The present invention relates to small molecule compounds and their use as agonists of farnesoid X receptor (FXR) and/or peroxisome proliferator-activated receptor delta (PPAR6). The present invention also relates to the use of said compounds in the treatment of metabolic diseases and respective methods of treatment.

BACKGROUND OF THE INVENTION

The farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4) is a nuclear receptor that is encoded by the NR1H4 gene in humans. FXR is expressed at high levels in the liver and intestine. Chenodeoxycholic acid and other bile acids are natural ligands for FXR. Similar to other nuclear receptors, when activated, FXR translocates to the cell nucleus, forms a dimer (in this case a heterodimer with RXR) and binds to hormone response elements on DNA, which up- or down-regulates the expression of certain genes. One of the primary functions of FXR activation is the suppression of cholesterol 7 alpha- hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis from cholesterol. FXR does not directly bind to the CYP7A1 promoter. Rather, FXR induces expression of small heterodimer partner (SHP), which then functions to inhibit transcription of the CYP7A1 gene. In this way, a negative feedback pathway is established in which synthesis of bile acids is inhibited when cellular levels are already high. FXR has also been found to be important in regulation of hepatic triglyceride levels and glucose homeostasis. Studies have also shown the FXR to regulate the expression and activity of epithelial transport proteins involved in fluid homeostasis in the intestine, such as the cystic fibrosis transmembrane conductance regulator (CFTR).

The natural bile acid, chenodeoxycholic acid, was identified in 1999 as the most active physiological ligand for the FXR, which is involved in many physiological and pathological processes. Obeticholic acid (abbreviated to OCA, trade name Ocaliva), is a semi-synthetic bile acid analogue which has the chemical structure 6a-ethyl-chenodeoxycholic acid. It is used as a drug to treat primary biliary cholangitis, and is undergoing development for several other liver diseases and related disorders. Obeticholic acid is undergoing development in phase 2 and 3 studies for specific liver and gastrointestinal conditions, in particular, nonalcoholic steatohepatitis (NASH).

Non-alcoholic steatohepatitis is a common cause of abnormal liver function with histological features of fatty liver, inflammation and fibrosis. It may progress to cirrhosis and is becoming an increasing indication for liver transplantation. It is increasing in prevalence. OCA is proposed to treat NASH. A phase 2 trial published in 2013 showed that administration of OCA at 25 mg or 50 mg daily for 6 weeks reduced markers of liver inflammation and fibrosis and increased insulin sensitivity.

Peroxisome proliferator-activated receptor beta or delta (PPAR-β or PPAR-δ), also known as NR1C2 (nuclear receptor subfamily 1, group C, member 2) is a nuclear receptor that in humans is encoded by the PPARD gene. This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. PPAR5 is a nuclear hormone receptor that governs a variety of biological processes and is involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer. PPAR8 may function as an integrator of transcription repression and nuclear receptor signaling. It activates transcription of a variety of target genes by binding to specific DNA elements. Well described target genes of PPAR5 include PDK4, ANGPTL4, PLIN2, and CD36. PPAR5 is an important regulator of lipid metabolism and insulin sensitivity in liver and peripheral tissues such as skeletal muscle. Knockout studies in mice also suggest a role of PPAR5 in myelination of the corpus callosum, epidermal cell proliferation, and glucose and lipid metabolism. This protein has been shown to be involved in differentiation, lipid accumulation, directional sensing, polarization, and migration in keratinocytes.

Elafibranor is an experimental medication that is being studied and developed for the treatment of cardiometabolic diseases including diabetes, insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). Elafibranor is a dual PPARa/δ agonist.

There is a need in the art for improved agonists and dual modulators of FXR and/or PPAR5.

SUMMARY OF THE INVENTION According to the present invention this object is solved by providing a compound having general formula I

wherein

X ₁ and X ₂ are each independently selected from CH ₂ or NH,

Ri and R ₂ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), CF ₃ 0, CF ₃ , OH, halogen, R ₁ and R ₂ can form a ring,

R ₃ to R6 are each independently selected from hydrogen, C ₁ to C ₃ alkyl, alkoxy (preferably methoxy), halogen,

R ₇ and R ₈ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen,

X3 is selected from CH, N or O,

A is selected from

wherein

R ₉ to R ₃₁ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), halogen,

X ₄ and X ₅ are each independently selected from CH, O or S, and

Χ ₆ is selected from CH, N or O, or a derivative or a pharmaceutically accepted salt thereof.

According to the present invention this object is solved by providing a compound having general formula I

wherein

X ₁ and X ₂ are each independently selected from CH ₂ or NH,

R ₁ and R ₂ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), CF ₃ O, CF ₃ , OH, halogen, R ₁ and R ₂ can form a ring,

R ₃ to R ₆ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, alkoxy (preferably methoxy), halogen,

R ₇ and Rs are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen,

X ₃ is selected from CH, N or O,

A is selected from

and

wherein

R32 to R ₄₇ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy

(preferably methoxy), halogen, and

X ₇ to X ₁₃ are each independently selected from CH, N or O, preferably N or O, or a derivative or a pharmaceutically accepted salt thereof.

According to the present invention this object is solved by providing a compound having general formula la

wherein X ₁ and X ₂ , R ₁ and R ₂ , R ₃ to R ₆ , X3 and A are as defined above, and

R ₇ and R ₈ and R ₄₈ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen. or a derivative or a pharmaceutically accepted salt thereof.

According to the present invention this object is solved by using a compound according to the present invention as an agonist of farnesoid X receptor (FXR) and/or peroxisome proliferator- activated receptor delta (PPAR5),

preferably as dual agonist of FXR and PPAR5.

According to the present invention this object is solved by a pharmaceutical composition comprising

(a) at least one compound according to the present invention,

(b) optionally, pharmaceutically acceptable excipient(s) and/or carrier.

According to the present invention this object is solved by providing the compound(s) or the pharmaceutical composition of the present invention for use as a medicament.

According to the present invention this object is solved by providing the compound(s) or the pharmaceutical composition of the present invention for use in a method of treatment of metabolic disease(s). According to the present invention this object is solved by providing the compound(s) or the pharmaceutical composition of the present invention for use in a method of treatment of atherosclerosis and/or cardiovascular disease(s).

DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

Before the present invention is described in more detail below, it is to be understood that this invention is not limited to the particular methodology, protocols and reagents described herein as these may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. For the purpose of the present invention, all references cited herein are incorporated by reference in their entireties.

Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. As an illustration, a numerical range of "0.03 to 60 mg per kg" should be interpreted to include not only the explicitly recited values of 0.03 to 60, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 0.03, 0.035, 0.04,0.045, ... 59 , 60 and sub-ranges such as from 14 to 20, from 14 to 30, from 15 to 25, from 19 to 25, from 20 to 25, from 20 to 30 and from 15 to 30, etc. This same principle applies to ranges reciting only one numerical value, such as "at least 0.03 mg per kg". Furthermore, such an interpretation should apply regardless of the breadth of the range or the characteristics being described.

Agonists of FXR and/or PPARS

As discussed above, the present invention provides a class of small molecule compounds and their use as agonists of FXR and/or PPAR5.

A compound of the present invention is a compound having the general formula I:

wherein

X ₁ and X ₂ are each independently selected from CH ₂ or NH,

R ₁ and R ₂ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), CF ₃ 0, CF ₃ , OH, halogen, Ri and R ₂ can form a ring,

R ₃ to R ₆ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, alkoxy (preferably methoxy), halogen,

R ₇ and R ₆ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen, X3 is selected from CH, N or O,

A is selected from

wherein

R ₉ to R ₃₁ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), halogen,

X ₄ and X ₅ are each independently selected from CH, O or S, and

X ₆ is selected from CH, N or O, or a derivative or a pharmaceutically accepted salt thereof. A compound of the present invention is a com ound having general formula I:

wherein

X ₁ and X ₂ are each independently selected from CH ₂ or NH,

R ₁ and R ₂ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), CF ₃ O, CF ₃ , OH, halogen, Ri and R ₂ can form a ring,

R ₃ to R ₆ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, alkoxy (preferably methoxy), halogen,

R ₇ and R ₈ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen,

X ₃ is selected from CH, N or O,

and

A is selected from

and

wherein

R ₃₂ to R4 ₇ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), halogen, and

X ₇ to X ₁₃ are each independently selected from CH, N or O, preferably N or O, or a derivative or a pharmaceutically accepted salt thereof. A compound of the present invention is a compound having general formula la

wherein X ₁ and X ₂ , R ₆ and R ₂ , R ₃ to R, X ₃ and A are as defined in claim 1 or 2, and

R ₇ and R ₈ and R ₄₈ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen, or a derivative or a pharmaceutically accepted salt thereof.

A compound of the present invention can be a compound having the general formula I or la:

wherein

X ₁ and X ₂ are each independently selected from CH ₂ or NH,

Ri and R ₂ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), CF ₃ 0, CF ₃ , OH, halogen, ¾ and R ₂ can form a ring,

R ₃ to Re are each independently selected from hydrogen, C ₁ to C ₃ alkyl, alkoxy (preferably methoxy), halogen,

R ₇ and R ₈ and R ₄₈ are each independently selected from hydrogen, C ₁ to C ₃ alkyl, halogen, X ₃ is selected from CH, N or O,

A is selected from

wherein

R ₉ to R ₁₇ are each independently selected from hydrogen, C ₁ to C ₄ alkyl, alkoxy (preferably methoxy), halogen,

X ₄ and X5 are each independently selected from CH, O or S, and

X ₆ is selected from CH, N or O,

X ₇ to X ₁₃ are each independently selected from CH, N or O, preferably N or O, or a derivative or a pharmaceutically accepted salt thereof.

Examples for "C ₁ to C ₄ alkyl" are: methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, or tert-butyl.

Examples for "C ₁ to C ₃ alkoxy" or "alkoxy" are: methoxy, ethoxy, or propoxy.

Preferably, the compounds of the present invention are compounds, wherein A is selected from

with R ₉ to R ₃₁ as defined above, and/or wherein A is selected from

with R ₃₂ to R ₄₇ as defined above, More preferably, A is selected from

Preferably, the compounds of the present invention are compounds, wherein X ₁ and X ₂ are each NH and X ₃ is CH.

Said compounds have general formula II or Ila

Preferably, the compounds of the present invention are compounds are selected from

Preferably the compounds of the present invention are compounds are selected from

Said compounds are preferably dual agonists of FXR and PPAR5. See below. More preferably, the compounds of the present invention are selected from Compound # 5 in Table 1 (see below):

Compound # 24 in Table 1 (see below):

Compound # 23 in Table 1 (see below):

Compound # 1 in Table 1 (see below):

Compound # 14 in Table 1 (see below):

Compound # 34 in Table 1 (see below):

Compound # 38 in Table 1 (see below):

In one embodiment, the compounds of the present invention are compounds selected from

Said compounds are preferably agonists of PPAR5. See below.

In one embodiment, the compounds of the present invention are compounds selected from

In one embodiment, the compounds of the present invention are compounds selected from

As discussed above, the present invention provides the use of the compounds of the present invention as agonists of farnesoid X receptor (FXR) and/or peroxisome proliferator-activated receptor delta (PPAR5).

Preferably, the compounds are dual agonists of FXR and PPAR5. Agonists of the farnesoid X receptor (FXR), such as obeticholic acid, and agonists of the peroxisome proliferator-activated receptor delta (PPAR8), such as elafibranor, are studied in phase 3 clinical trials for the treatment of non-alcoholic steatohepatitis (NASH). Both agents revealed therapeutic efficacy and have been granted fast-track and breakthrough medication designation respectively by the FDA. Although both agents target nuclear receptors their efficacy is established mainly via different mechanisms and in different tissues.

Hepatic and intestinal FXR activation by obeticholic acid improves hepatic steatosis by reducing lipid synthesis and enhancing lipid degradation in the liver. Moreover, FXR activation has cell-protective and anti-inflammatory effects in the liver leading to reduced hepatic inflarnmation, reduced hepatocyte apoptosis and reduced liver damage from oxidative stress.

PPAR6 activation by elafibranor improves hepatic fat content predominantly through peripheral effects because the receptor's expression is especially high in skeletal muscle. It leads to enhanced peripheral lipid utilization and an improved overall lipid profile which in turn has beneficial effects on liver health and reduces hepatic steatosis.

Thus, combining hepatic (FXR activation) and extrahepatic (PPAR5 activation) anti-NASH activity establishes additive or synergistic efficacy due to the above discussed different mechanisms of action. Dual modulators of FXR and PPAR5, therefore, represent a novel superior therapeutic principle to treat non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and related metabolic disorders. Such dual modulators are presented in this invention.

The combination of two activities in a single drug molecule can produce a synergistic therapeutic efficacy. In contrast to the use of two selective drugs, a dual modulator is superior since it only comprises a single toxicity/side-effect potential and a single pharmacokinetic profile. Additionally, it requires only developmental costs for one compound.

Pharmaceutical compositions and medical uses

As discussed above, the present invention provides a pharmaceutical composition comprising

(a) at least one compound according to the present invention,

(b) optionally, pharmaceutically acceptable excipient(s) and/or carrier. The pharmaceutical composition can optionally comprise further agent(s) and/or drug(s).

In one embodiment, the pharmaceutical composition of the present invention further comprises

(c) agent(s) or drug(s) for the treatment of metabolic disorder(s),

and/or

(d) agent(s) or drug(s) to treat non-alcoholic steatohepatitis.

Agent(s) or drug(s) for the treatment of metabolic disorder(s) can be PPAR agonist(s), SGLT2 inhibitor(s), incretin mimetic(s), metformin and/or HMG-CoA reductase inhibitor(s).

Agent(s) or drug(s) for the treatment of non-alcoholic steatohepatitis can be inhibitor(s) of the soluble epoxide hydrolase, inhibitor(s) of the apoptosis regulating kinase 1, and/or caspase inhibitor (s).

As discussed above, the present invention provides a compound according to the present invention or the pharmaceutical composition according to the present invention for use as a medicament.

As discussed above, the present invention provides a compound according to the present invention or the pharmaceutical composition according to the present invention for use in a method of treatment of a metabolic disease.

The metabolic disease is preferably selected from

non-alcoholic fatty liver disease (NAFLD),

non-alcoholic steatohepatitis (NASH),

type 2 diabetes mellitus,

obesity,

dyslipidemia.

As discussed above, the present invention provides a compound according to the present invention or the pharmaceutical composition according to the present invention for use in a method of treatment of atherosclerosis and/or cardiovascular disease. Preferably, the medical use of the present invention comprises the administration of a therapeutically effective amount of a compound of the present invention or of a pharmaceutical composition of the present invention.

Methods for treatment

The present invention provides a method of treatment of a metabolic disease.

Said treatment method comprises the step of

administering to a subject a therapeutically effective amount of at least one compound according to the invention or a pharmaceutical composition of the invention.

A "therapeutically effective amount" of a compound according to the invention preferably refers to the amount necessary to achieve the therapeutic outcome.

The dosage of the compounds according to the invention is carried out in the order of magnitude customary for FXR agonists and/or for ΡΡΑΙΙδ agonists. For example, the customary dose in the case of systemic therapy (p.o.) may be between 0.03 and 60 mg/kg body weight per day, (i. v.) may be between 0.03 and 60 mg/kg/h. In another embodiment, the customary dose in the case of systemic therapy (p.o.) is between 0.3 and 30 mg/kg per day, (i. v.) is between 0.3 and 30 mg/kg/h. The choice of the optimal dosage regime and duration of medication, particularly the optimal dose and manner of administration of the active compounds necessary in each case can be determined by a person skilled in the art on the basis of his/her expert knowledge.

Preferably, the metabolic disease is selected from

non-alcoholic fatty liver disease (NAFLD),

non-alcoholic steatohepatitis (NASH),

type 2 diabetes mellitus,

obesity,

dyslipidemia.

In one embodiment, the treatment method of the invention comprises administering to a subject a therapeutically effective amount of a compound according to the invention or a pharmaceutical composition of the invention

in combination with further agent(s) or drug(s),

such as agent(s) or drug(s) for the treatment of metabolic disorder(s), and/or agent(s) or drug(s) to treat non-alcoholic steatohepatitis.

as discussed above.

Agent(s) or drug(s) for the treatment of metabolic disorder(s) can be PPAR agonist(s), SGLT2 inhibitor(s), incretin mimetic(s), metformin and/or HMG-CoA reductase inhibitor(s).

Agent(s) or drug(s) for the treatment of non-alcoholic steatohepatitis can be inbibitor(s) of the soluble epoxide hydrolase, inhibitor(s) of the apoptosis regulating kinase 1, and/or caspase inhibitor(s).

The present invention further provides a method of treatment of atherosclerosis, and/or a cardiovascular disease.

Said treatment method comprises the step of

administering to a subject a therapeutically effective amount of at least one compound according to the invention or a pharmaceutical composition of the invention.

A "therapeutically effective amount" of a compound according to the invention preferably refers to the amount necessary to achieve the therapeutic outcome.

The dosage of the compounds according to the invention is carried out in the order of magnitude customary for FXR agonists and/or for PPAR5 agonists. For example, the customary dose in the case of systemic therapy (p.o.) may be between 0.03 and 60 mg/kg body weight per day, (i. v.) may be between 0.03 and 60 mg/kg/h. In another embodiment, the customary dose in the case of systemic therapy (p.o.) is between 0.3 and 30 mg/kg per day, (i. v.) is between 0.3 and 30 mg/kg/h. The choice of the optimal dosage regime and duration of medication, particularly the optimal dose and manner of administration of the active compounds necessary in each case can be determined by a person skilled in the art on the basis of his/her expert knowledge. The following examples and drawings illustrate the present invention without, however, limiting the same thereto.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1. Structure of FXR and PPAR3 agonists.

Figure 2. Pharmacological characteristics of FXR and PPARd agonists.

Shown are the metabolic stability (A), aqueous stability (B) and toxicity (C) of the five compounds GF054, GF098, GF104, PH023 and PH141, i.e. compounds # 10, 24, 23, 1 and 14 in Table 1 below.

EXAMPLES

EXAMPLE 1 Methods for in vitro characterization

1. Full length FXR transactivation assay

1.1 Plasmid

pcDNA3-hFXR contains the sequence of human FXR and was already published elsewhere (Steri et al, 2012). pGL3basic (Promega Corporation, Fitchburg, WI, USA) was used as a reporter plasmid, with a shortened construct of the promotor of the bile salt export protein (BSEP) cloned into the Sacl/Nhel cleavage site in front of the luciferase gene (Ananthanarayanan et al, 2001). pRL-SV40 (Promega) was transfected as a control for normalization of transfection efficiency and cell growth. pSG5-hRXR was published elsewhere (Seuter et al, 2007).

1.2 Assay procedure

HeLa cells were grown in DMEM high glucose supplemented with 10% FCS, sodium pyruvate (1 mM), penicillin (100 U/mL) and streptomycin (100 μg/mL) at 37 °C and 5% C0 ₂ . 24 h before transfection, HeLa cells were seeded in 96-well plates with a density of 8000 cells per well. 3.5 h before transfection, medium was changed to DMEM high glucose, supplemented with sodium pyruvate (1 mM), penicillin (100 U/mL), streptomycin (100 μg/mL) and 0.5% charcoal-stripped FCS. Transient transfection of HeLa cells with BSEP-pGL3, pRL-SV40 and the expression plasmids pcDNA3-hFXR and pSG5-hRXR was carried out using calcium phosphate transfection method. 16 h after transfection, medium was changed to DMEM high glucose, supplemented with sodium pyruvate (1 mM), penicillin (100 U/mL), streptomycin (100 μg/mL) and 0.5% charcoal-stripped FCS. 24 h after transfection, medium was changed to DMEM without phenol red, supplemented with sodium pyruvate (1 mM), penicillin (100 U/mL), streptomycin (100 μg/mL), L-glutamine (2 mM) and 0.5% charcoal-stripped FCS, now additionally containing 0.1% DMSO and the respective test compound or 0.1% DMSO alone as untreated control. Each concentration was tested in triplicate wells and each experiment was repeated independently at least three times. Following 24 h incubation with the test compounds, cells were assayed for luciferase activity using Dual-Glo™ Luciferase Assay System (Promega) according to the manufacturer's protocol. Luminescence was measured with a Tecan Spark 10M luminometer (Tecan Deutschland GmbH, Crailsheim, Germany). Normalization of transfection efficiency and cell growth was done by division of firefly luciferase data by renilla luciferase data multiplied by 1000 resulting in relative light units (RLU). Fold activation was obtained by dividing the mean RLU of the tested compound at a respective concentration by the mean RLU of untreated control. Relative activation was obtained by dividing the fold activation of the tested compound at a respective concentration by the fold activation of FXR full agonist GW4064 at 3 μΜ. EC ₅₀ and standard error of the mean values were calculated with the mean relative activation values of at least three independent experiments by OriginPro 2017 (OriginLab Corporation, Northampton, MA, USA) using a four parameter logistic regression. The assay was validated with FXR agonists chenodeoxycholic acid (EC ₅₀ = 18 ± 1 μΜ, 88 ± 3% rel. max. act), obeticholic acid (EC ₅₀ = 0.16 ± 0.02 μΜ, 87 ± 3% rel. max. act) and GW4064 (EC ₅₀ = 0.51 ± 0.16 μΜ, 3 μΜ defined as 100%) (Merk et al, 2014).

2. Hybrid reporter gene assay for PPAR5

2.1 Plasmids

The Gal4-fusion receptor plasmid pFA-CMV-hPPAR5-LBD (Rau et al, 2006) has been reported previously. pFR-Luc (Stratagene) was used as reporter plasmid and pRL-SV40 (Promega) for normalization of transfection efficiency and cell growth.

2.2 Assay procedure

HEK293T cells were grown in DMEM high glucose, supplemented with 10% FCS, sodium pyruvate (1 mM), penicillin (100 U/mL) and streptomycin (100 μg/mL) at 37 °C and 5% C0 ₂ . The day before transfection, HEK293T cells were seeded in 96-well plates (3 · 10 ⁴ cells/well). Before transfection, medium was changed to Opti-MEM without supplements. Transient transfection was carried out using Lipofectamine LTX reagent (Invitrogen) according to the manufacturer's protocol with pFR-Luc (Stratagene), pRL-SV40 (Promega) and pFA-CMV-hPPAR5-LBD. 5 h after transfection, medium was changed to Opti-MEM supplemented with penicillin (lOO U/mL), streptomycin (100 μg/mL), now additionally containing 0.1% DMSO and the respective test compound or 0.1% DMSO alone as untreated control. Each concentration was tested in duplicates and each experiment was repeated independently at least three times. Following overnight (12-14 h) incubation with the test compounds, cells were assayed for luciferase activity using Dual-Glo™ Luciferase Assay System (Promega) according to the manufacturer's protocol. Luminescence was measured with a Tecan Spark 10M luminometer (Tecan Deutschland GmbH, Crailsheim, Germany). Normalization of transfection efficiency and cell growth was done by division of firefly luciferase data by renilla luciferase data and multiplying the value by 1000 resulting in relative light units (RLU). Fold activation was obtained by dividing the mean RLU of a test compound at a respective concentration by the mean RLU of untreated control. Relative activation was obtained by dividing the fold activation of a test compound at a respective concentration by the fold activation of LI 65,041 at 1 μΜ. The hybrid assay was validated with the above mentioned reference agonist which yielded values in agreement with literature.

3. Results

Table 1

Results expressed as mean ± SEM. n = 3-12; inactive - no activity at 10 μΜ if not else indicated.

