Heterocyclic compounds as antiviral and anticancer compounds

Abstract

The present invention relates to the use of compounds of formula (I) for use in methods of treating and / or preventing conditions, disorders or diseases that are mediated or caused by a virus or cancer. In particular, the compounds described herein are useful in the treatment and / or prevention of conditions, disorders or diseases that are mediated or caused by cancer or an animal pathogenic virus which uses cellular mechanisms in the human or animal host for its replication and / or for its transcription.

Description

HETEROCYCLIC COMPOUNDS AS ANTIVIRAL AND ANTICANCER COMPOUNDSTECHNICAL FIELD OF THE INVENTION

[0001] The present invention relates to the use of compounds in methods of treating and / or preventing cancer or conditions, disorders or diseases that are mediated or caused by a virus. In particular, the compounds described herein are useful in the treatment and / or prevention of conditions, disorders or diseases that are mediated or caused by cancer or a pathogenic virus which uses cellular mechanisms in the human or animal host for its replication and / or for its transcription.BACKGROUND ART

[0002] In todays highly interconnected world, where air and sea travel are commonplace, the spread of new pathogens is a continual serious concern. The close proximity of humans and animals increases the likelihood of zoonotic transmission of viruses. In addition, climate change and rising global temperatures are increasingly leading to migrations of disease-transmitting virus vectors such as the tiger mosquito, which has already been observed in regions like Europe, further increasing the risk of spreading pathogens such as dengue, West Nile or Chikungunya viruses

[0003] These factors contribute to the ongoing risk of pandemics, illustrated by the SARS-CoV-2 pandemic breaking out in 2020-2023. Current treatment options for many vector-borne diseases remain limited, with no antiviral treatments available for pathogens like dengue virus, yellow fever virus, West Nile virus, Rift Valley fever virus, or chikungunya virus.There are no antiviral treatment options for pathogens such as dengue virus, yellow fever virus, West Nile virus, Rift Valley fever virus or Chikungunya virus.

[0004] This situation underscores the urgent need for the development of new, broadly applicable antiviral agents and the creation of efficient, affordable therapies to manage these pathogens, which are already endemic in many parts of Asia, Africa, and South America, and to better prepare for future pandemics.SUMMARY OF THE INVENTION

[0005] The invention relates to a compound having the general formula (I),and hydrates, solvates, salts, complexes, racemic mixtures, diastereomers, diastereomeric mixtures, enantiomers, and tautomers thereof and isotopically enriched forms of any of the foregoing, whereinQ is selected from the group consistingandR1and R2are independently selected from the group consisting of -H, -(Ci-Cw)alkyl , -(Cs- Cw)aryl, -(Cs-Cio)heteroaryl, wherein optionally -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl are substituted with one or more residues independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2- Cw)alkenyl, -(C2-C )alkynyl, -(C3-Cio)cycloalkyl, -(Ci-Cio)alkyl(C3-C6)cycloalkyl, -(C1-C10- )alkyl(Ce-Cio)aryl, -(Ci-C )alkyl(C3-Cio)heteroaryl, -(Ci-Cio)alkyl(C3-C6)heterocyclyl, -OH, -OR3, - N(R4)(R5), -N(R3)(OR3), -S(O)0-2R3, S(O)I-2OR3, -OS(O)I-2R3, OS(O)I-2OR3, -S(O)I-2N(R4)(R5), - OS(O)I-2N(R4)(R5), -N(R3)S(O)I-2R3, -N(R3)S(O)I-2OR3, -N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, - C(=X)XR3, -XC(=X)R3, and -XC(=X)XR3, antibody- -conjugate (AC) wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid;P is selected from the group consisting of -OR3, -(Ci-Cio)alkyl, preferably -OMe, -ethyl, more preferably -OMe;A is selected from the group consisting of (Cs-Cio)aryl, (Cs-Cio)heteroaryl, wherein optionally -(Cs- Cw)aryl, -(Cs-Cio)heteroaryl are substituted with one or more residues independently selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci- Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)-cycloalkyl, -(Ci-Cw)alkyl(C3- Cejcycloalkyl, -(Ci-Cio)alkyl(Ce-Cio)aryl, -(Ci-Cio)alkyl(C3-Cw)heteroaryl, -(Ci-Cw)alkyl(C3- C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), N(R3)(OR3), -S(O)0.2R3, S(O)I-2OR3, -OS(O)I-2R3, OS(O)i- 2OR3, -S(O)I.2N(R4)(R5), -OS(O)I-2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I-2OR3, -N(R3)S(O)I.2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, -N=N-R3, -C(R3)=N=N, -(Ci-Cs)alkyloxiranyl, -O-O- R3, -S-S-R3, and -XC(=X)XR3, antibody- conjugate (AC), two adjacent residues may form a ring:wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid, and antibody- conjugate (AC); p is is an integer from 1 to 3;M is selected from the group consisting of a bond, -(Ci-C4)alkyldiyl-, -NH-C(O)-, -C(O)-NH-, -C=C- or -(C2-Ce)alkyndiyl-, wherein optionally -(C2-C4)alkyldiyl- is substituted with one or more residue selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(C1- Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(C1- Cio)alkyl(C3-C6)cycloalkyl, -(Ci-Cio)alkyl(Ce-Cio)aryl, -(Ci-Cw)alkyl(C3-Cio)heteroaryl, -(C1- Cio)alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), N(R3)(OR3), -S(O)0-2R3, -S(O)I-2OR3, - OS(O)I.2R3, -OS(O)I-2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I. 2OR3, N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, and -XC(=X)XR3;B is selected from the group consisting of H, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, wherein optionally -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl are substituted with one or more independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(C1- Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Ci-C )alkyl(C3-C6)cycloalkyl, -(Ci-C )alkyl(C6-Cio)aryl, -(Ci-Cio)alkyl(C3-C )heteroaryl, -(C1-C10- )alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), -N(R3)(OR3), -S(O)0-2R3, -S(O)I-2OR3, -OS(O)i- 2R3, -OS(O)I-2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I-2OR3, -N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, -N=N-R3, -C(R3)=N=N, -(CI- Cs)alkyloxiranyl, -O-O-R3, -S-S-R3, and -XC(=X)XR3, antibody- conjugate (AC), two adjacent rests may form a ring:p is is an integer from 1 to 3; wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid, and antibody- conjugate (AC);X is independently selected from O, S, and N(R6);R3is, in each case, selected from the group consisting of -H, -(Ci-Cw)alkyl, -(C2-Cio)alkenyl, -(C2- Cw)alkynyl, -(C3-C )cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(Cs-Cejheterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independetely selected R10;R4and R5are, in each case, independently selected from the group consisting of -H, -(C1- Cw)alkyl, -(C2-Cio)alkenyl, -(Ci-Cw)alkynyl, -(Cs-Cwjcycloalkyl, -(C3-C )aryl, -(C3-C )heteroaryl, and heterocyclyl, or R4and R5may join together with the nitrogen atom to which they are attached to form the group -N=CR7R8, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independetely selected R10;R6is independently selected from from the groups consisting of H, -(Ci-Cw)alkyl, -(C2-Cw)alkenyl, -(C2-Cio)alkynyl, -(C3-C )cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(Cs-Cejheterocyclyl and OR3, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R10;R7and R8are independently selected from the group consisting of - H, -(Ci-Cw)alkyl, -(C2- Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-C )cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(C3- Cejheterocyclyl, and -NHyR92-y, or R7and R8may join together with the atom to which they are attached to form a ring which is optionally substituted with one or more independently selectedR10, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally susbstituted with one more independently selected R10; y is an integer from 0 to 2;R9is selected from the group consisting of -(Ci-Cio)alkyl, -(C2-C )alkenyl, -(C2-C )alkynyl, -(C3- Cw)cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(C3-C6)heterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R10.R10is a 1stlevel substituent and is, in each case independently selected from the group consisting of -(Ci-Cw)alkyl, -(C2-C )alkenyl, -(C2-C )alkynyl, -(C3-C )cycloalkyl, -(Cs-Cio)aryl, -(C5- Cw)heteroaryl, and -(Cs-Cejheterocyclyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(C1- Cw)alkyl, -(Ci-Cw)haloalkyl, -(Ci-Cw)alkenyl, -(Ci-Cw)alkynyl, -(C3-C )-cycloalkyl, -(C1- Cio)alkyl(C3-C6)cycloalkyl, -(Ci-C )alkyl(C6-Cio)aryl, -(Ci-C )alkyl(C3-Cio)heteroaryl, -(C1- Cio)alkyl(C3-C6)heterocyclyl, -OH, -OR11, -N(R12)(R13), -N(R11)(OR11), -S(O)0-2R11, -S(O)I-2OR11, - OS(O)I.2R11, OS(O)I-2OR11, -S(O)I.2N(R12)(R13), -OS(O)I.2N(R12)(R13), -N(R11)S(O)I.2R11, - N(R11)S(O)I-2OR11, -N(R11)S(O)I-2N(R12)(R13), -C(=X1)R11, -C(=X1)X1R11, -X1C(=X1)R11, and - X1C(=X1)X1R11, and / or any two R10which are bound to the same carbon atom of a cycloalkyl or heterocyclyl may join together to form =X1, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups being a 1stlevel substituent is optionally substituted by one or more 2ndlevel substituents, wherein said 2ndlevel substituent is, in each case, independently selected from the group consisting of (Ci-Ce)alkyl, (C2-Ce)alkenyl, (C2- Ce)alkynyl, -(C3-Ci4)aryl, -(Cs-Cujheteroaryl, -(C3-Ci4)cycloalkyl, -(Cs-Cujheterocyclyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -OR14, -N(R15)(R16), -N(R14)(OR14), -S(0)o- 2R14, -S(O)I-2OR14, -OS(O)I.2R14, -OS(O)I-2OR14, -S(O)I.2N(R15)(R16), -OS(O)I.2N(R15)(R16), -N(R14)S(O)I.2R14, -N(R14)S(O)I-2OR14, N(R14)S(O)I.2N(R15)(R16), -C(=X2)R14, -C(=X2)X2R14, -X2C(=X2)R14, and -X2C(=X2)X2R14, and / or any two 2ndlevel substituents which are bound to the same carbon atom of a cycloalkyl or heterocyclyl group being a 1stlevel substituent may join together to form =X2, wherein each of the (Ci-e)al kyl , (C2-6) alkenyl, (C2-6) alkynyl, 3 -(Cs-Cujaryl, -(Cs-Cujheteroaryl, 3 -(C3-Ci4)cycloalkyl, -(C3- Ci4)heterocyclyl groups being a 2ndlevel substituent is optionally substituted with one or more 3rdlevel substituents, wherein said 3rdlevel substituent is, in each case, independently selected from the group consisting of -(Ci-C3)alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -O(Ci-C3)alkyl), -S(Ci-C3)alkyl, -NH2, -NH(Ci-C3)alkyl), -N((CI-C3)alkyl)2, -NHS(O)2((Ci-C3)alkyl), -S(O)2NH2.z((Ci-C3) alkyl)z, -C(=O)((Ci-C3)alkyl), -C(=O)O((Ci-C3) alkyl), -C(=O)NH2.z((Ci-C3)alkyl)z, -OC(=O)(Ci-C3)alkyl), -OC(=O)O((Ci-C3)alkyl), -OC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=O)((Ci-C3)alkyl), -NHC(=O)NH2.z(Ci-C3)alkyl)z, -NHC(=NH)NH2.Z((CI- C3)alkyl)z, and -N((Ci-C3) alkyl)C(=NH)NH2.z((Ci-C3)alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3)alkyl is methyl, ethyl, propyl or isopropyl, and / or any two 3rdlevel substituents which are bound to the same carbon atom of a -(C3-Ci4)cycloalkyl or heterocyclyl group being a 2ndlevel substituent may join together to form =0, =S, =NH, or =N(Ci-3)alkyl); whereinR11, R12, and R13are independently selected from the group consisting of -H, -(Ci-Ce)alkyl, -(C2-Ce)alkenyl, -(C2-Ce)alkynyl, -(C3-C7)cycloalkyl, -(Cs- Ce)aryl, -(Cs-Cejheteroaryl, and -(C3-C7)heterocyclyl, wherin each of the -(Ci-Ce)alkyl, -(C2. Ce)alenyl, -(C2-Ce)alkynyl, -(C3-C7)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3- C7)heterocyclyl groups is obtainally substituted with one, two or three substituents selected from the group consisting of (Ci-C3) alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, - O((Ci-C3)alkyl), -S(Ci-C3)alkyl), -NH2, -NH((Ci-C3)alkyl), -N((Ci-C3)alkyl)2, -NHS(O)2(CI-C3alkyl), -S(O)2NH2.z(Ci-C3)alkyl)z, -C(=O)((Ci-C3)alkyl), -C(=O)O((Ci-C3)alkyl), -C(=O)NH2.Z((CI- C3)alkyl)z, -OC(=O)((Ci-C3)alkyl), -OC(=O)O((Ci-C3)alkyl), -OC(=O)NH2.z((Ci-C3)alkyl)z, - NHC(=O)(Ci-C3)alkyl), -NHC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=NH)NH2.Z((CI-C3) alkyl)z, and - N((Ci-C3) alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3)alkyl is methyl, ethyl, propyl or isopropyl;R14, R15, and R16are independently selected from the group consisting of -H, (Ci-Ce)alkyl, (C2- Ce)alkenyl, (C2-Ce)alkynyl, -(C3-C7)cycloalkyl -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3- C7)heterocyclyl, wherein each of the (Ci-Ce)alkyl, (C2.C6)alkenyl, (C2-Ce)alkynyl, -(C3- C7)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3-C7)heterocyclyl groups is obtainally substituted with one, two or three substituents selected from the group consisting of (Ci-C3) alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -O(Ci-C3)alkyl), -S(Ci- C3)alkyl), -NH2, -NH(Ci-C3)alkyl, -N((CI-C3alkyl))2, -NHS(O)2(Ci-C3)alkyl, -S(O)2NH2.Z((CI- C3)alkyl)z, -C(=O)(Ci.C3)alkyl, -C(=O)O(Ci-C3)alkyl, -C(=O)NH2.Z((CI-C3) alkyl)z, -OC(=O)(Ci- C3)alkyl, -OC(=O)O(Ci-C3)alkyl, -OC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=O)(Ci-C3)alkyl, -NHC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=NH)NH2.z((Ci-C3)alkyl)z, and -N(Ci- C3)alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3)alkyl is methyl, ethyl, propyl or isopropyl;X1and X2are independently selected from O, S, and N(R17), wherein R17is -H or (Ci-C3)alkyl.

[0006] The invention is further related to a pharmaceutical composition comprising the compound and at least one pharmaceutically acceptable carrier.

[0007] Further, the invention is directed to the compound and the pharmaceutical composition for use of the treatment of a virus infection, wherein the virus infection is caused by a virus selected from the group consisting of Retroviridae, Herpesviridae, Hepadnaviridae, Orthomyxoviridae, Paramyxoviridae, Flaviviridae, Papillomaviridae, Phenuiviridae, Nairoviridae, Hantaviridae, Arenaviridae, Togaviridae, Coronaviridae, Adenoviridae, Filoviridae, Rhabdoviridae, Pneumoviridae, Poxviridae.

[0008] Moreover, the invention is directed to the compound or the pharmaceutical composition for use of the treatment of a virus infection wherein the virus infection is caused by a virus selected from the group consisting of HIV-1 , HIV-2, HTLV-1 , HTLV-2, HSV-1 , HSV-2, VZV, human CMV (HCMV), EBV type 1 , EBV type 2, HHV6, HHV7, HBV-A, influenzavirus A, influenzavirus B, Measles Virus (MV), Nipah virus, HCV, DENV-1.DENV-2, DENV-3, DENV-4, ZIKV, WNV, TBEV Toro, TBEV Hypr, YFV, HPV-16, HPV-18, RVFV, CCHFV, Hantavirus, Lassa virus, CHIKV, SARS-CoV, SARS-CoV-2, MERS, Human Adenovirus 5 (hAdV5), Zaire EBOV, MARV-A, MARV- B, Rabies lyssavirus, HRSV, Monkeypox virus (MPXV), preferably SARS-CoV-2, HIV-1 , HRSV and DENV-2.

[0009] Human immunodeficiency virus = HIV, human T-lymphotropic virus = HTLV, Herpes simplex virus = HSV, Varicella-Zoster-Virus = VZV, human Cytomegalievirus = HCMV, Epstein- Barr virus = EBV, human herpesvirus = HHV, Hepatitis B virus = HBV, dengue virus = DENV, Zika virus = ZIKV, West nile virus = WNV, tick-borne encephalitis virus strain Torb= TBEV Toro, yellow fever virus = YFV, Human papillomaviruses = HPV, Rift Valley Fever Virus = RVFV, Crimean-Congo hemorrhagic fever virus= CCHFV, Chikungunya virus = CHIKV, Severe acute respiratory syndrome coronavirus = SARS-CoV, Middle East Respiratory Syndrome = MERS, Marburg virus = MARV.

[0010] Furthermore, the invention is directed to the compound or the pharmaceutical composition for use in the treatment of cancer.DETAILED DESCRIPTION OF THE INVENTION

[0011] The solution of the present invention is described in the following, exemplified in the appended examples, and reflected in the claims.Definitions****

[0012] It is noted that as used herein, the singular forms “a”, “an”, and “the”, include plural references unless the context clearly indicates otherwise. Thus, for example, reference to “a reagent” includes one or more of such different reagents and reference to “the method” includes reference to equivalent steps and methods known to those of ordinary skill in the art that could be modified or substituted for the methods described herein.

[0013] The term "and / or" wherever used herein includes the meaning of "and", "or" and "all or any other combination of the elements connected by said term".

[0014] Throughout this specification and the claims which follow, unless the context requires otherwise, the word “comprise”, and variations such as “comprises” and “comprising”, will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integer or step.

[0015] All publications cited throughout the text of this specification (including all patents, patent application, scientific publications, instructions, etc.), whether supra or infra, are hereby incorporated by reference in their entirety. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention. To the extent the material incorporated by reference contradicts or is inconsistent with this specification, the specification will supersede any such material.

[0016] The content of all documents and patent documents cited herein is incorporated by reference in their entirety.

[0017] The term "alkyl" refers to a monoradical of a saturated straight or branched hydrocarbon while “alkyldiyl” or “alkylene” refers to a diradical of a saturated straight or branched hydrocarbon. Preferably, the alkyl group comprises 1 to 10 carbon atoms, i.e., 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10, carbon atoms, more preferably 1 to 8 carbon atoms, such as 1 to 6 or 1 to 4 carbon atoms. Exemplary alkyl groups include methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, tert-butyl, n- pentyl, iso-pentyl, sec-pentyl, neo-pentyl, 1 ,2-dimethyl-propyl, iso-amyl, n-hexyl, iso-hexyl, sec-hexyl, n-heptyl, iso-heptyl, n-octyl, 2-ethyl-hexyl, n-nonyl, n-decyl, and the like.

[0018] The term "aryl" refers to a monoradical of an aromatic cyclic hydrocarbon. Preferably, the aryl group contains 3 to 14 carbon atoms which can be arranged in one ring (e.g., phenyl) or two or more condensed rings (e.g., naphthyl). Exemplary aryl groups include cyclopentadienyl, phenyl, indenyl, naphthyl, azulenyl, fluorenyl, anthryl, and phenanthryl. Preferably, "aryl" refers to a monocyclic ring containing 6 carbon atoms or an aromatic bicyclic ring system containing 10 carbon atoms. Preferred examples are phenyl and naphthyl.

[0019] The term "heteroaryl" means an aryl group as defined above in which one or more carbon atoms in the aryl group are replaced by heteroatoms of O, S, or N. Preferably, heteroaryl refers to a five or six-membered aromatic monocyclic ring wherein 1 , 2, or 3 carbon atoms are replaced by the same or different heteroatoms of O, N, or S. Alternatively, it means an aromatic bicyclic or tricyclic ring system wherein 1 , 2, 3, 4, or 5 carbon atoms are replaced with the same or different heteroatoms of O, N, or S. Preferably, in each ring of the heteroaryl group the maximum number of O atoms is 1 , the maximum number of S atoms is 1 , and the maximum total number of O and S atoms is 2. Exemplary heteroaryl groups include furanyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl (1 ,2,5- and 1 ,2,3-), pyrrolyl, imidazolyl, pyrazolyl, triazolyl (1 ,2,3- and 1 ,2,4-), tetrazolyl, thiazolyl, isothiazolyl, thiadiazolyl (1 ,2,3- and 1 ,2,5-), pyridyl, pyrimidinyl, pyrazinyl, triazinyl (1 ,2,3-, 1 ,2,4-, and 1 ,3,5-), benzofuranyl (1- and 2-), indolyl, isoindolyl, benzothienyl (1- and 2-), 1 H-indazolyl, benzimidazolyl, benzoxazolyl, indoxazinyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzotriazolyl, quinolinyl, isoquinolinyl, benzodiazinyl, quinoxalinyl, quinazolinyl, benzotriazinyl (1 ,2,3- and 1 ,2,4-benzotriazinyl), pyridazinyl, phenoxazinyl, thiazolopyridinyl, pyrrolothiazolyl, phenothiazinyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathiinyl, pyrrolizinyl, indolizinyl, indazolyl, purinyl, quinolizinyl, phthalazinyl, naphthyridinyl (1 ,5-, 1 ,6-, 1,7- , 1 ,8-, and 2,6-), cinnolinyl, pteridinyl, carbazolyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl (1 ,7-, 1 ,8-, 1 ,10-, 3,8-, and 4,7-), phenazinyl, oxazolopyridinyl, isoxazolopyridinyl, pyrrolooxazolyl, and pyrrolopyrrolyl. Exemplary 5- or 6-memered heteroaryl groups include furanyl, thienyl, oxazolyl, isoxazolyl, oxadiazolyl (1 ,2,5- and 1 ,2,3-), pyrrolyl, imidazolyl, pyrazolyl, triazolyl (1 ,2,3- and 1 ,2,4-), thiazolyl, isothiazolyl, thiadiazolyl (1 ,2,3- and 1 ,2,5-), pyridyl, pyrimidinyl, pyrazinyl, triazinyl (1 ,2,3-, 1 ,2,4-, and 1 ,3,5-), and pyridazinyl.

[0020] The term "cycloalkyl" represents cyclic non-aromatic versions of "alkyl" and "alkenyl" with preferably 3 to 14 carbon atoms, such as 3 to 10 carbon atoms, i.e. , 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, more preferably 3 to 8 carbon atoms, even more preferably 3 to 7 carbon atoms. Exemplary cycloalkyl groups include cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl,cyclooctenyl, cyclononyl, cyclononenyl, cylcodecyl, cylcodecenyl, and adamantyl. The term "cycloalkyl" is also meant to include bicyclic and tricyclic versions thereof. If bicyclic rings are formed it is preferred that the respective rings are connected to each other at two adjacent carbon atoms, however, alternatively the two rings are connected via the same carbon atom, i.e., they form a spiro ring system or they form "bridged" ring systems. Preferred examples of cycloalkyl include -(Cs-Csjcycloalkyl, in particular cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, spiro[3,3]heptyl, spiro[3,4]octyl, spiro[4,3]octyl, bicyclo[4.1.0]heptyl, bicyclo[3.2.0]heptyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, bicyclo[5.1.0]octyl, and bicyclo[4.2.0]octyl.

[0021] The term "heterocyclyl" means a cycloalkyl group as defined above in which from 1 , 2, 3, or 4 carbon atoms in the cycloalkyl group are replaced by heteroatoms of O, S, or N. “heterocycloalkyldiyl” refers to the corresponding diradical. Preferably, in each ring of the heterocyclyl group the maximum number of O atoms is 1 , the maximum number of S atoms is 1 , and the maximum total number of O and S atoms is 2. The term "heterocyclyl" or “heterocycloalkyldiyl” is also meant to encompass partially or completely hydrogenated forms (such as dihydro, tetrahydro or perhydro forms) of the above-mentioned heteroaryl groups. Exemplary heterocyclyl groups include morpholino, isochromanyl, chromanyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, indolinyl, isoindolinyl, di- and tetrahydrofuranyl, di- and tetrahydrothienyl, di- and tetrahydrooxazolyl, di- and tetrahydroisoxazolyl, di- and tetrahydrooxadiazolyl (1 ,2,5- and 1 ,2,3-), dihydropyrrolyl, dihydroimidazolyl, dihydropyrazolyl, di- and tetrahydrotriazolyl (1 ,2,3- and 1 ,2,4-), di- and tetrahydrothiazolyl, di- and tetrahydrothiazolyl, di- and tetrahydrothiadiazolyl (1 ,2,3- and 1 ,2,5-), di- and tetrahydropyridyl, di- and tetrahydropyrimidinyl, di- and tetrahydropyrazinyl, di- and tetrahydrotriazinyl (1 ,2,3-, 1 ,2,4-, and 1 ,3,5-), di- and tetrahydrobenzofuranyl (1- and 2-), di- and tetrahydroindolyl, di- and tetrahydroisoindolyl, di- and tetrahydrobenzothienyl (1- and 2), di- and tetrahydro-1 H-indazolyl, di- and tetrahydrobenzimidazolyl, di- and tetrahydrobenzoxazolyl, di- and tetrahydroindoxazinyl, di- and tetrahydrobenzisoxazolyl, di- and tetrahydrobenzothiazolyl, di- and tetrahydrobenzisothiazolyl, di- and tetrahydrobenzotriazolyl, di- and tetrahydroquinolinyl, di- and tetrahydroisoquinolinyl, di- and tetrahydrobenzodiazinyl, di- and tetrahydroquinoxalinyl, di- and tetrahydroquinazolinyl, di- and tetrahydrobenzotriazinyl (1 ,2,3- and 1 ,2,4-), di- and tetrahydropyridazinyl, di- and tetrahydrophenoxazinyl, di- and tetrahydrothiazolopyridinyl (such as 4,5,6-7-tetrahydro[1 ,3]thiazolo[5,4-c]pyridinyl or 4,5,6-7-tetrahydro[1 , 3]thiazolo[4, 5-c]pyridinyl , e.g., 4,5,6-7-tetrahydro[1 , 3]thiazolo[5,4-c]pyridin-2-yl or 4,5,6-7-tetrahydro[1 ,3]thiazolo[4,5- c]pyridin-2-yl), di- and tetrahydropyrrolothiazolyl (such as 5,6-dihydro-4H-pyrrolo[3,4- d][1 ,3]thiazolyl), di- and tetrahydrophenothiazinyl, di- and tetrahydroisobenzofuranyl, di- and tetrahydrochromenyl, di- and tetrahydroxanthenyl, di- and tetrahydrophenoxathiinyl, di- andtetrahydropyrrolizinyl, di- and tetrahydroindolizinyl, di- and tetrahydroindazolyl, di- and tetrahydropurinyl, di- and tetrahydroquinolizinyl, di- and tetrahydrophthalazinyl, di- and tetrahydronaphthyridinyl (1 ,5-, 1 ,6-, 1 ,7-, 1 ,8-, and 2,6-), di- and tetrahydrocinnolinyl, di- and tetrahydropteridinyl, di- and tetrahydrocarbazolyl, di- and tetrahydrophenanthridinyl, di- and tetrahydroacridinyl, di- and tetrahydroperimidinyl, di- and tetrahydrophenanthrolinyl (1 ,7-, 1 ,8-, 1 ,10-, 3,8-, and 4,7-), di- and tetrahydrophenazinyl, di- and tetrahydrooxazolopyridinyl, di- and tetrahydroisoxazolopyridinyl, di- and tetrahydropyrrolooxazolyl, and di- and tetrahydropyrrolopyrrolyl. Exemplary 5- or 6-memered heterocyclyl groups include morpholino, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, di- and tetrahydrofuranyl, di- and tetrahydrothienyl, di- and tetrahydrooxazolyl, di- and tetrahydroisoxazolyl, di- and tetrahydrooxadiazolyl (1 ,2,5- and 1 ,2,3-), dihydropyrrolyl, dihydroimidazolyl, dihydropyrazolyl, di- and tetrahydrotriazolyl (1 ,2,3- and 1 ,2,4-), di- and tetrahydrothiazolyl, di- and tetrahydroisothiazolyl, di- and tetrahydrothiadiazolyl (1 ,2,3- and 1 ,2,5-), di- and tetrahydropyridyl, di- and tetrahydropyrimidinyl, di- and tetrahydropyrazinyl, di- and tetrahydrotriazinyl (1 ,2,3-, 1 ,2,4- , and 1 ,3,5-), and di- and tetrahydropyridazinyl.

[0022] The term "alkenyl" refers to a monoradical of an unsaturated straight or branched hydrocarbon having at least one carbon-carbon double bond. Generally, the maximal number of carbon-carbon double bonds in the alkenyl group can be equal to the integer which is calculated by dividing the number of carbon atoms in the alkenyl group by 2 and, if the number of carbon atoms in the alkenyl group is uneven, rounding the result of the division down to the next integer. For example, for an alkenyl group having 9 carbon atoms, the maximum number of carbon-carbon double bonds is 4. Preferably, the alkenyl group has 1 to 4, i.e., 1 , 2, 3, or 4, carbon-carbon double bonds. Preferably, the alkenyl group comprises from 2 to 10 carbon atoms, i.e., 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, more preferably 2 to 8 carbon atoms, such as 2 to 6 carbon atoms or 2 to 4 carbon atoms. Thus, in a preferred embodiment, the alkenyl group comprises from 2 to 10 carbon atoms and 1 , 2, 3, 4, or 5 carbon-carbon double bonds, more preferably it comprises 2 to 8 carbon atoms and 1 , 2, 3, or 4 carbon-carbon double bonds, such as 2 to 6 carbon atoms and 1 , 2, or 3 carbon-carbon double bonds or 2 to 4 carbon atoms and 1 or 2 carbon-carbon double bonds. The carbon-carbon double bond(s) may be in cis (Z) or trans (E) configuration. Exemplary alkenyl groups include vinyl, 1-propenyl, 2-propenyl (i.e., allyl), 1-butenyl, 2-butenyl, 3-butenyl, 1- pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1 -hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5- hexenyl, 1 -heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1 -octenyl, 2- octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenyl, 3-nonenyl, 4- nonenyl, 5-nonenyl, 6-nonenyl, 7-nonenyl, 8-nonenyl, 1 -decenyl, 2-decenyl, 3-decenyl, 4- decenyl, 5-decenyl, 6-decenyl, 7-decenyl, 8-decenyl, 9-decenyl, and the like. If an alkenyl group is attached to a nitrogen atom, the double bond cannot be alpha to the nitrogen atom.

