Benzothiophene compounds intermediate compositions and methods for inhibiting aortal smooth muscle proliferation

• US 5,492,922 A
• Filed: 06/06/1995
• Issued: 02/20/1996
• Est. Priority Date: 02/28/1995
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Palkowitz, Alan D.
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US08/469,952
• Time in Patent Office: 259 Days
• Field of Search: 514/212, 514/233.5, 514/320, 514/374, 514/422, 514/443, 514/470, 549/52, 549/466, 548/525, 546/196, 546/202, 544/146, 544/157, 540/596
• US Class Current: 514/324
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• CPC Class Codes: A61K 31/4535 containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
• CPC Class Codes: A61K 31/5355 Non-condensed oxazines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 5/24 of the sex hormones
• CPC Class Codes: C07D 333/62 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 333/64 Oxygen atoms
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention provides pharmaceutically active compounds of formula I ##STR1## wherein R¹ is --H, --OH, --O(C₁ -C₄ alkyl), --OCOC₆ H₅, --OCO(C₁ -C₆ alkyl), or --OSO₂ (C₂ -C₆ alkyl);

R² is --H, --OH, --O(C₁ -C₄ alkyl), --OCOC₆ H₅, --OCO(C₁ -C₆ alkyl), --OSO₂ (C₂ -C₆ alkyl), or halo, providing when Z is --S--, R² is not halo;

R³ is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino;

n is 2 or 3; and

z is --O-- or --S--;

or a pharmaceutically acceptable salt thereof, for inhibiting aortal smooth muscle proliferation.

Claims

1. A method for inhibiting aortal smooth muscle cell proliferation comprising administering to a human in need of treatment an effective amount of a compound of formula I ##STR66## wherein R¹ is --H, --OH, --O(C₁ -C₄ alkyl), --OCOC₆ H₅, --OCO(C₁ -C₆ alkyl), or --OSO₂ (C₂ -C₆ alkyl);

R² is --H, --OH, --OC₁ -C₄ alkyl), --OCOC₆ H₅, --OCO(C₁ -C₆ alkyl), --OSO₂ (C₂ -C₆ alkyl), or halo, providing when Z is --S--, R² is not halo;

R³ is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino;

n is 2 or 3; and

z is --O-- or --S--;

or a pharmaceutically acceptable salt thereof.