Compounds capable of triggering an immune response to a pathogen, pharmaceutical composition comprising said compounds, use thereof for the treatment of a disease or disorder mediated and / or caused by an infectious agent, and process for preparing the same.

Description

1 / 84 “COMPOUNDS WITH THE CAPABILITY OF ElicitING AN IMMUNE RESPONSE TO A PATHOGEN, PHARMACEUTICAL COMPOSITION COMPRISING SAID COMPOUNDS, USE THEREOF FOR THE TREATMENT OF A DISEASE OR DISORDER MEDIATED AND / OR CAUSED BY AN INFECTIOUS AGENT AND PROCESS FOR PREPARING THEREOF” Divided from BR 11 2019 004877 4, deposited on 09 / 13 / 2017 FIELD OF THE INVENTION

[001] The invention relates to novel compounds capable of eliciting an immune response to a pathogen, to the use of said compounds in a disease or disorder mediated and / or caused by an infectious agent, to compositions containing said compounds, to processes for their preparation and to novel intermediates used in said process. FUNDAMENTALS OF THE INVENTION

[002] There is a need to find new ways to recruit an individual's immune system to fight disease. The human immune system continually scans the body for foreign signals to identify potentially harmful pathogens or mutated human cells (which can become a cause of cancerous growth) and direct them for elimination. There are natural antibodies that can be recruited to said pathogens or mutated human cells to drive the immune system to eliminate the threat. The invention details the use of a novel set of binding molecules that are designed to attract these natural antibodies so as to be able to maximize the effectiveness of immune recruitment while minimizing potential side effects.

[003] There is an urgent need to identify new ways to treat bacterial, viral, and fungal infections. Drug resistance is becoming a major threat to global health. For example, more than 2 million people in Petition 870260070784, dated 07 / 16 / 2026, page 12 / 130 2 / 84 In the US, bacteria resistant to at least one class of antibiotics have been infected (Centers for Disease Control and Prevention, 2013). Overall, identifying new antibiotics targeting resistant strains of Gram-negative organisms has been particularly difficult, in part due to the complex and evolutionary strategy these bacteria use to prevent antibiotic action (e.g., production of antibiotic-inactivating enzymes, the ability to transfer resistance between strains, efflux pumps to prevent intracellular action) along with their naturally impermeable cell membranes that hinder the identification of drugs that penetrate the cell and inhibit key targets. Furthermore, many strains utilize multiple resistance mechanisms, making it difficult to overcome a single antibiotic.

[004] An innovative method for the treatment of infectious diseases was disclosed in WO 01 / 45734 which describes a set of novel immunity binders. Examples of said binder portions include compounds or agents that are recognized by the individual's immune system as foreign and which would therefore trigger an immune response. One example is a carbohydrate molecule capable of binding to a human anti-alpha-galactosyl antibody (i.e., galactosyl-alpha-1,3-galactosyl-beta-1,4-N-acetylglucosamine) resulting in the redirection of the natural human serum anti-alpha-galactosyl antibody. The resulting effect of said immunity-binding molecule is that the individual's immune response is diverted from the individual's pre-existing immune response to the target, i.e., the pathogen.

[005] There is therefore a need for alternative immune-binding molecules for the treatment of a disease or disorder mediated and / or caused by an infectious agent. SUMMARY OF THE INVENTION

[006] According to a first aspect of the invention, a Petition 870260070784, dated 07 / 16 / 2026, p. 13 / 130 3 / 84 compound of formula (I) or a pharmaceutically acceptable salt thereof: [F-S2-Y2]ní Cy ] §1 L (I) where: L represents a selected binding moiety of a cationic antimicrobial peptide linked to Xi by an amine; Si represents a linkage or spacer selected from a (CH2)a- or -(CH2)b-(CH2-CH2-O)c-(CH2)d- group, wherein one to five of said -CH2 groups may optionally be replaced by a -C(O)NH- or -NHC(O)- group; 'a' represents an integer selected from 1 to 40; b represents an integer selected from 0 to 25; c represents an integer selected from 1 to 20; d represents an integer selected from 1 to 15; S2 represents a spacer selected from a -(CH2)e- or -(CH2)f(CH2-CH2-O)g-(CH2)h- group, where one to three of the so-called -CH2- groups may optionally be replaced by a -C(O)NH- or -NHC(O)- group; and represents a selected integer from 1 to 20; f represents an integer selected from 1 to 10; g represents an integer selected from 1 to 15; h represents an integer selected from 1 to 5; X1 represents a bond or -C(O)-; Y1 and Y2 independently represent a bond, -O-, -S-, -NH-, -C(O)-, -NHC(O)- group or -C(O)NH- group; F represents a carbohydrate molecule capable of binding to a human anti-alpha-galactosyl antibody; m represents an integer selected from 1 to 5; and Petition 870260070784, dated 07 / 16 / 2026, p. 14 / 130 4 / 84 Cy represents phenyl, biphenyl or triphenyl, such that when Cy represents biphenyl or triphenyl, said -Y1-S1-X1-L group may be present in any of said phenyl rings and said [F-S2-Y2]m- group or groups may be present in any of said phenyl rings. BRIEF DESCRIPTION OF THE FIGURES

[007] Figure 1: Shift of DPMB bound to LPS from E. coli to 'PMB_std', 'PMB_nona' and Example 1. The percent fluorescence intensity was plotted as a function of the concentration of the test compound. The 100% fluorescence intensity was defined by the positive control of DPMB + LPS. The 0% fluorescence intensity was defined by a negative control of DPMB + water. Samples were conducted in triplicate for 'PMB_std'. Samples were conducted in duplicate for 'PMB_nona' and Example 1. Error bars represent SD.

[008] Figure 2: Displacement of DPMB bound to LPS from E. coli or LPS from P. aeruginosa. The percent fluorescence intensity was plotted as a function of the concentration of the test compound. The 100% fluorescence intensity was defined by the positive control of DPMB + LPS. The 0% fluorescence intensity was defined by a negative control of DPMB + water. Samples were conducted in triplicate for 'PMB_std' and 'PMB_int'. Samples were conducted in duplicate for 'PMB_nona' and Example 1. Error bars represent SD.

[009] Figure 3: Flow cytometry results for the recruitment of C3b from human serum to the surface of E. coli, e.g., 4, 5, 6, 7 and 9. DETAILED DESCRIPTION OF THE INVENTION

[010] According to a particular aspect of the invention that may be mentioned, a compound of formula (I) or a pharmaceutically acceptable salt thereof is provided: Petition 870260070784, dated 07 / 16 / 2026, p. 15 / 130 5 / 84 [F-S2-Y2]mz CyYK ^Si L (I) where: L represents a selected binding moiety of a cationic antimicrobial peptide linked to Xi by an amine; Si represents a linkage or spacer selected from a (CH2)a- or -(CH2)b-(CH2-CH2-O)c-(CH2)d- group, wherein one or two of said -CH2 groups may optionally be replaced by a -C(O)NH- or -NHC(O)- group; 'a' represents an integer selected from 1 to 15; b represents an integer selected from 0 to 5; c represents an integer selected from 1 to 20; d represents an integer selected from 1 to 5; S2 represents a spacer selected from a -(CH2)e- or -(CH2)f(CH2-CH2-O)g-(CH2)h- group, where one or two of the so-called -CH2- groups may optionally be replaced by a -C(O)NH- or -NHC(O)- group; and represents a selected integer from 1 to 15; f represents an integer selected from 1 to 10; g represents an integer selected from 1 to 15; h represents an integer selected from 1 to 5; X1 represents a bond or -C(O)-; Y1 and Y2 independently represent a bond, -O-, -S-, -NH-, -C(O)-, -NHC(O)- group or -C(O)NH- group; F represents a carbohydrate molecule capable of binding to a human anti-alpha-galactosyl antibody; m represents an integer selected from 1 to 5; and Cy represents phenyl, biphenyl, or triphenyl, such that when Cy represents biphenyl Petition 870260070784, dated 07 / 16 / 2026, p. 16 / 130 6 / 84 or triphenyl, said -Y1-S1-X1-L group may be present on any of said phenyl rings and said [F-S2-Y2]m- group(s) may be present on any of said phenyl rings.

[011] The invention comprises a conjugate of a cationic peptide (which binds specifically to bacteria) and one or more units of a carbohydrate molecule capable of binding to a human anti-alpha-galactosyl antibody (i.e., alpha-Gal trisaccharide) connected by a linker. An example of a cationic peptide is polymyxin B (or polymyxin nonapeptide, colistin, or a derivative thereof). This family of cationic peptides binds to lipid A on the surface of the bacterial cell and, upon conjugation with alpha-Gal ligands, will present alphaGal, resulting in anti-Gal antibody recruitment and cell death. Resistance rates are likely to be low, since lipid A is important in the survival of Gram-negative bacteria. In fact, even polymyxin-resistant strains retain binding sites for cationic peptides and, as such, the alpha-Gal peptide conjugate. Thus, the invention can maintain its effectiveness even against these strains.

[012] Clearly, innovative new therapies that work through novel mechanisms and are not affected by antibiotic resistance mechanisms are particularly attractive. The solution provided by the invention, that is, the combination of the broad-spectrum bacterial binding capacity of a cationic peptide with the unique ability to specifically recruit naturally occurring anti-Gal antibodies to the bacterial surface and redirect these antibodies to promote complement activation, phagocytosis, and killing, is very attractive. The invention has the potential to provide a novel therapy for bacterial infections with broad-spectrum activity. The efficacy, which is independent of antibiotic resistance mechanisms, has the potential to be effective against multidrug-resistant strains. The invention can function as a standalone agent as well as with Petition 870260070784, dated 07 / 16 / 2026, page 17 / 130 7 / 84 standard care treatments to reduce the dose and duration of therapy.

[013] In one embodiment, Si represents: a link or a spacer selected from: - (CH2)a-, wherein one to five of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)5-CONH-(CH2)5, (CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-, (CH2)2-, -CH2-CONH-(CH2)2-, -CH2-NHCO-(CH2)4-CONH-(CH2)2- or -(CH2)6-); or - (CH2)b-(CH2-CH2-O)c-(CH2)d-, wherein one to five of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as (CH2CH2O)8-(CH2)2-, -(CH2CH2O)8-(CH2)2-CONH-(CH2)5-CONH-(CH2)5- or -(CH2)5CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2CH2O)8-(CH2)2-).

[014] In another embodiment, Si represents a linkage or spacer selected from -(CH2)a-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)5-CONH-(CH2)5, (CH2)2-, -CH2-CONH-(CH2)2-, -CH2-NHCO-(CH2)4-CONH-(CH2)2- or -(CH2)6-) or (CH2)b-(CH2-CH2-O)c-(CH2)d-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as (CH2CH2O)8-(CH2)2-).

[015] In another embodiment, Si represents a linkage or spacer selected from -(CH2)a-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)5-CONH-(CH2)5) or -(CH2)b-(CH2-CH2-O)c-(CH2)d-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as (CH2CH2O)8-(CH2)2-).

[016] In another embodiment, Si represents: a link or a spacer selected from: - (CH2)a-, wherein one or five of said -CH2- groups are optionally Petition 870260070784, dated 07 / 16 / 2026, page 18 / 130 8 / 84 replaced by a -C(O)NH- group (such as -(CH2)5-CONH-(CH2)5 or -(CH2)5CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-); or - (CH2)b-(CH2-CH2-O)c-(CH2)d-, wherein two of said -CH2- groups are optionally replaced by a -C(O)NH- group (such as -(CH2CH2O)8-(CH2)2-, (CH2CH2O)8-(CH2)2-CONH-(CH2)5-CONH-(CH2)5- or -(CH2)5-CONH-(CH2)5-CONH(CH2)5-CONH-(CH2)5-CONH-(CH2CH2O)8-(CH2)2-).

[017] In one embodiment, Si represents a linkage. In an alternative embodiment, Si represents -(CH2)a-, wherein one or five of said -CH2- groups are optionally replaced by a -C(O)NH- group (such as -(CH2)5-CONH-(CH2)5 or -(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5). In an alternative embodiment, Si represents -(CH2)b-(CH2-CH2-O)c-(CH2)d-, wherein two of said -CH2- groups are optionally replaced by a C(O)NH- group (such as -(CH2CH2O)8-(CH2)2-, -(CH2CH2O)8-(CH2)2-CONH-(CH2)5-CONH(CH2)5- or -(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2CH2O)8(CH2)2-).

[018] In another embodiment, Si represents a spacer selected from: -(CH2)a-, wherein one of said -CH2- groups is replaced by a -C(O)NH- group (such as -(CH2)5-CONH-(CH2)5); or -(CH2)b-(CH2-CH2-O)c-(CH2)d-(such as (CH2CH2O)8-(CH2)2-).

[019] In another embodiment, Si represents a spacer selected from: -(CH2)a-, in which one of said -CH2- groups is replaced by a -C(O)NH- group (such as -(CH2)5-CONH-(CH2)5).

[020] It will be evaluated that a, b, c, d, e, f, g, and h are selected to maintain an adequate ligand length between the F and L groups. Examples of adequate ligand lengths between F and L range from about 5A to about 50A or more in length, about 6A to about 45A, about 7A to about 40A, about 8A to about 35A, about 9A to about 30A, about 10A to about 25A, about Petition 870260070784, dated 07 / 16 / 2026, p. 19 / 130 9 / 84 11A to approximately 20A, approximately 12A to approximately 15A. Thus, in one embodiment, a, b, c, d, e, f, g, h represent a total integer number of no more than 30, such as between 5 and 30, such as between 7 and 29.

[021] In another modality, a represents an integer selected from 1 to 35. In another modality, a represents an integer selected from 1 to 10. In another modality, a represents an integer selected from 2 to 13. In another modality, a represents an integer selected from 2, 4, 6, 9, or 11. In another modality, a represents an integer selected from 10 to 35. In another modality, a represents an integer selected from 11 or 35. In another modality, a represents an integer selected from 11.

[022] In one form, b represents an integer selected from 0 to 24. In another form, b represents an integer selected from 0 to 3. In another form, b represents an integer selected from 0, 2, or 3. In another form, b represents an integer selected from 0 or 24. In another form, b represents an integer selected from 0.

[023] In one form, c represents an integer selected from 1 to 15. In another form, c represents an integer selected from 1 to 12. In another form, c represents an integer selected from 1 to 10. In another form, c represents an integer selected from 8.

[024] In one form, d represents an integer selected from 1 to 3. In another form, d represents an integer selected from 1 or 2. In yet another form, d represents an integer selected from 2.

[025] In one embodiment, Yi represents -C(O)NH- or -C(O)-. In another embodiment, Yi represents -C(O)NH-.

[026] In one embodiment, S2 represents a spacer selected from: - (CH2)e-, where one to three of said -CH2- groups are optionally Petition 870260070784, dated 07 / 16 / 2026, p. 20 / 130 10 / 84 replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)3-NHCO-CH2-, (CH2)3-NHCO-(CH2)5-NHCO-(CH2)5-NHCO-CH2-, -(CH2)3-NHCO-, -(CH2)3-, -(CH2)3NHCO-(CH2)4-CONH-CH2- or -(CH2)3-NH-CH2-); or - (CH2)f-(CH2-CH2-O)g-(CH2)h-, wherein one to three of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)3NHCO-(CH2CH2O)4-(CH2)2-NHCO-CH2-, -(CH2)3-NHCO-(CH2)2-(CH2CH2O)4-NHCOCH2- or -(CH2)4-NHCO-(CH2)2-(CH2CH2O)4-NHCO-CH2-).

[027] In another embodiment, S2 represents a spacer selected from: - (CH2)e-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)3-NHCO-CH2-, (CH2)3-NHCO-, -(CH2)3-, -(CH2)3-NHCO-(CH2)4-CONH-CH2- or -(CH2)3-NH-CH2-); or - (CH2)f-(CH2-CH2-O)g-(CH2)h-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)3NHCO-(CH2)2-(CH2CH2O)4-NHCO-CH2- or -(CH2)4-NHCO-(CH2)2-(CH2CH2O)4NHCO-CH2-).

[028] In another embodiment, S2 represents a selected spacer of -(CH2)e-, wherein one or two of said -CH2- groups are optionally replaced by a -C(O)NH- or -NHC(O)- group (such as -(CH2)3-NHCO-CH2-).

[029] In another embodiment, S2 represents a spacer selected from: - (CH2)e-, wherein one or three of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as -(CH2)3-NHCO-CH2- or -(CH2)3-NHCO(CH2)5-NHCO-(CH2)5-NHCO-CH2-); or - (CH2)f-(CH2-CH2-O)g-(CH2)h-, wherein two of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as -(CH2)3-NHCO(CH2CH2O)4-(CH2)2-NHCO-CH2-).

[030] In one embodiment, S2 represents a selected (CH2)e- spacer, wherein one or three of said -CH2- groups are optionally substituted. Petition 870260070784, dated 07 / 16 / 2026, page 21 / 130 11 / 84 by an -NHC(O)- group (such as -(CH2)3-NHCO-CH2- or -(CH2)3-NHCO-(CH2)5NHCO-(CH2)5-NHCO-CH2-). In an alternative embodiment, S2 represents a spacer selected from -(CH2)f-(CH2-CH2-O)g-(CH2)h-, wherein two of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as (CH2)3-NHCO-(CH2CH2O)4-(CH2)2-NHCO-CH2-).

