Novel compounds for the treatment of cancer and metabolic diseases

Abstract

The present invention relates to novel compounds of formulae (I) and (III), to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN 1, yet more in particular for the prevention or treatment of cancer or metabolic diseases. The present invention also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds as well as to said compositions or preparations for use as a medicine, more preferably for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer or metabolic diseases. The present invention also relates to processes for the preparation of said compounds.

Description

NOVEL COMPOUNDS FIELD OF THE INVENTION The present invention relates to novel compounds. The present invention also relates to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer. The present invention also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds as well as to said compositions or preparations for use as a medicine, more preferably for the prevention or treatment of diseases mediated by activity of PTPN2 and / or PTPN1, yet more in particular for the prevention or treatment of cancer. The present invention also relates to processes for the preparation of said compounds. The invention also relates to combinations of the novel compounds with other therapeutic agents. BACKGROUND OF THE INVENTION Tyrosine-protein phosphatase non-receptor type 2 (PTPN2), also known as T cell protein tyrosine phosphatase (TC-PTP), is an enzyme that in humans is encoded by the PTPN2 gene. It is a member of the PTP family of signaling proteins and regulates a variety of cellular processes by dephosphorylating either receptor protein tyrosine kinases, such as EGFR (epidermal growth factor receptor), CSF1R (Colony stimulating factor 1 receptor), PDGFR (Platelet-derived growth factor receptor), IR (insulin receptor) or non-receptor protein tyrosine kinases, such as JAK (janus family kinases), Src (src family kinases), or STAT (signal transducers and activators of transcription) family kinases, either in the cytoplasm or nucleus (J. Song et al, Int. J. Mol. Sci 2022, 23(17), 10025). PTPN2 is associated with pathological processes, including inflammatory responses, immune disorders, and tumor development. The anti-inflammatory cytosolic protein tyrosine phosphatase, PTPN2, was identified as a cancer immunotherapy target after a CRISPR–Cas9- mediated genome editing study showed that deletion of PTPN2 in murine tumor cells promotes susceptibility of the tumor to checkpoint inhibitor therapy by enhancing IFN ^-mediated effects on antigen presentation and growth suppression. Enhanced anti-PD-1 response was accompanied by the recruitment of cytotoxic CD8+ T cells, increased antigen presentation, as reflected by the increased expression of MHC-I on tumor cells, and the increased activation of recruited T-cells. PTPN2-deficient tumor cells expressed higher levels of IFN-γ / STAT1 target genes, including those encoding T cell chemo-attractants as well as components of the antigen-processing and presentation pathway (Manguso, R.T. et al. Nature 2017, 547, 413–418). More recently, PTPN2 deficiency has also been shown to enhance programmed T cell expansion and survival capacity of activated T cells (Flosbach, M. et al. Cell Rep.2020, 32, 107957). Hence, inhibitors of PTPN2can be considered as a valuable approach as cancer immunotherapeutics. Protein tyrosine phosphatase non-receptor type 1 (PTPN1), also known as protein tyrosine phosphatase-1B (PTP1B), has been shown to play a key role in insulin and leptin signaling and is a primary mechanism for down-regulating both the insulin and leptin receptor signaling pathways (Kenner K. A. et al., J Biol Chem 271: 19810-19816, 1996). Animals deficient in PTPN1 have improved glucose regulation and lipid profiles and are resistant to weight gain when treated with a high fat diet (Elchebly M. et al., Science 283: 1544-1548, 1999). Therefore, it is expected that PTPN1 inhibitors are useful for the treatment of metabolic diseases such as type 2 diabetes, obesity, and metabolic syndrome. Protein tyrosine phosphatases (PTPs) have been traditionally considered challenging drug targets due to the positively charged and highly conserved nature of their catalytic site. For the former reason potent orthosteric PTP inhibitors are negatively charged and often characterized by poor cell-permeability / bioavailability. Recent patent applications from Calico / Abbvie describe inhibitors of PTPN2 and / or PTPN1: WO / 2020 / 186199A1 and WO / 2021 / 127499A1 describe small molecule inhibitors and WO / 2021 / 127586 proposed protein degradation via PROTACs targeting PTPN2. Kumquat recently disclosed PTPN2 inhibitors in WO / 2022 / 192598 and WO / 2023 / 096928A1. However, there is still a great need for novel, alternative or better therapeutics for the prevention or treatment of cancer and potentially other disease indications mediated by PTPN2 and / or PTPN1. Therapeutics with better target engagement, (cellular) potency, less side-effects, a higher activity, a lower toxicity, better pharmacokinetic or –dynamic properties, a better (oral) bioavailability, higher (hepatocyte) metabolic stability, varied volume of distribution, effective dosage or combinations thereof would be very welcome. The present invention provides a class of novel compounds which can be used as inhibitors of PTPN2 and / or PTPN1 in cancer (immuno)therapy and potentially other disease indications mediated by PTPN2 and / or PTPN1. SUMMARY OF