EXAMPLE 2 Chemical synthesis

General procedure A: The amine (1.0 eq.) was dissolved in boiling ethanol (c = 0.2 M) and isatoic anhydride (2.0 eq.) was added. The mixture was heated for 1.5 hours under reflux, cooled to room temperature and filtered. Subsequently, the solvent was evaporated under reduced pressure and the product was isolated by column chromatography on silica.

General procedure B: The corresponding acid (1.0 eq.) was dissolved in a 20:1 (v/v) mixture of ethanol and concentrated sulfuric acid (c = 0.5 M) and heated to reflux for two hours. Then, the solution was neutralized with sodium carbonate and the crude product was extracted three the solution was neutralized with sodium carbonate and the crude product was extracted three times with dichloromethane. The organic layers were combined, dried over sodium sulfate and the solvent was evaporated. If required, the product was further purified by column chromatography on silica.

General procedure CI: A mixture of carboxylic acid (1.1 eq.), EDC (1.2 eq.), and 4-DMAP (0.2 eq.) were dissolved in dry dichloromethane (c = 0.2 M) under argon atmosphere. Then, a solution of the corresponding amine (1.0 eq.) in dry DCM (c = 0.4 M) was added slowly and the mixture heated to reflux for six hours. After cooling, the solvent was evaporated and the product purified by column chromatography on silica.

General procedure C2: If the acid chloride was not available commercially, a solution of the corresponding acid (1.3 eq.) in thionyl chloride (c = 1.0 M) was heated to reflux for two hours. Excessive thionyl chloride was removed by distillation and the acid chloride was washed twice with toluene, which was distilled off, as well. Subsequently, the acid chloride was redissolved in dry THF (c = 0.6 M) under argon atmosphere. Pyridine (3.0 eq.) and a solution of the corresponding amine (1.0 eq.) in dry THF (c = 1 M) were added and the mixture was heated to reflux for one hour. Then, 5% HC1 was added and the product was extracted three times with EA. The combined organic layers were dried over Na ₂ S0 ₄ and the solvent removed by evaporation under reduced pressure. The product was purified by column chromatography on silica.

General procedure Dl: The nitro compound (1.0 eq.) was dissolved in EA (c = 0.05 M). Palladium (10%) on charcoal (0.1 eq.) was added, the suspension flushed with argon and then stirred under hydrogen atmosphere overnight. On the next day, the charcoal was filtered off on celite or silica, the solvent was evaporated. If necessary, the product was further purified by column chromatography on silica.

General procedure D2: The nitroarene (1.0 eq) was dissolved in a 2:1 mixture of EA and acetic acid (c = 0.05 M). Then, iron turnings (5.0 eq.) were added. Alternatively, the reduction was carried out with 4.2 equivalents tin(II) chloride in THF/10% HC1 (c = 0.1 M). The resulting suspension were stirred at 50 °C. After TLC had indicated complete reaction, the suspension was filtered over celite. Water was added to the filtrate and the crude product was extracted three times with EA. The combined organic layers were dried over sodium sulfate and subsequently, the solvent was removed under reduced pressure. The pure product was obtained after column chromatography on silica.

General procedure E: To a solution of the ester (1.0 eq.) in THF (c = 0.05 M) was added an aqueous solution of lithium hydroxide (6.0 eq, c = 1.0 M). The resulting mixture was either heated to 50 °C or stirred at ambient temperature until TLC indicated complete conversion. Subsequently, the solution was acidified with 5% HC1 and the product extracted three times with EA. If necessary, further purification was achieved by column chromatography on silica.

General procedure F: Chromenes were synthesized out of the corresponding salicylaldehyde (1.0 eq.), which was heated to reflux in acrylonitrile (c = 1 M) and 1,4- diazabicyclo[2.2.0]octane (0.2 eq.) for 15 hours under argon atmosphere. After cooling to room temperature, EA and 1 M NaOH (1 :1) were added. The organic layer was dried over Na ₂ S0 ₄ and the solvent removed by evaporation. Column chromatography provided the pure product.

General procedure G: Chromene-3-carbonitriles (1.0 eq.) were hydrolyzed to the respective carboxylic acid in a 0.2 M suspension of 10% NaOH under reflux for six hours. The obtained solution was then acidified with 10% HC1. If the product precipitated, it was filtered, washed with water and dried under vacuum. In the other case, the product was extracted three times with EA, dried over sodium sulfate and the solvent evaporated.

General procedure H: Methoxyaromatics (1.0 eq.) were dissolved in dry DCM (c = 0.03 M) at 0 °C under argon atmosphere. After careful addition of the Lewis acid, which was either 3.0 equivalents of aluminium chloride or a 1 M solution of BBr ₃ (10 eq.), the solution was allow to warm to ambient temperature and stirred overnight. The reaction was terminated by addition of water followed by 5% HC1. The crude product was extracted three times with EA, dried over Na ₂ S0 ₄ , and the solvent evaporated under reduced pressure. Column chromatography on silica provided the pure product.

General procedure I: To a solution of the aromatic compound (1.0 eq.) in acetic anhydride or acetic acid (c = 0.5 M) was dropped an ice-cold mixture of concentrated nitric acid (10 eq.) and glacial acetic acid (6 eq.) with catalytic amounts of concentrated sulfuric acid at 0 °C. The reaction was monitored by TLC. After complete conversion, the mixture was poured into an ice-bath and the product extracted three times with EA. The combined organic layers were dried over sodium sulfate, the solvent removed, and the pure product obtained after column chromatography on silica.

General procedure J: The toluene (1.0 eq.) was added to a 1 :1 (v/v) mixture of pyridine and water (c = 0.2 M) and heated to 100 °C. A 0.5 M aqueous solution of potassium permanganate (5.0 eq.) was dropped to the solution and the mixture stirred for additional four hours. The resulting suspension was filtered, acidified with 10% HCl, and the product extracted three times with EA. The organic layers were dried over Na ₂ S0 ₄ , the solvent removed under reduced pressure and purified by column chromatography on silica.

General procedure K: To a solution of the toluene derivative (1.0 eq., c = 0.6 M) and copper(II) sulfate (3.0 eq.) in acetonitrile/water (1 :1) was added ammonium persulfate (3.0 eq.). The mixture was heated to reflux for 30 minutes under vigorous stirring. The product was extracted three times with DCM, dried over Na ₂ S0 ₄ , and the solvent evaporated. Further purification by column chromatography on silica provided the product.

General procedure L: The iodoarene (1.0 eq.) and sodium carbonate (3.0 eq.) were dissolved in a 4:1 mixture of 1,4-dioxane and water (c = 0.1 M) under argon atmosphere and degassed. A catalytic amount of Pd(PPh ₃ ) ₄ (5.0 mol-%) and boronic acid (1.2 eq.) were added. The mixture was heated to reflux for 2 hours and cooled to room temperature. The product was extracted three times with EA after addition of 5% HCl, dried over sodium sulfate, and purified by column chromatography on silica.

General procedure M: The chromenone (1.0 eq.) was dissolved in dry DMF (2.5 eq.) under argon atmosphere and 2.0 equivalents of POCl ₃ were added. The mixture was heated to 60 °C for 6 hours. The reaction was quenched with ice-cold water and the product extracted three times with ethyl acetate. After drying over sodium sulfate, the solvent was evaporated and the product processed without further purification.

General procedure N: Fresh silver oxide was prepared by adding a solution of silver nitrate (2.2 eq.) in 10 mL water dropwisely to a solution of sodium hydroxide (4.0 eq.) in 10 mL water and 20 mL EtOH. Subsequently, a solution of the aldehyde (1.0 eq.) in 5 rnL EtOH was added and the resulting mixture stirred for 75 minutes at 85 °C. The suspension was filtered after cooling to room temperature, and the residue rinsed three times with a 1 : 1 (v/v) mixture of EtOH and water. The filtrate's ethanol was evaporated under reduced pressure and the product acidified with 5% HCl, extracted three times with ethyl acetate and purified by column chromatography on silica.

General procedure O: Under argon atmosphere, the bromoarene (1.0 eq.) and copper(I) cyanide (1.0 eq.) were suspended in dry DMF (0.5 mL/mmol) and heated to 150 °C for one hour. Subsequently, 2.7 mL/mmol toluene were added and the mixture heated to reflux for 60 minutes under stirring. After cooling to room temperature, water was added and the product extracted once with EA, dried over sodium sulfate, and the solvent removed under vacuum. Purification by column chromatography afforded the pure product.

General procedure P: 55% sulfuric acid (5 mL) was added to the nitrile (1.0 eq.) and the suspension was heated to reflux for 15 hours. After cooling to ambient temperature, the product was extracted three times with EA. The combined organic layers were extracted three times with 1 M NaOH (10 mL). The product was obtained after reacidification with 10% HCl and extraction with EA (3x). The organic layer was dried over Na ₂ S0 ₄ , and the solvent removed under reduced pressure.

General procedure Q: The corresponding alcohol or amine (1.0 eq.), alkyl bromide (0.5 - 1.4 eq.) and 1.2 equivalents of potassium carbonate were suspended in dry DMF (4 mL/mmol) and stirred under argon atmosphere for 16 hours. Ethyl acetate (30 mL) was added and the product washed three times with water (30 mL). The organic layer was dried over sodium sulfate and the solvent evaporated. Column chromatography on silica afforded the pure product.

General procedure R: A solution of bromine (1.0 eq.) in glacial acetic acid (9 mL/mmol) was added dropwisely to a solution of the ketone (1.0 eq.) in glacial acetic acid (5 ml/mmol) and stirred for 17 hours. Water and 5% sodium thiosulfate solution (20 mL and 10 mL respectively) were added and the product three times extracted with ethyl acetate. The combined organic layers were dried over Na ₂ S0 ₄ and the solvent removed under reduced pressure. The product was not further purified. General procedure S: The bromoacetophenone (1.0 eq.) and ammonium formate (3.0 eq.) were dissolved in formic acid (5 mL) and DMF (2 mL) and heated to reflux for 5 hours. After cooling to ambient temperature, the solution was neutralized with NaHC0 ₃ solution and ethyl acetate was added (50 mL). Phases were separated and the organic layer washed two more times with water. The organic layer was dried over Na ₂ S0 ₄ and the solvent evaporated. The product was purified by column chromatography on silica.

General procedure T: The amine (2.0 eq.) was dissolved in 2 mL water at 0 °C. Then, a solution of potassium carbonate (2.0 eq.) in 3 mL water was added dropwisely and stirred for 15 minutes after complete addition. THF (10 mL), methanol (3 mL), and /7-toluenesulfonyl chloride (1.0 eq.) were added (the latter in portions). The mixture was next allowed to warm to room temperature and stirred for another three hours. Water was added (30 mL) and the product extracted twice with ethyl acetate (30 mL). The solvent was evaporated after drying over sodium sulfate.

General procedure U: The iodoarene (1.0 eq.), acrolein diethyl acetal (3.0 eq.), palladium(II) acetate (3 mol-%), potassium carbonate (2.5 eq.), tetrabutylammonium acetate (2.0 eq.) and potassium chloride (1.0 eq.) were suspended in dry DMF (2 mL) and heated in the microwave reactor to 90 °C for two hours. 3 mL 5% HC1 and 10 mL THF were added and the mixture stirred for one hour at room temperature. Ethyl acetate was added (40 mL) and the product was three times with 20 mL water, dried over sodium sulfate. The solvent was evaporated and the product purified by column chromatography on silica.

General procedure V: The acryl aldehyde derivative (1.0 eq.), N-hydroxyl-p- toluenesulfonamide (4.0 eq.) and K ₂ C0 ₃ (6.0 eq.) were dissolved in methanol (12 mL/mmol) and water (8 mL/mmol) and stirred at room temperature until TLC indicated complete consumption of starting material. The solution was then heated to reflux for 21 hours. Ethyl acetate (30 mL) was added and the product washed with diluted HC1 twice and water (20 mL each) once. The organic layer was dried over sodium sulfate and the solvent removed under reduced pressure. The crude product was purified by column chromatography on silica.

3-(3-[2-Aminobenzamido]phenyl)propanoic acid: Preparation according to general procedure A. Yield: 98%. Beige solid. 1H-NMR (400 MHz, DMSO-d6): δ = 2.54 (t, ³ J= 7.7 Hz, 2H), 2.81 (t, ³ J = 7.6 Hz, 2H), 6.30 (br s, 2H), 6.58 (ddd, ³ J = 7.5, 7.5 Hz, V= 1.1 Hz, 1H), 6.74 (dd, ³ J = 8.3 Hz, ⁴ J = 0.9 Hz, 1H), 6.94 (d, ⁵ J = 7.7, Hz, 1H), 7.12-7.32 (m, 2H), 7.48-7.65 (m, 3H), 9.92 (s, 1H), 12.10 (br s, 1H) ppm. ¹³ C-NMR (100 MHz, DMSO-d6): δ = 30.5, 35.2, 114.7, 115.3, 116.4, 118.4, 120.4, 123.3, 128.4, 128.7, 132.1, 139.2, 141.2, 149.7,

167.8, 173.7 ppm.

3-(3-[2-{2-Naphthamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure C2. Yield: 24%. White solid. 1H-NMR (400 MHz, DMSO-d6): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 7.01 (d, ³ J= 7.6 Hz, 1H), 7.24 - 7.35 (m, 2H), 7.56 - 7.70 (m, 5H), 7.92 - 8.04 (m, 3H), 8.05 - 8.12 (m, 2H), 8.49 (d, ³ J = 8.2 Hz, 1H), 8.55 (s, 1H), 10.51 (s, 1H), 11.80 (s, 1H) ppm. ¹³ C-NMR (100 MHz, DMSO-d6): δ = 30.4, 35.2,

118.9, 120.9, 121.6, 123.3, 123.4, 123.5, 124.2, 127.1, 127.7, 127.9, 128.1, 128.6, 128.6, 129.0, 129.1, 131.9, 132.2, 132.2, 134.4, 138.5, 138.6, 141.4, 164.8, 167.4, 173.7 ppm. ESI- MS: m/z = 437.13 ([M-H] ^" ).

2H-Chromene-3-carboxylic acid: Preparation according to general procedures F and G in a sequential one-pot manner. Yield: 52%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): δ = 4.90 (d, ⁴ J = 1.4 Hz, 2H), 6.84 (d, ³ J= 8.1 Hz, 1H), 6.95 (ddd, ³ J= 7.5, 7.5 Hz, ⁴ J= 1.0 Hz, 1H), 7.26 (ddd, ³ J= 7.9, 7.9 Hz, ⁴ J= 1.6 Hz, 1H), 7.32 (dd, ³ J= 7.5 Hz, ⁴ J= 1.5 Hz, 1H), 7.44 (s, 1H), 12.83 (s, 1H) ppm. ¹³ C-NMR (100 MHz, DMSO-d6): δ = 64.1, 115.7, 120.8, 121.7, 123.4, 129.1, 131.8, 132.3, 154.4, 165.5 ppm.

Ethyl 3-(2-Aminobenzamido)phenylacetate: Preparation according to general procedure Dl. Yield: 98%. Beige solid. ¹ H-NMR (400 MHz, CDC13): δ = 1.26 (t, ³ J = 1.1 Hz, 3H), 3.62 (s, 2H), 4.16 (q, ³ J= 7.2 Hz, 2H), 5.50 (br s, 2H), 6.65 - 6.77 (m, 2H), 7.06 (d, ³ J= 7.7 Hz, 1H), 7.25 (ddd, ³ J= 7.7, 7.7 Hz, ⁴ J= 1.4 Hz, 1H), 7.31 (dd, ³ J= 8.1, 8.1 Hz, 1H), 7.45 (dd, ³ J= 8.2 Hz, ⁴ J= 1.4 Hz, 1H), 7.47-7.53 (m, 2H), 7.79 (br s, 1H) ppm. ¹³ C-NMR (100 MHz, CDC13): δ = 14.3, 41.4, 61.1, 116.3, 117.0, 117.7, 119.4, 121.4, 125.5, 127.3, 129.4, 132.9, 135.2, 138.3, 149.1, 167.7, 171.6 ppm.

Ethyl 3-(2-[2H-Chromene-3-carboxamido]benzamido)phenylacetate: Preparation according to general procedure C2. Yield: 37%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ = 1.18 (t, ³ J = 7.1 Hz, 3H), 3.66 (s, 2H), 4.08 (q, ³ J = 7.1 Hz, 2H), 4.99 (d, ⁴ J = 0.8 Hz, 2H), 6.88 (d, ³ J= 8.1 Hz, 1H), 6.97 (ddd, ³ J= 7.5, 7.5 Hz, ⁴ J= 0.8 Hz, 1H), 7.04 (d, ³ J= 7.6 Hz, 1H), 7.22-7.38 (m, 5H), 7.59 (ddd, ⁵ J = 7.8, 7.8 Hz, ⁴ J= 1.2 Hz, 1H), 7.63 (d, ³ J = 8.5 Hz, 1H), 7.68 (s, 1H), 7.90 (dd, ³ J= 7.8 Hz, ⁴ J= 1.1 Hz, 1H), 8.28 (d, ³ J= 8.2 Hz, 1H), 10.50 (s, 1H), 11.28 (s, 1H) ppm. ¹³ C-NMR (100 MHz, DMSO-d6): δ = 14.1, 40.5, 60.3, 64.2, 115.7, 119.5, 120.9, 121.7, 121.9, 123.3, 123.4, 125.2, 127.1, 127.9, 128.6, 128.8, 129.0, 131.5,

132.1, 134.9, 137.8, 138.1, 138.6, 154.2, 162.7, 167.2, 171.0 ppm.

3-(2-[2H-Chromene-3-carboxamido]benzamido)phenylacetic acid: Preparation according to general procedure E. Yield: 99%. Yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ = 3.57 (s, 2H), 4.99 (d, ⁴ J= 0.9 Hz, 2H), 6.88 (d, ³ J= 8.0 Hz, 1H), 6.98 (ddd, ³ J = 7.5, 7.5 Hz, ^¥ J= 0.9 Hz, 1H), 7.04 (d, ³ J= 7.5 Hz, 1H), 7.24 - 7.38 (m, 5H), 7.52 - 7.68 (m, 3H), 7.90 (dd, ³ J= 7.8 Hz, V= 1.1 Hz, 1H), 8.29 (d, ³ J= 7.9 Hz, 1H), 10.50 (s, 1H), 11.31 (s, 1H) ppm. ¹³ C-NMR (100 MHz, DMSO-d6): δ - 40.9, 64.2, 115.7, 119.5, 120.9, 121.6, 121.9, 121.9, 123.2, 123.3,

125.3, 127.1, 127.9, 128.5, 128.9, 129.0, 131.5, 132.1, 135.5, 138.2, 138.5, 154.2, 162.7,

167.2, 172.6 ppm. ESI-MS: m/z = 383.16 [M-COOH] ^" , 427.14 ([M-H] ^" ).

Ethyl 3-(3-Aminophenyl)propanoate: Preparation according to general procedure A. Yield: 93%. Brown oil. 1H-NMR (400 MHz, CDC13): δ = 1.24 (t, ⁵ J= 7.1 Hz, 3H), 2.59 (t, ³ J= 7.9 Hz, 2H), 2.86 (t, ³ J = 7.9 Hz, 2H), 3.62 (br s, 2H), 4.13 (q, ³ J = 7.1 Hz, 2H), 6.50-6.56 (m, 2H), 6.60 (d, ³ J = 7.8 Hz, 1H), 7.07 (dd, V = 8.1, 8.1 Hz, 3H) ppm. ¹³ C-NMR (75 MHz, CDC13): δ = 14.4, 31.1, 36.0, 65.0, 113.2, 115.2, 118.7, 129.5, 142.0, 146.6, 173.2 ppm.

Ethyl 3-(3-[2-Nitrobenzamido]phenyl)propanoate: Preparation according to general procedure C2. Yield: 103%) yield (did not dry completely despite vigorous attempts). Brown oil. 1H-NMR (400 MHz, CDC13): δ = 1.23 (t, ³ J= 7.0 Hz, 3H), 2.61 (t, ³ J= 7.8 Hz, 2H), 2.93 (t, ³ J= 7.7 Hz, 2H), 4.11 (q, ³ J= 7.1 Hz, 2H), 7.01 (t, ³ J= 7.6 Hz, 1H), 7.27 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.41 (d, ³ J= 8.1 Hz, 1H), 7.45 (br s, 1H), 7.56-7.65 (m, 2H), 7.66-7.76 (m, 2H), 8.08 (d, ³ J = 8.1 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC13): δ = 14.3, 31.0, 35.9, 60.7, 118.5,

120.4, 124.8, 125.2, 128.8, 129.4, 130.9, 133.0, 134.0, 137.7, 141.9, 146.4, 164.5, 173.0 ppm. Ethyl 3-(3-[2-Aminobenzamido]phenyl)propanoate: Preparation according to general procedure Dl. Yield: 82%. Beige solid. 1H-NMR (400 MHz, CDC13): δ = 1.24 (t, ³ J = 7.1 Hz, 3H), 2.63 (t, ³ J= 7.8 Hz, 2H), 2.95 (t, ³ J= 7.8 Hz, 2H), 4.13 (q, ³ J= 7.1 Hz, 2H), 5.51 (br s, 2H), 6.64 - 6.77 (m, 2H), 6.98 (d, ³ J= 7.6 Hz, 1H), 7.20-7.31 (m, 2H), 7.41 (d, ³ J= 8.1 Hz, 1H), 7.43-7.49 (m, 2H), 7.79 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC13): δ = 14.3, 31.0, 35.9, 60.6, 116.3, 116.9, 117.6, 118.6, 120.5, 124.6, 127.3, 129.3, 132.9, 138.1, 141.8, 149.1, 167.7, 173.0 ppm.

Ethyl 3-(3-[2-{2H-Chromene-3-carboxamido}benzamido]phenyl)propanoa te: Preparation according to general procedure C2. Yield: 62%>. Pale yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 4.99 (d, V= 1.1 Hz, 2H), 6.87 (d, ³ J= 8.1 Hz, 1H), 6.94-7.05 (m, 2H), 7.23-7.33 (m, 4H), 7.35 (s, 1H), 7.54-7.63 (m, 3H), 7.89 (dd, ³ J = 7.9 Hz, ⁴ J = 1.2 Hz, 1H), 8.30 (d, ³ J = 8.2 Hz, 1H), 10.45 (br s, 1H), 11.31 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ = 14.1, 30.4, 35.0, 59.9, 64.2, 115.7, 118.9, 120.9, 120.9, 121.6, 121.9, 123.3, 123.4, 124.2, 127.1, 127.9, 128.6, 128.9, 129.0, 131.6, 132.1, 138.2, 138.6, 141.0, 154.2, 162.7, 167.2, 172.1 ppm.

3-(3-[2-{2H-Chromene-3-carboxamido}benzamido]phenyl)propanoi c acid: Preparation according to general procedure E. Yield: 100%. Yellow solid. 1H-NMR (400 MHz, DMSO- d6): δ - 2.55 (t, ³ J= 7.6 Hz, 2H), 2.84 (t, ³ J = 7.5 Hz, 2H), 5.00 (s, 2H), 6.87 (d, ³ J= 8.0 Hz, 1H), 6.92 - 7.08 (m, 2H), 7.20-7.32 (m, 4H), 7.35 (s, 1H), 7.52-7.67 (m, 3H), 7.90 (d, ³ J= 7.2 Hz, 1H), 8.31 (d, ³ J = 8.1 Hz, 1H), 10.46 (s, 1H), 11.34 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): 5 = 30.4, 35.1, 64.2, 115.8, 118.9, 120.9, 120.9, 121.6, 122.0, 123.1, 123.3, 124.2, 127.1, 127.9, 128.6, 128.9, 129.0, 131.6, 132.1, 138.2, 138.6, 141.4, 154.3, 162.7, 167.2, 173.7 ppm. ESI-MS: m/z = 383.16 [M-COOH] ^" , 427.14 ([M-H] ^" ).