[0023] The term "alkynyl" refers to a monoradical of an unsaturated straight or branched hydrocarbon having at least one carbon-carbon triple bond, while “alkyndiyl” corresponds to the respective diradical. Generally, the maximal number of carbon-carbon triple bonds in the alkynyl group can be equal to the integer which is calculated by dividing the number of carbon atoms in the alkynyl group by 2 and, if the number of carbon atoms in the alkynyl group is uneven, rounding the result of the division down to the next integer. For example, for an alkynyl group having 9 carbon atoms, the maximum number of carbon-carbon triple bonds is 4. Preferably, the alkynyl group has 1 to 4, i.e., 1 , 2, 3, or 4, more preferably 1 or 2 carbon-carbon triple bonds. Preferably, the alkynyl group comprises from 2 to 10 carbon atoms, i.e., 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms, more preferably 2 to 8 carbon atoms, such as 2 to 6 carbon atoms or 2 to 4 carbon atoms. Thus, in a preferred embodiment, the alkynyl group comprises from 2 to 10 carbon atoms and 1 , 2, 3, 4, or 5 (preferably 1 , 2, or 3) carbon-carbon triple bonds, more preferably it comprises 2 to 8 carbon atoms and 1 , 2, 3, or 4 (preferably 1 or 2) carbon-carbon triple bonds, such as 2 to 6 carbon atoms and 1 , 2 or 3 carbon-carbon triple bonds or 2 to 4 carbon atoms and 1 or 2 carboncarbon triple bonds. Exemplary alkynyl groups include ethynyl, 1-propynyl, 2-propynyl, 1 -butynyl,2-butynyl, 3-butynyl, 1 -pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1 -hexynyl, 2-hexynyl, 3- hexynyl, 4-hexynyl, 5-hexynyl, 1 -heptynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 5-heptynyl, 6- heptynyl, 1 -octynyl, 2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 7-octynyl, 1 -nonylyl, 2- nonynyl, 3-nonynyl, 4-nonynyl, 5-nonynyl, 6-nonynyl, 7-nonynyl, 8-nonynyl, 1 -decynyl, 2-decynyl,3-decynyl, 4-decynyl, 5-decynyl, 6-decynyl, 7-decynyl, 8-decynyl, 9-decynyl, and the like. If an alkynyl group is attached to a nitrogen atom, the triple bond cannot be alpha to the nitrogen atom.

[0024] The term "halogen" or "halo" means fluoro, chloro, bromo, or iodo, preferably fluoro or chloro.

[0025] The term "cyano" means the group -CN. The term "isocyano" means the group -NC. The term "cyanato" means the group -OCN. The term "isocyanate" means the group -NCO. The term "thiocyanate" means the group -SCN. The term "isothiocyanate" means the group -NCS. The term "azido" means the group -N3. The term “nitro” means the group -NO2.

[0026] "Isomers" are compounds having the same molecular formula but differ in structure ("structural isomers") or in the geometrical positioning of the functional groups and / or atoms ("stereoisomers"). "Enantiomers" are a pair of stereoisomers which are non-superimposable mirror-images of each other. A "racemic mixture" or "racemate" contains a pair of enantiomers in equal amounts and is denoted by the prefix (±).

[0027] "Diastereomers" are stereoisomers which are non-superimposable non-mirror-images of each other. "Tautomers" are structural isomers of the same chemical substance that spontaneously interconvert with each other, even when pure.

[0028] As used herein and throughout the entire description, the term "solvate" as used refers to an addition complex of a dissolved material in a solvent (such as an organic solvent (e.g., an aliphatic alcohol (such as methanol, ethanol, n-propanol, isopropanol), acetone, acetonitrile, ether, and the like), water or a mixture of two or more of these liquids), wherein the addition complex exists in the form of a crystal or mixed crystal. The amount of solvent contained in the addition complex may be stoichiometric or non-stoichiometric. A "hydrate" is a solvate wherein the solvent is water.

[0029] The present invention provides a compound according to general formula (I),and hydrates, solvates, salts, complexes, racemic mixtures, diastereomers, diastereomeric mixtures, enantiomers, and tautomers thereof and isotopically enriched forms of any of the foregoing.

[0030] P is selected from the group consisting of -OR3, -(Ci-Cio)alkyl, preferably -OMe, -ethyl, more preferably -OMe;

[0031] Q is selected from the group consisting

[0032] Preferably, the alkene group inconnected to Ri and A has a (Z) configuration.

[0033] R1and R2are independently selected from the group consisting of -H, -(Ci-Cw)alkyl, (Cs- Cw)aryl, -(Cs-Cw)heteroaryl, wherein optionally -(Cs-Cw)aryl, -(Cs-Cw)heteroaryl are substituted with one or more residues independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2- Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Ci-Cio)alkyl(C3-C6)cycloalkyl, -(C1-C10- )alkyl(Ce-Cio)aryl, -(Ci-Cw)alkyl(C3-Cw)heteroaryl, -(Ci-Cw)alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), -N(R3)(OR3), -S(O)0-2R3, S(O)I-2OR3, -OS(O)I-2R3, OS(O)i. 2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I.2OR3, -N(R3)S(O)I.2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, and -XC(=X)XR3, antibody- conjugate (AC) wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid.

[0034] P is selected from the group consisting of -OR3, -(Ci-Cio)alkyl, preferably -OMe, -ethyl, more preferably -Ome;

[0035] A is selected from the group consisting of -(Cs-Cw)aryl, -(Cs-Cwjheteroaryl, wherein optionally -(Cs-Cw)aryl, -(Cs-Cw)heteroaryl are substituted with one or more residues independently selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3- Cwjcycloalkyl, -(Ci-Cw)alkyl(C3-C6)cycloalkyl, -(Ci-Cw)alkyl(Cs-Cw)aryl, -(Ci-Cw)alkyl(C3- Cwjheteroaryl, -(Ci-Cw)alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), N(R3)(OR3), -S(O)0-2R3, S(O)I.2OR3, -OS(O)I.2R3, OS(O)I.2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I. 2R3, -N(R3)S(O)I-2OR3, -N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, -N=N- R3, -C(R3)=N=N, -(Ci-Cs)alkyloxiranyl, -O-O-R3, -S-S-R3, and -XC(=X)XR3, antibody- -conjugate(AC), two adjacent rests may form a ring:wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid, and antibody- conjugate (AC); p is is an integer from 1 to 3.

[0036] M is selected from the group consisting of a bond, -(Ci-C4)alkanediyl, -NH-C(O)-, -C(O)- NH-, -C=C- or -(C2-Ce)alkyndiyl-, wherein optionally -(C2-C4)alkyldiyl- is substituted with one or more residue selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2-C )alkenyl, -(C2-C )alkynyl, -(C3- Cw)cycloalkyl, -(Ci-C )alkyl(C3-C6)cycloalkyl, -(Ci-C )alkyl(C6-Cio)aryl, -(Ci-Cio)alkyl(C3- Cw)heteroaryl, -(Ci-Ci0)alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), N(R3)(OR3), -S(O)0- 2R3, -S(O)I-2OR3, -OS(O)I.2R3, -OS(O)I-2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I. 2R3, -N(R3)S(O)I-2OR3, N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, and -XC(=X)XR3.

[0037] B is selected from the group consisting of H, (Cs-Cio)aryl, (Cs-Cio)heteroaryl, wherein optionally (Cs-Cio)aryl, (Cs-Cio)heteroaryl are substituted with one or more independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(C1- Cw)alkyl, -(Ci-Cio)haloalkyl, -(C2-C )alkenyl, -(C2-C )alkynyl, -(C3-C )cycloalkyl, -(C1- Cio)alkyl(C3-C6)cycloalkyl, -(Ci-Cio)alkyl(Ce-Cio)aryl, -(Ci-Cio)alkyl(C3-C )heteroaryl, -(C1-C10- )alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), -N(R3)(OR3), -S(O)0-2R3, -S(O)I-2OR3, -OS(O)i- 2R3, -OS(O)I-2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I. 2OR3, -N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, -N=N-R3, -C(R3)=N=N, -(CI- Cs)alkyloxiranyl, -O-O-R3, -S-S-R3, and -XC(=X)XR3, antibody -conjugate (AC), two adjacent rests may form a ring:p is is an integer from 1 to 3; wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid, and antibody- conjugate (AC).X is independently selected from O, S, and N(R6).

[0038] R3is, in each case, selected from the group consisting of -H, -(Ci-Cw)alkyl, -(C2- Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cw)aryl, -(Cs-Cw)heteroaryl, and -(C3- C6)heterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independetely selected R10.

[0039] R4and R5are, in each case, independently selected from the group consisting of -H, -(C1- Cw)alkyl, -(C2-Cio)alkenyl, -(Ci-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(C3-C )aryl, -(C3-Cw)heteroaryl, and -(C3-Cw)heterocyclyl, or R4and R5may join together with the nitrogen atom to which they are attached to form the group -N=CR7R8, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independetely selected R10.

[0040] R6is independently selected from from the groups consisting of -H, -(Ci-Cw)alkyl, -(C2- Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cw)aryl, -(Cs-Cw)heteroaryl, and -(C3- Csjheterocyclyl and OR3, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R10.

[0041] R7and R8are independently selected from the group consisting of -H, -(Ci-Cw)alkyl, -(C2- Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cw)aryl, -(Cs-Cw)heteroaryl, and -(C3- Csjheterocyclyl, and -NHyR92-y, or R7and R8may join together with the atom to which they are attached to form a ring which is optionally substituted with one or more independently selected R10, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally susbstituted with one more independently selected R10.

[0042] y is an integer from 0 to 2.

[0043] R9is selected from the group consisting of -(Ci-Cw)alkyl, -(C2-Cw)alkenyl, -(C2- Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cw)aryl, -(Cs-Cw)heteroaryl, and -(Cs-Csjheterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R10; and R10is a 1stlevel substituent and is, in each case independently selected from the group consisting of -(C1- Cwjalkyl, -(C2-Cio)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cwjaryl, -(Cs-Cw)heteroaryl, and -(Cs-Csjheterocyclyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(C1- Cwjhaloalkyl, -(Ci-Cw)alkenyl, -(Ci-Cw)alkynyl, -(C3-Cw)-cycloalkyl, -(Ci-Cw)alkyl(C3- Csjcycloalkyl, -(Ci-Cw)alkyl(Cs-Cw)aryl, -(Ci-Cw)alkyl(C3-Cw)heteroaryl, -(Ci-Cw)alkyl(C3- C6)heterocyclyl, -OH, -OR11, -N(R12)(R13), -N(R11)(OR11), -S(O)0-2R11, -S(O)I-2OR11, -OS(O)I-2R11,OS(O)1-2OR11, -S(O)I-2N(R12)(R13), -OS(O)I-2N(R12)(R13), -N(R11)S(O)I-2R11, -N(R11)S(O)I-20R11, -N(R11)S(O)I-2N(R12)(R13), -C(=X1)R11, -C(=X1)X1R11, -X1C(=X1)R11, and -X1C(=X1)X1R11, and / or any two R10which are bound to the same carbon atom of a cycloalkyl or heterocyclyl may join together to form =X1, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups being a 1stlevel substituent is optionally substituted by one or more 2ndlevel substituents, wherein said 2ndlevel substituent is, in each case, independently selected from the group consisting of -(Ci-Ce)alkyl, -(C2-Ce)alkenyl, -(C2-Ce)alkynyl, -(C3-Ci4)aryl, -(C3- Cujheteroaryl, -(Cs-Cujcycloalkyl, -(Cs-Cujheterocyclyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -OR14, -N(R15)(R16), -N(R14)(OR14), -S(O)0.2R14, -S(O)I-2OR14, -OS(O)i-2R14, -OS(O)I-2OR14, -S(O)I.2N(R15)(R16), -OS(O)I.2N(R15)(R16), -N(R14)S(O)I.2R14, -N(R14)S(O)I.2OR14, N(R14)S(O)I-2N(R15)(R16), -C(=X2)R14, -C(=X2)X2R14, -X2C(=X2)R14, and -X2C(=X2)X2R14, and / or any two 2ndlevel substituents which are bound to the same carbon atom of a cycloalkyl or heterocyclyl group being a 1stlevel substituent may join together to form =X2, wherein each of the -(Ci-Ce)alkyl, -(C2-C6)alkenyl, -(C2-Ce)alkynyl, -(Cs-Cujaryl, -(Cs-Cujheteroaryl, -(C3- Ci4)cycloalkyl, -(Cs-Cujheterocyclyl groups being a 2ndlevel substituent is optionally substituted with one or more 3rdlevel substituents, wherein said 3rdlevel substituent is, in each case, independently selected from the group consisting of -(Ci-Cs’alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -O(Ci-C3alkyl), -S(Ci-C3)alkyl, -NH2, -NH(CI-C3) alkyl), -N((CI-C3) alkyl)2, -NHS(O)2((CI-C3) alkyl), -S(O)2NH2.Z((CI-C3) alkyl)z, -C(=O)OH, -C(=O)((Ci-C3) alkyl), -C(=O)O((Ci-C3) alkyl), -C(=O)NH2.Z((CI-C3) alkyl)z, -OC(=O)(Ci-C3) alkyl), -OC(=O)O((Ci- C3)alkyl), -OC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=O)((CI-C3) alkyl), -NHC(=O)NH2.Z(CI-C3alkyl)z, -NHC(=NH)NH2.z((Ci-C3) alkyl)z, and -N((Ci-C3) alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (C1-C3) alkyl is methyl, ethyl, propyl or isopropyl, and / or any two 3rdlevel substituents which are bound to the same carbon atom of a -(Cs-Cujcycloalkyl or heterocyclyl group being a 2ndlevel substituent may join together to form =0, =S, =NH, or =N(CI-3 alkyl);

[0044] R11, R12, and R13are independently selected from the group consisting of -H, -(Ci-Ce)alkyl, -(C2-Ce)alkenyl, -(C2-Ce)alkynyl, -(C3-Cy)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3- Cy)heterocyclyl, wherein each of the -(Ci-Ce)alkyl, -(C2.C6)alkenyl, -(C2-Ce)alkynyl, -(C3- Cy)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3-Cy)heterocyclyl groups is obtainally substituted with one, two or three substituents selected from the group consisting of -(Ci-Csjalkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -O((Ci-C3)alkyl), -S(Ci- C3)alkyl), -NH2, -NH((Ci-C3)alkyl), -N((Ci-C3)alkyl)2, -NHS(O)2(Ci-C3)alkyl), -S(O)2NH2.Z(CI- C3)alkyl)z, -C(=O)((Ci-C3)alkyl), -C(=O)O((Ci-C3)alkyl), -C(=O)NH2.z((Ci-C3)alkyl)z, -OC(=O)((Ci-C3)alkyl), -OC(=O)O((Ci-C3)alkyl), -OC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=O)(Ci- C3)alkyl), -NHC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=NH)NH2.z((Ci-C3)alkyl)z, and -N((CI-C3) alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3)alkyl is methyl, ethyl, propyl or isopropyl;

[0045] R14, R15, and R16are independently selected from the group consisting of -H, -(Ci-Ce)alkyl, -(C2-C6)alkenyl, -(C2-C6)alkynyl, -(C3.-C7)cycloalkyl, -(Cs-Cejaryl, (Cs-Cejheteroaryl, and -(C3.- C7)heterocyclyl, wherein each of the (Ci-Ce)alkyl, (C2.C6)alkenyl, (C2-C6)alkynyl, -(C3.- C7)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3.-C7)heterocyclyl groups is obtainally substituted with one, two or three substituents selected from the group consisting of (Ci-C3)alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanate, azido, pentafluorosulfanyl, -OH, -O(Ci-C3)alkyl), -S(Ci-C3)alkyl), - NH2, -NH(Ci-C3)alkyl, -N((Ci-C3)alkyl))2, -NHS(O)2(Ci-C3)alkyl, -S(O)2NH2.z((Ci-C3)alkyl)z, - C(=O)(Ci-C3)alkyl, -C(=O)O(Ci-C3)alkyl, -C(=O)NH2.z((Ci-C3)alkyl)z, -OC(=O)(Ci-C3)alkyl, - OC(=O)O(Ci-C3)alkyl, -OC(=O)NH2.z((Ci-C3)alkyl)z, -NHC(=O)(Ci-C3)alkyl, -NHC(=O)NH2.Z((CI- C3)alkyl)z, -NHC(=NH)NH2.z((Ci-C3)alkyl)z, and -N((Ci-C3)alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3)alkyl is methyl, ethyl, propyl or isopropyl;

[0046] X1and X2are independently selected from O, S, and N(R17), wherein R17is -H or (Ci- C3)alkyl.

[0047] If in a general formula (I), a bond is replaced by, that indicates that all possible stereoisomers in particular for the respective carbon atoms which are connected by this bond are included, including E-Z isomers, enantiomers, etc. However, ifplaced in a 90° angle at the end of a normal bond, such asthat indicates a connection point to another group.

[0048] The compound according to general formula (I) may be an antibody-drug conjugate, if the compound comprises the antibody- conjugate (AC) substituent, wherein the antibody- conjugate (AC) substituent has the general formula (II)-L-L0-LI-L2-Z(II)

[0049] L is selected from the group consisting of -O-, -NR17-, -NH-, -NHC(O)-, -C(O)NR18- , -N(OR3)-, -S(O)0-2-, S(O)i-2O-, -OS(O)i-2-, -OS(O)i-2O-, -S(O)I-2N(R4)-, -OS(O)I-2N(R4)-, -N(R3)S(O)I-2-, -N(R3)S(O)I-2O-, -N(R3)S(O)I-2N(R4)-, -C(=X)-, -C(=X)X-, -XC(=X)-, and -XC(=X)X-

[0050] Lo is a group consisting of one or more of the elements selected from the group: a bond,-(CH2)ni-, -(Ci-Cw)alkyldiyl-, -(Ci-C6)cycloalkyldiyl-, -(Ci-C6)heterocycloalkyldiyl,phenyl-, -NR17-, -NH-, -NR18C(O)-, -OC(O)NH-, -C(O)NR18-, -S-, -CH(OH)-, and -CH(OR19)-,-(Ci-C6)heterocycloalkyldiyl is optionally substituted with one or more substituents selected from the group consisting of -NH2, -NHC(=NH)NH2, -COOH, -CONH2, halogen, -NHR18, -NHC(O)NH2, -OR19; for example Lo may be a polyether group, consisting of alternating -O- and -(CH2)ni- elements.

[0051] n1is an integer between 1 to 30, preferably 1 to 20, more preferably 1 to 10.

[0052] Li is a suitable linking moiety; preferably Li is selected from the group consisting of a bond,

[0053] L2is a bond, -(CH2)ni-, -(Ci-Cio)alkyldiyl-, -(Ci-C6)cycloalkyldiyl-, -(C, -(Ci-Cw)alkyldiyl-, -phenyl, -(Ci-C6)heterocycloalkyldiyl is optionally substituted with one or more substituents selected from the group consisting of -NH2, -NHC(=NH)NH2, -COOH, -CONH2, halogen, -NHR18, -NHC(O)NH2, -OR19; for example L2may be a polyether group, consisting of alternating -O- and -(CH2)ni- elements;

[0054] R18, R19, R20, R22and R23are independently selected from the group consisting of H and (Ci-Ce)alkyl, preferably methyl;

[0055] R21is H, -(Ci-Cio)alkyl;

[0056] Z is an antibody, single-chain antibody or nanobody, preferably selected from the group consisting of antibodies such as EGFR targeting antibodies like cetuximab, panitutumab, depatuxizumab, HER2 targeting antibodies such as trastuzumab, disitamab, pertuzumab, CEA targeting antibodies like cergutuzumab, VEGFR targeting antibodies such as bevatuzumab, ramucirumab, CD19 targeting antibodies such as loncastuximab, CD22 targeting antibodies such as inotuzumab, moxetumomab, CD30 targeting antibodies such as brentuximab, CD33 targeting antibodies such as gemtuzumab, CD79b targeting antibodies such as polatuzumab, Nectin-4 targeting antibodies such as enfortumab, TROP2 targeting antibodies such as sacituzumab, datopotamab, tissue factor targeting antibodies such as tisotumab, BCMA (B-cell maturation antigen) targeting antibodies such as belantamab, FRa (Folate Receptor alpha) targeting antibodies such as mirvetuximab, DLL targeting antibodies such as rovalpituzumab, NaPi2 targeting antibodies such as lifastuzumab, CD22 targeting antibodies such as inotuzumab.

[0057] Preferably, for treating cancer, the compound comprises the antibody- conjugate (AC).

[0058] In one embodiment, Ri is H; and / orR2 is H; and / orA is (Cs-Cio)aryl or (Cs-Cio)heteroaryl; and / orM is a bond; and / orB is (Cs-Cio)aryl or (Cs-Cio)heteroaryl.

[0059] In one embodiment,R1and R2are independently selected from the group consisting of -H, -(Ci-Cw)alkyl; and / orA is selected from the group consisting of phenyl, naphthyl, pyridyl, quinolyl, quinoxalinyl, wherein optionally each of the phenyl, naphthyl, pyridyl, quinolyl, and quinoxalinyl is substituted with one or more residues independently selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, -(Ci-Cw)alkyl, -cyano, -OR3,M is a bond;B is selected from the group consisting of phenyl, pyridyl, wherein optionally each of the phenyl, and pyridyl is substituted with one or more residues independently selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, -(Ci-Cio)alkyl, -cyano, -OR3.

[0060] In one embodiment,R1and R2are independently selected from the group consisting of -H, -(Ci-C3)alkyl; and / orA is selected from the group consisting of phenyl, naphthyl, thienyl, pyridyl, pyridimyl, quinolyl, isoquinolyl, quinoxalinyl, wherein optionally each of the phenyl, naphthyl, pyridyl, quinolyl, and quinoxalinyl is substituted with one or more residues independently selected from the group consisting of halogen, -OH, -NH2, -COOH, trifluoromethyl, trifluoromethoxy, -(Ci-Cw)alkyl, -cyano, -OR3,M is a bond;B is selected from the group consisting of phenyl, naphthyl, thienyl, pyridyl, pyridimyl, quinolyl, isoquinolyl, quinoxalinyl, wherein optionally each of the phenyl, naphthyl, pyridyl, quinolyl, and quinoxalinyl is substituted with one or more residues independently selected from the group consisting of halogen, -OH, -NH2, -COOH, trifluoromethyl, trifluoromethoxy, -(Ci-Cw)alkyl, -cyano, -OR3, -cyclopropyl, -methylenecyclopyl, -CONH2.

[0061] Table 1 : Exemplary compounds of the present invention

[0062] The invention further comprises a pharmaceutical composition comprising the compound as described above and at least one pharmaceutically acceptable carrier.Pharmaceutical composition

[0063] Pharmaceutically acceptable "carrier" refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, including but not limited to peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a preferred carrier when the pharmaceutical composition is administered orally. Saline and aqueous dextrose are preferred carriers when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions are preferably employed as liquid carriers for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders, sustained-release formulations and the like. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc. Examples of suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences" by E.W. Martin. Such compositions will contain a therapeutically effective amount of the therapeutic, preferably in purified form, together with a suitable amount of carrier to provide the form for proper administration to the patient. The formulation should suit the mode of administration.Medical application

[0064] The invention is further directed to the compound or the pharmaceutical composition for use in medicine.

[0065] The compound or the pharmaceutical composition may be for use in the treatment of a virus infection, wherein the virus infection is caused by a virus selected from the group consisting of Retroviridae, Herpesviridae, Hepadnaviridae, Orthomyxoviridae, Paramyxoviridae, Flaviviridae, Papillomaviridae, Phenuiviridae, Nairoviridae, Hantaviridae, Arenaviridae, Togaviridae, Coronaviridae, Adenoviridae, Filoviridae, Rhabdoviridae, Pneumoviridae, Poxviridae.

[0066] The compound or the pharmaceutical composition may be for use in the treatment of a virus infection wherein the virus infection is caused by a virus selected from the group consisting of HIV-1 , HIV-2, HTLV-1 , HTLV-2, HSV-1 , HSV-2, VZV, human CMV (HCMV), EBV type 1 , EBV type 2, HHV6, HHV7, HBV-A, influenzavirus A, influenzavirus B, Measles Virus (MV), Nipah virus, HCV, DENV-1 , DENV-2, DENV-3, DENV-4, ZIKV, WNV, TBEV Toro, TBEV Hypr, YFV, HPV-16, HPV-18, RVFV, CCHFV, Hantavirus, Lassa virus, CHIKV, SARS-CoV, SARS-CoV-2, MERS, Human Adenovirus 5 (hAdV5), Zaire EBOV, MARV-A, MARV-B, Rabies lyssavirus, HRSV, Monkeypox virus (MPXV), preferably SARS-CoV-2, HIV-1 , HRSV and DENV-2.

[0067] The compound according or the pharmaceutical composition may be for use in the treatment of a condition, disorder or disease which is mediated or caused by a virus strain which is resistant to one or more antiviral drugs. Preferably, the the antiviral drugs responsible for resistance is selected from the group of drugs consisting of entry inhibitors, reverse transcriptase (RT) inhibitors, integrase inhibitors, protease inhibitors, inhibitors of DNA synthesis, uncoating inhibitors, assembly inhibitors, and release inhibitors.

[0068] The compound or pharmaceutical composition for the use as described above, wherein the treatment further comprises administering at least one additional active compound, in particular at least one antiviral agent and / or at least one anticancer agent.

[0069] The compound or the pharmaceutical composition may be for use in the treatment of cancer, preferably the cancer is selected from the group consisting of solid tumors, breast cancer like HER2 positive breast cancer or triple-negative breast cancer, leukemia like acute myeloid leukemia, relapsed, refractory B-cell precursor acute promyelocytic leukemia, acute lymphoblastic leukemia, hairy cell leukemia, acute lymphoblastic leukemia or chronic lymphocytic leukemia, lymphoma like Hodkin lymphoma, non-Hodkin lymphoma, systemic anaplastic large cell lymphoma, refractory diffuse large B-cell lymphoma, relapsed or refractory large B-cell lymphoma, urothelial cancer, cervical cancer like recurrent or metastatic cervical cancer, ovarian cancer, multiple myeloma, lung cancer like small cell lung cancer or non-small cell lung cancer, gastric cancer, prostate cancer, brain cancers like glioblastoma multiformae, astriocytoma,oligodendroglioma or medulloblastoma, pancreatic cancer or liver cancers like hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma or angiosarcoma. Preferably, the compound for treating these forms of cancer is an antibody-drug conjugate comprising at least one antibodyconjugate (AC) group.

[0070] The compound or pharmaceutical composition for the use in the treatment of cancer, wherein the treatment further comprises administering at least one additional active compound, in particular at least one anticancer agent.EXAMPLES OF THE INVENTIONExperimental Part1. General Information

[0071] All chemicals, reagents and solvents were purchased from commercial suppliers and used without further purification unless explicitly stated. Tetrahydrofuran (THF) was dried over Na / benzophenone and distilled under an atmosphere of argon. All novel compounds used for biochemical and / or biological testing were fully characterized.Nuclear Magnetic Resonance (NMR) Spectroscopy

[0072] 1H,13C and19F NMR spectra were recorded on Bruker Ascend-400, Avance-400, Avance- 500, or Avance-600 apparatus operating at 298 K. Chemical shifts (5) are reported in parts per million (ppm) downfield relative to tetramethylsilane and are referenced to the residual solvent peaks of CDCI3(1H, 7.26 ppm;13C 77.16 ppm) or DMSO-cfe (1H, 2.50 ppm;13C, 39.50 ppm). Coupling constants (J) are given in Hertz (Hz). The following abbreviations are used in the description of spectra: singlet (s), doublet (d), triplet (t), quadruplet (q), pentet (p), multiplet (m), doublet of doublets (dd), doublet of triplets (dt), triplet of doublets (td), triplet of triplets (tt), and broad signal (br s).Liquid Chromatography - Mass Spectroscopy

[0073] High Performance Liquid Chromatography (HPLC) measurements were performed using an LC pump, a diode-array (DAD) UV detector and a column as specified per method. Flow from the column was brought to the Mass Spectrometer, which was configured with an atmospheric pressure ion source. Data acquisition was performed with MassLynx software from Waters or Chromeleon CDS software from Thermo Fisher Scientific. Intermediates and final compounds are described by their retention times (Rt) and ions. Electrospray ionization (ES+and / or ES') was used as ionization method. If not specified differently, the reported molecular ion corresponds to the [M+H]+(protonated molecule) or [M-H (deprotonated molecule). In case a fragmentation or an adduct was observed, the type is specified, e.g., [M-tBu+H]+or [M+Na]+. For molecules with multiple isotopic patterns, e.g., molecules containing Br or Cl atoms, the values are reported for the different isotopes, or the reported value is the one obtained for the lowest monoisotopic mass. The LC-MS methods used are as follows:- Method 1 (acid, 5 min): MS instrument type: Waters LCT Premier mass spectrometer; HPLC instrument type: Waters 2795 separation module; HP 1050 UV multiwavelength detector; Phenomenex Aeris™ Widepore XB-C18, 2.1x50 mm, 3.6 pm column. Mobile phase A: 0.1 % formic acid in water; mobile phase B: 0.1% formic acid in acetonitrile; gradient: 0.0 min 95% A5 min 5% A; flow rate: 0.6 ml / min; column temperature: 25 °C.- Method 2 (acid, 13 min): MS instrument type: ISQ EC Mass Spectrometer; HPLC instrument type: Thermo Fisher Scientific UltiMate 3000 LIHPLC System; Variable Wavelength Detector; Macherey-Nagel Nucleodur PFP column, 2.0x50 mm, 3.0 pm column. Mobile phase A: 0.1 % formic acid in water; mobile phase B: 0.1 % formic acid in acetonitrile; gradient: -5.0 min 95% A8.0 min 5% A -> 13.0 min 5% A; flow rate: 0.3 ml / min; column temperature: 25 °C.High Resolution Mass Spectrometry (HRMS)

[0074] High Resolution Mass Spectrometry (HRMS) measurements were performed using a Waters Micromass LCT mass spectrometer with a lock-spray unit connected to a Waters Alliance 2695 system. Alternatively, a Micromass Q-TOF Premier mass spectrometer connected to a Waters Acquity Ultraperformance LC system was used. Ionization was carried out by electron spray ionization (ESI). The calculated (calc.) and detected masses are given.Thin-Layer Chromatography (TLC)

[0075] Thin-Layer Chromatography (TLC) was performed using ALUGRAM® Xtra SIL G / U 254 silica gel plates from Macherey-Nagel (reference: 818333) or silica gel-coated glass plates coated with fluorescence-indicator F254 from Merck (Reference: 1.15341.0001 and 1.05719.0001). After solvent evaporation, compounds were visualized by irradiation with UV light at 254 nm or by dipping in permanganate solution for non-UV active compounds. The permanganate solution is a solution of KMn©4 (4.5 g), K2CO3 (30 g), NaOH (0.75 g), and water (450 mL).Flash column chromatography

[0076] Purifications were conducted automatically using a Buchi Reveleris® PREP Flash Chromatography System and pre-packed silica gel cartridges from Buchi (FlashPure EcoFlex, FlashPure Select, RediSep®Rf, or RediSep Gold ®) or pre-packed C18 cartridges from Buchi (FlashPure EcoFlex or FlashPure Select).2. General Procedure A: Slow-addition Suzuki-Miyaura Cross-Coupling