THE INVENTION The present invention is based on the unexpected finding that at least one of the above- mentioned problems can be solved by the below described compounds. The present invention provides new compounds, especially a compound of formula (I), a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, hydrate, polymorph and / or prodrug thereof,wherein: - represents a double bond ( ) or a triple bond ( ); - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl; or a 4-, 5-, 6-, or 7-membered heterocycle, wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl, or a 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl;heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl,heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. The present invention also encompasses preferably a compound of formula (I), and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), a solvate, a hydrate, a polymorph, an isotope, and / or a prodrug thereof,wherein: - represents a double bond ( ) or a triple bond ( ); - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; heterocyclylheteroalkynyl; alkyl-oxy-alkyl; (mono or di)alkylamino; (mono or di-)alkyl-amino-alkyl; alkylthio; and alkyl-thio-alkyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, heterocyclylheteroalkynyl, alkyl-oxy-alkyl, (mono or di)alkylamino, (mono or di-)alkyl-amino-alkyl, alkylthio, and alkyl-thio-alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl;- or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3- , 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle;arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, - OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2. The present invention also provides in a particular embodiment compounds of formula (III) and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, polymorph and / or prodrug thereof,wherein: - cycle B is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; and heterocycle; - m is selected from 0; 1; 2; 3; 4; and 5; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl;wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. The present invention also provides in a particular embodiment compounds of formula (III) and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, hydrate, polymorph, isotope, and / or prodrug thereof,wherein: - cycle B is selected from heterocycle; cycloalkyl; cycloalkenyl; and cycloalkynyl; - m is selected from 0; 1; 2; 3; 4; and 5. - R3is selected from hydrogen and alkyl; - each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; - S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - - C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; - NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, hydroxyl, cycloalkyl, alkenyl, alkynyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; and -NHalkyl, -N(alkyl)2;- each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2. The present invention provides new compounds which have been shown to possess inhibitory activity on PTPN2 and / or PTPN1. The present invention furthermore demonstrates that these compounds efficiently inhibit the activity of PTPN2 and / or PTPN1. Therefore, these compounds constitute a useful class of new potent compounds that can be used in the treatment and / or prevention of PTPN2 and / or PTPN1 mediated disorders in animals, mammals and humans, more specifically for the treatment and / or prevention of (i) cancer, more specifically lung cancer, breast cancer, head and neck cancer, oesophageal cancer, kidney cancer, bladder cancer, colon cancer, ovarian cancer, cervical cancer, endometrial cancer, liver cancer, skin cancer, pancreatic cancer, gastric cancer, brain cancer and prostate cancer, yet more specifically colon cancer, kidney cancer, pancreatic cancer, breast cancer, melanoma, head and neck squamous cell carcinoma and non-small cell lung cancer and (ii) metabolic diseases. The present invention furthermore relates to the compounds of the invention for use as a medicine, to the use of such compounds as medicines and to their use for the manufacture of medicaments, more in particular for treating and / or preventing PTPN2 and / or PTPN1 mediated diseases, in particular (i) cancer and (ii) metabolic diseases in animals or mammals, more in particular in humans. The invention also relates to pharmaceutical compositions comprising the compounds of the invention in an effective amount, to said pharmaceutical compositions for use as a medicine, more in particular for use as a medicine for the prevention or treatment of PTPN2 and / or PTPN1 mediated disorders and to the method of preparation of manufacturing of said pharmaceutical compositions. The present invention also relates to a method of treatment or prevention of PTPN2 and / or PTPN1 mediated disorders in humans by the administration of one or more such compounds, optionally in combination with one or more other medicines, to a patient in need thereof. Alsodisclosed herein is a method of treating cancer in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein in combination with an additional therapeutic agent. In some embodiments, the additional medicine is an immunotherapeutic agent. For example, in some embodiments, the immunotherapeutic agent is selected from the group consisting of an anti-PD-1 antibody, an anti- PD-L1 antibody and an anti- CTLA-4 antibody. When reference is made to the treatment or prevention of PTPN2 and / or PTPN1 mediated diseases, this in particular embodiment refers to (i) cancer, more in particular lung cancer, breast