[031] In one embodiment, S2 represents a selected (CH2)e- spacer, wherein three of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as -(CH2)3-NHCO-(CH2)5-NHCO-(CH2)5-NHCO-CH2-).

[032] In one form, and represents an integer selected from 1 to 17. In another form, and represents an integer selected from 1 to 10. In another form, and represents an integer selected from 4 to 10. In another form, and represents an integer selected from 4, 5, or 10. In another form, and represents an integer selected from 5 or 17. In another form, and represents an integer selected from 5. In another form, and represents an integer selected from 17.

[033] In one embodiment, f represents an integer selected from 1 to 8. In another embodiment, f represents an integer selected from 2 to 6. In another embodiment, f represents an integer selected from 6. In another embodiment, f represents an integer selected from 4.

[034] In one embodiment, g represents an integer selected from 1 to 5. In another embodiment, g represents an integer selected from 1 to 4. In yet another embodiment, g represents an integer selected from 4.

[035] In one form, h represents an integer selected from 1 to 4. In another form, h represents an integer selected from 1 to 3. In another form, h represents an integer selected from 1 or 2. In another form, h represents an integer selected from 2. In another form, h represents an integer selected from 4. Petition 870260070784, dated 07 / 16 / 2026, page 22 / 130 12 / 84

[036] In one embodiment, Xi represents -C(O)-.

[037] In one embodiment, Y2 represents -O-.

[038] In one form, m represents an integer selected from 1 to 4. In another form, m represents an integer selected from 1 to 3. In another form, m represents an integer selected from 1, 2, or 3. In another form, m represents an integer selected from 1 or 3. In another form, m represents an integer selected from 1 or 2. In another form, m represents an integer selected from 1.

[039] In one embodiment, Cy represents phenyl or biphenyl. In another embodiment, Cy represents biphenyl.

[040] References herein cited to the term “carbohydrate molecule capable of binding to a human anti-alpha-galactosyl antibody” include sugar (i.e., carbohydrate) moieties capable of binding to an immune response component (i.e., an anti-alpha-galactosyl antibody) of said human and consequently eliciting an immune response in a human. Examples of such carbohydrate molecules include alpha-galactosyl compounds and modified derivatives thereof. Other examples of suitable carbohydrate molecules include the alpha-gal epitopes listed in US 2012 / 0003251 as being suitable for use in the selective targeting and killing of tumor cells, the epitopes of which are hereby incorporated by reference. In one embodiment, F is selected from galactosyl-alpha-1,3-galactosylbeta-1,4-N-acetylglucosamine, alpha1-3-galactobiose, alpha1-3-beta1-4-galactotriose, or gallylipentasaccharide.

[041] In a particular embodiment, F has a structure as shown in one of the following formulas: HQ-OH, oh^oh s2 NHAc2; or Petition 870260070784, dated 07 / 16 / 2026, p. 23 / 130 13 / 84 where S2 refers to the attachment point to group S2.

[042] In a particular embodiment, F has a structure as shown in the following formula: where S2 refers to the attachment point to the S2 group.

[043] References herein to the term “linking moiety” refer to any suitable moiety that is capable of binding to another component. The invention requires that the linking moiety be a cationic antimicrobial peptide linked to X1 by an amine.

[044] In one embodiment, L represents a lipopeptide. In another embodiment, the lipopeptide comprises a polymyxin or a derivative thereof. Examples of suitable polymyxins and derivatives thereof are described in Velkov et al (2016) Future Med Chem 8(10), 1017 - 1025, the polymyxins and derivatives thereof are incorporated herein by reference. In one embodiment, the polymyxin or a derivative thereof is selected from Polymyxin B, Polymyxin B2, Polymyxin Nonapeptide, Colistin A, Colistin B, CB-182,204 (Cubist Pharmaceuticals), 5a (Pfizer), 5x (Pfizer), CA 14 (Cantab Anti-Infectives), CA824 (Cantab Anti-Infectives), NAB739 (Northern Antibiotics), NAB741 (Northern Antibiotics), NAB7061 (Northern Antibiotics), 38 (University of Queensland), FADDI-002 (Monash University), FADDI-100 (Monash University), or derivatives thereof. In another embodiment, the polymyxin is Polymyxin B or a derivative having the following structure: Petition 870260070784, dated 07 / 16 / 2026, page 24 / 130 14 / 84

[045] In another embodiment, the Polymyxin B derivative comprises the following structures (where the attachment point with Xi is shown): H2N-[L-OctilGly]-Dab-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* Nonanamide-Dab(NH2)-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* H2N-Dab-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* Petition 870260070784, dated 07 / 16 / 2026, page 25 / 130 15 / 84 H2N-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* H2N-[L-OctilGly]-Dab-Thr-Dab(NH2)-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* Nonanamide-Dab-Thr-Dab(NH2)-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* H2N-Thr-[D-Ser]-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* Xi N H2

[046] It will be evaluated that the cationic antimicrobial peptides of the present invention will be configured to bind to a specific pathogen or infectious agent. Petition 870260070784, dated 07 / 16 / 2026, page 26 / 130 16 / 84

[047] In one embodiment, the invention provides a compound of formula (I) comprising a compound of Examples 1 to 25 or a pharmaceutically acceptable salt thereof.

[048] In another embodiment, the invention provides a compound of formula (I) comprising a compound of Examples 1 to 14 or a pharmaceutically acceptable salt thereof. In another embodiment, the invention provides a compound of formula (I) comprising a compound of Examples 1 to 10 or a pharmaceutically acceptable salt thereof. In another embodiment, the invention provides a compound of formula (I) comprising a compound of Examples 4, 6, 9, 17 or 22 or a pharmaceutically acceptable salt thereof. In another embodiment, the invention provides a compound of formula (I) comprising a compound of Example 17 or a pharmaceutically acceptable salt thereof.

[049] In one embodiment, the invention provides a compound of formula (I) comprising a compound of Examples 1 to 25 or a pharmaceutically acceptable salt thereof.

[050] In another embodiment, the invention provides a compound of formula (I) that is the free base or the trifluoroacetate salt of a compound of Examples 1 to 14. In another embodiment, the invention provides a compound of formula (I) that is the free base or the trifluoroacetate salt of a compound of Examples 1 to 10. In another embodiment, the invention provides a compound of formula (I) that is the free base or the trifluoroacetate salt of a compound of Examples 4, 6, 9, 17 or 22. In another embodiment, the invention provides a compound of formula (I) that is the free base or the trifluoroacetate salt of a compound of Example 17.

[051] A reference to a compound of formula (I) and subgroups thereof also includes ionic forms, salts, solvates, isomers (including geometric and stereochemical isomers), tautomers, N-oxides, esters, isotopes and their protected forms, for example, as discussed below; preferably, the salts or Petition 870260070784, dated 07 / 16 / 2026, page 27 / 130 17 / 84 tautomers or isomers or N-oxides or solvates thereof; and more preferably, the salts or tautomers or N-oxides or solvates thereof, even more preferably the salts or tautomers or solvates thereof. Hereafter, compounds and their ionic forms, salts, solvates, isomers (including geometric and stereochemical isomers), tautomers, N-oxides, esters, isotopes and their protected forms as defined in any aspect of the invention (except intermediate compounds in chemical processes) are referred to as “compounds of the invention”.

[052] The compounds of formula (I) may exist in the form of salts, for example, acid addition salts or, in certain cases, salts of organic and inorganic bases such as carboxylate, sulfonate and phosphate salts. All these salts are within the scope of this invention, and references to the compounds of formula (I) include the salt forms of the compounds.

[053] The salts of the present invention can be synthesized from the precursor compound containing a basic moiety by conventional chemical methods, such as the methods described in Pharmaceutical Salts: Properties, Selection, and Use, P. Heinrich Stahl (Editor), Camille G. Wermuth (Editor), ISBN: 390639-026-8, Hardcover, 388 pages, August 2002. Generally, such salts can be prepared by reacting the basic forms of these compounds with the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are used.

[054] Acid addition salts (mono- or di-salts) can be formed with a wide variety of acids, both inorganic and organic. Examples of acid addition salts include mono- or di-salts formed with an acid selected from the group consisting of acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid (e.g., L-ascorbic acid), L-aspartic acid, benzenesulfonic acid, benzoic acid, 4-acetamidobenzoic acid, butanoic acid, (+) camphoric acid, camphor-sulfonic acid, (+)-(1S)-camphor-10 Petition 870260070784, dated 07 / 16 / 2026, page 28 / 130 18 / 84 sulfonic, capric, caproic, caprylic, cinnamic, citric, cyclamic, dodecylsulfuric, ethane-1,2-disulfonic, ethanesulfonic, 2-hydroxyethanesulfonic, formic, fumaric, galacteric, gentisic, glucoheptonic, D-gluconic, glucuronic (e.g., D-glucuronic), glutamic (e.g., L-glutamic), α-oxoglutaric, glycolic, hippuric, hydrohalic (e.g., hydrobromic, hydrochloric, hydroiodic), isethionic acid, lactic (e.g., (+)-L-lactic, (±)-DL-lactic), lactobionic, maleic, malic, (-)-L-malic, malonic, (±)-DL-mandelic, methanesulfonic, naphthalene-2-sulfonic, naphthalene-1,5-disulfonic, 1-hydroxy-2-naphthoic, nicotinic, nitric, oleic, orotic, oxalic, palmitic, pamoic, phosphoric, propionic, pyruvic, L-pyroglutamic, salicylic, 4-aminosalicylic, sebacic, stearic, succinic, sulfuric, tannic, (+)-L-tartaric, thiocyanic, ptoluenesulfonic, undecylenic and valeric, as well as acylated amino acids and cation exchange resins.

[055] A particular group of salts consists of salts formed from acetic, hydrochloric, hydroiodic, phosphoric, nitric, sulfuric, citric, lactic, succinic, maleic, malic, isethionic, fumaric, benzenesulfonic, toluenesulfonic, methanesulfonic (mesylate), ethanesulfonic, naphthalenesulfonic, valeric, acetic, propanoic, butanoic, malonic, glucuronic, and lactobionic acids. One particular salt is the hydrochloride salt. Another particular salt is the hydrogen sulfate salt, also known as a hemisulfate salt.

[056] Where compounds of formula (I) contain an amine function, these can form quaternary ammonium salts, for example, by reacting with an alkylating agent according to methods well known to a skilled person. Such quaternary ammonium compounds are within the scope of formula (I).

[057] The compounds of the invention can exist as mono- or di-salts depending on the pKa of the acid from which the salt is formed.

[058] The salt forms of the compounds of the invention are typically pharmaceutically acceptable salts, and examples of pharmaceutically acceptable salts are Petition 870260070784, dated 07 / 16 / 2026, page 29 / 130 19 / 84 discussed in Berge et al., 1977, “Pharmaceutically Acceptable Salts”, J. Pharm. Sci., Vol. 66, pages 1 to 19. However, salts that are not pharmaceutically acceptable can also be prepared as intermediate forms that can then be converted into pharmaceutically acceptable salts. Such forms of non-pharmaceutically acceptable salts, which may be useful, for example, in the purification or separation of the compounds of the invention, are also part of the invention.

[059] Those skilled in the art of organic chemistry will appreciate that many organic compounds can form complexes with solvents in which they are reacted or from which they are precipitated or crystallized. These complexes are known as “solvates”. For example, a complex with water is known as a “hydrate”. Pharmaceutically acceptable solvates of the compound of the invention are within the scope of the invention.

[060] Compounds of formula (I) containing an amine function may also form N-oxides. A reference here to a compound of formula (I) containing an amine function also includes N-oxide.

[061] When a compound contains multiple amine functions, one or more nitrogen atoms can be oxidized to form an N-oxide. Particular examples of N-oxides are the N-oxides of a tertiary amine or a nitrogen atom of a nitrogen-containing heterocycle.

[062] N-oxides can be formed by treating the corresponding amine with an oxidizing agent such as hydrogen peroxide or a peracid (e.g., a peroxycarboxylic acid), see, for example, Advanced Organic Chemistry, by Jerry March, 4th Edition, Wiley Interscience, pages. More particularly, N-oxides can be made by the procedure of LW Deady (Sin. Comm. 1977, 7, 509-514) in which the amine compound reacts with mchloroperoxybenzoic acid (mCPBA), for example, in an inert solvent such as dichloromethane. Petition 870260070784, dated 07 / 16 / 2026, page 30 / 130 20 / 84

[063] It will be assessed by those skilled in the art that certain protected derivatives of compounds of formula (I), which may be made before a final deprotection stage, may not possess pharmacological activity as such, but may, in certain cases, be administered orally or parenterally and then metabolized in the body to form the compounds of the invention that are pharmacologically active. Such derivatives may therefore be described as “prodrugs”. All such prodrugs of compounds of the invention are included within the scope of the invention. Examples of prodrug functionalities suitable for the compounds of the present invention are described in Drugs of Today, Volume 19, Number 9, 1983, pp. 499-538 and in Topics in Chemistry, Chapter 31, pp. 306-316 and in “Design of Prodrugs” by H. Bundgaard, Elsevier, 1985, Chapter 1 (the disclosures in which the documents are incorporated herein by reference).It will also be evaluated by those skilled in the art whether certain portions, known to those skilled in the art as "pro-portions," for example, as described by H. Bundgaard in "Design of Prodrugs" (the disclosure in which this document is incorporated herein by reference), can be placed in appropriate functionalities when such functionalities are present within compounds of the invention.

[064] Also included within the scope of the compound and various salts of the invention are the polymorphs thereof.

[065] The compounds of formula (I) may exist in several different isomeric and tautomeric geometric forms and references to compounds of formula (I) include all such forms. For the avoidance of doubt, where a compound may exist in one of several isomeric or tautomeric geometric forms and only one is specifically described or shown, all others are nonetheless covered by formula (I).

[066] The present invention includes all compounds isotopically Petition 870260070784, dated 07 / 16 / 2026, page 31 / 130 21 / 84 pharmaceutically acceptable labeled versions of the invention, that is, compounds of formula (I), in which one or more atoms are replaced by atoms having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature.

[067] Examples of isotopes suitable for inclusion in the compounds of the invention comprise isotopes of hydrogen, such as 2H (D) and 3H (T), carbon, such as 11C, 13C and 14C, fluorine, such as 18F, nitrogen, such as 13N and 15N, oxygen, such as 15O, 17O and 18O.

[068] Certain isotopically labeled compounds of formula (I), for example, those incorporating a radioactive isotope, are useful in studies of drug and / or substrate tissue distribution. Compounds of formula (I) may also have valuable diagnostic properties, insofar as they can be used to detect or identify the formation of a complex between a labeled compound and other molecules, peptides, proteins, enzymes, or receptors. Detection or identification methods may use compounds that are labeled with labeling agents such as radioisotopes, enzymes, fluorescent substances, luminous substances (e.g., luminol, luminol derivatives, luciferin, aequorin, and luciferase), etc. The radioactive isotopes tritium, i.e., 3H(T), and carbon-14, i.e., 14C, are particularly useful for this purpose given their ease of incorporation and readily available detection means.

[069] Substitution with heavier isotopes such as deuterium, i.e., 2H(D), can provide certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements and, consequently, may be preferred in some circumstances.

[070] Substitution with positron-emitting isotopes, such as 11C, 18F, 15O and 13N, can be useful in Positron Emission Topography (PET) studies for Petition 870260070784, dated 07 / 16 / 2026, page 32 / 130 22 / 84 examine the target occupation.

[071] Isotopically labeled compounds of formula (I) can generally be prepared by conventional techniques known to those skilled in the field or by processes analogous to those described in the accompanying Examples and Preparations using appropriate isotopically labeled reagents in place of unlabeled reagents previously used. Methods for the Preparation of Compounds of Formula (I)

[072] In this section, as in all other sections of this application, unless the context indicates otherwise, references to formula (I) also include all other subgroups and examples thereof, as defined herein.

[073] The compounds belonging to the invention described herein can be prepared in a gradual synthetic sequence as illustrated in the schemes below. The syntheses involve the preparation of several central constructs (Cy) that allow the choice of valence for F and the choice of peptide for L within the molecule. The compounds of formula (I) can be prepared according to synthetic methods well known to a skilled person. For example, a person skilled in the art will assess that the chemical steps and the choice of protecting groups can be handled in any order to allow the success of the synthesis.

