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Peptidomimetics with glucagon antagonist activity and GLP-1 agonist
专利权人:
CADILA HEALTHCARE LIMITED
发明人:
BAHEKAR, RAJESH,JAIN, MUKUL,PATEL, PANKAJ
申请号:
ES08873860
公开号:
ES2382579T3
申请日:
2008.12.10
申请国别(地区):
ES
年份:
2012
代理人:
摘要:
An isolated peptidomimetic having a sequence of formula (I), including its tautomers, solvates A-Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10-Z11-B where, A represents the groups - NH-R1, R3-CO-, R3-O-CO- or R3-SO2-, where R1 represents hydrogen, or an optionally substituted linear or branched (C1-C10) alkyl chain; R3 is selected from the linear or branched (C1-C10) alkyl, C3-C6 cycloalkyl, aryl, heteroaryl or arylalkyl groups; B represents -COOR2, -CONHR2 or CH2OR2, where R2 represents H, optionally substituted groups selected from a linear or branched (C1-C10) alkyl group, aryl or aralkyl groups; Z1 to Z11 represent natural or unnatural amino acids, connected to each other by amide bond, where Z1 represents L-Histidine (H), DHistidine (dH) or Urocanic Acid (UA); ** Formula ** Uurocanic acid (UA) Z2 represents an amino acid of natural or unnatural origin selected from the group comprising L-Serine (S), D-Serine (dS), L-Alanine (A), D-Alanine (dA ), α-methylproline (α-Me-Pro), α-amino-isobutyric acid (Aib), 1-aminocyclopropanecarboxylic acid (ACP), 1-amino-cyclopentanecarboxylic acid (APP); ** Formula ** Z3 represents L-Glutamine (GIn; Q), D-Glutamine (dQ) or compounds of formula II (CNB or HfI); ** Formula ** 2-Amino-4-cyano-butyric acid (CNB) Hexafluoroleucine (HfI) Z4 represents Glycine (G) or the unnatural amino acids 1-aminocyclopropanecarboxylic acid (ACP) or 1-amino-cyclopentanecarboxylic acid (APP); Z5 represents an amino acid of natural or unnatural origin comprising a hydroxylated side chain; a preferred Z5 is L-Threonine (T), D-Threonine (dT), L-Alo-threonine (alo-Thr; alo-T), D-allotreonine (d-alo-Thr; d-alo-T); Z6 represents an amino acid of natural or unnatural origin with a disubstituted alpha carbon having two side chains, each of which can independently be an optionally substituted alkyl or aryl group or an aralkyl group where the substituents can be selected from one or more groups alkyl or one or more halo groups;Un peptidomimético aislado que tiene una secuenc
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