cancer, head and neck cancer, oesophageal cancer, kidney cancer, bladder cancer, colon cancer, ovarian cancer, cervical cancer, endometrial cancer, liver cancer, skin cancer, pancreatic cancer, gastric cancer, brain cancer and prostate cancer, yet more in particular colon cancer, kidney cancer, pancreatic cancer, breast cancer, melanoma, head and neck squamous cell carcinoma and non-small cell lung cancer and (ii) metabolic diseases, more specifically non- alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, type-2 diabetes, heart disease, atherosclerosis, arthritis, cystinosis, phenylketonuria, proliferative retinopathy, metabolic syndrome or Kearns-Sayre disease in animals or mammals, more in particular in humans. More in particular in relation to the treatment or prevention of cancer, the invention comprises administering to the patient an effective amount of a compound disclosed herein, also in combination with an additional therapeutic agent. In some embodiments, the additional therapeutic agent is an immunotherapeutic agent. For example, in some embodiments, the immunotherapeutic agent is selected from the group consisting of an anti-PD-1 antibody, an anti- PD-L1 antibody and an anti-CTLA-4 antibody. In particular related to the treatment or prevention of metabolic diseases comprises the treatment or prevention of type-2 diabetes in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein, or comprises treating and / or controlling obesity in a patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein. For example, disclosed herein is a method of inhibiting further weight gain in an overweight or obese patient in need thereof, comprising administering to the patient an effective amount of a compound disclosed herein. The present invention also relates to a method of preparation of the compounds of the invention comprising the steps for synthesis of the compounds as described herein. FIGURES Figure 1: In vivo tumor growth inhibition with cpd008. Antitumor activity of cpd008 in the treatment of colon cancer in a syngeneic subcutaneous MC38 mouse tumor model performed in accordance with example 45.DETAILED DESCRIPTION OF THE INVENTION The present invention will be further described and in some instances with respect to particular embodiments, but the invention is not limited thereto. The term “PTPN2 and / or PTPN1 mediated diseases” or “PTPN2 and / or PTPN1 mediated disorders” refers to diseases, disorders or conditions in which PTPN2 and / or PTPN1 signaling is active or activated and whereby PTPN2 and / or PTPN1 activity or activation is contributing, driving, sustaining, enabling or the like such disease. PTPN2 and / or PTPN1 mediated diseases includes cancer, but also includes metabolic diseases or any other disease, disorder or ailment favorably responsive to PTPN2 or PTPN1 inhibitor treatment. The term "cancer" as used herein refers to all types of animal, more specifically human cancers, neoplasm or (malignant) tumors including carcinomas, sarcomas, lymphomas, leukemias, germ cell tumors and blastomas and thus includes solid and lymphoid cancers. Exemplary cancers that may be treated with a compound, pharmaceutical composition, or method provided herein include lymphoma, sarcoma, bladder cancer, bone cancer, brain tumor, cervical cancer, colon cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, myeloma, thyroid cancer, leukemia, prostate cancer, breast cancer (e.g., ER positive, ER negative, chemotherapy resistant, herceptin resistant, HER2 positive, doxorubicin resistant, tamoxifen resistant, ductal carcinoma, lobular carcinoma, primary, metastatic), ovarian cancer, pancreatic cancer, liver cancer (e.g., hepatocellular carcinoma), lung cancer (e.g., non-small cell lung carcinoma, squamous cell lung carcinoma, adenocarcinoma, large cell lung carcinoma, small cell lung carcinoma, carcinoid, sarcoma), glioblastoma multiforme, glioma, or melanoma. Additional examples include, cancer of the thyroid, endocrine system, brain, breast, cervix, colon, head & neck, liver, kidney, lung, non-small cell lung, melanoma, mesothelioma, ovary, sarcoma, stomach, uterus or Medulloblastoma, Hodgkin's Disease, Non-Hodgkin's Lymphoma, multiple myeloma, neuroblastoma, glioma, glioblastoma multiforme, ovarian cancer, rhabdomyosarcoma, primary thrombocytosis, primary macroglobulinemia, primary brain tumors, cancer, malignant pancreatic insulanoma, malignant carcinoid, urinary bladder cancer, premalignant skin lesions, testicular cancer, lymphomas, thyroid cancer, neuroblastoma, esophageal cancer, genitourinary tract cancer, malignant hypercalcemia, endometrial cancer, adrenal cortical cancer, neoplasms of the endocrine or exocrine pancreas, medullary thyroid cancer, medullary thyroid carcinoma, melanoma, colorectal cancer, papillary thyroid cancer, hepatocellular carcinoma, Paget' s Disease of the Nipple, Phyllodes Tumors, Lobular Carcinoma, Ductal Carcinoma, cancer of the pancreatic stellate cells, cancer of the hepatic stellate cells, or prostate cancer. The term "carcinoma" refers to a malignant new growth made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. Exemplary carcinomas that may be treated with a compound, pharmaceutical composition, or method provided herein include, forexample, medullary thyroid carcinoma, familial medullary thyroid carcinoma, acinar carcinoma, acinous carcinoma, adenocystic carcinoma, adenoid cystic carcinoma, carcinoma adenomatosum, carcinoma of adrenal cortex, alveolar carcinoma, alveolar cell carcinoma, basal cell