Pyrrolidinyl benzopyrans as hypotensive agents

{
  "publication_number": "US4831050A",
  "country": "US",
  "kind": "A",
  "title": "Pyrrolidinyl benzopyrans as hypotensive agents",
  "abstract": "Compounds of formula (I): ##STR1## wherein: either one of R 1 and R 2 is hydrogen and the other is selected from the class of C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonyloxy, C 1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C 1-6 alkylsulphinyl, C 1-6 alkylsulphonyl, C 1-6 alkoxysulphinyl, C 1-6 alkoxysulphonyl, C 1-6 alkylcarbonylamino, C 1-6 alkoxycarbonylamino, C 1-6 alkyl-thiocarbonyl, C 1-6 alkoxy-thiocarbonyl, C 1-6 alkyl-thiocarbonyloxy, 1-mercapto C 2-7 alkyl, formyl, or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C 1-6 alkyl groups, or C 1-6 alkylsulphinylamino, C 1-6 alkylsulphonylamino, C 1-6 alkoxysulphinylamino or C 1-6 alkoxysulphonylamino, or ethylenyl terminally substituted by C 1-6 alkylcarbonyl, nitro or cyano, or --C(C 1-6 alkyl(NOH or --C(C 1-6 alkyl)NNH 2, or one of R 1 and R 2 is nitro, cyano or C 1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C 1-6 alkyl or by C 2-7 alkanoyl; one of R 3 and R 4 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R 3 and R 4 together are C 2-5 polymethylene; either R 5 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 acyloxy and R 6 is hydrogen or R 5 and R 6 together are a bond; and n is 1 or 2; the hydroxy group substituting the lactam group is other than at position a; and the substituted lactam group being trans to the R 5 group when R 5 is hydroxy, C 1-6 alkoxy or C 1-7 acyloxy; or a pharmaceutically acceptable salt thereof; having antihypertensive activity, a process for their preparation and their use as pharmaceuticals.",
  "claims": [
    "1. A compound of formula (I): ##STR10## wherein: either one of R 1 and R 2 is hydrogen and the other is C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, nitro, cyano or trifluoromethyl, or one of R 1 and R 2 is nitro, cyano or C 1-3 alkylcarbonyl and the other is amino unsubstituted or substituted by one or two C 1-6 alkyl or by C 2-7 alkanoyl; one of R 3 and R 4 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl or R 3 and R 4 together are C 2-5 polymethylene; either R 5 is hydrogen, hydroxy, C 1-6 alkoxy or C 1-7 alkanoloxy and R 6 is hydrogen or R 5 and R 6 together are a bond; and n is 1; the hydroxy group substituting the lactam group is other than at the position a; and the substituted lactam group being trans to the R 5 group when R 5 is hydroxy, C 1-6 alkoxy of C 1-7 alkanoyloxy; or a pharmaceutically acceptable salt thereof.",
    "2. A compound according to claim 1 wherein R 1 is nitro, cyano or C 1-3 alkylcarbonyl and R 2 is hydrogen.",
    "3. A compound according to claim 1 wherein R 3 and R 4 are both methyl groups.",
    "4. A compound according to claim 1 wherein R 5 is hydroxy and R 6 is hydrogen.",
    "5. A compound according to claim 1 wherein the hydroxy substituent on the lactam ring is at position 3- or 4-relative to the lactam nitrogen atom, and n is 1.",
    "6. A compound according to claim 1 which is selected from the group consisting of (±)-trans-6-cyano-3,4-dihydro-2,2-dimethyl-4-(3'-α-hydroxy-2-oxo-1-pyrrolidinyl)-2H-1-benzopyran-3-ol; (±)-trans-6-cyano-3,4-dihydro-2,2-dimethyl-4-(4'α-hydroxy-2-oxo-1-pyrrolidinyl)-2H-1-benzopyran-3-ol, or the single (-)-isomer thereof.",
    "7. A compound according to claim 1 in pharmaceutically acceptable form.",
    "8. An antihypertensive pharmaceutical composition comprising an antihypertensive effective amount of a compound according to claim 1, and a pharmaceutically acceptable carrier.",
    "9. A method of treatment of hypertension in mammals, which comprises the administration of an antihypertensive effective amount of a compound according to claim 1."
  ],
  "cpc": [
    "C07D 405/04",
    "A61P 9/12"
  ],
  "assignees": [
    "BEECHAM GROUP PLC"
  ],
  "filing_date": "1987-10-21",
  "publication_date": "1989-05-16",
  "grant_date": "1989-05-16",
  "priority_date": "1986-10-21",
  "application_number": "US-11177087-A",
  "family_id": "10606077",
  "citations": [
    "GB1548221A",
    "US4446113A",
    "US4446113B1",
    "US4510152A",
    "US4542149A",
    "US4555509A",
    "US4610992A",
    "US4640928A",
    "US4644070A",
    "US4647670A"
  ]
}