Treasurywala - Web page: https://patentgrep.com/patent/US4391816A ## CPC - C07D 207/277: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals - C07C 51/29: with halogen-containing compounds which may be formed in situ - C07C 63/72: Polycyclic acids - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract Herein disclosed are N-(naphthalenylthioxomethyl)aminoacid derivatives having aldose reductase inhibiting activity. The derivatives are useful for treating diabetic complications. ## Claims ### Claim 1 A compound of formula I ##STR4## wherein R.sup.1 is lower alkyl, carboxymethyl, phenyl or phenyl substituted with a substituent selected from halo, lower alkyl or lowe alkoxy; R.sup.2 is hydrogen or lower alkyl; n is the integer O, 1 or 2; or n is the integer O and R.sup.1 and R.sup.2 form a (CH.sub.2).sub.3 bridge to complete a pyrrolidine ring with the nitrogen and carbon to which R.sup.1 and R.sup.2 are joined; and R.sup.3 is a halo substituent at position 3, 5, 6 or 7 of the naphthalene ring, or R.sup.3 is two or three substituents on the naphthalene ring selected from the group consisting of 4-lower alkoxy-5-[di(lower alkyl)aminosulfonyl] and 3-halo-4-lower alkoxy-5-[(di(lower alkyl)aminosulfonyl]; with the proviso that when R.sup.1 is lower alkyl, then R.sup.3 is a halo substituent at position 3, 6 or 7 of the naphthalene ring or R.sup.3 is two or three substituents as defined herein, or a therapeutically acceptable salt thereof with an organic or inorganic base. ### Claim 2 (depends on 1) The compound of claim 1 wherein R.sup.1 is lower alkyl, carboxymethyl or phenyl substituted with a halo, R.sup.2 is hydrogen or lower alkyl, n is O or 2, or n is O and R.sup.1 and R.sup.2 form a (CH.sub.2).sub.3 bridge to complete a pyrrolidine ring with the nitrogen and carbon to which R.sup.1 and R.sup.2 are joined; and R.sup.3 is as defined in claim 1; or a therapeutically acceptable salt thereof with an organic or inorganic base. ### Claim 3 (depends on 1) The compound of claim 1 wherein R.sup.1 is methyl, carboxymethyl or 4-chlorophenyl, R.sup.2 is hydrogen or methyl, n is O or 2, or n is O and R.sup.1 and R.sup.2 form a pyrrolidine ring with the nitrogen and carbon to which R.sup.1 and R.sup.2 are joined; and R.sup.3 is a bromo substitutent at position 3, 5, 6 or 7 of the naphthalene ring, or R.sup.3 is two or three substituents on the naphthalene ring selected from the group of 4-methoxy-5-(dimethylaminosulfonyl) and 3-chloro-4-methoxy-5-(dimethylaminosulfonyl); or a therapeutically acceptable salt thereof with an organic or inorganic base. ### Claim 4 (depends on 1) N-[(3-Bromo-1-naphthalenyl)thioxomethyl]-N-methylglycine, as claimed in claim 1. ### Claim 5 (depends on 1) N-[(6-Bromo-1-naphthalenyl)thioxomethyl]-N-methylglycine, as claimed in claim 1. ### Claim 6 (depends on 1) N-[(7-Bromo-1-naphthalenyl)thioxomethyl]-N-methylglycine, as claimed in claim 1. ### Claim 7 (depends on 1) N-[[4- Methoxy-5-(dimethylaminosulfonyl)-1-naphthalenyl]thioxomethyl]-N-methylglyc ine, as claimed in claim 1. ### Claim 8 (depends on 1) N-[[3-Chloro-4-methoxy-5 -(dimethylaminosulfonyl)-1-naphthalenyl]-thioxomethyl]-N-methylglycine, as claimed in claim 1. ### Claim 9 (depends on 1) N-[(5-Bromo-1-naphthalenyl)thioxomethyl]-N-(4-chlorophenyl)glycine, as claimed in claim 1. ### Claim 10 (depends on 1) N-[(5-Bromo-1-naphthalenyl)thioxomethyl]-N-methyl-4-aminobutanoic acid, as claimed in claim 1. ### Claim 11 (depends on 1) N-[(5-Bromo-1-naphthalenyl)thioxomethyl]-N-methyl-D-alanine, as claimed in claim 1. ### Claim 12 (depends on 1) N-[(5-Bromo-1-naphthalenyl)thioxomethyl]-N-methyl-L-alanine, as claimed in claim 1. ### Claim 13 (depends on 1) N-[(5-Bromo-1-naphthalenyl)thioxomethyl]-L-proline, as claimed in claim 1. ### Claim 14 (depends on 1) N-[(5-Bromo-1-naphthalenyl)thioxomethyl]-N-(carboxymethyl)glycine, as claimed in claim 1. ### Claim 15 (depends on 1) A pharmaceutical composition for preventing or relieving diabetic complications in a diabetic mammal which comprises a compound of claim 1, or a therapeutically acceptable salt thereof with an organic or inorganic base, and a pharmaceutically acceptable carrier. ### Claim 16 (depends on 15) The pharmaceutical composition of claim 15 which also comprises an oral hypoglycemic agent. ### Claim 17 (depends on 1) A method of preventing or relieving diabetic complications in a diabetic mammal which comprises administering to said mammal an alleviating or prophylactic amount of a compound of claim 1, or a therapeutically acceptable salt thereof with an organic or inorganic base. ### Claim 18 (depends on 1, 17) The method of claim 17 in which the administration of the compound of claim 1 is performed simultaneously or sequentially with the administration of an effective blood glucose lowering amount of insulin or an oral hypoglycemic agent. ### Claim 19 A compound of the formula ##STR5## wherein R.sup.1 is lower alkyl, carboxymethyl, phenyl or phenyl substituted with a substituent selected from halo, lower alkyl or lower alkoxy; R.sup.2 is hydrogen or lower alkyl; n is the integer O, 1 or 2; or n is the integer O and R.sup.1 and R.sup.2 form a (CH.sub.2).sub.3 bridge to complete a pyrrolidine ring with the nitrogen and carbon to which R.sup.1 and R.sup.2 are joined; and R.sup.3 is a halo substituent at position 3, 5, 6 or 7 of the naphthalene ring, or R.sup.3 is two or three substituents on the naphthalene ring selected form the group consisting of 4-lower alkoxy-5-[di(lower alkyl)aminosulfonyl] and 3-halo-4-lower alkoxy-5-[di(lower alkyl)aminosulfonyl]; with the proviso that when R.sup.1 is lower alkyl, then R.sup.3 is a halo substituent at position 3, 6 or 7 of the naphthalene ring or R.sup.3 is two or three substituents as defined herein; and R.sup.4 is lower alkyl or ar(lower)alkyl.