carcinoma, carcinoma basocellulare, basaloid carcinoma, basosquamous cell carcinoma, bronchioalveolar carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, cerebriform carcinoma, cholangiocellular carcinoma, chorionic carcinoma, colloid carcinoma, comedo carcinoma, corpus carcinoma, cribriform carcinoma, carcinoma en cuirasse, carcinoma cutaneum, cylindrical carcinoma, cylindrical cell carcinoma, duct carcinoma, ductal carcinoma, carcinoma durum, embryonal carcinoma, encephaloid carcinoma, epiermoid carcinoma, carcinoma epitheliale adenoides, exophytic carcinoma, carcinoma ex ulcere, carcinoma fibrosum, gelatiniforni carcinoma, gelatinous carcinoma, giant cell carcinoma, carcinoma gigantocellulare, glandular carcinoma, granulosa cell carcinoma, hair-matrix carcinoma, hematoid carcinoma, hepatocellular carcinoma, Hurthle cell carcinoma, hyaline carcinoma, hypernephroid carcinoma, infantile embryonal carcinoma, carcinoma in situ, intraepidermal carcinoma, intraepithelial carcinoma, Krompecher's carcinoma, Kulchitzky-cell carcinoma, large-cell carcinoma, lenticular carcinoma, carcinoma lenticulare, lipomatous carcinoma, lobular carcinoma, lymphoepithelial carcinoma, carcinoma medullare, medullary carcinoma, melanotic carcinoma, carcinoma molle, mucinous carcinoma, carcinoma muciparum, carcinoma mucocellulare, mucoepidermoid carcinoma, carcinoma mucosum, mucous carcinoma, carcinoma myxomatodes, nasopharyngeal carcinoma, oat cell carcinoma, carcinoma ossificans, osteoid carcinoma, papillary carcinoma, periportal carcinoma, preinvasive carcinoma, prickle cell carcinoma, pultaceous carcinoma, renal cell carcinoma of kidney, reserve cell carcinoma, carcinoma sarcomatodes, schneiderian carcinoma, scirrhous carcinoma, carcinoma scroti, signet- ring cell carcinoma, carcinoma simplex, small-cell carcinoma, solanoid carcinoma, spheroidal cell carcinoma, spindle cell carcinoma, carcinoma spongiosum, squamous carcinoma, squamouscell carcinoma, string carcinoma, carcinoma telangiectaticum, carcinoma telangiectodes, transitional cell carcinoma, carcinoma tuberosum, tubular carcinoma, tuberous carcinoma, verrucous carcinoma, or carcinoma villosum. The term "leukemia" refers broadly to progressive, malignant diseases of the blood- forming organs and is generally characterized by a distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemia is generally clinically classified on the basis of (1) the duration and character of the disease-acute or chronic; (2) the type of cell involved; myeloid (myelogenous), lymphoid (lymphogenous), or monocytic; and (3) the increase or non-increase in the number abnormal cells in the blood-leukemic or aleukemic (subleukemic). Exemplary leukemias that may be treated with a compound, pharmaceutical composition, or method provided herein include, for example, acute nonlymphocytic leukemia, chronic lymphocytic leukemia, acute granulocytic leukemia, chronic granulocytic leukemia, acutepromyelocytic leukemia, adult T-cell leukemia, aleukemic leukemia, a leukocythemic leukemia, basophylic leukemia, blast cell leukemia, bovine leukemia, chronic myelocytic leukemia, leukemia cutis, embryonal leukemia, eosinophilic leukemia, Gross' leukemia, hairy- cell leukemia, hemoblastic leukemia, hemocytoblastic leukemia, histiocytic leukemia, stem cell leukemia, acute monocytic leukemia, leukopenic leukemia, lymphatic leukemia, lymphoblastic leukemia, lymphocytic leukemia, lymphogenous leukemia, lymphoid leukemia, lymphosarcoma cell leukemia, mast cell leukemia, megakaryocyte leukemia, micromyeloblastic leukemia, monocytic leukemia, myeloblasts leukemia, myelocytic leukemia, myeloid granulocytic leukemia, myelomonocytic leukemia, Naegeli leukemia, plasma cell leukemia, multiple myeloma, plasmacytic leukemia, promyelocytic leukemia, Rieder cell leukemia, Schilling's leukemia, stem cell leukemia, subleukemic leukemia, or undifferentiated cell leukemia. The term "sarcoma" generally refers to a tumor which is made up of a substance like the embryonic connective tissue and is generally composed of closely packed cells embedded in a fibrillar or homogeneous substance. Sarcomas that may be treated with a compound, pharmaceutical composition, or method provided herein include a chondrosarcoma, fibrosarcoma, lymphosarcoma, melanosarcoma, myxosarcoma, osteosarcoma, Abemethy's sarcoma, adipose sarcoma, liposarcoma, alveolar soft part sarcoma, ameloblastic sarcoma, botryoid sarcoma, chloroma sarcoma, chorio carcinoma, embryonal sarcoma, Wilms' tumor sarcoma, endometrial sarcoma, stromal sarcoma, Ewing's sarcoma, fascial sarcoma, fibroblastic sarcoma, giant cell sarcoma, granulocytic sarcoma, Hodgkin's sarcoma, idiopathic multiple pigmented hemorrhagic sarcoma, immunoblastic sarcoma of B cells, lymphoma, immunoblastic sarcoma of T-cells, Jensen's sarcoma, Kaposi's sarcoma, Kupffer cell sarcoma, angiosarcoma, leukosarcoma, malignant mesenchymoma sarcoma, parosteal sarcoma, reticulocytic sarcoma, Rous sarcoma, serocystic sarcoma, synovial sarcoma, or telangiectaltic sarcoma. The term "melanoma" refers to a tumor arising from the melanocytic system of the skin and other organs. Melanomas that may be treated with a compound, pharmaceutical composition, or method provided herein include, for example, acral-lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, nodular melanoma, subungal melanoma, or superficial spreading melanoma. PTPN2 and / or PTPN1 mediated diseases also includes cancers that have developed resistance to prior treatments such has EGFR inhibitors, MEK