[074] According to another aspect of the invention, a process is provided for preparing a compound of formula (I) as defined above comprising: (a) Prepare a compound of formula (I) wherein Yi represents -CONH- (i.e., a compound of formula (IA)) by reacting a compound of formula (II) with a compound of formula (III) followed by a suitable deprotection step: Petition 870260070784, dated 07 / 16 / 2026, p. 33 / 130 23 / 84 (II) (IA) where S2, Y2, m, Cy, Si, Xi, L and F are as defined herein above and PG is a suitable peptide protecting group such as Dde; or (b) prepare a compound of formula (I) wherein Yi represents -CONH- and Xi represents -C(O)- (i.e., a compound of formula (IB)) by reacting a compound of formula (IV) with a compound of formula (V) followed by a suitable deprotection step: where S2, Y2, m, Cy, Si, L and F are as defined herein above and PG is a suitable peptide protecting group such as Dde; or (c) prepare a compound of formula (I) by reacting a compound of formula (VI) with a compound of formula (VII) followed by a suitable deprotection step: OS2Y2 HO m ^Ks / i^l] l JPG F\^-\ / NH2(VI) (i), (ii) F—S2-Y2m V^L (I) (VII) where S2, Y2, m, Cy, Si, Xi, L and F are as defined herein above, PG is a suitable peptide protecting group such as Dde; or (d) prepare a compound of formula (I) by reacting a compound of formula (XII) with a compound of formula (XIII) followed by a suitable deprotection step, wherein Yi represents a CONH group: Petition 870260070784, dated 07 / 16 / 2026, p. 34 / 130 24 / 84 wherein S2, Y2, m, Cy, Xi, L and F are as defined herein above, Sia and SiB together form a Si group and PG is a suitable peptide protecting group such as Dde; or (e) interconversion of a compound of formula (I) or protected derivative thereof to another compound of formula (I) or protected derivative thereof.

[075] Step (i) in processes (a) to (d) typically comprises an amide bond-forming reaction, which typically comprises activation of the carboxylic acid with phosphate-containing reagents, triazine-based reagents or carbodi-imide-containing reagents in the presence of an organic base in an organic solvent. Preferred conditions comprise HATU (3-oxide-hexafluorophosphate of (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium)) with diisopropylethylamine in DMF.

[076] Step (ii) in processes (a) to (d) typically comprises any suitable deprotection reaction, the conditions of which will depend on the nature of the protecting group. When the protecting group comprises Dde, this deprotection will typically comprise the use of hydrazine on DMF. When the protecting group comprises Cbz or benzyl, this deprotection will typically comprise hydrogenation over a suitable catalyst such as palladium on carbon. When the protecting group comprises tert-butoxycarbonyl or tert-butyl, this deprotection will be acid-mediated and will typically comprise TFA on DCM.

[077] Process (e) typically comprises interconversion procedures known to one skilled in the art. For example, in compounds of formula (I), a first substituent can be converted, by methods known to one skilled in the art, into an alternative second substituent. A wide Petition 870260070784, dated 07 / 16 / 2026, page 35 / 130 25 / 84 A variety of well-known functional group interconversions are known to a person skilled in the art to convert a precursor compound into a compound of formula (I) and are described in Advanced Organic Chemistry by Jerry March, 4th Edition, John Wiley & Sons, 1992. For example, possible metal-catalyzed functionalizations, such as using organotin reagents (the Stille reaction), Grignard reagents, and reactions with nitrogen nucleophiles are described in 'Palladium Reagents and Catalysts' [Jiro Tsuji, Wiley, ISBN 0-470-85032-9] and Handbook of OrganoPalladium Chemistry for Organic Synthesis [Volume 1, Edited by Ei-ichi Negishi, Wiley, ISBN 0-471-31506-0].

[078] If appropriate, the reactions previously described in processes (a), (b), (c), (d) and (e) are followed or preceded by one or more reactions known to those skilled in the art and are carried out in an order appropriate to obtain the necessary substitutions at S2, Y2, m, Cy, S1, Xi, Yi, L and F defined above to provide other compounds of formula (I). Non-limiting examples of such reactions, conditions of which can be found in the literature, include: Protection of reactive functions, deprotection of reactive functions, halogenation, dehalogenation, dealkylation, alkylation and arylation of amines, aniline, alcohols and phenols, Mitsunobu reaction at hydroxyl groups, cycloaddition reactions at appropriate groups, reduction of nitro, esters, cyano, aldehydes, transition metal-catalyzed coupling reactions, acylation, sulfonylation / introduction of sulfonyl groups. Petition 870260070784, dated 07 / 16 / 2026, page 36 / 130 26 / 84 saponification / hydrolysis of ester groups, amidification or transesterification of ester groups, esterification or amidification of carboxylic groups, halogen exchange, nucleophilic substitution with amine, thiol or alcohol, reductive amination, oxime formation in carbonyl and hydroxylamine groups, S-oxidation, N-oxidation, salification.

[079] The compounds of formula (II) can be prepared according to the methods described in Scheme 1 from compounds of formula (VIII) and (VI) according to the process steps (i) and (ii) as described above. m (VIII) (11) Scheme 1 where m, Cy, Y2, S2 and F are as defined herein above and PG1 is a protecting group comprising benzyl.

[080] Additionally, compounds of formula (V) can be prepared from compounds of formula (II) according to process steps (i) and (ii) as described above, using a suitably chosen ligand (S1) comprising a suitable protecting group, such as benzyl, which is commercially available or prepared as described in the literature by a person skilled in the art.

[081] The compounds of formula (VII) can be prepared according to the methods described in Scheme 2 from compounds of formula (III) and (IX) of Petition 870260070784, dated 07 / 16 / 2026, p. 37 / 130 27 / 84 in accordance with process steps (i) and (ii) as described above. h2n Xi^ri Scheme 2 where m, Cy, Y2, Si, S2, Xi and F are as defined here previously, Y1 is -CONH-, PG2 is a protecting group comprising tert-butyl and PG is a suitable peptide protecting group such as Dde,

[082] The compounds of formula (VIII) can be prepared according to the methods described in Scheme 3 from compounds of formula (X) and (XI) according to process steps (iii) and (ii), an alkylation reaction followed by a deprotection reaction as described above, respectively. Scheme 3 where m and Cy are as defined herein above, PG2 is a protecting group comprising tert-butyl, PG1 is a protecting group comprising benzyl and Hal is a halide such as Cl, Br or I.

[083] Step (iii) typically comprises alkylation conditions with compounds of formula (XI) in an inorganic base in a polar organic solvent at room temperature. Preferred conditions comprise potassium carbonate in DMF.

[084] Similarly, compounds of formula (IX) can also be prepared according to Scheme 3 wherein the alternative conditions of Petition 870260070784, dated 07 / 16 / 2026, page 38 / 130 28 / 84 deprotection can be used. After the alkylation step, in which PGi is benzyl, PGi can preferably be deprotected under hydrogenation conditions as previously described herein.

[085] When Cy is biphenyl, compounds of formula (X) can be prepared using a Suzuki reaction to construct the biphenyl unit. Preferred conditions comprise tetrakistriphenyl phosphine palladium (0) with sodium carbonate in dioxane and water at 100 °C. When suitable necessary protecting groups are used, such as TBS, such protecting groups can be deprotected using a fluoride-mediated deprotection. Preferred conditions comprise TBAF in THF at room temperature.

[086] The compounds of formula (XII) and (XIII) in which Si contains Sia or Sib can be prepared according to Scheme 1, according to the methods described herein, or prepared according to the literature.

[087] The compounds of formula (III), (IV), (VI) and (XI) are commercially available, prepared according to the methods described herein or prepared according to the literature. Pharmaceutical Compositions

[088] Although it is possible for the compound of formula (I) to be administered alone, it is preferable to present it as a pharmaceutical composition (e.g., formulation).

[089] Thus, according to another aspect, the invention provides a pharmaceutical composition, and methods for manufacturing a pharmaceutical composition comprising (for example, by mixing) at least one compound of the invention where L represents a cationic antimicrobial peptide, together with one or more pharmaceutically acceptable excipients and optionally other therapeutic or prophylactic agents, as described herein.

[090] Pharmaceutically acceptable excipients may be selected Petition 870260070784, dated 07 / 16 / 2026, page 39 / 130 29 / 84 of, for example, carriers (e.g., a solid, liquid or semi-solid carrier), adjuvants, diluents, fillers or bulking agents, granulating agents, coating agents, release control agents, binding agents, disintegrants, lubricating agents, preservatives, antioxidants, buffering agents, suspending agents, thickening agents, flavoring agents, sweeteners, flavor masking agents, stabilizers or any other excipients conventionally used in pharmaceutical compositions. Examples of excipients for various types of pharmaceutical compositions are presented in more detail below.

[091] The term “pharmaceutically acceptable”, as used herein, refers to compounds, materials, compositions and / or dosage forms that are, within the scope of medical judgment, suitable for use in contact with the tissues of a subject (e.g., human) without excessive toxicity (i.e., generally recognized as safe (GRAS)), irritation, allergic response or other problem or complication, proportionate to a reasonable risk / benefit ratio. Each carrier, excipient, etc. must also be “acceptable” in the sense of being compatible with the other ingredients of the formulation.

[092] Pharmaceutical compositions containing compounds of the invention can be formulated according to known techniques, see, for example, Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA, USA.

[093] Pharmaceutical compositions may be in any form suitable for parenteral, intranasal, intrabronchial, sublingual, ophthalmic, otic, rectal, intravaginal or transdermal administration. When compositions are intended for parenteral administration, they may be formulated for intravenous, intramuscular, intraperitoneal, subcutaneous administration or for direct delivery to a target organ or tissue by injection, infusion or other means of delivery. Delivery may be by bolus injection, short-term infusion or long-term infusion and may Petition 870260070784, dated 07 / 16 / 2026, page 40 / 130 30 / 84 can be achieved through passive delivery or through the use of a suitable infusion pump or syringe driver.

[094] Pharmaceutical formulations adapted for parenteral administration include sterile aqueous and non-aqueous injectable solutions that may contain antioxidants, buffers, bacteriostats, co-solvents, surfactants, mixtures of organic solvents, cyclodextrin complexing agents, emulsifying agents (to form and stabilize emulsion formulations), liposome components to form liposomes, gelling polymers to form polymeric gels, lyophilization protectants and combinations of agents for, inter alia, stabilizing the active ingredient in a soluble form and making the formulation isotonic with the blood of the intended recipient. Pharmaceutical formulations for parenteral administration can also take the form of sterile aqueous and non-aqueous suspensions that may include suspending agents and thickening agents (RG Strickly, Solubilizing Excipients in oral and injectable formulations, Pharmaceutical Research, Vol 21(2) 2004, p.201 - 230).

[095] The formulations may be presented in single-dose or multi-dose containers, for example sealed ampoules, vials and pre-filled syringes, and may be stored in a freeze-dried (lyophilized) condition, requiring only the addition of a sterile liquid carrier, for example water for injections, immediately before use.

[096] The pharmaceutical formulation can be prepared by freeze-drying a compound of the invention. Freeze-drying refers to the procedure of freezing a composition. Freeze-drying and freeze-drying are therefore used here synonymously.

[097] Extemporaneous injectable solutions and suspensions can be prepared from sterile powders, granules and tablets.

[098] The pharmaceutical compositions of the present invention for injection Petition 870260070784, dated 07 / 16 / 2026, page 41 / 130 31 / 84 parenteral products may also include pharmaceutically acceptable sterile aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions immediately prior to use.

[099] Examples of suitable aqueous and non-aqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (such as sunflower oil, safflower oil, corn oil or olive oil) and injectable organic esters such as ethyl oleate. Appropriate flowability may be maintained, for example, by the use of thickeners or coating materials such as lecithin, by maintaining the required particle size in the case of dispersions, and by the use of surfactants.

[0100] The compositions of the present invention may also contain adjuvants such as preservatives, humectants, emulsifying agents and dispersing agents. Prevention of microorganism action can be ensured by the inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid and the like. It may also be desirable to include agents to adjust tonicity such as sugars, sodium chloride and the like. Prolonged absorption of the injectable pharmaceutical form can be achieved by the inclusion of agents that retard absorption, such as aluminum monostearate and gelatin.

[0101] In a preferred embodiment of the invention, the pharmaceutical composition is in a form suitable for IV administration, for example, by injection or infusion. For intravenous or subcutaneous administration, the solution can be metered or injected into an infusion bag (containing a pharmaceutically acceptable excipient, such as 0.9% saline solution or 5% dextrose) before administration. Petition 870260070784, dated 07 / 16 / 2026, p. 42 / 130 32 / 84

[0102] In another preferred embodiment, the pharmaceutical composition is in a form suitable for subcutaneous (sc) administration.

[0103] The compound of the invention can be formulated with a carrier and administered in the form of nanoparticles, the increased surface area of ​​the nanoparticles aiding their absorption. Furthermore, the nanoparticles offer the possibility of direct penetration into the cell. Nanoparticle drug delivery systems are described in “Nanoparticle Technology for Drug Delivery”, edited by Ram B Gupta and Uday B. Kompella, Informa Healthcare, ISBN 9781574448573, published March 13, 2006. Nanoparticles for drug delivery are also described in J. Control. Release, 2003, 91 (1-2), 167-172, and in Sinha et al., Mol. Cancer Ther. August 1 (2006) 5, 1909.

[0104] Pharmaceutical compositions typically comprise from approximately 1% (w / w) to approximately 95% (w / w) of active ingredient and from 99% (w / w) to 5% (w / w) of a pharmaceutically acceptable excipient or combination of excipients. Preferably, the compositions comprise from approximately 20% (w / w) to approximately 90% (w / w) of active ingredient and from 80% (w / w) to 10% of a pharmaceutically acceptable excipient or combination of excipients. Pharmaceutical compositions comprise from approximately 1% to approximately 95%, preferably from approximately 20% to approximately 90% of active ingredient. The pharmaceutical compositions according to the invention may be, for example, in unit dose form, such as in the form of ampoules, vials, suppositories, pre-filled syringes, coated tablets, tablets or capsules.

[0105] Pharmaceutically acceptable excipients may be selected according to the desired physical form of the formulation and may, for example, be selected from diluents (e.g., solid diluents such as fillers or bulking agents; and liquid diluents such as solvents and co-solvents), Petition 870260070784, dated 07 / 16 / 2026, page 43 / 130 33 / 84 disintegrants, buffering agents, lubricants, flow aids, release control agents (e.g., polymers or waxes that retard or delay release), binders, granulating agents, pigments, plasticizers, antioxidants, preservatives, flavoring agents, flavor masking agents, tonicity adjusting agents, and coating agents.

[0106] The qualified person will have the expertise to select the appropriate quantities of ingredients for use in formulations. For example, tablets and capsules typically contain 0 to 20% disintegrants, 0 to 5% lubricants, 0 to 5% flow aids and / or 0 to 99% (w / w) fillers / or bulking agents (depending on the drug dose). They may also contain 0 to 10% (w / w) polymeric binders, 0 to 5% (w / w) antioxidants, 0 to 5% (w / w) pigments. Slow-release tablets would additionally contain 0 to 99% (w / w) release-controlling polymers (e.g., delaying) (depending on the dose). Tablet or capsule film coatings typically contain 0 to 10% (w / w) polymers, 0 to 3% (w / w) pigments, and / or 0 to 2% (w / w) plasticizers.

[0107] Parenteral or subcutaneous formulations typically contain 0 to 20% (w / w) buffers, 0 to 50% (w / w) co-solvents and / or 0 to 99% (w / w) Water for Injection (WFI) (depending on the dose and whether lyophilized). Formulations for intramuscular injections may also contain 0 to 99% (w / w) oils.

[0108] The compounds of the invention can also be formulated as solid dispersions. Solid dispersions are extremely fine and homogeneous dispersed phases of two or more solids. Solid solutions (molecularly dispersed systems), a type of solid dispersion, are well known for use in pharmaceutical technology (see (Chiou and Riegelman, J. Pharm. Sci., 60, 1281 - 1300 (1971)) and are useful in increasing dissolution rates and increasing the bioavailability of poorly water-soluble drugs.

[0109] Pharmaceutical formulations can be presented to a patient Petition 870260070784, dated 07 / 16 / 2026, page 44 / 130 34 / 84 in “patient packages” containing a complete course of treatment in a single package, usually a blister pack. Patient packages have an advantage over traditional prescriptions, where a pharmacist divides a patient's drug supply from a bulk supply, in that the patient always has access to the information leaflet contained in the patient package, which is normally absent from patient prescriptions. The inclusion of an information leaflet has been shown to improve patient compliance with physician instructions. An example of a patient package includes a pre-filled syringe. Such pre-filled syringes already contain the pharmacological substance. The front end portion of a pre-filled syringe to which a needle is to be attached is sealed with a cap on the nozzle. Before injection, the cap on the nozzle is removed from the front end portion and a needle is attached to it.A gasket is then slid in, pushing a plunger rod towards the front end so that the drug is expelled.

[0110] Nasal release compositions include ointments, creams, sprays, plasters, gels, liquid drops and inserts (e.g., intraocular inserts). Such compositions may be formulated according to known methods.

[0111] Examples of formulations for rectal or intravaginal administration include pessaries and suppositories which may, for example, be formed from a moldable or waxy material containing the active compound. Solutions of the active compound may also be used for rectal administration.

[0112] Compositions for inhalation administration may take the form of inhalable powder or liquid compositions or powder sprays, and may be administered in standard form using powder inhalers or aerosol dispensing devices. Such devices are well known. For inhalation administration, powder formulations typically comprise the Petition 870260070784, dated 07 / 16 / 2026, p. 45 / 130 35 / 84 active compound together with an inert solid powdered diluent, such as lactose.

