Amide inhibitors of microsomal triglyceride transfer protein

• US 6,780,883 B2
• Filed: 12/12/2001
• Issued: 08/24/2004
• Est. Priority Date: 11/05/1998
• Status: Expired due to Fees

• Current Assignee: Warner-Lambert Company (Pfizer Inc.)
• Original Assignee: Warner-Lambert Company (Pfizer Inc.)
• Inventors: Lee, Helen Tsenwhei, Roth, Bruce David, Ramharack, Randy Ranjee, Pontrello, Jason Keith, Booth, Richard John
• Primary Examiner(s): Morris, Patricia L.
• Application Number:
  US10/021,633
• Publication Number:
  US 20020156281A1
• Time in Patent Office: 986 Days
• Field of Search: 514/352, 546/309
• US Class Current: 514/352
• CPC Class Codes: C07D 213/40 Acylated substituent nitrogen atom
• CPC Class Codes: C07D 213/75 Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 215/38 Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention provides compounds having the Formula I

The present invention also provides pharmaceutical compositions comprising a compound of Formula I and methods of treatment of atherosclerosis, obesity, restenosis, coronary heart disease, hyperlipoproteinemia, hypercholesterolemia, and hypertriglyceridemia.

Claims

1. A compound having the Formula I

wherein

R¹ is pyridyl, CH₂ pyridyl, or pyridyl substituted by OC₁-C₆alkyl;

n is 1 or 2;

R² is phenyl, substituted by OC₁-C₆alkyl,

 

Obenzyl-halogen or NO₂; and

or phenyl substituted by C₁-C₆alkyl, or a pharmaceutically acceptable salt thereof.

2. A compound in accordance with claim 1 wherein R³ is

R² is ethoxy-phenyl; and R¹ is pyridyl.

3. A compound in accordance with claim 1 wherein

R¹ is pyridyl.

8. A pharmaceutical composition comprising a compound of claim 1 in ad-mixture with a pharmaceutically acceptable carrier.

4. The compounds:

N-(4-tert-Butylbenzyl)-2-ethoxy-N-pyridin-3-yl-benzamide; and

N-Biphenyl-2-ylmethyl-2-ethoxy-N-pyridin-3-yl-benzamide.

5. The compounds:

N-Biphenyl-2-ylmethyl-2-nitro-N-pyridin-3-ylmethyl-benzamide;

2-Benzyloxy-N-biphenyl-2-ylmethyl-N-pyridin-3-ylmethyl-benzamide;

N-Biphenyl-2-ylmethyl-4-ethoxy-N-pyridin-3-ylmethyl-benzamide;

Benzo[1,3]dioxole-4-carboxylic acid biphenyl-2-ylmethyl-(6-methoxy-pyridin-3-yl)-amide.

6. The compounds:

N-Biphenyl-2-ylmethyl-2-ethoxy-N-pyridin-2-yl-benzamide;

N-Biphenyl-2-ylmethyl-2-bromo-N-pyridin-2-yl-benzamide;

N-Biphenyl-2-ylmethyl-2-nitro-N-pyridin-2-yl-benzamide;

2-Benzyloxy-N-piphenyl-2-ylmethyl-N-pyridin-2-yl-benzamide;

N-Biphenyl-2-ylmethyl-2-bromo-N-pyridin-3-yl-benzamide;

N-Biphenyl-2-ylmethyl-2-nitro-N-pyridin-3-yl-benzamide;

N-Biphenyl-2-ylmethyl-2-ethoxy-N-pyridin-4-yl-benzamide; and

N-Biphenyl-2-ylmethyl-2-methoxy-N-pyridin-4-yl-benzamide.

7. The compounds:

Benzo[1,3 dioxole-4-carboxylic acid biphenyl-2-ylmethyl-pyridin-4-yl-amide;

N-Biphenyl-2-ylmethyl-2-bromo-N-pyridin-4-yl-benzamide;

N-Biphenyl-2-ylmethyl-2-nitro-N-pyridin-4-yl-benzamide;

2-Benzyloxy-N-biphenyl-2-ylmethyl-N-pyridin-4-yl-benzamide; and

N-Biphenyl-2-ylmethyl-4-ethoxy-N-pyridin-4-yl-benzamide.