inhibitors, AXL inhibitors, B-RAF inhibitors, RAS inhibitors, immunomodulatory agents and others. The term “metabolic disease" as used herein refers to a disease or condition affecting a metabolic process in a subject and includes non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, heart disease, atherosclerosis, arthritis, cystinosis, diabetes (e.g., Type I diabetes, Type II diabetes, or gestational diabetes),metabolic syndrome, phenylketonuria, proliferative retinopathy, or Kearns- Sayre disease. In some embodiments, the treatment or prevention of a metabolic disease comprises decreasing or eliminating a symptom of such metabolic disease comprising elevated blood pressure, elevated blood sugar level, weight gain, fatigue, blurred vision, abdominal pain, flatulence, constipation, diarrhea, jaundice, and the like. The term “treat” or “treating” as used herein is intended to refer to administration of a compound or composition of the invention to a subject for the purpose of effecting a therapeutic benefit or prophylactic benefit, here in particular through inhibition of PTPN2 and / or PTPN1. Treating includes reversing, ameliorating, alleviating, inhibiting the progress of, lessening the severity of, or preventing a disease, disorder, or condition, or one or more symptoms, complications or biochemical indicia of such disease, disorder or condition, here in particular mediated through PTPN2 and / or PTPN1. By "therapeutic benefit" is meant eradication, amelioration, reversing, alleviating, inhibiting the progress of or lessening the severity of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient is afflicted with the underlying disorder in some embodiments. For prophylactic benefit, in some embodiments, the compositions are administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease has not been made. For example certain methods herein treat cancer by decreasing or reducing or preventing the occurrence, growth, metastasis, or progression of cancer or decreasing a symptom of cancer. The term “subject” as used herein, refers to an animal, preferably a mammal, most preferably a human, a patient, who has been the object of treatment, observation or experiment or who is in need of such treatment. The term “therapeutically effective amount” as used herein, means that amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician, which includes alleviation or partial alleviation of the symptoms of the disease or disorder being treated. The term “composition” as used herein is intended to encompass a product comprising the specified ingredients in the therapeutically effective amounts, as well as any product which results, directly or indirectly, from combinations of the specified ingredients in the specified amounts. The term “antagonist” or “inhibitor” as used herein in reference to inhibitors of the PTPN2 and / or PTPN1 activity or activation, refers to a compound capable of producing, depending onthe circumstance, a functional antagonism or inhibition of PTPN2 and / or PTPN1 activity or activation. It is to be noticed that the term "comprising", used in the claims, should not be interpreted as being restricted to the means listed thereafter; it does not exclude other elements or steps. Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments. Where an indefinite or definite article is used when referring to a singular noun e.g. "a" or "an", "the", this includes a plural of that noun unless something else is specifically stated. Similarly it should be appreciated that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. In each of the following definitions, the number of carbon atoms represents the maximum number of carbon atoms generally optimally present in the substituent or linker; it is understood that where otherwise indicated in the present application, the number of carbon atoms represents the optimal maximum number of carbon atoms for that particular substituent or linker. The term “leaving group” or “LG” as used herein means a chemical group which is susceptible to be displaced by a nucleophile or cleaved off or hydrolyzed in basic or acidic conditions. In a particular embodiment, a leaving group is selected from a halogen atom (e.g., Cl, Br, I) or a sulfonate (e.g., mesylate, tosylate, triflate). The term “protecting group” refers to a moiety of a compound that masks or alters the properties of a functional group or the properties of the compound as a whole. The chemical substructure of a protecting group varies widely. One function of a protecting group is to serve as intermediates in the synthesis of the parental drug substance. Chemical protecting groups and strategies for protection / deprotection are well known in the art. See: “Protective Groups in Organic Chemistry”, Theodora W. Greene (John Wiley & Sons, Inc., New York, 1991. Protecting groups are often utilized to mask the reactivity of certain functional groups, to assist in the efficiency of desired chemical reactions, e.g. making and breaking chemical bonds in an ordered and planned fashion. Protection of functional groups of a compound alters other physical properties besides the reactivity of the protected functional group, such as the polarity, lipophilicity (hydrophobicity), and other properties which can be measured by common analytical tools. Chemically protected intermediates may themselves be biologically active or inactive.Protected compounds may also exhibit altered, and in some cases, optimized properties in vitro and in vivo, such as passage through cellular membranes