[0077] To a flask containing 2-methoxy-3,5-dimethyl-6-(4-((4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (1.0 eq.) and (hetero-)aryl bromide (1.1 - 1.2 eq.) was added DMF (c = 0.1 M). The resulting mixture was degassed under sonication for 10 minutes. In parallel, CS2CO3 (2.0 eq.) was dissolved in water (c = 0.5 M) and degassed under sonication for 10 minutes. Subsequently, Pd(dppf)Cl2*DCM (0.1 eq.) was added to the first solution, before which it was degassed under sonication for 2 minutes. The reaction mixture was heated to 65-75 °C and stirred. CS2CO3 (aq. 0.5 M) was added slowly via a syringe pump over 5 hours. The reaction mixture was allowed to cool down to room temperature,diluted with DCM, filtered, and concentrated in vacuo. The residue was purified by column chromatography to afford the desired product.3. General procedure B: Suzuki-Miyaura Cross-coupling

[0078] To a flask containing aryl bromide, aryl boronic acid or aryl boronic acid pinacol ester (1.1 - 1.2 eq.), Pd(PPh3)4or Pd(dppf)CI2*DCM) (0.05 - 0.15 eq.) and base (K2CO3, Cs2CO3, or K3PO4) (3.0 eq.) was added degassed 1 ,4-dioxane:H2O mixture (4:1 , c = 0.2 M). The reaction mixture was heated to 80 °C and stirred. After 16 hours, the reaction mixture was allowed to cool down to room temperature, diluted with water and extracted three times with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by column chromatography to afford the desired product.Preparation of Intermediate A1 : 2-((trimethylsilyl)methyl)allyl acetateStep 1 : Preparation of 2-iodoprop-2-en-1-ol

[0079] To a solution of Nal (19.2 g, 128 mmol, 1.2 eq.) in MeCN (215 mL) were added TMSCI (20.3 mL, 128 mmol, 1.2 eq.) and water (1.17 mL, 64.2 mmol, 0.6 eq.). The resulting mixture was stirred at room temperature for 20 minutes, before propargyl alcohol (6.17 mL, 107 mmol) was added. After stirring at room temperature for 3 hours, the reaction mixture was quenched with Na2S2O3(aq. 5 wt%, 200 mL) and water (200 mL), and extracted three times with diethyl ether (3 x 200 mL). The combined organic phases were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo to afford the title compound (6.91 g) as a red liquid, which was used in the next step without further purification. Yield: 35%.1H NMR (400 MHz, CDCI3) 5 (ppm) 6.39 (q, J = 1.7 Hz, 1 H), 5.86 (dt, J = 2.0, 1.2 Hz, 1 H), 4.17 (t, J = 1.5 Hz, 2H), 2.47 (t, J = 2.4 Hz, 1 H).13C NMR (101 MHz, CDCI3) 5 (ppm) 124.5, 110.6, 71.2. Spectroscopic data are in agreement with those reported in literature.1Step 2: Preparation of 2-iodoallyl acetate

[0080] To a solution of 2-iodoprop-2-en-1-ol (6.93 g, 37.7 mmol) in DCM (40 mL) were added triethylamine (10.4 mL, 75.3 mmol, 2.0 eq.) and 4-dimethylaminopyridine (0.460 g, 3.77 mmol). The solution was cooled to 0 °C, before acetic anhydride (4.27 mL, 45.2 mmol, 1 .2 eq.) was added dropwise. The resulting mixture was allowed to warm to room temperature and stirred for twohours. The reaction mixture was quenched with NH4CI (aq. sat.) and extracted three times with diethyl ether. The combined organic phases were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo to afford the title compound (8.60 g) as a red liquid, which was used in the next step without further purification. Yield: quantitative.1H NMR (400 MHz, CDCI3) 5 (ppm) 6.35 (q, J = 1.6 Hz, 1 H), 5.93 (dt, J = 2.0, 1.0 Hz, 1 H), 4.70 - 4.64 (m, 2H), 2.13 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 170.0, 127.4, 102.3, 71.0, 20.9. Spectroscopic data are in agreement with those reported in literature.2Step 3: Preparation of 2-((trimethylsilyl)methyl)allyl acetate

[0081] Anhydrous Cobalt(ll) chloride (27 mg, 0.21 mmol, 0.05 eq.) was placed under vacuum and warmed with a heat gun for 2-3 minutes until it turned blue. The flask was then vented to argon, the solid dissolved in THF (2 mL), and the resulting solution cooled to 0 °C. Subsequently, 2- iodoallyl acetate (0.95 g, 4.2 mmol) was added, followed by dropwise addition of trimethylsilylmethylmagnesium chloride (6.3 mL, 6.3 mmol, 2.0 M in Et20). The reaction mixture was allowed to warm to room temperature and stirring was continued for one hour. The reaction mixture was quenched with NH4CI (aq. sat.) and extracted three times with EtOAc. The combined organic phases were dried (Na2SC>4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 0 - 10%) to afford the title compound (3.03 g) as an off-white liquid. Yield: 35%.1H NMR (400 MHz, CDCI3) 6 (ppm) 4.90 - 4.85 (m, 1 H), 4.74 - 4.70 (m, 1 H), 4.43 (s, 2H), 2.10 (s, 3H), 1.54 (s, 2H), 0.04 (s, 9H).13C NMR (101 MHz, CDCI3) 5 (ppm) 170.9, 141.8, 109.8, 68.0, 23.7, 21.1 , -1.3. Spectroscopic data are in agreement with those reported in literature.23Preparation of intermediate B1 : 2-methoxy-3,5-dimethyl-6-(4-((4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-oneStep 1 : Preparation of dimethyl 2,4-dimethyl-3-oxopentanedioate

[0082] To a solution of dimethyl-3-oxopentanedioate (45.0 g, 0.26 mol) in THF (350 mL) was slowly added K2CO3 (89.3 g, 0.65 mol, 2.5 eq.). The solution was heated to 45 °C and lodomethane (73.4 g, 0.52 mol, 2.0 eq.) was slowly added under continuous stirring. The temperature of the reaction solution did not exceed 60 °C during addition. After heating at 55 °C for one hour, the reaction mixture was filtered, and the filter cake was washed with THF. The filtrate was concentrated in vacuo to afford the title compound (48.7 g) as a yellow oil, which wasused in the next step without further purification. Yield: 93%.1H NMR (400 MHz, CDCh) 5 (ppm) 3.86-3.74 (m, 2H), 3.71 (s, 6H), 1.37-1.34 (m, 6H).13C NMR (101 MHz, CDCh) 5 (ppm) 201.1 , 107.7, 170.4, 52.6, 52.5, 51.7, 51.5, 13.1 , 12.8. HR-MS: [M+Na]+calculated for C9Hi4O5Na 225.0739; found 225.0739. Spectroscopic data are in agreement with those reported in literature.4Step 2: Preparation of 2,6-dimethoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0083] To fuming sulfuric acid (oleum; 20% SO3 in H2SO4) (16.6 mL, 0.31 mol, 7.0 eq.) was added dropwise at 0 °C dimethyl 2,4-dimethyl-3-oxopentanedioate (9.00 g, 0.05 mol). After 24 hours, the reaction mixture was added to a mixture of ice (140 g) NaOH (26.7 g) and water (65 mL) while stirring. The pH was adjusted to 6 and the resulting solid was filtered off. The aqueous phase was extracted three times with DCM. The combined organic phases were washed with brine, dried (Na2SC>4), filtered, and the filtrate was concentrated in vacuo to afford the title compound (6.0 g) as a white solid, which was used in the next step without further purification. Yield: 73%.1H NMR (400 MHz, CDCh) <5 (ppm) 3.99 (s, 6h), 1.84 (s, 6H).13C NMR (101 MHz, CDCh) 5 (ppm) 182.7, 158.8, 99.3, 56.2, 7.2 ppm. HR-MS: [M+Na]+calculated for C9Hi2O4Na 207.0633; found 207.0622. Spectroscopic data are in agreement with those reported in literature.4Step 3: Preparation of 2-(1 ,3-dithian-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one OJ JC

[0084] To a solution of 1 ,3-dithiane (15.7 g, 131 mmol, 3.5 eq.) in anhydrous THF (120 mL) was slowly added f-BuLi (1.9 M in hexanes, 41.5 mL, 78.0 mmol, 2.1 eq.) at -20 °C under argon atmosphere. The reaction mixture was stirred at -20 °C for one hour. Subsequently, 2,6- dimethoxy-3,5-dimethyl-4 / 7-pyran-4-one (6.90 g, 37.0 mmol) in anhydrous THF (180 mL) was added slowly at -78 °C over a period of 30 minutes. The reaction mixture was stirred at -78 °C for one hour and then quenched with MeOH (100 mL). The reaction mixture was stirred for another 19 hours and allowed to slowly warm to room temperature. The reaction mixture was diluted with water (300 mL) and extracted with DCM. The organic phase was washed with brine, dried (Na2SC>4), filtered, and the filtrate was concentrated in vacuo. The residue was recrystallized from n-pentane, aspirated and dried. The product was then purified by normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford the title compound (6.72 g) as a white solid. Yield: 66%.1H NMR (400 MHz, CDCh) 5 (ppm) 5.29 (s, 1 H), 4.04 (s, 3H), 3.12 - 3.02 (m, 2H), 3.00 - 2.93 (m, 2H), 2.22 - 2.14 (m, 1 H), 2.05 (s, 3H), 2.03 - 1.91 (m, 1 H), 1.84 (s, 3H).13C NMR(101 MHz, CDCI3) 6 (ppm) 180.4, 162.3, 153.0, 119.6, 100.2, 56.0, 46.6, 31.4 (2C), 25.2, 10.1 , 7.1 ppm. LC-MS: Rt= 7.20 min, ES+= 273.11 , method 2. HR-MS: [M+Na]+calculated for Ci2Hi6C>3NaS2 295.0439, found 295.0430. Spectroscopic data are in agreement with those reported in literature.4Step 4: Preparation of 6-methoxy-3-,5-dimethyl-4-oxo-4 / 7-pyran-2-carbaldehyde

[0085] To a solution of 2-(1 ,3-dithian-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one (6.72 g, 25 mmol) in MeCN (240 mL) was added a NaOAc-HOAc buffer (pH = 4) (60 mL). Subsequently (bis(trifluoroacetoxy)iodo)benzene (21.2 g, 74 mmol, 2.0 eq.) was added and the reaction mixture was stirred at room temperature for 10 minutes, before which another batch of (bis(trifluoroacetoxy)iodo)benzene (10.6 g, 25 mmol, 1.0 eq.) was added. NaHCCh (21 g), Na2S2C>3 (20 g) and water were added. The aqueous phase was extracted three times with DCM. The combined organic phases were washed with brine, dried (Na2SC>4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford the title compound (3.82 g) as a white solid. Yield: 66%.1H NMR (400 MHz, CDCI3) 5 (ppm) 10.05 (s, 1 H), 4.09 (s, 3H), 2.36 (s, 3H), 1.90 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 183.0, 180.4, 147.5, 132.2, 128.7, 128.5, 55.9, 8.5, 7.2. HR-MS: [M+H]+calculated for C9H11O4 183.0657; found at 183.0663. Spectroscopic data are in agreement with those reported in literature.4Step 5: Preparation of 2-methoxy-3,5-dimethyl-6-(4-methylenetatrahydrofuran-2-yl)-4 / 7-pyran-4- one

[0086] A solution of ln(acac)3 (212 mg, 0.52 mmol, 0.1 eq.) and Pd(PPhs)4 (596 mg, 0.52 mmol, 0.1 eq.) in anhydrous THF (40 mL) was stirred at room temperature for 10 minutes. To this solution was added a solution of 7 (939 mg, 5.2 mmol) in anhydrous THF (50 mL) and 2- [(acetoxymethyl)allyl]trimethylsilane (Intermediate A1) (1.42 mL, 6.70 mmol, 1.3 eq.). The reaction mixture was stirred for 2 hours at reflux. The reaction mixture was concentrated in vacuo and the residue was purified by normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford the title compound (1.09 g) as a yellow solid. Yield: 90%. Rt (PE / EtOAc; 1 / 1): 0.28 [SiC>2, UV],1H NMR (400 MHz, CDCI3): 5 (ppm) 5.21 - 5.16 (m, 1 H), 5.10 (quin., J = 2.2 Hz, 1 H), 5.02 (quin., J = 2.2 Hz, 1 H), 4.58 - 4.40 (m, 2H), 3.94 (s, 3H), 2.96 - 2.73 (m, 2H), 2.00 (s, 3H), 1.84 (s, 3H).13C NMR (101 MHz, CDCI3): 5 (ppm) 180.8, 162.2, 155.2, 146.6, 120.0, 105.3, 100.0, 75.1 , 71.9, 55.4, 36.2, 9.5, 7.0. LC-MS: Rt= 2.54 min, ES+= 237.09, method 1. HR-MS: [M+Na]+calculated for CisHieOtNa 259.0946; found 259.0948. Spectroscopic data are in agreement with those reported in literature.5Step 6: Preparation of 2-methoxy-3,5-dimethyl-6-(4-((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0087] To a solution of 2-methoxy-3,5-dimethyl-6-(4-methylenetatrahydrofuran-2-yl)-4 / 7-pyran-4- one (500 mg, 2.12 mmol) in anhydrous DCM (30 mL) under an argon atmosphere were added vinylboronic acid pinacol ester (718 pL, 4.23 mmol, 2.0 eq.) and Grubbs-Il catalyst (180 mg, 0.21 mmol, 0.1 eq.). The reaction mixture was refluxed for 3 hours. The reaction mixture was allowed to cool down to room temperature, concentrated in vacuo, and purified by normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford the title compound (730 mg, 1 :1 ratio E / Z according to1H NMR) as a brown oil. Yield: 95%.1H NMR (400 MHz, CDCI3): 5 (ppm) 5.48 - 5.45 (m, 1 H), 5.36 - 5.33 (m, 1 H), 5.24 - 5.20 (m, 1 H), 5.19 - 5.16 (m, 1 H), 4.83 - 4.44 (m, 4H), 3.91 (s, 3H), 3.90 (s, 3H), 3.19 - 2.81 (m, 2H), 2.03 (s, 3H), 2.01 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H), 1.27 - 1.24 (m, 24H).13C NMR (101 MHz, CDCI3): 5 (ppm) 180.8, 180.8, 163.5, 163.0, 162.3, 162.2, 155.4, 155.2, 120.1 , 119.9, 108.6, 107.7, 100.0, 100.0, 83.4 (2C), 83.4 (2C), 75.6, 74.1 , 73.8, 72.4, 55.4, 55.4, 39.1 , 36.2, 25.0 (2C), 25.0 (2C), 25.0 (2C), 24.9 (2C), 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.17 min, ES+= 363.26, method 2. HR-MS: [M+Na]+calculated for Cig^eOeNaB 385.1798; found 385.1800. Spectroscopic data are in agreement with those reported in literature.5

[0088] Preparation of intermediate B2: 2-methoxy-3,5-dimethyl-6-(4-(1-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)ethylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0089] To a solution of 2-methoxy-3,5-dimethyl-6-(4-methylenetetrahydrofuran-2-yl)-4 / 7-pyran-4- one (25 mg, 0.11 mmol) and isopropenyl boronic acid pinacol ester (0.99 mL, 0.53 mmol) in anhydrous DCM (degassed, 0.5 mL) under Argon at 40 °C was added a solution of Hoveyda- Grubbs M720 catalyst (66 mg, 0.11 mmol) in anhydrous DCM (degassed, 0.5 mL). After 3 hours, the reaction mixture was allowed to cool down to room temperature and concentrated in vacuo. The residue was purified by normal phase column chromatography (heptane / EtOAc, 5-100%) to afford the title compound (14 mg, 10:8 ratio E / Z according to1H NMR) as a brown oil. Yield: 32%.1H NMR of E-isomer (400 MHz, CDCI3): 5 (ppm) 5.20 - 5.15 (m, 1 H), 4.82 - 4.59 (m, 1 H), 3.89 (s, 3H), 2.94 - 2.69 (m, 1 H), 2.01 (s, 3H), 1.84 (s, 3H), 1.75 (p, J = 1.8 Hz, 3H), 1.28 - 1.21 (m, 12H).13C NMR of E-isomer (101 MHz, CDCh): 5 (ppm) 180.8, 162.2, 155.6 or 155.4, 155.0, 120.0 or 119.8, 99.9, 83.4 (2C), 74.2, 72.7, 55.3, 35.2, 25.0 (m, 4C), 17.7, 9.6, 7.0. Tertiary Carbon next to Boron not observed.1H NMR of Z-isomer (400 MHz, CDCh): 5 (ppm) 5.20 - 5.15 (m, 1 H), 4.59 - 4.45 (m, 1 H), 3.89 (s, 3H), 3.19 - 2.94 (m, 1 H), 2.01 (s, 3H), 1.84 (s, 3H), 1.66 (p, J = 1.8 Hz, 3H), 1.28 - 1.21 (m, 12H).13C NMR of Z-isomer (101 MHz, CDCh): 5 (ppm) 180.8, 162.2, 155.6 or 155.4, 154.4,120.0 or 119.8, 99.9, 83.4 (2C), 74.2, 71.6, 55.3, 36.2, 25.0 (m, 4C), 16.8, 9.6, 7.0. Tertiary Carbon next to Boron not observed. LC-MS: Rt = 8.37 min, ES+= 377.21 , method 2. HRMS: [M+Na]+calculated for C2oH290eNaB 399.1955; found 399.1955.EXAMPLE 1 : Preparation of 1.E, 1.Z and 1 : (E)-2-(4-(n ,1'-biphenyl1-4- ylmethylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one 1.E and (Z)-2-(4- biphenyl1-4-ylmethylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one 1.Z

[0090] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (428 mg, 1.18 mmol) and 4-bromo-1 ,1’-biphenyl (331 mg, 1.42 mmol, 1.2 eq.). Purification was performed by reverse phase column chromatography (water / MeCN, 0 - 100%) to afford 1.E (51 mg, 100 / 0 ratio E / Z according to1H NMR) as an off-white powder, 1.Z (59 mg, 7 / 100 ratio E / Z according to1H NMR) as an off-white powder, and 1 (62 mg, 10 / 11 ratio E / Z according to1H NMR) as an off-white powder. Yield: 45% (combined).1H NMR 1.E (400 MHz, CDCh): 5 (ppm) 7.65 - 7.60 (m, 4H), 7.50 - 7.43 (m, 2H), 7.41 - 7.37 (m, 3H), 6.51 (t, J = 2.2 Hz, 1 H), 5.34 (dd, J = 7.6, 5.6 Hz, 1 H), 4.82 - 4.66 (m, 2H), 3.89 (s, 3H), 3.30 - 3.06 (m, 2H), 2.07(s, 3H), 1.86 (s, 3H).13C NMR 1.E (101 MHz, CDCh) 5 (ppm) 180.8, 162.3, 155.2, 140.6, 140.0, 139.4, 136.0, 129.0, 128.6, 127.6, 127.4, 127.1 , 120.3, 120.1 , 100.1 , 75.8, 73.8, 55.5, 34.5, 9.6,7.1 .1H NMR 1.Z (400 MHz, CDCh) 5 (ppm) 7.63 - 7.58 (m, 4H), 7.48 - 7.42 (m, 2H), 7.38 - 7.33 (m, 1 H), 7.22 - 7.17 (m, 2H), 6.56 (t, J = 2.2 Hz, 1 H), 5.23 (dd, J = 7.5, 5.4 Hz, 1 H), 4.94 - 4.78 (m, 2H), 3.83 (s, 3H), 3.23 - 2.98 (m, 2H), 2.05 (s, 3H), 1.85 (s, 3H).13C NMR 1.Z (101 MHz, CDCh) 5 (ppm) 180.8, 162.4, 155.4, 140.5, 139.9, 139.9, 135.9, 129.0, 128.4, 127.6, 127.5,127.1 , 121.6, 120.0, 100.1 , 73.5, 70.5, 55.5, 38.4, 9.6, 7.1. LC-MS: Rt= 3.81 min, ES+= 389.10, method 1. HR-MS: [M+Na]+calculated for C25H24O4Na 411.1572; found 411.1571.EXAMPLE 2: Preparation of 2.E, 2.Z and 2: (E)-2-methoxy-3,5-dimethyl-6-(4-(naphthalen-2- ylmethylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one 2.E and (Z)-2-methoxy-3,5-dimethyl-6-(4- (naphthalen-2-ylmethylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one 2.Z

[0091] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (425 mg, 1.17 mmol) and 2-bromonaphthalene (292 mg, 1.41 mmol, 1.2 eq.). Purification was performed by reverse phase column chromatography (water / MeCN, 0 - 100%) to afford 2.E (20 mg, 100 / 0 ratio E / Z according to1H NMR) as an off-white powder, 2.Z (48 mg, 10 / 100 ratio E / Z according to1H NMR) as an off-white powder, and 2 (43 mg, 10 / 14 ratio E / Z according to1H NMR). Yield: 28% (combined).1H NMR 2.E (400 MHz, CDCh) 5 (ppm) 7.85 - 7.76 (m, 3H), 7.74 - 7.69 (m, 1 H), 7.53 - 7.40 (m, 3H), 6.60 (t, J = 2.3 Hz, 1 H), 5.33 (dd, J = 7.6, 5.6 Hz, 1 H), 4.83 - 4.67 (m, 2H), 3.85 (s, 3H), 3.35 - 3.11 (m, 2H), 2.05 (s, 3H), 1.83 (s, 3H).13C NMR 2.E (101 MHz, CDCh) 5 (ppm) 180.7, 162.3, 155.1 , 139.7, 134.5, 133.5, 132.5, 128.3, 128.1 , 127.8, 127.1 , 126.6, 126.3, 126.2, 120.8, 120.1 , 100.1 , 75.8, 73.8, 55.4, 34.5, 9.6, 7.1.1H NMR 2.Z (400 MHz, CDCh) 5 (ppm) 7.85 - 7.80 (m, 4H), 7.56 - 7.54 (m, 1 H), 7.51 - 7.47 (m, 2H), 6.69 (br s, 1 H), 5.26 (br s, 1 H), 5.00 - 4.86 (m, 2H), 3.82 (s, 3H), 3.28 - 3.02 (m, 2H), 2.08 (s, 3H), 1.88 (s, 3H).13C NMR 2.Z (101 MHz, CDCh) 5 (ppm) 180.6, 162.7, 155.8, 140.1 , 134.4, 133.6, 132.4, 128.5, 128.1 , 127.8, 127.0, 126.7, 126.4, 126.0, 122.2, 119.8, 100.3, 73.4, 70.6, 55.7, 38.6, 9.7, 7.3. LC-MS: Rt= 3.60 min, ES+= 363.10, method 1. HR-MS: [M+Na]+calculated for C23H22O4Na 385.1416; found 384.1405.EXAMPLE 3: Preparation of 3: 2-(4-(n ,1'-biphenyl1-3-ylmethylen)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0092] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (75 mg, 0.21 mmol) and 3-bromo-1 ,1’-biphenyl (56 mg, 0.27 mmol, 1.3 eq.), Pd2(dba)3 (38 mg, 0.04 mmol, 0.2 eq.) and dppf (46 mg, 0.08 mmol, 0.4 eq.) in 1 ,4-dioxane. Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) and reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-95%) to afford 3 (34 mg, 1 :1 ratio E / Z according to1H NMR) as a yellow oil. Yield: 42%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.60-7.55 (m, 4H), 7.50-7.28 (m, 13H), 7.14-7.08 (m, 1 H), 6.62-6.58 (m, 1 H), 6.53-6.50 (m, 1 H), 5.32 (dd, J = 5.8, 7.6 Hz, 1 H), 5.23 (dd, J = 5.8, 7.6 Hz, 1 H), 4.94-4.64 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.30-2.97 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.85 (s, 3H), 1.84 (s, 3H).13C NMR (101 MHZ, CDCI3) 5 (ppm) 181.1 , 181.1 , 162.6, 162.6, 155.7, 155.4, 141.9, 141.9, 141.0, 141.0, 140.0, 139.5, 137.5, 137.3, 129.3, 129.2, 129.0 (2C), 129.0 (2C), 127.7, 127.7, 127.6, 127.6, 127.3 (2C), 127.3 (2C), 127.1 , 127.0, 126.9, 126.7, 122.1 , 120.7, 120.2, 120.0, 100.3, 100.2, 75.7, 73.7, 73.4, 70.5, 55.5, 55.5, 38.3, 34.4, 9.7, 9.7, 7.1 , 7.1. HR-MS: [M+Na]+calculated for C2sH24C>4Na 411.1572; found 411.1564.EXAMPLE 4: Preparation of 4: 2-methoxy-3,5-dimethyl-6-(4-((4'-(trifluoromethyl)-n ,1'-biphenyl1- 4-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-oneStep 1 : Preparation of 4-bromo-4’-(trifluoromethyl)-1 ,1’-biphenyl

[0093] Prepared according to general procedure B using 4-bromoiodobenzene (200 mg, 0.707 mmol), 4,4,5,5-tetramethyl-2-(4-(trifluoromethyl)phenyl)-1 ,3,2-dioxaborolane (212 mg, 0.778 mmol, 1.1 eq.), Pd(PPhs)4 (41 mg, 0.035 mmol, 0.05 eq.), and K2CO3 (293 mg, 2.12 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 50%) to afford the title compound (85 mg) as a white powder. Yield: 38%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.72 - 7.68 (m, 2H), 7.68 - 7.63 (m, 2H), 7.63 - 7.58 (m, 2H), 7.49 - 7.44 (m, 2H).13CNMR (101 MHz, CDCI3) 5 (ppm) 143.7 (d, J = 1.6 Hz), 138.8, 132.30, 129.9 (q, J = 32.5 Hz), 129.0, 127.4, 126.0 (q, J = 3.8 Hz), 125.7 (q, J = 272.4 Hz), 122.8. Spectroscopic data are in agreement with those reported in literature.6Step 2: Preparation of 2-methoxy-3,5-dimethyl-6-(4-((4'-(trifluoromethyl)-[1 , 1 '-bi pheny l]-4- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0094] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (50 mg, 0.138 mmol) and 4-bromo-4'-(trifluoromethyl)-1 ,1'-biphenyl (48 mg, 0.160 mmol, 1.1 eq.). Purification was performed by reverse phase column chromatography (Water / MeCN, 0 - 100%) to afford 4 (15 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 24%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.70 (d, J = 2.8 Hz, 8H), 7.64 - 7.57 (m, 4H), 7.40 (d, J = 7.9 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 6.57 (br s, 1 H), 6.49 (br s, 1 H), 5.37 - 5.28 (m, 1 H), 5.27 - 5.19 (m, 1 H), 4.94 - 4.64 (m, 4H), 3.87 (s, 3H), 3.83 (s, 3H), 3.29 - 2.98 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) <5 (ppm) 180.7 (2C), 162.3, 162.2, 155.2, 155.0, 144.1 , 144.0, 140.7, 140.2, 138.4, 138.3, 137.0, 136.8, 129.7 (q, J = 32.4 Hz, 2C), 128.8, 128.5, 127.64, 127.56, 127.34, 127.33, 126.0 (q, J = 4.0 Hz, 2C), 124.38 (q, J= 271.8 Hz, 2C), 121.3, 120.2, 120.1 , 120.0, 100.1 (2C), 75.8, 73.7, 73.5, 70.5, 55.41 , 55.40, 38.4, 34.5, 9.63, 9.62, 7.1 , 7.0.19F NMR (376 MHz, CDCI3) 5 (ppm) -62.69. LC-MS: Rt= 9.36 min, ES+= 457.22, method 2. HR-MS (El; LCT): [M+Na]+calculated for C26H23O4NaF3479.1446; found 479.1446.EXAMPLE 5: Preparation of 5: 2-(4-((4'-chloro-3'-(trifluoromethyl)-f1 ,1'-biphenyl1-4- yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 4'-bromo-4-chloro-3-(trifluoromethyl)-1 ,1'-biphenyl

[0095] Prepared according to general procedure B using 4-bromoiodobenzene (200 mg, 0.707 mmol), 2-(4-chloro-3-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (238 mg, 0.778 mmol, 1.1 eq.), Pd(PPha)4 (41 mg, 0.035 mmol, 0.05 eq.), and K2CO3 (293 mg, 2.12 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 50%) to afford the title compound (102 mg) as a white solid. Yield: 39%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.87 (d, J = 2.2 Hz, 1 H), 7.68 - 7.55 (m, 4H), 7.49 - 7.42 (m, 2H).13C NMR (101 MHz, CDCI3) 5 (ppm) 139.2, 137.7, 133.6, 132.4, 132.2, 131.2, 129.0, 128.7, 126.1 (q, J = 5.2 Hz), 122.91 , 121.90 (q, J = 275.2 Hz). Spectroscopic data are in agreement with those reported in literature.7Step 2: Preparation of 2-(4-((4'-chloro-3'-(trifluoromethyl)-[1 , 1 '-bi pheny l]-4- yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0096] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (50 mg, 0.138 mmol) and 4'-bromo-4-chloro-3-(trifluoromethyl)-1 ,1'-biphenyl (51 mg, 0.152 mmol, 1.1. eq.). Purification was performed by reverse phase column chromatography (Water / MeCN, 0 - 100%) and then normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford 5 (4.8 mg, 69 / 100 ratio E / Z according to1H NMR) as an off-white powder. Yield: 7%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.93 - 7.90 (m, 2H), 7.73 - 7.68 (m, 2H), 7.62 - 7.57 (m, 6H), 7.43 - 7.40 (m, 2H), 7.27 - 7.23 (m, 2H), 6.59 (p, J = 2.3 Hz, 1 H), 6.51 (p, J = 2.3 Hz, 1 H), 5.35 (dd, J = 7.6, 5.9 Hz, 1 H), 5.25 (dd, J = 7.6, 5.9 Hz, 1 H), 4.94 - 4.79 (m, 2H), 4.82 - 4.67 (m, 2H), 3.89 (s, 3H), 3.86 (s, 3H), 3.30 - 3.00(m, 4H), 2.07 (s, 3H), 2.06 (s, 3H), 1.87 (s, 3H), 1.86 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8 (2C), 162.3, 162.2, 155.2, 155.0, 140.9, 140.4, 139.5, 139.5, 137.3, 137.2, 137.1 , 137,0, 132.1 (2C), 131.5 (2C), 131.1 (2C), 129.0(q, J = 30.9 Hz, 2C), 128.9 (2C), 128.7 (2C), 127.4 (2C), 127.3 (2C), 126.1 (q, J = 5.6 Hz, 2C), 123.0 (q, J = 273.5 Hz, 2C), 121.2, 120.2, 120.1 , 119.9, 100.1 (2C), 75.77, 73.75, 73.5, 70.5, 55.40, 55.39, 38.4, 34.5, 9.62, 9.60, 7.04, 7.02.19F NMR (376 MHz, CDCI3) 6 -62.87. LC-MS: Rt= 9.57 min, ES+= 491.15, method 2. HR-MS (El; LCT): [M+Na]+calculated for C26H22O4F3NaCI 513.1056; found 513.1040.EXAMPLE 6: Preparation of 6: 2-(4-((6-(4-fluorophenyl)pyridin-3-yl)methylene)tetrahydrofuran-2- yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 5-bromo-2-(4-fluorophenyl)pyridine