[0113] The compound of the invention will generally be presented in unit dosage form and, as such, will typically contain sufficient compound to provide a desired level of biological activity. For example, a formulation may contain from 1 nanogram to 2 grams of active ingredient, for example, from 1 nanogram to 2 milligrams of active ingredient. Within these ranges, the particular sub-ranges of compound are from 0.1 milligrams to 2 grams of active ingredient (more usually from 10 milligrams to 1 gram, for example, from 50 milligrams to 500 milligrams), or from 1 microgram to 20 milligrams (for example, from 1 microgram to 10 milligrams, for example, from 0.1 milligrams to 2 milligrams of active ingredient).

[0114] The active compound will be administered to a patient in need of it (e.g., a human or animal patient) in a quantity sufficient to obtain the desired therapeutic effect. Therapeutic Uses

[0115] According to another aspect of the invention, a compound of formula (I), as defined herein, is provided for use in therapy.

[0116] According to another aspect of the invention, a compound of formula (I), as defined herein, is provided for use in the treatment of a disease or disorder mediated and / or caused by an infectious agent.

[0117] According to another aspect of the invention, the use of a compound of formula (I), as defined herein, is provided in the manufacture of a medicament for use in the treatment of a disease or disorder mediated and / or caused by an infectious agent.

[0118] According to another aspect of the invention, a method is provided for treating a disease or disorder mediated and / or caused by an infectious agent comprising administering to an individual in need thereof a compound of formula (I) as defined herein. Petition 870260070784, dated 07 / 16 / 2026, page 46 / 130 36 / 84

[0119] Examples of infectious agents include any pathogen such as a bacterium, fungus, parasite, or virus. Thus, in one embodiment, the disease or disorder mediated and / or caused by an infectious agent is a bacterial infection.

[0120] Examples of bacterial infection include infection by the following bacteria: Staphylococcus sp. such as Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus (MRSA)), Clostridium sp. (e.g., Clostridium difficile, Clostridium tetani, and Clostridium botulinum), Enterobacter species, Mycobacterium tuberculosis, Shigella sp. such as Shigella dysenteriae, Campylobacter sp. such as Campylobacter jejuni, Enterococcus sp.such as Enterococcus faecalis, Bacillus anthracis, Yersinia pestis, Bordetella pertussis, Streptococcus species, Salmonella typhimurium, Salmonella enterica, Chlamydia species, Treponema pallidum, Neisseria gonorrhoeae, Borrelia burgdorferi, Vibrio cholerae, Corynebacterium diphtheriae, Helicobacter pylori, Gram-negative pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli (including strains that are resistant to one or more classes of antibiotics, especially multidrug-resistant (MDR) strains).

[0121] The compound of the invention is generally administered to a subject in need of such administration, for example, a human or animal patient, preferably a human.

[0122] The compound of the invention will typically be administered in amounts that are therapeutically or prophylactically useful and that are generally not toxic. However, in certain situations (for example, in the case of potentially fatal diseases), the benefits of administering a compound of the invention may outweigh the disadvantages of any toxic effects or side effects, in which case it may be considered desirable to administer a compound of the invention in amounts that are associated with a degree of toxicity.

[0123] The compound of the invention can be administered for a period Petition 870260070784, dated 07 / 16 / 2026, p. 47 / 130 37 / 84 prolonged (i.e., chronic administration) to maintain beneficial therapeutic effects or it can be administered for a short period only (i.e., acute administration). Alternatively, it can be administered in a continuous manner or in a manner that provides intermittent dosing (e.g., a pulsatile manner).

[0124] A typical daily dose of the compound of the invention may be in the range of 100 picograms to 100 milligrams per kilogram of body weight, more typically 5 nanograms to 25 milligrams per kilogram of body weight, and most usually 10 nanograms to 15 milligrams per kilogram (e.g., 10 nanograms to 10 milligrams, and more typically 1 microgram to 20 milligrams per kilogram, e.g., 1 microgram to 10 milligrams per kilogram) per kilogram of body weight, although higher or lower doses may be administered as needed. The compound of the invention may be administered daily or repeatedly every 2, 3, 4, 5, 6, 7, 10, 14, 21, or 28 days, for example. Alternatively, the compound of the invention may be administered by infusion several times a day.

[0125] The compound of the invention can be administered in a range of doses, for example, from 1 to 1,500 mg, 2 to 800 mg or 5 to 500 mg, for example, from 2 to 200 mg or 10 to 1,000 mg, particular examples of doses include 10, 20, 50 and 80 mg. The compound of the invention can be administered once or more than once a day. The compound of the invention can be administered continuously (i.e., taken every day without a break during the duration of the treatment regimen). Alternatively, the compound of the invention can be administered intermittently (i.e., taken continuously for a given period such as a week, then discontinued for a period such as a week and then taken continuously for another period such as a week and so on, during the duration of the treatment regimen). Examples of treatment regimens involving Petition 870260070784, dated 07 / 16 / 2026, p. 48 / 130 38 / 84 Intermittent administration includes regimens in which administration is in cycles of one week on, one week off; or two weeks on, one week off; or three weeks on, one week off; or two weeks on, two weeks off; or four weeks on and two weeks off; or one week on and three weeks off - for one or more cycles, for example, 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more cycles.

[0126] In a particular dosage regimen, a patient will be given an infusion of a compound of the invention for periods of one hour per day for up to ten days, in particular up to five days per week, and the treatment is repeated at a desired interval, such as two to four weeks, in particular every three weeks.

[0127] More specifically, a patient may receive an infusion of a compound of the invention for periods of one hour per day for 5 days and the treatment is repeated every three weeks.

[0128] In another particular dosing regimen, a patient receives an infusion over 30 minutes to 1 hour, followed by maintenance infusions of varying duration, for example, 1 to 5 hours, for example, 3 hours.

[0129] In another particular dosage regimen, a patient receives a continuous infusion for a period of 12 hours to 5 days and, in particular, a continuous infusion for 24 hours to 72 hours.

[0130] Finally, however, the amount of the compound of the invention administered and the type of composition used will be proportional to the nature of the disease or physiological condition being treated and will be at the discretion of the physician.

[0131] It will be evaluated whether the compound of the invention can be used as a single agent or in combination with other therapeutic agents. Combination experiments can be performed, for example, as described in Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regulat 1984; 22: 27 - 55. Petition 870260070784, dated 07 / 16 / 2026, p. 49 / 130 39 / 84

[0132] When the compound of the invention is administered in combination therapy with one, two, three, four or more other therapeutic agents (preferably one or two, more preferably one), the agents may be administered simultaneously or sequentially. In the latter case, the two or more agents will be administered within a period and in a quantity and manner sufficient to ensure that an advantageous or synergistic effect is obtained. When administered sequentially, it may be administered at very close intervals (e.g., over a period of 5 to 10 minutes) or at longer intervals (e.g., 1, 2, 3, 4 or more hours apart, or even longer periods apart when necessary), the precise dosage regimen being proportional to the properties of the therapeutic agent(s).These dosages can be administered, for example, once, twice, or more per course of treatment, which can be repeated, for example, every 7, 14, 21, or 28 days.

[0133] It will be assessed that the preferred method and order of administration and the respective amounts and dosage regimens for each component of the combination will depend on the other particular medicinal agent and compound of the invention to be administered, its route of administration, the particular tumor to be treated and the particular host to be treated. The ideal method and order of administration and the amounts and dosage regimens can be readily determined by those skilled in the art using conventional methods and in view of the information presented herein.

[0134] The weight ratio of the compound of the invention and one or more other therapeutic agents when given as a combination can be determined by a person skilled in the art. Said ratio and the exact dosage and frequency of administration depend on the particular compound of the invention and the other therapeutic agents used, the particular condition to be treated, the severity of the condition to be treated, age, weight, gender, diet, time of administration and physical condition. Petition 870260070784, dated 07 / 16 / 2026, page 50 / 130 40 / 84 general of the particular patient, the method of administration as well as other medication that the individual may be taking, as is well known to those skilled in the art. Furthermore, it is evident that the effective daily amount may be decreased or increased depending on the response of the treated subject and / or depending on the assessment of the physician prescribing the compound of the present invention. A particular weight ratio for the compound of the invention and another therapeutic agent may vary from 1 / 10 to 10 / 1, more particularly from 1 / 5 to 5 / 1, even more particularly from 1 / 3 to 3 / 1. EXAMPLES

[0135] The invention will now be illustrated, but not limited to, by reference to the specific embodiments described in the following examples. The compounds are named using an automated naming package (ChemDraw) or are named by the chemical supplier.

[0136] The following synthetic procedures are provided for illustration of the methods used; for a given preparation or step, the precursor used may not necessarily be derived from the individual batch synthesized according to the step in the given description. Analytical Methods

[0137] In examples and preparations that cite analytical data, the following analytical methods have been used unless otherwise specified: LCMS

[0138] System: Agilent 1100 LCMS (quaternary pump); mass spectrometer: Waters Micromass ZQ

[0139] Column: XBridge C18 4.6 x 50 mm, 5 pm.

[0140] Solvent: A = water; B = acetonitrile, C = ammonium formate (10 mM) in water; D = 0.05% formic acid in acetonitrile

[0141] Column temperature: 25 °C, injection volume: 5 μL LCMS Method A: 4.5 minutes of acid conduction. Petition 870260070784, dated 07 / 16 / 2026, page 51 / 130 41 / 84 Time (min) A (%) B (%) C (%) D (%) Flow (mL / min) 0 95 0 0 5 2.0 3.5 0 95 0 5 2.0 4.5 0 95 0 5 2.0 4.6 95 0 0 5 2.0 LCMS Method B: 4.5 minutes of buffered conduction Time (min) A (%) B (%) C (%) D (%) Flow (mL / min) 0 0 5 95 0 2.0 3.5 0 95 5 0 2.0 4.5 0 95 5 0 2.0 4.6 0 5 95 0 2.0 NMR

[0142] The NMR details were recorded on an Oxford Instruments AS400. MS

[0143] In which MS data are reported, for large molecular weight compounds a mass-to-charge ratio (m / z) is typically observed. Abbreviations

[0144] Where the following abbreviations have been used, the following meanings apply: Ahx is aminohexyl; Alloc is allyloxycarbonyl; aq. means aqueous; Boc is tert-butyloxycarbonyl; br s is a broad singlet; CDClaé deuterochloroform; CTC resin is chlorotritile chloride resin; d is a doublet; Dab is 2,4-diaminobutyric acid; Petition 870260070784, dated 07 / 16 / 2026, page 52 / 130 42 / 84 DCM stands for dichloromethane; Dde is (1,(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-ethyl); DIPEA is diisopropylethylamine; DMF stands for dimethylformamide; DMSO is dimethyl sulfoxide; d6-DMSO is deuterated DMSO; ES is an electrospray ionization technique; EtOAc is ethyl acetate; Fmoc is 9-fluorenylmethoxycarbonyl; g is gram; Gly is glycine; HATU is O-(7-azabenzotriazol-1-yl)-N,N,N',N'tetramethyluronium hexafluorophosphate; HBTU is O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; HCl is hydrochloric acid; HOBt is hydroxybenzotriazole; HPLC stands for high-performance liquid chromatography; KHCO3 is potassium bicarbonate; L stands for liter; LCMS stands for liquid chromatography coupled with mass spectrometry; Leu is leucine; m is a multiplet; mg stands for milligram; M is molar; MeCN is acetonitrile; MeOH is methanol; MgSO4 is magnesium sulfate; Petition 870260070784, dated 07 / 16 / 2026, page 53 / 130 43 / 84 MHz stands for megahertz, mL stands for milliliter; mmol is millimole; MS stands for mass spectrometry; NaHCO3 is sodium bicarbonate; NaOH is sodium hydroxide; NH3 is ammonia; NMR stands for nuclear magnetic resonance; Pd / C is palladium in carbon; Pd(PPh3)4 is tetracis(triphenylphosphine)palladium(O); Pd(PPh3)2Cl2is bis(triphenylphosphine)palladium(II) dichloride Phe is phenylalanine; PhSiH3 is phenylsilane; Psi stands for pounds per square inch; Rt is retention time; s is a singleton; t is a triplet; TBTU is O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; TEA is triethylamine; Thr is threonine; TIS stands for tri-isopropylsilane; TFA stands for trifluoroacetic acid; μL is microliter and ev is volume.

[0145] Where alpha-Gal is referred to, the following intermediate applies: 3-(((2R,3R,4R,5S,6R)-3-acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H Petition 870260070784, dated 07 / 16 / 2026, page 54 / 130 44 / 84 pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2Hpyran-2-yl)oxy)propyl)amine

[0146] This intermediate can be prepared according to the methods described by Bovin et al (Mendeleev Communications (2002), (4), 143 - 145). Synthesis of peptide intermediates

[0147] PMB scaffolds were constructed according to standard Solid Phase Peptide Synthesis (SPPS) using appropriately protected amino acids and CTC resin. Fmoc-Dab(Dde)-CTC resin, FmocThr(OtBu)-CTC resin, or Fmoc-Leu-CTC resin was chosen as suitable starting points, and the scaffolds were cyclized at an appropriate location in the synthesis. All protected amino acids and binding starting materials are commercially available or prepared according to the references cited herein.

[0148] Using SPPS, three alternative polymyxin scaffolding strategies were used:

[0149] Method 1: wherein the Polymyxin scaffold is synthesized with no ligand

[0150] Method 2: wherein the Polymyxin scaffold is synthesized with the addition of a solution-phase binder after cleavage of the resin.

[0151] Method 3: wherein the Polymyxin scaffold is synthesised with the addition of a binder as an extra resin step

[0152] The protected amino acids were chosen from: Fmoc-Leu-OH, Fmoc[D-Phe]-OH, Fmoc-Dab(Dde)-OH, Fmoc-Dab(Alloc)-OH, Fmoc-Thr-(OtBu)-OH, Fmoc[D-Ser(OtBu)]-OH and Boc-Dab(Dde)-OH.

[0153] The starting binder materials were chosen from Boc-PEGs-OH, Petition 870260070784, dated 07 / 16 / 2026, p. 55 / 130 45 / 84 Boc-Ahx-Ahx-OH (WO2008123844), Boc-[L-OctylGly]-OH, Fmoc-[L-OctylGly]-OH or combinations thereof.

[0154] Additionally, some peptide scaffolds were terminated with nonanoic acid.

[0155] Peptide scaffolds were analyzed using HPLC: Agilent 1260 LCMS: Agilent 1200+6410 MS. Preparation 1 H2N-Dab(Dde)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)Dab(Dde)-Thr(OH)* Method 1

[0156] The peptide chain was elongated in CTC resin starting with Fmoc-Leu-OH [for CTC resin (1 mmol, 1 g, 1.0 mmol / g) and Fmoc-Leu-OH (0.353 g, 1.0 mmol, 1.0 eq) in DCM (10.00 mL) DIPEA (4.0 eq) was added and the reaction was mixed for 2 hours. MeOH (1.0 mL) was added and the reaction was capped and mixed for 30 minutes]. Piperidine at 20% in DMF was used to unlock, and the desired amino acid sequence was constructed using HBTU and DIPEA in DMF for all residues except for Fmoc-Dab(Alloc)-OH, which was coupled using HATU and DIPEA in DMF to provide the resin Boc-Dab(Dde)-Thr(OtBu)Dab(Dde)-Dab(Alloc)-Dab(Dde)-[D-Phe]-Leu-O-CTC. At this point, the resin was treated with Pd(PPh3)2Cl2 (0.1 eq) and PhSiHa (10 eq) in DCM followed by resin washing with DMF and MeOH to affect the deprotection of alloc. The peptide was then further elongated as above with the remaining required amino acids. The peptide was Petition 870260070784, dated 07 / 16 / 2026, page 56 / 130 46 / 84 was cleaved from the resin with 1% TFA in DCM for 2 minutes and adjusted to pH=7 with DIPEA in DCM. TBTU (2 eq) and HOBt (2 eq) were then added and the reaction was stirred for 1 hour to affect cyclization. The reaction was washed with 5% aqueous HCl and concentrated under vacuum to provide Boc-Dab(Dde)-Thr(OtBu)-Dab(Dde)Dab*-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)-Dab(Dde)-Thr(OtBu)*. The crude peptide was treated with TFA / water (95% TFA, 5% water, 20 mL) and stirred at room temperature for 2 hours. The reaction was treated with cold isopropyl ether and centrifuged three times. The residue was dried under vacuum and purified using reversed-phase column chromatography (HPLC: Mobile Phase: A: TFA at 0.1% in H2O, B: TFA at 0.1% in MeCN; Flow: 1.0 mL / min T=50 °C; Column: YMC-Pack ODS-A 150*4.6 mm, 5 μμm; Instrument: Agilent 1200 HPLC (5-521)) followed by lyophilization to provide the title compound (80 mg).

