Novel reversible fluorescent probes for CB1

Abstract

The present invention provides reversible fluorescent probes for cannabinoid receptor 1 ("CB1") having the general formula (I) wherein A and B are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.

Description

[0001] Novel reversible fluorescent probes for CB1 Field of the Invention The present invention relates to organic compounds useful as reversible fluorescent probes for the cannabinoid receptor type 1 (CB1R). The probes are achieved by a novel, convergent synthetic blueprint from a central reactive motif. Background of the Invention Cannabinoid receptor type 1 (CB1R) is one of the central elements of the endocannabinoid system regulating a variety of signaling cascades. Extensive efforts on CB1R have validated its essential roles in physiology such as appetite regulation, pain perception, memory formation and thermoregulation. Yet, there is a surprising lack of clear understanding of its cellular signaling, distribution and expression dynamics. CB1R detection by visualization in real-time is therefore crucial for addressing these open questions in cannabinoid research. Dysregulation of the endocannabinoid system, specifically of signaling pathways encompassed by cannabinoid receptor type 1 (CB1R), has been implicated in a range of diseases including tissue injury, neurodegenerative conditions and inflammation. CB1R is a class a GPCR (G-protein coupled receptor), which is predominantly expressed in cells associated with the nervous system and therefore has become an attractive therapeutic target for a vast variety of pathological conditions such as neurodegenerative diseases, inflammatory and metabolic disorders. In spite of the therapeutic potential, no CB1R-selective drug has made its way to market permanently. This is in part attributed to the complexity of CB1R signaling pathways at the cellular level and a lack of precise understanding of its function as well as its expression and localization dynamics. For translation of novel promising CB1R drug candidates emerging from pre- clinical studies to clinical trials, visualization tools for spatio-temporally resolved CB1R pharmacological characterization are urgently required. Herein, we designed a matched agonist and inverse agonist fluoroprobe pair based on a common drug-derived chemotype to selectively address and visualize both the active and inactive states of CB1R. We have established a simple synthetic strategy to give access to a series of CB1R-selective fluoroprobes attached to various dyes (e.g. cell-permeable and cell-impermeable) suitable for diverse biological settings such as in vitro, ex vivo and in vivo. Pharmacological characterization alongside with extensive cross-validation (FACS and confocal microscopy) indicated the selectivity, specificity and imageability of our probes. The application of these diverse fluoroprobes in not limited to visualization of both the membrane and internal receptor pools, but also monitoring the expression level, dimerization, target engagement, pharmacokinetic and dynamics (e.g. receptor internalization and trafficking) in-real time. Moreover, they can be used as kinetic tracer to study the receptor-ligand engagement as an alternative for radioligand binding assay. Detailed Description of the Invention Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein, unless incompatible therewith. All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and / or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. The invention is not restricted to the details of any foregoing embodiments. The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel one, or any novel combination, of the steps of any method or process so disclosed. The term “alkylene”, alone or in combination, denotes a linear saturated divalent hydrocarbon group of 1 to 7 carbon atoms or a divalent branched saturated divalent hydrocarbon group of 3 to 7 carbon atoms. Examples of alkylene groups include methylene, ethylene, propylene, 2-methylpropylene, butylene, 2-ethylbutylene, pentylene, hexylene. The term “alkenylene”, alone or in combination, denotes a linear divalent hydrocarbon chain of 2 to 7 carbon atoms or a branched divalent hydrocarbon chain of 3 to 7 carbon atoms with at least one double bond. Exemplary alkenylene include ethenylene, 2,2- dimethylethenylene, propenylene, 2-methylpropenylene, butenylene, and pentenylene. The term “alkynylene” alone or in combination, denotes a linear divalent hydrocarbon chain of 2-6 carbon atoms or a branched divalent hydrocarbon chain of 3-6 carbon atoms with at least one triple bond. Exemplary alkynylene include ethynylene, 2,2- dimethylethynylene, propynylene, 2-methylpropynylene, butynylene, and pentynylene. The term “heteroalkylene”, alone or in combination, denotes an “alkylene” group comprising 1, 2, or 3 ring heteroatoms selected from N, O and S, the remainder being hydrocarbon. The term “heteroalkenylene”, alone or in combination, denotes an “alkenylene” group comprising 1, 2, or 3 ring heteroatoms selected from N, O and S, the remainder being hydrocarbon. The term “heteroalkynylene”, alone or in combination, denotes an “alkynylene” group comprising 1, 2, or 3 ring heteroatoms selected from N, O and S, the remainder being hydrocarbon. The term “alkyl”, alone or in combination, refers to a mono- or multivalent, e.g., a mono- or bivalent, linear or branched saturated hydrocarbon group of 1 to 12 carbon atoms. In some preferred embodiments, the alkyl group contains 1 to 6 carbon atoms, e.g., 1, 2, 3, 4, 5, or 6 carbon atoms (“C1-C6-alkyl”). In other embodiments, the alkyl group contains 1 to 3 carbon atoms, e.g., 1, 2 or 3 carbon atoms. Some non-limiting examples of alkyl include methyl, ethyl, propyl, 2-propyl (isopropyl), n-butyl, iso-butyl, sec-butyl, tert-butyl, and 2,2- dimethylpropyl. A particularly preferred, yet non-limiting example of alkyl is methyl. The term "pharmaceutically acceptable salt" refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. The salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, in particular hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcystein and the like. In addition, these salts may be prepared by addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium salts and the like. Salts derived from organic bases include, but are not limited to salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N- ethylpiperidine, piperidine, polyimine resins and the like. Particular pharmaceutically acceptable salts of compounds of formula (I) are hydrochloride and trifluoroacetate salts, more particularly trifluoroacetate salts. The term “solvate” denotes crystal forms having either stoichiometric or nonstoichiometric amounts of a solvent incorporated in the crystal lattice. If the incorporated solvent is water, the solvate formed is a hydrate. When the incorporated solvent is alcohol, the solvate formed is an alcoholate. The term “protective group” (PG) denotes the group which selectively blocks a reactive site in a multifunctional compound such that a chemical reaction can be carried out selectively at another unprotected reactive site in the meaning conventionally associated with it in synthetic chemistry. Protective groups can be removed at the appropriate point. Exemplary protective groups are amino-protective groups, carboxy-protective groups or hydroxy-protective groups. Particular protective groups are the tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc) and benzyl (Bn). Further particular protective groups are the tert-butoxycarbonyl (Boc) and the fluorenylmethoxycarbonyl (Fmoc). More particular protective group is the tert- butoxycarbonyl (Boc). Exemplary protective groups and their application in organic synthesis are described, for example, in “Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M. Wutts, 5th Ed., 2014, John Wiley & Sons, N.Y. The term “equilibrium and kinetic binding data” is to be understood in broad terms as generally known to the person skilled in the art. Kinetic binding describes the dynamic binding interaction between two molecules, typically expressed as ka(the rate of association), kd (rate of disassociation) and KD (equilibrium dissociation constant, also 'affinity'). ka(also termed kon) describes the rate at which the studied molecules form a complex. The binding constant, or affinity constant / association constant, is a special case of the equilibrium constant K, and is the inverse of the dissociation constant. It is associated with the binding and unbinding reaction of receptor (R) and ligand (L) molecules, which is formalized as: R + L ⇌ RL. The term “occupancy” is to be understood in broad term as generally known to the person skilled in the art and as described for instance in ”A Pharmacology Primer (Fourth Edition)”, Kenakin, Terry P. , ISBN 978-0-12-407663-1. The term “agonist” denotes a compound that enhances the activity of another compound or receptor site as defined e.g. in Goodman and Gilman's “The Pharmacological Basis of Therapeutics, 7th ed.” in page 35, Macmillan Publ. Company, Canada, 1985. A “full agonist” effects a full response whereas a “partial agonist” effects less than full activation even when occupying the total receptor population. An “inverse agonist” produces an effect opposite to that of an agonist, yet binds to the same receptor binding-site. The term “fluorescent label” or “fluorescent probe” denotes a molecule that is attached chemically to derivatives of fluorophores that selectively bind to a target protein, antibody or amino acid and aid in Its detection. The term “tautomer” refers to a constitutional isomer with the same molecular formula but different connectivity which can interconvert in a rapid equilibrium. The compounds of formula (I) can contain several asymmetric centers and can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, optically pure diastereoisomers, mixtures of diastereoisomers, diastereoisomeric racemates or mixtures of diastereoisomeric racemates. According to the Cahn-Ingold-Prelog Convention, the asymmetric carbon atom can be of the "R" or "S" configuration. The abbreviations “CB1” and “CB1R” refer to the cannabinoid receptor 1. The invention thus relates to: SPECIFICALLY NUMBERED EMBODIMENTS 1. A compound of formula (I) or a pharmaceutically acceptable salt, tautomer or solvate thereof; formula (a) RaLa wherein a double line indicates the point of attachment to the rest of formula (I); and wherein Laand Lbare each independently selected from: 1-30 membered alkylene, 1-30 membered heteroalkylene, 2-30 membered alkenylene, 2- 30 membered heteroalkenylene, 2-30 membered alkynylene, and 2-30 membered heteroalkynylene; each of which is optionally substituted, wherein the optionally substituted 1-30 membered heteroalkylene, 2-30 membered heteroalkenylene, and 2-30 membered heteroalkynylene each comprise 1-15 heteroatoms selected from the group consisting of N, S, O, NR5, S(O), SO2and C(O), wherein R5is H or C1-6 alkyl; preferably, heteroatoms are selected from the group consisting of N, S, O, NR5and C(O); Raand Rbare each independently a fluorescent label or one half of a biotin or biotin derivative binding pair, or a protecting group; and wherein B is selected from: formula (i) are independently a halogen atom; R4is H, or C1-6 alkyl R6is H or R4and R6taken together with the groups to which they are attached form a C5-8 membered ring; X is CH or N; or formula (ii) R is a halogen atom; X is CH or N; or formula (iii) independently a trihalomethyl group; R10is a C3-6heterocycle; X is CR11or N R11is H or C1-6alkyl; or formula (iv) R12 R12is a halogen atom; R13is a C3-6cycloalkyl or (CH2)0-3-O-(CH2)0-3-H X and Y are each independently CH or N; wherein at least one of X or Y is N. 1a. A compound according to embodiment 1, wherein the compound of formula (I) is a compound of formula (Ia) . according to embodiment 1, wherein the compound of formula (I) is a compound of formula (Ib) . according to embodiments 1, 1a or 1b, wherein B is formula (i), preferably B is: . 3. A compound according to embodiments 1, 1a or 1b, wherein B is formula (ii), preferably B is: . 4. A compound according to embodiments 1, 1a or 1b, wherein B is formula (iii), preferably B is: . 5. A compound according to embodiments 1, 1a or 1b, wherein B is formula (iv), preferably B is: . 6. A compound according to embodiments 1, 1a or 1b, wherein B is: . 7. A compound according to embodiments 1, 1a or 1b, wherein B is: 8. A compound according to embodiments 1, 1a or 1b, wherein B is: . 9. A compound according to any of the preceding embodiments, wherein Raand Rbare each independently a fluorescent label or one half of a biotin or biotin derivative binding pair. 10. A compound according to any of the preceding embodiments, wherein any Laand / or Lbis independently selected from: any of the preceding embodiments, wherein Raand Rbare each independently

[0002] , each n is independently an integer selected from 1, 2, 3, 4, 5, 6, and 7; a wavy line indicates the point of attachment to Raor Rb; and an asterisk indicates the point of attachment of Laor Lbto rest of the fragment A. 11. A compound according to any of the preceding embodiments, wherein any Laand / or Lbis independently selected from: * 12. A compound according to any of the preceding embodiments wherein A is formula (a) and Lais: * each n is independently an integer selected from 1, 2, 3, 4, 5, 6, and 7; a wavy line indicates the point of attachment to Ra; and an asterisk indicates the point of attachment of Lato rest of the fragment A; preferably n is 3. 13. A compound according to any of the preceding embodiments, wherein A is formula (b) and Lbis: each n is independently an integer selected from 1, 2, 3, 4, 5, 6, and 7; a wavy line indicates the point of attachment to Rb; and an asterisk indicates the point of attachment of Lbto rest of the fragment A; preferably n is 2. 14. A compound according to any one of embodiments 10 to 13, wherein n is independently an integer selected from 1, 2, 3 and 4. 15. A compound according to embodiment 14, wherein n is independently an integer selected from 2 or 3; preferably, n is 2. 16. A compound according to any one of embodiments 1 to 12 and 14 to 15, wherein A is formula (a). 17. A compound according to any one of embodiments 1 to 11 and 13 to 15, wherein A is formula (b). 18. A compound according to any one of the preceding embodiments, wherein any Raand / or Rbare independently selected from the following structures or their tautomers: one half of a biotin or biotin derivative binding pair or , , , ,

[0003] , , , , ,

[0004] , whe 19. A compound according to any one of the preceding embodiments wherein any of Raand / or Rbare each independently selected from the following structures or their tautomers: one half of a biotin or biotin derivative binding pair, , , ; to thea b L or L ; preferably wherein any of Raand / or Rbare each independently selected from the following structures or their tautomers:

[0005] ,b; more preferably wherein any of Raand / or Rbare each independently selected from:

[0006] ; A compound according to any of the preceding embodiments, selected from: tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamidex; tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan- 16-yl)carbamate; tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide; tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate; 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide; Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate; Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate; Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate; Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate; Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate; Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate; 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13- ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan- 16-yl)carbamate; tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide; tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide; Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate; Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate; Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate; Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate; Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate; Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate; 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate; 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro- 1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan- 16-yl)carbamate; tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide; tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate; 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide; tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate; 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13- ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof. A compound according to embodiment 20, selected from: Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate; Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate; Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate; Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate; Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate; Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; and Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; or a pharmaceutically acceptable salt, tautomer or solvate thereof. 28. A compound according to any one of embodiments 1, 1a, 1b, 2, 4-6, 9-22 and 25-27 which is an inverse agonist of cannabinoid receptor type 1 (CB1). 30. A compound according to any one of embodiments 1, 1a, 1b, 3, 5, 7, 9-21, 23 and 25-27 which is an agonist of cannabinoid receptor type 1 (CB1). 31. A compound according to any one of embodiments 1, 1a, 1b, 2, 8, 9-21, 24 and 25- 27 which is an antagonist of cannabinoid receptor type 1 (CB1). 32. A compound according to any one of embodiments 1 to 31, for use in a cannabinoid receptor type 1 (CB1) occupancy study. 35. A compound according to any one of embodiments 1 to 31, for use in diagnostic imaging of cannabinoid receptor type 1 (CB1) in a mammal. 36. A compound according to any one of embodiments 1 to 31, for use in generating cannabinoid receptor type 1 (CB1) equilibrium and kinetic binding data. 37. Use of a compound according to any one of embodiments 1 to 31, in diagnostic imaging of cannabinoid receptor type 1 (CB1) in a mammal. 38. Use of a compound according to any one of embodiments 1 to 31, in generating cannabinoid receptor type 1 (CB1) equilibrium and kinetic binding data. 39. A method of studying cannabinoid receptor type 1 (CB1) occupancy, comprising contacting CB1 with a compound according to any one of embodiments 1 to 31. 40. A method of diagnostic imaging of cannabinoid receptor type 1 (CB1) in a mammal, comprising contacting CB1 with a compound according to any one of embodiments1 to 31. 41. A method of diagnostic imaging of cannabinoid receptor type 1 (CB1) in biological tissue, cells or cell preparation of mammalian origin, comprising contacting CB1 with a compound according to any one of embodiments1 to 31. 42. A method of generating cannabinoid receptor type 1 (CB1) equilibrium and kinetic binding data, comprising contacting CB1 with a compound according to any one of embodiments 1 to 31. Processes of Manufacturing Processes of Manufacturing The invention further also relates to methods for manufacturing a compound according to the invention as described herein, for instance wherein the method comprises the steps of either sequence (1), (2) or (3): (1) (a) the reaction of a compound of formula (AC) solvent and a suitable acid; and (b) the reaction of the unprotected derivative of the compound of formula (AC) with a carboxylic acid or carboxylic ester of formula Ra-OH / OR or Ra-X in presence of a suitable solvent and a suitable base, and in case carboxylic acid or ester is applied, also in presence of a suitable coupling reagent, to yield a compound of formula (Ia) (a) the reaction of a compound of formula (BC) in presence of a suitable solvent and a suitable acid; and (b) the reaction of the unprotected derivative of the compound of formula (BC) with a carboxylic acid or carboxylic ester of formula Rb-OH / OR or Rb-X in presence of a suitable solvent and a suitable base, and in case carboxylic acid or ester is applied, also in presence of a suitable coupling reagent, to yield a compound of formula (Ib) (3) (a) the reaction of a compound of formula (BD) in presence of a suitable solvent and a suitable base; and (b) the reaction of the unprotected derivative of the compound of formula (BC) with a compound of formula (BX) suitable coupling reagent, a suitable solvent and a suitable base, to yield a compound of formula (Ib) ). wherein in the reactions above, B, La, Lb, Raand Rbare according to any one of the preceding embodiments, PG1is a suitable protecting group, such as for instance Boc, and X is a suitable leaving group such as for instance halogen, in particular fluoro and chloro; R can be for instance succinimidyl, pentafluorophenyl or sulfodichlorophenyl; in the reaction of step (1)(a) the acid can be for instance TFA or HCl; in the reaction of step (1)(a) the solvent can be for instance DCM, dioxane or hexafluoroisopropanol; in the reaction of step (1)(a) the temperature can be for instance set at between around 0 °C and 150 °C, in particular at between around 0 °C and 65 °C, and more particularly between around 0 °C and room temperature; in the reaction of step (1)(b) the base can be for instance Huenig’s base, trimethylamine, DIPEA, NMM, NaHCO3 or Cs2CO3 or a mixture thereof; in the reaction of step (1)(b) the solvent can be for instance N,N-dimethylformamide, DMA, DMSO, DCM, ACN, MeOH, 1,4-dioxane, ACN, MeOH, H2O or mixtures thereof; in the reaction of step (1)(b) the coupling reagent can be for instance N,N'-carbonyl- diimidazole (CDI), N,N'-dicyclohexylcarbodiimide (DCC), 1-(3- dimethylaminopropyl)- 3-ethylcarbodiimide hydrochloride (EDCI), 1-bis(dimethylamino)-methylene)-1H-1,2,3- triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU), O-benzotriazol-1-yl- N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) or O-benzotriazole-N,N,N',N'- tetramethyl-uronium-hexafluoro-phosphate (HBTU), in particular HATU; in the reaction of step (1)(b) conveniently the temperature is kept at between around 0 °C and 65 °C; in the reaction of step (2)(a) the acid can be for instance TFA or HCl; in the reaction of step (2)(a) the solvent can be for instance DCM, dioxane or hexafluoroisopropanol; in the reaction of step (2)(a) the temperature can be for instance set at between around 0 °C and 150 °C, in particular at between around 0 °C and 65 °C, and more particularly between around 0 °C and room temperature; in the reaction of step (2)(b) the base can be for instance Huenig’s base, trimethylamine, DIPEA, NMM, NaHCO3or Cs2CO3or a mixture thereof; in the reaction of step (2)(b) the solvent can be for instance N,N-dimethylformamide, DMA, DMSO, DCM, ACN, MeOH, 1,4-dioxane, ACN, MeOH, H2O or mixtures thereof; in the reaction of step (2)(b) the coupling reagent can be for instance N,N'-carbonyl- diimidazole (CDI), N,N'-dicyclohexylcarbodiimide (DCC), 1-(3- dimethylaminopropyl)- 3-ethylcarbodiimide hydrochloride (EDCI), 1-bis(dimethylamino)-methylene)-1H-1,2,3- triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU), O-benzotriazol-1-yl- N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) or O-benzotriazole-N,N,N',N'- tetramethyl-uronium-hexafluoro-phosphate (HBTU), in particular HATU; in the reaction of step (2)(b) conveniently the temperature is kept at between around 0 °C and 65 °C; in the reaction of step (3)(a) the base can be for instance a primary amine, such as for instance piperidine or the like; in the reaction of step (3)(a) the solvent can be for instance DMU, DMF, DCM or a mixture thereof; in the reaction of step (3)(a) the temperature can be for instance set at between around 0 °C and 100 °C, in particular at between around 0 °C and 65 °C, and more particularly between around 0 °C and room temperature; in the reaction of step (3)(b) the base can be for instance Huenig’s base, trimethylamine, DIPEA, NMM or a mixture thereof; in the reaction of step (3)(b) the solvent can be for instance N,N-dimethylformamide, DMA, DMSO, DCM, ACN, MeOH, 1,4-dioxane or a mixture thereof; in the reaction of step (3)(b) the coupling reagent can be for instance N,N'-carbonyl- diimidazole (CDI), N,N'-dicyclohexylcarbodiimide (DCC), 1-(3- dimethylaminopropyl)- 3-ethylcarbodiimide hydrochloride (EDCI), 1-bis(dimethylamino)-methylene)-1H-1,2,3- triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU), O-benzotriazol-1-yl- N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) or O-benzotriazole-N,N,N',N'- tetramethyl-uronium-hexafluoro-phosphate (HBTU), in particular HATU; in the reaction of step (3)(b) conveniently the temperature is kept at between 0 °C and 50 °C, in particular at between around 0 °C and room temperature. The preparation of compounds of formula (I) of the present invention may be carried out in sequential or convergent synthetic routes. Syntheses of the invention are shown in the following general schemes. The skills required for carrying out the reaction and purification of the resulting products are known to those persons skilled in the art. The substituents and indices used in the following description of the processes have the significance given herein, unless indicated to the contrary. If one of the starting materials, intermediates or compounds of formula (I) contain one or more functional groups which are not stable or are reactive under the reaction conditions of one or more reaction steps, appropriate protective groups (as described e.g., in “Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M. Wutts, 5th Ed., 2014, John Wiley & Sons, N.Y.) can be introduced before the critical step applying methods well known in the art. Such protective groups can be removed at a later stage of the synthesis using standard methods described in the literature. If starting materials or intermediates contain stereogenic centers, compounds of formula (I) can be obtained as mixtures of diastereomers or enantiomers, which can be separated by methods well known in the art e.g., chiral HPLC, chiral SFC or chiral crystallization. Racemic compounds can e.g., be separated into their antipodes via diastereomeric salts by crystallization with optically pure acids or by separation of the antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. It is equally possible to separate starting materials and intermediates containing stereogenic centers to afford diastereomerically / enantiomerically enriched starting materials and intermediates. Using such diastereomerically / enantiomerically enriched starting materials and intermediates in the synthesis of compounds of formula (I) will typically lead to the respective diastereomerically / enantiomerically enriched compounds of formula (I). A person skilled in the art will acknowledge that in the synthesis of compounds of formula (I) - insofar not desired otherwise - an “orthogonal protection group strategy” will be applied, allowing the cleavage of several protective groups one at a time each without affecting other protective groups in the molecule. The principle of orthogonal protection is well known in the art and has also been described in literature (e.g. Barany and R. B. Merrifield, J. Am. Chem. Soc.1977, 99, 7363; H. Waldmann et al., Angew. Chem. Int. Ed. Engl.1996, 35, 2056). A person skilled in the art will acknowledge that the sequence of reactions may be varied depending on reactivity and nature of the intermediates. In more detail, the compounds of formula (I) can be manufactured by the methods given below, by the methods given in the examples or by analogous methods. Appropriate reaction conditions for the individual reaction steps are known to a person skilled in the art. Also, for reaction conditions described in literature affecting the described reactions see for example: Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition, Richard C. Larock. John Wiley & Sons, New York, NY.1999). It was found convenient to carry out the reactions in the presence or absence of a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. The described reactions can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the described reactions in a temperature range between -78 °C to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 hours to several days will usually suffice to yield the described intermediates and compounds. The reaction sequence is not limited to the one displayed in the schemes, however, depending on the starting materials and their respective reactivity, the sequence of reaction steps can be freely altered. If starting materials or intermediates are not commercially available or their synthesis not described in literature, they can be prepared in analogy to existing procedures for close analogues or as outlined in the experimental section. The following abbreviations are used in the present text: ACN = acetonitrile, Boc = tert-butyloxycarbonyl, CAS = chemical abstract service; Cbz = benzyloxycarbonyl; CDI = N,N'-carbonyl-diimidazole; CsCO3 = cesium carbonate, DBU = 1,8-Diazabicyclo[5.4.0]undec-7-en, DCM = dichloromethane, DMA = dimethylacetamide; DMAP = 4-dimethylaminopyridine; DMF = N,N-dimethylformamide, DMSO = dimethylsulfoxide, DIPA = diisopropylamie, DIPEA = N,N- diisopropylethylamine (Huenig’s base), EDCI = N-(3-dimethylaminopropyl)-N′- ethylcarbodiimide hydrochloride, equiv. = equivalent, ESI = electrospray ionization, EtOAc = ethyl acetate, EtOH = ethanol, Fmoc = fluorenylmethoxycarbonyl; h = hour(s), H2O = water, HATU = 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium-3-oxide hexafluorophosphate, HCl = hydrogen chloride, HOAt = 1-hydroxy- 7-azabenzotriazole; HPLC = high performance liquid chromatography, KI = potassium iodide, LC = liquid chromatography, LDA = lithium diisopropyl amide, M = molarity, MeOH = methanol, mg = milligram, min = minute(s), mL = milliliter, µmol = mircomol(s),mmol = millimole(s), MS = mass spectrometry, m / z = mass by charge ratio, NBD = nitrobenzoxadiazole; NaHCO3= sodium hydrogen carbonate, NaOH = sodium hydroxide, Na2CO3 = sodium carbonate, Na2SO4 = sodium sulfate, n-BuLi = n- butyllithium, NEt3= triethylamine (TEA), NH4Cl = ammonium chloride, NMM = N- methyl morpholine, OAc = Acetoxy, PG = protection group; R = any group, rt = room temperature, TEA = triethylamine, TFA = trifluoroacetic acid, THF = tetrahydrofuran, The synthesis of compounds with formula Ia can, for example, be accomplished according to the following scheme 1. Scheme 1 A benzylidene protected ethyl 2-aminobutanoate AA can be first deprotonated using a suitable base and solvent and then reacted with various electrophilic linkers La. Bases for this type of reaction include but are not limited to LDA, diisopropylhexadisilazane, n- BuLi or sodium amides in solvents such as THF, dioxane or diethylether. Reactions of this type are typically carried out at temperatures between -78 °C and 100°C. Preferred linkers Laare N-PG1polyethylene glycol halides including, but not limited to, N-Boc protected iodinated polyethylene glycols of the type Boc−NH−CH2−CH2−(O−CH2−CH2)n−I, with n between 1 and 4. A person skilled in the art will acknowledge that also other protecting groups (PG1), linkers (La) and leaving groups can be used instead of Boc, polyethylene glycols or iodine, respectively. Removal of benzylidene protecting group via an acidic work up gives access to the main building blocks of formula AB (step a). To obtain compounds of the formula AB containing a sulphur atom in the linker La, the synthesis route described by Gazzi et al. can be applied (Chem. Sci., 2022,13, 5539-5545). Compound AC can be prepared from AB and the corresponding substituted heterocyclic carboxylic acids by suitable amide bond forming reactions (step b). These reactions are known in the art. For example, coupling reagents like N,N'-carbonyl-diimidazole (CDI), N,N'-dicyclohexylcarbodiimide (DCC), 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 1-bis(dimethylamino)-methylene)-1H-1,2,3-triazolo[4,5- b]pyridinium-3-oxide hexafluorophosphate (HATU), O-benzotriazol-1-yl-N,N,N',N'- tetramethyluronium tetrafluoroborate (TBTU), and O-benzotriazole-N,N,N',N'- tetramethyl-uronium-hexafluoro-phosphate (HBTU) can be employed to affect such a transformation. A convenient method is to use for example HATU and a base, such as Huenig’s base, trimethylamine or NMM in a solvent such as N,N-dimethylformamide, DMA, DMSO, DCM, ACN, MeOH or 1,4-dioxane, preferably between 0 °C and room temperature. The substituted heterocyclic carboxylic acids are either commercially available or can be synthesized by a person skilled in the art following procedures described in the literature. (US5624941A, WO2005108393A1, WO2006106054A1, WO2009106982A1, WO0132663A2, US2007293509A1). Compound AC can be converted into compound Ia by I) removal of the protecting group PG1and II) subsequent coupling to a suitable reporting unit Ra(step c). Methods known in the art for removal of protecting groups (e.g., tert-butyloxycarbonyl (Boc)) comprise the use of TFA in DCM or HCl in dioxane at temperatures between 0 °C and room temperature or the use of hexafluoroisopropanol in a microwave reactor at temperatures between 100 °C and 150 °C (as described for example in “Protective Groups in Organic Chemistry” by T.W. Greene and P.G.M. Wuts, 4th Ed., 2006, Wiley N.Y.; Choy et al. Synthetic Communications, (2008) 38:21, 3840-3853). The coupling of a reporter group Rasuch as biotin, fluorescein-carboxylic acid or any other fluorescent dye with carboxylic acid functionality can be achieved by amide bond formation. For amide couplings the previously mentioned reagents and conditions can be applied to achieve Ia. Alternatively, in combination with a suitable solvent such as DMF and a suitable base such as DIPEA, commercially available activated esters of fluorescent dyes can be used, such as succinimidyl esters, pentafluorophenyl esters or sulfodichlorophenyl esters to accomplish Ia. Halogenated aryls such as NBD-F, NBD-Cl and other sulfur, selenium or carbon containing congeners, as described by Benson et al. (Angew.Chem.Int.Ed.2019, 58, 6911 –6915), can be used as reporter group Ra. Halogenated aryls can react with deprotected primary amines via nucleophilic aromatic substitution in the presence of a suitable base such as Huenig’s base, trimethylamine, NMM, NaHCO3 or Cs2CO3 in a solvent such as N,N-dimethylformamide, DMA, DCM, ACN, MeOH, H2O or 1,4-dioxane, preferably between 0 °C and 65 °C to achieve Ia. A person skilled in the art will acknowledge that compounds of formula AB possess a chiral center and hence may be obtained as mixtures of diastereomers or enantiomers. Racemic mixtures can e.g. be separated into their antipodes via diastereomeric salts by crystallization. Alternatively, the amine functional group in intermediate AB can be first protected by a suitable protecting group (e.g. Fmoc or Cbz protecting group), separated into their antipodes by specific chromatographic methods using either a chiral adsorbent or a chiral eluent. The intermediate protecting groups can be removed at a later stage of the synthesis using standard methods known in the art. The synthesis of compounds with formulae Ib can, for example, be accomplished according to the following scheme 2. Compound BB can be prepared from the N-PG2protected amino acid BA and corresponding linkers containing a terminal amine by suitable amide bond forming reactions (step f). Suitable protecting groups for BA include, but are not limited to, Fmoc or Cbz. Preferred linkers (Lb) for the amide bond formation include, but are not limited to, N-PG1protected polyethylene glycol amines of the type PG1−NH−CH2−CH2−(O−CH2−CH2)n−NH2, with n between 0 and 4. A person skilled in the art will acknowledge that an orthogonal protecting scheme is preferred in BB, e.g. PG1= Boc and PG2= Fmoc. Coupling reagents suited for the a transformation of BA with N-PG1protected polyethylene glycol amines to BB are for example SOCl2, N,N'- carbonyldiimidazole (CDI), N,N'-dicyclohexylcarbodiimide (DCC), 1-(3- dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 1- bis(dimethylamino)-methylene)-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU), O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU), and O-benzotriazole-N,N,N',N'-tetramethyl-uronium- hexafluorophosphate (HBTU). A convenient method is to use for example HATU and a base, such as Huenig’s base, trimethylamine, DMAP or NMM in a solvent such as N,N- dimethylformamide, DMA, DMSO, DCM, ACN, MeOH or 1,4-dioxane, preferably between 0 °C and room temperature. Compounds of formula BA and various protected polyethylene glycol diamines are either commercially available or can be prepared according to literature methods. Compound BB can be converted to BC by I) selective removal of the protection group PG2applying suitable methods known in literature (e.g., a Fmoc group using for example piperidine, DBU or KF in DMF or DCM, as described for example in “Houben-Weyl Methods of Organic Chemistry. Volume E22A. Synthesis of Peptides and Peptidomimetics”, edited by Murray Goodman, Arthur Felix, Luis Moroder, and Claudio Toniolo; Georg Thieme Verlag; Stuttgart, Germany; 2001) and II) a subsequent amide coupling with corresponding substituted heterocyclic carboxylic acids (step g) using suitable amide coupling reagents as described before. The amide coupling step might be performed in situ or after purification of the deprotected intermediate amine. The substituted heterocyclic carboxylic acids are either commercially available or can be synthesized by a person skilled in the art following procedures described in the literature. (US5624941A, WO2005108393A1, WO2006106054A1, WO2009106982A1, WO0132663A2, US2007293509A1). Compound BC can be converted into compound Ib by I) removal of the protecting group PG1and II) subsequent coupling to a suitable reporting unit (Rb) (step h). Methods known in the art for removal of protecting groups (e.g., tert-butyloxycarbonyl (Boc)) comprise the use of TFA in DCM or HCl in dioxane at temperatures between 0 °C and room temperature or the use of hexafluoroisopropanol in a microwave reactor at temperatures between 100 °C and 150 °C (as described for example in “Protective Groups in Organic Chemistry” by T.W. Greene and P.G.M. Wuts, 4th Ed., 2006, Wiley N.Y.; Choy et al. Synthetic Communications, (2008) 38:21, 3840-3853). The coupling of a reporter group Rbsuch as biotin, fluorescein-carboxylic acid or any other fluorescent dye with carboxylic acid functionality can be achieved by amide bond formation. For amide couplings the previously mentioned reagents and conditions can be applied to achieve Ib. Alternatively, in combination with a suitable solvent such as DMF and a suitable base such as DIPEA, commercially available activated esters of fluorescent dyes can be used, such as succinimidyl esters, pentafluorophenyl esters or sulfodichlorophenyl esters to accomplish Ib. Halogenated aryls such as NBD-F, NBD-Cl and other sulfur, selenium or carbon containing congeners, as described by Benson et al. (Angew.Chem.Int.Ed.2019, 58, 6911 –6915), can be used as reporter group Rb. Halogenated aryls can react with deprotected primary amines via nucleophilic aromatic substitution in the presence of a suitable base such as Huenig’s base, trimethylamine, NMM, NaHCO3 or Cs2CO3 in a solvent such as N,N-dimethylformamide, DMA, DCM, ACN, MeOH, H2O or 1,4- dioxane, preferably between 0 °C and 65 °C to achieve Ib. Alternatively, compound BD can be synthesized from BB by I) removal of the protecting group PG1and II) subsequent coupling to a suitable reporting unit Rb(step h). Methods known in the art for removal of protecting groups (e.g., tert-butyloxycarbonyl (Boc)) comprise the use of TFA in DCM or HCl in dioxane at temperatures between 0 °C and room temperature or the use of hexafluoroisopropanol in a microwave reactor at temperatures between 100 °C and 150 °C (as described for example in “Protective Groups in Organic Chemistry” by T.W. Greene and P.G.M. Wuts, 4th Ed., 2006, Wiley N.Y.; Choy et al. Synthetic Communications, (2008) 38:21, 3840-3853). The coupling of a reporter group Rbsuch as biotin, fluorescein-carboxylic acid or any other fluorescent dye with carboxylic acid functionality can be achieved by amide bond formation. For amide couplings the previously mentioned reagents and conditions can be applied to achieve Ib. Alternatively, in combination with a suitable solvent such as DMF and a suitable base such as DIPEA, commercially available activated esters of fluorescent dyes can be used, such as succinimidyl esters, pentafluorophenyl esters or sulfodichlorophenyl esters to accomplish Ib. Halogenated aryls such as NBD-F, NBD-Cl and other sulfur, selenium or carbon containing congeners, as described by Benson et al. (Angew.Chem.Int.Ed.2019, 58, 6911 –6915), can be used as reporter group Rb. Halogenated aryls can react with deprotected primary amines via nucleophilic aromatic substitution in the presence of a suitable base such as Huenig’s base, trimethylamine, NMM, NaHCO3 or Cs2CO3 in a solvent such as N,N-dimethylformamide, DMA, DCM, ACN, MeOH, H2O or 1,4-dioxane, preferably between 0 °C and 65 °C to achieve BD. Compound BD can be converted to Ib by I) removal of the protection group PG2applying suitable methods known in literature (e.g., a Fmoc group using piperidine, DBU or KF in DMF or DCM, as described for example in “Houben-Weyl Methods of Organic Chemistry. Volume E22A. Synthesis of Peptides and Peptidomimetics”, edited by Murray Goodman, Arthur Felix, Luis Moroder, and Claudio Toniolo; Georg Thieme Verlag; Stuttgart, Germany; 2001) and II) a subsequent amide coupling with corresponding substituted heterocyclic carboxylic acids (step g) using suitable coupling reagents as described before. The amide coupling step might be performed in situ or after purification of the deprotected intermediate amine. The substituted heterocyclic carboxylic acids are either commercially available or can be synthesized by a person skilled in the art following procedures described in the literature. (US5624941A, WO2005108393A1, WO2006106054A1, WO2009106982A1, WO0132663A2, US2007293509A1).