[0097] Prepared according to general procedure B using 5-bromo-2-iodopyridine (200 mg, 0.704 mmol), 2-(4-fluorophenyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (172 mg, 0.775 mmol, 1.1 eq.), Pd(dppf)Cl2*DCM (86 mg, 0.106 mmol, 0.15 eq.), and CS2CO3 (689 mg, 2.11 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / DCM, 5 - 40%) to afford the title compound (44 mg) as colorless crystals. Yield: 24%.1H NMR (400 MHz, CDCI3) 6 (ppm) 8.71 (dd, J = 2.4, 0.8 Hz, 1 H), 7.97 - 7.91 (m, 2H), 7.84 (dd, J = 8.5, 2.4 Hz, 1 H), 7.55 (dd, J = 8.5, 0.8 Hz, 1 H), 7.18 - 7.11 (m, 2H).13C NMR (101 MHz, CDCI3) 5 (ppm) 163.8 (d, J = 249.1 Hz), 155,0, 150.8, 139.5, 134.5 (d, J = 3.2 Hz), 128.7 (d, J = 8.5 Hz), 121.4 (d, J = 0.8 Hz), 119.4 (d, J = 0.8 Hz), 115.9 (d, J = 21.7 Hz). Spectroscopic data are in agreement with those reported in literature.8Step 2: Preparation of 2-(4-((6-(4-fluorophenyl)pyridin-3-yl)methylene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0098] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (50 mg, 0.138 mmol) and 5-bromo-2-(4-fluorophenyl)pyridine (42 mg, 0.166 mmol, 1.2 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford 6 (16 mg, 33:67 ratio E / Z according to1H NMR) as an off-white powder. Yield: 28%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.61 (t, J = 1 .6 Hz, 1 H), 8.48 (d, J = 2.4 Hz, 1 H), 8.03 - 7.94 (m, 4H), 7.73 - 7.63 (m, 3H), 7.47 (dd, J = 8.3, 2.4 Hz, 1 H), 7.21 - 7.10 (m, 4H), 6.56 - 6.51 (m, 1 H), 6.47 - 6.43 (m, 1 H), 5.32 (dd, J = 7.5, 6.0 Hz, 1 H), 5.23 (dd, J = 7.5, 6.1 Hz, 1 H), 4.92 - 4.64 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.27 - 3.00 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) <5 (ppm) 180.7, 180.7, 163.8 (d, J = 248.8 Hz), 163.7 (d, J = 248.8 Hz), 162.3, 162.2, 154.9, 154.7, 154.7, 154.6, 149.5, 149.2, 142.4, 141.9, 135.6, 135.4, 135.0 (d, J = 3.2 Hz), 134.9 (d, J = 3.2 Hz), 131.1 , 130.9, 128.70, 128.66, 120.4, 120.2, 120.0 (d, J = 0.6 Hz), 119.9 (d, J = 0.6 Hz), 118.2, 117.0, 115.9 (d, J = 21.7 Hz), 115.9 (d, J = 21.7 Hz), 100.2, 100.2, 75.8, 73.66, 73.65, 70.5, 55.4, 55.4, 38.3, 34.5, 9.6, 9.6, 7.0, 7.0. LC- MS: Rt= 7.90 min, ES+= 408.21 , method 2. HR-MS (El; LCT): [M+Na]+calculated for C24H22NO4FNa 430.1431 , found 430.1424.EXAMPLE 7: Preparation of 7: 2-(4-((2'-chloro-n ,T-biphenyl1-4-yl)methylene)tetrahydrofuran-2- yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 4'-bromo-2-chloro-1 ,1'-biphenyl

[0099] Prepared according to general procedure B using 4-bromoiodobenzene (200 mg, 0.707 mmol), (2-chlorophenyl)boronic acid (122 mg, 0.778 mmol, 1.1 eq.), Pd(dppf)CI2*DCM (58 mg, 0.071 mmol, 0.10 eq.), and K2CO2(293 mg, 2.12 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / DCM, 0 - 10%) to afford the title compound (71 mg) as a colorless oil. Yield: 36%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.59 - 7.54 (m, 2H), 7.50 - 7.45 (m, 1 H), 7.35 - 7.29 (m, 5H).13C NMR (101 MHz, CDCI3) 5 (ppm) 139.5, 138.4, 132.5, 131.4, 131.3, 131.3, 130.2, 129.0, 127.1 , 122.1. Spectroscopic data are in agreement with those reported in literature.9Step 2: Preparation of 2-(4-((2'-chloro-[1 ,1'-biphenyl]-4-yl)methylene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0100] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.138 mmol) and 4’-bromo-2-chloro-1 ,1’-biphenyl (41 mg, 0.152 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 100%) and consecutive reverse phase column chromatography (Water / MeCN, 0 - 100%) to afford 7 (2 mg, 37 / 63 ratio E / Z according to1H NMR) as an off-white powder. Yield: 3%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.55 - 7.26 (m, 14H), 7.19 (d, J = 8.2 Hz, 2H), 6.57 (t, J = 2.3 Hz, 1 H), 6.49 (d, J = 2.4 Hz, 1 H), 5.32 (dd, J = 7.7, 5.8 Hz, 1 H), 5.23 (dd, J = 7.6, 5.8 Hz, 1 H), 4.94 - 4.65 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.29 - 2.97 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.85 (s, 3H), 1.84 (s, 3H).13C NMR (101 MHZ, CDCI3) 5 (ppm) 180.9, 180.8, 162.4, 162.3, 155.3, 155.1 , 140.2, 140.0, 140.0, 139.7, 138.3, 138.2, 136.4, 136.2, 132.6 (2C), 131.4 (2C), 130.21 , 130.20, 129.9 (2C), 129.9 (2C), 128.9, 128.7, 127.9 (2C), 127.6 (2C), 127.1 (2C), 121.6, 120.3, 120.2, 120.0, 100.1 , 100.1 , 75.8, 73.8, 73.5, 70.5, 55.4 (2C), 38.3, 34.5, 9.6, 9.6, 7.1 , 7.1. LC-MS: Rt= 9.03 min, ES+= 423.16, method 2. HR-MS (El; LCT): [M+Na]+calculated for C25H23O4NaCI 445.1183, found 445.1179.EXAMPLE 8: Preparation of 8: 2-(4-((2-fluoro-n ,1'-biphenyl1-4-yl)methylene)tetrahydrofuran-2- yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0101] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.138 mmol) and 4-bromo-2-fluoro-1 ,1’-biphenyl (38 mg, 0.152 mmol, 1.1 eq.). Purification was performed by reverse phase column chromatography (water / MeCN), 0- 100%) to afford 8 (11 mg, 44 / 56 ratio E / Z according to1H NMR) as an off-white powder. Yield: 19%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.59 - 7.53 (m, 4H), 7.48 - 7.41 (m, 6H), 7.41 - 7.35 (m, 2H), 7.16-7.06 (m, 2H), 7.01-6.87 (m, 2H), 6.52 (t, J =2.4 Hz, 1H), 6.44 (t, J=2.4Hz, 1H), 5.32 (dd, J = 7.6, 5.9 Hz, 1 H), 5.23 (dd, J = 7.5, 5.9 Hz, 1 H), 4.92 - 4.64 (m, 4H), 3.88 (s, 3H), 3.85 (s, 3H), 3.29 - 2.97 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.85 (s, 3H), 1.84 (s, 3H).13C NMR (101 MHz, CDCh) <5 (ppm) 180.7, 180.7, 162.3, 162.2, 161.1 (d, J= 248.0 Hz), 158.6 (d, J = 248.0 Hz), 155.1, 154.8, 141.5, 140.9, 138.2 (d, J= 7.9 Hz), 138.0 (d, J= 8.1 Hz), 135.4 (d, J= 1.4 Hz), 135.4 (d, J= 1.4 Hz), 131.0 (d, J = 4.2 Hz), 130.9 (d, J = 4.4 Hz), 129.0 (2C), 129.0 (2C), 128.7 (2C), 128.7 (2C), 128.0, 128.0, 127.8 (d, J= 13.6 Hz), 127.6 (d, J= 13.6 Hz), 124.3 (d, J = 3.2 Hz), 124.0 (d, J = 3.2 Hz), 120.6 (d, J = 2.2 Hz), 120.3, 120.1, 119.4 (d, J = 2.3 Hz), 115.5 (d, J = 23.7 Hz), 115.2 (d, J= 23.7 Hz), 100.13, 100.13, 75.8, 73.7, 73.5, 70.4, 55.4 (2C), 38.3, 34.5, 9.6, 9.6, 7.1, 7.0. LC-MS: Rt= 8.97 min, ES+= 407.21, method 2. HR-MS (El; LCT): [M+Na]+calculated for C2sH23C>4NaF 429.1478, found 429.1467.EXAMPLE 9: Preparation of 9: 2-(4-((4'-Fluoro-f1,T-biphenyl1-4-yl)methylene)tetrahydrofuran-2- yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0102] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.121 mmol) and 4-bromo-4’-fluoro-1,1’-biphenyl (32 mg, 0.128 mmol, 1.05 eq.). Purification was performed by reverse phase column chromatography (water / MeCN, 0 - 100%) to afford 9 (7 mg, 1:1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 13%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.58-7.52 (m, 8H), 7.38-7.33 (m, 2H), 7.20-7.17 (m, 2H), 7.16-7.10 (m, 4H), 6.56 (p, J = 2.4 Hz, 1H), 6.47 (p, J= 2.3 Hz, 1H), 5.32 (dd, J =7.7, 5.8 Hz, 1H), 5.22 (dd, J= 7.6, 5.8 Hz, 1H), 4.94-4.64 (m, 4H), 3.87 (s, 3H), 3.83 (s, 3H), 3.27-2.97 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.8, 180.8, 162.7 (d, J= 247.2 Hz), 162.7 (d, J= 247.2 Hz), 162.3, 162.2, 155.3, 155.1, 140.1, 139.6, 139.0, 138.9, 136.7 (d, J= 3.2 Hz), 136.6 (d, J= 3.2 Hz), 136.1, 135.9, 128.7 (4C), 128.6 (d, J= 1.2 Hz, 2C), 128.5 (2C), 127.3 (2C), 127.2 (2C), 121.5, 120.2, 120.1, 120.0, 116.0 (2C), 115.8 (2C), 100.1, 100.1, 75.8, 73.8, 73.5, 70.5, 55.4 (2C), 38.3, 34.5, 9.6, 9.6, 7.1, 7.0.19F NMR(376 MHz, CDCI3) 5 (ppm) -115.54. LC-MS: Rt= 9.11 min, ES+= 407.26, method 2. HR-MS (El;LCT): [M+Na]+calculated for C25H23O4FNa 429.1478, found 429.1479.EXAMPLE 10: Preparation of 10: 2-(4-((4'-(tert-butyl)-ri,1'-biphenyl1-4- yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0103] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.126 mmol) and 4-bromo-4’-tert-butyl-1 ,T-biphenyl (44 mg, 0.151 mmol, 1.2 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water / MeCN, 0 - 100%) to afford 10 (14 mg, 69:100 ratio E / Z according to1H NMR) as an off-white powder. Yield: 24%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.65 - 7.54 (m, 8H), 7.53 - 7.48 (m, 4H), 7.41 - 7.36 (m, 2H), 7.23 - 7.18 (m, 2H), 6.58 (t, J = 2.4 Hz, 1 H), 6.50 (d, J = 2.4 Hz, 1 H), 5.35 (dd, J = 7.7, 5.8 Hz, 1 H), 5.25 (dd, J = 7.6, 5.6 Hz, 1 H), 4.96 - 4.66 (m, 4H), 3.89 (s, 3H), 3.85 (s, 3H), 3.32 - 2.99 (m, 4H), 2.07 (s, 3H), 2.07 (s, 3H), 1.87 (s, 3H), 1.86 (s, 3H), 1.39 (s, 9H), 1.39 (s, 9H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.9, 180.8, 162.4, 162.3, 155.5, 155.2, 150.74, 150.71 , 139.8, 139.7, 139.6, 139.2, 137.6, 137.5, 135.8, 135.6, 128.6 (2C), 128.4 (2C), 127.3 (2C), 127.2 (2C), 126.7 (2C), 126.7 (2C), 126.0 (2C), 126.0 (2C), 121.6, 120.3, 120.1 , 119.9, 100.1 (2C), 75.8, 73.8, 73.4, 70.5, 55.4 (2C), 38.4, 34.7 (2C), 34.5, 31.5 (3C), 31.5 (3C), 9.6, 9.6, 7.05, 7.0, 7.0. LC-MS: Rt= 9.65 min, ES+= 445.26, method 2. HR-MS (El; LCT): [M+Na]+calculated for C29H32O4Na 467.2198, found 467.2179.EXAMPLE 11: Preparation of 11 : 2-(4-((4'-(methyl)-f1 ,T-biphenyl1-4- yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0104] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.126 mmol) and 4-bromo-4’-methyl-1 ,1’-biphenyl (37 mg, 0.151 mmol, 1.2 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5- 100%) and reverse phase column chromatography (water / MeCN, 0 - 100%) to afford 11 (17 mg, 67:33 ratio E / Z according to1H NMR) as an off-white powder. Yield: 31 %.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.65 - 7.57 (m, 4H), 7.56 - 7.48 (m, 4H), 7.37 (d, J = 8.2 Hz, 2H), 7.30 - 7.24 (m, 4H), 7.20 (d, J = 8.2 Hz, 2H), 6.58 (p, J = 2.3 Hz, 1 H), 6.50 (p, J = 2.3 Hz, 1 H), 5.34 (dd, J = 7.7, 5.7 Hz, 1 H), 5.25 (dd, J = 7.6, 5.7 Hz, 1 H), 4.95 - 4.65 (m, 4H), 3.89 (s, 3H), 3.85 (s, 3H), 3.30 - 2.98 (m, 4H), 2.42 (s, 6H), 2.07 (s, 3H), 2.07 (s, 3H), 1.88 (s, 3H), 1.87 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8, 180.8, 162.3, 162.3, 155.4, 155.1 , 139.9, 139.8, 139.7, 139.2, 137.6, 137.6, 137.5, 137.5, 135.7, 135.6, 129.7 (2C), 129.7 (2C), 128.6 (2C), 128.4 (2C), 127.2 (2C), 127.1 (2C), 126.9 (2C), 126.9 (2C), 121.6, 120.3, 120.1 , 119.9, 100.0 (2C), 75.7, 73.8, 73.4, 70.5, 55.4, 55.4, 38.3, 34.4, 21.2 (2C), 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 9.11 min, ES+= 403.25, method 2. HR-MS (El; LCT): [M+Na]+calculated for C26H26O4Na 425.1729, found 425.1734.EXAMPLE 12: Preparation of 12: 4'-((5-(6-methoxy-3,5-dimethyl-4-oxo-4 / 7-pyran-2- yl)dihydrofuran-3(2 / - / )-ylidene)methyl)-f 1 , 1 '-biphenyll-4-carbonitrile

[0105] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (50 mg, 0.126 mmol) and 4'-bromo-[1 ,T-biphenyl]-4-carbonitrile (30 mg, 0.119 mmol, 0.95 eq.). The crude was concentrated in vacuo and extracted twice with EtOAc. The combined organic phases were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo. Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford 12 (24 mg, 56:44 ratio E / Z according to1H NMR) as an off-white powder. Yield: 45%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.74 - 7.66 (m, 8H), 7.62 - 7.57 (m, 4H), 7.43 - 7.38 (m, 2H), 7.25 - 7.21 (m, 2H), 6.57 (p, J = 2.4 Hz, 1 H), 6.48 (p, J = 2.4 Hz, 1 H), 5.32 (dd, J = 7.6, 5.9 Hz, 1 H), 5.22 (dd, J = 7.5, 5.9 Hz, 1 H), 4.92 - 4.64 (m, 4H), 3.87 (s, 3H), 3.83 (s, 3H), 3.27 - 2.98 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 155.1 , 154.9, 145.0, 144.9, 141.1 , 140.6, 137.7, 137.6, 137.5, 137.3, 132.8 (4C), 128.9 (2C), 128.6 (2C) 127.6 (2C), 127.6 (2C), 127.6 (2C), 127.5 (2C), 121.2, 120.15 (2C), 120.12, 119.9, 119.0, 111.1 , 111.1 , 100.1 , 100.1 , 75.7, 73.7, 73.5, 70.5, 55.4 (2C), 38.3, 34.5, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.69 min, ES+= 414.23, method 2. HR-MS (El; LCT): [M+Na]+calculated for C2eH23NO4Na 436.1525, found 436.1532.EXAMPLE 13: Preparation of 13: 2-methoxy-6-(4-((4'-methoxy-n ,T-biphenyl1-4- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0106] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (56 mg, 0.141 mmol) and 4-bromo-4'-methoxy-1 ,1'-biphenyl (35 mg, 0.134 mmol, 0.95 eq.). The crude was concentrated in vacuo and extracted twice with EtOAc. The combined organic phases were dried (Na2SC>4), filtered, and the filtrate was concentrated in vacuo. Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (Water / MeCN, 5-100%) to afford 13 (14 mg, 52:48 ratio E / Z according to1H NMR) as an off-white powder. Yield: 22%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.57 - 7.52 (m, 8H), 7.34 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.00 - 6.96 (m, 4H), 6.54 (t, J = 2.4 Hz, 1 H), 6.46 (t, J = 2.4 Hz, 1 H), 5.32 (dd, J = 7.5, 5.8 Hz, 1 H), 5.22 (dd, J = 7.5, 5.8 Hz, 1 H), 4.91 - 4.65 (m, 4H), 3.86 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H), 3.82 (s, 3H), 3.26 - 2.97 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) 6 (ppm)180.8, 180.8, 162.3, 162.3, 159.5, 159.4, 155.4, 155.2, 139.6, 139.5, 139.5, 139.0, 135.4, 135.3, 133.0, 133.0, 128.6 (2C), 128.4 (2C), 128.1 (2C), 128.1 (2C), 127.0 (2C), 126.9 (2C), 121.6, 120.3, 120.1, 119.9, 114.4 (2C), 114.4 (2C), 100.0 (2C), 75.7, 73.8, 73.4, 70.5, 55.5 (2C), 55.4 (2C), 38.3, 34.4, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 9.00 min, ES+= 419.24, method 2. HR-MS (El; LCT): [M+Na]+calculated for C26H26O5Na 441.1678, found 441.1669.EXAMPLE 14: Preparation of 14: 2-methoxy-3,5-dimethyl-6-(4-((4'-(trifluoromethoxy)-n,1'- biphenyl1-4-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-oneStep 1 : Preparation of 4-bromo-4’-(trifluoromethoxy)-1 ,1’-biphenyl

[0107] Prepared according to general procedure B using 4-bromoiodobenzene (150 mg, 0.53 mmol), (4-(trifluoromethoxy)phenyl)boronic acid (120 mg, 0.758 mmol, 1.1 eq.), Pd(dppf)CI2«DCM (43 mg, 0.053 mmol, 0.10 eq.), and K3PO4 (338 mg, 1.59 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 100%) to afford the title compound (104 mg) as a white film. Yield: 61%.1H NMR (400 MHz, CDCI3) 6 (ppm) 7.60 - 7.54 (m, 4H), 7.44 - 7.40 (m, 2H), 7.32 - 7.27 (m, 2H).13C NMR (101 MHz, CDCI3) 5 (ppm) 149.1, 138.9, 132.2, 128.8, 128.6 (d, J = 2.2 Hz), 128.5, 122.2, 121.5 (q, J = 1.0 Hz), 120.6 (q, J = 257.3 Hz). Spectroscopic data are in agreement with those reported in literature.10Step 2: Preparation of 2-methoxy-3,5-dimethyl-6-(4-((4'-(trifluoromethoxy)-[1 , 1 '-biphenyl]-4- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0108] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.121 mmol) and 4-bromo-4’-(trifluoromethoxy)-1,1’-biphenyl (40 mg, 0.128 mmol, 1.05 eq.). Purification was performed by normal phase column chromatography(PE / EtOAc, 5-100%) and reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford 14 (20 mg, 1 :1 ratio E / Z according to1H NMR) as a colorless oil. Yield: 33%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.62 - 7.54 (m, 8H), 7.37 (d, J = 8.2 Hz, 2H), 7.31 - 7.27 (m, 4H), 7.20 (d, J = 8.2 Hz, 2H), 6.56 (p, J = 2.3 Hz, 1 H), 6.48 (p, J = 2.3 Hz, 1 H), 5.32 (dd, J = 7.7, 5.8 Hz, 1 H), 5.22 (dd, J = 7.6, 5.8 Hz, 1 H), 4.92 - 4.64 (m, 4H), 3.87 (s, 3H), 3.83 (s, 3H), 3.28 - 2.97 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 155.2, 155.0, 148.9 (2C), 140.4, 139.8, 139.3, 139.2, 138.5, 138.4, 136.5, 136.3, 128.7 (2C), 128.5 (2C), 128.4 (2C), 128.4 (2C), 127.4 (2C), 127.3 (2C), 121.4 (4C), 121.4, 120.6 (q, = 257.1 Hz, 2C), 120.1 , 120.1 , 120.0, 100.1 (2C), 75.8, 73.7, 73.5, 70.5, 55.4 (2C), 38.3, 34.5, 9.6, 9.6, 7.0, 7.0.19F NMR (376 MHz, CDCI3) 6 (ppm) -58.1. LC-MS: Rt = 4.30 min, ES+= 473.32, method 1.EXAMPLE 15: Preparation of 15: 2-(4-((2',4'-difluoro-f1 ,T-biphenyl1-4- yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 4’-bromo-2,4-difluoro-1 ,1'-biphenyl

[0109] Prepared according to general procedure B using 4-bromoiodobenzene (200 mg, 0.707 mmol), (2,4-difluorophenyl)boronic acid (123 mg, 0.778 mmol, 1.1 eq.), Pd(dppf)Cl2*DCM) (58 mg, 0.071 mmol, 0.10 eq.), and K2CO3 (293 mg, 2.12 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 5%) to afford the title compound (130 mg) as an off-white solid. Yield: 58%.1H NMR (400 MHz, DMSO-cfe) 5 (ppm) 7.69 - 7.65 (m, 2H), 7.59 (td, J = 8.9, 6.6 Hz, 1 H), 7.51 - 7.45 (m, 2H), 7.41 - 7.33 (m, 1 H), 7.20 (tdd, J = 8.5, 2.7, 1.0 Hz, 1 H).13C NMR (101 MHz, DMSO-cfe) 5 (ppm) 162.0 (dd, J = 247.4, 12.3 Hz), 159.0 (dd, J = 248.9, 12.3 Hz), 133.5 (d, J = 1.4 Hz), 131.9 (dd, J = 9.7, 4.6 Hz), 131.7, 130.9 (d, J = 3.0 Hz), 123.7 (dd, J = 13.2, 3.9 Hz), 121.5, 112.3 (dd, J = 21.3, 3.8 Hz), 104.7 (dd, J = 27.1 , 25.7 Hz).19F NMR (376 MHz, CDCI3) 6 (ppm) -110.91 , -113.63.Step 2: Preparation of 2-(4-((2',4'-difluoro-[1 , 1 '-biphenyl]-4-yl)methylene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0110] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.126 mmol) and 4’-bromo-2,4-difluoro-1 ,1'-biphenyl (41 mg, 0.128 mmol, 1.05 eq.). The crude was concentrated in vacuo and extracted twice with EtOAc. The combined organic phases were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo. Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (Water / MeCN, 5-100%) to afford 15 (5 mg, 1 :1 ratio E / Z according to1H NMR) as a colorless oil. Yield: 10%.1H NMR (400 MHz, CDCI3) <5 (ppm) 7.52 - 7.49 (m, 4H), 7.43 - 7.39 (m, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 6.99 - 6.89 (m, 4H), 6.56 (t, J = 2.4 Hz, 1 H), 6.48 (t, J = 2.4 Hz, 1 H), 5.32 (dd, J = 7.7, 5.8 Hz, 1 H), 5.22 (dd, J = 7.6, 5.8 Hz, 1 H), 4.91 - 4.64 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.26 - 2.98 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8, 180.8, 162.5 (dd, J = 249.7, 11.6 Hz, 2C), 162.3, 162.3, 159.9 (dd, J = 250.1 , 11.7 Hz, 2C), 155.3, 155.0, 140.4, 139.9, 136.5, 136.3, 133.8 (dd, J= 12.1 , 1.1 Hz, 2C), 131.4 (dd, J = 9.4, 4.8 Hz, 2C), 129.3 (dd, J = 12.7, 3.2 Hz, 4C), 128.3 (2C), 128.1 (2C), 124.8 (ddd, J = 13.4, 7.9, 4.0 Hz, 2C), 121.5,120.2, 120.0 (2C), 111.8 (dd, J = 21.2, 3.9, 2C), 104.6 (dd, J = 26.9, 25.1 , 2C), 100.1 , 100.1 , 75.8, 73.8, 73.5, 70.5, 55.4, 55.4, 38.3, 34.5, 9.6, 9.6, 7.1 , 7.0.19F NMR (376 MHz, CDCI3) 5 (ppm) -111.3, -113.7. LC-MS: Rt= 9.10 min, ES+= 425.19, method 2. HR-MS (El; LCT) [M+Na]+calculated for C2sH22C>4NaF2 447.1384, found 447.1379.EXAMPLE 16: Preparation of 16: 2-methoxy-3,5-dimethyl-6-(4-(4-(pyridin-3- yl)benzylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-oneStep 1 : Preparation of 3-(4-bromophenyl)pyridine

[0111] Prepared according to general procedure B using 4-bromoiodobenzene (150 mg, 0.53 mmol), 3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridine (120 mg, 0.58 mmol, 1.1 eq.), Pd(dppf)Cl2*DCM) (43 mg, 0.053 mmol, 0.10 eq.), and K3PO4 (338 mg, 1.59 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (75 mg) as an off-white solid. Yield: 54%.1H NMR (400 MHz, CDCI3) 6 (ppm) 8.80 (s, 1 H), 8.63 - 8.57 (m, 1 H), 7.82 (d, J = 7.9 Hz, 1 H), 7.61 - 7.56 (m, 2H), 7.45 - 7.40 (m, 2H), 7.36 (dd, J = 7.9, 4.6 Hz, 1 H).13C NMR (101 MHz, CDCI3) 6 (ppm) 148.9, 148.1 , 136.8, 135.7, 134.3, 132.3, 128.8, 123.8, 122.7. Spectroscopic data are in agreement with those reported in literature.11Step 2: Preparation of 2-methoxy-3,5-dimethyl-6-(4-(4-(pyridin-3-yl)benzylidene)tetrahydrofuran- 2-yl)-4 / 7-pyran-4-one

[0112] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.121 mmol) and 3-(4-bromophenyl)pyridine (39 mg, 0.121 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0- 10%) and reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5- 100%) to afford 16 (16 mg, 1 :1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 33%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.88 - 8.83 (m, 2H), 8.58 (d, J = 4.8 Hz, 2H), 7.91 - 7.84 (m, 2H), 7.61 - 7.56 (m, 4H), 7.42 - 7.35 (m, 4H), 7.25 - 7.20 (m, 2H), 6.56 (p, J = 2.4 Hz, 1 H), 6.48 (p, J = 2.4 Hz, 1 H), 5.31 (dd, J = 7.6, 5.8 Hz, 1 H), 5.22 (dd, J = 7.6, 5.8 Hz, 1 H), 4.92 - 4.63 (m, 4H), 3.86 (s, 3H), 3.82 (s, 3H), 3.27 - 2.97 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 180.7, 162.2, 162.2, 155.2, 155.0, 148.6, 148.6, 148.2, 148.1 , 140.7, 140.2, 136.9, 136.7, 136.5, 136.3, 136.1 , 136.0, 134.3, 134.3, 128.9 (2C), 128.6 (2C), 127.4 (2C), 127.4 (2C), 123.8 (2C), 121.3, 120.1 , 120.0, 120.0, 100.1 , 100.0, 75.7, 73.7, 73.5, 70.5, 55.4, 55.4, 38.3, 34.5, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 6.76 min, ES+= 390.24, method 2. HR-MS (El; LCT) [M+H]+calculated for C24H24NO4 390.1705, found 390.1689.EXAMPLE 17: Preparation of 17: 2-methoxy-3,5-dimethyl-6-(4-(4-(pyridin-4- yl)benzylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-oneStep 1 : Preparation of 4-(4-bromophenyl)pyridine

[0113] Prepared according to general procedure B using 4-bromoiodobenzene (150 mg, 0.53 mmol), 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridine (120 mg, 0.58 mmol, 1.1 eq.), Pd(dppf)Cl2*DCM) (43 mg, 0.053 mmol, 0.10 eq.), and K3PO4 (338 mg, 1.59 mmol, 3.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (65 mg) as an off-white solid. Yield: 47%.1H NMR (400 MHz, CDCI3) 6 (ppm) 8.70 - 8.63 (m, 2H), 7.63 - 7.58 (m, 2H), 7.51 - 7.44 (m, 4H).13C NMR (101 MHz, CDCI3) 5 (ppm) 150.4, 147.4, 137.1 , 132.4, 128.7, 123.8, 121.5. Spectroscopic data are in agreement with those reported in literature.12Step 2: Preparation of 2-methoxy-3,5-dimethyl-6-(4-(4-(pyridin-4-yl)benzylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0114] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.121 mmol) and 4-(4-bromophenyl)pyridine (39 mg, 0.121 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0- 10%) and reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5- 100%) to afford 17 (14 mg, 1 :1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 27%.1H NMR (400 MHz, CDCI3) 6 (ppm) 8.68 - 8.60 (m, 4H), 7.67 - 7.62 (m, 4H), 7.53 - 7.48 (m, 4H), 7.43 - 7.38 (m, 2H), 7.25 - 7.21 (m, 2H), 6.56 (p, J = 2.4 Hz, 1 H), 6.48 (p, J = 2.4 Hz, 1 H), 5.31 (dd, J = 7.6, 5.9 Hz, 1 H), 5.22 (dd, J = 7.6, 5.9 Hz, 1 H), 4.92 - 4.63 (m, 4H), 3.86 (s, 3H), 3.82 (s, 3H), 3.27 - 2.98 (m, 4H), 2.03 (s, 3H), 2.02 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHZ, CDCI3) 5 (ppm) 180.7, 180.7, 162.2, 162.2, 155.1 , 154.9, 150.3 (4C), 147.7, 147.7, 141.2, 140.7, 137.9, 137.7, 136.7, 136.5, 128.9 (2C), 128.6 (2C), 127.4 (2C), 127.3 (2C), 121.5 (4C), 121.2, 120.2, 120.1 , 119.9, 100.1 , 100.1 , 75.7, 73.7, 73.5, 70.5, 55.4, 55.4, 38.3, 34.5, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 6.26 min, ES+= 390.23, method 2. HR-MS (El; LCT) [M+H]+calculated for C24H24NO4 390.1705, found 390.1707.Example 18: Preparation of 18: 2-methoxy-3,5-dimethyl-6-(4-((6-phenylpyridin-3- yl)methylene)tetrahydrofuran-2-yl)-4H-pyran-4-oneStep 1 : Preparation of 5-bromo-2-phenylpyridine