[0157] The intermediate was taken directly to the next step. Preparation 2 H2N-Dab-Thr(OH)-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr(OH)*

[0158] After global deprotection of the Dde protecting groups of the Preparation (3% hydrazine / MeOH), the following data were obtained: Rt = 14.23 minutes, ES+MS m / z 1063.4 [M+1] and 532.2 [M+2] / 2; theoretical mass: 1062.6. Preparation 3 H2N-L-octylGly-Dab(Dde)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[D-Phe]-LeuDab(Dde)-Dab(Dde)-Thr(OH)* Petition 870260070784, dated 07 / 16 / 2026, page 57 / 130 47 / 84

[0159] The title compound can be prepared according to Method 1 using Fmoc-Dab(Dde)-CTC resin or Fmoc-Leu-CTC resin as starting points along with Boc-[L-octylGly]-OH.

[0160] The intermediary was taken directly to the next stage. Preparation 4 Nonanamide-Dab(NH2)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[D-Phe]-LeuDab(Dde)-Dab(Dde)-Thr(OH)*

[0161] The title compound was prepared according to Method 1 using Fmoc-Dab(Dde)-CTC resin or Fmoc-Leu-CTC resin as starting points along with nonanoic acid.

[0162] The intermediary was taken directly to the next stage. Preparation 5 Nonanamide-Dab(Dde)-Thr(OH)-Dab(PEG8NH2)-Dab*-Dab(Dde)-[D-Phe]Leu-Dab(Dde)-Dab(Dde)-Thr(OH)* Petition 870260070784, dated 07 / 16 / 2026, page 58 / 130 48 / 84 Method 2

[0163] The peptide chain was elongated in CTC resin starting with Fmoc-Thr(OtBu)-OH [For CTC resin (0.5 mmol, 0.5 g, 1.0 mmol / g) and Fmoc-Thr(OtBu)-OH (200 mg, 0.5 mmol, 1.0 eq) in DCM (5.0 mL), DIPEA (4.0 eq) was added and the reaction was mixed for 2 hours. MeOH (0.5 mL) was added and the reaction was capped and mixed for 30 minutes]. 20% piperidine in DMF was used to unlock and the desired amino acid sequence was constructed using HATU (2.85 eq) and DIPEA (6.0 eq) in DMF (2.0 mL) to provide the nonanamide-Dab(Dde)Thr(OtBu)-Dab(Boc)-Dab(Alloc)-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)-O-CTC resin. At this point, the resin was treated with Pd(PPh3)2Cl2 (0.1 eq) and PhSiHa (10 eq) in DCM followed by resin washing with DMF and MeOH to affect alloc deprotection and dried under nitrogen overnight. The peptide was further elongated as above with the required remaining amino acids. The peptide was cleaved from the resin with TFA at 1% / DCM (2 x 5 mL) for 2 minutes and adjusted to pH=7 with DIPEA in DCM.TBTU (2 eq) and HOBt (2 eq) were added followed by DIPEA (2 eq), and the mixture was stirred for 1 hour to affect cyclization. The reaction was washed with 5% aqueous HCl and concentrated under vacuum to provide Nonanamida-Dab(Dde)Thr(OH)-Dab(Boc)-Dab*-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)-Dab(Dde)-Thr(OH)*.

[0164] The crude peptide was treated with 95% TFA / 2.5% H2O / 2.5% TSI (5 mL) at room temperature and stirred for 30 minutes. The reaction was precipitated. Petition 870260070784, dated 07 / 16 / 2026, p. 59 / 130 49 / 84 with chilled isopropyl ether (50 mL) and centrifuged (3 min at 3,000 rpm). The crude peptide was washed with isopropyl ether (2 x 50 mL), centrifuged, and purified using Preparative HPLC (Mobile Phase A: 0.1% TFA in H2O, B: H2O) followed by lyophilization to provide the scaffold without the ligand.

[0165] To a solution of the peptide in DCM, Boc-PEGsOH (1.2 eq) and HBTU (1.2 eq) were added followed by DIPEA (2 eq) and the reaction was stirred for 30 minutes at room temperature. The reaction was washed twice with 5% HCl (aq) and concentrated under vacuum. The residue was treated with 20% TFA / DCM for 20 minutes and concentrated under vacuum. The residue was purified using preparative HPLC (Mobile Phase A: 0.1% TFA in H2O, B: H2O) and lyophilized to provide the title compound.

[0166] ES+ MS m / z 1142.6 [M+2] / 2 and 762.1 [M+3] / 3; theoretical mass: 2283.8 Preparation 6 H2N-PEG8-[L-octylGly]-Dab(Dde)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[DPhe]-Leu-Dab(Dde)-Dab(Dde)-Thr(OH)* Method 3

[0167] The peptide chain was elongated in CTC resin starting with Fmoc-Dab(Dde)-OH [For CTC resin (2 mmol, 2 g, 1.0 mmol / g) and Fmoc-Dab(Dde)-OH (1.08 g, 2 mmol, 1.0 eq) in DCM (30 mL), DIPEA (4.0 eq) was added and the reaction was mixed for 2 hours. MeOH (2 mL) was added and the reaction was capped and mixed for 30 minutes]. 20% piperidine in DMF was used to unlock and the desired amino acid sequence was constructed using HATU (2.85 eq) and DIPEA (6.0 eq) in DMF (10 mL) to provide the Boc(PEG8)-[L-octylGly]-Dab(Dde) resin. Petition 870260070784, dated 07 / 16 / 2026, pp. 60 / 130 50 / 84 Thr(OtBu)-Dab(Dde)-Dab(Alloc)-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)-O-CTC.

[0168] At this point, the resin was treated with Pd(PPh3)2Cl2 (0.1 eq) and PhSiH3 (10 eq) in DCM followed by resin washing with DMF and MeOH to affect alloc deprotection and dried under nitrogen overnight. The peptide was further elongated as above with the remaining required amino acids. The peptide was treated with TFA at 1% / DCM (2 x 20 mL) for 2 minutes and adjusted to pH=7 with DIPEA and diluted with DCM. TBTU (2 eq) and HOBt (2 eq) were added followed by DIPEA (2 eq), and the mixture was stirred for 1 hour to affect cyclization. The reaction was washed with 5% aqueous HCl and concentrated under vacuum to give Boc(PEGs)[L-octylGly]-Dab(Dde)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)Dab(Dde)-Thr(OH)*.

[0169] The crude peptide was treated with 95% TFA / 2.5% H2O / 2.5% TIS (5 mL) at room temperature and stirred for 30 minutes. The reaction was precipitated with chilled isopropyl ether (300 mL) and centrifuged (3 min at 3,000 rpm). The crude peptide was washed with isopropyl ether (2 x 100 mL), centrifuged, and purified using Preparative HPLC (Mobile Phase A: 0.1% TFA in H2O, B: H2O) followed by lyophilization to provide the title compound.

[0170] Rt = 10.6 - 11.9 minutes, ES+ MS m / z 1239.2 [M+2] / 2 and 826.4 [M+3] / 3; theoretical mass: 2477.0 Preparation 7 Nonanamide-Dab(Ahx-Ahx-NH2)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[DPhe]-Leu-Dab(Dde)-Dab(Dde)-Thr(OH)*

[0171] The title compound can be prepared according to Method 2 Petition 870260070784, dated 07 / 16 / 2026, pp. 61 / 130 51 / 84 using Fmoc-Dab(Dde)-CTC resin as a starting point along with nonanoic acid and Boc-Ahx-Ahx-OH.

[0172] Rt = 8.2 to 9.3 minutes, ES+ MS m / z 1043.7 [M+2] / 2 and 696.3 [M+3] / 3; theoretical mass: 2086.6 Preparation 8 H2N-Ahx-Ahx-[L-octylGly]-Dab(Dde)-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[DPhe]-Leu-Dab(Dde)-Dab(Dde)-Thr(OH)*

[0173] The title compound can be prepared according to Method 3 using Fmoc-Dab(Dde)-CTC resin as a starting point along with Boc-AhxAhx-OH and Fmoc-[L-octylGly]-OH.

[0174] Rt = 11.9 to 12.9 minutes, ES+MS m / z 1140.2 [M+2] / 2 and 760.7 [M+3] / 3; theoretical mass: 2279.9 Preparation 9 Fmoc-[L-octylGly]-Dab(Dde)-Thr(OH)-Dab(PEG8NH2)-Dab*-Dab(Dde)-[DPhe]-Leu-Dab(Dde)-Dab(Dde)-Thr(OH)*

[0175] The title compound can be prepared according to Method 2 Petition 870260070784, dated 07 / 16 / 2026, p. 62 / 130 52 / 84 using Fmoc-Thr(OtBu)-CTC resin as a starting point along with BocPEG8-OH and Fmoc-[L-octylGly]-OH.

[0176] The intermediary was taken directly to the next stage. Preparation 10 H2N-PEG8-Ahx-Ahx-Thr(OH)-[D-Ser(OH)]-Dab*-Dab(Dde)-[D-Phe]-LeuDab(Dde)-Dab(Dde)-Thr(OH)*

[0177] The title compound can be prepared according to Method 2 using Fmoc-Dab(Dde)-CTC resin as a starting point along with BocPEG8-OH and Boc-Ahx-Ahx-OH.

[0178] The intermediary was taken directly to the next stage. Preparation 11 H2N-PEG8-Ahx-Ahx-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[D-Phe]-LeuDab(Dde)-Dab(Dde)-Thr(OH)*

[0179] The title compound can be prepared according to Method 2 using Fmoc-Dab(Dde)-CTC resin as a starting point along with BocPEG8-OH and Boc-Ahx-Ahx-OH.

[0180] The intermediary was taken directly to the next stage. Preparation 12 H2N-Ahx-Ahx-Thr(OH)-[D-Ser(OH)]-Dab*-Dab(Dde)-[D-Phe]-Leu-Dab(Dde) Petition 870260070784, dated 16 / 07 / 2026, page 63 / 130 53 / 84 Dab(Dde)-Thr(OH)*

[0181] The title compound can be prepared according to Method 3 using Fmoc-Dab(Dde)-CTC resin as a starting point along with Boc-AhxAhx-OH.

[0182] The intermediary was taken directly to the next stage. Preparation 13 H2N-Ahx-Ahx-Thr(OH)-Dab(Dde)-Dab*-Dab(Dde)-[D-Phe]-Leu-Dab(Dde)Dab(Dde)-Thr(OH)*

[0183] The title compound can be prepared according to Method 3 using Fmoc-Dab(Dde)-CTC resin as a starting point along with Boc-AhxAhx-OH.

[0184] The intermediate was taken directly to the next step. Synthesis of alpha-Gal intermediates Preparation 14 Acid 6-(6-(4'-(2-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5-(((2S,3R,4S,5S,6R)3,5-di-hydr oxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-tri-hydroxy-6(hydroxymethyl)tet ra-hydro-2H-pyran-2-yl)oxy)tetra-hydro-2H-pyran-2-yl)oxy)-4-hydroxy-6(hydroxymethyl)tetra-hydro-2H-pyran-2-yl)oxy)propyl)amino)-2-oxoethoxy)-[1,1'-biphenyl]-3 lcarboxam ido)hexanamide)hexanoic Petition 870260070784, of 16 / 07 / 2026, p. 64 / 130 54 / 84

[0185] To a solution of Preparation 15 (30 mg, 0.035 mmol) and benzyl 6-(6-aminohexanamido)hexanoate (JACS 136 (52) 18034 - 18043 (2014), 14.1 mg, 0.042 mmol) in DMF (600 μL) was added triethylamine (17 μL 0.123 mmol) followed by HATU (16 mg, 0.042 mmol). The reaction was stirred at room temperature overnight. The reaction was concentrated under vacuum, dissolved in DMSO and purified using reversed-phase column chromatography eluting with 7-60% MeCN / water with 0.1% ammonia to provide the desired benzyl-protected intermediate (19.8 mg, 48%).

[0186] LCMS (Method B) Rt = 2.45 minutes; ES+MS m / z 1173.9 [M+H]+

[0187] The isolated intermediate was dissolved in MeOH / water (1:1 (v / v), 10 mL) and Pd / C (10%, 10 mg) was added. The reaction was carried out under a hydrogen atmosphere (50 psi) and stirred for 3 hours at room temperature. The catalyst was removed by filtration through a syringe filter and the solvent removed under reduced pressure to provide the title compound as a colorless solid (20.4 mg, >99%).

[0188] LCMS (Method B) Rt = 1.70 minutes; ES-MS m / z 1081.8 [MH] Preparation 15 Acid 4'-(2-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5-(((2S,3R,4S,5S,6R)-3,5dihydroxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro -2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-2-oxoethoxy)-[1,1'-biphenyl]-3-carboxylic

[0189] To 2-((3'-((benzyloxy)carbonyl)-[1,1'-biphenyl]-4-yl)oxy)acetic acid (Preparation 16, 55 mg, 152 μmol) in DMF (7.5 mL) was added TEA (63.4 μL, 455 Petition 870260070784, dated 07 / 16 / 2026, page 65 / 130 55 / 84 μmol) followed by a solution of alpha-Gal (119 mg, 197 μmol) in DMSO (500 μL). HATU (86.6 mg, 228 μmol) was added as a solution in DMF (500 μL), and the reaction was left to stir for 16 hours under nitrogen at room temperature. The solvent was removed under vacuum and the residue purified using reversed-phase column chromatography eluting with 7-60% MeCN / water with 0.1% NH3 to provide the desired benzyl-protected intermediate as a colorless solid (93.5 mg, 65%).

[0190] LCMS (Method B) Rt = 2.54 minutes, ES+ MS m / z 947.6 [M+H]+

[0191] The isolated intermediate was dissolved in MeOH / water (1:1 (v / v), 5 mL), and Pd / C (10%, 10 mg) was added to the solution. The reaction was carried out under a hydrogen atmosphere (50 psi) and stirred for 3 hours at room temperature. The catalyst was removed by filtration through a syringe filter and the solvent removed under vacuum. The residue was purified using reversed-phase column chromatography eluting with 5-40% MeCN / water with 0.1% NH3 to provide the title compound as a colorless solid (71.6 mg, 84%).

[0192] LCMS (Method A) Rt = 1.83 minutes, ES+MS m / z 857.6 [M+H]+Preparation 16 2-((3'-((benzyloxy)carbonyl)-[1, 1'-biphenyl]-4-yl)oxy)acetic acid

[0193] A solution of 4'-(2-(tert-butoxy)-2-oxoethoxy)-[1,1'-biphenyl]-3-benzyl carboxylate (Preparation 17, 7.80 g, 18.6 mmol) in DCM / TFA / water (10:10:1 (v / v / v), 80 mL) was stirred for 2 hours at room temperature. The reaction was concentrated under vacuum, subjected to azeotropy with dioxane / toluene (1:1, (v / v), 80 mL), triturated with toluene, filtered, and dried in a vacuum oven to provide the title compound as a colorless solid (6.11 g, 90%). Petition 870260070784, dated 07 / 16 / 2026, p. 66 / 130 56 / 84

[0194] LCMS (Method B) Rt = 2.43 minutes, ES+MS m / z 363.2 [M+H]+

[0195] 1H NMR (400 MHz, d6-DMSO): δ ppm 13.00 (1H, s), 8.15 (1H, t), 7.95 - 7.90 (2H, m), 7.65 - 7.55 (3H, m), 7.50 - 7.45 (2H, m), 7.45 - 7.30 (3H, m) 7.05 - 7.00 (2H, m), 5.40 (2H, s), 4.70 (2H, s). Preparation 17 4'-(2-(tert-Butoxy)-2-oxoethoxy)-[1,1'-biphenyl]-3-benzyl carboxylate

[0196] To benzyl 4'-hydroxy-[1,1'-biphenyl]-3-carboxylate (Preparation 18, 15 g, 49.3 mmol) dissolved in DMF (150 mL) were added tert-butyl bromoacetate (10.9 mL, 73.9 mmol) and potassium carbonate (20.4 g, 148 mmol). The resulting suspension was stirred for 16 hours at room temperature under nitrogen. The reaction was concentrated under vacuum and the residue was dissolved in water (150 mL) and extracted with EtOAc (2 x 150 mL). The combined organic layers were washed with brine (150 mL), NaOH (2M aqueous, 150 mL), dried over MgSO4 and concentrated under vacuum. The residue was purified using silica gel column chromatography eluting with 5-40% EtOAc / heptane to provide the title compound as a colorless oil (17.8 g, 86%).

[0197] LCMS (Method B) Rt = 4.14 minutes, no mass ion observed.

