Peptide-compound cyclization method

Abstract

An object of the present invention is to provide methods of discovering drugs effective for tough targets, which have conventionally been discovered only with difficulty. The present invention relates to novel methods for cyclizing peptide compounds, and novel peptide compounds and libraries comprising the same, to achieve the above object.

1 .- 38 . (canceled) 
     
     
         39 . A peptide compound having a cyclic portion, wherein:
 (i) the peptide compound contains a cyclic portion, and has 9 to 13 amino acids and amino acid analogs in total,   (ii) the peptide compound contains at least two N-substituted amino acids and at least one N-unsubstituted amino acid,   (iii) the peptide compound has a ClogP value of 6 or more, and   (iv) the bond of the amino acids or the amino acid analogs forming the cyclic portion has at least one bond formed between an active ester group at the side chain of the amino acid or the amino acid analog and an amine group of another amino acid or amino acid analog.   
     
     
         40 . The peptide compound according to  claim 39 , wherein the amino acids and the amino acid analogs contained in the peptide compound are amino acids or amino acid analogs selected from amino acids or amino acid analogs that may be translationally synthesized, or amino acids or amino acid derivatives obtained by chemically modifying the side chain or the N-substitution site of translatable amino acids or amino acid analogs. 
     
     
         41 . (canceled) 
     
     
         42 . The peptide compound according to  claim 39 , wherein the bond of the amino acids or the amino acid analogs forming the cyclic portion is an amide bond or a carbon-carbon bond. 
     
     
         43 . The peptide compound according to  claim 39 , wherein the cyclic portion includes an intersection unit represented by the following general formula (I): 
       
         
           
           
               
               
           
         
         wherein
 R51 is a C1-C6 alkyl group, a C5-C10 aryl group, an aralkyl group or an ester group which optionally has a substituent, or an amide represented by the formula 1, 
 R52 is a C1-C6 alkyl group, an aryl group or an aralkyl group which optionally has a substituent, 
 R53 is a C1-C6 alkyl group which optionally has a substituent, or a hydrogen atom, or 
 R53 and R51 optionally be bonded to each other to form a C3-C5 alkylene group and form a 5-to 7-membered ring containing a nitrogen atom, 
 R54 is a peptide composed of 0 to 8 amino acid residues, 
 R55 is a C1-C6 alkyl group, a C5-C10 aryl group, an aralkyl group or an ester group which optionally has a substituent, or an amido group which optionally has a substituent, and 
 * represents a binding site in the cyclic portion. 
 
       
     
     
         44 . A pharmaceutical composition comprising the peptide compound according to  claim 39 . 
     
     
         45 . The pharmaceutical composition according to  claim 44 , wherein the pharmaceutical composition is an oral formulation. 
     
     
         46 .- 54 . (canceled)