[0115] Prepared according to general procedure B using phenylboronic acid (183 mg, 1.50 mmol), 5-bromo-2-iodopyridine (511 mg, 1.80 mmol, 1.2 eq.), Pd(dppf)Cl2*DCM (123 mg, 0.150 mmol, 0.15 eq.), and K2CO3 (415 mg, 3.00 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (250 mg) as a white powder. Yield: 65%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.76 - 8.72 (m, 1 H), 7.98 - 7.94 (m, 2H), 7.87 (dd, J = 8.5, 2.4 Hz, 1 H), 7.63 (dd, J = 8.5, 0.8 Hz, 1 H), 7.52 - 7.40 (m, 3H).13C NMR (101 MHz, CDCI3) 6 (ppm) 156.1 , 150.8, 139.5, 138.4, 129.5, 129.0, 126.9, 121.8, 119.5. Spectroscopic data are in agreement with those reported in literature.13Step 2: preparation of 2-methoxy-3,5-dimethyl-6-(4-((6-phenylpyridin-3- yl)methylene)tetrahydrofuran-2-yl)-4H-pyran-4-one

[0116] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.125 mmol) and 5-bromo-2-phenylpyridine (32 mg, 0.125 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0 - 100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA,5-100%) to afford the title compound (17 mg, 1 :1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 33%.1H NMR (400 MHz, CDCI3) <5 (ppm) 8.64 (d, J = 2.3 Hz, 1 H), 8.50 (d, J = 2.3 Hz, 1 H), 8.02 - 7.98 (m, 4H), 7.76 - 7.72 (m, 2H), 7.70 - 7.65 (m, 1 H), 7.51 - 7.45 (m, 5H), 7.45 - 7.40 (m, 2H), 6.54 (p, J = 2.5 Hz, 1 H), 6.45 (p, J = 2.3 Hz, 1 H), 5.32 (dd, J = 7.6, 6.0 Hz, 1 H), 5.23 (dd, J = 7.5, 6.0 Hz, 1 H), 4.92 - 4.64 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.27 - 3.00 (m, 4H), 2.04 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 180.7, 162.2, 162.2, 155.7, 155.6, 154.9, 154.6, 149.5, 149.2, 142.3, 141.8, 138.8, 138.7, 135.5, 135.4, 131.2, 131.0, 129.3, 129.3, 129.0, 129.0, 126.9, 126.9, 120.4, 120.3, 120.2, 120.2, 118.3, 117.1 , 100.2, 100.2, 75.8, 73.7, 73.6, 70.5, 55.4, 55.4, 38.3, 34.4, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 6.57 min, ES+= 390.21 , method 2. HR-MS: [M+H]+calculated for C24H24NO4 390.1705; found 390.1702.EXAMPLE 19: Preparation of 19: 2-methoxy-6-(4-((6-(4-methoxyphenyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 5-bromo-2-(4-methoxyphenyl)pyridine

[0117] Prepared according to general procedure B using 4-methoxyphenylboronic acid (228 mg, 1.50 mmol), 5-bromo-2-iodopyridine (511 mg, 1.80 mmol, 1.2 eq.), Pd(dppf)Cl2*DCM (123 mg, 0.150 mmol, 0.15 eq.), and K2CO3 (415 mg, 3.00 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (240 mg) as a white powder. Yield: 59%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.71 - 8.66 (m, 1 H), 7.95 - 7.88 (m, 2H), 7.81 (dd, J = 8.5, 2.4 Hz, 1 H), 7.55 (dd, J = 8.5, 0.6 Hz, 1 H), 7.03 - 6.95 (m, 2H), 3.86 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 160.9, 155.7, 150.6, 139.3, 130.9, 128.2, 121.0, 118.5, 114.4, 55.5. Spectroscopic data are in agreement with those reported in literature.14Step 2: Preparation of 2-methoxy-6-(4-((6-(4-methoxyphenyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0118] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.125 mmol) and 5-bromo-2-(4-methoxyphenyl)pyridine (34 mg, 0.125 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (12 mg, 1 :1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 21 %.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.61 (d, J = 2.3 Hz, 1 H), 8.48 (d, J = 2.3 Hz, 1 H), 8.00 - 7.96 (m, 4H), 7.72 - 7.64 (m, 3H), 7.47 (dd, J = 8.4, 2.4 Hz, 1 H), 7.04 - 7.00 (m, 4H), 6.53 (p, J = 2.3 Hz, 1 H), 6.46 (p, J = 2.3 Hz, 1 H), 5.34 (dd, J = 7.6, 6.0 Hz, 1 H), 5.25 (dd, J = 7.6, 6.0 Hz, 1 H), 4.94 - 4.66 (m, 4H), 3.89 (s, 6H), 3.88 (s, 3H), 3.86 (s, 3H), 3.29 - 3.02 (m, 4H), 2.06 (s, 3H), 2.06 (s, 3H), 1.86 (s, 3H), 1.85 (s, 3H).13C NMR (101 MHz, CDCI3) <5 (ppm) 180.7, 180.7, 162.3, 162.2, 160.8, 160.8, 155.4, 155.3, 155.0, 154.7, 149.3, 149.0, 141.8, 141.3, 135.5, 135.3, 131.4, 131.4, 130.5, 130.3, 128.2 (4C), 120.3, 120.1 , 119.6, 119.5, 118.4, 117.2, 114.4 (2C), 114.4 (2C), 100.2, 100.2, 75.8, 73.7, 73.6, 70.5, 55.5 (2C), 55.4, 55.4, 38.3, 34.4, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 7.34 min, ES+= 420.25, method 2. HRMS: [M+Na]+calculated for C2sH25NOsNa 442.1630; found 442.1649.EXAMPLE 20: Preparation of 20: 2-methoxy-6-(4-((6-(3-methoxyphenyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / - / -pyran-4-oneStep 1 : Preparation of 5-bromo-2-(3-methoxyphenyl)pyridine

[0119] Prepared according to general procedure B using 3-methoxyphenylboronic acid (228 mg, 1.50 mmol), 5-bromo-2-iodopyridine (511 mg, 1.80 mmol, 1.2 eq.), Pd(dppf)Cl2*DCM (123 mg, 0.150 mmol, 0.15 eq.), and K2CO3 (415 mg, 3.00 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the titlecompound (272 mg) as a white powder. Yield: 67%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.73 (dd, J = 2.4, 0.7 Hz, 1 H), 7.86 (dd, J = 8.5, 2.4 Hz, 1 H), 7.61 (dd, J = 8.5, 0.8 Hz, 1 H), 7.55 (dd, J = 2.6, 1 .6 Hz, 1 H), 7.52 - 7.49 (m, 1 H), 7.38 (t, J = 7.9 Hz, 1 H), 7.02 - 6.96 (m, 1 H), 3.89 (s, 3H).13C NMR (101 MHZ, CDCI3) <5 (ppm) 160.3, 155.8, 150.7, 139.8, 139.4, 130.0, 121.9, 119.6, 119.3, 115.5, 112.1 , 55.5. Spectroscopic data are in agreement with those reported in literature.15Step 2: Preparation of 2-methoxy-6-(4-((6-(3-methoxyphenyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0120] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.125 mmol) and 5-bromo-2-(3-methoxyphenyl)pyridine (34 mg, 0.125 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (22 mg, 1 :1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 38%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.63 (d, J = 2.2 Hz, 1 H), 8.49 (d, J = 2.3 Hz, 1 H), 7.74 - 7.70 (m, 2H), 7.69 - 7.65 (m, 1 H), 7.61 - 7.58 (m, 2H), 7.57 - 7.52 (m, 2H), 7.47 (dd, J = 8.3, 2.4 Hz, 1 H), 7.38 (td, J = 8.0, 1.9 Hz, 2H), 6.99 - 6.94 (m, 2H), 6.53 (p, J = 2.5 Hz, 1 H), 6.45 (p, J = 2.3 Hz, 1 H), 5.31 (dd, J = 7.6, 6.0 Hz, 1 H), 5.22 (dd, J = 7.5, 6.0 Hz, 1 H), 4.91 - 4.64 (m, 4H), 3.89 (s, 3H), 3.88 (s, 3H), 3.86 (s, 3H), 3.83 (s, 3H), 3.26 - 2.99 (m, 4H), 2.03 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 160.3, 160.3, 155.5, 155.4, 154.9, 154.7, 149.4, 149.1 , 142.4, 141.8, 140.3, 140.2, 135.5, 135.3, 131.3, 131.1 , 130.0, 129.9, 120.5, 120.4, 120.4, 120.2, 119.3 (2C), 118.2, 117.1 , 115.4, 115.3, 112.1 , 112.0, 100.2, 100.2, 75.8, 73.6, 73.6, 70.5, 55.5, 55.5, 55.4, 55.4, 38.3, 34.5, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 7.83 min, ES+= 420.23, method 2. HRMS: [M+Na]+calculated for C25H25NO5Na 442.1630; found 442.1638.EXAMPLE 21 : Preparation of 21 : 2-methoxy-3,5-dimethyl-6-(4-((6-(p-tolyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-oneStep 1 : Preparation of 5-bromo-2-(p-tolyl)pyridine

[0121] Prepared according to general procedure B using p-tolylboronic acid (204 mg, 1 .50 mmol), 5-bromo-2-iodopyridine (511 mg, 1.80 mmol, 1.2 eq.), Pd(dppf)Ch’DCM (123 mg, 0.150 mmol, 0.15 eq.), and K2CO3 (415 mg, 3.00 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (310 mg) as a white powder. Yield: 67%.1H NMR (400 MHz, CDCh) 5 (ppm) 8.74 - 8.69 (m, 1 H), 7.89 - 7.82 (m, 3H), 7.60 (dt, J = 8.5, 1.0 Hz, 1 H), 7.31 - 7.25 (m, 2H), 2.41 (s, 3H).13C NMR (101 MHz, CDCh) <5 (ppm) 156.0, 150.6, 139.5, 139.2, 135.5, 129.6, 126.6, 121.4, 118.9, 21.3. Spectroscopic data are in agreement with those reported in literature.16Step 2: Preparation of 2-methoxy-3,5-dimethyl-6-(4-((6-(p-tolyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0122] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (58 mg, 0.120 mmol) and 5-bromo-2-(p-tolyl)pyridine (37 mg, 0.2120 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (9 mg, 10:9 ratio E / Z according to1H NMR) as an off-white film. Yield: 16%.1H NMR (400 MHz, CDCh) 5 (ppm) 8.62 (d, J = 2.2 Hz, 1 H), 8.49 (d, J = 2.4 Hz, 1 H), 7.93 - 7.87 (m, 4H), 7.74 - 7.63 (m, 3H), 7.49 - 7.45 (m, 1 H), 7.31 - 7.28 (m, 4H), 6.53 (p, J = 2.3 Hz, 1 H), 6.45 (p, J = 2.4 Hz, 1 H), 5.32 (dd, J = 7.6, 6.0 Hz, 1 H), 5.24 (dd, J = 7.5, 6.0 Hz, 1 H), 4.92 - 4.64 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.27 - 3.01 (m, 4H), 2.41 (s, 6H), 2.05 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.84 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.7 (2C), 162.3, 162.2, 155.8, 155.7, 155.0, 154.7, 149.4, 149.1 , 142.1 , 141.5, 139.5, 139.4, 136.0, 136.0, 135.5, 135.4, 130.9, 130.7, 129.8 (2C), 129.7 (2C), 126.8 (2C), 126.8 (2C), 120.4, 120.2, 120.0, 120.0, 118.4, 117.2, 100.2, 100.2, 75.8, 73.7, 73.6, 70.5, 55.4, 55.4, 38.4, 34.5, 21.5 (2C), 9.6,9.6, 7.1 , 7.1. LC-MS: Rt= 7.78 min, ES+= 404.25, method 2. HRMS: [M+Na]+calculated for C25H25NO4Na 426.1681 ; found 426.1674.EXAMPLE 22: Preparation of 22: 2-(4-((6-(3-fluorophenyl)pyridin-3-yl)methylene)tetrahvdrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 5-bromo-2-(3-fluorophenyl)pyridine

[0123] Prepared according to general procedure B using (3-fluorophenyl)boronic acid (210 mg, 1.50 mmol), 5-bromo-2-iodopyridine (511 mg, 1.80 mmol, 1.2 eq.), Pd(dppf)CI2*DCM (123 mg, 0.150 mmol, 0.15 eq.), and K2CO3 (415 mg, 3.00 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (218 mg) as a white powder. Yield: 55%.1H NMR (400 MHz, CDCI3) 6 (ppm) 8.73 (dd, J = 2.4, 0.8 Hz, 1 H), 7.87 (dd, J = 8.5, 2.4 Hz, 1 H), 7.75 - 7.68 (m, 2H), 7.60 (dd, J = 8.5, 0.8 Hz, 1 H), 7.46 - 7.39 (m, 1 H), 7.12 (dddd, J = 9.2, 8.3, 2.6, 1.0 Hz, 1 H).13C NMR (101 MHz, CDCI3) 5 (ppm) 163.5 (d, J = 246.0 Hz), 154.6 (d, J = 2.8 Hz), 150.9, 140.6 (d, J = 7.7 Hz), 139.6, 130.5 (d, J = 8.1 Hz), 122.4 (d, J = 2.8 Hz), 121.7, 120.0, 116.3 (d, J = 21.3 Hz), 113.9 (d, J = 23.0 Hz).19F NMR (376 MHz, CDCI3) 5 (ppm) -112.73 - -112.82 (m). LC-MS: Rt= 7.46 min, ES+= 252.04, 254.03, method 2. HRMS: [M+H]+calculated for CnH8NBrF 251.9824; found 251.9833.Step 2: Preparation of 2-(4-((6-(3-fluorophenyl)pyridin-3-yl)methylene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0124] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (80 mg, 0.166 mmol) and 5-bromo-2-(3-fluorophenyl)pyridine (44 mg, 0.166 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) and consecutive reverse phase column chromatography (Water+0.05%TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (24 mg, 10:8 ratio E / Z according to1H NMR) as an off-white film. Yield: 30%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.64 (d, J = 2.2 Hz, 1 H), 8.51 (d, J = 2.3 Hz, 1 H), 7.80 - 7.67 (m, 7H), 7.51 - 7.40 (m, 3H), 7.14 - 7.08 (m, 2H), 6.54 (p, J = 2.4 Hz, 1 H), 6.46 (p, J = 2.4 Hz, 1 H), 5.32 (dd, J = 7.5, 6.1 Hz, 1 H), 5.23 (dd, J = 7.5, 6.1 Hz, 1 H), 4.93 - 4.65 (m, 4H), 3.88 (s, 3H), 3.85 (s, 3H), 3.27 - 3.01 (m, 4H), 2.04 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.6, 180.6, 163.4 (d, J = 245.8 Hz), 163.4 (d, J = 245.2 Hz), 162.1 , 162.1 , 154.7, 154.5, 154.2 (d, J = 2.8 Hz), 154.1 (d, J = 2.8 Hz), 149.4, 149.1 , 142.7, 142.2, 141.0 (d, J = 7.0 Hz), 140.9 (d, J = 7.0 Hz), 135.5, 135.3, 131.6, 131.4, 130.3 (d, J = 8.1 Hz), 130.3 (d, J = 8.2 Hz), 122.2 (d, J = 2.8 Hz), 120.5, 120.3, 120.3, 120.3, 120.2 (d, J = 2.8 Hz), 118.0, 116.8, 116.1 (d, J = 21.8 Hz), 116.0 (d, J = 21.3 Hz), 113.7 (d, J = 23.0 Hz), 113.7 (d, J = 23.1 Hz), 100.1 , 100.1 , 75.7, 73.6, 73.5, 70.3, 55.3, 55.3, 38.2, 34.4, 9.5, 9.5, 6.9, 6.9.19F NMR (376 MHz, CDCI3) 6 -112.95 (dddd, J = 10.2, 8.4, 7.3, 5.9 Hz). LC-MS: Rt= 8.23 min, ES+= 408.22, method 2. HRMS: [M+Na]+calculated for C24H22NO4NaF 430.1431 ; found 430.1409.EXAMPLE 23: Preparation of 23: 2-(4-((6-(3,4-difluorophenyl)pyridin-3- yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneStep 1 : Preparation of 5-bromo-2-(3,4-difluorophenyl)pyridine

[0125] Prepared according to general procedure B using (3,4-difluorophenyl)boronic acid (237 mg, 1.50 mmol), 5-bromo-2-iodopyridine (511 mg, 1.80 mmol, 1.2 eq.), Pd(dppf)CI2*DCM (123 mg, 0.150 mmol, 0.15 eq.), and K2COs (415 mg, 3.00 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (240 mg) as a white powder. Yield: 54%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.74 - 8.70 (m, 1 H), 7.91 - 7.81 (m, 2H), 7.73 - 7.66 (m, 1 H), 7.57 (dd, J = 8.5, 0.8 Hz, 1 H), 7.28 - 7.20 (m, 1 H).13C NMR (101 MHz, CDCI3) 5 (ppm) 153.7 (dd, J = 2.3, 1.3 Hz), 151.4 (dd, J = 253.8, 14.9 Hz), 151.0, 150.8 (dd, J = 251.3, 15.8 Hz), 139.6, 135.4 (dd, J = 5.8, 3.8 Hz), 122.9 (dd, J = 6.6, 3.6 Hz), 121.3 (d, J = 0.8 Hz), 120.0 (d, J = 1.0 Hz), 117.8 (dd, J = 17.1 , 1.4 Hz), 116.1 (dd, J = 18.3, 1.2 Hz).19F NMR (376 MHz, CDCI3) 5 (ppm) -137.0 - -137.2 (m), -136.9 - -137.3 (m). LC-MS: Rt= 7.71 min, ES+= 270.05, 272.02, method 2. HRMS: [M+H]+calculated for CnH7NBrF2269.9730; found 269.9741.Step 2: Preparation of 2-(4-((6-(3,4-difluorophenyl)pyridin-3-yl)methylene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4H-pyran-4-one

[0126] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (92 mg, 0.216 mmol) and 5-bromo-2-(3,4-difluorophenyl)pyridine (64 mg, 0.216 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (31 mg, 1 :1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 32%.1H NMR (600 MHz, CDCI3) 5 (ppm) 8.61 (t, J = 1.5 Hz, 1 H), 8.47 (d, J = 2.3 Hz, 1 H), 7.90 - 7.84 (m, 2H), 7.75 - 7.70 (m, 2H), 7.69 - 7.64 (m, 3H), 7.48 (dd, J = 8.3, 2.4 Hz, 1 H), 7.26 - 7.21 (m, 2H), 6.53 (p, J = 2.4 Hz, 1 H), 6.45 (p, J = 2.3 Hz, 1 H), 5.31 (dd, J = 7.6, 6.1 Hz, 1 H), 5.22 (dd, J = 7.5, 6.2 Hz, 1 H), 4.90 - 4.65 (m, 4H), 3.87 (s, 3H), 3.84 (s, 3H), 3.24 - 3.02 (m, 4H), 2.03 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (151 MHz, CDCI3) 5 (ppm) 180.6, 180.6, 162.2, 162.2, 154.8, 154.6, 153.3, 153.2, 151.2 (dd, J = 253.1 , 14.2 Hz), 151.2 (dd, J = 253.1 , 14.7 Hz), 150.9 (dd, J = 250.5, 14.2 Hz), 150.8 (dd, J= 249.9, 14.9 Hz), 149.5, 149.2, 142.9, 142.4, 136.0 - 135.8 (m, 2C), 135.6, 135.5, 131.7, 131.5, 122.9 - 122.7 (m, 2C), 120.4, 120.3, 119.9, 119.9, 118.0, 117.8 - 117.6 (m, 2C), 116.9, 116.0 - 115.8 (m, 2C), 100.2, 100.2, 75.8, 73.7, 73.6, 70.4, 55.4, 55.4, 38.3, 34.5, 9.6, 9.6, 7.0, 7.0.19F NMR (376 MHz, CDCh) 5 (ppm) -137.29 - -137.42 (m). LC-MS: Rt= 8.55 min, ES+= 426.20, method 2. HRMS: [M+Na]+calculated for C24H2iNC>4NaF2 448.1336; found 448.1335.EXAMPLE 24: Preparation of 24: 2-methoxy-3,5-dimethyl-6-(4-(4-(4-methylpyridin-3- yl)benzylidene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-oneStep 1 : Preparation of 3-(4-bromophenyl)-4-methylpyridine

[0127] Prepared according to general procedure B using 4-methyl-3-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)pyridine (300 mg, 1.37 mmol), 1-bromo-4-iodobenzene (387 mg, 1.37mmol, 1.0 eq.), Pd(dppf)CI2*DCM (112 mg, 0.137 mmol, 0.10 eq.), and K2COs (378 mg, 2.74 mmol, 2.0 eq.). Purification was performed by normal phase column chromatography (heptane / EtOAc, 10-50%) to afford the title compound (297 mg) as a brown solid. Yield: 87%.1H NMR (400 MHz, CDCI3) <5 (ppm) 8.46 (d, J = 5.1 Hz, 1 H), 8.41 (s, 1 H), 7.64 - 7.53 (m, 2H), 7.22 - 7.15 (m, 3H), 2.28 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 149.44, 148.37, 144.77, 136.66, 131.69, 130.92, 125.35, 122.06, 19.83. HRMS: [M+H]+calculated for Ci2HnBrN 248.0051 ; found 248.0045.Step 2: Preparation of 2-methoxy-3,5-dimethyl-6-(4-(4-(4-methylpyridin-3- yl)benzylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0128] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (56 mg, 0.132 mmol) and 3-(4-bromophenyl)-4-methylpyridine (35 mg, 0.132 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (DCM / MeOH, 0-10%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (18 mg, 4:1 ratio E / Z according to1H NMR) as an off-white solid. Yield: 32%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.48 - 8.41 (m, 2H), 7.41 - 7.35 (m, 2H), 7.35 - 7.30 (m, 2H), 7.24 - 7.18 (m, 1 H), 6.57 (t, J = 2.3 Hz, 0.2H, Z- isomer) and 6.51 - 6.47 (m, 0.8H, E-isomer), 5.32 (dd, J = 7.6, 5.9 Hz, 0.8H, E-isomer) and 5.22 (dd, J = 7.5, 6.0 Hz, 0.2H, Z-isomer), 4.93 - 4.64 (m, 2H), 3.86 (s, 3H), 3.29 - 2.98 (m, 2H), 2.31 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 162.2, 155.1 (Z- isomer) and 155.0 (E-isomer), 149.7, 148.2, 145.0, 140.6 (Z-isomer) and 140.0 (E-isomer), 136.6 (E-isomer) and 136.51 (Z-isomer), 136.47 (E-isomer) and 136.3 (Z-isomer), 129.7 (2C), 128.2 (2C, E-isomer) and 128.0 (2C, Z-isomer), 125.5, 121.4, 120.13 (E-isomer) and 120.10 (Z-isomer), 120.09, 100.1 , 75.8 (E-isomer) and 73.5 (Z-isomer), 73.7 (E-isomer) and 70.5 (Z-isomer), 55.4, 34.5, 20.0, 9.6, 7.0. LC-MS: Rt= 6.28 min, ES+= 404.26, method 2. HRMS: [M+Na]+calculated for C25H25NO4Na 426.1681 ; found 426.1671.EXAMPLE 25: Preparation of 25: 2-methoxy-3,5-dimethyl-6-(4-(4-(piperidin-1- yl)benzylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0129] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (67 mg, 0.157 mmol) and 1-(4-bromophenyl)piperidine (40 mg, 0.157 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (DCM / MeOH, 0- 10%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (8 mg, 4:1 ratio E / Z according to1H NMR) as an off- white sticky solid. Yield: 12%.1H NMR of E-isomer (in mixture) (400 MHz, CDCh) 3 (ppm) 7.19 (d, J = 8.3 Hz, 2H), 6.91 (s, 2H), 6.34 (p, J = 2.3 Hz, 1 H), 5.28 (dd, J =7.6, 5.5, 1 H), 4.73 - 4.59 (m, 2H), 3.84 (s, 3H), 3.23 - 3.17 (m, 4H), 3.16 - 2.94 (m, 2H), 2.02 (s, 3H), 1.82 (s, 3H), 1.70 (s, 4H), 1.59 (s, 2H).1H NMR of Z-isomer (in mixture) (400 MHz, CDCh) 6 (ppm) 7.01 (d, J = 8.2 Hz, 2H), 6.91 (s, 2H), 6.42 (p, J = 2.3 Hz, 1 H), 5.18 (dd, J = 7.6, 5.5 Hz, 1 H), 4.86 - 4.73 (m, 2H), 3.79 (s, 3H), 3.23 - 3.17 (m, 4H), 3.16 - 2.94 (m, 2H), 2.03 (s, 3H), 1.83 (s, 3H), 1.70 (s, 4H), 1.59 (s, 2H).13C NMR (101 MHZ, CDCh) <5 (ppm) 180.8, 162.2, 155.4, 151.0, 135.0, 129.1 , 120.3, 119.9, 119.7, 116.1 , 99.9, 75.7, 73.8, 55.4, 50.3, 34.3, 25.7, 24.3, 9.6, 7.0. The13C NMR of the Z- isomer (in the mixture) was not determined. LC-MS: Rt= 6.08 min, ES+= 396.33, method 2. HRMS: [M+Na]+calculated for C24H29NO4Na 418.1994; found 418.2005.EXAMPLE 26: Preparation of 26: 2-(4-(4-cyclohexylbenzylidene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0130] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B1) (49 mg, 0.115 mmol) and 1-bromo-4-cyclohexylbenzene (29 mg, 0.115 mmol,1.0 eq.). Purification was performed by normal phase column chromatography (heptane / EtOAc, 5-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (8 mg, 8:10 ratio E / Z according to1H NMR) as an off-white solid. Yield: 26%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.23 - 7.13 (m, 6H), 7.04 (d, J = 8.1 Hz, 2H), 6.48 (p, J = 2.2 Hz, 1 H), 6.41 (p, J = 2.2 Hz, 1 H), 5.28 (dd, J = 7.7, 5.6 Hz, 1 H), 5.19 (dd, J = 7.5, 5.6 Hz, 1 H), 4.88 - 4.60 (m, 4H), 3.84 (s, 3H), 3.81 (s, 3H), 3.23 - 2.92 (m, 4H), 2.54 - 2.44 (m, 2H), 2.03 (s, 3H), 2.02 (s, 3H), 1.88 - 1.81 (m, 8H), 1.84 (s, 3H),1.83 (s, 3H), 1.78 - 1.73 (m, 2H), 1.43 - 1.36 (m, 8H), 1.31 - 1.23 (m, 2H).13C NMR (126 MHz, CDCh) 5 (ppm) 180.8, 180.8, 162.3, 162.3, 155.5, 155.3, 147.3, 147.2, 138.6, 138.1 , 134.6, 134.5, 128.2 (2C), 128.0 (2C), 127.3 (2C), 127.2 (2C), 121.9, 120.6, 120.0, 119.9, 100.0, 100.0, 75.7, 73.7, 73.4, 70.5, 55.4, 55.4, 44.4 (2C), 38.2, 34.5, 34.5, 34.5 (2C), 34.4, 27.0 (4C), 26.3, 26.3, 9.6, 9.6, 7.1 , 7.0. LC-MS: Rt= 9.29 min, ES+= 395.24, method 2. HRMS: [M+Na]+calculated for C25H3o04Na 417.2042; found 417.2029.EXAMPLE 27: Preparation of 27: 2-methoxy-3,5-dimethyl-6-(4-((1-phenyl-1 H-pyrazol-4- yl)methylene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-one

[0131] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (56 mg, 0.132 mmol) and 4-bromo-1-phenyl-1 / 7-pyrazole (31 mg, 0.132 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (DCM / MeOH, 0- 10%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (20 mg, 4:1 ratio E / Z according to1H NMR) as an off- white solid. Yield: 37%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.86 (s, 1 H), 7.73 (s, 1 H), 7.71 (s, 1 H), 7.70 - 7.65 (m, 4H), 7.58 (s, 1 H), 7.50 - 7.42 (m, 4H), 7.34 - 7.28 (m, 2H), 6.41 (p, J = 2.3 Hz, 1 H), 6.33 (p, J = 2.4 Hz, 1 H), 5.33 (dd, J = 7.7, 6.0 Hz, 1 H), 5.24 (dd, J = 7.5, 5.8 Hz, 1 H),4.83 - 4.59 (m, 4H), 3.88 (s, 3H), 3.85 (s, 3H), 3.17 - 2.92 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H),1.84 (s, 6H).13C NMR (126 MHz, CDCh) 5 (ppm) 180.8 (2C), 162.3, 162.3, 155.2, 155.0, 140.3,140.2, 139.9, 139.9, 137.9, 137.4, 129.7 (2C), 129.7 (2C), 126.9 (2C), 124.7, 124.5, 121.3, 121.1 ,120.2, 120.0, 119.2 (2C), 119.2 (2C), 110.7, 110.0, 100.1 (2C), 75.7, 74.4, 73.1 , 71.1 , 55.4, 55.4, 37.3, 34.8, 9.7, 9.6, 7.0, 7.0. LC-MS: Rt= 8.16 min, ES+= 379.18, method 2. HRMS: [M+Na]+calculated for C22H22N2O4Na 401.1477; found 401.1485.EXAMPLE 28: Preparation of 28: 2-methoxy-6-(4-((6-methoxynaphthalen-2- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0132] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.138 mmol) and 2-bromo-6-methoxynaphthalene (37 mg, 0.155 mmol, 1.1 eq.). Purification was performed by reverse phase column chromatography (Water / MeCN, 0 - 100%) to afford 18 (30 mg, 75 / 100 ratio E / Z according to1H NMR) as an off-white powder. Yield: 52%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.71 (dd, J = 8.7, 2.4 Hz, 4H), 7.66 - 7.64 (m, 1 H), 7.49 - 7.46 (m, 1 H), 7.40 (dd, J = 8.5, 1.8 Hz, 1 H), 7.24 (dd, J = 8.5, 1.8 Hz, 1 H), 7.18 - 7.13 (m, 2H), 7.13 - 7.10 (m, 2H), 6.64 (p, J = 2.3 Hz, 1 H), 6.56 (p, J = 2.4 Hz, 1 H), 5.33 (dd, J = 7.7, 5.8 Hz, 1 H), 5.23 (dd, J = 7.7, 5.6 Hz, 1 H), 4.97 - 4.83 (m, 2H), 4.81 - 4.66 (m, 2H), 3.93 (s, 3H), 3.93 (s, 3H), 3.84 (s, 3H), 3.79 (s, 3H), 3.32 - 2.97 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHZ, CDCI3) <5 (ppm) 180.8, 180.8, 162.3, 162.2, 158.1 , 158.1 , 155.5, 155.1 , 139.1 , 138.6, 133.6, 133.5, 132.4, 132.3, 129.6, 129.6, 129.0, 129.0, 127.3, 127.1 , 127.0,126.8, 126.8, 126.6, 122.1 , 120.8, 120.1 , 119.9, 119.5, 119.5, 105.8, 105.8, 100.0, 100.0, 75.8,73.8, 73.4, 70.6, 55.5, 55.5, 55.4, 55.4, 38.4, 34.4, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.66 min, ES+= 393.20, method 2. HR-MS (El; LCT) [M+Na]+calculated for C24H24O5Na 415.1521 , found 415.1523.EXAMPLE 29: Preparation of 29: methyl 6-((5-(6-methoxy-3,5-dimethyl-4-oxo-4 / 7-pyran-2- yl)dihydrofuran-3(2 / - / )-ylidene)methyl)-2-naphthoate