[0007] Examples: The invention will be more fully understood by reference to the following examples. The claims should not, however, be construed as limited to the scope of the examples. In case the preparative examples are obtained as a mixture of enantiomers, the pure enantiomers can be separated by methods described herein or by methods known to the man skilled in the art, such as e.g., chiral chromatography (e.g., chiral SFC) or crystallization. Example 1 tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate Step f) (9H-Fluoren- butoxycarbonyl)amino)ethyl)carbamoyl)pentan-3-yl)carbamate To a solution of 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-ethylbutanoic acid (CAS RN 218926-46-6) (300 mg, 0.85 mmol, 1.0 equiv.) in anhydrous ACN (10 mL) were added anhydrous DIPEA (432 µL, 2.55 mmol, 3.0 eqiuv.) and HATU (322 mg, 0.85 mmol, 1.0 equiv.) and stirred for 20 min. Then a solution of tert-butyl (2- aminoethyl)carbamate (CAS RN 57260-73-8) (150 mg, 0.93 mmol, 1.1 equiv.) in anhydrous ACN (4 mL) was added. The reaction was stirred for 1 h and the solvent was removed under reduced pressure. The crude was dissolved in EtOAc and washed with NaHCO3 solution (1M) and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The title compound (295 mg, 70%) was obtained as white powder after automated silica gel chromatography (cyclohexane:EtOAC 0-80%). ESI-MS (m / z) 518.2 ([M+Na]+). Step g) tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethyl)carbamate Mixture A: To a solution of (9H-fluoren-9-yl)methyl (3-((2-((tert- butoxycarbonyl)amino)ethyl)carbamoyl)pentan-3-yl)carbamate (30.5 mg, 61.6 µmol, 1.0 equiv.) in anhydrous DMF (2 mL) was added DBU (13.3 µL, 92.4 µmol, 1.5 equiv.). After 30 min HOAt (13.3 mg, 98.6 µmol, 1.6 equiv.) was added and the resulting mixture was allowed to stir for another 10 min. Mixture B: To a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxylic acid (CAS RN 162758-35-2) (25.9 mg, 67.8 µmol, 1.1 equiv.) in anhydrous DMF (2 mL) were added anhydrous DIPEA (31.4 µL, 185 µmol, 3.0 equiv.) and HATU (29.1 mg, 67.8 µmol, 1.1 equiv.) and stirred for 20 min. Then mixture A and B were combined and the progress of the reaction was judged by LC-MS. If necessary after 3 h another potion of freshly prepared mixture B was added to the reaction mixture and the progress of the reaction was judged by LC-MS. The solvent was removed under reduced pressure and the crude material purified by preparative HPLC (40-95% ACN in H2O) to yield the title compound as white powder (28.5 mg, 73%). ESI- MS (m / z) 658.2 ([M+Na]+). Example 2 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide Step h) 5-(4- - - ((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H-pyrazole-3- carboxamide To a solution of tert-butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamido)-2-ethylbutanamido)ethyl)carbamate (24.6 mg, 38.7 µmol, 1.0 equiv.) in anhydrous DCM (1.8 mL) was added TFA (0.2 mL) and stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The residue was dissolved in anhydrous DMF (1 mL) in a brown glass flask. To the solution were added anhydrous DIPEA (20.0 µL, 116 µmol, 3.0 equiv.) and 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2) (14.2 mg, 77.3 µmol, 2.0 equiv.) and the reaction mixture was allowed to stir for 16 h. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The title compound (25.7 mg, 95%) was obtained as orange powder. ESI-MS (m / z) 699.1 ([M+H]+). Example 3 tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole- 3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate Step f) (9H-Fluoren-9-yl)methyl (13-ethyl-2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11- diazapentadecan-13-yl)carbamate To a solution of 2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-ethylbutanoic acid acid (CAS RN 218926-46-6) (200 mg, 0.57 mmol, 1.0 equiv.) in anhydrous DMF (6 mL) were added anhydrous DIPEA (148.0 µL, 0.85 mmol, 1.5 eqiuv.) and HATU (215.2 mg, 0.57 mmol, 1.0 equiv.) and stirred for 20 min. Then a solution of tert-butyl (2-(2- aminoethoxy)ethyl)carbamate (CAS RN 127828-22-2) (127.1 mg, 0.62 mmol, 1.1 equiv.) in anhydrous DMF (2 mL) was added. The reaction was stirred for 1 h and the solvent was removed under reduced pressure. The crude was dissolved in EtOAc and washed with NaHCO3 solution (1M) and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The title compound (255 mg, 83%) was obtained as white powder. ESI-MS (m / z) 562.3 ([M+Na]+). Step g) tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate Mixture A: To a solution of (9H-fluoren-9-yl)methyl (13-ethyl-2,2-dimethyl-4,12-dioxo- 3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate (25.0 mg, 46.3 µmol, 1.0 equiv.) in anhydrous DMF (0.2 mL) was added DBU (10.0 µL, 69.5 µmol, 1.5 equiv.). After 30 min HOAt (10.0 mg, 74.1 µmol, 1.6 equiv.) was added and the resulting mixture was allowed to stir for another 10 min. Mixture B: To a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxylic acid (CAS RN 162758-35-2) (21.0 mg, 55.6 µmol, 1.2 equiv.) in anhydrous DMF (0.2 mL) were added anhydrous DIPEA (27.5 µL, 162.1 µmol, 3.5 equiv.) and HATU (21.0 mg, 55.6 µmol, 1.2 equiv.) and stirred for 20 min. Then mixture A and B were combined and the progress of the reaction was judged by LC-MS. If necessary after 3 h another potion of freshly prepared mixture B was added to the reaction mixture and the progress of the reaction was judged by LC-MS. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (40-95% ACN in H2O) to yield the title compound as white powder (21.2 mg, 65%). ESI-MS (m / z) 702.2 ([M+Na]+). Example 4 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide

[0008] Step h) 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide To a solution of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate (10.0 mg, 14.7 µmol, 1.0 equiv.) in anhydrous DCM (1.8 mL) was added TFA (0.2 mL) and stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The residue was dissolved in anhydrous DMF (1 mL) in a brown glass flask. To the solution were added anhydrous DIPEA (7.5 µL, 44.1 µmol, 3.0 equiv.) and 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56- 2) (5.4 mg, 29.4 µmol, 2.0 equiv.) and the reaction mixture was allowed to stir for 16 h. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The title compound (12.8 mg, 62%) was obtained as orange powder. ESI-MS (m / z) 764.5 ([M+H]+). Example 5 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide and 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl-1H- pyrazole-3-carboxamide

[0009] Step h) 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3,6'-dihydroxy-3-oxo- 3H-spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide and 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl-1H-pyrazole-3- carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that a mixture of 2,5-dioxopyrrolidin-1-yl 3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran- 1,9'-xanthene]-5-carboxylate and 2,5-dioxopyrrolidin-1-yl 3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxylate (CAS RN 117548-22-8, Fluorescein- OSu, 5 / 6-isomer mixture, Ambeed) was used instead of 4-fluoro-7- nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2). The compound was obtained as yellow powder. ESI-MS (m / z) 937.5 ([M+H]+). Example 6 tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate (CAS RN 153086-78-3) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 606.3 ([M+Na]+). Step g) tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3- yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate. The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 746.2 ([M+Na]+). Example 7 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide Step h) 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)- 1H-pyrazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate. The compound was obtained as orange powder. ESI-MS (m / z) 809.1 ([M+Na]+). Example 8 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide and 5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide

[0010] Step h) 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide and 5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]- 6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-4-methyl-1H-pyrazole- 3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate and a mixture of 2,5- dioxopyrrolidin-1-yl 3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-5- carboxylate and 2,5-dioxopyrrolidin-1-yl 3',6'-dihydroxy-3-oxo-3H-spiro[isobenzofuran- 1,9'-xanthene]-6-carboxylate (CAS RN 117548-22-8, Fluorescein-OSu, 5 / 6-isomer mixture, Ambeed) (1.5 equiv.) was used instead of 4-fluoro-7- nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2). The compound was obtained as yellow powder. ESI-MS (m / z) 981.4 ([M+H]+). Example 9 N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide and N-(1-(3',6'- bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12- dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide Step h) N-(1- - 1,9'-xanthen]-5- yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide and N-(1-(3',6'- bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12- dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)- 4-methyl-1H-pyrazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate and a mixture of 2,5- dioxopyrrolidin-1-yl 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-5-carboxylate and 2,5-dioxopyrrolidin-1-yl 3',6'-bis(dimethylamino)-3-oxo- 3H-spiro[isobenzofuran-1,9'-xanthene]-6-carboxylate (CAS RN 246256-50-8, TAMRA- SE, 5 / 6-isomer mixture, AATBioquest) (1.5 equiv.) was used instead of 4-fluoro-7- nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2). The compound was obtained as red powder. ESI-MS (m / z) 1036.1 ([M+H]+). Example 10 N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide Step h) N-(1- - spiro[dibenzo[b,e]siline-10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate and 2,5-dioxopyrrolidin-1-yl 3,7-bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline-10,1'- isobenzofuran]-6'-carboxylate (CAS RN 1808181-14-7, SiR-OSu, Spirochrome) (0.9 equiv.) was used instead of 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270- 56-2). The compound was obtained as blue powder. ESI-MS (m / z) 1077.5 ([M+H]+). Example 11 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)-3- oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid Step h) 3',6'- - -4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)-3- oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate and trisodium 3',6'-diamino-5- ((2,6-dichloro-4-sulfonatophenoxy)carbonyl)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-4',5'-disulfonate (AlexaFluor®4885-SDP ester, Molecular Probes™) (1.1 equiv.) was used instead of 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270- 56-2). The compound was obtained as dark purple powder. ESI-MS (m / z) 1139.7 ([M+H]+). Example 12 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate - - -3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1-(3- sulfopropyl)-3H-indol-1-ium-5-sulfonate Mixture A: To a solution of tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate (3.7 mg, 5.1 µmol, 1.2 equiv.) in anhydrous DCM (0.9 mL) was added TFA (0.1 mL) and stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The residue was dissolved in anhydrous DMF (50 µL). Mixture B: To a solution tris(triethylammonium) 3-(5-carboxypentyl)-2-((1E,3E)-5-((E)- 3,3-dimethyl-5-sulfonato-1-(3-sulfonatopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3- methyl-1-(3-sulfonatopropyl)-3H-indol-1-ium-5-sulfonate (AlexaFluor®647 carboxylic acid, tris(triethylammonium) salt, Molecular Probes™) (5 mg, 4.3 µmol, 1.0 equiv.) in anhydrous DMF (200 µL) in a brown glass flask was added anhydrous DIPEA (2.2 µL, 12.3 µmol, 3.0 equiv.) and HATU (1.8 mg, 4.7 µmol, 1.1 equiv.). The solution was stirred for 20 min before mixture A and B were combined. The reaction mixture was allowed to stir for 16 h before the solvent was removed under reduced pressure. The crude material was purified by reversed-phase preparative HPLC (5-95% CAN + 0.1% TFA / H2O + 0.1% TFA) to obtain the title compound (5.4 mg, 86%) as blue powder. ESI- MS (m / z) (ESI+): 732.8 ([M+H]2+). Example 13 tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (19-ethyl-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa- 5,17-diazahenicosan-19-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)carbamate (CAS RN 101187-40- 0) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828- 22-2). The compound was obtained as white powder. ESI-MS (m / z) 650.4 ([M+Na]+). Step g) tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3- yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (19-ethyl-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17- diazahenicosan-19-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate. The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 790.1 ([M+Na]+). Example 14 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide Step h) 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14-yl)- 4-methyl-1H-pyrazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole- 3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate. The compound was obtained as orange powder. ESI-MS (m / z) 853.2 ([M+Na]+). Example 15 tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (22-ethyl-2,2-dimethyl-4,21-dioxo-3,8,11,14,17- pentaoxa-5,20-diazatetracosan-22-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (14-amino-3,6,9,12-tetraoxatetradecyl)carbamate (CAS RN 811442-84-9) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 694.3 ([M+Na]+). Step g) tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3- yl)-3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (22-ethyl-2,2-dimethyl-4,21-dioxo-3,8,11,14,17-pentaoxa- 5,20-diazatetracosan-22-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13- ethyl-2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate. The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 834.3 ([M+Na]+). Example 16 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide Step h) - - nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15-azanonadecan- 17-yl)-4-methyl-1H-pyrazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate. The compound was obtained as orange powder. ESI-MS (m / z) 897.2 ([M+Na]+). Example 17 tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate 4,12-dioxo-3,8-dioxa-5,11- diazapentadecan-13-yl)carbamate The compound was obtained as described in Example 3, step f). Step g) tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that 5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)- 1H-pyrrole-3-carboxylic acid (WO2005108393A1) was used instead of 5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 742.7 ([M+Na]+). Example 18 tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran- 2-yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate Step f) (9H- trioxa-5,14- diazaoctadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate (CAS RN 153086-78-3) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 606.3 ([M+Na]+).

