US 12,441,760 B2
Amino diacids containing peptide modifiers
Kleomenis Barlos, Patras (GR); Dimitrios Gatos, Patras (GR); Kostas K. Barlos, Patras (GR); and Zoi Vasileiou, Patras (GR)
Assigned to CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A., Patras (GR)
Filed by CHEMICAL & BIOPHARMACEUTICAL LABORATORIES OF PATRAS S.A., Patras (GR)
Filed on Mar. 23, 2023, as Appl. No. 18/189,057.
Application 16/195,145 is a division of application No. 14/914,374, abandoned, previously published as PCT/IB2014/064123, filed on Aug. 28, 2014.
Application 18/189,057 is a continuation of application No. 16/195,145, filed on Nov. 19, 2018, granted, now 11,634,455.
Claims priority of application No. 1315335 (GB), filed on Aug. 29, 2013.
Prior Publication US 2024/0002433 A1, Jan. 4, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 1/04 (2006.01); A61K 47/54 (2017.01); C07C 269/04 (2006.01); C07C 269/06 (2006.01); C07C 271/02 (2006.01); C07C 323/60 (2006.01); C07K 1/107 (2006.01); C07K 14/00 (2006.01); C07K 14/47 (2006.01); C07K 14/505 (2006.01); C07K 14/575 (2006.01); C07K 14/605 (2006.01); C07K 14/62 (2006.01); C07K 14/635 (2006.01); C07K 14/695 (2006.01); A61K 38/00 (2006.01)
CPC C07K 1/1075 (2013.01) [A61K 47/542 (2017.08); C07C 269/04 (2013.01); C07C 269/06 (2013.01); C07C 271/02 (2013.01); C07C 323/60 (2013.01); C07K 1/04 (2013.01); C07K 1/1077 (2013.01); C07K 14/00 (2013.01); C07K 14/4703 (2013.01); C07K 14/473 (2013.01); C07K 14/505 (2013.01); C07K 14/575 (2013.01); C07K 14/57509 (2013.01); C07K 14/605 (2013.01); C07K 14/62 (2013.01); C07K 14/635 (2013.01); C07K 14/695 (2013.01); A61K 38/00 (2013.01); C07C 2603/18 (2017.05)] 8 Claims
 
1. A process for preparing a peptide of Formula 22,

OG Complex Work Unit Chemistry
wherein:
AaaxAaay . . . Aaaz and Aaa1Aaa2 . . . Aaan are each independently a natural or synthetic peptide comprising 1 to 100 natural or unnatural amino acid residues, each of which is optionally protected:
Pr is an amino protecting group:
a is an integer from 1 to 10;
b is an integer from 1 to 7;
each Y is independently a bivalent group selected from:
(a) a group of Formula 2′

OG Complex Work Unit Chemistry
where* denotes the point of attachment;
** indicates a bond to a group Z as defined above or another group Y;
r is an integer from 1 to 12; and
R1 is NH2 or OR3, where R3 is selected from H, alkyl, aryl and aralkyl; and
(b) a group of Formula 11′ or Formula 12′,

OG Complex Work Unit Chemistry
where* denotes the point of attachment;
** denotes a bond to a group Z as defined above or another group Y;
X is absent, or is selected from CH2, O, S and NR, where R is H, alkyl or aralkyl; and
m, n, and p are each independently an integer from 1 to 25; and
is an integer from 0 to 25;
Z is a terminal group selected from:
(a) a group of Formula 6, 7, 8 or 37,

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where * denotes the point of attachment to Y;
** indicates a bond to a group selected from OH, OR, and NRR′ and Formula 9;

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k and l are each independently an integer from 0 to 25;
p is an integer from 1 to 20;
q is an integer from 5 to 20; and
R and R′ are each independently selected from H, alkyl and aralkyl; and
(b) a group of Formula 5,

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where* denotes the point of attachment to Y; and
k and l are each independently an integer from 0 to 25;
said process comprising the steps of:
(i) reacting a compound of Formula 19 with a compound of Formula Z—(Y)b—OH to form a compound of Formula 1:

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(ii) reacting a resin-bound peptide of formula H-Aaa1-Aaa2- . . . Aaan-Resin with a compound of Formula 1 to form a compound of Formula 20:

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(iii) removing the protecting group from the compound of Formula 20 and coupling with an at least N-terminally protected amino acid or peptide having a free or activated carboxylic acid function and optionally repeating this step to give a compound of Formula 21,

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and
(iv) removing said compound of Formula 21 from the resin to form a compound of Formula 22,

OG Complex Work Unit Chemistry