8-Methoxy-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 43%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ = 3.77 (s, 3H), 4.85 (d, ⁴ J = 1.3 Hz, 2H), 6.87 (dd, ³ J = 7.6 Hz, ⁴ J = 1.3 Hz, 1H), 6.95 (dd, ³ J = 7.9, 7.9 Hz, 1H), 7.07 (dd, ³ J = 8.2 Hz, ⁴ J = 1.3 Hz, 1H), 7.57 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ = 55.8, 63.5, 103.2, 115.9, 116.7, 120.3, 120.8, 122.1, 139.2, 143.0, 147.7 ppm.

8-Methoxy-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 92%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): δ = 3.76 (s, 3H), 4.87 (d, ⁴ J = 1.4 Hz, 2H), 6.85-6.96 (m, 2H), 7.01 (dd, ⁵ J= 7.2 Hz, ⁴ J= 2.4 Hz, 1H), 7.42 (dd, ⁴ J= 1.3, 1.3 Hz, 1H), 12.84 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ = 55.7, 64.0, 115.1, 120.8, 121.5, 121.5, 123.5, 132.5, 143.4, 147.6, 165.5 ppm.

Ethyl 3-(3-[2-{8-Methoxy-2H-chromene-3-carboxamido}benzamido]pheny l)propanoate:

Preparation according to general procedure C2. Yield: 65%. Yellow solid. ^-NMR (400 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.86 (t, ⁵ J= 7.5 Hz, 2H), 3.77 (s, 3H), 4.04 (q, ³ J= 7.1 Hz, 2H), 4.97 (s, 2H), 6.85 - 6.98 (m, 2H), 6.97 - 7.04 (m, 2H), 7.28 (dd, ³ J = 7.8, 7.8 Hz, 2H), 7.33 (s, 1H), 7.51 - 7.64 (m, 3H), 7.89 (d, ³ J = 7.2 Hz, 1H), 8.29 (d, ³ J= 8.2 Hz, 1H), 10.45 (s, 1H), 11.31 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO- d6): δ = 14.1, 30.4, 35.0, 55.7, 59.9, 64.1, 114.8, 118.9, 120.5, 120.8, 121.6, 121.6, 123.3, 123.4, 124.2, 127.2, 128.1, 128.6, 129.0, 132.1, 138.2, 138.6, 141.0, 143.2, 147.6, 147.6, 162.7, 167.1, 172.1 ppm.

3-(3-[2-{8-Methoxy-2H-chromene-3-carboxamido}benzamido]pheny l)propanoic acid:

Preparation according to general procedure E. Yield: 97%. Yellow solid. ^-NMR (400 MHz, DMSO-d6): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 3.77 (s, 3H), 4.96 (s, 2H), 6.87 - 6.95 (m, 2H), 6.99 - 7.04 (m, 2H), 7.23 - 7.30 (m, 2H), 7.33 (s, 1H), 7.53 - 7.63 (m, 3H), 7.89 (d, ³ J = 7.3 Hz, 1H), 8.29 (d, ³ J = 8.2 Hz, 1H), 10.45 (s, 1H), 11.31 (s, 1H), 12.11 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d6): δ = 30.4, 35.1, 55.7, 64.1, 114.9, 118.9, 120.6, 120.9, 121.6, 121.7, 123.2, 124.2, 127.2, 128.1, 128.6, 129.0, 132.1, 138.2, 138.6, 141.4, 143.2, 147.6, 147.6, 162.7, 167.2, 173.7 ppm. ESI-MS: m/z = 471.21 ([M-H] ^" ). 7-Methyl-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 73%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ = 2.26 (s, 3H), 4.83 (d, V = 1.3 Hz, 2H), 6.72 (s, 1H), 6.82 (dd, ³ J = 7.7 Hz, ⁴ J = 0.8 Hz, 1H), 7.15 (d, ³ J= 7.7 Hz, 1H), 7.52 (s, 1H) ppm. ^I3 C-NMR (125 MHz, DMSO-d6): δ = 21.3, 63.6, 101.8, 116.5, 116.9, 117.7, 123.1, 128.6, 139.0, 143.3, 153.9 ppm.

7-Methyl-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 93%. White solid. 1H-NMR (400 MHz, DMSO-d6): δ = 2.25 (s, 3H), 4.87 (d, V= 1.2 Hz, 2H), 6.68 (s, 1H), 6.77 (d, ³ J= 7.7 Hz, 1H), 7.19 (d, ³ J= 7.7 Hz, 1H), 7.41 (s, 1H), 12.74 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ = 21.2, 64.2, 116.2, 118.3, 122.2, 122.6, 129.0, 132.5, 142.3, 154.5, 165.6 ppm.

Ethyl 3-(3-[2-{7-Methyl-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate:

Preparation according to general procedure C2. Yield: 52%. Pale yellow solid. ¹ H-NMR (500 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.27 (s, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.85 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 4.96 (d, ⁴ J= 0.8 Hz, 2H), 6.71 (s, 1H), 6.80 (d, ³ J = 7.6 Hz, 1H), 7.01 (d, ³ J= 7.6 Hz, 1H), 7.19 (d, ⁵ J= 7.6 Hz, 1H), 7.23 - 7.30 (m, 2H), 7.32 (s, 1H), 7.52 - 7.65 (m, 3H), 7.89 (d, ³ J = 7.7 Hz, 1H), 8.29 (d, ³ J = 8.1 Hz, 1H), 10.45 (s, 1H), 11.27 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ 14.1, 21.2, 30.3, 35.0, 59.9, 64.2, 116.2, 118.3, 118.9, 120.9, 121.5, 122.7, 123.2, 123.3, 124.2, 125.9, 128.0, 128.6, 128.7, 128.9, 132.1, 138.2, 138.6, 141.0, 141.9, 154.2, 162.7, 167.2, 172.1 ppm.

3-(3-[2-{7-Methyl-2H-chromene-3~carboxamido}benzamido]phe nyl)propanoic acid: Preparation according to general procedure E. Yield: 99%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d6): δ = 2.27 (s, 3H), 2.54 (t, ³ J = 7.6 Hz, 2H), 2.83 (t, ³ J = 7.6 Hz, 2H), 4.96 (d, ⁴ J= 0.9 Hz, 2H), 6.71 (s, 1H), 6.80 (dd, ³ J= 7.6 Hz, ⁴ J= 0.6 Hz, 1H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.19 (d, ⁵ J = 7.7 Hz, 1H), 7.23 - 7.31 (m, 2H), 7.32 (s, 1H), 7.53 - 7.63 (m, 3H), 7.89 (dd, ³ J = 7.8 Hz, ⁴ J = 1.0 Hz, 1H), 8.30 (d, ³ J = 8.3 Hz, 1H), 10.45 (s, 1H), 11.29 (s, 1H), 12.18 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ 21.2, 30.4, 35.2, 64.2, 116.2, 118.3, 1 18.9, 120.9, 121.5, 122.7, 123.1, 123.3, 124.2, 125.9, 128.1, 128.6, 128.7, 129,0, 132.1, 138.3, 138.5, 141.4, 141.9, 154.2, 162.7, 167.2, 173.7 ppm. ESI-MS: m/z = 455.21 ([M-H] ^" ). 6-Chloro-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 61%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d ₆ ): δ - 4.91 (d, ⁴ J= 1.4 Hz, 2H), 6.92 (d, ³ J= 8.6 Hz, 1H), 7.34 (dd, ³ J= 8.6 Hz, ⁴ J= 2.6 Hz, 1H), 7.37 (d, ^¥ J= 2.6 Hz, 1H), 7.53 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 63.8, 104.7, 116.3, 118.0, 121.5, 125.8, 127.8, 131.9, 137.7, 152.6 ppm.

6-Chloro-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 70%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d ₆ ): δ = 4.92 (d, ⁴ J= 1.4 Hz, 2H), 6.86 (d, ³ J = 8.7 Hz, 1H), 7.27 (dd, ³ J = 8.6 Hz, ⁴ J= 2.6 Hz, 1H), 7.38 - 7.47 (m, 2H), 12.97 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 64.5, 117.5, 122.6, 124.8, 125.3, 128.3, 131.1, 131.1, 153.2, 165.3 ppm.

Ethyl 3-(3-[2-{6-Chloro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate:

Preparation according to general procedure CI. Yield: 84%. Pale yellow solid. ¹ H-NMR (400 MHz, DMSO-d ₆ ): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.85 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 5.02 (d, ⁴ J= 0.9 Hz, 2H), 6.90 (d, ³ J= 8.6 Hz, 1H), 7.01 (d, ³ J = 7.6 Hz, 1H), 7.22 - 7.31 (m, 3H), 7.33 (s, 1H), 7.42 (d, ³ J = 2.6 Hz, 1H), 7.53 - 7.62 (m, 3H), 7.89 (d, ³ J = 6.9 Hz, 1H), 8.27 (d, ³ J = 8.0 Hz, 1H), 10.45 (s, 1H), 11.28 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 59.8, 64.5, 117.4, 118.9, 120.8, 121.7, 122.6, 123.4, 123.5, 124.2, 125.4, 126.7, 127.9, 128.5, 128.6, 128.9, 130.8, 132.1, 138.0, 138.5, 141.0, 152.9, 162.4, 167.1, 172.1 ppm.

3-(3-[2-{6-Chloro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoic acid:

Preparation according to general procedure E. Yield: 72%. Pale yellow solid. ¹ H-NMR (500 MHz, DMSO-dg): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.5 Hz, 2H), 5.02 (d, ⁴ J= 1.1 Hz, 2H), 6.90 (d, ⁵ J = 8.6 Hz, 1H), 7.01 (d, ³ J = 7.6 Hz, 1H), 7.25 - 7.31 (m, 3H), 7.33 (s, 1H), 7.43 (dd, ³ J= 2.7 Hz, 1H), 7.51 - 7.65 (m, 3H), 7.89 (d, ³ J= 7.8 Hz, 1H), 8.27 (d, ³ J= 8.2 Hz, 1H), 10.47 (s, 1H), 11.28 (s, 1H), 12.13 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 64.5, 117.5, 118.9, 120.8, 121.7, 122.6, 123.4, 123.5, 124.2, 125.4, 126.8, 128.0, 128.5, 128.6, 129.0, 130.8, 132.1, 138.0, 138.5, 141.4, 152.9, 162.4, 167.1, 173.7 ppm. ESI- MS: m/z = 475.05 ([M-H] ^" ).

6-Fluoro-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 76%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d ₆ ): δ = 4.88 (d, ⁴ J= 1.3 Hz, 2H), 6.89 - 6.97 (m, 1H), 7.12 - 7.21 (m, 2H), 7.54 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 63.8, 105.0, 114.5, 116.4, 117.7, 119.0, 121.2, 138.1, 150.2, 156.9 ppm.

6-Fluoro-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 85%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d ₆ ): δ = 4.89 (d, ⁴ J= \A Hz, 2H), 6.86 (dd, ³ J= 8.9 Hz, ⁴ J= 4.6 Hz, 1H), 7.08 (ddd, ⁵ J= 8.7, 8.7 Hz, ⁴ J= 3.1 Hz, 1H), 7.23 (dd, ³ J = 8.7 Hz, ⁴ J = 3.1 Hz, 1H), 7.42 (s, 1H), 12.92 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 64.3, 114.9, 116.9, 117.9, 122.1, 125.0, 131.4, 150.6, 156.9, 165.3 ppm.

Ethyl 3-(3-[2-{6-Fluoro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate: Preparation according to general procedure CI. Yield: 90%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d ₆ ): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.85 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ⁵ J= 7.1 Hz, 2H), 4.98 (d, ^¥ J = 1.0 Hz, 2H), 6.90 (dd, ³ J = 8.9 Hz, ⁴ J = 4.6 Hz, 1H), 7.01 (d, ³ J= 7.6 Hz, 1H), 7.10 (ddd, ³ J= 8.7, 8.7 Hz, V= 3.1 Hz, 1H), 7.20 - 7.31 (m, 3H), 7.33 (s, 1H), 7.53 - 7.63 (m, 3H), 7.89 (dd, ³ J = 7.8 Hz, V= 1.0 Hz, 1H), 8.27 (d, ³ J = 7.9 Hz, 1H), 10.45 (s, 1H), 11.29 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0,

30.3, 35.0, 59.8, 64.3, 114.6, 117.0, 117.6, 118.9, 120.8, 121.7, 122.1, 123.4, 123.5, 124.2, 127.1, 128.6, 128.9, 132.1, 138.0 , 138.5, 141.0, 150.3, 156.9, 162.4, 167.1, 172.1 ppm.

3-(3-[2-{6-Fluoro-2H-chromene-3-carboxamido}benzamido]phe nyl)propanoic acid: Preparation according to general procedure E. Yield: 62%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 4.99 (d, ⁴ J= 1.1 Hz, 2H), 6.90 (dd, ³ J= 8.9 Hz, ⁴ J= 4.6 Hz, 1H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.10 (ddd, ³ J= 8.7, 8.7 Hz, ⁴ J = 3.1 Hz, 1H), 7.24 (dd, ³ J = 8.6 Hz, ^¥ J = 3.1 Hz, 1H), 7.26 - 7.31 (m, 2H), 7.33 (s, 1H), 7.53 - 7.63 (m, 3H), 7.89 (dd, ⁵ J = 7.8 Hz, ⁴ J = 0.9 Hz, 1H), 8.27 (d, ³ J = 8.1 Hz, 1H), 10.46 (s, 1H), 11.30 (s, 1H), 12.09 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ =

30.4, 35.1, 64.4, 114.7, 117.0, 117.6, 118.9, 120.9, 121.7, 122.2, 123.4, 123.5, 124.2, 124.9, 127.2, 128.7, 129.0, 132.1, 138.0 , 138.5, 141.4, 150.4, 156.9, 162.5, 167.1, 173.7 ppm. ESI- MS: m/z = 459.08 ([M-H] ^* ).

8~Chloro~2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 35%. White solid. 1H-NMR (400 MHz, DMSO-d6): δ = 5.02 (d, V= 1.4 Hz, 2H), 7.02 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.25 (dd, ³ J= 7.6 Hz, ⁴ J= 1.4 Hz, 1H), 7.45 (dd, ³ J= 8.1 Hz, ⁴ J = 1.4 Hz, 1H), 7.62 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d6): 64.3, 104.4, 116.3, 120.2, 121.6, 122.9, 127.6, 132.7, 138.2, 149.4 ppm.

8-Chloro-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 88%. Pale yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ = 5.03 (d, ⁴ J = 1.4 Hz, 2H), 6.96 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.30 (dd, ⁵ J= 7.6 Hz, V= 1.4 Hz, 1H), 7.38 (dd, ⁵ J= 8.0 Hz, ⁴ J = 1.5 Hz, 1H), 7.45 (t, V= 1.3 Hz, 1H), 12.95 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d6): 65.0, 119.8, 122.3, 122.4, 124.4, 127.9, 131.4, 131.8, 149.9, 165.2 ppm.

Ethyl 3-(3-[2-{8-chloro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate: Preparation according to general procedure CI . Yield: 89%. Pale yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.85 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ⁵ J= 7.1 Hz, 2H), 5.12 (d, ⁴ J= 1.0 Hz, 2H), 6.91 - 7.05 (m, 2H), 7.22 - 7.34 (m, 3H), 7.37 (s, 1H), 7.40 (dd, ³ J= 8.0 Hz, ⁴ J = 1.3 Hz, 1H), 7.52 - 7.67 (m, 3H), 7.89 (d, ⁵ J = 7.9 Hz, 1H), 8.27 (d, ³ J= 7.9 Hz, 1H), 10.45 (s, 1H), 11.29 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d6): 14.1, 30.3, 35.0, 59.8, 65.0, 118.9, 119.8, 120.9, 121.7, 122.5, 122.5, 123.5, 123.5, 124.2, 127.1, 127.6, 127.9, 128.6, 129.0, 131.5, 132.1, 137.9, 138.5, 141.0, 149.7, 162.3, 167.1, 172.1 ppm.

3-(3-[2-{8-Chloro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoic acid:

Preparation according to general procedure E. Yield: 97%. White solid. ^NMR (500 MHz, DMSO-d6): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 5.12 (d, ⁴ J= 1.2 Hz, 2H), 6.98 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.01 (d, ⁵ J= 7.7 Hz, 1H), 7.25 - 7.32 (m, 3H), 7.37 (s, 1H), 7.39 (dd, ⁵ J= 8.0 Hz, ⁴ J= 1.4 Hz, 1H), 7.52 - 7.64 (m, 3H), 7.90 (d, ³ J= 7.8 Hz, 1H), 8.28 (d, ³ J = 8.1 Hz, 1H), 10.47 (s, 1H), 11.32 (s, 1H), 12.10 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): 30.4, 35.1, 65.0, 118.9, 119.8, 120.9, 121.7, 122.5, 122.5, 123.4, 123.5, 124.2, 127.2, 127.7, 128.0, 128.6, 129.0, 131.6, 132.1, 138.0, 138.5, 141.4, 149.7, 162.4, 167.1, 173.7 ppm. ESI-MS: m/z = 475.06 ([M-H] ^" ).

6-Methyl-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 72%. Pale yellow solid. ¹ H-NMR (400 MHz, CDC1 ₃ ): δ = 2.27 (s, 3H), 4.77 (d, ⁴ J = 1.3 Hz, 2H), 6.77 (d, ³ J= 8.3 Hz, 1H), 6.90 (d, ⁴ J = 1.6 Hz, 1H), 7.07 (dd, ³ J = 8.3 Hz, ⁴ J = 1.6 Hz, 1H), 7.13 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): 20.5, 64.5, 103.4, 116.4, 116.7, 120.0, 128.8, 132.0, 133.5, 139.1, 152.3 ppm.

6-Methyl-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 40%. Yellow solid. 1H-NMR (400 MHz, DMSO-d ₆ ): δ = 2.21 (s, 3H), 4.85 (d, ⁴ J= 1.4 Hz, 2H), 6.74 (d, ³ J = 8.2 Hz, 1H), 7.07 (dd, ³ J= 8.2 Hz, ⁴ J = 1.6 Hz, 1H), 7.12 (d, ⁴ J= 1.7 Hz, 1H), 7.39 (s, 1H), 12.73 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): 20.0, 64.1, 115.4, 120.7, 123.5, 129.2, 130.6, 132.2, 132.4, 152.3, 165.5 ppm.

Ethyl 3-(3-[2-{6-Methyl-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate:

Preparation according to general procedure CI . Yield: 94%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.23 (s, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 4.95 (s, 2H), 6.77 (d, ³ J= 8.1 Hz, 1H), 7.01 (d, ³ J = 7.6 Hz, 1H), 7.08 (d, ³ J = 8.3 Hz, 1H), 7.10 (s, 1H), 7.23 -7.33 (m, 3H), 7.48 - 7.66 (m, 3H), 7.89 (d, ³ J = 7.2 Hz, 1H), 8.30 (d, ⁵ J = 8.2 Hz, 1H), 10.45 (s, 1H), 11.30 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): 14.0, 20.0, 30.3, 35.0, 59.8, 64.1, 115.5, 119.0, 120.7, 120.9, 121.5, 123.1, 123.3, 124.2, 127.1, 128.0, 128.6, 129.0, 129.0, 130.7, 132.0, 132.1, 138.2, 138.5, 141.0, 152.1, 162.7, 167.2, 172.1 ppm.

3-(3-[2-{6-Methyl-2H-chromene-3-carboxamido}benzamido]phenyl )propanoic acid:

Preparation according to general procedure E. Yield: 96%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d6): δ - 2.23 (s, 3H), 2.55 (t, ³ J = 7.6 Hz, 2H), 2.83 (t, ³ J = 7.6 Hz, 2H), 4.95 (d, ⁴ J= 1.0 Hz, 2H), 6.77 (d, ³ J= 8.1 Hz, 1H), 7.02 (d, ³ J= 7.6 Hz, 1H), 7.07 (dd, ³ J= 8.2 Hz, ⁴ J= 1.7 Hz, 1H), 7.10 (s, 1H), 7.21 - 7.33 (m, 3H), 7.52 - 7.64 (m, 3H), 7.90 (dd, ³ J= 7.8 Hz, ⁴ J= 1.0 Hz, 1H), 8.31 (d, ³ J= 8.2 Hz, 1H), 10.46 (s, 1H), 11.32 (s, 1H), 12.13 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): 20.0, 30.4, 35.1, 64.1, 115.5, 119.0, 120.7, 120.9, 121.5, 123.1, 123.3, 124.2, 127.2, 128.1, 128.6, 129.0, 129.0, 130.8, 132.0, 132.1, 138.2, 138.5,

141.4, 152.1, 162.7, 167.2, 173.7 ppm. ESI-MS: m/z = 455.10 ([M-H] ^" ).

8-Methyl-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 83%. Pale yellow solid. 1H-NMR (400 MHz, CDC1 ₃ ): δ = 2.19 (s, 3H), 4.83 (d, ⁴ J= 1.3 Hz, 2H), 6.87 (dd, ⁵ J= 7.5, 7.5 Hz, 1H), 6.95 (dd, ³ J= 7.5 Hz, ⁴ J= 1.3 Hz, 1H), 7.14 (dd, ³ J= 7.4 Hz, ⁴ J= 0.8 Hz, 1H), 7.16 (dd, ⁴ J= 1.1, 1.1 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): 15.5, 64.5, 103.0, 116.7, 119.7, 121.9, 126.2, 126.3, 134.4, 139.4, 152.5 ppm.

8-Methyl-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 79%. Yellow solid. 1H-NMR (400 MHz, DMSO-d ₆ ): δ = 2.12 (s, 3H), 4.92 (d, ⁴ J= 1.4 Hz, 2H), 6.85 (dd, ³ J= 7.5, 7.5 Hz, 1H), 7.14 (d, ³ J= 7.6 Hz, 2H), 7.42 (dd, ⁴ J= 1.3, 1.3 Hz, 1H), 12.82 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): 15.2, 64.2, 120.4, 121.2, 123.1, 124.6, 126.8, 132.7, 133.2, 152.5, 165.6 ppm.

Ethyl 3-(3-[2-{8~Methyl-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate:

Preparation according to general procedure CI. Yield: 99%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.14 (s, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 5.01 (s, 2H), 6.87 (dd, ³ J= 7.5, 7.5 Hz, 1H), 7.01 (d, ³ J = 7.6 Hz, 1H), 7.10 - 7.20 (m, 2H), 7.21 - 7.30 (m, 2H), 7.33 (s, 1H), 7.53 - 7.65 (m, 3H), 7.89 (d, ³ J = 7.8 Hz, 1H), 8.31 (d, ⁵ J = 8.3 Hz, 1H), 10.45 (s, 1H), 11.30 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): 14.1, 15.2, 30.3, 35.0, 59.8, 64.2, 119.0, 120.4, 120.9, 121.3,

121.5, 123.1, 123.3, 124.2, 124.6, 126.5, 126.7, 128.3, 128.6, 128.9, 132.1, 132.9, 138.2, 138.5, 141.0, 152.2, 162.6, 167.2, 172.1 ppm.