[0011] Step g) tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5- diazatridecan-13-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-Fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate and 5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3- carboxylic acid (WO2005108393A1) was used instead of 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 787.3 ([M+Na]+). Example 19 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide Step h) 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)- 1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide A solution of tert-butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5- diazatridecan-13-yl)carbamate (9.5 mg, 12.4 µmol, 1.0 equiv.) in HFIP (5 mL) in a microwave vial was heated to 150 °C for 80 min in a microwave. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The obtained free amine was lyophilized and dissolved in DMF (0.5 mL). To the solution were added anhydrous DIPEA (6.3 µL, 37.1 µmol, 3.0 equiv.) and 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2) (4.5 mg, 24.7 µmol, 2.0 equiv.) and the reaction mixture was allowed to stir for 18 h. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The title compound (12.8 mg, 62%) was obtained as orange powder. ESI-MS (m / z) 828.3 ([M+H]+). Example 20 tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran- 2-yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5- diazahexadecan-16-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (19-ethyl-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa- 5,17-diazahenicosan-19-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)carbamate (CAS RN 101187-40-0) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22-2). The compound was obtained as white powder. ESI-MS (m / z) 650.4 ([M+Na]+). Step g) tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5- diazahexadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (19-ethyl-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17- diazahenicosan-19-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate and 5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3- carboxylic acid (WO2005108393A1) was used instead of 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (ESI+): 831.1 ([M+Na]+). Example 21 tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate Step f) (9H-Fluoren-9-yl)methyl (13-ethyl-2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11- diazapentadecan-13-yl)carbamate The compound was obtained as described in Example 3, step f). Step g) tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that 6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinic acid (CAS RN 912454-39-8) was used instead of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 608.8 ([M+Na]+). Example 22 tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate Step f) (9H- trioxa-5,14- diazaoctadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate (CAS RN 153086-78-3) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 606.3 ([M+Na]+). Step g) tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3- diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate and 6- (cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinic acid (CAS RN 912454-39-8) was used instead of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 653.4 ([M+Na]+). Example 23 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide Step h) (9H-fluoren-9-yl)methyl (3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)carbamate A solution of (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa- 5,14-diazaoctadecan-16-yl)carbamate ( 77.2 mg, 132.3 µmol) in anhydrous DCM (4.5 mL) and TFA (0.5 mL) was stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. A portion of the obtained ammonium salt (45.12 mg, 75.7 µmol, 1 equiv.) was dissolved in anhydrous DMF (1 mL) in a brown glass flask. To the solution were added anhydrous DIPEA (64.0 µL, 49.0 µmol, 5.0 equiv.) and 4-fluoro-7- nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2) (20.7 mg, 113.2 µmol, 1.5 equiv.) and the reaction mixture was allowed to stir for 20 h. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The title compound (19.1 mg, 63%) was obtained as orange powder. ESI-MS (m / z) 647.3 ([M+H]+). Step g) 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide To a solution of (9H-fluoren-9-yl)methyl (3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol- 4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)carbamate (12.0 mg, 18.6 µmol, 1.0 equiv.) in anhydrous DMF (1 mL) was added DBU (3.5 µL, 27.8 µmol, 1.5 equiv.). After 30 min HOAt (4.0 mg, 29.7 µmol, 1.6 equiv.) was added and the resulting mixture was allowed to stir for another 10 min. To the solution was added 6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinic acid (CAS RN 912454-39-8) (6.4 mg, 22.3 µmol, 1.1 equiv.), EDCI (4.3 mg, 22.3 µmol) and DIPEA (15.7 µL, 92.8 µmol, 5.0 equiv.). The progress of the reaction was judged by LC- MS and additional equivalents of EDCI and DIPEA were added, if necessary. The reaction was stirred for 16 h, the solvent removed under reduced pressure and the crude material was purified by preparative HPLC (40-95% ACN in H2O) to yield the title compound as orange powder (8.35 mg, 65%). ESI-MS (m / z) 694.3 ([M+H]+). Example 24 tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- -2-ethylbutanamido)ethoxy)ethyl)carbamate Step f) (9H- 3,8-dioxa-5,11- diazapentadecan-13-yl)carbamate The compound was obtained as described in Example 3, step f). Step g) tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that 6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxylic acid (CAS RN 960248-07-1) was used instead of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl- 1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 629.8 ([M+Na]+). Example 25 tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate (CAS RN 153086-78-3) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 606.3 ([M+Na]+). Step g) tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate and 6-(4- chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxylic acid (CAS RN 960248-07-1) was used instead of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 674.3 ([M+Na]+). Example 26 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide Step h) 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2- (2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate. The compound was obtained as orange powder. ESI-MS (m / z) 737.2 ([M+Na]+). Example 27 N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo- 3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamide Step h) N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5- yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamide To a solution of tert-butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3- diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate (13.7 mg, 21.0 µmol, 1.0 equiv.) in anhydrous DCM (0.9 mL) was added TFA (0.1 mL) and stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The residue was dissolved in anhydrous DMF (1 mL) in a brown glass flask. To the solution were added anhydrous DIPEA (14.4 µL, 84.1 µmol, 4.0 equiv.), HOAt (4.6 mg, 33.7 µmol, 1.6 equiv.), EDCI (6.5 mg, 33.7 µmol, 1.6 equiv.) and a mixture of 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]- 5-carboxylic acid and 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-6-carboxylic acid (CAS RN 98181-63-6, TAMRA-COOH, 5 / 6-isomer mixture) (13.5 mg, 31.05 µmol, 1.5 equiv.). The solution was stirred for 18 h and the solvent removed under reduced pressure. The crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The title compound (8.4 mg, 41%) was obtained as red powder. ESI-MS (m / z) 964.3 ([M+H]+). Example 28 tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate (CAS RN 153086-78-3) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 606.3 ([M+Na]+). Step g) tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate and 1-(3- fluorobenzyl)-1H-indazole-3-carboxylic acid (CAS RN 50264-64-7) was used instead of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as faint yellow viscous oil. ESI- MS (m / z) 636.3 ([M+Na]+). Example 29 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide Step h) 1-(3- - 4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate. The compound was obtained as orange powder. ESI-MS (m / z) 737.2 ([M+Na]+). Example 30 N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H-indazole-3-carboxamide Step h) N-(1-(3',6'- - oxo- 1,9'-xanthen]-5- yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H-indazole-3-carboxamide The title compound was prepared analogously to Example 27 step h), with the difference that tert-butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (1-(6-(4-chlorophenyl)- 5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan- 13-yl)carbamate. The compound was obtained as red powder. ESI-MS (m / z) 926.4 ([M+H]+). Example 31 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide Step h) 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19- ((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14- diazanonadecan-3-yl)-4-methyl-1H-pyrazole-3-carboxamide The title compound was prepared analogously to Example 27 step h), with the difference tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate was used instead tert- butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4-dioxo- 8,11-dioxa-2,5-diazatridecan-13-yl)carbamate and 5-((3aS,4S,6aR)-2-oxohexahydro-1H- thieno[3,4-d]imidazol-4-yl)pentanoic acid (biotin, CAS RN 58-85-5) (1.3 equiv.) was used instead of a mixture of 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-5-carboxylic acid and 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran- 1,9'-xanthene]-6-carboxylic acid (TAMRA-COOH, 5 / 6-isomer mixture). The compound (5.0 mg, 72%) was obtained as white powder. ESI-MS (m / z) 926.4 ([M+H]+). Example 32 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide Step h) 5-(4- - - dimethyl-7-nitro- 2H-benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide To a solution of tert-butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate (23.2 mg, 32.0 µmol, 1.0 equiv.) in anhydrous DCM (1.8 mL) was added TFA (0.2 mL) and stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The crude was dissolved together with 4-fluoro-2,2-dimethyl-7-nitro-2H-benzo[d]imidazole (CAS RN 2351931- 72-9) (S. Benson et al., Angew. Chem. Int. Ed., 2019, 58, 6911) (11.4 mg, 54.0 µmol, 1.7 equiv.) in ACN (1 mL) with H2O (20 µL) and NaHCO3(7.0 mg, 129 µmol, 2.6 equiv.). The resulting mixture was stirred over 16 h at 65oC. The mixture was directly purified by HPLC (30 to 85% ACN in H2O). The title compound (26.0 mg, 18%) was obtained as purple powder. ESI-MS (m / z) 812.6 ([M+H]+). Example 33 Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate Step a) Ethyl 2-amino-4- -2-ethylbutanoate LDA preparation: An oven-dried schlenk tube was sealed and evacuated and backfilled with N2three times. Then it was charged with DIPA (288 µL, 2.06 mmol, 1.10 equiv.) and anhydrous THF (11 mL) under positive N2 pressure and placed in dry ice / acetone bath (-78 °C). After 10 min, n-BuLi (748 µL of 2.5 M solution in hexane, 1.87 mmol, 1.0 equiv.) was added dropwise and the reaction mixture was allowed to stir for 15 min at -78 °C under N2atmosphere. Then, a solution of ethyl-2-((4-chlorobenzylidene)amino)butanoate (CAS RN 126385-72- 6) (237 mg, 0.94 mmol, 1.0 equiv.) in anhydrous THF (3 mL) was added to the freshly prepared LDA and the resulting mixture was stirred at –78 °C. After 15 min, tert-butyl (2-(2-iodoethoxy)ethyl)carbamate (CAS RN 629626-40-0) (325 mg, 1.03 mmol, 1.1 equiv.) solution in anhydrous THF (3 mL) was added dropwise and the mixture was stirred at –78 °C for an additional 15 min. Then it was allowed to gradually warm and stirred overnight. The reaction mixture was diluted with EtOAc and quenched with sat. NH4Cl. The organic phase was separated, dried over anhydrous Na2SO4, filtered and concentrated. After dissolving the residue in a mixture of THF:MeOH (3 mL, 3:1 v / v), a solution of citric acid (5 mL, 10%) was added and the mixture was stirred overnight. After removal of the organic solvent under reduced pressure, the residue was extracted with Et2O (2×). The aqueous phase was basified to pH 8 with NaOH (1 M) and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude mixture was obtained as faint yellow viscous oil and used for the next step without further purification. ESI-MS (m / z) 319.3 ([M+H]+). Step b) Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate To a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxylic acid (CAS RN 162758-35-2) (47.0 mg, 123.9 µmol, 1.1 equiv.) in anhydrous DMF (2 mL) were added anhydrous DIPEA (57.0 µL, 162.1 µmol, 3.0 equiv.) and HATU (47 mg, 123.9 µmol, 1.1 equiv.). The reaction mixture was stirred for 20 min. Then a solution of ethyl 2-amino-4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- ethylbutanoate (35.9 mg, 1127 µmol, 1.0 equiv.) in anhydrous DMF (1 mL) was added to the mixture. The progress of the reaction was judged by LC-MS. If necessary another portion of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxylic acid (1.1 equiv.) was dissolved with and anhydrous DIPEA (3.0 equiv.) HATU (1.1 equiv.) in anhydrous DMF (1 mL), stirred for 20 min and added to the mixture to bring the reaction to completion. The reaction was stirred for 16 h. After removal of the solvent under reduced pressure, the residue was purified by preparative HPLC (50-95% ACN / H2O). The title compound (25.1 mg, 30%) was obtained as faint yellow viscous oil. LC-MS (ESI+): 703.1 ([M+Na]+). Example 34 Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate Step c) Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate To a solution of ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate (12.0 mg, 17.3 µmol, 1.0 equiv.) in anhydrous DCM (0.9 mL) was added TFA (0.1 mL) and stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The residue was dissolved in anhydrous DMF (1 mL) in a brown glass flask. To the solution were added anhydrous DIPEA (8.80 µL, 51.8 µmol, 3.0 equiv.) and 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2) (6.30 mg, 34.5 µmol, 2.0 equiv.) were added and stirred for 18 h. The solvent was removed under reduced pressure and the crude material purified by reversed- phase preparative HPLC (50-95% ACN + 0.1% TFA / H2O + 0.1% TFA). The title compound (8.10 mg, 10.9 µmol, 63%) was obtained as orange powder. ESI-MS (m / z) 744.1 ([M+H]+). Example 35 Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate Step a) Ethyl 14-amino-14- oxo- trioxa-5-azapentadecan-15- oate The title compound was prepared analogously to Example 33 step a), with the difference that tert-butyl (2-(2-(2-iodoethoxy)ethoxy)ethyl)carbamate (CAS RN 1820026-89-8) was used instead of tert-butyl (2-(2-iodoethoxy)ethyl)carbamate (CAS RN 629626-40-0). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 363.3 ([M+H]+). Step b) Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate The title compound was prepared analogously to Example 33 step b), with the difference that ethyl 14-amino-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate was used instead of ethyl 2-amino-4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- ethylbutanoate. The compound was obtained as faint yellow viscous oil. ESI-MS (m / z): 747.2 ([M+Na]+). Example 36 Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate Step c) Ethyl 2-(5-(4- - -4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate The title compound was prepared analogously to 34 step c), with the difference that ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)- 14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate was used instead of ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate. The compound was obtained as orange powder. ESI-MS (m / z) 810.1 ([M+Na]+). Example 37 Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate Step a) Ethyl 17-amino-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan- 18-oate The title compound was prepared analogously to Example 33 step a), with the difference that tert-butyl (2-(2-(2-(2-iodoethoxy)ethoxy)ethoxy)ethyl)carbamate (CAS RN 1801273-41-5) was used instead of tert-butyl (2-(2-iodoethoxy)ethyl)carbamate (CAS RN 629626-40-0). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 407.3 ([M+H]+). Step b) Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate The title compound was prepared analogously to Example 33 step b), with the difference that ethyl 17-amino-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate was used instead of ethyl 2-amino-4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- ethylbutanoate. The compound was obtained as faint yellow viscous oil. ESI-MS (m / z): 791.3 ([M+Na]+). Example 38 Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate

[0012] Step c) Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate The title compound was prepared analogously to 34 step c), with the difference that ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)- 17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate was used instead of ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate. The compound was obtained as orange powder. ESI-MS (m / z) 832.3 ([M+H]+). Example 39 Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate

[0013] Step a) Ethyl 20-amino-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5- azahenicosan-21-oate To a solution of 2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azanonadecan-19-yl 4- methylbenzenesulfonate (CAS RN 1404111-69-8) (1.0 equiv.) in acetone was added KI (2.0 equiv.) in one portion and the resulting mixture was refluxed for 16 h (acetone). After removal of solvent under reduced pressure, the residue was partitioned between EtOAc and H2O. The organic layer was separated and washed with Na2S2O3, dried over anhydrous Na2SO4, filtered and concentrated to yield tert-butyl (14-iodo-3,6,9,12- tetraoxatetradecyl)carbamate. The crude was used for the next step without further purification. The title compound was prepared analogously to Example 33 step a), with the difference that tert-butyl (14-iodo-3,6,9,12-tetraoxatetradecyl)carbamate was used instead of tert- butyl (2-(2-iodoethoxy)ethyl)carbamate (CAS RN 629626-40-0). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 451.3 ([M+H]+). Step b) Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan-21- oate The title compound was prepared analogously to Example 33 step b), with the difference that ethyl 20-amino-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate was used instead of ethyl 2-amino-4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- ethylbutanoate. The compound was obtained as faint yellow viscous oil. ESI-MS (m / z): 835.1 ([M+Na]+). Example 40 Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate

[0014] Step c) Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate The title compound was prepared analogously to 34 step c), with the difference that ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)- 20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan-21-oate was used instead of ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate. The compound was obtained as orange powder. ESI-MS (m / z) 898.3 ([M+Na]+). Example 41 Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate

[0015] Step b) Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole- 3-carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate Ethyl 17-amino-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate (400 mg, 0.984 mmol, 1.0 equiv.) was suspended in a KHCO3 solution (10 mL, 1M) and stirred at 0 °C for 10 min. To the resulting mixture was added a solution of (9H-fluoren- 9-yl)methyl (2,5-dioxopyrrolidin-1-yl) carbonate (CAS RN 82911-69-1) (830 mg, 2.46 mmol, 2.5 equiv.) in 1,4-dioxane (10 mL) at 0 °C, allowed to warm to rt and stirred for 3 h. The completion of the reaction was judged by LCMS. The mixture was diluted with H2O and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by automated flash chromatography on silica (cyclohexane:EtOAc 10 to 50%) to give access to ethyl 17-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-17-ethyl-2,2-dimethyl-4-oxo- 3,8,11,14-tetraoxa-5-azaoctadecan-18-oate (600 mg, 65%) as brown viscous oil. ESI-MS (m / z) 651.3[M+Na]+. The enantiomers were separated by chiral HPLC (Chiralpak IG from Daicel, H2O:MeOH 20% to 40% MeOH). Mixture A: To a solution of ethyl (R)-17-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)- 17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate (10.16 mg, 16.2 µmol, 1.0 equiv.) in anhydrous DMF (1 mL) was added DBU (3.7 µL, 24.2µmol, 1.5 equiv.). After 30 min HOAt (3.5 mg, 25.9 µmol, 1.6 equiv.) was added and the resulting mixture was allowed to stir for another 10 min. Mixture B: To a solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxylic acid (CAS RN 162758-35-2) (6.20 mg, 16.2 µmol, 1.0 equiv.) in anhydrous DMF (1 mL) were added anhydrous DIPEA (8.20 µL, 48.5 mmol, 3 equiv.) and HATU (6.10 mg, 16.2 µmol, 1.0 equiv.) and stirred for 20 min. Then mixtures A and B were combined and the progress of the reaction was judged by LC-MS. If necessary after 3 h another potion of freshly prepared mixture B was added to the reaction mixture and stirred overnight. The solvent was removed under reduced pressure and the crude material was purified by preparative HPLC (40-95% ACN in H2O) to yield the title compound as white powder (9.81 mg, 79%). ESI-MS (m / z) 790.6 ([M+Na]+). Example 42 Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate Step b) Ethyl (S)-17-(5- - -4-methyl-1H-pyrazole- 3-carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate The title compound was prepared analogously to Example 41 step b), with the difference that ethyl (S)-17-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-17-ethyl-2,2-dimethyl-4- oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18-oate was used instead of ethyl (R)-17-((((9H- fluoren-9-yl)methoxy)carbonyl)amino)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa- 5-azaoctadecan-18-oate. The compound was obtained as white powder. ESI-MS (m / z) 790.6 ([M+Na]+). Example 43 Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate Step a) Ethyl 18-amino- oxo- trioxa-14-thia-5- azanonadecan-19-oate The title compound was prepared as racemic mixture as described in literature (T. Gazzi et al., Chem. Sci., 2022, 13, 5539-5545). Step b) Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14- thia-5-azanonadecan-19-oate To a solution of 5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxylic acid (WO2005108393A1) (21.9 mg, 52.0 µmol, 1.0 equiv.) in anhydrous DCM / ACN (1 mL, v / v 1:1) was added anhydrous DIPEA (13.3 µL, 78.3 µmol, 1.5 equiv.) and HATU (19.8 mg, 123.9 µmol, 1.0 equiv.). The reaction mixture was stirred for 20 min. Then a solution of ethyl 18-amino-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate (35.9 mg, 112.7 µmol, 1.0 equiv.) in anhydrous DCM / ACN (1 mL, v / v 1:1) was added to the mixture. The progress of the reaction was judged by LC-MS. After removal of the solvent under reduced pressure, the residue was purified by preparative HPLC (50-95% ACN / H2O). The title compound (32.1 mg, 73%) was obtained as brown viscous oil. ESI-MS (m / z) 862.3 ([M+Na]+). Example 44 Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate

[0016] Step a) Ethyl 18-amino-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5- azanonadecan-19-oate The title compound was prepared as racemic mixture as described in literature (T. Gazzi et al., Chem. Sci., 2022, 13, 5539-5545). Step b) Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate The title compound was prepared analogously to Example 44 step b), with the difference that 6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxylic acid (CAS RN 960248-07-1) was used instead of 5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxylic acid (WO2005108393A1). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 749.2 ([M+Na]+). Example 45 Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate Step a) Ethyl 18-amino-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5- azanonadecan-19-oate The title compound was prepared as racemic mixture as described in literature (T. Gazzi et al., Chem. Sci., 2022, 13, 5539-5545). Step b) Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate The title compound was prepared analogously to Example 44 step b), with the difference that 6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinic acid (CAS RN 912454-39-8) was used instead of 5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran- 2-yl)methyl)-1H-pyrrole-3-carboxylic acid (WO2005108393A1). The compound was obtained as faint yellow viscous oil. ESI-MS (m / z) 728.2 ([M+Na]+). Example 46 tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate Step f) (9H-Fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate The title compound was prepared analogously to Example 3 step f), with the difference that tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate (CAS RN 153086-78-3) was used instead of tert-butyl (2-(2-aminoethoxy)ethyl)carbamate (CAS RN 127828-22- 2). The compound was obtained as white powder. ESI-MS (m / z) 606.3 ([M+Na]+). Step g) tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate The title compound was prepared analogously to Example 3 step g), with the difference that (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa-5,14- diazaoctadecan-16-yl)carbamate was used instead of (9H-fluoren-9-yl)methyl (13-ethyl- 2,2-dimethyl-4,12-dioxo-3,8-dioxa-5,11-diazapentadecan-13-yl)carbamate and 8-chloro- 1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxylic acid (CAS RN 337526-61-1) was used instead of 5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid (CAS RN 162758-35-2). The compound was obtained as colorless viscous oil. ESI-MS (m / z) 772.1 ([M+Na]+). Example 47 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide Step h) - nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)- 1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide The title compound was prepared analogously to Example 4 step h), with the difference that tert-butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate was used instead of tert-butyl (2-(2-(2-(5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate. The compound was obtained as orange powder. ESI-MS (m / z) 835.1 ([M+Na]+). Example 48 N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran- 1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8- chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2- c]pyrazole-3-carboxamide Step h) N-(1- - oxo- 1,9'-xanthen]-5- yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide The title compound was prepared analogously to Example 27 step h), with the difference that tert-butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate was used instead tert-butyl (1-(6-(4-chlorophenyl)-5- (2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate. The compound was obtained as red powder. ESI-MS (m / z) 1062.0 ([M+H]+). Example 49 N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamide Step h) (9H- - 3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)carbamate and (9H-fluoren-9-yl)methyl (1-(3',6'- bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12- dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)carbamate A solution of (9H-fluoren-9-yl)methyl (16-ethyl-2,2-dimethyl-4,15-dioxo-3,8,11-trioxa- 5,14-diazaoctadecan-16-yl)carbamate (40.0 mg, 68.5 µmol, 1 equiv.) in anhydrous DCM (1.8 mL) and TFA (0.2 mL) was stirred for 2 h. The solvent was co-evaporated with toluene (3×) and the crude material was used for the next step without further purification. The obtained ammonium salt was dissolved in anhydrous DMF (1 mL) in a brown glass flask. To the solution were added anhydrous DIPEA (47 µL, 274.1 µmol, 4.0 equiv.), HOAt (12.0 mg, 89.1 µmol, 1.3 equiv.), EDCI (17.0 mg, 89.1 µmol, 1.3 equiv.) and a mixture of 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthene]-5-carboxylic acid and 3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran- 1,9'-xanthene]-6-carboxylic acid (CAS RN 98181-63-6, TAMRA-COOH, 5 / 6-isomer mixture) (35.0 mg, 82.2 µmol, 1.2 equiv.). The solution was stirred for 18 h and the solvent removed under reduced pressure. The crude material was purified by preparative HPLC (50-95% ACN + 0.1% TFA in H2O + 0.1% TFA). The title compound (13.1 mg, 21%) was obtained as red powder. ESI-MS (m / z) 896.4 ([M+H]+). Step g) N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5- yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamide The title compound was prepared analogously to Example 23 step g), with the difference that a mixture of (9H-fluoren-9-yl)methyl (1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)carbamate and (9H-fluoren-9-yl)methyl (1-(3',6'- bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12- dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)carbamate was used instead of (9H-fluoren- 9-yl)methyl (3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)carbamate. The title compound was obtained as red powder (9.47 mg, 69%). ESI-MS (m / z) 943.3 ([M+H]+). Example 50 N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide Step h) N-(1-(3',6'- - 1,9'-xanthen]-5- yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3- carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3- carboxamide The title compound was prepared analogously to Example 19 step h), with the difference that a mixture of 2,5-dioxopyrrolidin-1-yl 3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxylate and 2,5-dioxopyrrolidin-1-yl 3',6'- bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-6-carboxylate (CAS RN 246256-50-8, TAMRA-SE, 5 / 6-isomer mixture, AATBioquest) (1.5 equiv.) was used instead of 4-fluoro-7-nitrobenzo[c][1,2,5]oxadiazole (CAS RN 29270-56-2). The title compound was obtained as red powder. ESI-MS (m / z) 1077.2 ([M+H]+). Example 51 - [3H]CP55940 displacement assay Experimentals Cell culture and membrane preparation CHOK1hCB1_bgal cells (DiscoverRx, Fremont, CA, USA) were cultured in Dulbecco’s Modified Eagle’s Medium / Nutrient Mixture F-12 Ham supplemented with 10% fetal calf serum, 1 mM glutamine, 50 µg / mL penicillin, 50 µg / mL streptomycin, 300 mg / mL hygromycin and 800 µg / mL geneticin in a humidified atmosphere at 37°C and 5% CO2. Cells were subcultured twice a week at a ratio of 1:20 on 10-cm diameter plates by trypsinization. For membrane preparation the cells were subcultured with a ratio of 1:10 and transferred to 15-cm diameter plates. The cells were collected by scraping in 5 mL phosphate-buffered saline (PBS) and centrifuged at 1,000 g for 5 min. Pellets derived from 30 plates were combined and resuspended in 20 mL cold Tris-HCl, MgCl2buffer (50 mM Tris-HCl (pH 7.4), 5 mM MgCl2). The cell suspension was homogenized using an UltraTurrax homogenizer (Heidolph Instruments Schwabach, Germany). Membranes and cytosolic fractions were separated by centrifugation in a Beckman Optima LE-80K ultracentrifuge (Beckman Coulter Inc., Fullerton, CA, USA) at 100,000 g for 20 min at 4°C. The supernatant was discarded. The pellet was resuspended in 10 mL cold Tris-HCl, MgCl2buffer and homogenization and centrifugation steps were repeated. The membranes were resuspended in 10 mL cold Tris-HCl, MgCl2 buffer. Aliquots of 100 µL were stored at -80°C until further use. The protein concentration was determined using the Pierce™ BCA Protein Assay Kit (ThermoFisher Scientific, Waltham, MA, USA). [3H]CP55940 Displacement assay [3H]CP55940 displacement assays on 96-well plates were performed in 50 mM Tris-HCl (pH 7.4), 5 mM MgCl2, 0.1% BSA assay buffer. Membrane aliquots of CHOK1hCB1_bgal containing 1 µg membrane protein respectively, were incubated at 25°C for 2h in the presence of ~1.5 nM [3H]CP55940 (specific activity 106.5 Ci / mmol; PerkinElmer, Waltham, MA). At first, all compounds were tested at a final concentration of 10 µM compound. When radioligand displacement was greater than 50%, full curves were recorded to determine the affinity (Ki) values of the compounds. To determine the total binding, a control without test compound was included. Nonspecific binding was determined in the presence of 10µM Rimonabant (CHOK1hCB1_bgal). The total assay volume was 100 µL. The final concentration of DMSO was 0.25%. The incubation was terminated by rapid vacuum filtration through GF / C 96-well filter plates (PerkinElmer, Waltham, MA), to separate the bound and free radioligand, using a PerkinElmer Filtermate-harvester (PerkinElmer, Groningen, The Netherlands). Filters were subsequently washed twenty times with ice-cold assay buffer. The filter-bound radioactivity was determined by scintillation spectrometry using a Microbeta2® 2450 microplate counter (PerkinElmer, Boston, MA), after addition of 25μl MicroScint-O (PerkinElmer, Groningen, The Netherlands) and 3h incubation. Data Analysis All experimental data were analyzed using GraphPad Prism 9 (GraphPad Software Inc., San Diego, CA). The data were normalized to % specific radioligand binding, where total binding is 100% and nonspecific binding is 0%. Nonlinear regression for one-site was used to determine the IC50values from the full curve [3H]CP55940 displacement assays. ^^^^ The Ki values were obtained using the Cheng-Prusoff equation1: ^^50^^= [^^] 1+ , where [L] is ^^^^the exact concentration [3H]CP55940 determined per experiment and the KD is the dissociation constant of [3H]CP55940, which is 0.84 for CB1R (data not shown). All data were obtained from at least three separate experiments performed in duplicate. Example 52 – Time-resolved Förster resonance transfer (TR-FRET) Assay Cell Culture Cells were maintained in a humidified environment at 37°C and 5% CO2in Dulbecco’s modified Eagle’s medium (DMEM) with 10% fetal bovine serum (FBS) containing blasticidin (5 µg / ml; Invitrogen) and (Zeocin; 20 µg / ml; Invitrogen). For inducible expression, SNAP-tagged human CB1R cDNAs, in pcDNA4 / TO were introduced through transfection, using PEI into HEK293TR cells (Invitrogen, which express Tet repressor protein to allow inducible expression). A mixed population stable line was selected by resistance to blasticidin (TR vector, 5 µg / ml) and Zeocin; (receptor plasmid, 20 µg / ml). For receptor-inducible expression, cells were seeded into t175 cm2flasks, grown to 70% confluence and DMEM containing 1 µg / ml tetracycline added.24h later cells were labelled with SNAP-Lumi4-Tb (CisBio) and membranes prepared as described in detail below. Terbium labeling of SNAP-tagged CB1 HEK293-TR cells Cell culture medium was removed from the t175 cm2flasks containing confluent adherent CB1 HEK293-TR cells. Cells were washed 1× in PBS (GIBCO Carlsbad, CA) followed by 1x Tag-lite labeling medium (LABMED, CisBio) to remove the excess cell culture media, then ten millilitre of LABMED containing 100 nM of SNAP-Lumi4-Tb was added to the flask and incubated for 1 h at 37 °C under 5% CO2. Cells were washed 1× in PBS (GIBCO Carlsbad, CA) to remove the excess of SNAP-Lumi4-Tb then detached using 5 ml of GIBCO enzyme-free Hank’s-based cell dissociation buffer (GIBCO, Carlsbad, CA) and collected in a vial containing 5 ml of DMEM (Sigma- Aldrich) supplemented with 10% fetal calf serum. Cells were pelleted by centrifugation (5 min at 1500 rpm) and the pellets were frozen to −80 °C. To prepare membranes, homogenization steps were conducted at 4 °C (to avoid receptor degradation) as described in Herenbrink et al., 2016. Fluorescent ligand-binding assays All fluorescent ligand binding experiments were conducted in white 384-well Optiplate plates, in assay binding buffer, either Hanks Balanced Salt Solution (HBSS), 5mM HEPES, 0.5% BSA, 0.02% pluronic F-127 pH 7.4, and 100 μM GppNHp or LABMED (Cisbio, Codolet, France) containing 5mM HEPES, 0.5% BSA, 0.02% pluronic acid pH 7.4, and 100 μM GppNHp. GppNHp was included to remove the G protein-coupled population of receptors that can result in two distinct populations of binding sites in membrane preparations, since the Motulsky-Mahan model is only appropriate for ligands competing at a single site. In all cases, nonspecific binding was determined by the presence of 1 μM SR144528. Determination of fluorescent ligand binding kinetics and equilibrium affinity To accurately determine association rate (kon) and dissociation rate (koff) values, the observed rate of association (kob) was calculated using at least five different concentrations fluorescent ligand. The appropriate concentration of fluorescent ligand binding was incubated with human CB1R HEK293-TR cell membranes (4 μg per well) in assay binding buffer (final assay volume, 40 μl). The degree of fluorescent ligand bound to the receptor was assessed at multiple time points by HTRF detection to allow construction of association kinetic curves. The resulting data were globally fitted to the association kinetic model (Eq.1, see signal detection and data analysis section below) to derive a single best-fit estimate for kon and koff as described under data analysis. Saturation analysis was performed at equilibrium, by simultaneously fitting total and Nonspecific (NSB) binding data (Eq.2, see see signal detection and data analysis section below) allowed the determination of fluorescent ligand binding affinity. Competition binding To determine the affinity of CB1R-specific ligands, we used a simple competition kinetic binding assay. This approach involves the simultaneous addition of both fluorescent ligand and competitor to the CB1R preparation. Compounds were added simultaneously with increasing concentrations of the unlabeled compound to CB1R cell membranes (4 μg per well) in 40 μl of assay buffer in a 384-well plate incubated at room temperature with orbital mixing. The degree of fluorescent ligand bound to the receptor was assessed at equilibrium by HTRF detection. Nonspecific binding was determined as the amount of HTRF signal detected in the presence of SR144528 (1 μM) and was subtracted from total binding, to calculate specific binding for construction of IC50curves. Signal detection and data analysis Signal detection was performed on a Pherastar FSX (BMG Labtech, Offenburg, Germany). The terbium donor was always excited with eight laser flashes at a wavelength of 337 nm. TR-FRET signals were collected at 665 (acceptor) and 620 nm (donor) when using the red acceptor fluorescent ligand, at 590 (acceptor) and 620 nm (donor) when using the orange acceptor fluorescent ligand or at 520 (acceptor) and 620 nm (donor) when using the green acceptor fluorescent ligand. HTRF ratios were obtained by dividing the acceptor signal by the donor signal and multiplying this value by 10,000. All experiments were analyzed by non-regression using Prism 8.0 (GraphPad Software, San Diego, USA). Fluorescent ligand association data were fitted as follows to a global fitting model using GraphPad Prism 8.0 to simultaneously calculate kon and koff using the following equation, kob = [L]*kon + koff (Eq.1) Y = Ymax*(1-exp(-1*kob*X)) Where, kob equals the observed rate of ligand association and kon and koff are the association and dissociation-rate constants respectively of the fluorescent ligand. In this globally fitted model of tracer binding, tracer concentrations [L] are fixed, kon and koff are shared parameters whilst kobsis allowed to vary. Here, Y is the level of receptor-bound tracer, Ymax is the level of tracer binding at equilibrium, X is in units of time (eg. min) and kobs is the rate in which equilibrium is approached (eg. min−1). Saturation binding data were analysed by non-linear regression according to a one-site (Eq.2) equation by globally ligand dissociation constant (Kd) were calculated using the following equations where L is the fluorescent ligand concentration: Fitting the total and NSB data sets globally (simultaneously), sharing the value of slope, provides one best-fit value for both the Kd and the Bmax. Competition displacement binding data were fitted to sigmoidal (variable slope) curves using a ‘four-parameter logistic equation’: Y = Bottom + (Top-Bottom) / (1+10(logIC50-X).Hill coefficient) (Eq.3) IC50values obtained from the inhibition curves were converted to Kivalues using the method of Cheng and Prusoff.1Ki = IC50 / (1+[fluorescent tracer concertation] / Kd) (Eq.4) (1) Cheng, Y.; Prusoff, W. H. Relationship between Inhibition Constant (K1) and Concentration of Inhibitor Which Causes 50 Per Cent Inhibition (I50) of an Enzymatic- Reaction. Biochem Pharmacol 1973, 22 (23), 3099-3108. Example 53 - HTRF cAMP assay for CB1R The homogeneous time-resolved fluorescence (HTRF) cAMP assay was conducted following the manufacturer's protocol for the cAMP-Gs Dynamic kit. Briefly, the CHO cell line stably overexpressing the CB1 receptor were cultured in Ham’s F12 supplemented with 10% FBS, 10 μg / mL blasticidin, and 400μg / mL zeocin. For the CB1 agonist or inverse agonist test, dissociated cells were resuspended in Ham’s F12 and dispensed into 384-well low volume plates at 6000 cells / 5 μL per well. The cells were then stimulated with compounds diluted in Stimulation Buffer (2.5 μL / well) for 15 min at room temperature, followed by the addition of 2.5 μL 5 μM forskolin. After 15 mins, reactions were stopped by the 1× cAMP-d2 conjugate in lysis buffer (5 μL / well), followed by 1× anti-cAMP cryptate conjugate in lysis buffer (5 μL / well). Following a 1 h incubation at room temperature, the plates were read in a PerkinElmer Envision reader for time- resolved fluorescence resonance energy transfer detection at 620 nm and 665 nm. The HTRF ratio versus compound concentrations was plotted using Prism 8.1 (GraphPad). HTRF Ratio = (Signal 665 nm / Signal 620 nm) × 104All HTRF ratio data sets of test compounds were normalized to the Emax of CP55940 (100%) and obtained the means ± standard error of the mean (SEM) of three independent experiments performed in technical replicates. Materials cAMP-Gs Dynamic kit (PerkinElmer, 62AM4PEC) Ham’s F12 (Gibco, C11330500BT) FBS (Gibco, A5669701) Forskolin (MCE, HY-15371) Zeocin (Gibco, R25001) Blasticidin (Gibco, A1113903) Example 54 - In Vitro Pharmacology Data Functional Ki / Kd (HTRF Ki (radioligand Example activity (cAMP Emda bax binding) (nM) binding) (nM) HTRF)c(nM) 1 2.2 33 n.d. n.d. 46 n.d. n.d. n.d. 33 37 n.d. n.d. 68 >10000 n.d. n.d. 2291 n.d. n.d. n.d. 54 139 64.6 -44% 2134 428 60.3 -41% 132 n.d. n.d. n.d. n.d. >10000 n.d. n.d. 821 >10000 n.d. n.d. 1035 2291 n.d. n.d. 146 1096 n.d. n.d. 40 397 n.d. n.d. 228 n.d. n.d. n.d. 84 603 n.d. n.d. 613 n.d. n.d. n.d. 38 1425 n.d. n.d. 65 811 131 -69% 29.2 97 16.6 -62% 75 1219 n.d. n.d. 493 n.d. n.d. n.d. n.d. 3055 n.d. n.d. n.d. >10000 n.d. n.d. 36 n.d. n.d. n.d. n.d. >10000 n.d. n.d. n.d. >10000 n.d. n.d. n.d. >10000 n.d. n.d. n.d. >10000 n.d. n.d. n.d. 1174 n.d. n.d. n.d. >10000 n.d. n.d. 58 n.d. n.d. n.d. 55 n.d. n.d. n.d. 255 n.d. n.d. n.d. 112 n.d. n.d. n.d. 335 n.d. n.d. n.d. 142 n.d. n.d. n.d. 127 n.d. n.d. n.d. 3673 n.d. n.d. n.d. 2999 n.d. n.d. n.d. n.d. 165 n.d. n.d. n.d. 5294 n.d. n.d. n.d. 565 n.d. n.d. n.d. >10000 n.d. n.d. 47 n.d. >10000 n.d. n.d. 48 n.d. >10000 n.d. n.d. 49 n.d. >10000 n.d. n.d. 50 335.5 2077 102 -64% aKi (nM) values obtained for non-fluorescent examples by displacement assay with fluorescent reference tracer on HEK293TR cell membranes with SNAP-terbium-hCB1R. Kd(nM) values obtained for fluorescent examples from saturation assay on HEK293TR cell membranes with SNAP-terbium-hCB1R.bKi(nM) values obtained from [3H]CP55,940 displacement assays on CHO membranes stably expressing human CB1R.cThe activity levels (IC50) were measured using cells stably expressing hCB1R in homogeneous time- resolved fluorescence (HTRF) cAMP assay.dMaximum effect (Emaxin %) was normalized to reference full agonist CP55,940. n.d. is not determined.

Claims

Claims 1. A compound of formula (I) or a pharmaceutically acceptable salt, tautomer or solvate thereof;formula (a) RaLaor formula (b)wherein a double line indicates the point of attachment to the rest of formula (I); and wherein Laand Lbare each independently selected from:1-30 membered alkylene, 1-30 membered heteroalkylene, 2-30 membered alkenylene, 2- 30 membered heteroalkenylene, 2-30 membered alkynylene, and 2-30 membered heteroalkynylene; each of which is optionally substituted, wherein the optionally substituted 1-30 membered heteroalkylene, 2-30 membered heteroalkenylene, and 2-30 membered heteroalkynylene each comprise 1-15 heteroatoms selected from the group consisting of N, S, O, NR5, S(O), SO2and C(O), wherein R5is H or C1-6 alkyl; Raand Rbare each independently a fluorescent label or one half of a biotin or biotin derivative binding pair, or a protecting group; and wherein B is selected from: formula (i)are independently a halogen atom; R4is H, or C1-6alkyl R6is H or R4and R6taken together with the groups to which they are attached form a C5-8membered ring; X is CH or N; or formula (ii)R is a halogen atom; X is CH or N; or formula (iii)independently a trihalomethyl group; R10is a C3-6heterocycle; X is CR11or N R11is H or C1-6alkyl; or formula (iv) R12R12is a halogen atom; R13is a C3-6cycloalkyl or (CH2)0-3-O-(CH2)0-3-H X and Y are each independently CH or N;wherein at least one of X or Y is N.

