Amino amides, peptides and peptidomimetics

• US 6,946,542 B2
• Filed: 04/01/2003
• Issued: 09/20/2005
• Est. Priority Date: 04/01/2002
• Status: Expired due to Fees

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Yao, Xin, Petasis, Nicos A.
• Primary Examiner(s): Campbell, Bruce R.
• Assistant Examiner(s): Kosar, Andrew D.
• Application Number:
  US10/405,927
• Publication Number:
  US 20040010162A1
• Time in Patent Office: 903 Days
• Field of Search: 530/300, 530333-337
• US Class Current: 530/333
• CPC Class Codes: C07C 231/12 by reactions not involving the formation of carboxamide groups
• CPC Class Codes: C07D 333/24 Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

Synthetic methods and compounds involving amino amides, peptides and peptidomimetics. Amino amide derivatives are prepared via the one-step three-component reaction of a glyoxamide, an amine, and an organoboron derivative. Conversion of the product to another glyoxamide intermediate allows the iterative use of this chemistry for the synthesis of peptides and peptidomimetics.

Claims

1. A method for preparing a peptide, the method comprising:

providing an amino derivative of formula 6

 

wherein;

R¹, R² and R⁴ are independently selected from a group consisting of hydrogen, alkyl, allyl, alkenyl, aryl, heteroaryl, acyl, sulfonyl, amino, alkylamino, dialkylamino, acylamino, sulfonylamino, and alkoxy, provided that two or more of R¹, and R² R⁴ can be connected together forming one or more rings;

R³ is alkyl, aryl, heteroaryl, allyl, alkenyl, alkynyl or allenyl; and

Rw is hydrogen, alkyl, aryl, heteroaryl;

converting the amino amide derivative of formula 6 to a compound of formula 7

 

wherein;

Rw′

is hydrogen, alkyl, aryl, heteroaryl;

contacting the compound of formula 7 with an amine of formula 8 and an organoboron compound of formula 9 to form a reaction mixture

 

wherein;

R⁵ is alkyl, aryl, heteroaryl, allyl, alkenyl, alkynyl, or allenyl;

Rc and Rd are independently selected from a group consisting of hydrogen, alkyl, allyl, benzyl, aryl, heteroaryl, acyl, sulfonyl, amino, acylamino, sulfonylamino, and alkoxy, provided that Rc and Rd can be joined together forming a ring; and

X and Y are independently selected from a group consisting of hydroxy, alkoxy, aryloxy, amino, alkylamino, and dialkylamino, provided that X and Y can also be joined together forming a ring; and

allowing the reaction mixture to react to form a peptide of formula 10

2. The method of claim 1, further comprising:

converting the peptide of formula 10 into a peptide of formula 11

 

wherein;

R⁶ is hydrogen, alkyl, allyl, alkenyl, aryl, heteroaryl, acyl, sulfonyl, amino, alkylamino, dialkylamino, acylamino, sulfonylamino, or alkoxy.

3. The method of claim 1, wherein:

one of R¹, R², R³, R⁴, R⁶, Rc, Rd, Rw, X or Y is connected to a polymeric chain or other solid phase material.

4. The method of claim 1, wherein:

one or more of Rw and Rw′

are hydrogen.

5. The method of claim 1, wherein:

the peptide of formula 10 is formed as a member of a combinatorial library.

6. The method of claim 3, wherein:

the peptide of formula 10 is formed as a member of a combinatorial library.