[0133] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.138 mmol) and methyl 6-bromo-2-naphthoate (40 mg, 0.152 mmol,1.1 eq.). Purification was performed by reverse phase column chromatography (water / MeCN, 0 - 100%) to afford 19 (28 mg, 44 / 56 ratio E / Z according to1H NMR) as an off-white powder. Yield: 46%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.57 (s, 2H), 8.14 - 7.99 (m, 2H), 7.98 - 7.78 (m, 4H), 7.74 (s, 1 H), 7.56 (s, 1 H), 7.49 (d, J = 8.7 Hz, 1 H), 7.33 (d, J = 8.6 Hz, 1 H), 6.68 (s, 1 H), 6.60 (s, 1 H), 5.33 (t, J = 6.5 Hz, 1 H), 5.24 (t, J = 6.9 Hz, 1 H), 5.02 - 4.84 (m, 2H), 4.84 - 4.64 (m, 2H), 3.97 (s, 6H), 3.84 (s, 3H), 3.80 (s, 3H), 3.38 - 2.99 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.82 (s, 3H), 1.81 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7 (2C), 167.2, 167.2, 162.2, 162.2, 155.1 , 154.8, 141.9, 141.3, 136.9, 136.7, 135.7, 135.7, 131.4, 131.3, 130.8 (2C), 129.9, 129.8, 128.3, 128.2, 127.7, 127.7, 127.0, 126.8, 126.8, 126.6, 126.0, 126.0, 121.7, 120.4, 120.2, 120.1 ,100.1 (2C), 75.8, 73.8, 73.5, 70.5, 55.4, 55.4, 52.4, 52.4, 38.5, 34.6, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.56 min, ES+= 421.21 , method 2. HR-MS (El; LCT): [M+Na]+calculated for C25H24O6Na 443.1471 , found 443.1476.EXAMPLE 30: Preparation of 30: 2-methoxy-3,5-dimethyl-6-(4-(quinolin-7- ylmethylene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-one

[0134] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.138 mmol) and 7-bromoquinoline (30 mg, 0.145 mmol, 1.05 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 20 (4 mg, 70 / 100 ratio E / Z according to1H NMR) as an off-white powder. Yield: 7%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.94 - 8.89 (m, 2H), 8.17 - 8.12 (m, 2H), 8.01 (s, 1 H), 7.83 - 7.77 (m, 3H), 7.49 (dd, J = 8.4, 1.8 Hz, 1 H), 7.42 - 7.37 (m, 2H), 7.36 (dd, J = 8.5, 1.7 Hz, 1 H), 6.71 (p, J = 2.3 Hz, 1 H), 6.63 (p, J = 2.4 Hz, 1 H), 5.34 (dd, J = 7.7, 5.8 Hz, 1 H), 5.25 (dd, J = 7.7, 5.8 Hz, 1 H), 5.02 - 4.68 (m, 4H), 3.86 (s, 3H), 3.81 (s, 3H), 3.38 - 3.03 (m, 4H), 2.05 (s, 3H), 2.03 (s, 3H), 1.84 (s, 3H), 1.81 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 155.2, 154.9, 151.2, 151.2, 148.5, 148.5, 142.4, 141.8, 138.3, 138.0, 135.9, 135.9, 128.3, 128.1 , 128.1 , 127.9, 127.3, 127.3, 127.2, 127.1 , 121.5, 121.4, 121.3, 120.3, 120.2, 120.1 , 100.1 ,100.1 , 75.8, 73.8, 73.5, 70.7, 55.4, 55.4, 38.5, 34.7, 9.6, 9.6, 7.1 , 7.0. LC-MS: Rt= 7.94 min, ES+= 364.23, method 2. HR-MS (El; LCT): [M+Na]+calculated for C22H2iNO4Na 386.1368, found 386.1364.EXAMPLE 31 : Preparation of 31 : 2-(4-(isoquinolin-6-ylmethylene)tetrahydrofuran-2-yl)-6- methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0135] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.129 mmol) and 6-bromoisoquinoline (28 mg, 0.136 mmol, 1.05 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 21 (21 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 43%.1H NMR (400 MHz, CDCI3) 5 (ppm) 9.25 (s, 2H), 8.50 (s, 2H), 7.99 (d, J = 8.5 Hz, 2H), 7.71 (s, 1 H), 7.68 (d, J = 5.7 Hz, 2H), 7.59 (d, J = 8.5 Hz, 1 H), 7.52 (s, 1 H), 7.42 (d, J = 8.5 Hz, 1 H), 6.70 (p, J = 2.5 Hz, 1 H), 6.61 (p, J = 2.5 Hz, 1 H), 5.32 (t, J = 6.8 Hz, 1 H), 5.23 (t, J = 6.8 Hz, 1 H), 5.00 - 4.66 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H), 3.34 - 3.03 (m, 4H), 2.03 (s, 3H), 2.02 (s, 3H), 1.82 (s, 3H), 1.80 (s, 3H).13C NMR (101 MHz, CDCI3) 3 (ppm) 180.7, 180.6, 162.2, 162.2, 154.8, 154.6, 151.4, 151.3, 143.8, 143.2, 142.2, 142.1 , 139.7, 139.5, 136.4, 136.4, 128.5, 128.4, 128.2, 127.9, 127.3, 127.2, 125.3, 125.0, 121.3, 121.1 , 121.0, 120.3, 120.2, 120.0, 100.1 , 100.1 , 75.8, 73.8, 73.5, 70.4, 55.4, 55.3, 38.5, 34.6, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 5.85 min, ES+= 364.23, method 2. HR-MS (El; LCT): [M+Na]+calculated for C22H2iNO4Na 386.1368, found 386.1369.EXAMPLE 32: Preparation of 32: 2-methoxy-3,5-dimethyl-6-(4-(quinolin-6- ylmethylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0136] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.129 mmol) and 6-bromoquinoline (28 mg, 0.136 mmol, 1.05 eq.). Purification was performed by reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 22 (11 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 22%.1H NMR (400 MHz, CDCh) 5 (ppm) 8.91 - 8.88 (m, 2H), 8.13 (d, J = 8.4 Hz, 2H), 8.08 (d, J = 9.0 Hz, 2H), 7.70 - 7.66 (m, 2H), 7.53 - 7.50 (m, 2H), 7.44 - 7.38 (m, 2H), 6.69 (s, 1 H), 6.61 (s, 1 H), 5.33 (t, J = 6.8 Hz, 1 H), 5.24 (t, J = 6.7 Hz, 1 H), 4.99 - 4.84 (m, 2H), 4.84 - 4.67 (m, 2H), 3.85 (s, 3H), 3.80 (s, 3H), 3.34 - 3.01 (m, 4H), 2.05 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 155.1 , 154.8, 150.7, 150.6, 147.4, 147.3, 141.6, 141.0, 136.2, 136.1 , 135.3, 135.2, 130.0, 129.9, 129.9, 129.7, 128.5, 128.4, 126.7, 126.4, 121.8, 121.8, 121.4, 121.4, 120.3, 120.1 , 100.1 , 100.1 , 75.8, 73.8, 73.5, 70.5, 55.7, 55.4, 38.4, 34.5, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 6.40 min, ES+= 364.22, method 2. HR-MS (EI; LCT): [M+H]+calculated for C22H22NO4364.1549, found 364.1467.EXAMPLE 33: Preparation of 33: 2-methoxy-3,5-dimethyl-6-(4-(quinoxalin-6- ylmethylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0137] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (55 mg, 0.129 mmol) and 6-bromoquinoxaline (28 mg, 0.136 mmol, 1.05 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0-10%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 23 (7 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 14%.1H NMR (400 MHz, CDCh) 5 (ppm) 8.86 - 8.80 (m, 4H), 8.09 (d, J = 8.7 Hz, 2H), 8.00 (d, J = 2.0 Hz, 1 H), 7.79 (d, J = 2.0 Hz, 1 H), 7.72 (dd, J = 8.8, 2.0 Hz, 1 H), 7.58 (dd, J = 8.8, 2.1 Hz, 1 H), 6.73 (p, J = 2.1 Hz, 1 H), 6.65 (p, J = 2.1 Hz, 1 H), 5.34 (dd, J = 7.6, 6.0 Hz, 1 H), 5.26 (dd, J = 7.6, 6.0 Hz, 1 H), 5.03 - 4.69 (m, 4H), 3.86 (s, 3H), 3.82 (s, 3H), 3.38 - 3.05 (m, 4H), 2.05 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 154.9,154.6, 145.7, 145.7, 145.0, 145.0, 143.7, 143.3, 143.2, 143.1 , 142.2, 142.1 , 138.9, 138.7, 130.8,130.6, 129.9, 129.8, 127.8, 127.6, 120.9, 120.4, 120.2, 119.6, 100.2, 100.2, 75.8, 73.8, 73.5, 70.6,55.4, 55.4, 38.5, 34.6, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 7.36 min, ES+= 365.20, method 2. HR-MS(El; LCT): [M+Na]+calculated for C2iH2oN204Na 387.1321 , found 387.1312.EXAMPLE 34: Preparation of 34: 2-methoxy-6-(4-((2-methoxyquinolin-7- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0138] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.117 mmol) and 7-bromo-2-methoxyquinoline (31 mg, 0.129 mmol, 1.1 eq.) in 1 ,4-dioxane (1.5 mL). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 24 (16 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 33%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.93 (dd, J = 8.9, 0.7 Hz, 2H), 7.75 (d, J = 1.7 Hz, 1 H), 7.67 (d, J = 8.3 Hz, 2H), 7.57 - 7.54 (m, 1 H), 7.30 (dd, J = 8.3, 1.8 Hz, 1 H), 7.15 (dd, J = 8.3, 1.8 Hz, 1 H), 6.88 (dd, J = 8.8, 2.0 Hz, 2H), 6.66 (p, J = 2.3 Hz, 1 H), 6.58 (p, J = 2.3 Hz, 1 H), 5.34 (dd, J = 7.7, 5.7 Hz, 1 H), 5.24 (dd, J = 7.7, 5.6 Hz, 1 H), 5.01 - 4.86 (m, 2H), 4.82 - 4.67 (m, 2H), 4.07 (s, 3H), 4.06 (s, 3H), 3.84 (s, 3H), 3.80 (s, 3H), 3.37 - 3.00 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8, 180.7, 163.0, 163.0, 162.3, 162.2, 155.4, 155.1 , 146.9, 146.9, 141.4, 140.8, 138.4, 138.3, 138.2, 138.0, 127.8, 127.7, 126.2, 126.1 , 124.6, 124.2, 124.1 , 124.0, 121.8, 120.5, 120.2, 119.9, 113.4, 113.3, 100.0, 100.0, 75.8, 73.8, 73.4, 70.6, 55.4 (2C), 53.6, 53.6, 38.5, 34.6, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.41 min, ES+= 394.23, method 2. HR-MS (El; LCT): [M+Na]+calculated for C23H23NO5Na 416.1474, found 416.1456.EXAMPLE 35: Preparation of 35: 2-methoxy-3,5-dimethyl-6-(4-((2-methylquinolin-6- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0139] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (65 mg, 0.153 mmol) and 6-bromo-2-methylquinoline (31 mg, 0.137 mmol, 0.9 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0- 10%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 25 (15 mg, 85 / 100 ratio E / Z according to1H NMR) as an off-white powder. Yield: 23%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.04 - 7.98 (m, 4H), 7.65 - 7.61 (m, 2H), 7.49 - 7.45 (m, 2H), 7.30 (dd, J = 8.5, 3.4 Hz, 2H), 6.68 - 6.65 (m, 1 H), 6.60 - 6.57 (m, 1 H), 5.32 (dd, J = 7.6, 5.9 Hz, 1 H), 5.23 (dd, J = 7.6, 5.8 Hz, 1 H), 4.97 - 4.66 (m, 4H), 3.84 (s, 3H), 3.79 (s, 3H), 3.32 - 3.00 (m, 4H), 2.75 (s, 3H), 2.74 (s, 3H), 2.04 (s, 3H), 2.03 (s, 2H), 1.83 (s, 3H), 1.81 (s, 3H). LC-MS: Rt= 2.18 min, ES+= 378.14, method 1.EXMAPLE 36: Preparation of 36: 2-methoxy-3,5-dimethyl-6-(4-((7-methylquinolin-6- yl)methylene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-one

[0140] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (65 mg, 0.129 mmol) and 6-bromo-7-methylquinoline (26 mg, 0.116 mmol, 0.9 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0- 10%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 26 (18 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 34%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.84 (ddd, J = 4.6, 3.1 , 1.8 Hz, 2H), 8.07 (dq, J = 8.4, 1 .5 Hz, 2H), 7.90 (d, J = 1 .9 Hz, 2H), 7.63 (s, 1 H), 7.38 (s, 1 H), 7.34 (ddd, J = 8.2, 5.2, 4.3 Hz, 2H), 6.73 (p, J = 2.1 Hz, 1 H), 6.65 (p, J = 2.1 Hz, 1 H), 5.26 (dd, J = 7.5, 6.3 Hz, 1 H), 5.22 (dd, J = 7.5, 6.5 Hz, 1 H), 4.85 - 4.66 (m, 4H), 3.89 (s, 3H), 3.85 (s, 3H), 3.23 - 2.97 (m, 4H), 2.52 (s, 3H), 2.50 (s, 3H), 2.04 (s, 3H), 1.99 (s, 3H), 1.84 (s, 3H), 1.81 (s, 3H).13C NMR (101 MHz, CDCI3) 6 (ppm) 180.7, 180.7, 162.2, 162.2, 155.0, 154.9, 150.5, 150.5, 147.6, 147.6, 141.7, 141.4, 138.7,138.5, 135.7, 135.7, 135.7, 135.5, 129.7, 129.6, 126.8, 126.8, 126.3, 126.1 , 121.0, 120.9, 120.1 , 120.1 , 119.5, 118.3, 100.2, 100.1 , 75.4, 73.7, 73.3, 70.2, 55.4, 55.4, 37.9, 34.3, 20.8, 20.7, 9.6,9.5, 7.0, 7.0. LC-MS: Rt= 6.27 min, ES+= 378.23, method 2. HR-MS (El; LCT): [M+H]+calculated for C23H24NO4 378. 705, found 378.1718.EXAMPLE 37: Preparation of 37: 2-methoxy-3,5-dimethyl-6-(4-((8-methylquinolin-7- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0141] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (65 mg, 0.153 mmol) and 7-bromo-8-methylquinoline (31 mg, 0.137 mmol, 0.9 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0- 10%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 27 (22 mg, 100 / 80 ratio E / Z according to1H NMR) as an off-white powder. Yield: 36%.1H NMR (400 MHz, CDCI3) <5 (ppm) 8.94 (m, 2H), 8.10 (dt, J = 8.2, 1.4 Hz, 2H), 7.64 (d, J = 8.5 Hz, 2H), 7.46 (d, J = 8.5 Hz, 1 H), 7.38 (ddd, J = 8.2, 4.2, 1.6 Hz, 2H), 7.27 (d, J = 8.5 Hz, 1 H), 6.90 (p, J = 2.1 Hz, 1 H), 6.82 (p, J = 2.1 Hz, 1 H), 5.26 (dd, J = 7.6, 6.3 Hz, 1 H), 5.22 (dd, J = 7.6, 6.3 Hz, 1 H), 4.86 - 4.61 (m, 4H), 3.90 (s, 3H), 3.87 (s, 3H), 3.25 - 2.86 (m, 4H), 2.80 (s, 3H), 2.78 (s, 3H), 2.04 (s, 3H), 1.99 (s, 3H), 1.84 (s, 3H), 1.81 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8, 180.7, 162.2, 162.2, 155.1 , 155.0, 149.8, 149.7, 147.4, 147.4, 141.1 (2C), 136.3 (2C), 136.3, 136.1 , 134.8, 134.6, 127.4 (2C), 126.8, 126.4, 125.5, 125.3, 121.0 (2C), 120.9, 120.1 , 120.0, 119.8, 100.1 , 100.0, 75.5, 73.9, 73.3, 70.2, 55.4, 55.4, 37.8, 34.2, 14.0, 13.9, 9.6, 9.5, 7.0, 7.0. LC-MS: Rt= 6.54 min, ES+= 378.21 , method 2. HR-MS (El; LCT): [M+H]+calculated for C23H24NO4 378.1705, found 378.1702.EXAMPLE 38: Preparation of 38: 2-methoxy-6-(4-((4-methoxyquinolin-6- yl)methylene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0142] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (65 mg, 0.129 mmol) and 6-bromo-4-methoxyquinoline (26 mg, 0.110 mmol, 0.9 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol,0-10%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 28 (18 mg, 85 / 100 ratio E / Z according to1H NMR) as an off-white powder. Yield: 33%.1H NMR (400 MHz, CDCI3) 5 (ppm) 8.72 (dd, J = 5.4, 1.6 Hz, 2H), 8.07 (d, J = 2.0 Hz, 1 H), 8.00 (d, J = 8.7 Hz, 2H), 7.89 (d, J = 2.0 Hz, 1 H), 7.63 (dd, J = 8.8, 2.1 Hz, 1 H), 7.47 (dd, J = 8.8, 2.1 Hz, 1 H), 6.75 (dd, J = 5.3, 1.4 Hz, 2H), 6.68 (p, J = 2.4 Hz, 1 H), 6.59 (p, J = 2.3 Hz, 1 H), 5.33 (dd, J = 7.7, 5.8 Hz, 1 H), 5.23 (dd, J = 7.6, 5.6 Hz, 1 H), 4.98 - 4.82 (m, 2H), 4.81 - 4.66 (m, 2H), 4.06 (s, 3H), 4.05 (s, 3H), 3.83 (s, 3H), 3.78 (s, 3H), 3.34 - 2.99 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.82 (s, 3H), 1.81 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.7 (2C), 162.4, 162.4,162.2, 162.2, 155.3, 155.0, 151.5, 151.5, 148.0, 147.9, 141.0, 140.5, 134.4, 134.3, 130.2, 130.0,129.3, 129.2, 121.6, 121.5, 121.5, 120.7, 120.5, 120.3, 120.2, 119.9, 100.7, 100.6, 100.0 (2C), 75.8, 73.7, 73.5, 70.5, 56.0, 56.0, 55.4, 55.4, 38.4, 34.3, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt = 5.86 min, ES+= 394.21 , method 2. HR-MS (El; LCT): [M+Na]+calculated for C23H23NO5Na 416.1474, found 416.1476.EXAMPLE 39: Preparation of 39: 2-methoxy-3,5-dimethyl-6-(4-((8-(trifluoromethyl)quinolin-6- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0143] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (65 mg, 0.153 mmol) and 6-bromo-8-(trifluoromethyl)quinoline (38 mg, 0.137 mmol, 0.9 eq.). Purification was performed by normal phase column chromatography (DCM / Methanol, 0-10%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 29 (21 mg, 90 / 100 ratio E / Z according to1H NMR) as a yellow sticky solid. Yield: 29%.1H NMR (400 MHz, CDCI3) 5 (ppm) 9.04 (dt, J = 4.1 , 2.0 Hz, 2H), 8.20 (dt, J = 8.4, 2.1 Hz, 2H), 8.02 (d, J = 2.0 Hz, 1 H), 7.88 - 7.85 (m, 2H), 7.67 (d, J = 2.0 Hz, 1 H), 7.52 (dt, J = 8.3, 4.1 Hz, 2H), 6.69 (p, J = 2.4 Hz, 1 H), 6.61 (p, J = 2.4 Hz, 1 H), 5.33 (dd, J = 7.5, 6.3 Hz, 1 H), 5.23 (dd, J = 7.4, 6.4 Hz, 1 H), 4.98 - 4.67 (m, 4H), 3.88 (s, 3H), 3.84 (s, 3H), 3.34 - 3.05 (m, 4H), 2.04 (s, 3H), 2.03 (s, 3H), 1.83 (s, 3H), 1.82 (s, 3H). LC-MS: Rt= 3.39 min, ES+= 432.08, method 1.EXAMPLE 40: Preparation of 40: 2-(4-((6-fluoronaphthalen-2-yl)methylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-oneF

[0144] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (50 mg, 0.121 mmol) and 2-bromo-6-fluoronaphthalene (29 mg, 0.128 mmol, 1.05 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5- 100%) and reverse phase column chromatography (water+0.05% TFA / MeCN+0.05% TFA, 0 - 100%) to afford 30 (11 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white powder. Yield: 11%.1H NMR (400 MHz, CDCI3) <5 (ppm) 7.80 (ddd, J = 8.7, 5.6, 2.9 Hz, 2H), 7.77 (s, 1 H), 7.75 (s, 1H), 7.71 (s, 1H), 7.53 (s, 1 H), 7.48 - 7.41 (m, 3H), 7.31 - 7.24 (m, 3H), 6.65 (p, J = 2.3 Hz, 1 H), 6.57 (p, J = 2.3 Hz, 1 H), 5.33 (dd, J = 7.6, 5.8 Hz, 1 H), 5.23 (dd, J = 7.6, 5.7 Hz, 1 H), 4.98 - 4.66 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H), 3.32 - 2.99 (m, 4H), 2.05 (s, 3H), 2.04 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8 (2C), 162.3, 162.2, 160.6 (d, J = 247.2 Hz), 160.5 (d, J = 247.2 Hz), 155.3, 155.0, 140.3 (d, J = 1.1 Hz), 139.8 (d, J = 1.1 Hz), 133.9, 133.9, 133.8, 133.8, 133.1 (d, J = 8.2 Hz), 133.0 (d, J = 8.2 Hz), 130.5, 130.4, 127.8 (d, J = 5.5 Hz), 127.7 (d, J = 5.5 Hz), 127.3, 127.0, 127.0, 126.8, 121.7, 120.4, 120.2, 120.0, 117.1 (d, J = 25.5 Hz), 117.0 (d, J = 25.5 Hz), 111.0 (d, J = 20.7 Hz), 110.9 (d, J = 20.7 Hz), 100.1 (2C), 75.8, 73.8, 73.5, 70.5, 55.4, 55.4, 38.4, 34.5, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.88 min, ES+= 381.21, method 2. HR-MS (El; LCT) calculated for C23H2iO4FNa ([M+Na]+) 403.1322, found 403.1310.EXAMPLE 41 : Preparation of 41 : 2-(4-benzylidenetetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0145] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (100 mg, 0.28 mmol) and bromobenzene (30 pl, 0.31 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) andreverse phase column chromatography (water / MeCN, 0-100%) to afford 31 (13 mg, 85 / 100 ratio E / Z according to1H NMR) as a yellow solid. Yield: 20%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.38- 7.34 (m, 4H), 7.30-7.22 (m, 4H), 7.13-7.10 (d, J = 7.6 Hz, 2H), 6.52 (m, 1 H), 6.44 (m, 1 H), 5.31- 5.27 (dd, J = 7.6, 5.8 Hz, 1 H), 5.23-5.19 (dd, J = 7.6, 5.8 Hz, 1 H), 4.88-4.62 (m, 4H), 3.84 (s, 3H), 3.80 (s, 3H), 3.23-2.95 (m, 4H), 2.03 (s, 3H), 2.02 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.8 (2C), 162.3, 162.2, 155.4, 155.1 , 139.7, 139.2, 137.0, 136.9, 128.8 (2C), 128.7 (2C), 128.2 (2C), 127.9 (2C), 127.2, 127.2, 122.0, 120.7, 120.1 , 119.9, 100.0 (2C), 75.7, 73.7, 73.4, 70.4, 55.4 (2C), 38.3, 34.3, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt= 8.16 min, ES+= 313.26, method 2. HR-MS: [M+Na]+calculated for Ci9H2o04Na 335.3530; found 335.0854.EXAMPLE 42: Preparation of 42: 2-methoxy-3,5-dimethyl-6-(4-(4- methylbenzylidene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-one

[0146] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (80 mg, 0.22 mmol) and 1-bromo-4-methylbenzene (30 pl, 0.24 mmol). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water / MeCN, 0-100%) to afford 32 (1 mg, 80 / 100 ratio E / Z according to1H NMR) as a yellow solid. Yield: 2%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.21- 7.14 (m, 6H), 7.03-6.99 (d, J = 7.9 Hz, 2H), 6.49 (m, 1 H), 6.40 (m, 1 H), 5.32 (m, 1 H), 5.20 (m, 1 H), 4.87-4.60 (m, 4H), 3.84 (s, 3H), 3.80 (s, 3H), 3.22-2.92 (m, 4H), 2.35 (s, 6H), 2.04 (s, 3H), 2.03 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.6 (2C), 165.2 (2C), 155.4, 155.1 , 138.5, 138.0, 137.0, 136.9, 134.1 , 134.0, 129.4 (2C), 129.3 (2C), 128.0 (2C), 127.8 (2C), 121.7, 120.4, 120.1 , 119.9, 99.9 (2C), 75.8, 73.6, 73.4, 70.3, 55.3 (2C), 38.1 , 34.2, 21.2, 21.2, 9.4 (2C), 6.9 (2C). LC-MS: Rt= 8.45 min, ES+= 327.19, method 2. HR-MS: [M+H]+calculated for C20H23O4 327.1588; found 327.1596.EXAMPLE 43: Preparation of 43: 2-methoxy-6-(4-(4-methoxybenzylidene)tetrahydrofuran-2-yl)-3,5-dimethyl-4 / 7-pyran-4-one

[0147] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (92 mg, 0.25 mmol) and 1-bromo-4-methoxybenzene (40 pl, 0.28 mmol,1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5- 100%) and reverse phase column chromatography (water / MeCN, 0-100%) to afford 33 (18 mg, 8 / 10 ratio E / Z according to1H NMR) as a yellow solid. Yield: 21 %.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.24-7.21 (m, 2H), 7.07-7.03 (m, 2H), 6.91-6.88 (m, 4H), 6.46 (m, 1 H), 6.38 (m, 1 H), 5.31- 5.26 (dd, J = 7.8, 5.7 Hz, 1 H), 5.21-5.17 (dd, J = 7.8, 5.7 Hz, 1 H), 4.84-4.59 (m, 4H), 3.84 (s, 3H),3.82 (s, 3H), 3.81 (s, 3H), 3.79 (s, 3H), 3.19-2.91 (m, 4H), 2.03 (s, 3H), 2.02 (s, 3H), 1.83 (s, 3H),1.82 (s, 3H).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.8 (2C), 162.3, 162.3, 158.7, 158.7, 155.6, 155.3, 137.2, 136.8, 129.8, 129.7, 129.4 (2C), 129.2 (2C), 121.4, 120.1 , 120.0, 119.8, 114.2 (2C),114.1 (2C), 100.0 (2C), 75.7, 73.7, 73.4, 70.4, 55.4, 55.4, 55.4, 55.4, 38.2, 34.2, 9.6, 9.6, 7.0, 7.0. LC-MS: Rt = 8.14 min, ES+= 343.21 , method 2. HR-MS: [M+Na]+calculated for C2oH220sNa 365.1357; found 365.1365.EXAMPLE 44: Preparation of 44: 2-(4-(4-fluorobenzylidene)tetrahydrofuran-2-yl)-6-methoxy-3,5- dimethyl-4 / 7-pyran-4-one

[0148] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (88 mg, 0.24 mmol) and 1-bromo-4-fluorobenzene (30 pl, 0.26 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water / MeCN, 0-100%) to afford 34 (16 mg, 1 / 1 ratio E / Z according to1H NMR) as an off-white solid. Yield: 20%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.27 - 7.23 (m, 2H), 7.10 - 7.01 (m, 6H), 6.48 (p, J = 2.3 Hz, 1 H), 6.40 (p, J = 2.3 Hz, 1 H), 5.29 (dd, J = 7.6, 5.8 Hz, 1 H), 5.20 (dd, J = 7.6, 5.8 Hz, 1 H), 4.84 - 4.59 (m, 4H), 3.85 (s, 3H), 3.80 (s, 3H),3.19 - 2.92 (m, 4H), 2.03 (s, 3H), 2.02 (s, 3H), 1.84 (s, 3H), 1.83 (s, 3H).13C NMR (101 MHz, CDCh) 5 (ppm) 180.7, 180.7, 162.3, 162.2, 161.8 (d, J = 248 Hz), 161.7 (d, J = 248 Hz), 155.2, 155.0, 139.4 (d, J = 2.0 Hz), 138.9 (d, J = 2.0 Hz), 133.2 (d, J = 3.6 Hz), 133.1 (d, J = 3.2 Hz), 129.7 (d, J = 8.0 Hz, 2C), 129.5 (d, J = 8.0 Hz, 2C), 120.9, 120.2, 120.0, 119.6, 115.9 (d, J = 21.3 Hz, 2C), 115.7 (d, J = 21.3 Hz, 2C), 100.1 , 100.1 , 75.7, 73.6, 73.5, 70.3, 55.36, 55.34, 38.2, 34.2, 9.6, 9.6, 7.0, 7.0.19F NMR (376 MHz, CDCh) 5 (ppm) -114.7. LC-MS: Rt= 8.26 min, ES+= 331 .18, method 2.EXAMPLE 45: Preparation of 45: 4-((5-(6-Methoxy-3,5-dimethyl-4-oxo-4 / 7-pyran-2- yl)dihydrofuran-3(2 / - / )-ylidene)methyl)benzonitrile