2. A compound according to claim 1, wherein B is formula (i), preferably B is:or .

3. A compound according to claim 1, wherein B is formula (ii), preferably B is: .

4. A compound according to claim 1, wherein B is formula (iii), preferably B is:

5. A compound according to claim 1, wherein B is formula (iv), preferably B is: .

6. A compound according to claim 1, wherein B is: .

7. A compound according to claim 1, wherein B is:

8. A compound according to claim 1, wherein B is: .

9. A compound according to any of the preceding claims, wherein Raand Rbare each independently a fluorescent label or one half of a biotin or biotin derivative binding pair.

10. A compound according to any of the preceding claims, wherein any Laand / or Lbis independently selected from: any of the preceding claims, wherein Raand Rbare each independently ,wherein each n is independently an integer selected from 1, 2, 3, 4, 5, 6, and 7; a wavy line indicates the point of attachment to Raor Rb; and an asterisk indicates the point of attachment of Laor Lbto rest of the fragment A.

11. A compound according to any of the preceding claims, wherein any Laand / or Lbis independently selected from: *12. A compound according to any of the preceding claims wherein A is formula (a) and Lais: *each n is independently an integer selected from 1, 2, 3, 4, 5, 6, and 7; a wavy line indicates the point of attachment to Ra; and an asterisk indicates the point of attachment of Lato rest of the fragment A.

13. A compound according to any of the preceding claims, wherein A is formula (b) and Lbis:wherein each n is independently an integer selected from 1, 2, 3, 4, 5, 6, and 7; a wavy line indicates the point of attachment to Rb; and an asterisk indicates the point of attachment of Lbto rest of the fragment A.

14. A compound according to any one of claims 10 to 13, wherein n is independently an integer selected from 1, 2, 3 and 4.

15. A compound according to claim 14, wherein n is independently an integer selected from 2 or 3; preferably, n is 2.

16. A compound according to any one of claims 1 to 12 and 14 to 15, wherein A is formula (a).

17. A compound according to any one of claims 1 to 11 and 13 to 15, wherein A is formula (b).

18. A compound according to any one of the preceding claims, wherein any Raand / or Rbare independently selected from the following structures or their tautomers: one half of a biotin or biotin derivative binding pair or ,, , ,, ,, ,,,, ,, whe 19. A compound according to any one of the preceding claims wherein any of Raand / or Rbare each independently selected from the following structures or their tautomers: one half of a biotin or biotin derivative binding pair,, , ,, La bor L ; preferably wherein any of Raand / or Rbare each independently selected from the following structures or their tautomers:,; more preferably wherein any of Raand / or Rbare each independently selected from:; 20. A compound according to any of the preceding claims, selected from: tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate;5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide;tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan- 16-yl)carbamate; tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide; tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate;6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate; 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide; Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate;Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate; Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate; Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate; Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate; Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate; Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate;Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate; 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

21. A compound according to any of the preceding claims, selected from: 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13- ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

22. A compound according to claim 20, selected from:tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide;N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate;tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan- 16-yl)carbamate; tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide; tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide;5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide; Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate; Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate; Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate; Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate; Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate;Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

23. A compound according to claim 20, selected from:tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate; 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

24. A compound according to claim 20, selected from: tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate; 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'- xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro- 1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

25. A compound according to claim 20, selected from:tert-Butyl (2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethylbutanamido)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H- pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-5-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthene]-6-carboxamido)ethoxy)ethyl)carbamoyl)pentan- 3-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-5-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(1-(3',6'-dihydroxy-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-4-methyl-1H-pyrazole-3-carboxamide;N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; N-(1-(3,7-Bis(dimethylamino)-5,5-dimethyl-3'-oxo-3'H,5H-spiro[dibenzo[b,e]siline- 10,1'-isobenzofuran]-6'-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13- yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide; 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 3-(1-(5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)-3,3- diethyl-1,4,15-trioxo-8,11-dioxa-2,5,14-triazaicosan-20-yl)-2-((1E,3E)-5-((E)-3,3- dimethyl-5-sulfo-1-(3-sulfopropyl)indolin-2-ylidene)penta-1,3-dien-1-yl)-3-methyl-1- (3-sulfopropyl)-3H-indol-1-ium-5-sulfonate; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan-16-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(14-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-13-oxo-3,6,9-trioxa-12-azahexadecan-14- yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl)- 3,3-diethyl-1,4-dioxo-8,11,14,17-tetraoxa-2,5-diazanonadecan-19-yl)carbamate; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(17-ethyl-1-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-16-oxo-3,6,9,12-tetraoxa-15- azanonadecan-17-yl)-4-methyl-1H-pyrazole-3-carboxamide; tert-Butyl (2-(2-(2-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate;tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13- yl)carbamate; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; tert-Butyl (1-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrol-3-yl)-3,3-diethyl-1,4-dioxo-8,11,14-trioxa-2,5-diazahexadecan- 16-yl)carbamate; tert-Butyl (2-(2-(2-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-2- ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)pyridin-3-yl)-3,3-diethyl- 1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(Cyclopropylmethoxy)-5-(4-fluorophenyl)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)nicotinamide; tert-Butyl (2-(2-(2-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2- carboxamido)-2-ethylbutanamido)ethoxy)ethyl)carbamate; tert-Butyl (1-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazin-2-yl)-3,3-diethyl-1,4- dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamate; 6-(4-Chlorophenyl)-5-(2-methoxyethoxy)-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(4-chlorophenyl)-5-(2- methoxyethoxy)pyrazine-2-carboxamide;tert-Butyl (3,3-diethyl-1-(1-(3-fluorobenzyl)-1H-indazol-3-yl)-1,4-dioxo-8,11-dioxa- 2,5-diazatridecan-13-yl)carbamate; 1-(3-Fluorobenzyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1H-indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-1-(3-fluorobenzyl)-1H- indazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-ethyl-4,15-dioxo-19-((3aS,4S,6aR)- 2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-8,11-dioxa-5,14-diazanonadecan-3- yl)-4-methyl-1H-pyrazole-3-carboxamide; 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((2,2-dimethyl-7-nitro-2H- benzo[d]imidazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-4-methyl- 1H-pyrazole-3-carboxamide; tert-Butyl (1-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11- dioxa-2,5-diazatridecan-13-yl)carbamate; 8-Chloro-1-(2,4-dichlorophenyl)-N-(3-((2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3-yl)-1,4,5,6- tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-8-chloro-1-(2,4- dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3- carboxamide;N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-6-(cyclopropylmethoxy)- 5-(4-fluorophenyl)nicotinamide; N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-6-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

26. A compound according to claim 20, selected from: 3',6'-Diamino-5-((1-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazol-3-yl)-3,3-diethyl-1,4-dioxo-8,11-dioxa-2,5-diazatridecan-13-yl)carbamoyl)- 3-oxo-3H-spiro[isobenzofuran-1,9'-xanthene]-4',5'-disulfonic acid; 5-(2,5-Bis(trifluoromethyl)phenyl)-2-methyl-N-(3-((2-(2-(2-((7- nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)ethoxy)ethoxy)ethyl)carbamoyl)pentan-3- yl)-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide; and N-(1-(3',6'-Bis(dimethylamino)-3-oxo-3H-spiro[isobenzofuran-1,9'-xanthen]-5-yl)- 13-ethyl-1,12-dioxo-5,8-dioxa-2,11-diazapentadecan-13-yl)-5-(2,5- bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2-yl)methyl)-1H- pyrrole-3-carboxamide and N-(1-(3',6'-bis(dimethylamino)-3-oxo-3H- spiro[isobenzofuran-1,9'-xanthen]-6-yl)-13-ethyl-1,12-dioxo-5,8-dioxa-2,11- diazapentadecan-13-yl)-5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)- tetrahydrofuran-2-yl)methyl)-1H-pyrrole-3-carboxamide;or a pharmaceutically acceptable salt, tautomer or solvate thereof.

27. A compound according to claim 20, selected from: Ethyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-(5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamido)-2-ethylbutanoate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)butanoate; Ethyl 14-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-14-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-5-azapentadecan-15-oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)butanoate; Ethyl 17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 2-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-2-ethyl-4-(2-(2-(2-((7-nitrobenzo[c][1,2,5]oxadiazol-4- yl)amino)ethoxy)ethoxy)ethoxy)butanoate; Ethyl 20-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-20-ethyl-2,2-dimethyl-4-oxo-3,8,11,14,17-pentaoxa-5-azahenicosan- 21-oate; Ethyl 15-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-15-ethyl-1-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)-3,6,9,12- tetraoxahexadecan-16-oate; Ethyl (R)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate;Ethyl (S)-17-(5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamido)-17-ethyl-2,2-dimethyl-4-oxo-3,8,11,14-tetraoxa-5-azaoctadecan-18- oate; Ethyl 18-(5-(2,5-bis(trifluoromethyl)phenyl)-2-methyl-1-(((R)-tetrahydrofuran-2- yl)methyl)-1H-pyrrole-3-carboxamido)-18-ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa- 14-thia-5-azanonadecan-19-oate; Ethyl 18-(6-(4-chlorophenyl)-5-(2-methoxyethoxy)pyrazine-2-carboxamido)-18- ethyl-2,2-dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; and Ethyl 18-(6-(cyclopropylmethoxy)-5-(4-fluorophenyl)nicotinamido)-18-ethyl-2,2- dimethyl-4-oxo-3,8,11-trioxa-14-thia-5-azanonadecan-19-oate; or a pharmaceutically acceptable salt, tautomer or solvate thereof.

28. A compound according to any one of claims 1, 2, 4-6, 9-22 and 25-27 which is an inverse agonist of cannabinoid receptor type 1 (CB1).

30. A compound according to any one of claims 1, 3, 5, 7, 9-21, 23 and 25-27 which is an agonist of cannabinoid receptor type 1 (CB1).

31. A compound according to any one of claims 1, 2, 8, 9-21, 24 and 25-27 which is an antagonist of cannabinoid receptor type 1 (CB1).

32. A method of manufacturing a compound according to any one of the preceding embodiments, wherein the method comprises the steps of either sequence (1), (2) or (3): (1) (a) the reaction of a compound of formula (AC)C) in presence of a suitable solvent and a suitable acid; and (b) the reaction of the unprotected derivative of the compound of formula (AC) with a carboxylic acid or carboxylic ester of formula Ra-OH / OR or Ra-X in presence of a suitable solvent and a suitable base, and in case carboxylic acid or ester is applied, also in presence of a suitable coupling reagent, to yield a compound of formula (Ia)(a) the reaction of a compound of formula (BC)in presence of a suitable solvent and a suitable acid; and (b) the reaction of the unprotected derivative of the compound of formula (BC) with a carboxylic acid or carboxylic ester of formula Rb-OH / OR or Rb-X in presence of asuitable solvent and a suitable base, and in case carboxylic acid or ester is applied, also in presence of a suitable coupling reagent, to yield a compound of formula (Ib)(3) (a) the reaction of a compound of formula (BD)in presence of a suitable solvent and a suitable base; and (b) the reaction of the unprotected derivative of the compound of formula (BC) with a compound of formula (BX) (BX) in presence of a suitable coupling reagent, a suitable solvent and a suitable base, to yield a compound of formula (Ib)). wherein in the reactions above, B, La, Lb, Raand Rbare according to any one of the preceding claims, PG1is a suitable protecting group and X is a suitable leaving group.

33. A compound according to any one of claims 1 to 31, for use in a cannabinoid receptor type 1 (CB1) occupancy study.

34. A compound according to any one of claims 1 to 31, for use in diagnostic imaging of cannabinoid receptor type 1 (CB1) in a mammal.

35. A compound according to any one of claims 1 to 31, for use in generating cannabinoid receptor type 1 (CB1) equilibrium and kinetic binding data.

36. Use of a compound according to any one of claims 1 to 31, in diagnostic imaging of cannabinoid receptor type 1 (CB1) in a mammal.

37. Use of a compound according to any one of claims 1 to 31, in generating cannabinoid receptor type 1 (CB1) equilibrium and kinetic binding data.

38. A method of studying cannabinoid receptor type 1 (CB1) occupancy, comprising contacting CB1 with a compound according to any one of claims 1 to 31.

39. A method of diagnostic imaging of cannabinoid receptor type 1 (CB1) in a mammal, comprising contacting CB1 with a compound according to any one of claims 1 to 31.

40. A method of generating cannabinoid receptor type 1 (CB1) equilibrium and kinetic binding data, comprising contacting CB1 with a compound according to any one of claims 1 to 31. ***

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