[0198] 1H NMR (400 MHz, CDCla): δ ppm 8.25 (1H, s), 8.00 (1H, d), 7.70 (1H, d), 7.55 (2H, d), 7.50 - 7.25 (6H, m), 7.00 (2H, d), 5.40 (2H, s), 4.55 (2H, s), 1.50 (9H, s). Preparation 18 Benzyl 4'-Hydroxy-[1,1'-biphenyl]-3-carboxylate Petition 870260070784, dated 07 / 16 / 2026, p. 67 / 130 57 / 84

[0199] A mixture of benzyl 3-bromobenzoate (Preparation 19, 15 g, 51.5 mmol), sodium carbonate (19.1 g, 180 mmol) and (4-hydroxyphenyl)boronic acid (8.53 g, 61.8 mmol) dissolved in dioxane / water (5:1 (v / v), 450 mL) was deoxygenated for 30 minutes under nitrogen. Pd(PPh3)4 (5.95 g, 5.15 mmol) was added and the reaction was heated to 100 °C for 90 minutes under nitrogen. After cooling to room temperature, EtOAc (450 mL) and water (450 mL) were added and the layers were separated. The aqueous layer was extracted with EtOAc (2 x 450 mL) and the combined organic layers washed with brine (450 mL). The organic layer was dried over MgSO4 and the solvent removed under vacuum to provide a black residue. The residue was filtered through a silica washing pad with EtOAc / heptane (1:1 (v / v), 2 L) and concentrated under vacuum. The residue was ground with toluene (75 mL) and filtered.The resulting solid was washed with toluene (25 mL) and dried under reduced pressure to give the title compound as a beige solid (12.7 g, 81%).

[0200] LCMS (Method B) Rt = 3.39 minutes, ES-MS m / z 303.3 [MH]-

[0201] 1H NMR (400 MHz, CDCla): δ ppm 8.25 (1H, s), 8.00 (1H, d), 7.70 (1H, d), 7.50 - 7.30 (8H, m), 6.90 (2H, d), 5.40 (2H, s), 5.00 (1H, br s). Preparation 19 3-Benzyl bromobenzoate

[0202] To a solution of 3-bromobenzoic acid (20 g, 99.5 mmol) dissolved in DMF (100 mL) was added KHCO3 (9.96 g, 99.5 mmol). Benzyl bromide (11.8 mL, 99.5 mmol) was added dropwise and the reaction was stirred at room temperature under nitrogen overnight. The reaction was concentrated under vacuum. The residue was partitioned between EtOAc (200 mL) and water (200 mL). The layers were separated and the organic layer was washed with citric acid (1M, 200 mL), NaHCO3 Petition 870260070784, dated 07 / 16 / 2026, page 68 / 130 58 / 84 (saturated, aqueous, 200 mL) and brine (200 mL). The organic layer was dried over MgSO4 and the solvent removed under reduced pressure to provide the title compound as a light yellow oil (28.3 g, 97%).

[0203] LCMS (Method B) Rt = 3.80 minutes, no ionization observed.

[0204] 1H NMR (400 MHz, CDCla): δ ppm 8.20 (1H, s), 8.00 (1H, s), 7.65 (1H, s), 7.50 - 7.25 (6H, m), 5.35 (2H, s). Preparation 20 Acid 6-(6-(3',5,5'-tris(2-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5(((2S,3R,4S,5S,6R)-3,5-dihydro xi-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H -pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-2-oxoethoxy)-[1,1'biphenyl]-3-carboxamido)hexanamido)hexanoic

[0205] The title compound was prepared using Preparation 21 and benzyl 6-(6-amino-hexanamido)hexanoate (JACS 136 (52) 18034 - 18043 (2014)) according to Preparation 14.

[0206] LCMS (Method B) Rt = 1.47 minutes, ES+ MS m / z 1201.3 [M+2H]+ / 2; theoretical mass: 2400.0 Preparation 21 Acid 3',5,5'-tris(2-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl )tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-2-oxoethoxy)-[1,1'Petition 870260070784, of 07 / 16 / 2026, p. 69 / 130 59 / 84 biphenyl]-3-carboxylic

[0207] The title compound was prepared using alpha-Gal and 2,2',2''-((5'((benzyloxy)carbonyl)-[1,1'-biphenyl]-3,3',5-triyl)tris(oxy))triacetic acid (WO2017060729) according to Preparation 14.

[0208] LCMS (Method B) Rt = 1.27 minutes, ES+ MS m / z 1088.4 [M+2H]+ / 2, theoretical mass: 2174.0. Preparation 22 Acid 4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-acetamide-5(((2S,3R,4S,5S,6R)-3,5-di-hydroxy-6-(hyd roxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetra-hydro-2H-pyran-2-yl) oxy)tetra-hydro-2H-pyran-2-yl)oxy)-4hydroxy-6-(hydroxymethyl)tetra-hydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxo-hexyl)amino)6-oxo-hexyl)amino)-2-oxoethoxy,11'-3-lico-biphenyl

[0209] 4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-Acetamido-5(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hid roxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl) oxy)tetrahydro-2H-pyran-2-yl)oxy)-4hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxohexyl)amino)6-oxohexyl)amino)-2-oxoethoxy)-[1,1'-biphenyl]-3-carboxylate benzyl (Preparation 23, 215 mg) was dissolved in a solution of TEA and water (1:1 (v / v), 10 mL) and stirred overnight. The reaction was concentrated under vacuum and the residue was purified using Petition 870260070784, dated 07 / 16 / 2026, pp. 70 / 130 60 / 84 reversed-phase column chromatography eluting with MeCN 1-30% / water with NH3 at 0.1%. The resulting residue containing starting material was further treated with TEA solution and water (1:1 (v / v), 10 mL) and stirred for 5 days. The reaction was concentrated under vacuum and the residue was purified using reversed-phase column chromatography eluting with MeCN 1-30% / water with NH3 at 0.1% followed by MeCN 1-20% / water with NH3 at 0.1% to provide the title compound as a colorless solid (total = 172 mg, 87%).

[0210] LCMS (Method B) Rt = 1.65 minutes, ES+ MS m / z 1083.9 [M+H]+ Preparation 23 4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-Acetamido-5-(((2S,3R,4S,5S,6R)-3,5 dihydroxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetra benzyl hydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxohexyl)amino)-6-oxohexyl)amino)-2oxoethoxy)-[1,1'-biphenyl]-3-carboxylate

[0211] To a solution of 6-(6-(2-((3'-((benzyloxy)carbonyl)-[1,1'-biphenyl]-4yl)oxy)acetamido)hexanamido)hexanoic acid (Preparation 24, 110 mg, 187 μmol) dissolved in DMF (2.2 mL) were added HATU (106 mg, 280 μmol) and TEA (80 μL, 560 μmol). A solution of alpha-Gal (146 mg, 243 μmol) in DMSO (1 mL) was added and the reaction was stirred for 1 hour. The reaction was purified directly using reversed-phase column chromatography eluting with MeCN between 10 and 70% in water with 0.1% NH3 to provide the title compound as a colorless solid (215 mg, 98%).

[0212] LCMS (Method B) Rt = 2.62 minutes, ES+MS m / z 1173.7 [M+H]+ Preparation 24 Petition 870260070784, dated 07 / 16 / 2026, pp. 71 / 130 61 / 84 6-(6-(2-((3'-((benzyloxy)carbonyl)-[1, 1'-biphenyl]-4yl)oxy)acetamido)hexanamido) hexanoic acid the

[0213] 4'-(2-((6-((6-(tert-Butoxy)-6-oxo-hexyl)amino)-6-oxo-hexyl)amino)-2oxoethoxy)-[1,1'-biphenyl]-3-benzyl carboxylate (Preparation 25, 320 mg, 496 μmol) was dissolved in a solution of DCM, TFA and water (10:10:1 (v / v / v), 10 mL) and stirred for 3 hours. The reaction was concentrated under vacuum and the residue subjected to azeotropy with dioxane / toluene (1:1 (v / v), 3 x 24 mL). The crude material was purified using reversed-phase column chromatography eluting with MeCN between 10 and 80% / water with 0.1% formic acid to provide the title compound as a colorless solid (168 mg, 66%).

[0214] LCMS (Method B) Rt = 2.81 minutes, ES-MS m / z 589.2 [M]-

[0215] 1H NMR (400 MHz, CDCla): δ ppm 8.25 (1H, s), 8.02 (1H, d), 7.72 (1H, d), 7.59 (2H, d), 7.52 - 7.45 (3H, m), 7.42 - 7.35 (3H, m), 7.00 (2H, d), 6.74 (1H, br s), 5.71 (1H, br s), 5.40 (2H, s), 4.56 (2H, s), 3.44 - 3.39 (2H, m), 3.32 - 3.28 (2H, m), 2.37 (2H, t), 2.15 (2H, t), 1.68 - 1.51 (6H, m), 1.41 - 1.33 (6H, m) ppm. Preparation 25 Benzyl 4'-(2-((6-((6-(tert-Butoxy)-6-oxohexyl)amino)-6-oxohexyl)amino)-2-oxoethoxy)[1,1'-biphenyl]-3-carboxylate the

[0216] To a solution of 2-((3'-((benzyloxy)carbonyl)-[1,1'-biphenyl]-4-yl)oxy)acetic acid (Preparation 16, 150 mg, 414 μmol, 1 eq) dissolved in DMF (3 mL) was added TEA (173 μmol 1.2 mmol) and a solution of 6-(6-amino Petition 870260070784, dated 07 / 16 / 2026, p. 72 / 130 62 / 84 hexanamido) tert-butyl hexanoate (Preparation 31, 162 mg, 538 μmol) in DMF (2 mL). HATU was then added (236 mg, 621 μmol) and the reaction was stirred for 1 hour at room temperature. The reaction was purified directly using silica gel column chromatography eluting with EtOAc between 0 and 100% in Heptanes to provide the title compound as a colorless oil (320 mg, >100%).

[0217] LCMS (Method B) Rt = 3.70 minutes, ES-MS m / z 645.3 [M] (2H, d), 7.50 - 7.45 (3H, m), 7.40 - 7.35 (3H, m), 7.00 (2H, d), 6.70 (1H, br s), 5.60 (1H, br s), 5.40 (2H, s), 4.55 (2H, s), 2.25 - 2.10 (4H, m), 1.70 1.55 (9H, m), 1.55 - 1.45 (3H, m), 1.45 (9H, s), 1.40 - 1.30 (4H, m) ppm. Preparation 26 Ácido 1-(4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5(((2S,3R,4S,5S,6R)-3,5-dihydroxy) i-6-(hidroximetil)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihidróxi-6-(hidroximetil)tetra-hidro- 2H-piran-2-il)oxy)tetra-hidro-2H-piran-2-il)oxy)-4hidróxi-6-(hidroximetil)tetra-hidro-2H-piran-2-il)oxy)propyl)amino)-6-oxo-hexil)amino)6-oxo-hexil)amino)-2-oxoetóxi)-[1,1'-bifenil]-3-il)-1,8,15,22-tetraoxo-2,9,16,23-tetraazanonacosan-29-óico

[0219] To a solution of 1-(4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-acetamido5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy i-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro- 2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxohexyl)amino)6-oxohexyl)amino)-2-oxoethoxy)-[1, 1 Benzyl '-biphenyl]-3-yl)-1,8,15,22-tetraoxo-2,9,16,23-tetraazanonacosan-29-oate (Preparation 27, 50 mg, 30 μmol) in MeOH (5 mL) and water (5 mL) was added to 5% Pd / C (5 mg). The reaction was degassed and stirred under a hydrogen atmosphere (flask) overnight. The reaction was filtered through a syringe filter and the concentrated solution vacuum-sealed to yield the compound. Petition 870260070784, dated 07 / 16 / 2026, p. 73 / 130 63 / 84 of the title as a light gray solid (26 mg, 60%).

[0220] LCMS (Method B) Rt = 1.88 minutes, ES-MS m / z 1537.4 [M] Preparation 27 1-(4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-Acetamido-5-(((2S,3R,4S,5S,6R)3,5-di-hidróxi-6-(hidroximetil)-4-(((2R,3R,4S,5R,6R)-3,4,5-tri-hidróxi-6(hidroximetil)tetra-hidro- [1, 1] '-bifenil]-3-il)-1,8,15,22-tetraoxo-2,9,16,23-tetraazanonacosan-29-oato of benzyl

[0221] To an acidic solution 4'-(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hid roxymethyl)-4(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl )oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2yl)oxy)propyl)amino)-6-oxohexyl)amino)-6-oxohexyl)amino)-2-oxoethoxy)-[1,1'-biphenyl]-3carboxylic (Preparation 22, 50 mg, 46 μmol) in DMF (2 mL) were added HATU (26 mg, 69 μmol) and TEA (19 μL, 138 μmol). A solution of benzyl 6-(6-(6-(6-(6-amino-hexanamido)hexanamido)hexanamido)hexanoate hydrochloride (WO2017060729, 36 mg, 60 pmol) in DMF (2 mL) and TEA (13 pL, 92 pmol) was added to provide a yellow solution, and the reaction was stirred for 1 hour at room temperature. The reaction was purified directly using reversed-phase column chromatography eluting with MeCN between 2 and 70% in water with NH3 at 0.1% to provide the title compound as a colorless solid (50 mg, 66%).

[0222] LCMS (Method B) Rt = 2.41 minutes, ES+MS m / z 1627.5 [M+H]+Preparation 28 Acid 1-(4',5-bis(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5(((2S,3R,4S,5S, 6R)-3,5-di-hydroxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-triPetition 870260070784, of 16 / 07 / 2026, page 74 / 130. 64 / 84 hydroxy-6-(hydroxymethyl)tetra-hydro-2H-pyran-2-yl)oxy)tetra-hydro-2H-pyran-2-yl)oxy)-4hydroxy-6-(hydroxy imethyl)tetra-hydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxo-hexyl)amino)6-oxo-hexyl)amino)-2-oxoethoxy)-[1, 1 '-biphenyl]-3-yl)-1,8,15,22-tetraoxo-2,9,16,23-tetraazanonocosan-29-oic

[0223] The title compound was prepared according to the methods described for Preparations 27 and 26 using acid 4',5-bis(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6- (hydroxymethyl)-4(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2- yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2yl)oxy)propyl)amino)-6-oxohexyl)amino)-6-oxohexyl)amino)-2-oxoethoxy)-[1,1'-biphenyl]-3carboxylic (Preparation 29) and benzyl 6-(6-(6-(6-amino-hexanamido)hexanamido)hexanamido)hexanoate (WO2017060729).

[0224] LCMS (Method B) Rt = 1.72 minutes, ES+ MS m / z 1211.7 [M+2H]+ / 2; theoretical mass: 2420.7 Preparation 29 4',5-bis(2-((6-((6-((3-(((2R,3R,4R,5S,6R)-3-acetamido-5 (((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4-(((2R,3R,4S,5R,6R)-3,4,5-tri hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4 hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)propyl)amino)-6-oxohexyl)amino)6-oxohexyl)amino)-2-oxoethoxy)-[1,1'-biphenyl]-3-carboxylic

[0225] The title compound was prepared according to the methods Petition 870260070784, dated 07 / 16 / 2026, pp. 75 / 130 65 / 84 described for Preparations 22 and 23 using 6,6'-((6,6'-((2,2'-((5((benzyloxy)carbonyl)-[1,1'-biphenyl]-3,4'-di-yl)bis(oxy))bis(acetyl))bis(azanodiyl))bis(hexanoyl))bis(azanodiyl))dihexanoic acid (Preparation 30) and alpha-Gal.

[0226] LCMS (Method B) Rt = 1.55 minutes, ES-MS m / z 1967.3 [MH]- Preparation 30 6,6'-((6,6'-((2,2'-((5-((benzyloxy)carbonyl)-[1,1'-biphenyl]-3,4'-diyl)bis(oxy))bis(acetyl))bis(azanodi-yl))bis(hexanoyl))bis(azanodi-yl))dihexanoic acid,,

[0227] The title compound was prepared according to the methods described for Preparations 25 and 24 using tert-butyl 6-(6-amino-hexanamido)hexanoate (Preparation 31) and 2,2'-((5-((benzyloxy)carbonyl)-[1,1'-biphenyl]-3,4-diyl)bis(oxy))diacetic acid (WO2017060729).

[0228] LCMS (Method B) Rt = 2.67 minutes, ES-MS m / z 889.5 [MH]- Preparation 31 6-(6-Aminohexanamido)hexanoate tert-butyl

[0229] The title compound was prepared according to the methods described for Preparations 27 and 26 using tert-butyl 6-aminohexanoate and 6-{[(benzyloxy)carbonyl]amino}hexanoic acid.

[0230] 1H NMR (400 MHz, CDCla): δ ppm 5.71 (1H, br s), 3.30 - 3.20 (2H, m), 2.80 - 2.70 (2H, m), 2.28 - 2.07 (4H, m), 1.72 - 1.29 (21H, m). Summary of Examples Example 1 Petition 870260070784, dated 07 / 16 / 2026, page 76 / 130 66 / 84

[0231] To a solution of Preparation 14 (1.2 mg, 0.0011 mmol) in DMF (0.5 mL) was added DIPEA (4.0 eq) and a solution of Preparation 1 (2.5 mg, 0.0024 mmol) in DMF (200 μL). HATU (1.2 eq) was then added and the reaction was stirred at room temperature for 1 hour. The reaction was purified by reversed-phase column chromatography (C-18, 4 g, MeCN between 0 and 70% / water) and dried under vacuum. The residue was dissolved in hydrazine at 3% / MeOH (0.5 mL) and the reaction was stirred for 30 minutes. The material was purified using preparative HPLC column chromatography (column: Gemini-NX 5u C18 110A 150*4.6 mm; Flow: 1.0 ml / min T = 30 °C; Mobile Phase A: TFA at 0.1% in H2O B: TFA at 0.1% in MeCN; Instrument: Agilent 1260 HPLC-(5-521)) and lyophilized to provide the title compound as the trifluoroacetate salt (0.1 mg).