and resistance to enzymatic degradation or sequestration. In this role, protected compounds with intended therapeutic effects may be referred to as prodrugs. Another function of a protecting group is to convert the parental drug into a prodrug, whereby the parental drug is released upon conversion of the prodrug in vivo. Because active prodrugs may be absorbed more effectively than the parental drug, prodrugs may possess greater potency in vivo than the parental drug. Protecting groups are removed either in vitro, in the instance of chemical intermediates, or in vivo, in the case of prodrugs. With chemical intermediates, it is not particularly important that the resulting products after deprotection, e.g. alcohols, be physiologically acceptable, although in general it is more desirable if the products are pharmacologically innocuous. The term “alkyl” or “C1-18alkyl” as used herein means C1-C18 normal, secondary, or tertiary, linear, branched or straight hydrocarbon with no site of unsaturation. Examples are methyl, ethyl, 1-propyl (n-propyl), 2-propyl (iPr), 1-butyl, 2-methyl-1-propyl(i-Bu), 2-butyl (s-Bu), 2-dimethyl-2- propyl (t-Bu), 1-pentyl (n-pentyl), 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl- 1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4- methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n- hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl, and n-icosyl. In particular embodiments, the term alkyl refers to C1-12alkyl (C1-12 hydrocarbons), yet more in particular to C1-9alkyl (C1-9 hydrocarbons), yet more in particular to C1-6alkyl (C1-6hydrocarbons) as further defined herein above. The term "haloalkyl" as a group or part of a group, refers to an alkyl group having the meaning as defined above wherein one, two, or three hydrogen atoms are each replaced with a halogen as defined herein. Non-limiting examples of such haloalkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl and the like. The term “alkoxy" or “alkyloxy”, as a group or part of a group, refers to a group having the formula –ORbwherein Rbis C1-6alkyl as defined herein above. Non-limiting examples of suitable C1-6alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert- butoxy, pentyloxy and hexyloxy. The term “haloalkoxy”, as a group or part of a group, refers to a group of formula -O-Rc, wherein Rcis haloalkyl as defined herein. Non-limiting examples of suitable haloalkoxy include fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy, 2,2,2-trichloroethoxy, trichloromethoxy, 2- bromoethoxy, pentafluoroethyl, 3,3,3-trichloropropoxy, 4,4,4-trichlorobutoxy. The term “cycloalkyl” or “C3-18cycloalkyl” as used herein and unless otherwise stated means a saturated hydrocarbon monovalent group having from 3 to 18 carbon atoms consistingof or comprising a C3-10 monocyclic or C7-18 polycyclic saturated hydrocarbon, such as for instance cyclopropyl, cyclobutyl, cyclopentyl, cyclopropylethylene, methylcyclopropylene, cyclohexyl, cycloheptyl, cyclooctyl, cyclooctylmethylene, norbornyl, fenchyl, trimethyltricycloheptyl, decalinyl, adamantyl and the like. In particular embodiments, the term cycloalkyl refers to C3-12cycloalkyl (saturated cyclic C3-12hydrocarbons), yet more in particular to C3-9cycloalkyl (saturated cyclic C3-9hydrocarbons), still more in particular to C3-6cycloalkyl (saturated cyclic C3-6hydrocarbons) as further defined herein above. For the avoidance of doubt, fused systems of a cycloalkyl ring with a heterocyclic ring are considered as heterocycle irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkyl ring with an aryl ring are considered as aryl irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkyl ring with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure. The term “alkenyl” or “C2-18alkenyl” as used herein is C2-C18 normal, secondary or tertiary, linear, branched or straight hydrocarbon with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond. Examples include, but are not limited to: ethylene or vinyl (-CH=CH2), allyl (-CH2CH=CH2), and 5-hexenyl (-CH2CH2CH2CH2CH=CH2). The double bond may be in the cis or trans configuration. In particular embodiments, the term alkenyl refers to C2-12alkenyl (C2-12hydrocarbons), yet more in particular to C2-9 alkenyl (C2-9 hydrocarbons), still more in particular to C2-6 alkenyl (C2-6hydrocarbons) as further defined herein above with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond. The term “alkenyloxy”, as a group or part of a group, refers to a group having the formula –ORdwherein Rdis alkenyl as defined herein above. The term “cycloalkenyl” as used herein refers to a non-aromatic hydrocarbon group having from 5 to 18 carbon atoms with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond and consisting of or comprising a C5-10 monocyclic or C7-18 polycyclic hydrocarbon. Examples include, but are not limited to: cyclopentenyl (-C5H7), cyclopentenylpropylene, methylcyclohexenylene and cyclohexenyl (-C6H9). The double bond may be in the cis or trans configuration. In particular embodiments, the term cycloalkenyl refers to C5-12cycloalkenyl (cyclic C5-12hydrocarbons), yet more in particular to C5-9cycloalkenyl (cyclic C5-9hydrocarbons), still more in particular to C5-6cycloalkenyl (cyclic C5-6hydrocarbons) as further defined herein above with at least one site of unsaturation, namely a carbon-carbon, sp2 double bond. For the avoidance of doubt, fused systems of a cycloalkenyl ring with a heterocyclic ring are considered as heterocycle irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkenyl ring with an aryl ring are considered as aryl irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkenyl ring with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure. The term “alkynyl” or “C2-18alkynyl” as used herein refers to C2-C18normal, secondary,tertiary, linear, branched or straight hydrocarbon with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond. Examples include, but are not limited to: ethynyl (-C ^CH), 3-ethyl-cyclohept-1-ynylene, and 1-propynyl (propargyl, -CH2C ^CH). In particular embodiments, the term alkynyl refers to C2-12alkynyl (C2-12hydrocarbons), yet more in particular to C2-9alkynyl (C2-9hydrocarbons) yet more in particular to C2-6alkynyl (C2-6hydrocarbons) as further defined herein above with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond. The term “alkynyloxy”, as a group or part of a group, refers to a group having the formula –ORewherein Reis alkynyl as defined herein above. The term “cycloalkynyl” as used herein refers to a non-aromatic hydrocarbon group having from 5 to 18 carbon atoms with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond and consisting of or comprising a C5-10 monocyclic or C7- 18 polycyclic hydrocarbon. Examples include, but are not limited to: cyclohept-1-yne, 3-ethyl- cyclohept-1-ynylene, 4-cyclohept-1-yn-methylene and ethylene-cyclohept-1-yne. In particular embodiments, the term cycloalkynyl refers to C5-10 cycloalkynyl (cyclic C5-10 hydrocarbons), yet more in particular to C5-9 cycloalkynyl (cyclic C5-9 hydrocarbons), still more in particular to C5-6 cycloalkynyl (cyclic C5-6 hydrocarbons) as further defined herein above with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond. For the avoidance of doubt, fused systems of a cycloalkynyl ring with a heterocyclic ring are considered as heterocycle irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkynyl ring with an aryl ring are considered as aryl irrespective of the ring that is bound to the core structure. Fused systems of a cycloalkynyl ring with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure. The term “alkylene” as used herein each refer to a saturated, branched or straight chain hydrocarbon group of 1-18 carbon atoms (more in particular C1-12, C1-9 or C1-6 carbon atoms), and having two monovalent group centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkane. Typical alkylene include, but are not limited to: methylene (-CH2-), 1,2-ethyl (-CH2CH2-), 1,3-propyl (-CH2CH2CH2-), 1,4-butyl (- CH2CH2CH2CH2-), and the like. The term “alkenylene” as used herein each refer to a branched or straight chain hydrocarbon of 2-18 carbon atoms (more in particular C2-12, C2-9 or C2-6 carbon atoms) with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp2 double bond, and having two monovalent centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkene. The term “alkynylene” as used herein each refer to a branched or straight chain hydrocarbon of 2-18 carbon atoms (more in particular C2-12, C2-9or C2-6carbon atoms) with at least one site (usually 1 to 3, preferably 1) of unsaturation, namely a carbon-carbon, sp triple bond, andhaving two monovalent centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkyne. The term “heteroalkyl” as used herein refers to an alkyl wherein one or more carbon atoms are replaced by one or more atoms selected from the group comprising oxygen, nitrogen or sulphur atom. The term heteroalkyl thus comprises –O-Rb, -NRo-Rb, -Ra-O-Rb, and –S-Rb, wherein Rais alkylene, Rbis alkyl, and Rois hydrogen or alky as defined herein. In particular embodiments, the term refers to C1-12heteroalkyl, C1-9heteroalkyl or C1-6heteroalkyl. In some embodiments heteroalkyl is selected from the group comprising alkyloxy, alkyl-oxy-alkyl, (mono or di)alkylamino, (mono or di-)alkyl-amino-alkyl, alkylthio, and alkyl-thio-alkyl. The term “heteroalkenyl” as used herein refers to an acyclic alkenyl wherein one or more carbon atoms are replaced by one or more atoms selected from oxygen, nitrogen or sulphur atom. The term heteroalkenyl thus comprises –O-Rd, -NH-(Rd), -N(Rd))2, -N(Rb)(Rd), and –S-Rdwherein Rbis alkyl and Rdis alkenyl as defined herein. In particular embodiments, the term refers to C2- 12heteroalkenyl, C2-9heteroalkenyl or C2-6heteroalkenyl. In some embodiments heteroalkenyl is selected from the group comprising alkenyloxy, alkenyl-oxy-alkenyl, (mono or di-)alkenylamino, (mono or di-)alkenyl-amino-alkenyl, alkenylthio, and alkenyl-thio-alkenyl, The term “heteroalkynyl” as used herein refers to an acyclic alkynyl wherein one or more carbon atoms are replaced by an oxygen, nitrogen or sulphur atom. The term heteroalkynyl thus comprises but is not limited to -O-Rd, -N(Rd)2, NHRd, -N(Rb)(Re), -N(Rd)(Re), and -S-Rdwherein Rbis alkyl, Reis alkynyl and Rdis alkenyl as defined herein. In particular embodiments, the term refers to C2-12heteroalkynyl, C2-9heteroalkynyl or C2-6heteroalkynyl. In some embodiments the term heteroalkynyl is selected from the group comprising alkynyloxy, alkynyl-oxy-alkynyl, (mono or di-)alkynylamino, (mono or di-)alkynyl-amino-alkynyl, alkynylthio, alkynyl-thio-alkynyl, The term “heteroalkylene” as used herein refers to an alkylene wherein one or more carbon atoms are replaced by one or more oxygen, nitrogen or sulphur atoms. The term “heteroalkenylene” as used herein refers to an alkenylene wherein one or more carbon atoms are replaced by one or more oxygen, nitrogen or sulphur atoms. The term “heteroalkynylene” as used herein refers to an alkynylene wherein one