US005187183A
United States Patent [19] [in Patent Number: 5,187,183
Loscalzo et al. [45] Date of Patent: Feb. 16,1993
[54] S-NUROSO DERIVATIVES OF ACE
INHIBITORS AND THE USE THEREOF
[75] Inventors: Joseph Loscalzo, Dedham; John Cooke, Needham Heights, both of Mass.
[73] Assignee: Brigham & Women's Hospital,
Boston, Mass.
[21] Appl. No.: 715,588
[22] Filed: Jun. 14,1991
Related U.S. Application Data
[60] Division of Ser. No. 328,397, Mar. 24, 1989, Pat. No. 5,025,001, which is a continuation-in-part of Ser. No. 206,763, Jun. 15, 1988, Pat. No. 5,002,864.
[51] Int. CI.' A61K 31/415
[52] U.S. CI 514/400; 514/419;
514/542; 514/550; 514/562; 514/616; 560/16; 560/125; 560/147; 562/426; 562/507; 562/557;
562/556; 564/153; 564/154
[58] Field of Search 562/566, 556, 557, 426,
562/507; 560/147, 16, 125; 564/102, 154, 153;
514/400, 419, 542, 550, 562, 616
[56] References Cited
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International Search Report for the corresponding PCT Application, PCT/US89/02611 filed Jun. 15, 1989, of this application.
Primary Examiner—Michael L. Shippen
Attorney, Agent, or Firm—Sterne, Kessler, Goldstein &
Fox
[57] ABSTRACT
The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.
The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.
0088341 9/1983 European Pat. Off.
21 Claims, 6 Drawing Sheets