[0232] HPLC (Method 1) Rt = 15.11 - 15.76 minutes;

[0233] MS m / z 1064.0 [M+2H]+ / 2 and 710 [M+3H]+ / 3, theoretical mass: 2127.0.

[0234] The following Examples 2 to 25 were prepared using the appropriate Preparations contained herein and in accordance with Example 1 (amide bond formation followed by hydrazinolysis). The Examples were isolated as TFA Salts and analyzed by HPLC as described below:

[0235] Method 1: Gemini-NX 5um, C18, 110A, 150 x 4.6 mm; Flow: 1.0 mL / min. Mobile Phase A: 0.1% TFA in H2O B: 0.1% TFA in MeCN; Instrument: Agilent 1200 HPLC-BE (1-614). Gradient: 0 min (A at 85%), 20 min (A at 55%), 20.1 min (A at 10%), 23 min (A at 10%).

[0236] Method 2: XBridge C18, 3.5 µm, 2.1 x 30 mm. Flow rate: 1.0 mL / min. Mobile Phase A: TFA at 0.1% in water; Mobile Phase B: MeCN. Gradient: 0 min (B at 5%), 6 Petition 870260070784, dated 07 / 16 / 2026, p. 77 / 130 67 / 84 min (B at 95%), 7 min (B at 95%), 8 min (B at 5%). Temp.: 40 °C. Example 2

[0237] The compound of Example 2 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 20 and Preparation 1.

[0238] HPLC (Method 1) Rt = 6.31 to 7.31 minutes

[0239] MS m / z 1149.0 [M+3H]+ / 3, theoretical mass: 3445.6 Example 3

[0240] The compound of Example 3 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 21 and Preparation 3.

[0241] HPLC (Method 1) Rt = 9.66 to 10.84 minutes

[0242] MS m / z 1130 [M+3H]+ / 3, theoretical mass: 3388.6 Example 4

[0243] The compound of Example 4 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 14 and Preparation 3. Petition 870260070784, dated 07 / 16 / 2026, page 78 / 130 68 / 84

[0244] HPLC (Method 1) Rt = 9.82 to 10.24 minutes

[0245] MS m / z 1149.0 [M+2H]+ / 2, theoretical mass: 2297.7 Example 5

[0246] The compound in Example 5 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 20 and Preparation 3.

[0247] HPLC (Method 1) Rt = 10.23 to 10.81 minutes

[0248] MS m / z 904.0 [M+4H]+ / 4, theoretical mass: 3614.9 Example 6

[0249] The compound of Example 6 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 6.

[0250] HPLC (Method 1) Rt = 9.71 to 10.55 minutes

[0251] HPLC (Method 2) Rt = 2.953 minutes

[0252] MS m / z 832 [M+3H]+ / 3, theoretical mass: 2493.0 Example 7 Petition 870260070784, dated 07 / 16 / 2026, pp. 79 / 130 69 / 84

[0253] The compound of Example 7 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 21 and Preparation 6.

[0254] HPLC (Method 1) Rt = 10.06 to 10.98 minutes

[0255] HPLC (Method 2) Rt = 2,640 minutes

[0256] MS m / z 1271 [M+3H]+ / 3, theoretical mass: 3809.0 Example 8

[0257] The compound of Example 8 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 20 and Preparation 4.

[0258] HPLC (Method 1) Rt = 14.43 to 15.24 minutes

[0259] MS m / z 897 [M+4H]+ / 4, theoretical mass: 3585.8 Example 9

[0260] The compound in Example 9 was prepared in a manner analogous to Petition 870260070784, dated 07 / 16 / 2026, pp. 80 / 130 70 / 84 procedure described in Example 1 using Preparation 14 and Preparation 4.

[0261] HPLC (Method 1) Rt = 17.57 to 17.84 minutes

[0262] MS m / z 1134 [M+2H]+ / 2, theoretical mass: 2268.6 Example 10

[0263] The compound of Example 10 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 21 and Preparation 4.

[0264] HPLC (Method 1) Rt = 13.70 to 14.50 minutes

[0265] MS m / z 1120 [M+3H]+ / 3, theoretical mass: 3359.5 Example 11

[0266] The compound of Example 11 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 11.

[0267] HPLC (Method 1) Rt = 9.75 to 10.79 minutes

[0268] MS m / z 817.9 [M+3H]+ / 3, theoretical mass: 2450.3 Example 12 Petition 870260070784, dated 07 / 16 / 2026, page 81 / 130 71 / 84

[0269] The compound of Example 12 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 10.

[0270] HPLC (Method 1) Rt = 10.77 to 11.23 minutes

[0271] HPLC (Method 2) Rt = 3.065 minutes

[0272] MS m / z 1219.8 [M+2H]+ / 2, theoretical mass: 2437.3 Example 13

[0273] The compound of Example 13 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 13.

[0274] HPLC (Method 1) Rt = 8.77 to 11.14 minutes

[0275] MS m / z 1014.0 [M+2H]+ / 2, theoretical mass: 2026.0 Example 14

[0276] The compound of Example 14 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 12.

[0277] HPLC (Method 1) Rt = 10.71 to 11.64 minutes Petition 870260070784, dated 07 / 16 / 2026, p. 82 / 130 72 / 84

[0278] MS m / z 1007.8 [M+2H]+ / 2, theoretical mass: 2013.6 Example 15

[0279] The compound of Example 15 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 9.

[0280] HPLC (Method 2) Rt = 8.390 minutes

[0281] MS m / z 1248.3 [M+2H]+ / 2, 832.3 [M+3H]+ / 3 theoretical mass: 2493.3 Example 16

[0282] The compound of Example 16 was prepared in a manner analogous to the procedure described in Example 1 using acid 4'-((22-(((2R,3R,4R,5S,6R)-3acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2 H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-2,18dioxo-6,9,12,15-tetraoxa-3,19-diazadocosyl)oxy)-[1, 1'-biphenyl]-3-carboxylic acid (WO2017060729) Preparation 8.

[0283] HPLC (Method 2) Rt = 2.944 minutes

[0284] MS m / z 1273.0 [M+2H]+ / 2, 849.1 [M+3H]+ / 3; theoretical mass: 2543.4 Example 17 Petition 870260070784, dated 07 / 16 / 2026, page 83 / 130 73 / 84

[0285] The compound of Example 17 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 22 and Preparation 8.

[0286] HPLC (Method 2) Rt = 2.964 minutes

[0287] MS m / z 1262.5 [M+2H]+ / 2, 841.9 [M+3H]+ / 3; theoretical mass: 2522.41 Example 18

[0288] The compound of Example 18 was prepared in a manner analogous to the procedure described in Example 1 using acid 4'-((22-(((2R,3R,4R,5S,6R)-3acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2 H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-2,18dioxo-6,9,12,15-tetraoxa-3,19-diazadocosyl)oxy)-[1, 1'-biphenyl]-3-carboxylic acid (WO2017060729) Preparation 6.

[0289] HPLC (Method 2) Rt = 2.963 minutes

[0290] MS m / z 914.9 [M+3H]+ / 3, 686.3 [M+4H]+ / 4; theoretical mass: 2740.5 Example 19

[0291] The compound of Example 19 was prepared in a manner analogous to Petition 870260070784, dated 07 / 16 / 2026, page 84 / 130 74 / 84 procedure described in Example 1 using Preparation 22 and Preparation 6.

[0292] HPLC (Method 2) Rt = 2.998 minutes

[0293] MS m / z 1361.6 [M+2H]+ / 2, 907.9 [M+3H]+ / 3; theoretical mass: 2719.49 Example 20

[0294] The compound of Example 20 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 26 and Preparation 6.

[0295] HPLC (Method 2) Rt = 3.033 minutes

[0296] MS m / z 1058.7 [M+3H]+ / 3, 794.1 [M+4H]+ / 4; theoretical mass: 3173.82 Example 21

[0297] The compound of Example 21 was prepared in a manner analogous to the procedure described in Example 1 using acid 4',5-Bis((22-(((2R,3R,4R,5S,6R)3-acetamido-5-(((2S,3R,4S,5S,6R)-3,5-dihydroxy-6-(hydroxymethyl)-4(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro -2H-pyran-2-yl)oxy)tetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)-2,18dioxo-6,9,12,15-tetraoxa-3,19-diazadocosyl)oxy)-[1, 1'-biphenyl]-3-carboxylic acid (WO2017060729) and Preparation 8.

[0298] HPLC (Method 2) Rt = 2.761 minutes

[0299] MS m / z 1151.3 [M+3H]+ / 3, 863.6 [M+4H]+ / 4; theoretical mass: 3448.8 Example 22 Petition 870260070784, dated 07 / 16 / 2026, page 85 / 130 75 / 84

[0300] The compound of Example 22 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 29 and Preparation 8.

[0301] HPLC (Method 2) Rt = 2.791 minutes

[0302] MS m / z 1137.1 [M+3H]+ / 3, 853.2 [M+4H]+ / 4; theoretical mass: 3406.8 Example 23

[0303] The compound of Example 23 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 15 and Preparation 5.

[0304] HPLC (Method 2) Rt = 2.983 minutes

[0305] MS m / z 1233.7 [M+2H]+ / 2, 822.7 [M+3H]+ / 3; theoretical mass: 2464.30 Example 24

[0306] The compound of Example 24 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 28 and Preparation 8.

[0307] HPLC (Method 2) Rt = 2.852 minutes

[0308] MS m / z 1287.6 [M+3H]+ / 3, 966.3 [M+4H]+ / 4; theoretical mass: 3861.5 Example 25 Petition 870260070784, dated 07 / 16 / 2026, page 86 / 130 76 / 84

[0309] The compound of Example 25 was prepared in a manner analogous to the procedure described in Example 1 using Preparation 26 and Preparation 8.

[0310] HPLC (Method 2) Rt = 2,990 minutes

[0311] MS m / z 993.0 [M+3H]+ / 3, 745.1 [M+4H]+ / 4; theoretical mass: 2976.6 Biological Tests Binding of compounds to purified LPS

[0312] The binding of compounds to LPS from Gram-negative bacteria is evaluated by measuring the displacement of a dansylated polymyxin B derivative from LPS in an established assay (J. Pharm. Sci. (2016), 105(2), 1006-10; Antimicrob Agents Chemother. (1986), 29(3), 495-550; Anal. Biochem (2011), 409(2), 273-283). Dansylated polymyxin B was titrated in an LPS solution and the fluorescence intensity was measured (exc 485 nm, at 535 nm). Titration of increasing concentrations of lead conjugates or polymyxin B in a solution containing LPS and dansylated polymyxin B corresponding to 95% probe occupancy resulted in decreased fluorescence emission due to displacement of dansylated polymyxin B towards the candidate.

[0313] The lipopolysaccharide (LPS) binding activities of synthetic peptide-derived polymyxin and the Examples contained herein are evaluated by measuring the displacement of Dansyl-Polymyxin B (DPMB) bound to E. coli LPS and P. aeruginosa LPS. Materials

[0314] Escherichia coli LPS was purchased from Sigma Aldrich, cat#L3024. Pseudomonas aeruginosa LPS was purchased from Sigma Aldrich, cat#L9143. Polymyxin B sulfate (PMB_std) was purchased from Alfa Aesar, cat#J63074. Polymyxin B nonapeptide hydrochloride (PMB_nona) was purchased from Sigma Aldrich, cat#P2076. Petition 870260070784, dated 07 / 16 / 2026, p. 87 / 130 77 / 84 Nuclease-free water was purchased from Qiagen, cat#129114. Test Protocol

[0315] Bacterial LPS was prepared to 20 μg / ml in nuclease-free water. DPMB was made to 4 μM in nuclease-free water. Bacterial LPS at 20 μg / ml (40 μg) or a negative water control (40 μg) was equilibrated with DPMB at 4 μm (20 μg) by holding for 5 minutes at room temperature with stirring (450 rpm) in a 96-well black solid plate. Titrations of the test compounds at 4x the final assay concentration (20 μg) were added to the LPS and DPMB, and the assay plate was held for 10 minutes at room temperature with stirring (450 rpm). Fluorescence intensity was captured on an Envision 2102 multi-label plate reader (Em340, Ex485). The compound from Example 1 was tested in the aforementioned binding assay, and the results are shown in Figures 1 and 2. Antibody recruitment assay by flow cytometry using anti-alpha-galactosyl IgM antibody

[0316] Flow cytometry was used to demonstrate the binding of L (as a cationic antimicrobial peptide) to E. coli and F (as the carbohydrate molecule capable of binding to a human anti-alpha-galactosyl antibody). A secondary FITC-labeled anti-human IgM antibody was used to detect the binding of anti-alpha-galactosyl to the compound. Method 1

[0317] The assays were performed in 96-well U-bottom polystyrene plates (Costar). The 96-well plates were pre-blocked with casein blocking buffer (Thermo Fisher 37528) and then washed three times with (HBSS+ / +) (Life Technologies 14025-050) before the assay. E. coli K12 (Public Health England, NCTC 10538) were cultured in LB broth (Fisher BP1426-500) to the late exponential phase. Subsequently, the bacteria were centrifuged. Petition 870260070784, dated 07 / 16 / 2026, page 88 / 130 78 / 84 at 10,000 rpm for 5 minutes and resuspended in HBSS+ / + at a bacterial density of 2*109 CFU / mL. Baclight red bacterial stain (ThermoFisher B35001) was added to the bacteria at a final concentration of 1 μM and incubated at room temperature for 10 min. The bacteria were centrifuged (10,000 rpm, 5 minutes) and resuspended in HBSS+ / + at a concentration of 2*109 CFU / mL. 1 x 108 CFU were then incubated with 20 μM of Examples 2 to 14 (see Table 1) or buffer alone, at room temperature, shaking at 450 rpm for 1 hour. The bacteria were washed with 3 x 200 μL of HBSS+ / + (centrifuged at 4,000 rpm for 5 minutes) before adding 50 μL of human IgM M86 anti-alpha galactosyl antibody (Absolute Antibody Ab00532) at 25 μg / mL in HBSS+ / +. The plate was incubated at room temperature for 1 hour, shaking at 450 rpm. The bacteria were washed with 3 x 200 μL of HBSS+ / + (centrifuged for 4 minutes).The bacteria were incubated at room temperature for 1 hour, agitated at 450 rpm (5 minutes), before adding 100 μL of anti-human IgMFITC antibody (Biolegend 314506) at a 1:10 dilution in HBSS+ / + and incubated at room temperature for 1 hour, shaking at 450 rpm. After a final wash of 3 x 200 μL of HBSS+ / +, the bacteria were resuspended in 200 μL of HBSS+ / + and evaluated on an FC500 (Beckman Coulter). Live bacteria were infected in the FL-4 channel, and the median fluorescent shift was recorded in the FL-1 channel. Data from all samples were analyzed using the Kaluza software package (Beckman Coulter). The experiment was repeated twice.

[0318] Table 1 demonstrates the capture of anti-alpha galactosyl IgM antibodies on the surface of bacteria using the flow cytometry assay described above. The fold shift over the background was calculated by dividing the Median Fluorescence Intensity obtained in the presence of 20 μM of the Examples by the Median Fluorescence Intensity obtained in the absence of the Examples. The shift in fluorescence intensity (FITC) occurs due to the binding event at each end of the molecule. Petition 870260070784, dated 07 / 16 / 2026, pp. 89 / 130 79 / 84 Table 1 Example N2: Recruitment of anti-alpha galactosyl IgM at 20 μM (Median fold shift over vehicle) Number of Tests (n) 1 3 n = 2 2 5 n = 1 3 7 n = 2 4 14 n = 2 5 17 n = 2 6 24 n = 2 7 28 n = 2 8 10 n = 2 9 21 n = 4 10 2 n = 2 14 1 n = 2 13 2 n = 2 11 1 n = 2 12 1 n = 2 Method 2

[0319] The assays were performed in 96-well U-bottom polystyrene plates (Costar). K12 E. coli (Public Health England, NCTC 10538) were cultured in LB broth (Fisher BP1426-500) to the late exponential phase. Subsequently, the bacteria were washed once with HBSS+ / + by centrifuging at 10,000 rpm for 5 minutes and resuspended in HBSS+ / +. The bacteria were centrifuged at 10,000 rpm for 5 minutes and resuspended in HBSS+ / + at a bacterial density of 2*109 CFU / mL. 1 x 10⁸ CFU were then incubated with 20 μM of Examples 15 to 25 (see Table 2) or buffer alone, at room temperature, shaking at 450 rpm for 1 hour. The bacteria were washed with 3 x 200 μL of HBSS+ / + (centrifuged at 4,000 rpm, 5 minutes) before adding 50 μL of human anti-alpha galactosyl IgM M86 antibody (Absolute Antibody Ab00532) at 25 μg / mL in HBSS+ / +. The plate was incubated at room temperature for 1 hour, shaking at 450 rpm.The bacteria were washed with 3 x 200 μL of HBSS+ / + (centrifuged at 4,000 rpm for 5 minutes) before adding 100 μL of anti-human IgM-FITC antibody (Biolegend 314506) at a 1:10 ratio. Petition 870260070784, dated 07 / 16 / 2026, pp. 90-130 80 / 84 dilution in HBSS+ / + and incubated at room temperature for 1 hour, shaking at 450 rpm. After a final wash of 3 x 200 μL of HBSS+ / +, the bacteria were resuspended in 200 μL of HBSS+ / + and evaluated in a Cytoflex (Beckman Coulter). 50,000 bacterial counts were collected. The median fluorescent shift was recorded in the FITC-A channel. Data from all samples were analyzed using the Kaluza software package (Beckman Coulter). The experiment was repeated twice.