[0149] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (80 mg, 0.22 mmol) and 4-bromobenzonitrile (44 mg, 0.23 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water / MeCN, 0-100%) to afford 35 (32 mg, 9 / 10 ratio E / Z according to1H NMR) as a yellow solid. Yield: 43%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.66- 7.63 (dd, J = 8.3, 1.4 Hz, 4H), 7.40-7.36 (d, J = 8.4 Hz, 2H), 7.23-7.18 (d, J = 8.4 Hz, 2H), 6.55 (m, 1 H), 6.46 (m, 1 H), 5.32-5.28 (m, 1 H), 5.24-5.19 (dd, J = 7.2, 1.0 Hz, 1 H), 4.88-4.63 (m, 4H), 3.86 (s, 3H), 3.82 (s, 3H), 3.22-3.00 (m, 4H), 2.03 (s, 3H), 2.02 (s, 3H), 1.84 (s, 3H), 1.83 (3H).13C NMR (101 MHZ, CDCh) 5 (ppm) 180.7, 180.7, 162.3, 162.3, 154.7, 154.5, 144.4, 143.7 ,141.4, 141.2, 132.6 (2C), 132.5 (2C), 128.6 (2C), 128.4 (2C), 120.6, 120.5, 120.4, 119.4, 118.8, 118.8, 110.6, 110.6, 100.3, 100.3, 75.8, 73.7, 73.6, 70.4, 55.4, 55.4, 38.4, 34.6, 9.6, 9.6, 7.1 , 7.0. LC- MS: Rt = 8.21 min, ES+= 338.12, method 2. HR-MS: [M+Na]+calculated for C2oHig04NNa 360.1219; found 360.1212.EXAMPLE 46: Preparation of 46: 2-(4-Benzyltetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7- pyran-4-one

[0150] A solution of 31 (15 mg, 0.05 mmol) in methanol was hydrogenated in an H-Cube (10% Pd / C cartridge, 1 mL / min, 30 °C, 3 bar). After completion of the reaction, the reaction mixture was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 0-100%) to afford 36 (9 mg, 3:1 ratio of diastereomers) as an off-white solid. Yield: 60%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.34-7.28 (m, 3H), 7.25-7.14 (m, 4H), 5.17 (dd, J = 5.8, 8.1 Hz, 0.33H), 5.04 (dd, J = 6.7, 9.6 Hz, 1 H), 4.13-4.06 (m, 2.7H), 3.93 (s, 3H), 3.91 (s, 1 H), 3.63-3.75 (m, 1.33H), 2.86-2.66 (m, 4H), 2.38-2.09 (m, 2H), 1.99 (s, 1 H), 1.96 (s, 3H), 1.85 (s, 3H), 1.83 (s, 1 H). HR-MS: [M+Na]+calculated for Ci9H22O4Na 337.1416; found 337.1431.Example 47: Preparation of 47: 2-methoxy-3,5-dimethyl-6-(4-((2-methylpyridin-4- yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one

[0151] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (44 mg, 0.102 mmol) and 4-bromo-2-methylpyridine (0.012 mL, 0.102 mmol, 1.0 eq.). Purification was performed by normal phase column chromatography (DCM / MeOH, 0- 10%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (0.6 mg, 1 :4 ratio E / Z according to1H NMR) as an off- white film. Yield: 1%.1H NMR of Z-isomer (500 MHz, CDCh): 5 (ppm) 8.52 - 8.43 (m, 1 H), 6.94 (s, 1 H), 6.92 - 6.89 (m, 1 H), 6.47 (t, J = 2.4 Hz, 1 H), 5.22 (dd, J = 7.4, 6.3 Hz, 1 H), 4.91 - 4.62 (m, 2H), 3.83 (s, 3H), 3.23 - 3.02 (m, 2H), 2.64 (s, 3H), 2.04 (s, 3H), 1.83 (s, 3H).13C NMR of Z- isomer (126 MHz, CDCh) 5 (ppm) 180.6, 162.2, 158.1 , 154.4, 147.8, 145.9, 122.7, 120.5, 119.9, 119.5, 100.4, 73.7, 70.5, 55.4, 38.5, 23.7, 9.6, 7.1. One carbon signal was not observed. LC-MS: Rt = 5.00 min, ES+= 328.30, method 2. HRMS: [M+Na]+calculated for Ci9H2iNO4Na 350.1368; found 350.1351.EXAMPLE 48: of 48: 2-methoxy-3,5-dimethyl-6-(4-(pyridin-3- ylmethylene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-one

[0152] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4- ((4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)methylene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B1) (75 mg, 0.16 mmol) and 3-bromopyridine (14 pl, 0.15 mmol, 0.9 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 5-100%) and reverse phase column chromatography (water / MeCN, 0-100%) to afford 37 (16 mg, 9 / 10 ratio E / Z according to1H NMR) as a yellow solid. Yield: 31 %.1H NMR (500 MHz, CDCI3) 5 (ppm) 8.57 - 8.54 (m, 1 H), 8.47 (d, J = 4.5 Hz, 2H), 8.43 (d, J = 2.2 Hz, 1 H), 7.60 (dt, J = 8.0, 2.0 Hz, 1 H), 7.41 (dt, J = 8.1 , 2.0 Hz, 1 H), 7.32 - 7.27 (m, 2H), 6.49 (p, J = 2.4 Hz, 1 H), 6.41 (p, J = 2.4 Hz, 1 H), 5.29 (dd, J = 7.6, 6.1 Hz, 1 H), 5.20 (dd, J = 7.5, 6.2 Hz, 1 H), 4.86 - 4.62 (m, 4H), 3.85 (s, 3H), 3.82 (s, 3H), 3.21 - 2.98 (m, 4H), 2.02 (s, 3H), 2.01 (s, 3H), 1.82 (s, 3H), 1.82 (s, 3H).13C NMR (126 MHz, CDCI3) 5 (ppm) 180.66, 180.65, 162.22, 162.17, 154.8, 154.6, 149.4, 149.2, 147.98, 147.96, 142.8, 142.2, 134.8, 134.6, 132.8, 132.6, 123.7, 123.6, 120.4, 120.2, 118.3, 117.1 , 100.18, 100.16, 75.8, 73.6, 73.5, 70.3, 55.4, 55.3, 38.2, 34.3, 9.58, 9.56, 7.01 , 7.00. LC-MS: Rt= 5.24 min, ES+= 314.20, method 2. HR-MS: [M+Na]+calculated for CisHigNCLNa 336.1212; found 336.1210.EXAMPLE 49: Preparation of 49: 2-(4-(n ,1'-biphenyl1-4-ylmethyl)tetrahydrofuran-2-yl)-6-

[0153] A solution of 1 (15 mg, 0.04 mmol) in methanol was hydrogenated in an H-Cube (10% Pd / C cartridge, 1 mL / min, 30 °C, 3 bar). After completion of the reaction, the reaction mixture was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 5-100%) to afford 38 (4 mg, 3:1 ratio of cis:trans diastereomers) as an off-white solid. Yield: 29%.1H NMR of cis-enantiomers (major) (600 MHz, CDCI3) 5 (ppm) 7.59 - 7.56 (m, 2H),7.55-7.52 (m, 2H), 7.46-7.42 (m, 2H), 7.36-7.33 (m, 1H), 7.27-7.23 (m, 2H), 5.06 (dd, J = 9.5, 6.7 Hz, 1 H), 4.08 (dd, J = 8.2, 7.0 Hz, 1 H), 3.93 (d, J = 1.2 Hz, 3H), 3.73 - 3.68 (m, 1H), 2.90-2.72 (m, 3H), 2.35 (dt, J= 13.0, 6.8 Hz, 1H), 1.98 (s, 3H), 1.89- 1.82 (m, 1H), 1.85 (s, 3H).13C NMRof cis-enantiomers (major) (151 MHz, CDCI3) <5 (ppm) 180.9, 162.3, 155.4, 140.8, 139.6, 138.8, 129.3, 129.0, 127.4, 127.4, 127.1, 119.7, 100.0, 75.2, 74.0, 55.5, 42.1, 38.0, 36.3, 9.5, 7.0.1H NMR of trans-enantiomers (minor) (600 MHz, CDCI3) 5 (ppm) 7.59 - 7.56 (m, 2H), 7.55 - 7.52 (m, 2H), 7.46 - 7.42 (m, 2H), 7.36 - 7.33 (m, 1 H), 7.27 - 7.23 (m, 2H), 5.20 (dd, J =8.2, 5.9 Hz, 1H), 4.14 (dd, J= 8.3, 5.7 Hz, 1H), 3.93 (d, J= 1.2 Hz, 3H), 3.73-3.68 (m, 1H), 2.90 -2.72 (m, 3H), 2.35, 2.24-2.19 (m, 1H), 2.09-2.05 (m, 1H),2.01 (s, 3H), 1.84 (s, 3H).13C NMR of trans-enantiomers (minor) (151 MHz, CDCI3) 5 (ppm) 180.9, 162.2, 156.0, 140.9, 139.6,139.2, 129.2, 128.9, 127.5, 127.4, 127.1, 119.5, 100.0, 74.3, 74.2, 55.4, 41.9, 38.5, 36.1, 9.5, 7.0. LC-MS: Rt = 3.89 min, ES+= 391.14, method 1. HR-MS: [M+Na]+calculated for C2sH2eO4Na 413.1729; found 413.1724.EXAMPLE 50: Preparation of 50: 2-methoxy-6-(4-((4'-methoxy-n,1'-biphenyll-4- yl)methyl)tetrahydrofuran-2-yl)-3,5-dimethyl-4H-pyran-4-one

[0154] A solution of 13 (9 mg, 0.02 mmol) in methanol was hydrogenated in an H-Cube (10% Pd / C cartridge, 1 mL / min, 30 °C, 3 bar). After completion of the reaction, the reaction mixture was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 5-100%) to afford 39 (5 mg, 3:1 ratio of cis:trans diastereomers) as an off-white solid. Yield: 58%.1H NMR of cis-enantiomers (major) (400 MHz, CDCI3) 5 (ppm) 7.56 - 7.50 (m, 4H), 7.27-7.22 (m, 2H), 7.02-6.97 (m, 2H), 5.08 (dd, J= 9.5, 6.7 Hz, 1H), 4.13-4.07 (m, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.73 (t, J= 8.5 Hz, 1H), 2.92-2.71 (m, 3H), 2.36 (dt, J= 12.8, 6.6 Hz, 1H), 2.00 (s, 3H), 1.88- 1.85 (m, 1H), 1.87 (s, 3H).13C NMR of cis-enantiomers (major) (126 MHz, CDCI3) 5 (ppm) 180.9, 162.3, 159.3, 155.4, 139.2, 138.1, 133.4, 129.3, 128.1, 127.0, 119.7, 114.4, 99.9, 75.3, 74.1, 55.5, 55.5, 42.1, 37.9, 36.3, 9.5, 7.0.1H NMR of trans-enantiomers (minor) (400 MHz, CDCI3) 5 (ppm) 7.56 - 7.50 (m, 4H), 7.27 - 7.22 (m, 2H), 7.02 - 6.97 (m, 2H), 5.21 (dd, J= 8.1, 5.8 Hz, 1H), 4.18-4.13 (m, 1H), 3.95 (s, 3H), 3.88 (s, 3H), 3.73 (t, J= 8.5 Hz, 1H), 2.92-2.71 (m, 3H), 2.23 (dt, J= 13.0, 6.4 Hz, 1H), 2.13-2.05 (m, 1H), 2.03 (s, 3H), 1.86 (s,3H).13C NMR of trans-enantiomers (minor) (126 MHz, CDCh) 5 (ppm) 180.9, 162.2, 159.3, 156.1, 139.2, 138.6, 133.4, 129.1, 128.1, 127.1, 119.4, 114.4, 100.0, 74.4, 74.3, 55.5, 55.4, 42.0, 38.5, 36.1, 9.5, 7.0. LC-MS: Rt= 7.98 min, ES+= 421.31, method 2. HR-MS: [M+Na]+calculated for C26H28O5Na 443.1834; found 443.1826.EXAMPLE 51: Preparation of 51: 2-methoxy-3,5-dimethyl-6-(4-(naphthalen-2- ylmethyl)tetrahydrofuran-2-yl)-4H-pyran-4-one

[0155] A solution of 2 (16 mg, 0.04 mmol) in methanol was hydrogenated in an H-Cube (10% Pd / C cartridge, 1 mL / min, 30 °C, 3 bar). After completion of the reaction, the reaction mixture was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 5-100%) to afford 40 (5 mg, 3:1 ratio of cis:trans diastereomers) as an off-white solid. Yield: 31%.1H NMR of cis-enantiomers (major) (400 MHz, CDCh) <5 (ppm) 7.84-7.76 (m, 3H), 7.62 - 7.59 (m, 1 H), 7.50 - 7.43 (m, 2H), 7.34 - 7.29 (m, 1 H), 5.06 (dd, J = 9.6, 6.7 Hz, 1 H), 4.07 (dd, J= 8.2, 7.0 Hz, 1H), 3.86 (s, 3H), 3.76-3.71 (m, 1H), 3.03-2.89 (m, 2H), 2.88-2.76 (m, 1H), 2.33 (dt, J= 12.5, 6.8 Hz, 1H),1.96 (s, 3H), 1.92 - 1.86 (m, 1H), 1.84 (s, 3H).13C NMR of cis-enantiomers (major) (101 MHz, CDCh) 5 (ppm) 180.9, 162.3, 155.4, 137.2, 133.7, 132.3, 128.4, 127.8, 127.5, 127.3, 127.1, 126.4, 125.7, 119.8, 99.9, 75.3, 74.1, 55.4, 42.0, 38.5, 36.3, 9.5, 7.0.1H NMR of trans-enantiomers (minor) (400 MHz, CDCh) 5 (ppm) 7.84 - 7.76 (m, 3H), 7.64-7.62 (m, 1H), 7.50-7.43 (m, 2H), 7.34-7.29 (m, 1H), 5.21 (dd, J= 8.1, 5.9 Hz, 1H), 4.12 (dd, J= 8.7, 6.2 Hz, 1H), 3.90 (s, 3H), 3.73-3.70 (m, 1H), 3.03-2.89 (m, 2H), 2.88-2.76 (m, 1H), 2.24 - 2.16 (m, 1H), 2.12 - 2.04 (m, 1H), 2.00 (s, 3H), 1.83 (s, 3H).13C NMR of trans- enantiomers (minor) (101 MHz, CDCh) 5 (ppm) 180.9, 162.2, 156.0, 137.7, 133.7, 132.3, 128.5, 127.8, 127.6, 127.3, 127.2, 126.4, 125.7, 119.5, 100.0, 74.4, 74.3, 55.4, 41.9, 39.0, 36.1, 9.5, 7.0. LC-MS: Rt = 8.76 min, ES+= 365.24, method 2. HR-MS: [M+Na]+calculated for C28H24O4Na 387.1572; found 387.1568.EXAMPLE 52: Preparation of 52: 2-methoxy-6-(4-((6-methoxynaphthalen-2- yl)methyl)tetrahydrofuran-2-yl)-3,5-dimethyl-4H-pyran-4-one

[0156] A solution of 18 (16 mg, 0.04 mmol) in methanol was hydrogenated in an H-Cube (10% Pd / C cartridge, 1 mL / min, 30 °C, 3 bar). After completion of the reaction, the reaction mixture was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 5-100%) to afford 41 (4 mg, 3:1 ratio of cis:trans diastereomers) as an off-white solid. Yield: 26%.1H NMR of cis-enantiomers (major) (400 MHz, CDCI3) 5 (ppm) 7.71 - 7.65 (m, 2H), 7.53 (s, 1H), 7.30-7.24 (m, 1H), 7.16-7.13 (m, 1H), 7.13-7.09 (m, 1H), 5.05 (dd, J= 9.5, 6.6 Hz, 1H), 4.10-4.04 (m, 1H), 3.92 (s, 3H), 3.86 (s, 3H), 3.75-3.69 (m, 1H), 2.99-2.86 (m, 2H), 2.84-2.75 (m, 1H), 2.32 (dt, J= 13.0, 6.8 Hz, 1H), 1.96 (s, 3H), 1.91 - 1.86 (m, 1H), 1.84 (s, 3H).13C NMR of cis-enantiomers (major) (126 MHz, CDCI3) <5 (ppm) 180.9, 162.3, 157.6, 156.1, 134.9, 133.4, 129.1, 129.0, 127.8, 127.2, 127.0, 119.7, 119.2, 105.8, 99.9, 75.3, 74.1, 55.5, 55.4, 42.1, 38.3, 36.3, 9.5, 7.0.1H NMR of trans-enantiomers (minor) (400 MHz, CDCI3) <5 (ppm) 7.71 -7.65 (m,2H), 7.55 (s, 1H), 7.30 - 7.24 (m, 1H), 7.16 - 7.13 (m, 1H), 7.13-7.09 (m, 1H), 5.20 (dd, J = 8.1, 5.7 Hz, 1H), 4.12 (dd, J= 6.6, 2.2 Hz, 1H), 3.92 (s, 3H), 3.90 (s, 3H), 3.75-3.69 (m, 1H), 2.99-2.86 (m, 2H), 2.84-2.75 (m, 1H), 2.23-2.15 (m, 1H), 2.12-2.05 (m, 1H), 2.00 (s, 3H), 1.83 (s, 3H).13C NMR of trans-enantiomers (minor) (126 MHz, CDCI3) 5 (ppm) 180.9, 162.2, 157.6, 155.4, 135.3, 133.4, 129.2, 129.0, 127.7, 127.3, 126.9, 119.4, 119.2, 105.8, 99.9, 74.4, 74.3, 55.5, 55.4, 42.0, 38.8, 36.1, 9.5, 7.0. LC-MS: Rt= 8.65 min, ES+= 395.26, method 2. HR-MS: [M+Na]+calculated for C24H26O4Na 417.1678; found 417.1670.Example 53: Preparation of 53: 2-(4-(1-(f1,T-biphenyl1-4-yl)ethylidene)tetrahydrofuran-2-yl)-6-

[0157] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-(1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one(Intermediate B2) (58 mg, 0.139 mmol) and 4-bromo-1,1'-biphenyl (34 mg, 0.139 mmol, 1.0 eq.).Purification was performed by normal phase column chromatography (heptane / EtOAc, 5-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (23 mg, 8:10 ratio E / Z according to1H NMR) as an off-white solid. Yield: 40%.1H NMR (400 MHz, CDCI3) 5 (ppm) 7.62 - 7.56 (m, 8H), 7.47 - 7.42 (m, 4H), 7.38 - 7.34 (m, 2H), 7.34 - 7.30 (m, 2H), 7.25 - 7.22 (m, 2H), 5.24 (dd, J = 7.7, 6.4 Hz, 1 H, Z- isomer ) and 5.17 (dd, J = 7.3, 6.2 Hz, 1 H, E-isomer), 4.77 - 4.61 (m, 2H, E-isomer) and 4.61 - 4.49 (m, 2H, Z-isomer), 3.94 (s, 3H, Z-isomer) and 3.93 (s, 3H, E-isomer) 3.10 - 2.80 (m, 4H), 2.13 (t, J = 1.7 Hz, 3H, Z-isomer) and 2.03 (t, J = 1.7 Hz, 3H, E-isomer), 2.05 (s, 3H, Z-isomer) and 1.99 (s, 3, E-isomer), 1.86 (s, 3H, Z-isomer) and 1.83 (s, 3H, E-isomer).13C NMR (101 MHz, CDCI3) 5 (ppm) 180.9, 180.8, 162.3, 162.2, 155.4, 155.2, 141.8, 141.6, 140.7, 140.6, 140.0, 139.9, 134.6, 134.5, 129.0 (4C), 127.8 (2C), 127.56, 127.53, 127.52, 127.48 (2C), 127.2 (2C), 127.12 (2C), 127.11 (4C), 126.8, 120.0, 119.9, 100.1 , 100.0, 75.6, 74.7, 71.6, 71.2, 55.4, 55.3, 35.3, 35.1 , 21.5, 20.5, 9.6, 9.5, 7.1 , 7.0. LC-MS: Rt= 9.04 min, ES+= 403.24, method 2. HRMS: [M+Na]+calculated for C26H26O4Na 425.1729; found 425.1725.Example 54: Preparation of 54: 2-methoxy-3,5-dimethyl-6-(4-(1-(naphthalen-2- yl)ethylidene)tetrahydrofuran-2-yl)-4 / - / -pyran-4-one

[0158] Prepared according to general procedure A using 2-methoxy-3,5-dimethyl-6-(4-(1- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)ethylidene)tetrahydrofuran-2-yl)-4 / 7-pyran-4-one (Intermediate B2) (117 mg, 0.155 mmol) and 2-bromonaphthalene (54 mg, 0.262 mmol, 1.6 eq.). Purification was performed by normal phase column chromatography (heptane / EtOAc, 5-100%) and consecutive reverse phase column chromatography (Water+0.05% TFA / MeCN+0.05% TFA, 5-100%) to afford the title compound (12 mg, 8:10 ratio E / Z according to1H NMR) as an off-white solid. Yield: 8%.1H NMR (400 MHz, CDCh) 5 (ppm) 7.88 - 7.80 (m, 6H), 7.61 - 7.59 (m, 1 H), 7.57 (s, 1 H), 7.54 - 7.46 (m, 4H), 7.39 (dd, J = 8.5, 1.8 Hz, 1 H), 7.33 (dd, J = 8.4, 1.8 Hz, 1 H), 5.26 (dd, J = 7.6, 6.2 Hz, 1 H), 5.18 (dd, J = 7.2, 6.3 Hz, 1 H), 5.00 - 4.52 (m, 4H), 3.96 (s, 3H), 3.95 (s, 3H), 3.36 - 2.81 (m, 4H), 2.20 (d, J = 1.5 Hz, 3H), 2.11 (t, J = 1.5 Hz, 3H), 2.07 (s, 3H), 1.99 (s, 3H), 1.89 (s, 3H), 1.84 (s, 3H). LC-MS: Rt= 8.84 min, ES+= 377.19, method 2. HRMS: [M+Na]+calculated for C24H24O4Na 399.1572; found 399.1574.Example 55: Preparation of 55: 2-(1- biphenyl1-4-yl)-5-oxaspirof2.41heptan-6-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one

[0159] To a solution of diethylzinc (1M in hexane, 0.1 mL, 0.100 mmol) and anhydrous DCM (0.1 mL) at 0 °C was slowly added a solution of trifluoroacetic acid (7.75 pL, 0.100 mmol) in anhydrous DCM (0.05 mL) over a period of five minutes. After stirring at 0 °C for 20 minutes, a solution of diiodomethane (8.1 pL, 0.100 mmol) in anhydrous DCM (0.05 mL) was added over a period of five minutes. After stirring at 0 °C for 20 minutes, a solution of (Z)-2-(4-([1 ,1'-biphenyl]- 4-ylmethylene)tetrahydrofuran-2-yl)-6-methoxy-3,5-dimethyl-4 / 7-pyran-4-one (1.Z) (21 mg, 0.050 mmol) in anhydrous DCM (0.05 mL) was added. After stirring at room temperature for 16 hours, the reaction mixture was quenched with HCI (0.1 N, 0.5 mL) and diluted with DCM. The aqueous phase was extracted two more times with heptane. The combined organic phases were washed with NaHCOs (aq. sat.) and brine, dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo to afford the title compound (9 mg) as an off-white solid. LC-MS: Rt= 8.72 min, ES+= 403.16, method 2.Example 56: Preparation of 56: 6-(6-methoxy-3,5-dimethyl-4-oxo-4 / 7-pyran-2-yl)-5- oxaspirof2.41heptane-1 -carboxylate

[0160] A solution of 2-methoxy-3,5-dimethyl-6-(4-methylenetetrahydrofuran-2-yl)-4 / 7- pyran-4-one (42 mg, 0.16 mmol) and Rhodium(ll) triphenylacetate dimer (12 mg, 0.0080 mmol) in anhydrous DCM (4 mL) was heated to 45 °C under argon, before which a solution of ethyl diazoacetate (42 pl, 0.40 mmol) in anhydrous DCM (0.60 mL) was added slowly via a syringe pump over 5 hours. The reaction mixture was allowed to cool down to room temperature and concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (25 mg, mixture of diastereomers) as a brownoil. Yield: 44%. LC-MS: Rt= 7.17 min, ES+= 323.21 , method 2. HRMS: [M+Na]+calculated for Ci7H22O6Na 345.1314; found 345.1320.Preparation of intermediate C1 : (Z)-2-((Dihydrofuran-3(2 / 7)-ylidene)methyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane

[0161] To a solution of 2,2,6,6-tetramethylpiperidine (0.91 mL, 5.37 mmol) in anhydrous THF (8 mL) was added dropwise at 0 °C n-BuLi (3.58 mL, 5.37 mmol, 1.5M in hexanes). After stirring at 0 °C for 30 minutes, the reaction mixture was cooled to -78 °C, and a solution of bis[(pinacolato)boryl]methane (1.20 g, 4.48 mmol) in anhydrous THF (8 mL) was added dropwise. After stirring at -78 °C for 30 minutes, a solution of dihydrofuran-3(2 / 7)-one (528 l, 6.71 mmol) in anhydrous THF (22 mL) was added dropwise. The reaction mixture was allowed to slowly warm to room temperature. After 16 hours, the reaction mixture was cooled to 0 °C and NH4CI (aq. sat., 12 mL) was added dropwise. After one hour, the reaction mixture was filtered and concentrated to minimal volume in vacuo. The residue was diluted with water, and the aqueous phase was extracted three times with EtOAc. The combined organic phases were washed with brine, dried (Na2SO4), filtered, and the filtrated was concentrated in vacuo. The residue was purified by normal phase column chromatography (PE / EtOAc, 5-100%) to afford the title compound (740 mg, 1 :10 ratio E / Z according to1H NMR) as a colourless liquid. Yield: 75%.1H NMR Z-isomer (400 MHz, CDCh) 5 (ppm) 5.38 (p, J = 2.3 Hz, 1 H), 4.45 (dt, J = 2.8, 1.5 Hz, 2H), 3.86 (t, J = 6.9 Hz, 2H), 2.67 - 2.58 (m, 2H), 1.31 - 1.20 (m, 12H);1H NMR E-isomer (400 MHz, CDCh) 5 (ppm) 5.30 - 5.24 (m, 1 H), 4.29 (m, 2H), 3.93 (t, J = 7.0 Hz, 2H), 2.82 - 2.75 (m, 2H), 1.31 - 1.20 (m, 12H).13C NMR (101 MHz, CDCh) 5 (ppm) 165.6, 83.2 (2C), 71.6, 67.8, 36.1 , 25.0 (4C). One C (next to Boron) not observable. Spectroscopic data are in agreement with those reported in literature.17The following Examples 57 to 59 are comparative Examples. The compounds of these Examples are negative controls. Biphenyl1-4-ylmethylene)tetrahydrofuran

[0162] Prepared according to general procedure A using (Z)-2-((Dihydrofuran-3(2 / 7)- ylidene)methyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (Intermediate C1) (590 mg, 2.67 mmol) and 4-bromobiphenyl (684 mg, 2.94 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) to afford the title compound (419 mg, 1 :10 ratio E / Z according to1H NMR) as a white powder. Yield: 63%.1H NMR of Z-isomer (400 MHz, CDCh) 6 (ppm) 7.64 - 7.57 (m, 4H), 7.48 - 7.42 (m, 2H), 7.38 - 7.32 (m, 1 H), 7.24 - 7.19 (m, 2H), 6.50 (p, J = 2.3 Hz, 1 H), 4.64 (q, J = 1.9 Hz, 2H), 3.93 (t, J = 6.9 Hz, 2H), 2.81 (tq, J = 6.9, 1.9 Hz, 2H).13C NMR of Z-isomer (101 MHz, CDCh) 5 (ppm) 141.9, 140.7, 139.3, 136.6, 128.9, 128.4, 127.4, 127.3, 127.1 , 120.7, 69.8, 67.5, 35.1. LC-MS: Rt= 7.99 min, ES+= 237.18, method 2. HR-GCMS: [M]+calculated for C17H16O 236.1201 ; found 236.1200.Example 58: Preparation of 58: (Z)-3-(Naphthalen-2-ylmethylene)tetrahydrofuran

[0163] Prepared according to general procedure A using (Z)-2-((Dihydrofuran-3(2 / 7)- ylidene)methyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (Intermediate C1) (50 mg, 0.219 mmol) and 2-bromonaphthalene (50 mg, 0.241 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) to afford the title compound (20 mg, 1 :10 ratio E / Z according to1H NMR) as a white powder. Yield: 40%.1H NMR of Z-isomer (400 MHz, CDCh) 5 (ppm) 7.85 - 7.78 (m, 3H), 7.57 - 7.53 (m, 1 H), 7.52 - 7.42 (m, 2H), 7.30 (dd, J = 8.5, 1.9 Hz, 1 H), 6.61 (p, J = 2.3 Hz, 1 H), 4.70 (q, J = 2.0 Hz, 2H), 3.94 (t, J = 6.9 Hz, 2H), 2.87 - 2.79 (m, 2H).13C NMR of Z-isomer (101 MHz, CDCh) 5 (ppm) 142.2, 135.2, 133.6, 132.1 , 128.2, 128.1 , 127.7, 126.6, 126.4, 126.3, 125.9, 121.2, 69.8, 67.5, 35.2. LC-MS: Rt= 8.45 min, ES+= 211.19, method 2. HR-GCMS: [M]+calculated for CI5HI4O 210.1045; found 210.1054.Example 59: Preparation of 59: (Z)-6-((Dihydrofuran-3(2 / 7)-ylidene)methyl)quinoline

[0164] Prepared according to general procedure A using (Z)-2-((Dihydrofuran-3(2 / 7)- ylidene)methyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (Intermediate C1) (200 mg, 0.90 mmol) and 6-bromoquinoline (207 mg, 0.99 mmol, 1.1 eq.). Purification was performed by normal phase column chromatography (PE / EtOAc, 0-100%) to afford the title compound (114 mg, 1 :10 ratio E / Zaccording to1H NMR) as a brown crystalline solid. Yield: 57%.1H NMR of Z-isomer (400 MHz, CDCI3) 6 (ppm) 8.87 (dd, J = 4.2, 1.7 Hz, 1H), 8.14 - 8.09 (m, 1H), 8.06 (d, J = 8.7 Hz, 1H), 7.55 - 7.49 (m, 2H), 7.39 (dd, J = 8.3, 4.2 Hz, 1 H), 6.61 (p, J = 2.4 Hz, 1 H), 4.68 (q, J = 1.9 Hz, 2H), 3.94 (t, J = 6.9 Hz, 2H), 2.84 (tq, J = 6.9, 1.8 Hz, 2H).13C NMR of Z-isomer (101 MHz, CDCh) 5 (ppm) 150.3, 147.2, 143.6, 136.1, 135.9, 130.0, 129.7, 128.5, 126.1, 121.6, 120.5, 69.8, 67.5, 35.2. LC-MS: Rt= 5.03 min, ES+= 212.19, method 2. HRMS: [M+H]+calculated for C14H14O4N 212.1075; found 212.1069.4. Biological Testing4.1 HIV-1