3-(3-[2-{8-Methyl-2H-chromene-3-carboxamido}benzamido]phenyl )propanoic acid: Preparation according to general procedure E. Yield: 88%). Yellow solid. ¹ H-NMR (500 MHz, DMSO-d6): δ = 2.14 (s, 3H), 2.54 (t, ³ J = 7.6 Hz, 2H), 2.83 (t, ³ J = 7.6 Hz, 2H), 5.01 (d, ⁴ J= 0.9 Hz, 2H), 6.87 (dd, ³ J= 7.5, 7.5 Hz, 1H), 7.02 (d, ³ J= 7.6 Hz, 1H), 7.11 - 7.18 (m, 2H), 7.23 - 7.32 (m, 2H), 7.33 (s, 1H), 7.53 - 7.65 (m, 3H), 7.90 (dd, ³ J= 7.8 Hz, ⁴ J= 0.9 Hz, 1H), 8.31 (d, ³ J = 8.2 Hz, 1H), 10.46 (s, 1H), 11.31 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): 15.3, 30.4, 35.1, 64.2, 118.9, 120.4, 120.9, 121.3, 121.5, 123.1, 123.3, 124.2,

124.6, 126.6, 126.7, 128.4, 128.6, 129.0, 132.1, 132.9, 138.2, 138.5, 141.4, 152.3, 162.7, 167.2, 173.7 ppm. ESI-MS: m/z - 455.11 ([M-H] ^" ).

Ethyl 3-(3-[2-{Quinoline-3-carboxamido}benzamido]phenyl)propanoate : Preparation according to general procedure CI . Yield: 78%. White solid. 1H-NMR (400 MHz, DMSO- d6): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 2.59 (t, ³ J= 7.5 Hz, 2H), 2.83 (t, ³ J= 7.5 Hz, 2H), 4.02 (q, ³ J = 7.1 Hz, 2H), 6.99 (d, ³ J = 7.6 Hz, 1H), 7.17 (d, ³ J = 7.3 Hz, 1H), 7.21 - 7.29 (m, 1H), 7.34 (ddd, ³ J= 7.8, 7.8 Hz, ⁴ J= 0.9 Hz, 1H), 7.55 - 7.62 (m, 2H), 7.65 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.73 (dd, ³ J= 7.5, 7.5 Hz, 1H), 7.86 - 7.99 (m, 1H), 8.12 (d, ³ J= 8.5 Hz, 1H), 8.16 (d, ³ J = 7.7 Hz, 1H), 8.34 (d, ³ J= 8.1 Hz, 1H), 8.91 (d, ⁴ J= 2.0 Hz, 1H), 9.34 (d, ⁴ J= 2.2 Hz, 1H), 10.49 (s, 1H), 11.71 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): 14.0, 30.3, 35.0, 59.8,

118.8, 120.7, 122.3, 123.9, 124.0, 124.6, 125.3, 126.5, 127.4, 127.7, 128.2, 128.6, 128.8,

128.9, 129.0, 129.3, 131.6, 132.0, 135.9, 137.8, 138.7, 141.0, 148.4, 148.7, 163.4, 167.0, 172.1 ppm.

3-(3-[2-{Quinoline-3-carboxamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 45%. White solid. ¹ H-NMR (500 MHz, DMSO-d6): δ = 2.52 (m, 2H), 2.81 (t, ³ J= 7.6 Hz, 2H), 6.99 (d, ³ J = 7.6 Hz, 1H), 7.25 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.34 (dd, ³ J= 7.6, 7.6 Hz, 1H), 7.55 - 7.67 (m, 3H), 7.72 (dd, ⁵ J= 7.5, 7.5 Hz, 1H), 7.86 - 7.96 (m, 2H), 8.11 (d, ³ J= 8.5 Hz, 1H), 8.15 (d, ³ J= 7.7 Hz, 1H), 8.36 (d, ³ J= 8.1 Hz, 1H), 8.90 (d, ⁴ J = 2.0 Hz, 1H), 9.34 (d, ⁴ J = 2.2 Hz, 1H), 10.53 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): 30.6, 35.5, 118.7, 120.8, 122.3, 123.9, 124.1, 124.6, 126.5, 127.4,

127.7, 128.6, 128.8, 129.1, 129.4, 131.7, 132.0, 135.9, 137.9, 138.7, 141.6, 148.4, 148.7, 163.5, 167.1, 173.9 ppm. ESI-MS: m/z = 438.07 ([M-H] ^" ).

2-Methoxy-6-methyl-benzaldehyde: Preparation according to general procedure K. Yield: 38%. Yellow oil. 1H-NMR (400 MHz, CDC1 ₃ ): δ = 2.57 (s, 3H), 3.90 (s, 3H), 6.76 - 6.88 (m, 2H), 7.38 (dd, ³ J = 8.0, 8.0 Hz, 1H), 10.65 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): 21.6, 55.9, 109.2, 124.2, 126.7, 134.6, 142.2, 163.3, 192.4 ppm.

2-Hydroxy-6-methyl-benzaldehyde: Preparation according to general procedure H with aluminium(III) chloride. Yield: 69%. Yellow oil. ¹ H-NMR (400 MHz, CDC1 ₃ ): δ = 2.61 (s, 3H), 6.71 (d, ³ J= 7.4 Hz, 1H), 6.81 (d, ³ J= 8.5 Hz, 1H), 7.37 (dd, ³ J= 7.9, 7.9 Hz, 1H), 10.32 (s, 1H), 11.90 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): 18.2, 116.3, 118.7, 122.0, 137.6, 142.3, 163.4, 195.5 ppm. 5-Methyl-2H-chromene-3-carbonitrile: Preparation according to general procedure F. Yield: 42%. Yellow solid. 1H-NMR (400 MHz, CDC1 ₃ ): δ = 2.34 (s, 3H), 4.75 (s, 2H), 6.73 (d, ⁵ J = 8.2 Hz, 1H), 6.81 (d, ³ J = 7.6 Hz, 1H), 7.16 (dd, ³ J= 7.9, 7.9 Hz, 1H), 7.38 (s, 1H) ppm. ¹³ C- NMR (75 MHz, CDC1 ₃ ): 18.5, 63.8, 102.9, 114.5, 116.9, 119.3, 124.1, 132.3, 136.4, 136.6, 154.8 ppm.

5-Methyl-2H-chromene-3-carboxylic acid: Preparation according to general procedure G. Yield: 84%. Yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ = 2.33 (s, 3H) ₅ 4.84 (d, ⁴ J= 0.7 Hz, 2H), 6.70 (d, ³ J = 8.1 Hz, 1H), 6.82 (d, ⁵ J= 7.6 Hz, 1H), 7.15 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.53 (s, 1H), 12.81 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d6): 18.0, 63.5, 113.7, 119.6, 123.2, 123.3, 129.3, 131.2, 136.7, 154.8, 165.6 ppm.

Ethyl 3-(3-f2-{5-Methyl-2H-chromene-3-carboxamido}benzamidoJphenyl )propanoate:

Preparation according to general procedure CI . Yield: 88%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d6): 5 = 1.15 (t, ⁵ J= 7.1 Hz, 3H), 2.37 (s, 3H), 2.60 (t, ³ J= 7.6 Hz, 2H), 2.84 (t, ³ J= 7.6 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 4.92 (s, 2H), 6.73 (d, ⁵ J= 8.1 Hz, 1H), 6.84 (d, ³ J = 7.5 Hz, 1H), 7.00 (d, ⁵ J= 7.7 Hz, 1H), 7.16 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.23 - 7.32 (m, 2H), 7.52 - 7.63 (m, 3H), 7.70 (s, 1H), 7.90 (d, ³ J= 7.7 Hz, 1H), 8.30 (d, ⁵ J- 8.3 Hz, 1H), 10.46 (s, 1H), 11.48 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): 14.1, 17.8, 30.4, 35.1, 59.8, 63.4,

113.6, 118.7, 119.7, 120.7, 121.4, 123.3, 123.3, 123.4, 124.1, 125.1, 126.8, 128.6, 128.9, 131.0, 132.1, 136.3, 138.2, 138.6, 141.0, 154.5, 162.7, 167.2, 172.0 ppm.

3-(3-[2-{5-Methyl-2H-chromene-3~carboxamido}benzamido]phe nyl)propanoic acid: Preparation according to general procedure E. Yield: 91%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d6): δ = 2.37 (s, 3H), 2.53 (t, ³ J= 7.7 Hz, 2H), 2.82 (t, ³ J = 7.6 Hz, 2H), 4.93 (d, V= 0.9 Hz, 2H), 6.73 (d, ⁵ J= 8.1 Hz, 1H), 6.83 (d, ³ J= 7.5 Hz, 1H), 7.01 (d, ⁵ J= 7.6 Hz, 1H), 7.16 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.24 - 7.30 (m, 2H), 7.55 (s, 1H), 7.57 - 7.63 (m, 2H), 7.69 (s, 1H), 7.91 (dd, ³ J= 7.8 Hz, V= 1.0 Hz, 1H), 8.31 (d, ³ J= 8.0 Hz, 1H), 10.47 (s, 1H), 11.49 (s, 1H), 12.15 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): 17.9, 30.5, 35.2, 63.4,

113.7, 118.6, 119.7, 120.7, 121.4, 123.3, 123.3, 123.4, 124.1, 125.2, 126.8, 128.6, 128.9, 131.0, 132.1, 136.4, 138.2, 138.7, 141.4, 154.5, 162.8, 167.2, 173.7 ppm. ESI-MS: m/z = 455.16 ([M-H]-).

Ethyl 3-(3-[5-Methyl-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI with dicyclohexylcarbodiimide instead of EDC. Yield: 58%. Yellow oil. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J= 7.1 Hz, 3H), 2.49 (s, 3H), 2.64 (t, ³ J= 7.7 Hz, 2H), 2.96 (t, ³ J= 7.7 Hz, 2H), 4.13 (q, ³ J= 7.1 Hz, 2H), 7.03 (d, ^S J= 7.5 Hz, 1H), 7.29 (dd, ³ J= 7.8, 7.6 Hz, 1H), 7.35 - 7.52 (m, 5H), 8.04 (d, ³ J = 8.0 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.4, 21.6, 31.0, 35.9, 60.6, 118.5, 120.5, 125.0, 125.3, 129.3, 129.4,

131.3, 133.2, 137.6, 142.0, 144.1, 145.8, 164.7, 173.0 ppm. ESI-MS: m/z = 379.16 [M-H] ^" . Ethyl 3-(3-[2-Amino-5-methylbenzamido]phenyl)propanoate: Preparation according to general procedure Dl in 95%. Brown solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J= 7.1 Hz, 3H), 2.28 (s, 3H), 2.64 (t, ³ J= 7.8 Hz, 2H), 2.96 (t, ³ J= 7.8 Hz, 2H), 4.13 (q, ³ J= 7.1 Hz, 2H), 5.14 (br s, 2H), 6.66 (d, ³ J= 8.3 Hz, 1H), 6.98 (d, ³ J= 7.8 Hz, 1H), 7.08 (dd, ³ J= 8.0 Hz, ⁴ J = 1.7 Hz, 1H), 7.24 - 7.31 (m, 2H), 7.41 - 7.47 (m, 2H), 7.81 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.4, 20.5, 31.1, 36.0, 60.6, 116.8, 118.1, 118.5, 120.5, 124.5, 126.5,

127.4, 129.3, 133.8, 138.2, 141.8, 146.4, 167.6, 173.0 ppm. ESI-MS: m/z = 349.21 [M+Na] ⁺ . Ethyl 3-(3-[2-{2-Naphthamido}-5-methylbenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 64%. White solid. ¹ H-NMR (300 MHz, DMSO- d ₆ ): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 2.40 (s, 3H), 2.60 (t, ³ J = 7.4 Hz, 2H), 2.85 (t, ³ J= 7.4 Hz, 2H), 4.03 (q, ³ J= 7.1 Hz, 2H), 7.00 (d, ³ J= 7.8, Hz, 1H), 7.27 (dd, ⁵ J= 8.7, 7.6 Hz, 1H), 7.45 (dd, ³ J= 8.5 Hz, ⁴ J = 1.6 Hz, 1H), 7.55 - 7.61 (m, 2H), 7.61 - 7.69 (m, 2H), 7.75 (d, ⁴ J= 1.7 Hz, 1H), 7.93 - 8.04 (m, 2H), 8.07 (d, ⁴ J= 0.8 Hz, 1H), 8.10 (s, 1H), 8.35 (d, ⁵ J= 8.4 Hz, 1H ), 8.53 (d, ⁴ J = 1.3 Hz, 1H), 10.45 (s, 1H), 11.64 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO- d ₆ ): δ = 14.0, 20.5, 30.3, 35.0, 59.8, 118.9, 120.8, 121.8, 123.4, 124.1, 127.0, 127.6, 127.7, 127.7, 128.0, 128.5, 128.6, 129.0, 129.2, 131.9, 132.2, 132.5, 132.6, 134.4, 136.1, 138.6, 141.0, 164.6, 167.3, 172.1 ppm. ESI-MS: m/z = 503.26 [M+Na] ⁺ .

3-(3-[2-{2-Naphthamido}-5-methylbenzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 90%. White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.45 (s, 3H), 2.50 - 2.62 (m, 2H), 2.87 (t, ³ J= 7.6 Hz, 2H), 7.05 (d, ³ J= 7.6, Hz, 1H), 7.32 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.50 (d, ³ J= 8.4 Hz, 1H), 7.62 (s, 1H), 7.64 - 7.73 (m, 3H), 7.81 (s, 1H), 8.01 (d, ³ J= 8.6 Hz, 1H), 8.06 (d, ³ J= 7.9 Hz, 1H), 8.11 - 8.17 (m, 2H), 8.40 (d, ³ J= 8.4 Hz, 1H), 8.58 (s, 1H), 10.53 (s, 1H), 11.72 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 20.5, 30.5, 35.4, 118.8, 120.8, 121.7, 123.4, 123.5, 124.1, 127.1, 127.7, 127.8, 128.1, 128.6, 128.6, 129.1, 129.3, 132.0, 132.2, 132.6, 132.6, 134.4, 136.1, 138.6, 141.5, 164.6, 167.4, 173.8 ppm. ESI-MS: m/z = 451.24 [M-H] ^" .

Ethyl 3-(3-[4-Methyl-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 66%. Yellow oil. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J= 7.1 Hz, 3H), 2.48 (s, 3H), 2.61 (t, ⁵ J= 7.8 Hz, 2H), 2.93 (t, ³ J= 7.7 Hz, 2H), 4.11 (q, ³ J= 7.1 Hz, 2H), 7.00 (d, ³ J= 7.5 Hz, 1H), 7.26 (dd, ³ J= 7.6, 7.6 Hz, 1H), 7.36 - 7.53 (m, 4H), 7.65 (s, 1H), 7.86 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 21.3, 31.0, 35.9, 60.6, 118.4, 120.4, 125.1, 128.6, 129.4, 129.4, 130.3, 134.4, 134.4, 137.7, 141.9, 146.6, 164.6, 173.0 ppm. ESI-MS: m/z = 379.16 [M-H] ^" .

Ethyl 3-(3-[2-Amino-4-methylbenzamido]phenyl)propanoate: Preparation according to general procedure Dl. Yield: 97%. Brown solid. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J = 7.1 Hz, 3H), 2.28 (s, 3H), 2.63 (t, ³ J = 7.7 Hz, 2H), 2.95 (t, ³ J = 7.8 Hz, 2H), 4.13 (q, ³ J = 7.1 Hz, 2H), 4.98 (br s, 2H), 6.50 - 6.57 (m, 2H), 6.98 (ddd, ³ J = 7.5 Hz, ⁴ J = 1.6, 1.1 Hz, 1H), 7.27 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.35 (d, ³ J= 8.6 Hz, 1H), 7.38 - 7.43 (m, 1H), 7.44 (dd, ⁴ J = 1.7, 1.7 Hz, 1H), 7.73 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.4, 21.6, 31.1, 36.0, 60.6, 113.8, 118.1, 118.4, 118.5, 120.5, 124.4, 127.2, 129.3, 138.3, 141.8, 143.6, 149.1,

167.6, 173.0 ppm. ESI-MS: m/z = 349.20 [M+Na] ⁺ .

Ethyl 3-(3-[2-{2~Naphthamido}-4-methylbenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 84%. Beige solid. 1H-NMR (300 MHz, DMSO- d ₆ ): δ = 1.17 (t, ³ J= 7.1 Hz, 3H), 2.48 (s, 3H), 2.65 (t, ³ J= 7.4 Hz, 2H), 2.90 (t, ³ J= 7.4 Hz, 2H), 4.08 (q, ³ J= 7.1 Hz, 2H), 7.05 (d, ⁵ J = 7.8, Hz, 1H), 7.17 (dd, ³ J= 8.0 Hz, ⁴ J= 1.1 Hz, 1H), 7.32 (dd, ³ J = 8.7, 7.6 Hz, 1H), 7.59 - 7.66 (m, 2H), 7.66 - 7.75 (m, 2H), 7.93 (d, ³ J =

8.0 Hz, 1H), 8.02 (dd, ³ J= 8.6 Hz, ⁴ J= 1.8 Hz, 1H), 8.04 - 8.09 (m, 1H), 8.11 - 8.19 (m, 2H), 8.47 (d, ⁴ J = 0.9 Hz, 1H), 8.58 (d, ⁴ J = 1.3 Hz, 1H), 10.49 (s, 1H), 12.06 (s, 1H) ppm. ¹³ C- NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 21.4, 30.3, 35.0, 59.8, 119.1, 119.7, 121.0, 121.6, 123.4, 123.9, 124.2, 127.0, 127.7, 127.7, 128.1, 128.6, 128.6, 128.9, 129.0, 132.0, 132.2, 134.4, 138.5, 139.1, 141.0, 142.5, 164.6, 167.4, 172.1 ppm. ESI-MS: m/z = 503.26 [M+Na] ⁺ . 3-(3-[2-{2-Naphthamido}-4-methylbenzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 84%. Beige solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.48 (s, 3H), 2.59 (t, ³ J = 7.6 Hz, 2H), 2.88 (t, ³ J = 7.6 Hz, 2H), 7.06 (d, ³ J = 7.7, Hz, 1H), 7.17 (dd, ³ J= 8.0 Hz, ⁴ J= 0.9 Hz, 1H), 7.32 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.61 - 7.66 (m, 2H), 7.67 - 7.73 (m, 2H), 7.93 (d, ³ J= 8.0 Hz, 1H), 8.02 (dd, ³ J= 8.6 Hz, V= 1.8 Hz, 1H), 8.06 (d, ³ J = 7.9 Hz, 1H), 8.12 - 8.18 (m, 2H), 8.47 (d, ⁴ J= 0.6 Hz, 1H), 8.58 (d, ⁴ J= 1.0 Hz, 1H), 10.50 (s, 1H), 12.08 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 21.5, 30.5, 35.3, 119.0,

119.7, 121.1, 121.6, 123.4, 123.9, 124.2, 127.1, 127.7, 127.8, 128.1, 128.6, 128.7, 129.0, 129.1, 132.0, 132.2, 134.4, 138.5, 139.0, 141.5, 142.6, 164.6, 167.5, 173.8 ppm. ESI-MS: m/z = 451.24 [M-Na] ^" .

Ethyl 3-(3-[5-Methoxy-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 40%. Yellow oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.20 (t, ³ J=

7.1 Hz, 3H), 2.52 (t, ³ J= 7.8 Hz, 2H), 2.82 (t, ³ J= 7.8 Hz, 2H), 3.81 (s, 3H), 4.06 (q, ³ J= 7.1 Hz, 2H), 6.82 - 6.90 (m, 2H), 6.92 (d, ³ J= 7.6 Hz, 1H), 7.16 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.27 - 7.37 (m, 2H), 7.92 (d, ³ J = 9.1 Hz, 1H), 8.47 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.2, 30.8, 35.7, 56.3, 60.6, 113.6, 115.2, 118.5, 120.3, 124.8, 127.0, 129.1, 135.3, 137.8, 138.4, 141.5, 163.8, 164.9, 173.0 ppm. ESI-MS: m/z = 371.17 [M-H] ^" .

Ethyl 3-(3-[2-Amino-5-methoxybenzamido]phenyl)propanoate: Preparation according to general procedure Dl. Yield: 47%. Yellow oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J=

7.1 Hz, 3H), 2.61 (t, ³ J = 7.7 Hz, 2H), 2.93 (t, ³ J= 7.8 Hz, 2H), 3.76 (s, 3H), 4.12 (q, ³ J= 7.1 Hz, 2H), 4.58 (br s, 2H), 6.69 (d, ³ J = 8.8 Hz, 1H), 6.89 (dd, ³ J = 8.8 Hz, ^¥ J = 2.9 Hz, 1H), 6.96 (d, ³ J = 7.6 Hz, 1H), 7.05 (d, ⁴ J = 2.9 Hz, 1H), 7.25 (dd, ³ J = 7.7, 7.7 Hz, 1H), 7.39 - 7.45 (m, 2H), 8.19 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.9, 56.1, 60.6, 112.4, 118.4, 118.5, 119.5, 119.8, 120.5, 124.5, 129.2, 138.2, 141.7, 141.9, 151.8, 167.2, 173.0 ppm. ESI-MS: m/z = 365.18 [M+Na] ⁺ .

