1-Phenyl-2-aminoethanol derivatives

{
  "publication_number": "US4303649A",
  "country": "US",
  "kind": "A",
  "title": "1-Phenyl-2-aminoethanol derivatives",
  "abstract": "The invention concerns new topical anti-inflammatory 1-phenyl-2-aminoethanol derivatives of the general formula: R.sup.1 ·CH(OH)·CH.sub.2 NH·CR.sup.2 R.sup.3 ·A 1 ·NH[CO·Y·NH] n ·Q wherein R 1 is a phenyl bearing specific combinations of (2-12C)alkanoyloxy,[(2-12C)alkanoyloxy]methyl,chloro and amino substituents, R 2 and R 3 are independently hydrogen or (1-4C)alkyl, A 1 is a (1-4C)alkylene, Y is a (1-4C)alkylene optionally bearing a (1-4C)alkyl or benzyl, n is an integer from 1 to 4, and Q is an optionally substituted benzoyl, phenylacetyl, or phenoxyacetyl together with the acid-addition salts thereof; and the pharmaceutical compositions thereof, for use in the treatment of inflammatory skin diseases and conditions. The invention also concerns processes for the manufacture of derivatives of formula I. A representative compound of the invention is 1-[3,4-bis(pivaloyloxy)phenyl]-2-{2-[(N-benzoylglycyl)amino]-1,1-dimethyl-ethylamino}ethanol.",
  "claims": [
    "1. A 1-phenyl-2-aminoethanol derivative of the formula: R 1.CH(OH).CH 2.NH.CR 2 R 3.A 1.NH.[CO.Y.NH] n.Q wherein R 1 is a 3,4-bis[(2-12C) alkanoyloxy]phenyl, 3,5-bis[2-12C)-alkanoyloxy]phenyl, 3-[(2-12 C)alkanoyloxymethyl]-4-[(2-12 C)alkanoyloxy]phenyl or 3,5-dichloro-4-aminophenyl radical; R 2 and R 3 are independently hydrogen or (1-4 C)alkyl radicals; A 1 is a (1-4 C)alkylene diradical; Y is a (1-4 C)alkylene diradical optionally bearing a (1-4 C)alkyl or benzyl substituent; n is an integer from 1 to 4; and Q is a benzoyl, phenylacetyl or phenoxyacetyl radical optionally bearing a nuclear substituent selected from halogeno, (1-4 C)alkyl, (1-4 C)alkoxy and trifluoromethyl radicals; provided that when n is other than 1, Y is the individual diradicals of the formula [CO.Y.NH] may have the same or different values; or a pharmaceutically acceptable acid-addition salt thereof.",
    "2. A compound as claimed in claim 1 wherein the (2-12 C)-alkanoyloxy radical of W 1 is a 2,2-dimethylpropionyloxy, isobutyryloxy, n-pentanoyloxy or 3,3-dimethylbutyryloxy radical; R 2 and R 3 are independently hydrogen or methyl radicals; A 1 is a methylene or ethylene diradical; Y is a methylene, ethylene or trimethylene diradical optionally bearing a methyl, ethyl or benzyl substituent; and Q is a benzoyl, phenylacetyl or phenoxyacetyl radical optionally bearing a nuclear substituent selected from fluoro, chloro, bromo, methyl, methoxy and trifluoromethyl radicals.",
    "3. A compound as claimed in claim 1 wherein the diradical of the formula [CO.Y.NH] is a glycyl, alanyl, β-alanyl or phenylalanyl diradical.",
    "4. A compound as claimed in claim 1, wherein the diradical of the formula [CO.Y.NH] n is a glycyl, alanyl, β-alanyl, phenylalanyl, glycylglycyl, glycylalanyl or alanylglycyl diradical.",
    "5. A compound as claimed in claim 1, wherein R 2 and R 3 are both hydrogen or methyl radicals; A 1 is a methylene diradical; the diradical of the formula [CO.Y.NH] n is a glycyl, alanyl, phenylalanyl or glycylglycyl diradical; and Q is a benzoyl, phenylacetyl or phenoxyacetyl radical.",
    "6. A 1-phenyl-2-aminoethanol derivative selected from the group consisting of 1-[3,4-bis(pivaloyloxy)phenyl]-2-{2-[(N-benzoyl-glycyl)amino]-1,1-dimethylethylamino}ethanol, 1-[3,4-bis(pivaloyloxy)phenyl]-2-{2-[(N-phenylacetyl-glycyl)amino]-1,1-dimethyl-ethylamino}ethanol, 1-[3,4-bis(pivaloyloxy)phenyl-2-{2-[(N-phenylacetylglycyl)glycyl-amino]-1,1-dimethyl-ethylamino}ethanol, 1-(3,5-dichloro-4-aminophenyl)-2-{2-[(N-phenoxyacetyl-glycyl)amino]-1,1-dimethyl-ethylamino}-ethanol, 1-(3,5-dichloro-4-aminophenyl)-2-{2-[(N-phenylacetyl-glycyl)glycyl-amino]-1,1-dimethyl-ethylamino}-ethanol, and the pharmaceutically acceptable acid-addition salts thereof.",
    "7. A pharmaceutically acceptable acid-addition salt as claimed in claim 1 which is a salt derived from hydrochloric, hydrobromic, phosphoric, sulphuric, oxalic, tartaric, lactic, fumaric, citric, acetic, slaicylic, benzoic, β-naphthoic, methane sulphonic or adipic acid.",
    "8. A method of treatment of an area of inflammation affecting the skin of a warm blooded animal which comprises topically administering to said area an effective amount of a compound of formula I, or a pharmaceutically acceptable acid-addition salt thereof: R 1.CH(OH).CH 2.NH.CR 2 R 3.A 1.NH.[CO.Y.NH] n Q I wherein R 1 is a radical of the formula: ##STR3## in which W 1 is a (2-12 C)alkanoyloxy, A 2 is a direct bond or a methylene diradical, one of W 2 and W 3 is hydrogen, and the other of W 2 and W 3 is a (2-12 C)alkanoyloxy radical; or R 1 is a phenyl, 2-chlorophenyl or 3,5-dichloro-4-aminophenyl radical; R 2 and R 3 are independently hydrogen or (1-4 C)alkyl radicals; A 1 is a (1-4 C)alkylene diradical; Y is a (1-4 C)alkylene diradical optionally bearing a (1-4 C)alkyl or benzyl substituent; n is an integer from 1 to 4; and Q is a benzoyl, phenylacetyl or phenoxyacetyl radical optionally bearing a nuclear substituent selected from halogeno, (1-4 C)alkyl, (1-4 C)alkoxy and trifluoromethyl radicals; provided that when n is other than 1, Y is the individual diradicals of the formula [CO.Y.NH] may have the same or different values.",
    "9. A pharmaceutical composition which comprises a compound of formula I or a pharmaceutically acceptable salt thereof as claimed in claim 1, in association with a pharmaceutically acceptable diluent or solvent, and in a form suitable for topical administration."
  ],
  "cpc": [
    "C07K 5/06026",
    "A61K 38/00",
    "A61P 17/00"
  ],
  "assignees": [
    "ICI LTD"
  ],
  "filing_date": "1979-05-29",
  "publication_date": "1981-12-01",
  "grant_date": "1981-12-01",
  "priority_date": "1978-06-15",
  "application_number": "US-4342579-A",
  "family_id": "10497984",
  "citations": [
    "DE2745222A1",
    "US3944611A",
    "US4038417A",
    "US4041075A"
  ]
}