[0320] Table 2 demonstrates the capture of anti-alpha galactosyl IgM antibodies to the surface of bacteria using the flow cytometry assay described above. The fold shift over the background was calculated by dividing the Median Fluorescence Intensity obtained in the presence of 20 μM of the Examples by the Median Fluorescence Intensity obtained in the absence of the Examples. The shift in fluorescence intensity (FITC) occurs due to the binding event at each end of the molecule. Table 2 Example N2: Recruitment of anti-alpha-galactosil IgM at 20 μM (Median fold displacement over vehicle) Number of Tests (n) 15 248 n = 4 16 70 n = 2 17 213 n = 2 18 65 n = 2 19 109 n = 2 20 145 n = 2 21 158 n = 2 22 149 n = 2 23 28 n = 2 24 269 n = 4 25 104 n = 4 Antibody recruitment assay by flow cytometry using antibody IgG anti-alpha-galactosyl

[0321] Flow cytometry was used to demonstrate the binding of L (as a cationic antimicrobial peptide) to E. coli and F (as the carbohydrate molecule Petition 870260070784, dated 07 / 16 / 2026, pp. 91 / 130 81 / 84 capable of binding to a human anti-alpha-galactosyl antibody). A secondary FITC-labeled anti-human IgG antibody was used to detect alpha-galactosyl binding to the compound.

[0322] The assays were performed in 96-well U-bottom polystyrene plates (Costar). The 96-well plates were pre-blocked with casein blocking buffer (Thermo Fisher 37528) and then washed three times with (HBSS+ / +) (Life Technologies 14025-050) before the assay. E. coli K12 (Public Health England, NCTC 10538) were cultured in LB broth (Fisher BP1426-500) to the late exponential phase. Subsequently, the bacteria were centrifuged at 10,000 rpm for 5 minutes and re-placed in HBSS+ / + suspension at a bacterial density of 2*109 CFU / mL. Baclight red bacterial stain (ThermoFisher B35001) was added to the bacteria at a final concentration of 1 μM and incubated at room temperature for 10 min. The bacteria were centrifuged (10,000 rpm, 5 minutes) and resuspended in HBSS+ / + at a concentration of 2*109 CFU / mL.1 x 10⁸ CFU were then incubated with 20 μM of Examples 1 to 10 (see Table 3) or buffer alone, at room temperature, shaking at 450 rpm for 1 hour. The bacteria were washed with 3 x 200 μL of HBSS+ / + (centrifuged at 4,000 rpm, 5 minutes) before adding 50 μL of anti-alpha galactosyl IgG antibody. (Anti-alpha galactosyl antibody was purified from human IVIG (Gammagard) by affinity purification using an alpha-galactosyl-TEM (Human Serum Albumin) sepharose column by Rockland Immunochemicals Inc.) at 42 μg / mL in HBSS+ / +. The plate was incubated at room temperature for 1 hour shaking at 450 rpm. The bacteria were washed with 3 x 200 μL of HBSS+ / + (centrifuged at 4,000 rpm for 5 minutes) before adding 100 μL of anti-human IgG-FITC antibody (Biolegend 409310) at a 1:20 dilution in HBSS+ / + and incubated at room temperature for 1 hour, shaking at 450 rpm. After a final wash with 3 x 200 μL of HBSS+ / +, the bacteria were... Petition 870260070784, dated 07 / 16 / 2026, pp. 92 / 130 82 / 84 bacteria were resuspended in 200 μL of HBSS+ / + and evaluated on an FC500 (Beckman Coulter). The bacteria were infected live in the FL-4 channel and the median fluorescent shift was recorded in the FL-1 channel. Data from all samples were analyzed using the Kaluza software package (Beckman Coulter). The experiment was repeated twice.

[0323] Table 3 demonstrates the capture of anti-alpha galactosyl IgG antibodies on the surface of bacteria using the flow cytometry assay described above. The fold shift over the background was calculated by dividing the Median Fluorescence Intensity obtained in the presence of 20 μM of the Examples by the Median Fluorescence Intensity obtained in the absence of the Examples. The shift in fluorescence intensity (FITC) occurs due to the binding event at each end of the molecule. Table 3 Example N2 Anti-alpha-galactosyl IgG recruitment at 20 μM (Median fold shift over vehicle) Number of Tests (n) 1 1 n = 1 2 2 n = 1 3 3 n = 2 4 8 n = 2 5 6 n = 2 6 7 n = 2 7 6 n = 2 8 3 n = 2 9 5 n = 2 10 1 n = 2 Complement deposition assay by flow cytometry

[0324] The assays were performed in 96-well U-bottom polystyrene plates (Costar). K1:O18ac:H7 E. coli (ATCC 700973) were cultured in LB broth (Fisher BP1426-500) to the late exponential phase. Subsequently, the bacteria were centrifuged at 10,000 rpm for 5 minutes and resuspended in PBS (Sigma D8537-500 mL). The bacteria were centrifuged (10,000 Petition 870260070784, dated 07 / 16 / 2026, pp. 93 / 130 The bacteria were centrifuged at 83 / 84 rpm for 5 minutes and resuspended in PBS with 1% BSA (Sigma A215350G) at a concentration of 2 x 10⁹ CFU / mL. One x 10⁸ CFU sample was then incubated with 20 μM and / or 10 μM of Examples 4 to 7, 9, and 15 to 25 (see Table 4 and Figure 3) or buffer alone at 4 °C for 45 min. The bacteria were washed with 1 x 200 μL of HBSS+ / + (centrifuged at 4,000 rpm for 5 minutes) before adding 100 μL of human serum (Innovate Research IPLA-CSER) in PBS + 1% BSA to a final serum concentration of 25%. The bacteria were incubated at 37 °C for 20 min. 100 μL of ice-cold PBS were added to each well. The plate was centrifuged at 4,000 rpm for 5 minutes at 4 °C and the supernatant discarded. The bacteria were washed twice more with 200 μL of HBSS+ / + (centrifuged at 4,000 rpm for 5 minutes) before adding 100 μL of anti-human C3b / C3bi-PE antibody (Biolegend 846104) at a 1:50 dilution in PBS + 1% BSA and incubated at 4 °C for 45 min.After a final wash of 3 x 200 μL of HBSS+ / +, the bacteria were resuspended in 200 μL of HBSS+ / + and evaluated in a Cytoflex (Beckman Coulter). The Median Fluorescence Intensity was recorded in the PE channel. Data from all samples were analyzed using the Kaluza software package (Beckman Coulter).

[0325] Table 4 demonstrates the deposition of C3b from human serum onto the surface of bacteria using the flow cytometry assay described above. The fold shift over the background was calculated by dividing the Median Fluorescence Intensity obtained in the presence of 20 μM of the Examples by the Median Fluorescence Intensity obtained in the absence of the Examples. The shift in fluorescence intensity (SI) occurs due to the recruitment of C3b to the surface of the bacteria. Table 4 Example: C3b recruitment at 10 μM (Median fold displacement over the vehicle) Number of Tests (n) 4 95 n = 4 5 17 n = 2 6 170 n = 4 Petition 870260070784, dated 07 / 16 / 2026, pp. 94 / 130 84 / 84 7 4 n =2 9 44 n =4 15 6 n = 2 16 47 n = 4 17 93 n = 4 18 49 n = 4 19 59 n = 4 20 14 n = 4 21 17 n = 4 22 16 n = 4 23 5 n = 2 24 105 n = 2 25 113 n = 2

[0326] Figure 3 demonstrates the recruitment of C3b from human serum to the surface of E. coli in the presence of Example 4 (Figure 3A), Example 5 (Figure 3B), Example 6 (Figure 3C), Example 7 (Figure 3D), and Example 9 (Figure 3E) at 20 μM. The shift in fluorescence intensity (PE) occurs due to the recruitment of C3b from serum to the surface of bacteria. Petition 870260070784, dated 07 / 16 / 2026, pp. 95 / 130

Claims

1 / 12 CLAIMS 1. Compound CHARACTERIZED in that it has formula (I) or a pharmaceutically acceptable salt thereof: wherein: L represents a Polymyxin B derivative selected from one of the following structures: H2N-[L-OctylGly]-Dab-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* (SEQ ID NO: 1) Nonanamida-Dab(NH2)-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* (SEQ ID NO: 2) H2N-Dab-Thr-Dab-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* (SEQ ID NO: 3) Petition 870260070784, of 16 / 07 / 2026, p. 96 / 130 2 / 12 H2N-[L-OctylGly]-Dab-Thr-Dab(NH2)-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* (SEQ ID NO: 4) Nonanamida-Dab-Thr-Dab(NH2)-Dab*-Dab-[D-Phe]-Leu-Dab-Dab-Thr* where Xi refers to the attachment point to the Xi group; Si represents a linkage or spacer selected from a (CH2)a- or -(CH2)b-(CH2-CH2-O)c-(CH2)d- group, wherein one to five of said -CH2 groups may optionally be replaced by a -C(O)NH- or -NHC(O)- group; a represents an integer selected from 1 to 40;b represents an integer selected from 0 to 25; c represents an integer selected from 1 to 20; d represents an integer selected from 1 to 15; S2 represents a spacer selected from a -(CH2)e- or -(CH2)f(CH2-CH2-O)g-(CH2)h- group, where one to three of the so-called -CH2- groups may optionally be replaced by a -C(O)NH- or -NHC(O)- group; e represents an integer selected from 1 to 20; f represents an integer selected from 1 to 10; g represents an integer selected from 1 to 15; h represents an integer selected from 1 to 5; Petition 870260070784, 16 / 07 / 2026, p. 97 / 130 3 / 12 Xi represents a linkage or -C(O)-; Yi and Y2 independently represent a linkage, -O-, -S-, -NH-, C(O)-, -NHC(O)-, or -C(O)NH- group; F is selected from galactosyl-alpha-1,3-galactosyl-beta-1,4-N-acetylglucosamine, alpha1-3-galactobiose, alpha1-3-beta1-4-galactotriose, or gallylipentasaccharide; m represents an integer selected from 1 to 5;and Cy represents phenyl, biphenyl or triphenyl, such that when Cy represents biphenyl or triphenyl, said -Y1-S1-X1-L group may be present in any of said phenyl rings and said [F-S2-Y2]m- group or groups may be present in any of said phenyl rings.

2. Compound according to claim 1, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that S1 represents a linkage or a spacer selected from: - (CH2)a-, wherein one or five of said -CH2- groups are optionally replaced by a -C(O)NH- group (such as -(CH2)5-CONH-(CH2)5 or -(CH2)5CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-CONH-(CH2)5-); or - (CH2)b-(CH2-CH2-O)c-(CH2)d-, wherein two of said -CH2- groups are optionally replaced by a -C(O)NH- group (such as -(CH2CH2O)8-(CH2)2-, (CH2CH2O)8-(CH2)2-CONH-(CH2)5-CONH-(CH2)5- or -(CH2)5-CONH-(CH2)5-CONH(CH2)5-CONH-(CH2)5-CONH-(CH2CH2O)8-(CH2)2-); or S1 represents a spacer selected from: - (CH2)a-, wherein one of said -CH2- groups is replaced by a C(O)NH- group (such as -(CH2)5-CONH-(CH2)5); or - (CH2)b-(CH2-CH2-O)c-(CH2)d- (such as -(CH2CH2O)8-(CH2)2-);or S1 represents a spacer selected from: -(CH2)a-, wherein one of said -CH2- groups is replaced by a -C(O)NH- group (such as -(CH2)5-CONH-(CH2)5).

3. Compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that: a represents an integer selected from: 1 to 35; or 10 to 35; or 11 or 35; or 11; and / or b represents an integer selected from 0 to 24; or 0 or 24; or 0; and / or c represents an integer selected from 1 to 15; or 1 to 10; or 8; and / or d represents an integer selected from 1 to 3; or 1 or 2; or 2; and / or Yi represents -C(O)NH- or -C(O)-; or -C(O)NH-.

4. A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that S2 represents a spacer selected from: -(CH2)e-, wherein one or three of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as -(CH2)3-NHCO-CH2- or -(CH2)3-NHCO(CH2)5-NHCO-(CH2)5-NHCO-CH2-); or -(CH2)f-(CH2-CH2-O)g-(CH2)h-, wherein two of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as -(CH2)3-NHCO(CH2CH2O)4-(CH2)2-NHCO-CH2-); or S2 represents a selected spacer of -(CH2)e-, wherein three of said -CH2- groups are optionally replaced by an -NHC(O)- group (such as (CH2)3-NHCO-(CH2)5-NHCO-(CH2)5-NHCO-CH2-).

5. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that: e represents an integer selected from 1 to 17; or 5 to 17; or 5 or 17; or 17; and / or f represents an integer selected from 1 to 8; or 2 to 6; or 4; and / or g represents an integer selected from 1 to 5; or 1 to 4; or 4; and / or h represents an integer selected from 1 to 4; or 4; and / or X1 represents -C(O)-; and / or Y2 represents -O-; and / or m represents an integer selected from 1 to 4; or 1, 2 or 3; either 1 or 2; or 1.

6. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that Cy stands for phenyl or biphenyl.

7. A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that F has a structure as shown in the following formula: ho^oh HOA^-Â Ol^OH 0¾ 0 OH H° OH 0 O. s2 NHAc 2 where S2 refers to the point of attachment to the S2 group.

8. Compound, according to claim 1, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that it is selected from any one of 1 to 10, 13 and 15 to 25: Petition 870260070784, dated 07 / 16 / 2026, p. 100 / 130 6 / 12 Petition 870260070784, dated 07 / 16 / 2026, p. 101 / 130 7 / 12 Petition 870260070784, dated 07 / 16 / 2026, p. 102 / 130 8 / 12 Petition 870260070784, dated 07 / 16 / 2026, p. 103 / 130 9 / 12 ho.-oh HO O NHAc Petition 870260070784, dated 16 / 07 / 2026, p. 104 / 130 10 / 12 9. Pharmaceutical composition CHARACTERIZED in that it comprises a compound, as defined in any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof.

10. A compound, according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that it is for use in therapy.

11. A compound, according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, CHARACTERIZED in that it is for use in the treatment of a disease or disorder mediated and / or caused by an infectious agent.

12. Process for preparing a compound of formula (I), as defined in claim 1, CHARACTERIZED in that it comprises: (a) preparing a compound of formula (I), wherein Yi represents -CONH- (i.e., a compound of formula (IA)), by reacting a compound of formula (II) with a compound of formula (III) followed by a suitable deprotection step: wherein S2, Y2, m, Cy, Si, Xi, L and F are as defined in claim 1 and PG is a suitable peptide protecting group, such as Dde; or (b) preparing a compound of formula (I), wherein Y1 represents -CONH- and X1 represents -C(O)- (i.e., a compound of formula (IB)), by reacting a compound of formula (IV) with a compound of formula (V) followed by a suitable deprotection step: Petition 870260070784, dated 16 / 07 / 2026, p.105 / 130 11 / 12 F-S2-Y2 O ILJPG (IV) (i), (ii) F-S2-Y2 O xSi Λ Cy-PN TO (V) (IB) where S2, Y2, m, Cy, Si, L and F are as defined in claim 1 and PG is a suitable peptide protecting group, such as Dde; or (c) prepare a compound of formula (I) by reacting a compound of formula (VI) with a compound of formula (VII) followed by a suitable deprotection step: (I) (vii) wherein S2, Y2, m, Cy, S1, X1, L and F are as defined in claim 1, PG is a suitable peptide protecting group, such as Dde; or (d) prepare a compound of formula (I) by reacting a compound of formula (XII) with a compound of formula (XIII) followed by a suitable deprotection step, where Y1 represents a CONH group: q H2N-S1B Xr[L]pc _ JQ rn H (XIII) _ v .1A 2 --~ [FS^Y^-FCy+YrSr^-L [F-s2-Y2im—çcy) H (')'() vjy (xii) (i) where S2, Y2, m, Cy, X1, L and F are as defined herein above, S1A and S1B together form an S1 group and PG is a suitable peptide protecting group, as is Dde.

13. Use of a compound of formula (I), as defined in any of claims 1 to 8, or of a pharmaceutically acceptable salt thereof, CHARACTERIZED in that it is for the preparation of a medicament for the treatment of a disease or disorder mediated and / or caused by an infectious agent. Petition 870260070784, dated 16 / 07 / 2026, p. 106 / 130 12 / 12

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