Ethyl 3-(3-[2-{2-Naphthamido}-5-methoxybenzamido]phenyl)propanoate : Preparation according to general procedure CI Yield: 92%. Brown solid. 1H-NMR (500 MHz, DMSO- d ₆ ): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 2.59 (t, ⁵ J= 7.5 Hz, 2H), 2.83 (t, ³ J= 7.5 Hz, 2H), 3.87 (s, 3H), 4.02 (q, ⁵ J = 7.1 Hz, 2H), 6.99 (d, ³ J= 7.7 Hz, 1H), 7.23 (dd, ⁵ J= 9.0 Hz, ⁴ J = 2.9 Hz, 1H), 7.26 (dd, ³ J = 8.6, 7.7 Hz, 1H), 7.42 (d, ^¥ J = 2.8 Hz, 1H), 7.54 - 7.59 (m, 2H), 7.59 - 7.67 (m, 2H), 7.95 (dd, ³ J= 8.6 Hz, ⁴ J= 1.7 Hz, 1H), 8.00 (d, ⁵ J = 7.8 Hz, 1H), 8.07 (d, ³ J=

8.2 Hz, 2H), 8.19 - 8.30 (m, 1H), 8.52 (d, ⁴ J= 1.0 Hz, 1H) 10.45 (s, 1H), 11.32 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 55.6, 59.8, 113.9, 117.4, 118.8, 118.9, 120.7, 120.8, 123.6, 124.0, 124.1, 127.0, 127.7, 127.7, 128.0, 128.5, 128.6, 129.0, 132.2, 134.3, 138.5, 138.6, 141.0, 155.1, 164.6, 166.7, 172.1 ppm. ESI-MS: m/z = 519.23 [M+Na] ⁺ . 3-(3-[2-{2-Naphthamido}-5-methoxybenzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 91%. Beige solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.53 (t, ³ J= 7.5 Hz, 2H), 2.82 (t, ³ J= 7.6 Hz, 2H), 3.87 (s, 3H), 7.00 (d, ⁵ J= 7.6, Hz, 1H), 7.23 (dd, ⁵ J= 9.0 Hz, ⁴ J= 2.9 Hz, 1H), 7.27 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.43 (d, ⁴ J= 2.4 Hz, 1H), 7.54 - 7.68 (m, 4H), 7.95 (d, ³ J= 8.6 Hz, 1H), 8.00 (d, ³ J= 7.9 Hz, 1H), 8.04 - 8.10 (m, 2H), 8.26 (d, ³ J = 9.0 Hz, 1H), 8.52 (s, 1H), 10.46 (s, 1H), 11.34 (s, 1H), 12.14 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 55.6, 113.9, 117.4, 118.8, 120.8, 123.6, 124.0, 124.1, 125.9, 127.0, 127.7, 127.8, 128.0, 128.5, 128.6, 129.0, 131.2, 132.0, 132.2, 134.3, 138.6, 141.4, 155.1, 164.6, 166.8, 173.7 ppm. ESI-MS: m/z = 467.24 [M-H] ^" . 3-(3-[2-{2-Naphthamido}-5-hydroxybenzamido]phenyl)propanoic acid: Preparation according to general procedure H with boron tribromide. Yield: 22%. Pale yellow solid. ¹ H- NMR (500 MHz, DMSO-d ₆ ): δ = 2.43 (t, ³ J= 7.7 Hz, 2H), 2.70 (t, ³ J= 7.6 Hz, 2H), 6.87 (d, ³ J= 7.7, Hz, 1H), 6.93 (dd, ⁵ J= 8.8 Hz, ⁴ J= 2.8 Hz, 1H), 7.11 - 7.17 (m, 2H), 7.44- 7.56 (m, 4H), 7.84 (d, ³ J = 8.5 Hz, ⁴ J = 1.7 Hz, 1H), 7.89 (d, ³ J = 7.8 Hz, 1H), 7.95 (d, ⁵ J = 8.5 Hz, 2H), 7.99 (d, ³ J = 8.8 Hz, 1H), 8.40 (s, 1H), 9.66 (br s, 1H), 10.32 (s, lH), 11.04 (s, 1H), 12.03 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 1 15.3, 118.4, 1 18.5, 120.5, 123.6, 124.0, 124.3, 126.7, 127.0, 127.7, 127.7, 127.9, 128.4, 128.6, 129.0, 129.5,

132.1, 132.2, 134.3, 138.8, 141.4, 153.6, 164.6, 167.0, 173.7 ppm. ESI-MS: m/z = 477.15

Ethyl 3-(3~[5-Chloro-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 45%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.20 (t, ³ J = 7.1 Hz, 3H), 2.52 (t, ³ J= 7.8 Hz, 2H), 2.82 (t, ³ J= 7.8 Hz, 2H), 4.05 (q, ³ J= 7.1 Hz, 2H), 6.94 (d, ³ J= 7.6 Hz, 1H), 7.17 (dd, ³ J= 7.7, 7.7 Hz, 1H), 7.24 - 7.33 (m, 2H), 7.40 - 7.47 (m, 2H), 7.90 (d, ³ J= 8.5 Hz, 1H), 8.58 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.2, 30.8, 35.7, 60.6, 118.6, 120.5, 125.2, 126.0, 128.9, 129.2, 130.5, 134.2, 137.4, 140.4, 141.6, 144.3, 163.4, 173.1 ppm. ESI-MS: m/z = 399.10 [M+Na] ⁺ .

Ethyl 3-(3-[2-Amino-5-chlorobenzamido]phenyl)propanoate: Preparation according to general procedure D2 with iron turnings. Yield: 61%. White solid. ^-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J = 7.1 Hz, 3H), 2.60 (t, ³ J = 7.7 Hz, 2H), 2.91 (t, ³ J = 77.8 Hz, 2H), 4.11 (q, ³ J= 7.1 Hz, 2H), 5.36 (br s, 2H), 6.62 (d, ³ J= 8.7 Hz, 1H), 6.96 (d, ³ J= 7.4 Hz, 1H), 7.15 (dd, ⁵ J= 8.7 Hz, ⁴ J= 2.4 Hz, 1H), 7.20 - 7.27 (m, 1H), 7.37 - 7.41 (m, 2H), 7.42 (d, ⁴ J= 2.4 Hz, 1H), 7.99 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.8, 60.6, 117.4, 118.8, 118.8, 120.7, 121.3, 124.7, 127.1, 129.2, 132.5, 137.9, 141.7, 147.3, 166.6, 173.1 ppm. ESI-MS: m/z = 369.12 [M+Na] ⁺ .

Ethyl 3-(3-[2-{2-Naphthamido}-5-chlorobenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 60%. White solid. 1H-NMR (500 MHz, DMSO- d ₆ ): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 2.60 (t, ³ J= 7.5 Hz, 2H), 2.84 (t, ³ J= 7.5 Hz, 2H), 4.02 (q, ³ J = 7.1 Hz, 2H), 7.01 (d, ³ J = 7.6, Hz, 1H), 7.28 (dd, V= 8.5, 7.8 Hz, 1H), 7.54 - 7.60 (m, 2H), 7.62 (ddd, ³ J = 7.4, 7.4 Hz, ⁴ J = 1.3 Hz, 1H), 7.66 (ddd, ³ J = 7.4, 7.4 Hz, V= 1.3 Hz, 1H), 7.70 (dd, ³ J= 8.9 Hz, ⁴ J= 2.5 Hz, 1H), 7.96 (dd, ⁵ J= 8.6, Hz, ⁴ J= 1.8 Hz, 1H), 7.98 (d, ⁴ J = 2.4 Hz, 1H), 8.01 (d, ³ J = 8.0 Hz, 1H), 8.06 - 8.11 (m, 2H), 8.45 (d, ³ J = 8.9 Hz, 1H), 8.54 (d, V= 0.7 Hz, 1H), 10.58 (s, 1H), 11.67 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 59.9, 118.9, 120.9, 123.5, 123.5, 124.3, 125.3, 127.1, 127.3, 127.7, 128.0,

128.2, 128.6, 128.6, 128.7, 129.1, 131.6, 131.7, 132.2, 134.5, 137.3, 138.4, 141.1, 164.9, 165.8, 172.1 ppm. ESI-MS: m/z = 523.18 [M+Naf.

3-(3-[2-{2-Naphthamido}-5-chlorobenzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 88%. White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.82 (t, ³ J= 7.6 Hz, 2H), 7.02 (d, ³ J= 7.6, Hz, 1H), 7.28 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.57 (s, 1H), 7.58 - 7.68 (m, 3H), 7.71 (dd, ³ J = 8.9 Hz, ⁴ J = 2.4 Hz, 1H), 7.92 -

8.00 (m, 2H), 8.01 (d, ³ J= 8.0 Hz, 1H), 8.06 - 8.12 (m, 2H), 8.45 (d, ³ J= 8.9 Hz, 1H), 8.54 (s, 1H), 10.60 (s, 1H), 11.68 (s, 1H), 12.16 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 118.9, 120.9, 123.5, 123.6, 124.4, 125.4, 127.1, 127.3, 127.8, 128.1, 128.2, 128.7, 128.7, 128.7, 129.1, 131.6, 131.8, 132.2, 134.5, 137.4, 138.4, 141.4, 164.9, 165.9, 173.7 ppm. ESI-MS: m/z - 471.22 [M-H]-.

Ethyl 3-(3-[4-Methoxy-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 82%. Beige solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J=

7.1 Hz, 3H), 2.61 (t, ³ J= 7.6 Hz, 2H), 2.93 (t, ³ J= 7.7 Hz, 2H), 3.91 (s, 3H), 4.12 (q, ³ J= 7.1 Hz, 2H), 7.00 (d, ³ J= 7.4 Hz, 1H), 7.17 (dd, ³ J = 8.5 Hz, ⁴ J = 2.4 Hz, 1H), 7.23 - 7.31 (m, 1H), 7.47 (m, 4H), 7.63 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.9, 56.3, 60.6, 109.9, 118.4, 119.4, 120.3, 125.1, 129.4, 129.9, 130.0, 137.8, 141.9, 148.0, 161.1, 164.3, 173.0 ppm. ESI-MS: m/z = 395.16 [M+Na] ⁺ .

Ethyl 3-(3-[2-Amino-4-methoxybenzamidoJphenyl)propanoate: Preparation according to general procedure Dl . Yield: 98%. Pale yellow solid. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J= 7.1 Hz, 3H), 2.63 (t, ³ J = 7.8 Hz, 2H), 2.95 (t, ³ J= 7.8 Hz, 2H), 3.80 (s, 3H), 4.13 (q, ³ J= 7.1 Hz, 2H), 5.80 (br s, 2H), 6.19 (d, ⁴ J= 2.4 Hz, 1H), 6.28 (dd, ³ J= 8.8 Hz, ⁴ J= 2.5 Hz, 1H), 6.97 (d, ³ J= 7.5 Hz, 1H), 7.26 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.35 - 7.45 (m, 3H), 7.65 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.4, 31.1, 36.0, 55.4, 60.6, 101.1, 104.6, 109.4, 118.6, 120.5, 124.3, 129.0, 129.2, 138.3, 141.8, 151.3, 163.4, 167.4, 173.0 ppm. ESI-MS: m/z

Ethyl 3-(3-[2-{2-Naphthamido}-4-methoxybenzamido]phenyl)propanoate : Preparation according to general procedure CI. Yield: 87%. White solid. 1H-NMR (500 MHz, DMSO- d ₆ ): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 2.62 (t, ³ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.4 Hz, 2H), 3.89 (s, 3H), 4.03 (q, ³ J= 7.1 Hz, 2H), 6.87 (dd, ³ J= 8.8 Hz, ⁴ J= 2.5 Hz, 1H), 7.01 (d, ³ J= 7.6 Hz, 1H), 7.28 (dd, ³ J= 8.1, 8.1 Hz, 1H), 7.54 - 7.60 (m, 2H), 7.60 - 7.71 (m, 2H), 7.98 (dd, ³ J = 8.6 Hz, V= 1.6 Hz, 1H), 7.99 - 8.05 (m, 2H), 8.08 - 8.13 (m, 2H), 8.35 (d, ⁴ J- 2.6 Hz, 1H), 8.55 (s, 1H), 10.39 (s, 1H), 12.50 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.4, 35.1, 55.5, 59.9, 105.9, 108.5, 113.6, 119.3, 121.3, 123.3, 124.2, 127.1, 127.8, 127.9, 128.2, 128.6, 128.8, 129.2, 130.8, 131.9, 132.3, 134.5, 138.5, 141.0, 141.5, 162.3, 164.8, 167.5, 172.2 ppm. ESI-MS: m/z = 519.23 [M+Na] ⁺ .

3-(3-[2-{2-Naphthamido}-4-methoxybenzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 86%. White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.56 (t, ³ J= 7.6 Hz, 2H), 2.84 (t, ³ J= 7.6 Hz, 2H), 3.89 (s, 3H), 6.87 (dd, ³ J= 8.8 Hz, ⁴ J=

2.6 Hz, 1H), 7.02 (d, ³ J = 7.6 Hz, 1H), 7.29 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.52 - 7.72 (m, 4H), 7.94 - 8.06 (m, 3H), 8.11 (dd, ³ J = 6.8, 6.8 Hz, 2H), 8.36 (d, ⁴ J = 2.5 Hz, 1H), 8.55 (s, 1H), 10.38 (s, 1H), 12.17 (br s, 1H), 12.51 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 55.5, 105.9, 108.5, 113.6, 119.3, 121.3, 123.3, 124.2, 127.1, 127.7, 127.9, 128.2,

128.6, 128.8, 129.2, 130.7, 131.9, 132.2, 134.5, 138.5, 141.4, 141.5, 162.3, 164.8, 167.5, 173.7 ppm. ESI-MS: m/z = 467.25 [M-H]\

3-(3-[2-{2-Naphthamido}-4-hydroxybenzamido]phenyl)propanoic acid: Preparation according to general procedure H with boron tribromide. Yield: 65%. White solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 6.66 (dd, ⁵ J =

8.7 Hz, ⁴ J = 2.4 Hz, 1H), 7.00 (d, ⁵ J = 7.6 Hz, 1H), 7.27 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.55 (s, 1H), 7.57 (d, ³ J= 8.1 Hz, 1H), 7.60 - 7.70 (m, 2H), 7.91 (d, ³ J= 8.7 Hz, 1H), 7.98 (dd, ³ J = 8.6 Hz, ⁴ J= 1.6 Hz, 1H), 8.02 (d, ³ J= 8.0 Hz, 1H), 8.1 1 (dd, ³ J= 8.3, 8.3 Hz, 2H), 8.26 (d, ⁴ J = 2.4 Hz, 1H), 8.54 (s, 1H), 10.28 (s, 1H), 11.42 (br s, 2H), 12.57 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.4, 107.1, 110.1, 111.7, 119.2, 121.2, 123.3, 124.1, 127.1,

127.7, 127.8, 128.1, 128.6, 128.7, 129.1, 130.8, 132.0, 132.3, 134.4, 138.5, 141.5, 141.7, 161.3, 164.6, 167.8, 172.1, 173.8 ppm. ESI-MS: m/z = 453.08 [M-H] ^" .

Ethyl 3-(3-[2-Nitro-5-{trifluoromethoxy}benzamido]phenyl)propanoat e: Preparation according to general procedure CI. Yield: 68%. Yellow solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.7 Hz, 2H), 2.93 (t, ³ J= 7.7 Hz, 2H), 4.10 (q, ³ J= 7.1 Hz, 2H), 7.03 (d, ³ J = 7.6 Hz, 1H), 7.27 (dd, ³ J= 7.7, 7.7 Hz, 1H), 7.36 - 7.47 (m, 4H), 7.78 (s, 1H), 8.18 (d, ³ J = 8.4 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.8, 60.7, 118.6, 120.6, 121.9, 121.9, 125.6, 127.2, 129.5, 135.3, 137.3, 142.0, 143.8, 152.7, 152.7, 162.9, 173.0 ppm. ESI-MS: m/z = 449.13 [M+Na] ⁺ .

Ethyl 3-(3~[2-Amino-5-{trifluoromethoxy}benzamido]phenyl)propanoat e: Preparation according to general procedure Dl . Yield: 97%. Brown solid. 1H-NMR (500 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J= 7.1 Hz, 3H), 2.63 (t, ³ J= 7.8 Hz, 2H), 2.94 (t, ³ J= 7.8 Hz, 2H), 4.13 (q, ³ J= 7.1 Hz, 2H), 5.58 (br s, 2H), 6.74 (d, ³ J= 8.9 Hz, 1H), 7.00 (d, ³ J= 7.6 Hz, 1H), 7.14 (dd, ³ J= 8.9 Hz, ⁴ J = 1.7 Hz, 1H), 7.27 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.33 (d, ⁴ J = 2.4 Hz, 1H), 7.39 - 7.44 (m, 2H), 7.82 (s, 1H) ppm. ¹³ C-NMR (125 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.9, 60.7, 116.9,

118.8, 118.8, 120.5, 120.8, 120.8, 125.0, 126.3, 129.3, 137.7, 139.8, 141.9, 147.0, 166.4, 173.0 ppm. ESI-MS: m/z = 419.13 [M+Na] ⁺ .

Ethyl 3-(3-[2-{2-Naphthamido}-5-{trifluowmethoxy}benzamido]phenyl) propanoate:

Preparation according to general procedure CI . Yield: 64%. White solid. ¹ H-NMR (300 MHz, Acetone-de): δ = 1.17 (t, ³ J= 7.1 Hz, 3H), 2.64 (t, ⁵ J= 7.5 Hz, 2H), 2.95 (t, ³ J= 7.5 Hz, 2H), 4.08 (q, ³ J= 7.1 Hz, 2H), 7.10 (ddd, ³ J= 7.6 Hz, ⁴ J= 1.6, 1.1 Hz, 1H), 7.33 (dd, ³ J= 8.7, 7.6 Hz, 1H), 7.59 - 7.71 (m, 5H), 7.98 - 8.05 (m, 2H), 8.07 - 8.14 (m, 3H), 8.61 (d, ⁴ J= 0.8 Hz, 1H), 8.97 (d, ⁵ J = 9.2 Hz, 1H), 9.96 (s, 1H), 12.19 (s, 1H) ppm. ¹³ C-NMR (75 MHz, Acetone-d ₆ ): δ = 14.5, 31.6, 36.2, 60.7, 120.1, 121.5, 122.1, 122.3, 123.4, 123.7, 124.4, 125.8, 126.0, 127.9, 128.7, 129.0, 129.0, 129.6, 129.7, 130.1, 133.0, 133.7, 136.0, 139.2, 140.2, 142.7, 144.3, 165.8, 167.4, 172.8 ppm. ESI-MS: m/z = 573.19 [M+Na] ⁺ .

3-(3-[2-{2-Naphthamido}-5-{trifluoromethoxy}benzamidoJphe nyl)propanoic acid: Preparation according to general procedure E. Yield: 97%. White solid. ¹ H-NMR (500 MHz, Acetone-d ₆ ): δ = 2.66 (t, ³ J= 7.6 Hz, 2H), 2.95 (t, ³ J= 7.6 Hz, 2H), 7.12 (d, ³ J= 7.8 Hz, 1H), 7.33 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.61 - 7.67 (m, 3H), 7.67 (s, 1H), 7.71 (d, ³ J = 8.1 Hz, 1H), 7.99 - 8.04 (m, 2H), 8.06 - 8.13 (m, 3H), 8.61 (s, 1H), 8.98 (d, ⁵ J= 9.2 Hz, 1H), 9.99 (s, 1H), 10.63 (br s, 1H), 12.22 (s, 1H) ppm. ¹³ C-NMR (125 MHz, Acetone-d ₆ ): 5 = 31.5, 35.7, 120.1, 121.5, 122.1, 122.3, 123.4, 123.6, 124.4, 125.8, 126.0, 127.9, 128.7, 129.0, 129.0, 129.6, 129.7, 130.1, 132.9, 133.7, 136.0, 139.2, 140.2, 142.8, 144.3, 165.7, 167.4, 173.8 ppm. ESI- MS: m/z = 521.04 [M-H] ^" .

Ethyl 3-(3-[4-Chloro-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI. Yield: 62%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J= 7.1 Hz, 3H), 2.59 (t, ³ J = 7.7 Hz, 2H), 2.91 (t, ³ J= 7.7 Hz, 2H), 4.10 (q, ³ J= 7.1 Hz, 2H), 7.01 (d, ⁵ J= 7.5 Hz, 1H), 7.24 (dd, ³ J= 7.7, 7.7 Hz, 1H), 7.31 - 7.43 (m, 2H), 7.53 (d, ³ J= 8.2 Hz, 1H), 7.64 (dd, ⁵ J= 8.2 Hz, ⁴ J= 1.9 Hz, 1H), 7.91 (s, 1H), 8.01 (d, ⁴ J= 1.9 Hz, 1H) ppm. ¹³ C- NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 30.9, 35.8, 60.7, 118.6, 120.5, 125.0, 125.4, 129.4, 129.9, 131.2, 133.9, 136.8, 137.4, 141.9, 147.0, 163.5, 173.0 ppm. ESI-MS: m/z = 399.09 [M+Na] ⁺ . Ethyl 3-(3-[2-Amino-4-chlorobenzamido]phenyl)propanoate: Preparation according to general procedure D2 with iron turnings. Yield: 92%. Brown solid. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ⁵ J= 7.7 Hz, 2H), 2.93 (t, ³ J= 7.8 Hz, 2H), 4.12 (q, ³ J= 7.1 Hz, 2H), 5.34 (br s, 2H), 6.64 (dd, ³ J= 8.4 Hz, ⁴ J= 2.0 Hz, 1H), 6.70 (d, ⁴ J= 2.0 Hz, 1H), 6.98 (d, ³ J= 7.4 Hz, 1H), 7.25 (dd, ³ J= 7.9, 7.9 Hz, 1H), 7.33 - 7.45 (m, 3H), 7.82 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.9, 60.6, 114.8, 117.0, 117.1, 118.7, 120.7, 124.7, 128.6, 129.3, 137.9, 138.6, 141.8, 149.9, 167.0, 173.0 ppm. ESI-MS: m/z = 345.14 [M-H] ^" .

Ethyl 3-(3-[2-{2-Naphthamido}-4-chlorobenzamido]phenyl)propanoate: Preparation according to general procedure CI. Yield: 56%. Pale yellow solid. ¹ H-NMR (300 MHz, DMSO-d ₆ ): δ = 1.12 (t, ³ J = 7.1 Hz, 3H), 2.59 (t, ³ J = 7.6 Hz, 2H), 2.84 (t, ³ J= 7.4 Hz, 2H), 4.02 (q, ³ J= 7.1 Hz, 2H), 7.01 (d, ³ J= 7.5 Hz, 1H), 7.28 (dd, ³ J= 8.4, 7.7 Hz, 1H), 7.38 (d, ³ J = 8.1 Hz, 1H), 7.54 - 7.61 (m, 2H), 7.61 - 7.70 (m, 2H), 7.94 - 8.05 (m, 3H), 8.06 - 8.13 (m, 2H), 8.54 (d, ⁴ J = 1.3 Hz, 1H), 8.62 (d, ⁴ J = 2.2 Hz, 1H), 10.58 (s, 1H), 11.98 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 30.3, 35.0, 59.8, 119.0, 120.8, 121.0, 121.5, 121.6,

123.5, 124.3, 127.1, 127.7, 128.0, 128.1, 128.6, 128.6, 129.1, 130.7, 132.2, 132.9, 134.5, 136.5, 138.4, 141.0, 141.0, 162.1, 166.4, 172.1 ppm. ESI-MS: m/z = 523.17 [M+Na] ⁺ .

3- (3-[2-{2-Naphthamido}-4-chlorobenzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 82%. Beige solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.55 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J = 7.6 Hz, 2H), 7.03 (d, ³ J = 7.7 Hz, 1H), 7.29 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.40 (dd, ³ J= 8.5 Hz, ⁴ J= 2.2 Hz, 1H), 7.54 - 7.61 (m, 2H), 7.63 (ddd, ³ J= 7.4, 7.4 Hz, ⁴ J= 1.2 Hz, 1H), 7.67 (ddd, ³ J= 7.4, 7.4 Hz, ⁴ J= 1.3 Hz, 1H), 7.96 (dd, ³ J= 8.6 Hz, ⁴ J= 1.8 Hz, 1H), 7.99 (d, ³ J = 8.5 Hz, 1H), 8.02 (d, ³ J= 7.9 Hz, 1H), 8.10 (dd, ⁵ J = 8.5, 8.5 Hz, 2H), 8.54 (s, 1H), 8.63 (d, ⁴ J = 2.1 Hz, 1H), 10.58 (s, 1H), 12.00 (s, 1H), 12.15 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 119.0, 120.7, 121.0, 121.4, 123.0, 123.4, 124.4, 127.2, 127.7, 128.1, 128.3, 128.7, 128.7, 129.1, 130.8, 131.5, 132.2, 134.5,

136.6, 138.3, 140.1, 141.4, 165.0, 166.5, 173.7 ppm. ESI-MS: m/z = 471.01 [M-H] ^" .

4- (tert-Butyl)-l-tnethyl-2-nitrobenzene: Preparation according to general procedure I. Yield: 52%. Yellow oil. ¹ H-NMR (500 MHz, CDC1 ₃ ): δ = 1.34 (s, 9H), 2.56 (s, 3H), 7.26 (d, ³ J =

8.0 Hz, 1H), 7.52 (dd, ³ J= 8.0 Hz, ⁴ J= 2.0 Hz, 1H), 7.97 (d, ⁴ J= 2.0 Hz, 1H) ppm. ¹³ C-NMR (125 MHz, CDC1 ₃ ): δ = 20.1, 31.2, 34.8, 121.6, 130.4, 130.7, 132.6, 149.2, 150.8 ppm. ESI- MS: not detectable.