[0165] To determine the ECso of the antiviral compounds, 2*104LC5-RIC cells were seeded in black, optical bottom 96-well plates (Greiner) one day prior to infection and treatment. The following day, cells were treated with the compounds at the indicated concentrations, followed by HIV-1 inoculation (co-treatment) at an MOI of 1. Infection and antiviral activity were scored 48 h post infection by measuring DsRed fluorescence using a Spark plate reader from Tecan. Cell metabolic activity, used to determine the CC50, was determined by incubating infected cells for 1 h at 37 °C with the CellTiter-Blue® reagent (Promega) according to manufacturer’s protocol. IC50 and CC50 values were calculated using GraphPad Prism 9 (GraphPad Software).Table 2: IC50 values of exemplary compoundsICso<1O pM: +ICso<3 pM: ++ICso<1 pM: +++ICso<3OO nM: ++++ICso<1OO nM: +++++4.2 Inhibition of infection assays (SARS-CoV-2)

[0166] CaCo2 cells were simultaneously treated with compounds and exposed to a reporter SARS-CoV-2 virus expressing a fluorophor upon replication. 48 h after infection, cells were fixed with 2% PFA and counterstained with Hoechst. Compound effects on infectious virus production were determined via measure of the fluorescent signal with a multiplate reader. Cells were exposed to the reporter virus at an MOI of 0.2.ICso<1O pM: +ICso<3 pM: ++ICso<1 pM: +++ICso<3OO nM: ++++ICso<1OO nM: +++++4.3 Inhibition of infection assays (DENV)

[0167] Huh7-Lunet reporter cell line was used to determine compounds antiviral effect. Huh7-Lunet reporter cells possess a GFP with a transmembrane domain anchored at the ER membrane. The GFP linker to the transmembrane domain is cleaved upon infection by DENV and relocates to the nucleus. Cells were treated with compounds and incubated for 24 h. They were then inoculated with virus and the GFP signal was monitored for 24 h. Compound effects on infectious virus production were estimated via determination of the GFP signal localization in the cells. Cells were exposed to the DENV virus strain at an MOI of 1.ICso<10 pM: +ICso<3 pM: ++ICso<1 pM: +++ICso<3OO nM: ++++ICso<100 nM: +++++5. Toxicity study

[0168] The toxicity of compounds of the present invention and a structurally similar reference compound has been tested in mice. The reference compound has the structureTable 3: Acute toxicity (24 h) single doseTable 4: Longterm (7 d) - multiple dosing, once every 24 h (signs of toxicity after dosing)REFERENCES(1) Ratushnyy, M.; Parasram, M.; Wang, Y; Gevorgyan, V. Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(Sp3)-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates. Angew. Chem. Int. Ed. 2018, 57 (10), 2712- 2715. https: / / doi.Org / 10.1002 / anie.201712775.(2) Riaz, M. T.; Pohorilets, I.; Hernandez, J. J.; Rios, J.; Totah, N. I. Preparation of 2- (Trimethylsilyl)Methyl-2-Propen-1-OI Derivatives by Cobalt Catalyzed Sp2-Sp3 Coupling. Tetrahedron Lett. 2018, 59 (29), 2809-2812. https: / / doi.Org / 10.1016 / j.tetlet.2018.06.018.(3) Trost, B. M.; Buch, M.; Miller, M. L. Convenient Alternative Approach to 2-(Acetoxymethyl)-3-(Trimethylsilyl)Propene. J. Org. Chem. 1988, 53 (20), 4887-4888. https: / / doi.org / 10.1021 / jo00255a048.(4) De Paolis, M.; Rosso, H.; Henrot, M.; Prandi, C.; d’Herouville, F.; Maddaluno, J. A ConciseRoute to A'-Methoxy-y-Pyrones and Verticipyrone Based Upon the Desymmetrization of a,A'- Dimethoxy-v-Pyrone. Chem. - Eur. J. 2010, 16 (37), 11229-11232. https: / / doi.org / 10.1002 / chem.201001780.(5) Jacobsen, M. F.; Moses, J. E.; Adlington, R. M.; Baldwin, J. E. A Short Total Synthesis ofAureothin and N-Acetylaureothamine. Org. Lett. 2005, 7 (4), 641-644. https: / / doi.org / 10.1021 / ol047594l.(6) Mizuta, S.; Stenhagen, I. S. R.; O’Duill, M.; Wolstenhulme, J.; Kirjavainen, A. K.; Forsback, S.J.; Tredwell, M.; Sandford, G.; Moore, P. R.; Huiban, M.; Luthra, S. K.; Passchier, J.; Solin, O.; Gouverneur, V. Catalytic Decarboxylative Fluorination for the Synthesis of Tri- and Difluoromethyl Arenes. Org. Lett. 2013, 15 (11), 2648-2651. https: / / doi.org / 10.1021 / ol4009377.(7) Ali, I.; Siyo, B.; Hassan, Z.; Malik, I.; Ullah, I.; Ali, A.; Nawaz, M.; Iqbal, J.; Patonay, T.; Villinger, A.; Langer, P. Synthesis of Trifluoromethyl-Substituted Bi- and Terphenyls by Site-Selective Suzuki-Miyaura Reactions of Various Dihalogenated Trifluoromethyl-Benzene Derivatives. J. Fluor. Chem. 2013, 145, 18-34. https: / / doi.Org / 10.1016 / j.jfluchem.2012.11.005.(8) Zhou, Q.; Zhang, B.; Su, L.; Jiang, T.; Chen, R.; Du, T.; Ye, Y; Shen, J.; Dai, G.; Han, D.; Jiang, H. Palladium-Catalyzed Highly Regioselective 2-Arylation of 2,x-Dibromopyridines and Its Application in the Efficient Synthesis of a 17P-HSD1 Inhibitor. Tetrahedron 2013, 69 (51), 10996-11003. https: / / doi.Org / 10.1016 / j . tet.2013.10.065.(9) Cacchi, S.; Caponetti, E.; Casadei, M. A.; Di Giulio, A.; Fabrizi, G.; Forte, G.; Goggiamani, A.; Moreno, S.; Paolicelli, P; Petrucci, F.; Prastaro, A.; Saladino, M. L. Suzuki-Miyaura CrossCoupling of Arenediazonium Salts Catalyzed by Alginate / Gellan-Stabilized Palladium Nanoparticles under Aerobic Conditions in Water. Green Chem 2012, 14 (2), 317-320. https: / / doi.org / 10.1039 / C2GC15679B.(10) Music, A.; Baumann, A. N.; Boser, F.; Muller, N.; Matz, F.; Jagau, T. C.; Didier, D.Photocatalyzed Transition-Metal-Free Oxidative Cross-Coupling Reactions of Tetraorganoborates**. Chem. - Eur. J. 2021 , 27 (13), 4322-4326. https: / / doi.org / 10.1002 / chem.202005282.(11)Patra, T.; Mukherjee, S.; Ma, J.; Strieth-Kalthoff, F; Glorius, F. Visible-Light-Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions. Angew. Chem. Int. Ed. 2019, 58 (31), 10514-10520. https: / / doi.org / 10.1002 / anie.201904671.(12) Tu, L.; Li, C.; Xiong, X.; Hyeon Kim, J.; Li, Q.; Mei, L.; Li, J.; Liu, S.; Seung Kim, J.; Sun, Y. Engineered Metallacycle-Based Supramolecular Photosensitizers for Effective Photodynamic Therapy. Angew. Chem. Int. Ed. 2023, 62 (15), e202301560. https: / / doi.Org / 10.1002 / anie.202301560.(13) Y. Fukazawa, A. E. Rubtsov, A. V. Malkov, Eur. J. Org. Chem. 2020, 22, 3317-3319.(14) D. Prajapati, C. Schulzke, M. K. Kindermann, et al., RSC Adv. 2015, 5, 53073-53085.(15) Z. M. Hudson, C. Sun, M. G. Helander, Adv. Fund. Mater. 2010, 20, 3426-3439.(16) R. B. Bedford, M. A. Hall, G. R. Hodges, et al., Chem. Commun. 2009, 42, 6430-6432.(17) Kovalenko, M.; Yarmoliuk, D. V.; Serhiichuk, D.; Chernenko, D.; Smyrnov, V.; Breslavskyi, A.; Hryshchuk, O. V.; Kleban, I.; Rassukana, Y; Tymtsunik, A. V.; Tolmachev, A. A.; Kuchkovska, Y. O.; Grygorenko, O. O. The Boron-Wittig Olefination of Aldehydes and Ketones with Bis[(Pinacolato)Boryl]Methane: An Extended Reaction Scope. Eur J Org Chem 2019, 2019 (33), 5624-5635.

Claims

1. Claims1 . A compound according to general formula (I),and hydrates, solvates, salts, complexes, racemic mixtures, diastereomers, diastereomeric mixtures, enantiomers, and tautomers thereof and isotopically enriched forms of any of the foregoing, whereinQ is selected from the group consisting ofandR1and R2are independently selected from the group consisting of -H, -(Ci-Cw)alkyl , (Cs-C jaryl, (Cs-Cio)heteroaryl, wherein optionally (Cs-Cio)aryl, (Cs-Cio)heteroaryl are substituted with one or more residues independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2- Cw)alkenyl, -(C2-C )alkynyl, -(C3-C )cycloalkyl, -(Ci-Cio)alkyl(C3-C6)cycloalkyl, -(C1-C10- )alkyl(C6-C )aryl, -(Ci-Cio)alkyl(C3-C )heteroaryl, -(Ci-C )alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), -N(R3)(OR3), -S(O)0-2R3, S(O)I-2OR3, -OS(O)I-2R3, OS(O)i- 2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I-2OR3, -N(R3)S(O)I.2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, and -XC(=X)XR3, antibody- conjugate (AC)wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups issubstituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid;P is selected from the group consisting of -OR3, -(Ci-Cio)alkyl, preferably -OMe, -ethyl, more preferably -OMe;A is selected from the group consisting of (Cs-Cio)aryl, (Cs-Cio)heteroaryl, wherein optionally -(Cs- Cw)aryl, -(Cs-Cio)heteroaryl are substituted with one or more residues independently selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci- Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Ci-Cw)alkyl(C3- Cejcycloalkyl, -(Ci-Cio)alkyl(Ce-Cio)aryl, -(Ci-Cio)alkyl(C3-Cw)heteroaryl, -(Ci-Cw)alkyl(C3- C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), N(R3)(OR3), -S(O)0-2R3, S(O)I-2OR3, -OS(O)I-2R3, OS(O)i- 2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I-2OR3, -N(R3)S(O)I.2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, -N=N-R3, -C(R3)=N=N, -(Ci-Cs)alkyloxiranyl, -O-O- R3, -S-S-R3, and -XC(=X)XR3, antibody- conjugate (AC), two adjacent rests may form a ring:wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid, and antibody -conjugate (AC); p is is an integer from 1 to 3;M is selected from the group consisting of a bond, (Ci-C4)alkanediyl, -NH-C(O)-, -C(O)-NH-, - C=C- or (C2-Ce)alkyndiyl, wherein optionally (C2-C4)alkanediyl is substituted with one or more residue selected from the group consisting of halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, - (Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(C1- Cw)alkyl(C3-C6)cycloalkyl, -(Ci-Cio)alkyl(Ce-Cio)aryl, -(Ci-Cw)alkyl(C3-Cio)heteroaryl, -(C1- Cio)alkyl(C3-C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), N(R3)(OR3), -S(O)0-2R3, -S(O)I-2OR3, - OS(O)I.2R3, -OS(O)I-2OR3, -S(O)I-2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I. 2OR3, N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, and -XC(=X)XR3;B is selected from the group consisting of H, (Cs-Cio)aryl, (Cs-Cio)heteroaryl, wherein optionally (Cs-Cio)aryl, (Cs-Cio)heteroaryl are substituted with one or more independently selected from the group consisting of hydrogen, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci- Cw)haloalkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Ci-Cw)alkyl(C3- C6)cycloalkyl, -(Ci-Cio)alkyl(C6-Cw)aryl, -(Ci-Cio)alkyl(C3-Cw)heteroaryl, -(Ci-Cw)alkyl(C3- C6)heterocyclyl, -OH, -OR3, -N(R4)(R5), -N(R3)(OR3), -S(O)0-2R3, -S(O)I-2OR3, -OS(O)i- 2R3, -OS(O)I-2OR3, -S(O)I.2N(R4)(R5), -OS(O)I.2N(R4)(R5), -N(R3)S(O)I.2R3, -N(R3)S(O)I. 2OR3, -N(R3)S(O)I-2N(R4)(R5), -C(=X)R3, -C(=X)XR3, -XC(=X)R3, -N=N-R3, -C(R3)=N=N, -C(R3)- N=N(R3), -(Ci-Cs)alkyloxiranyl, -O-O-R3, -S-S-R3, and -XC(=X)XR3, antibody-conjugate (AC), two adjacent rests may form a ring:p is is an integer from 1 to 3; wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl groups is optionally substituted with one or more substituents independently selected from the group consisting of R10, phosphoryl, folic acid, and antibody- conjugate (AC);X is independently selected from O, S, and N(R6);R3is, in each case, selected from the group consisting of -H, -(Ci-Cw)alkyl, -(C2-Cio)alkenyl, -(C2- Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(Cs-Cejheterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independetely selected R10;R4and R5are, in each case, independently selected from the group consisting of -H, -(C1- Cw)alkyl, -(C2-Cio)alkenyl, -(Ci-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(C3-Cw)aryl, -(C3-Cw)heteroaryl, and heterocyclyl, -N=CR7R8, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independetely selected R10;R6is independently selected from from the groups consisting of H, -(Ci-Cw)alkyl, -(C2-Cw)alkenyl, -(C2-Cw)alkynyl, -(C3-Cw)cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(Cs-Cejheterocyclyl and OR3, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R10;R7and R8are independently selected from the group consisting of - H, -(Ci-Cw)alkyl, -(C2- Cw)alkenyl, -(C2-C )alkynyl, -(C3-C )cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cio)heteroaryl, and -(C3- C6)heterocyclyl, and -NHyR92-y, or R7and R8may join together with the atom to which they are attached to form a ring which is optionally substituted with one or more independently selected R10, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally susbstituted with one more independently selected R10; y is an integer from 0 to 2;R9is selected from the group consisting of -(Ci-Cio)alkyl, -(C2-C )alkenyl, -(C2-C )alkynyl, -(C3- Cw)cycloalkyl, -(Cs-C jaryl, -(Cs-Cio)heteroaryl, and -(Cs-Cejheterocyclyl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl groups is optionally substituted with one or more independently selected R10; and R10is a 1stlevel substituent and is, in each case independently selected from the group consisting of -(Ci-Cw)alkyl, -(C2-Cio)alkenyl, -(C2- Cw)alkynyl, -(C3-C )cycloalkyl, -(Cs-Cio)aryl, -(Cs-Cwjheteroaryl, and -(Cs-Csjheterocyclyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -(Ci-Cw)alkyl, -(Ci-Cw)haloalkyl, -(C1- Cw)alkenyl, -(Ci-Cw)alkynyl, -(C3-Cw)-cycloalkyl, -(Ci-Cw)alkyl(C3-C6)cycloalkyl, -(C1- Cio)alkyl(C6-C )aryl, -(Ci-Cw)alkyl(C3-Cw)heteroaryl, -(Ci-Cw)alkyl(C3-C6)heterocyclyl, -OH, - OR11, -N(R12)(R13), -N(R11)(OR11), -S(O)0-2R11, -S(O)I-2OR11, -OS(O)I-2R11, OS(O)I-2OR11, -S(O)i-2N(R12)(R13), -OS(O)I.2N(R12)(R13), -N(R11)S(O)I-2R11, -N(R11)S(O)I-2OR11, -N(R11)S(O)I-2N(R12)(R13), -C(=X1)R11, -C(=X1)X1R11, -X1C(=X1)R11, and -X1C(=X1)X1R11, and / or any two R10which are bound to the same carbon atom of a cycloalkyl or heterocyclyl may join together to form =X1, wherein each of the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, and heterocyclyl groups being a 1stlevel substituent is optionally substituted by one or more 2ndlevel substituents, wherein said 2ndlevel substituent is, in each case, independently selected from the group consisting of -(Ci-Cs)alkyl, (C2-Cs)alkenyl, (C2-Ce)alkynyl, -(Cs-Cwjaryl, -(Cs-Cwjheteroaryl, -(C3- Cujcycloalkyl, -(Cs-Cwjheterocyclyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, - OR14, -N(R15)(R16), -N(R14)(OR14), -S(O)0-2R14, -S(O)I-2OR14, -OS(O)I-2R14, -OS(O)I-2OR14, -S(O)i-2N(R15)(R16), -OS(O)I-2N(R15)(R16), -N(R14)S(O)I.2R14, -N(R14)S(O)I-2OR14, N(R14)S(O)I.2N(R15)(R16), -C(=X2)R14, -C(=X2)X2R14, -X2C(=X2)R14, and -X2C(=X2)X2R14, and / or any two 2ndlevel substituents which are bound to the same carbon atom of a cycloalkyl or heterocyclyl group being a 1stlevel substituent may join together to form =X2, wherein each of the -(Ci-Cejalkyl, -(C2-Ce)alkenyl, -(Cs-Cejalkynyl, -(Cs-Cujaryl, -(Cs-Cwjheteroaryl, -(Cs-Cwjcycloalkyl, -(C3- Cwjheterocyclyl groups being a 2ndlevel substituent is optionally substituted with one or more 3rdlevel substituents, wherein said 3rdlevel substituent is, in each case, independently selected from the group consisting of -(Ci-Cs)alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano,isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, - O(Ci-C3alkyl), -S(Ci-C3)alkyl, -NH2, -NH(CI-C3) alkyl), -N((CI-C3) alkyl)2, - NHS(O)2((CI-C3) alkyl), -S(O)2NH2.Z((CI-C3) alkyl)z, -C(=O)((Ci-C3) alkyl), -C(=O)O((Ci-C3) alkyl), -C(=O)NH2.Z((CI-C3) alkyl)z, -OC(=O)(Ci-C3) alkyl), -OC(=O)O((Ci-C3)alkyl), -OC(=O)NH2.z((Ci-C3)alkyl)z, - NHC(=O)((CI-C3) alkyl), -NHC(=O)NH2.z(Ci-C3alkyl)z, -NHC(=NH)NH2.z((Ci-C3) alkyl)z, and - N((Ci-C3) alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or2 and (Ci-C3) alkyl is methyl, ethyl, propyl or isopropyl, and / or any two 3rdlevel substituents which are bound to the same carbon atom of a -(C3-Ci4)cycloalkyl or heterocyclyl group being a 2ndlevel substituent may join together to form =0, =S, =NH, or =N(CI-3alkyl); whereinR11, R12, and R13are independently selected from the group consisting of -H, -(Ci-Ce)alkyl, -(C2- Ce)alkenyl, -(C2-Ce)alkynyl, -(C3-C7)cycloalkyl, -(Cs-Ce) aryl, -(Cs-Cejheteroaryl, and -(C3- Cyjheterocyclyl, wherin each of the -(Ci-Ce)alkyl, -(C2.C6)alenyl, -(C2-Ce)alkynyl, -(C3- Cy)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and (C3-Cy)heterocyclyl groups is obtainally substituted with one, two or three substituents selected from the group consisting of (Ci-C3) alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -O((Ci-C3) alkyl), -S(Ci-C3alkyl), - NH2, -NH((Ci-C3)alkyl), -N((Ci-C3)alkyl)2, -NHS(O)2(CI-C3alkyl), -S(O)2NH2.Z(CI-C3) alkyl)z, - C(=O)((Ci-C3)alkyl), -C(=O)O((Ci-C3)alkyl), -C(=O)NH2.z((Ci-C3)alkyl)z, -OC(=O)((Ci-C3) alkyl), - OC(=O)O((C1-C3) alkyl), -OC(=O)NH2.z((Ci-C3) alkyl)z, -NHC(=O)(Ci-C3) alkyl), -NHC(=O)NH2.z((Ci-C3) alkyl)z, -NHC(=NH)NH2.z((Ci-C3) alkyl)z, and -N((CI-C3) alkyl)C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3) alkyl is methyl, ethyl, propyl or isopropyl;R14, R15, and R16are independently selected from the group consisting of -H, (Ci-Ce)alkyl, (C2- Ce)alkenyl, (C2-Ce)alkynyl, -(C3-C7)cycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3- Cy)heterocyclyl, wherein each of the (Ci-Ce)alkyl, (C2.C6)alkenyl, -(C2-Ce)alkynyl, -(C3- Cyjcycloalkyl, -(Cs-Cejaryl, -(Cs-Cejheteroaryl, and -(C3-Cy)heterocyclyl groups is obtainally substituted with one, two or three substituents selected from the group consisting of (Ci-C3) alkyl, halogen, trifluoromethyl, trifluoromethoxy, nitro, cyano, isocyano, cyanato, isocyanato, thiocyanato, isothiocyanato, azido, pentafluorosulfanyl, -OH, -O(Ci-C3) alkyl), -S(Ci-C3)alkyl), - NH2, -NH(CI-C3)alkyl, -N((CI-C3alkyl))2, -NHS(O)2(Ci-C3)alkyl, -S(O)2NH2.z((Ci-C3)alkyl)z, - C(=O)(Ci-C3)alkyl, -C(=O)O(Ci-C3)alkyl, -C(=O)NH2.Z((CI-C3) alkyl)z, -OC(=O)(Ci-C3) alkyl, - OC(=O)O(C1-C3) alkyl, -OC(=O)NH2.z((Ci-C3) alkyl)z, -NHC(=O)(Ci-C3)alkyl, -NHC(=O)NH2.Z((CI- C3)alkyl)z, -NHC(=NH)NH2.z((Ci-C3) alkyl)z, and -N(Ci-C3)alkyl C(=NH)NH2.z((Ci-C3) alkyl)z, wherein z is 0, 1 , or 2 and (Ci-C3) alkyl is methyl, ethyl, propyl or isopropyl;X1and X2are independently selected from O, S, and N(R17), wherein R17is -H or (C1-C3) alkyl.

2. The compound according to claim 1 , whereinR1 is H or methyl; and / orR2 is H or methyl; and / orA is (Cs-Cio)aryl or (Cs-Cio)heteroaryl; and / orM is a bond, (Ci-C2)alkanediyl, NH-C(O)-, -C(O)-NH- or -NH-C(O)-; and / orB is (Cs-Cio)aryl or (Cs-Cio)heteroaryl;3. The compound according to general formula (I) of claim 1 or 2, wherein for Q, the alkene group iconnected to R1 and A has a (Z) configuration.

4. The compound according to general formula (I) of claims 1 to 3, whereinR1and R2are independently selected from the group consisting of -H, -(Ci-C3)alkyl; and / orA is selected from the group consisting of phenyl, naphthyl, thienyl, pyridyl, pyridimyl, quinolyl, isoquinolyl, quinoxalinyl, wherein optionally each of the phenyl, naphthyl, pyridyl, quinolyl, and quinoxalinyl is substituted with one or more residues independently selected from the group consisting of halogen, -OH, -NH2, -COOH, trifluoromethyl, trifluoromethoxy, -(Ci-Cw)alkyl, -cyano, -OR3,M is a bond;B is selected from the group consisting of phenyl, naphthyl, thienyl, pyridyl, pyridimyl, quinolyl, isoquinolyl, quinoxalinyl, wherein optionally each of the phenyl, naphthyl, pyridyl, quinolyl, and quinoxalinyl is substituted with one or more residues independently selected from the group consisting of halogen, -OH, -NH2, -COOH, trifluoromethyl, trifluoromethoxy, -(Ci-Cw)alkyl, -cyano, -OR3, -cyclopropyl, -methylenecyclopyl, -CONH2.

5. The compound of claims 1 to 4, wherein the antibody- conjugate (AC) has the general formula (IV)-L-L0-LI-L2-Z(IV)L is selected from the group consisting of -O-, -NR17-, -NH-, -NHC(O)-, -C(O)NR18-, -N(OR3)-, - S(O)0-2-, S(O)i-2O-, -OS(O)i-2-, OS(O)i-2O-, -S(O)I-2N(R4)-, -OS(O)I.2N(R4)-, -N(R3)S(O)I-2-, - N(R3)S(O)I-2O-, -N(R3)S(O)I-2N(R4)-, -C(=X)-, -C(=X)X-, -XC(=X)-, and -XC(=X)X;Lo is a bond, -(CH2)ni-, -(Ci-Cw)alkyldiyl-, -(Ci-C6)cycloalkyldiyl-, -(Ci-C6)heterocycloalkyldiyl, ?c■ , -O-, -phenyl-, -NR17-, -NH-, -NR18C(O)-, -OC(O)NH-, -C(O)NR18-, -S-, -CH(OH)-, and -phenyl, -(Ci-C6)heterocycloalkyldiyl is optionally substituted with one or more substituents selected from the group consisting of -NH2, -NHC(=NH)NH2, -COOH, -CONH2, halogen, -NHR18,-NHC(O)NH2, -OR19; n1is an integer between 1 to 30, preferably 1 to 20, more prferably 1 to 10;Li is a suitable linking moiety; preferably Li is selected from the group consisting ofphenyl, -(Ci-C6)heterocycloalkyldiyl is optionally substituted with one or more substituents selected from the group consisting of -NH2, -NHC(=NH)NH2, -COOH, -CONH2, halogen, - NHR18, -NHC(O)NH2, -OR19;Zis an antibody, single-chain antibody or nanobody, preferably selected from the group consisting of antibodies such as EGFR targeting antibodies like cetuximab, panitutumab, Depatuxizumab, HER2 targeting antibodies such as trastuzumab, disitamab, pertuzumab CEA targeting antibodies like cergutuzumab, VEGFR targeting antibodies such as bevatuzumab, ramucirumab, CD19 targeting antibodies such as loncastuximab, CD22 targeting antibodies such as inotuzumab, moxetumomab, CD30 targeting antibodies such as brentuximab, CD33 targeting antibodies such as gemtuzumab, CD79b targeting antibodies such as polatuzumab, Nectin-4 targeting antibodies such as enfortumab, TROP2 targeting antibodies such as sacituzumab, datopotamab , tissue factor targeting antibodies such as tisotumab, BCMA (B-cell maturation antigen) targeting antibodies such as belantamab, FRa (Folate Receptor alpha) targeting antibodies such as mirvetuximab, DLL targeting antibodies such as rovalpituzumab, NaPi2 targeting antibodies such as lifastuzumab, CD22 targeting antibodies such as inotuzumab.

6. The compound according to claims 1 to 5, selected from the group consisting ofor hydrates, solvates, salts, complexes, racemic mixtures, diastereomers, diastereomeric mixtures enantiomers, and tautomers thereof and isotopically enriched forms of any of the foregoing.

7. A pharmaceutical composition comprising the compound according to claims 1 to 6 and at least one pharmaceutically acceptable carrier.

8. The compound according to claims 1 to6 or the pharmaceutical composition of claim 7 for use in the treatment of a virus infection, wherein the virus infection is caused by a virus selected from the group consisting of Retroviridae, Herpesviridae, Hepadnaviridae, Orthomyxoviridae,Paramyxoviridae, Flaviviridae, Papillomaviridae, Phenuiviridae, Nairoviridae, Hantaviridae, Arenaviridae, Togaviridae, Coronaviridae, Adenoviridae, Filoviridae, Rhabdoviridae, Pneumoviridae, Poxviridae.

9. The compound according to claims 1 to 6 or the pharmaceutical composition of claim 7 for use in the treatment of a virus infection wherein the virus infection is caused by a virus selected from the group consisting of HIV-1 , HIV-2, HTLV-1 , HTLV-2, HSV-1 , HSV-2, VZV, human CMV (HCMV), EBV type 1 , EBV type 2, HHV6, HHV7, HBV-A, influenzavirus A, influenzavirus B, Measles Virus (MV), Nipah virus, HCV, DENV-1 , DENV-2, DENV-3, DENV-4, ZIKV, WNV, TBEV Toro, TBEV Hypr, YFV, HPV-16, HPV-18, RVFV, CCHFV, Hantavirus, Lassa virus, CHIKV, SARS-CoV, SARS-CoV-2, MERS, Human Adenovirus 5 (hAdV5), Zaire EBOV, MARV-A, MARV- B, Rabies lyssavirus, HRSV, Monkeypox virus (MPXV), preferably SARS-CoV-2, HIV-1 , HRSV and DENV-2.

10. The compound according to any one of claims 1 to 6 for the use in the treatment of a condition, disorder or disease which is mediated or caused by a virus strain which is resistant to one or more antiviral drugs.

11. The compound for the use according to claim 10, wherein the antiviral drugs are selected from the group consisting of entry inhibitors, reverse transcriptase (RT) inhibitors, integrase inhibitors, protease inhibitors, inhibitors of DNA synthesis, uncoating inhibitors, assembly inhibitors, and release inhibitors.

12. The compound or pharmaceutical composition for the use according to any one of claims 8 to 11 , wherein the treatment further comprises administering at least one additional active compound, in particular at least one antiviral agent.

13. The compound according to claims 1 to 6 or the pharmaceutical composition of claim 7 for use in the treatment of cancer, preferably the cancer is selected from the group consisting of solid tumors, breast cancer like HER2 positive breast cancer or triple-negative breast cancer, leukemia like acute myeloid leukemia, relapsed, refractory B-cell precursor acute promyelocytic leukemia, acute lymphoblastic leukemia, hairy cell leukemia, acute lymphoblastic leukemia or chronic lymphocytic leukemia, lymphoma like Hodkin lymphoma, non-Hodkin lymphoma, systemicanaplastic large cell lymphoma, refractory diffuse large B-cell lymphoma, relapsed or refractory large B-cell lymphoma, urothelial cancer, cervical cancer like recurrent or metastatic cervical cancer, ovarian cancer, multiple myeloma, lung cancer like small cell lung cancer or non-small cell lung cancer, gastric cancer, prostate cancer, brain cancers like glioblastoma multiformae, astriocytoma, oligodendroglioma or medulloblastoma, pancreatic cancer or liver cancers like hepatocellular carcinoma, cholangiocarcinoma, hepatoblastoma or angiosarcoma.

14. The compound or the pharmaceutical composition for the use according to claim 13, wherein the compound comprises the antibody- conjugate (AC) according to claim 5.

15. The compound or pharmaceutical composition for the use according to claim 13, wherein the treatment further comprises administering at least one additional active compound, preferably at least one anticancer agent.INTERNATIONAL SEARCH REPORTBox No. IV Text of the abstract (Continuation of item 5 of the first sheet)The present invention relates to the use of compounds of formula (I) for use in methods of treating and / or preventing conditions, disorders or diseases that are mediated or caused by a virus or cancer. In particular, the compounds described herein are useful in the treatment and / or prevention of conditions, disorders or diseases that are mediated or caused by cancer or an animal pathogenic virus which uses cellular mechanisms in the human or animal host for its replication and / or for its transcription.

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