4-(tert-Butyl)-2-nitrobenzoic acid: Preparation according to general procedure J. Yield: 18%. Pale yellow solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.32 (s, 9H), 7.79 - 7.82 (m, 2H), 7.90 (dd, ⁴ J= 1.3, 0.9 Hz, 1H), 13.71 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 30.5, 35.2, 120.4, 123.8, 129.5, 130.0, 149.1, 156.3, 165.5 ppm. ESI-MS: not detectable.

Ethyl 3-(3-[4-{tert-Butyl}-2-nitrobenzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 75%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J=

7.1 Hz, 3H), 1.37 (s, 9H), 2.61 (t, ³ J= 7.7 Hz, 2H), 2.93 (t, ³ J= 7.7 Hz, 2H), 4.11 (q, ³ J= 7.1 Hz, 2H), 7.00 (d, ³ J= 7.6 Hz, 1H), 7.26 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.37 - 7.49 (m, 2H), 7.54 (d, ³ J= 8.0 Hz, 1H), 7.70 (dd, ³ J= 8.0 Hz, ⁴ J= 1.6 Hz, 1H), 7.74 (s, 1H), 8.07 (d, ⁴ J= 1.5 Hz, lH) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 31.1, 35.4, 35.9, 60.7, 118.4, 120.4, 121.8, 125.1, 128.5, 129.4, 130.2, 131.0, 137.8, 141.9, 146.6, 155.3, 164.7, 173.1 ppm. ESI- MS: m/z = 421.16 [M+Na] ⁺ . Ethyl 3-(3-[2-Amino-4-{tert-butyl}benzatnido]phenyl)propanoate: Preparation according to general procedure Dl. Yield: 69%. Brown oil. ¹ H-NMR (500 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J = 7.2 Hz, 3H), 1.30 (s, 9H), 2.63 (t, ³ J = 7.8 Hz, 2H), 2.95 (t, ³ J = 7.8 Hz, 2H), 4.13 (q, ³ J= 7.1 Hz, 2H), 5.40 (br s, 2H), 6.75 (d, ⁴ J = 1.6 Hz, 1H), 6.77 (dd, ³ J = 8.3 Hz, ⁴ J = 1.8 Hz, 1H), 6.98 (d, ⁵ J= 7.6 Hz, 1H), 7.27 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.38 - 7.43 (m, 2H), 7.45 (s, 1H), 7.78 (s, 1H) ppm. ¹³ C-NMR (126 MHz, CDC1 ₃ ): δ = 14.3, 31.1, 31.1, 34.9, 36.0, 60.6, 113.9, 114.9, 115.1, 118.5, 120.5, 124.5, 127.1, 129.3, 138.2, 141.8, 148.5, 156.7, 167.5, 173.0 ppm. ESI-MS: m/z = 391.22 [M+Na] ⁺ .

Ethyl 3-(3-[2-{2-Naphthamido}-4-{tert-butyl}benzamido]phenyl)propa noate: Preparation according to general procedure CI . Yield: 97%. White solid. 1H-NMR (300 MHz, DMSO- d ₆ ): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 1.36 (s, 9H), 2.60 (t, ³ J= 7.5 Hz, 2H), 2.85 (t, ³ J= 7.4 Hz, 2H), 4.03 (q, ³ J= 7.1 Hz, 2H), 6.99 (d, ³ J= 7.6, Hz, 1H), 7.27 (dd, ³ J= 7.7, 7.7 Hz, 1H), 7.34 (dd, ³ J= 8.3 Hz, ⁴ J= 2.0 Hz, 1H), 7.54 - 7.70 (m, 4H), 7.88 (d, ³ J= 8.4 Hz, 1H), 7.95 - 8.04 (m, 2H), 8.05 - 8.14 (m, 2H), 8.55 (d, V= 1.3 Hz, 1H), 8.62 (d, ⁴ J = 1.9 Hz, 1H), 10.42 (s, 1H), 11.87 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 30.3, 30.8, 34.9, 35.0,

59.8, 118.3, 118.9, 120.4, 120.8, 123.4, 124.1, 125.1, 127.0, 127.7, 127.8, 128.1, 128.6, 128.6, 128.8, 129.0, 132.0, 132.2, 134.4, 138.6, 138.6, 141.0, 155.2, 164.8, 167.3, 172.1 ppm. ESI- MS: m/z = 545.28 [M+Na] ⁺ .

3-(3-[2-{2-Naphthamido}-4-{tert-butyl}benzamido]phenyl)propa noic acid: Preparation according to general procedure E. Yield: 73%. White solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 1.36 (s, 9H), 2.54 (t, ³ J= 7.6 Hz, 2H), 2.82 (t, ⁵ J= 7.6 Hz, 2H), 7.00 (d, ³ J= 7.6, Hz, 1H), 7.27 (dd, ³ J= 8.6, 7.8 Hz, 1H), 7.34 (dd, ³ J= 8.3 Hz, ⁴ J= 1.9 Hz, 1H), 7.55 - 7.61 (m, 2H),

7.61 - 7.69 (m, 2H), 7.89 (d, ⁵ J= 8.3 Hz, 1H), 7.98 (dd, ³ J= 8.6 Hz, ⁴ J= 1.7 Hz, 1H), 8.02 (d, ³ J= 7.7 Hz, 1H), 8.09 (dd, ³ J= 8.2, 8.2 Hz, 2H), 8.55 (s, 1H), 8.62 (d, ⁴ J= 1.8 Hz, 1H), 10.44 (s, 1H), 11.89 (s, 1H), 12.17 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 30.9,

34.9, 35.2, 118.3, 118.8, 120.4, 120.5, 120.8, 123.5, 124.1, 127.1, 127.7, 127.8, 128.1, 128.6, 128.6, 128.8, 129.1, 132.0, 132.2, 134.4, 138.6, 138.7, 141.4, 155.3, 164.8, 167.3, 173.7 ppm. ESI-MS : m/z = 493.14 [M-H] ^" .

6-Nitrobenzo[d][l,3]dioxole-5-carboxylic acid: Preparation according to general procedure I. Yield: 76%. Yellow solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 6.28 (s, 2H), 7.30 (s, 1H),

7.62 (s, 1H), 13.63 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 103.9, 104.6, 108.2, 123.5, 143.1, 149.5, 150.8, 165.7 ppm. ESI-MS: m/z = 210.16 [M-H] ^" .

Ethyl 3-(3-[6-Nitrobenzo[d][l,3]dioxole-5-carboxamido]phenyl)propa noate: Preparation according to general procedure CI . Yield: 59%. Brown solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.23 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.8 Hz, 2H), 2.93 (t, ³ J= 7.7 Hz, 2H), 4.12 (q, ³ J= 7.1 Hz, 2H), 6.17 (s, 2H), 6.94 (s, 1H), 7.00 (d, ³ J= 7.5 Hz, 1H), 7.26 (dd, ³ J= 7.7, 7.7 Hz, 1H), 7.34 - 7.46 (m, 2H), 7.54 (s, 1H), 7.63 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.9, 60.6, 103.8, 105.4, 107.8, 118.5, 120.5, 125.2, 129.4, 129.4, 137.6, 140.7, 142.0,

149.0, 152.4, 164.2, 173.0 ppm. ESI-MS: m/z = 409.07 [M+Na] ⁺ .

Ethyl 3-(3-f 6-Aminobenzo[d][l,3]dioxole-5-carboxamido]phenyl)propanoate: Preparation according to general procedure Dl . Yield: 75%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.24 (t, ³ J= 7.1 Hz, 3H), 2.63 (t, ³ J= 7.8 Hz, 2H), 2.95 (t, ³ J= 7.8 Hz, 2H), 4.13 (q, ³ J = 7.1 Hz, 2H), 5.53 (br s, 2H), 5.91 (s, 2H), 6.23 (s, 1H), 6.91 (s, 1H), 6.96 (d, ³ J = 7.7 Hz, 1H), 7.26 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.34 - 7.39 (m, 1H), 7.40 - 7.43 (m, 1H), 7.62 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.4, 31.1, 36.0, 60.6, 98.5, 101.4, 105.7, 107.6, 118.6, 120.5, 124.4, 129.2, 138.3, 139.8, 141.8, 146.9, 151.7, 167.3, 173.0 ppm. ESI-MS: m/z = 379.11 [M+Na] ⁺ .

Ethyl 3-(3-[6-{2-Naphthamido}benzo[d][l,3]dioxole-5~carboxamido]ph enyl)-propanoate:

Preparation according to general procedure CI. Yield: 84%. Beige solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 1.12 (t, ³ J = 7.1 Hz, 3H), 2.60 (t, ³ J = 7.5 Hz, 2H), 2.85 (t, ³ J = 7.5 Hz, 2H), 4.02 (q, ³ J = 7.1 Hz, 2H), 6.18 (s, 2H), 7.00 (d, ³ J = 7.6, Hz, 1H), 7.27 (dd, ³ J = 7.7, 7.7 Hz, 1H), 7.52 - 7.57 (m, 2H), 7.58 (s, 1H), 7.62 (ddd, ³ J = 7.4, 7.4 Hz, ⁴ J = 1.2 Hz, 1H), 7.65 (ddd, ³ J= 7.4, 7.4 Hz, ⁴ J= 1.2 Hz, 1H), 7.96 (dd, ³ J= 8.6 Hz, ⁴ J= 1.7 Hz, 1H), 8.01 (d, ³ J=

8.0 Hz, 1H), 8.06 - 8.11 (m, 2H), 8.19 (s, 1H), 8.53 (d, ⁴ J= 0.8 Hz, 1H), 10.28 (s, 1H), 12.26 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 59.9, 102.2, 102.2, 108.1, 114.8, 119.2, 121.1, 123.3, 124.2, 127.1, 127.7, 127.8, 128.1, 128.6, 128.6, 129.1, 131.8, 132.2, 134.4, 135.6, 138.5, 141.0, 142.8, 150.1, 164.6, 167.0, 172.1 ppm. ESI-MS: m/z = 509.20 [M-H] ^' .

3-(3-[6-{2-Naphthamido}benzo[d][l,3]dioxole-5-carboxamido]ph enyl)propanoic acid:

Preparation according to general procedure E. Yield: 87%. White solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.55 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.5 Hz, 2H), 6.18 (s, 2H), 7.01 (d, ³ J= 7.5, Hz, 1H), 7.28 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.52 - 7.69 (m, 5H), 7.96 (d, ³ J = 8.5 Hz, 1H),

8.01 (d, ³ J= 7.9 Hz, 1H), 8.06 - 8.12 (m, 2H), 8.20 (s, 1H), 8.53 (s, 1H), 10.29 (s, 1H), 12.15 (br s, 1H), 12.29 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 102.2, 102.2,

108.1, 114.7, 119.1, 121.2, 123.3, 124.2, 127.1, 127.7, 127.8, 128.1, 128.6, 128.7, 129.1, 131.8, 132.2, 134.4, 135.7, 138.4, 141.4, 142.8, 150.1, 164.5, 167.0, 173.7 ppm. ESI-MS: m/z = 481.06 [M-H] ^" . Ethyl 3-(3-[2-{4-(2-Thienyl)benzamido}benzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 90%. Yellow solid. 1H-NMR (500 MHz, DMSO- d ₆ ): δ = 1.14 (t, ³ J = 7.1 Hz, 3H), 2.61 (t, ³ J = 7.5 Hz, 2H), 2.86 (t, ³ J = 7.5 Hz, 2H), 4.04 (q, ⁵ J = 7.1 Hz, 2H), 7.02 (d, ³ J = 7.6 Hz, 1H), 7.19 (dd, ³ J = 5.0, 3.7 Hz, 1H), 7.26 - 7.32 (m, 2H), 7.56 (s, 1H), 7.58 (d, ³ J = 8.1 Hz, 1H), 7.62 (ddd, ³ J = 7.9, 7.9 Hz, ⁴ J= 1.3 Hz, 1H), 7.65 (dd, ³ J= 5.1 Hz, ^¥ J= 0.9 Hz, 1H), 7.68 (dd, ³ J= 3.6 Hz, ^¥ J= 0.9 Hz, 1H), 7.86 (d, ⁵ J = 8.4 Hz, 2H), 7.93 (dd, ³ J = 8.0 Hz, ⁴ J = 1.0 Hz, 1H), 7.95 (d, ³ J= 8.5 Hz, 2H), 8.49 (d, ³ J = 8.0 Hz, 1H), 10.50 (s, 1H), 11.74 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 59.9, 119.1, 121.0, 121.3, 122.9, 123.3, 124.3, 125.2, 125.6, 127.2, 128.0, 128.6, 128.8, 129.0, 132.3, 133.0, 137.1, 138.5, 138.7, 141.0, 142.0, 164.0, 167.4, 172.1 ppm. ESI- MS: m/z = 497.18 [M-H] ^" .

3- (3-[2-{4-(2-Thienyl)benzamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 39%. Yellow solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.55 (t, ³ J= 7.6 Hz, 2H), 2.84 (t, ⁵ J= 7.5 Hz, 2H), 7.03 (d, ³ J= 7.6 Hz, 1H), 7.19 (dd, ³ J= 4.9, 3.8 Hz, 1H), 7.26 - 7.32 (m, 2H), 7.55 (s, 1H), 7.58 - 7.66 (m, 3H), 7.68 (d, ³ J = 3.5 Hz, 1H),

7.87 (d, ³ J= 8.4 Hz, 2H), 7.91 - 7.99 (m, 3H), 8.50 (d, ³ J= 8.2 Hz, 1H), 10.51 (s, 1H), 11.76 (s, 1H), 12.15 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 119.1, 121.1,

121.3, 122.8, 123.3, 124.3, 125.3, 125.6, 127.2, 128.0, 128.6, 128.8, 129.0, 132.3, 133.0, 137.1, 138.5, 138.7, 141.4, 142.1, 164.0, 167.4, 173.7 ppm. ESI-MS: m/z = 469.06 [M-Hf.

4- (2-Furyl) benzoic acid: Preparation according to general procedure L. Yield: 81%. Brown solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 6.65 (dd, ³ J= 3.4, 1.8 Hz, 1H), 7.13 (dd, ³ J= 3.4 Hz, ⁴ J= 0.6 Hz, 1H), 7.78 - 7.86 (m, 3H), 7.90 (ddd, ³ J= 8.5 Hz, ⁴ J= 1.8, 1.8 Hz, 2H), 12.92 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 108.2, 112.4, 123.2, 129.2, 130.0, 134.0, 144.1,

152.1, 166.9 ppm. ESI-MS: m/z = 187.04 [M-H]\

Ethyl 3-(3-[2-{4-(2-Furyl)benzamido}benzamido]phenyl)propanoate: Preparation according to general procedure CI. Yield: 48%. Brown solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.4 Hz, 2H), 2.86 (t, ³ J = 7.4 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 6.65 (dd, ³ J= 3.4, 1.8 Hz, 1H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.13 (dd, ³ J= 3.4 Hz, ⁴ J= 0.6 Hz, 1H), 7.24 - 7.34 (m, 2H), 7.54 - 7.66 (m, 3H), 7.83 (dd, ³ J= 1.7 Hz, ⁴ J = 0.6 Hz, 1H),

7.88 (d, ³ J = 8.6 Hz, 2H), 7.93 (dd, ³ J= 8.0 Hz, ⁴ J= 1.4 Hz, 1H), 7.97 (d, ³ J= 8.7 Hz, 2H), 8.48 (dd, ³ J= 8.3 Hz, ⁴ J= 0.9 Hz, 1H), 10.49 (s, 1H), 11.72 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 59.8, 108.0, 112.4, 119.1, 121.0, 121.4, 122.9, 123.3, 123.6,

124.2, 127.8, 128.6, 129.0, 132.2, 132.8, 133.3, 138.5, 138.6, 141.0, 144.0, 152.0, 164.1,

167.4, 172.1 ppm. ESI-MS: m/z = 481.18 [M-H]\ 3- (3-[2-{4-(2-Furyl)benzamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 91%. Brown solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.55 (t, ³ J = 7.6 Hz, 2H), 2.83 (t, ³ J = 7.5 Hz, 2H), 6.66 (dd, ³ J = 3.3, 1.8 Hz, 1H), 7.02 (d, ³ J = 7.6 Hz, 1H), 7.14 (d, ³ J = 3.3 Hz, 1H), 7.25 - 7.34 (m, 2H), 7.55 (s, 1H), 7.59 (d, ³ J = 8.3 Hz, 1H), 7.62 (ddd, ³ J= 7.9, 7.9 Hz, ^¥ J= 1.2 Hz, 1H), 7.84 (dd, ³ J= 1.2 Hz, 1H), 7.89 (d, ³ J= 8.4 Hz, 2H), 7.93 (d, ³ J= 7.2 Hz, 1H), 7.97 (d, ³ J= 8.5 Hz, 2H), 8.48 (d, ³ J= 8.2 Hz, 1H), 10.51 (s, 1H), 11.73 (s, 1H), 12.15 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 108.1, 112.5, 119.0, 121.0, 121.3, 122.9, 123.3, 123.6, 124.2, 127.8, 128.6, 129.0, 132.3, 132.8, 133.4, 138.5, 138.7, 141.4, 144.0, 152.1, 164.1, 167.4, 173.7 ppm. ESI-MS: m/z = 453.16 [M-H] ^" .

4- (3-Fury I) benzoic acid: Preparation according to general procedure L. Yield: 86% _> . White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 7.04 (d, ⁴ J = 0.8 Hz, 1H), 7.74 (d, *J = 8.3 Hz, 2H), 7.79 (s, 1H), 7.94 (d, ³ J = 8.3 Hz, 2H), 8.32 (s, 1H), 12.88 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 108.7, 125.1, 125.5, 129.0, 129.9, 136.4, 140.7, 144.7, 167.1 ppm. 3-(3-[2-{4-(3-Furyl)benzamido}benzamido]phenyl)propanoate: Preparation according to general procedure CI. Yield: 65%. Beige solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.4 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 7.02 (d, ³ J= 7.7 Hz, 1H), 7.05 (dd, ³ J= 1.9 Hz, ⁴ J= 0.8 Hz, 1H), 7.25 - 7.33 (m, 2H), 7.49 - 7.69 (m, 3H), 7.79 (dd, ⁴ J = 1.7, 1.7 Hz, 1H), 7.82 (d, ⁵ J = 8.5 Hz, 2H), 7.93 (d, ³ J= 8.5 Hz, 3H), 8.33 (dd, ³ J= I A Hz, ⁴ J= 0.9 Hz, 1H), 8.50 (dd, ³ J= 8.3 Hz, ⁴ J= 0.9 Hz, 1H), 10.49 (s, 1H), 11.73 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 30.3, 35.0, 59.8, 108.6, 119.1, 121.0, 121.2, 122.7, 123.2, 124.2, 125.0, 125.8, 127.6, 128.6, 129.0, 132.2, 132.6, 135.6, 138.4, 138.7, 140.6, 141.0, 144.6, 164.2, 167.4, 172.1 ppm.

3-(3-[2-{4-(3-Furyl)benzamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 99%. Beige solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.55 (t, ³ J = 7.6 Hz, 2H), 2.84 (t, ³ J= 7.6 Hz, 2H), 7.03 (d, ³ J= 7.6 Hz, 1H), 7.06 (d, ⁴ J= 0.9 Hz, 1H), 7.29 (dd, ⁵ J = 7.8, 7.8 Hz, 2H), 7.55 (s, 1H), 7.58 - 7.66 (m, 2H), 7.79 (dd, ⁴ J= 1.6, 1.6 Hz, 1H), 7.83 (d, ³ J = 8.3 Hz, 2H), 7.94 (d, ³ J = 8.4 Hz, 3H), 8.33 (s, 1H), 8.51 (d, ³ J= 8.2 Hz, 1H), 10.51 (s, 1H), 11.76 (s, 1H), 12.15 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 108.7, 119.0, 121.0, 121.2, 122.7, 123.2, 124.3, 125.0, 125.8, 127.7, 128.6, 129.0, 132.3, 132.6, 135.7, 138.5, 138.8, 140.6, 141.4, 144.7, 164.2, 167.5, 173.7 ppm. ESI-MS: m/z = 453.08 [M-H] ^" . 4-(3-Thienyl)benzoic acid: Preparation according to general procedure L. Yield: 90%. Beige solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 7.64 (dd, ³ J = 5.1 Hz, ⁴ J = 1.4 Hz, 1H), 7.69 (dd, ³ J= 5.0 Hz, ⁴ J = 2.9 Hz, 1H), 7.85 (ddd, ³ J = 8.7 Hz, ⁴ J = 1.8, 1.8 Hz, 2H), 7.97 (ddd, ³ J= 8.6 Hz, ⁴ J= 1.8, 1.8 Hz, 2H), 8.05 (dd, ⁴ J= 2.9, 1.4 Hz, 1H), 12.91 (br s, 1H) ppm. ¹³ C- NMR (75 MHz, DMSO-d ₆ ): δ = 122.8, 126.0, 126.2, 127.5, 129.1, 130.0, 139.1, 140.3, 167.1 ppm.

Ethyl 3-(3-[2-{4-(3-thienyl)benzamido}benzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 44%. Beige solid. ¹ H-NMR (300 MHz, DMSO- d ₆ ): δ = 1.14 (t, ³ J = 7.1 Hz, 3H), 2.61 (t, ³ J= 7.4 Hz, 2H), 2.86 (t, ³ J= 7.5 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 7.02 (d, ³ J= 7.8 Hz, 1H), 7.24 - 7.36 (m, 2H), 7.52 - 7.73 (m, 5H), 7.89 - 8.00 (m, 5H), 8.06 (dd, ³ J= 2.8 Hz, V= 1.4 Hz, 1H), 8.51 (dd, ⁵ J= 8.3 Hz, ⁴ J= 0.8 Hz, 1H), 10.50 (s, 1H), 11.74 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ - 14.0, 30.3, 35.0, 59.8,

119.1, 121.0, 121.2, 122.7, 122.7, 123.2, 124.2, 126.2, 126.3, 127.5, 127.7, 128.6, 129.0, 132.2, 132.7, 138.4, 138.4, 138.7, 140.3, 141.0, 164.2, 167.4, 172.1 ppm.

3- (3-[2-{4-(3-Thienyl)benzamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 99%. Pale yellow solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ⁵ J= 7.6 Hz, 2H), 7.02 (d, ³ J= 7.6 Hz, 1H), 7.26 - 7.33 (m, 2H), 7.54 (s, 1H), 7.57 - 7.65 (m, 2H), 7.65 - 7.71 (m, 2H), 7.91 - 7.99 (m, 5H), 8.06 (dd, ³ J = 2.8 Hz, ⁴ J= 1.3 Hz, 1H), 8.51 (d, ⁵ J= 8.3 Hz, 1H), 10.52 (s, 1H), 11.77 (s, 1H), 11.89 (br s, lH) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.2, 119.1, 121.1, 121.2, 122.7, 122.8,

123.2, 124.3, 126.2, 126.4, 127.5, 127.7, 128.6, 129.1, 132.3, 132.7, 138.4, 138.4, 138.8,

140.3, 141.5, 164.2, 167.5, 173.8 ppm. ESI-MS: m/z = 469.04 [M-H]\

4- Chloro-2H-chromene-3-carboxaldehyde: Preparation according to general procedure M. Yield: 97%. Yellow solid. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 5.00 (s, 2H), 6.90 (ddd, ³ J= 8.2 Hz, V= 1.1 Hz, ⁵ J= 0.3 Hz, 1H), 7.05 (ddd, ³ J= 7.8, 7.4 Hz, V= 1.1 Hz, 1H), 7.37 (ddd, ³ J = 8.2, 7.4 Hz, ⁴ J= 1.6 Hz, 1H), 7.69 (dd, ³ J= 7.9, ⁴ J= 1.6 Hz, 1H), 10.16 (s, 1H) ppm. ¹³ C- NMR (75 MHz, CDC1 ₃ ): δ = 64.5, 116.8, 120.7, 122.3, 125.0, 126.7, 134.2, 143.4, 156.8, 187.9 ppm.

4-Chloro-2H-chromene-3-carboxylic acid: Preparation according to general procedure N. Yield: 45%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 4.97 (s, 2H), 6.96 (dd, ³ J= 8.1 Hz, ⁴ J = 0.9 Hz, 1H), 7.10 (ddd, ³ J = 7.7, 7.7 Hz, ⁴ J = 1.1 Hz, 1H), 7.38 (ddd, ³ J = 8.0, 8.0 Hz, ⁴ J= 1.6 Hz, 1H), 7.63 (dd, ³ J = 7.8 Hz, ⁴ J = 1.5 Hz, 1H), 13.39 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 66.2, 116.1, 120.9, 121.2, 122.3, 126.4, 132.5, 132.6, 155.0, 164.1 ppm. Ethyl 3-(3-[2-{4-chloro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoate:

Preparation according to general procedure CI. Yield: 38%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ - 1.14 (t, ³ J= 7.1 Hz, 3H), 2.60 (t, ³ J = 7.5 Hz, 2H), 2.84 (t, ³ J= 7.5 Hz, 2H), 4.03 (q, ³ J= 7.1 Hz, 2H), 5.01 (s, 2H), 6.96 (dd, ³ J= 8.1 Hz, ⁴ J= 0.7 Hz, 1H), 6.99 (d, ³ J = 7.7 Hz, 1H), 7.10 (ddd, ³ J = 7.7, 7.7 Hz, ⁴ J = 0.9 Hz, 1H), 7.26 (dd, ³ J = 7.8. 7.8 Hz, 1H), 7.31 (d, ³ J= 7.6 Hz, 1H), 7.37 (ddd, ³ J = 8.0, 8.0 Hz, ⁴ J= \ .5 Hz, 1H), 7.53 - 7.63 (m, 4H), 7.83 (d, ³ J= 7.7 Hz, 1H), 8.27 (d, ³ J = 8.1 Hz, 1H), 10.46 (s, 1H), 11.13 (s, 1H) ppm. ¹³ C- NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.4, 35.0, 59.9, 66.6, 116.1, 118.7, 120.5, 120.6, 122.0, 122.3, 124.0, 124.1, 124.6, 125.8, 125.8, 125.9, 128.6, 128.9, 131.8, 132.2, 136.9, 138.6, 141.0, 154.5, 161.9, 166.7, 172.1 ppm.

3-(3-[2-{4-Chloro-2H-chromene-3-carboxamido}benzamido]phenyl )propanoic acid:

Preparation according to general procedure E. Yield: 54%. Yellow solid. ^-NMR (500 MHz, DMSO-d ₆ ): δ = 2.53 (t, ³ J = 7.7 Hz, 2H), 2.81 (t, ³ J = 7.6 Hz, 2H), 5.01 (s, 2H), 6.96 (dd, ³ J= 8.1 Hz, ⁴ J= 0.6 Hz, 1H), 7.00 (d, ³ J= 7.6 Hz, 1H), 7.10 (ddd, ³ J= 7.6, 7.6 Hz, ⁴ J = 0.9 Hz, 1H), 7.26 (dd, ³ J = 7.8, 7.8 Hz, 1H), 7.31 (dd, ³ J = 7.6, 7.6 Hz, 1H), 7.37 (ddd, ³ J = 8.0, 8.0 Hz, V= 1.5 Hz, 1H), 7.52 - 7.63 (m, 4H), 7.84 (d, ³ J= 7.1 Hz, 1H), 8.27 (d, ³ J= 8.1 Hz, 1H), 10.47 (s, 1H), 11.13 (s, 1H), 12.10 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO- d ₆ ): δ = 30.4, 35.1, 66.6, 116.1, 118.6, 120.5, 120.6, 122.0, 122.4, 122.4, 124.0, 124.1, 125.8, 125.8, 125.9, 128.6, 128.9, 131.9, 132.2, 136.9, 138.6, 141.4, 154.5, 161.9, 166.7, 173.7 ppm. ESI-MS: m/z = 475.00 [M-H] ^" .

2-Nitro-4-(trifluoromethoxy)benzonitrile: Preparation according to general procedure O. Yield: 92%. Yellow liquid. 1H-NMR (400 MHz, CDC1 ₃ ) δ = 7.66 (d, ³ J = 8.5 Hz, 1H), 8.00 (d, ³ J= 8.6 Hz, 1H), 8.18 (s, 1H). ¹³ C-NMR (75 MHz, CDC1 ₃ ) δ = 106.3, 114.0, 117.9, 120.2, 125.6, 137.3, 152.3, 152.3 ppm.

2-Nitro-4-(trifluoromethoxy)benzoic acid: Preparation according to general procedure P. Yield: 45%. Cream solid. ¹ H-NMR (300 MHz, DMSO-d ₆ ) δ = 7.74 (m, 1H), 7.96 (d, ³ J = 8.5 Hz, 1H), 8.02 (d, ⁴ J = 1.7 Hz, 1H). ¹³ C-NMR (75 MHz, DMSO-d ₆ ) δ = 116.4, 119.8, 124.5, 128.1, 132.3, 149.0, 149.5, 164.8 ppm.

Ethyl 3-(3-[2-nitro-4-{trifluoromethoxy}benzamido]phenyl)propanoat e: Preparation according to general procedure CI . Yield: 61%. Yellow oil. 1H-NMR (400 MHz, CDC1 ₃ ): δ = 1.22 (t, ³ J = 7.1 Hz, 3H), 2.60 (t, ³ J = 7.7 Hz, 2H), 2.92 (t, ³ J = 7.7 Hz, 2H), 4.10 (q, ³ J= 7.1 Hz, 2H), 7.01 (d, ³ J = 7.6 Hz, 1H), 7.22 - 7.30 (m, 1H), 7.38 (d, ³ J = 8.2 Hz, 1H), 7.41 (s, 1H), 7.54 (d, ³ J = 8.3 Hz, 1H), 7.67 (d, ³ J = 8.4 Hz, 1H), 7.91 (m, 2H) ppm. ¹³ C- NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 31.0, 35.8, 60.7, 117.4, 118.6, 120.3, 120.5, 125.5, 125.9, 129.4, 130.5, 131.3, 137.4, 142.0, 147.3, 150.0, 163.3, 173.0 ppm.

Ethyl 3-(3-[2-amino-4-{trifluoromethoxy}benzamido]phenyl)propanoat e: Preparation according to general procedure Dl. Yield: 90%. Yellow solid. 1H-NMR (400 MHz, CDC1 ₃ ): δ = 1.17 (t, ³ J = 7.1 Hz, 3H), 2.56 (t, ³ J = 7.7 Hz, 2H), 2.88 (t, ³ J = 7.7 Hz, 2H), 4.06 (q, ³ J = 7.1 Hz, 2H), 4.84 (s, 2H), 6.46 - 6.54 (m, 2H), 6.93 (d, ³ J= 7.5 Hz, 1H), 7.16 - 7.24 (m, 1H), 7.32 (d, ³ J = 8.1 Hz, 1H), 7.36 (s, 1H), 7.42 (d, ³ J = 9.1 Hz, 1H), 7.69 (br s, 1H) ppm. "C-NMR (75 MHz, CDC1 ₃ ): δ - 14.3, 31.0, 35.9, 60.6, 108.8, 109.0, 116.9, 118.7, 120.7, 124.9, 129.2, 129.3, 129.3, 137.8, 141.9, 150.2, 152.5, 166.7, 173.0 ppm.

Ethyl 3-(3-[2-{2-naphthamido}-4-{trifluoromethoxy}benzamido]phenyl )propanoate: Preparation according to general procedure CI. Yield: 20%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 1.12 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.4 Hz, 2H), 2.85 (t, ³ J= 7.3 Hz, 2H), 4.03 (q, ³ J= 7.0 Hz, 2H), 7.02 (d, ³ J= 7.4 Hz, 1H), 7.21 - 7.38 (m, 2H), 7.51 - 7.74 (m, 4H), 7.96 (d, ³ J= 8.5 Hz, 1H), 8.02 (d, ³ J= 8.0 Hz, 1H), 8.05 - 8.16 (m, 3H), 8.55 (d, ³ J= 8.9 Hz, 2H), 10.60 (s, 1H), 11.98 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 14.1, 30.3, 35.0, 59.9, 112.9, 115.0, 119.0, 120.0, 120.9, 121.8, 123.4, 124.4, 127.1, 127.7, 128.1, 128.3, 128.7, 128.7, 129.1, 131.3, 131.4, 132.2, 134.5, 138.4, 140.5, 141.1, 150.4, 165.1, 166.3, 172.1 ppm.

3-(3-[2-{2-Naphthamido}-4-{trifluoromethoxy}benzamido]phenyl )propanoic acid:

Preparation according to general procedure E. Yield: 56%. White solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.5 Hz, 2H), 7.03 (d, ⁵ J= 7.6 Hz, 1H), 7.24 - 7.37 (m, 2H), 7.53 - 7.72 (m, 4H), 7.96 (dd, ³ J = 8.6 Hz, ⁴ J = 1.3 Hz, 1H), 8.02 (d, ³ J= 8.0 Hz, 1H), 8.05 - 8.16 (m, 3H), 8.52 - 8.61 (m, 2H), 10.62 (s, 1H), 12.01 (m, 2H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.2, 112.8, 115.0, 119.0, 120.1, 121.0, 121.7, 123.4, 124.4, 127.2, 127.8, 128.1, 128.3, 128.7, 128.7, 129.1, 131.3, 131.4, 132.2, 134.6, 138.4, 140.5, 141.5, 150.4, 165.1, 166.3, 173.7 ppm. ESI-MS: m/z = 520.99 [M-H] ^" .

Ethyl 3-nitrophenoxyacetate: Preparation according to general procedure Q. Yield: 98%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.31 (t, ³ J= 7.1 Hz, 3H), 4.29 (q, ³ J = 7.1 Hz, 2H), 4.70 (s, 2H), 7.26 (ddd, ³ J = 8.3 Hz, ⁴ J = 2.6, 0.9 Hz, 1H), 7.46 (dd, ³ J = 8.2, 8.2 Hz, 1H), 7.72 (dd, ⁴ J = 2.3, 2.3 Hz, 1H), 7.87 (ddd, ³ J= 8.1 Hz, ⁴ J = 2.1, 0.9 Hz, 1H) ppm. ¹³ C- NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 61.9, 65.7, 109.2, 116.9, 121.9, 130.3, 149.3, 158.5, 168.1 ppm.

Ethyl 3-aminophenoxyacetate: Preparation according to general procedure Dl . Yield: 86%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.29 (t, ⁵ J= 7.1 Hz, 3H), 3.24 (br s, 2H), 4.26 (q, ³ J= 7.1 Hz, 2H), 4.57 (s, 2H), 6.29 - 6.39 (m, 3H), 7.02 - 7.10 (m, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 61.5, 65.6, 102.5, 104.8, 109.4, 130.4, 147.4, 159.2, 169.2 ppm. Ethyl 3-(2-nitrobenzamido)phenoxyacetate: Preparation according to general procedure CI . Yield: 66%. Yellow oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.28 (t, ³ J = 7.1 Hz, 3H), 4.24 (q, ³ J = 7.1 Hz, 2H), 4.59 (s, 2H), 6.70 (dd, ³ J = 8.2 Hz, ⁴ J = 1.8 Hz, 1H), 7.10 (d, ³ J = 8.1 Hz, 1H), 7.22 (dd, ³ J= 8.2, 8.2 Hz, 1H), 7.31 (s, 1H), 7.54 - 7.63 (m, 2H), 7.67 (d, ³ J = 6.9 Hz, 1H), 7.97 (s, 1H), 8.06 (d, ³ J= 8.0 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 61.6, 65.6, 107.1, 111.5, 113.7, 124.7, 128.8, 130.1, 130.9, 132.9, 134.0, 138.9, 146.4, 158.4, 164.6, 169.0 ppm.

Ethyl 3~(2-aminobenzamido)phenoxyacetate: Preparation according to general procedure Dl . Yield: 78%. Yellow oil. 1H-NMR (500 MHz, CDC1 ₃ ): δ = 1.30 (t, ³ J= 7.1 Hz, 3H), 4.28 (q, ³ J= 7.1 Hz, 2H), 4.63 (s, 2H), 6.69 (dd, ⁵ J= 8.2 Hz, ⁴ J= 2.5 Hz, 1H), 6.72 - 6.79 (m, 2H), 7.11 (dd, ³ J = 8.0 Hz, ⁴ J = 1.2 Hz, 1H), 7.21 - 7.29 (m, 2H), 7.36 (dd, ⁴ J= 2.2, 2.2 Hz, 1H), 7.47 (d, ³ J = 7.8 Hz/J = 1.1 Hz, 1H), 7.90 (s, 1H) ppm. ¹³ C-NMR (125 MHz, CDC1 ₃ ): δ = 14.3, 61.6, 65.6, 107.2, 110.9, 113.8, 117.0, 117.7, 118.2, 127.4, 130.0, 133.0, 139.3, 148.0, 158.5, 167.5, 169.1 ppm.

Ethyl 3-(2-[2-naphthamido]benzamido)phenoxyacetate: Preparation according to general procedure CI. Yield: 65%. Pale yellow solid. 1H-NMR (500 MHz, DMSO): δ = 1.17 (t, ³ J= 7.1 Hz, 3H), 4.14 (q, ³ J = 7.1 Hz, 2H), 4.75 (s, 2H), 6.70 (dd, ³ J = 8.2 Hz, ⁴ J = 1.9 Hz, 1H), 7.27 (dd, ³ J= 8.2, 8.2 Hz, 1H), 7.32 (ddd, ³ J= 7.7, 7.7 Hz, ⁴ J= 1.0 Hz, 1H), 7.37 (d, ³ J=

8.1 Hz, 1H), 7.42 (dd, ⁴ J = 2.1, 2.1 Hz, 1H), 7.59 - 7.70 (m, 3H), 7.91 (dd, ³ J = 7.8 Hz, ⁴ J =

1.2 Hz, 1H), 7.97 (dd, ³ J = 8.6 Hz, ⁴ J= 1.8 Hz, 1H), 8.02 (d, ³ J= 7.9 Hz, 1H), 8.10 (d, ³ J= 8.7 Hz, 2H), 8.45 (d, ³ J = 7.8 Hz, 1H), 8.54 (s, 1H), 10.54 (s, 1H), 11.68 (s, 1H) ppm. ¹³ C- NMR (125 MHz, DMSO): δ = 14.0, 60.6, 64.7, 107.4, 109.9, 113.8, 121.8, 123.5, 123.5, 123.7, 127.1, 127.7, 127.9, 128.1, 128.6, 129.0, 129.1, 129.5, 131.9, 132.2, 132.2, 134.4, 138.4, 139.8, 157.8, 164.8, 167.4, 168.7 ppm.

3-(2-[2-Naphthamido]benzamido)phenoxyacetic acid: Preparation according to general procedure E. Yield: 98%. Pale yellow solid. 1H-NMR (500 MHz, DMSO): δ = 4.67 (s, 2H), 6.70 (dd, ³ J = 7.9 Hz, ⁴ J = 2.0 Hz, 1H), 7.27 (dd, ³ J = 8.4, 8.4 Hz, 1H), 7.32 (dd, ³ J = 7.6, 7.6 Hz, 1H), 7.37 - 7.43 (m, 2H), 7.57 - 7.70 (m, 3H), 7.92 (d, ³ J = 7.8 Hz, 1H), 7.98 (dd, ³ J = 8.6 Hz, ⁴ J = 1.7 Hz, 1H), 8.01 (d, ³ J= 7.9 Hz, 1H), 8.06 - 8.14 (m, 2H), 8.47 (d, ⁵ J = 8.2 Hz, 1H), 8.55 (s, 1H), 10.55 (s, 1H), 11.71 (s, 1H), 13.01 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO): δ = 64.5, 107.3, 109.9, 113.6, 121.7, 123.4, 123.5, 123.6, 127.1, 127.7, 127.9, 128.1, 128.6, 129.0, 129.1, 129.5, 131.9, 132.2, 132.2, 134.4, 138.5, 139.8, 157.9, 164.8,

167.4, 170.1 ppm. ESI-MS: m/z = 438.93 [M-H] ^" .

Ethyl 3-(3-[2-{8-hydroxy-2H-chromene-3-carboxamido}benzamido]pheny l)propanoate:

Preparation according to general procedure H. Yield: 19%. Yellow solid. ¹ H-NMR (300 MHz, DMSO-d6): δ = 1.14 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ⁵ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.4 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 4.97 (d, ⁴ J= 1.2 Hz, 2H), 6.72 - 6.86 (m, 3H), 7.01 (d, ³ J= 7.8 Hz, 1H), 7.21 - 7.36 (m, 3H), 7.52 - 7.63 (m, 3H), 7.89 (dd, ³ J = 7.9 Hz, ⁴ J = 1.3 Hz, 1H), 8.31 (dd, ³ J= 8.3 Hz, ⁴ J = 1.0 Hz, 1H), 9.27 (s, 1H), 10.44 (s, 1H), 11.32 (s, 1H) ppm. ¹³ C- NMR (75 MHz, DMSO-d6): δ = 14.1, 30.4, 35.0, 59.9, 64.1, 118.8, 118.9, 119.2, 120.9,

121.5, 121.7, 121.8, 123.1, 123.3, 124.2, 127.0, 128.4, 128.6, 128.9, 132.1, 138.2, 138.5, 141.0, 142.0, 145.3, 162.7, 167.2, 172.1 ppm.

3-(3-[2-{8-Hydroxy-2H-chromene-3-carboxamido}benzamido]pheny l)propanoic acid:

Preparation according to general procedure E. Yield: 85%. Yellow solid. ¹ H-NMR (500 MHz, DMSO-d6): δ = 2.53 (t, ³ J= 7.7 Hz, 2H), 2.82 (t, ³ J= 7.5 Hz, 2H), 4.96 (s, 2H), 6.72 - 6.87 (m, 3H), 7.01 (d, ³ J = 7.5 Hz, 1H), 7.21 - 7.30 (m, 2H), 7.32 (s, 1H), 7.48 - 7.65 (m, 3H), 7.90 (d, ³ J = 7.7 Hz, 1H), 8.31 (d, ³ J = 8.2 Hz, 1H), 10.48 (s, 1H), 11.34 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d6): δ = 30.6, 35.5, 64.1, 118.8, 118.8, 119.2, 120.9, 121.5, 121.8, 121.8, 123.1, 123.3, 124.2, 127.0, 128.5, 128.6, 129.0, 132.1, 138.3, 138.5, 141.6, 142.0, 145.3, 162.8, 167.2, 173.9 ppm. ESI-MS: m/z = 457.16 [M-H]\

Ethyl 3-aminophenylglycinate: Preparation according to general procedure Q. Yield: 75%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.30 (t, ³ J = 7.1 Hz, 3H), 3.73 (br s, 3H), 3.86 (s, 2H), 4.24 (q, ³ J= 7.1 Hz, 2H), 5.94 (dd, ⁴ J= 2.2, 2.2 Hz, 1H), 6.05 (ddd, ³ J= 8.0 Hz, ⁴ J= 2.2, 0.7 Hz, 1H), 6.11 (ddd, ³ J= 7.9 Hz, ⁴ J= 2.1, 0.7 Hz, 1H), 6.97 (dd, ⁵ J= 7.9, 7.9 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 45.9, 61.3, 99.9, 104.0, 105.8, 130.2, 147.6, 148.3, 171.3 ppm.

Ethyl (3-[2-nitrobenzamido]phenyl)glycinate: Preparation according to general procedure CI . Yield: 93%. Yellow oil. 1H-NMR (500 MHz, CDC1 ₃ ): δ = 1.30 (t, ³ J= 7.1 Hz, 3H), 3.93 (s, 2H), 4.24 (q, ³ J= 7.1 Hz, 2H), 6.47 (d, ³ J= 7.7 Hz, 1H), 6.83 (d, ³ J = 7.7 Hz, 1H), 7.12 - 7.21 (m, 2H), 7.57 (br s, 1H), 7.59 - 7.66 (m, 2H), 7.72 (d, ³ J= 7.4 Hz, 1H), 8.11 (d, ³ J= 8.2 Hz, 1H), ppm. ¹³ C-NMR (125 MHz, CDC1 ₃ ): δ = 14.3, 46.2, 61.7, 105.6, 110.3, 110.6, 124.9, 128.7, 130.1, 130.9, 133.1, 134.0, 138.6, 146.5, 147.4, 164.4, 170.8 ppm.

Ethyl (3-[2-aminobenzamido]phenyl)glycinate: Preparation according to general procedure Dl. Yield: 80%. Yellow oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.26 (t, ³ J= 7.1 Hz, 3H), 3.83 (s, 2H), 4.19 (q, ³ J= 7.1 Hz, 2H), 4.99 (s, 3H), 6.32 (ddd, ³ J= 8.1 Hz, V= 2.2, 0.7 Hz, 1H), 6.57 - 6.69 (m, 2H), 6.82 (dd, ⁵ J= 8.0 Hz, ⁴ J = 1.2 Hz, 1H), 6.95 (dd, ⁴ J = 2.1, 2.1 Hz, 1H), 7.09 (dd, ³ J = 8.0, 8.0 Hz, 1H), 7.18 (dd, ³ J = 8.4, 7.2 Hz, ⁴ J = 1.5 Hz, 1H), 7.41 (dd, ³ J = 7.9 Hz, ⁴ J= 1.4 Hz, 1H), 7.99 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.1, 45.7, 61.3, 105.4, 108.9, 110.3, 116.6, 116.7, 117.3, 127.4, 129.6, 132.4, 139.0, 147.7, 148.7, 167.6, 171.2 ppm.

Ethyl (3-[2-aminobenzamido]phenyl)glycinate: Preparation according to general procedure C2. Yield: 42%. Beige solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 1.15 (t, ³ J = 7.1 Hz, 3H), 3.86 (d, ³ J = 6.4 Hz, 2H), 4.08 (q, ⁵ J= 7.1 Hz, 2H), 6.13 (dd, ³ J= 6.4, 6.4 Hz, 1H), 6.34 (dd, ⁵ J= 8.0 Hz, ⁴ J = 1.3 Hz, 1H), 6.90 - 7.12 (m, 3H), 7.30 (dd, ³ J = 7.1, 7.1 Hz, 1H), 7.57 - 7.71 (m, 3H), 7.92 (d, ³ J= 6.8 Hz, 1H), 7.95 - 8.05 (m, 2H), 8.10 (d, ³ J= 8.3 Hz, 2H), 8.47 -

8.58 (m, 2H), 10.34 (s, 1H), 11.87 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.1, 44.7, 60.2, 105.0, 108.4, 109.6, 121.4, 123.2, 123.3, 123.4, 127.0, 127.7, 127.8, 128.1, 128.6, 128.9, 129.0, 129.1, 131.9, 132.1, 132.2, 134.4, 138.6, 139.2, 148.5, 164.7, 167.2, 171.2 ppm. (3-[2-{2-Naphthamido}benzamido]phenyl)glycine: Preparation according to general procedure E. Yield: 99%. Brown solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 3.79 (s, 2H), 6.35 (dd, ⁵ J= 8.0 Hz, ⁴ J= 1.4 Hz, 1H), 6.99 (d, ³ J= 7.9 Hz, 1H), 7.02 (s, 1H), 7.06 (dd, ³ J= 8.0, 8.0 Hz, 1H), 7.30 (ddd, ³ J= 7.6, 7.6 Hz, ⁴ J = 0.9 Hz, 1H), 7.59 - 7.70 (m, 3H), 7.92 (d, ³ J= 7.8 Hz, 1H), 7.98 (dd, ³ J = 8.6 Hz, ⁴ J = 1.7 Hz, 1H), 8.02 (d, ³ J = 7.9 Hz, 1H), 8.11 (d, ³ J= 8.3 Hz, 2H), 8.53 (d, ³ J = 8.2 Hz, 1H), 8.55 (s, 1H), 10.36 (s, 1H), 11.89 (s, 1H), 12.38 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 44.6, 104.9, 108.5, 109.4, 121.4, 123.2,

123.3, 123.4, 127.1, 127.7, 127.9, 128.1, 128.7, 128.9, 129.0, 129.2, 131.9, 132.1, 132.2,

134.4, 138.7, 139.2, 148.6, 164.7, 167.3, 172.6 ppm. ESI-MS: m/z = 438.21 [M-H]\

Ethyl 2-(3-aminophenyl)-2-methylpropionate: Preparation according to general procedure Q. Yield: 50%. Brown oil. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.19 (t, ⁵ J = 7.1 Hz, 3H), 1.54 (s, 6H), 3.98 (br s, 3H), 4.17 (q, ⁵ J = 7.1 Hz, 2H), 5.99 (dd, ⁴ J = 2.2, 2.2 Hz, 1H), 6.05 (ddd, ³ J= 8.0 Hz, ⁴ J = 2.2, 0.7 Hz, 1H), 6.15 (ddd, ⁵ J = 7.9 Hz, ⁴ J = 2.1, 0.7 Hz, 1H), 6.93 (dd, ⁵ J= 7.9, 7.9 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.3, 26.4, 57.7, 61.4, 102.9, 106.6, 107.1, 130.0, 146.4, 146.7, 176.3 ppm.

Ethyl 2-methyl-2-([3-{2-nitrobenzamido}phenyl]amino)propionate: Preparation according to general procedure CI . Yield: 54%. Brown oil. ¹ H-NMR (300 MHz, CDC1 ₃ ): δ = 1.18 (t, ³ J= 7.1 Hz, 3H), 1.51 (s, 6H), 4.14 (q, ³ J = 7.1 Hz, 2H), 6.30 (dd, ³ J = 8.1 Hz, ⁴ J = 1.6 Hz, 1H), 6.74 (d, ³ J= 7.7 Hz, 1H), 6.95 - 7.11 (m, 2H), 7.50 (dd, ³ J= 7.0, 7.0 Hz, 2H), 7.60 (dd, ⁵ J= 7.1, 7.1 Hz, 1H), 7.92 - 8.03 (m, 1H), 8.07 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.2, 26.2, 57.6, 61.5, 107.7, 110.3, 111.5, 124.6, 128.7, 129.5, 130.6, 133.0, 133.9, 138.4,

146.2, 146.3, 164.5, 176.1 ppm.

Ethyl 2~([3-{2-aminobenzamido}phenyl]amino)-2-methylpropionate: Preparation according to general procedure Dl. Yield: 64%. Brown solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 1.20 (t, ³ J = 7.1 Hz, 3H), 1.56 (s, 6H), 4.18 (q, ³ J = 7.1 Hz, 2H), 5.01 (br s, 3H), 6.36 (ddd, ⁵ J = 8.1 Hz, ⁴ J = 2.3, 0.8 Hz, 1H), 6.64 - 6.73 (m, 2H), 6.82 (ddd, ³ J= 8.0 Hz, ⁴ J = 1.9, 0.7 Hz, 1H), 7.04 - 7.14 (m, 2H), 7.18 - 7.26 (m, 1H), 7.43 (dd, ³ J= 8.3 Hz, ⁴ J= 1.4 Hz, 1H), 7.74 (s, 1H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 14.2, 26.2, 57.8, 61.5, 107.9, 110.7, 111.4, 116.8, 116.9, 117.6, 127.3, 129.5, 132.7, 138.8, 146.1, 148.9, 167.6, 176.0 ppm.

Ethyl 2-([3-{2-(2-naphthamido)benzamido}phenyl]amino)-2-methylprop ionate: Preparation according to general procedure C2. Yield: 45%. Brown solid. 1H-NMR (300 MHz, DMSO- d ₆ ): δ = 1.03 (t, ³ J = 7.1 Hz, 3H), 1.48 (s, 6H), 4.04 (q, ³ J = 7.1 Hz, 2H), 6.00 (s, 1H), 6.28 (dd, ³ J= 8.1 Hz, ⁴ J= 1.5 Hz, 1H), 6.86 (d, ⁵ J= 8.0 Hz, 1H), 6.96 - 7.13 (m, 2H), 7.30 (dd, ³ J = 7.6, 7.6 Hz, 1H), 7.57 - 7.75 (m, 3H), 7.92 (dd, ³ J= 7.9 Hz, ⁴ J= 1.3 Hz, 1H), 7.96 - 8.06 (m, 2H), 8.06 - 8.19 (m, 2H), 8.50 - 8.61 (m, 2H), 10.35 (s, 1H), 11.94 (s, 1H) ppm. ¹³ C- NMR (75 MHz, DMSO-d ₆ ): δ = 13.9, 25.9, 56.3, 60.4, 106.2, 109.3, 110.2, 121.3, 122.9,

123.3, 123.3, 127.0, 127.7, 127.8, 128.1, 128.6, 128.6, 129.0, 129.1, 131.8, 132.1, 132.2,

134.4, 138.7, 138.9, 146.8, 164.6, 167.2, 175.6 ppm.

2-([3-{2-(2-Naphthamido)benzamido}phenyl]amino)-2-methylprop ionic acid: Preparation according to general procedure E. Yield: 99%. Yellow solid. 1H-NMR (500 MHz, DMSO- d ₆ ): δ = 1.47 (s, 6H), 6.31 (dd, ³ J = 8.1 Hz, ⁴ J= 1.6 Hz, 1H), 6.90 (d, ³ J= 7.9 Hz, 1H), 7.03 (dd, ³ J= 8.0, 8.0 Hz, 1H), 7.07 (s, 1H), 7.30 (ddd, ⁵ J = 7.8, 7.8 Hz, V= 1.0 Hz, 1H), 7.60 - 7.69 (m, 3H), 7.92 (dd, ³ J= 7.8 Hz, ⁴ J= 1.1 Hz, 1H), 7.99 (dd, ³ J = 8.6 Hz, ⁴ J= 1.8 Hz, 1H), 8.02 (d, ³ J = 7.9 Hz, 1H), 8.07 - 8.15 (m, 2H), 8.53 - 8.59 (m, 2H), 10.39 (s, 1H), 11.98 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 25.9, 56.1, 106.5, 109.2, 110.1, 121.3, 122.9, 123.3, 123.4, 127.1, 127.7, 127.9, 128.2, 128.6, 128.7, 129.0, 129.2, 131.8, 132.2, 132.3,

134.5, 138.8, 138.9, 147.1, 164.6, 167.3, 177.4 ppm. ESI-MS: m/z = 466.24 [M-H]\

Methyl 4-(bromoacetyl)benzoate: Preparation according to general procedure R. Yield: 90%. Yellow solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 3.89 (s, 3H), 4.39 (s, 2H), 7.94 - 8.01 (m, 2H), 8.06 - 8.13 (m, 2H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 30.8, 52.7, 129.0, 130.2, 134.8, 137.3, 166.1, 191.0 ppm.

Methyl 4-(oxazol-4-yl)benzoate: Preparation according to general procedure S. Yield: 27%. Yellow solid. 1H-NMR (300 MHz, CDC1 ₃ ): δ = 3.93 (s, 3H), 7.85 - 7.80 (m, 2H), 7.97 (d, ⁴ J= 0.9 Hz, 1H), 8.04 (d, ⁴ J = 0.9 Hz, 1H), 8.06 - 8.12 (m, 2H) ppm. ¹³ C-NMR (75 MHz, CDC1 ₃ ): δ = 52.3, 125.6, 129.8, 130.3, 135.1, 135.2, 139.8, 151.7, 166.9 ppm.

4-(Oxazol-4-yl) benzoic acid: Preparation according to general procedure E. Yield: 99%. White solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 7.87 - 7.96 (m, 2H), 7.97 - 8.05 (m, 2H), 8.52 (d, V= 0.9 Hz, 1H), 8.78 (d, ⁴ J = 0.9 Hz, 1H), 12.96 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 125.2, 129.9, 130.0, 134.9, 136.6, 138.4, 152.9, 167.0 ppm.

Ethyl 3-(3-[2-{4-(oxazol-4-yl)benzamido}benzamido]phenyl)propanoat e: Preparation according to general procedure CI . Yield: 55%. Pale yellow solid. ^-NMR (300 MHz, DMSO-d ₆ ): δ = 1.13 (t, ⁵ J= 7.1 Hz, 3H), 2.61 (t, ⁵ J= 7.5 Hz, 2H), 2.86 (t, ³ J = 7.4 Hz, 2H), 4.03 (q, ³ J= 7.1 Hz, 2H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.23 - 7.33 (m, 2H), 7.55 - 7.66 (m, 3H), 7.94 (dd, ³ J= 7.9 Hz, ⁴ J= 1.3 Hz, 1H), 7.99 (s, 4H), 8.45 - 8.55 (m, 2H), 8.75 (d/J= 0.9 Hz, 1H), 10.50 (s, 1H), 11.76 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 30.4, 35.0, 59.9, 119.1, 121.0, 121.4, 122.9, 123.3, 124.2, 125.5, 127.7, 128.6, 129.0, 132.2, 133.7, 134.2, 136.5, 138.4, 138.5, 138.7, 141.0, 152.9, 164.2, 167.4, 172.1 ppm.

3- (3-[2-{4-( Oxazol-4-yl) benzamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 68%. White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J = 7.6 Hz, 2H), 7.02 (d, ³ J = 7.7 Hz, 1H), 7.24 - 7.34 (m, 2H), 7.55 (s, 1H), 7.57 - 7.66 (m, 2H), 7.93 (dd, ³ J = 7.9 Hz, ⁴ J= 1.0 Hz, 1H), 7.99 (s, 4H), 8.47 (d, ³ J= 8.2 Hz, 1H), 8.53 (d, ⁴ J = 0.7 Hz, 1H), 8.77 (d, ⁴ J= 0.7 Hz, 1H), 10.50 (s, 1H), 11.72 (s, 1H), 12.07 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 119.0, 121.0, 121.4, 123.0, 123.4, 124.2, 125.5, 127.8, 128.6, 129.0, 132.3, 133.7, 134.2, 136.5, 138.4, 138.5, 138.6, 141.4, 153.0, 164.2, 167.4, 173.7 ppm. ESI-MS: m/z = 454.24 [M-H]\

N-Hydroxy-p-toluenesulfonamide: Preparation according to general procedure T. Yield: 42%. White solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 2.42 (s, 3H), 7.44 (dd, ³ J = 8.6 Hz, ⁴ J= 0.6 Hz, 2H), 7.70 - 7.78 (m, 2H), 9.49 (d, ⁴ J = 3.4 Hz, 1H), 9.55 (d, ⁴ J = 3.3 Hz, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 21.0, 128.1, 129.4, 134.5, 143.5 ppm.

4- ([2E]-Propenal-3-yl)benzoic acid: Preparation according to general procedure U. Yield: 24%. Yellow solid. ¹ H-NMR (300 MHz, DMSO-d ₆ ): δ = 6.95 (dd, ³ J= 16.0, 7.7 Hz, 1H), 7.74 - 7.92 (m, 3H), 7.95 - 8.05 (m, 2H), 9.72 (d, ⁵ J = 7.7 Hz, 1H), 13.09 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 128.8, 129.8, 130.3, 132.6, 138.0, 151.5, 166.7, 194.5 ppm.

4-(Isoxazol-3-yl)benzoic acid: Preparation according to general procedure V. Yield: 20%. White solid. 1H-NMR (300 MHz, DMSO-d ₆ ): δ = 7.27 (d, ⁴ J= 1.8 Hz, 1H), 8.02 - 8.07 (m, 2H), 8.07 - 8.16 (m, 2H), 9.09 (d, ⁴ J = 1.7 Hz, 1H), 13.16 (br s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 103.2, 126.9, 130.0, 132.1, 132.3, 160.3, 161.2, 166.8 ppm.

Ethyl 3-(3-[2-{4-(isoxazol-3-yl)benzamido}benzamido]phenyl)propano ate: Preparation according to general procedure CI. Yield: 41%. Brown solid. ¹ H-NMR (300 MHz, DMSO- d ₆ ): δ = 1.13 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ⁵ J= 7.5 Hz, 2H), 2.86 (t, ³ J= 7.4 Hz, 2H), 4.03 (q, ⁵ J= 7.1 Hz, 2H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.24 (d, ⁴ J= 1.7 Hz, 1H), 7.25 - 7.36 (m, 2H), 7.52 - 7.68 (m, 3H), 7.93 (dd, ³ J= 7.9 Hz, ⁴ J= 1.4 Hz, 1H), 8.03 - 8.07 (m, 2H), 8.08 - 8.13 (m, 2H), 8.47 (dd, ³ J= 8.3 Hz, ⁴ J= 0.9 Hz, 1H), 9.06 (d, ⁴ J = 1.7 Hz, 1H), 10.50 (s, 1H), 11.77 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 30.3, 35.0, 59.8, 103.2, 119.1, 121.0, 121.5, 123.2, 123.5, 124.2, 127.2, 127.9, 128.6, 129.0, 131.6, 132.2, 135.8, 138.5,

138.5, 141.0, 160.3, 161.1, 164.0, 167.3, 172.1 ppm.

3-(3-[2-{4-(Isoxazol-3-yl)benzamido}benzamido]phenyl)propano ic acid: Preparation according to general procedure E. Yield: 95%. Yellow solid. 1H-NMR (500 MHz, DMSO- d ₆ ): δ = 2.55 (t, ⁵ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 7.02 (d, ³ J= 7.6 Hz, 1H), 7.25 (d, ⁴ J= 1.7 Hz, 1H), 7.26 - 7.35 (m, 2H), 7.55 (s, 1H), 7.57 - 7.67 (m, 2H), 7.94 (d, ³ J= 7.8 Hz, 1H), 8.05 (d, ³ J= 8.5 Hz, 2H), 8.10 (d, ³ J= 8.5 Hz, 2H), 8.47 (d, ³ J= 8.2 Hz, 1H), 9.07 (d, ⁴ J= 1.7 Hz, 1H), 10.51 (s, 1H), 11.78 (s, 1H), 12.16 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 103.2, 119.0, 121.0, 121.5, 123.2, 123.5, 124.3, 127.2, 127.9,

128.6, 129.1, 131.6, 132.3, 135.8, 138.5, 138.5, 141.4, 160.3, 161.2, 164.0, 167.4, 173.7 ppm. ESI-MS: m/z = 454.20 [M-H] ^" .

Ethyl 3-(3-[2-{4-(oxazol-5-yl)benzamido}benzamido]phenyl)propanoat e: Preparation according to general procedure CI . Yield: 77%. White solid ¹ H-NMR (300 MHz, DMSO-d ₆ ): δ = 1.14 (t, ³ J = 7.1 Hz, 3H). 2.61 (t, ³ J = 7.5 Hz, 2H), 2.86 (t, ³ J = 7.4 Hz, 2H), 4.04- (q, ³ J= 7.1 Hz, 2H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.22 - 7.36 (m, 2H), 7.54 - 7.67 (m, 3H), 7.86 (s, 1H), 7.92 (d, ³ J = 8.3 Hz, 3H), 8.02 (d, ⁵ J = 8.5 Hz, 2H), 8.45 (d, ³ J = 8.3 Hz, 1H), 8.53 (s, 1H), 10.49 (s, 1H), 11.72 (s, 1H) ppm. ¹³ C-NMR (75 MHz, DMSO-d ₆ ): δ = 14.0, 30.3, 35.0, 59.8, 119.0, 121.0, 121.5, 123.2, 123.4, 123.8, 124.2, 124.4, 128.0, 128.6, 129.0, 130.5, 132.2, 134.0, 138.5, 138.5, 141.0, 149.7, 152.6, 163.9, 167.3, 172.1 ppm. ESI-MS: m/z = 482.26 [M-H] ^" .

3-(3-[2-{4-(Oxazol-5-yl)benzamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 20%. White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ⁵ J = 7.6 Hz, 2H), 2.83 (t, ⁵ J= 7.5 Hz, 2H), 7.02 (d, ³ J= 7.5 Hz, 1H), 7.26 - 7.34 (m, 2H), 7.55 (s, 1H), 7.59 (d, ³ J= 8.3 Hz, 1H), 7.63 (dd, ³ J= 7.9, 7.9 Hz, 1H), 7.86 (s, 1H), 7.93 (d, ⁵ J = 8.3 Hz, 3H), 8.02 (d, ³ J = 8.4 Hz, 2H), 8.46 (d, ³ J = 8.2 Hz, 1H), 8.54 (s, 1H), 10.51 (s, 1H), 11.74 (s, 1H), 12.21 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.1, 119.0, 121.0, 121.5, 123.1, 123.4, 123.9, 124.2, 124.4, 128.0, 128.6, 129.0, 130.5, 132.2, 134.0, 138.5, 138.5, 141.4, 149.7, 152.6, 163.9, 167.4, 173.7 ppm. ESI-MS: m/z - 454.16 [M-H]-.

Ethyl 3-(3-[2-{3-phenyl-2-propynamido}benzamido]phenyl)propanoate: Preparation according to general procedure CI . Yield: 30%. Pale yellow solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): 5 = 1.15 (t, ⁵ J= 7.1 Hz, 3H), 2.61 (t, ³ J = 7.5 Hz, 2H), 2.85 (t, ⁵ J = 7.4 Hz, 2H), 4.04 (q, ³ J= 7.1 Hz, 2H), 6.99 (d, ³ J= 7.6 Hz, 1H), 7.26 (dd, ⁵ J= 7.8, 7.8 Hz, 1H), 7.32 (dd, ³ J = 7.5, 7.5 Hz, 1H), 7.48 (dd, ³ J = 7.4, 7.4 Hz, 2H), 7.51 - 7.67 (m, 6H), 7.79 (d, ³ J = 7.6 Hz, 1H), 8.03 (d, ³ J = 8.0 Hz, 1H), 10.44 (s, 1H), 11.15 (s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ) δ = 14.1, 30.4, 35.1, 59.9, 83.9, 84.7, 118.6, 119.3, 120.5, 122.7, 124.0, 124.4, 125.6, 128.6, 128.9, 129.0, 130.7, 131.7, 132.3, 136.4, 138.9, 141.0, 150.3, 166.5, 172.1 ppm. ESI-MS: m/z = 439.31 [M-H]-.

3-(3-[2-{3-Phenyl-2-propynamido}benzamido]phenyl)propanoic acid: Preparation according to general procedure E. Yield: 93%. Brown solid. ¹ H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ⁵ J= 7.6 Hz, 2H), 2.82 (t, ³ J= 7.5 Hz, 2H), 7.00 (d, ³ J= 7.6 Hz, 1H), 7.27 (dd, ³ J= 7.8, 7.8 Hz, 1H), 7.32 (d, ³ J = 7.5, 7.5 Hz, 1H), 7.48 (dd, ^J J= 7.4, 7.4 Hz, 2H), 7.51 - 7.60 (m, 4H), 7.64 (d, ³ J= 7.2 Hz, 2H), 7.80 (d, ⁵ J= 7.6 Hz, 1H), 8.04 (d, ³ J= 7.9 Hz, 1H), 10.44 (s, 1H), 11.16 (s, 1H), 12.13 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ): δ = 30.4, 35.2, 83.9, 84.8, 118.5, 119.3, 120.5, 122.7, 124.0, 124.4, 125.6, 128.6, 128.9, 129.1, 130.7, 131.7, 132.4, 136.4, 138.9, 141.4, 150.3, 166.6, 173.7 ppm. ESI-MS: m/z = 411.13 [M-H] ^" .

Ethyl 3-(3-[2-{4-(lH-l,2,3-triazol-l-yl)benzamido}benzamido]phenyl )propanoate: Preparation according to general procedure CI. Yield: 30%. Yellow solid. ¹ H-NMR (400 MHz, DMSO-d ₆ ): δ = 1.13 (t, ³ J= 7.1 Hz, 3H), 2.61 (t, ³ J= 7.5 Hz, 2H), 2.85 (t, ³ J= 7.5 Hz, 2H), 4.03 (q, ³ J= 7.1 Hz, 2H), 7.01 (d, ³ J= 7.7 Hz, 1H), 7.24 - 7.35 (m, 2H), 7.53 - 7.60 (m, 2H), 7.61 - 7.67 (m, 1H), 7.93 (dd, ³ J = 7.0 Hz, ⁴ J = 0.9 Hz, 1H), 8.03 (d, ⁴ J = 1.1 Hz, 1H), 8.10 - 8.17 (m, 4H), 8.43 (d, ³ J= 8.2 Hz, 1H), 8.94 (d, ^V J= 0.9 Hz, 1H), 10.49 (s, 1H), 11.73 (s, 1H) ppm. ¹³ C-NMR (100 MHz, DMSO-d ₆ ): δ = 14.0, 30.3, 35.0, 59.8, 119.0, 120.2, 121.0, 121.6, 123.4, 123.5, 123.6, 124.2, 128.6, 128.9, 129.0, 132.2, 134.2, 134.7, 138.3, 138.5, 138.9, 141.0, 163.6, 167.3, 172.1 ppm. ESI-MS: m/z = 482.18 [M-H] ^" .

3-(3-[2-{4-(lH-l,2,3-Triazol-l-yl)benzamido}benzamido]phenyl )propanoic acid: Preparation according to general procedure E. Yield: 93%. White solid. 1H-NMR (500 MHz, DMSO-d ₆ ): δ = 2.54 (t, ³ J= 7.6 Hz, 2H), 2.83 (t, ³ J= 7.6 Hz, 2H), 7.02 (d, ³ J= 7.6 Hz, 1H), 7.28 (t, ³ J= 7.8 Hz, 1H), 7.32 (ddd, ³ J= 7.6, 7.6 Hz, ^¥ J= 1.0 Hz, 1H), 7.55 (s, 1H), 7.59 (d, ³ J= 8.2 Hz, 1H), 7.61 - 7.67 (m, 1H), 7.94 (dd, ³ J= 7.7 Hz, ⁴ J= 1.0 Hz, 1H), 8.03 (d, ⁴ J= 1.1 Hz, 1H), 8.11 - 8.17 (m, 4H), 8.44 (d, ³ J= 8.2 Hz, 1H), 8.94 (d, ⁴ J= 1.1 Hz, 1H), 10.51 (s, 1H), 11.75 (s, 1H), 12.14 (br s, 1H) ppm. ¹³ C-NMR (125 MHz, DMSO-d ₆ ) δ = 30.4, 35.1, 119.0, 120.2, 121.0, 121.6, 123.4, 123.4, 123.6, 124.2, 128.6, 128.9, 129.1, 132.2, 134.2, 134.8, 138.4, 138.5, 139.0, 141.4, 163.6, 167.3, 173.7 ppm. ESI-MS: m/z = 454.17 [M-H] ^" .

The features disclosed in the foregoing description, in the claims and/or in the accompanying drawings may, both separately and in any combination thereof, be material for realizing the invention in diverse forms thereof.

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