or more carbon atoms are replaced by one or more oxygen, nitrogen or sulphur atom. The term “aryl” as used herein means an aromatic hydrocarbon of 6-20 carbon atoms derived by the removal of hydrogen from a carbon atom of a parent aromatic ring system. Typical aryl groups include, but are not limited to 1 ring, or 2 or 3 rings fused together, derived from benzene, naphthalene, anthracene, biphenyl, and the like. In particular embodiments, the term aryl refers to a 6-14 carbon atoms membered aromatic cycle, yet more in particular refers to a 6- 10 carbon atoms membered aromatic cycle. Fused systems of an aryl ring with a cycloalkyl ring, or a cycloalkenyl ring, or a cycloalkynyl ring, are considered as aryl irrespective of the ring that is bound to the core structure. Fused systems of an aryl ring with a heterocycle are considered asheterocycle irrespective of the ring that is bound to the core structure. Thus, indoline, dihydrobenzofurane, dihydrobenzothiophene and the like are considered as heterocycle according to the invention. Fused systems of an aryl ring with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure. The term “aryloxy”, as a group or part of a group, refers to a group having the formula – ORgwherein Rgis aryl as defined herein above. The term “arylalkyl” or “arylalkyl-“ as used herein refers to an alkyl in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with an aryl. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-1-yl, 2- phenylethen-1-yl, naphthylmethyl, 2-naphthylethyl, and the like. The arylalkyl group comprises 6 to 20 carbon atoms, e.g. the alkyl moiety of the arylalkyl group is 1 to 6 carbon atoms and the aryl moiety is 6 to 14 carbon atoms. The term “arylalkyloxy”, as a group or part of a group, refers to a group having the formula -O-Ra-Rgwherein Rgis aryl, and Rais alkylene as defined herein above. The term “arylalkenyl” or “arylalkenyl-“ as used herein refers to an alkenyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an aryl. The arylalkenyl group comprises 6 to 20 carbon atoms, e.g. the alkenyl moiety of the arylalkenyl group is 1 to 6 carbon atoms and the aryl moiety is 6 to 14 carbon atoms. The term “arylalkynyl” or “arylalkynyl-“ as used herein refers to an alkynyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an aryl. The arylalkynyl group comprises 6 to 20 carbon atoms, e.g. the alkynyl moiety of the arylalkynyl group is 1 to 6 carbon atoms and the aryl moiety is 6 to 14 carbon atoms. The term “arylheteroalkyl” or “arylheteroalkyl-“ as used herein refers to a heteroalkyl in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with an aryl. The arylheteroalkyl group comprises 6 to 20 carbon atoms, e.g. the heteroalkyl moiety of the arylheteroalkyl group is 1 to 6 carbon atoms and the aryl moiety is 6 to 14 carbon atoms. In some embodiments arylheteroalkyl is selected from the group comprising aryl-O-alkyl, arylalkyl-O-alkyl, aryl-NH-alkyl, aryl-N(alkyl)2, arylalkyl-NH-alkyl, arylalkyl-N-(alkyl)2, aryl–S-alkyl, and arylalkyl-S-alkyl. The term “arylheteroalkenyl” or “arylheteroalkenyl-“ as used herein refers to a heteroalkenyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an aryl. The arylheteroalkenyl group comprises 6 to 20 carbon atoms, e.g. the heteroalkenyl moiety of the arylheteroalkenyl group is 1 to 6 carbon atoms and the aryl moiety is 6 to 14 carbon atoms. In some embodiments arylheteroalkenyl is selected from the group comprising aryl-O-alkenyl, arylalkenyl-O-alkenyl, aryl-NH-alkenyl, aryl-N(alkenyl)2, arylalkenyl-NH-alkenyl, arylalkenyl-N- (alkenyl)2, aryl–S-alkenyl, and arylalkenyl-S-alkenyl. The term “arylheteroalkynyl” or “arylheteroalkynyl-“ as used herein refers to aheteroalkynyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an aryl. The arylheteroalkynyl group comprises 6 to 20 carbon atoms, e.g. the heteroalkynyl moiety of the arylheteroalkynyl group is 1 to 6 carbon atoms and the aryl moiety is 6 to 14 carbon atoms. In some embodiments arylheteroalkynyl is selected from the group comprising aryl-O-alkynyl, arylalkynyl-O-alkynyl, aryl-NH-alkynyl, aryl-N(alkynyl)2, arylalkynyl-NH-alkynyl, arylalkynyl-N- (alkynyl)2, aryl–S-alkynyl, and arylalkynyl-S-alkynyl. The term “heterocycle” or “heterocyclyl” as used herein refer to non-aromatic, fully saturated or partially unsaturated ring system of 3 to 18 atoms including at least one N, O, S, or P (for example, 3 to 7 member monocyclic, 7 to 11 member bicyclic, or comprising a total of 3 to 10 ring atoms). Each ring of the heterocycle or heterocyclyl may have 1, 2, 3 or 4 heteroatoms selected from N, O and / or S, where the N and S heteroatoms may optionally be oxidized and the N heteroatoms may optionally be quaternized; and wherein at least one carbon atom of heterocyclyl can be oxidized to form at least one C=O. The heterocycle may be attached at any heteroatom or carbon atom of the ring or ring system, where valence allows. The rings of multi- ring heterocyclyls or heterocycles may be fused, bridged and / or joined through one or more spiro atoms. Fused systems of a heterocycle or heterocyclyl with an aryl ring are considered as heterocycle or heterocyclyl irrespective of the ring that is bound to the core structure. Fused systems of a heterocycle or heterocyclyl with a heteroaryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure. Non limiting exemplary heterocycles or heterocyclic groups include piperidinyl, piperazinyl, homopiperazinyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, pyrrolidinyl, aziridinyl, oxiranyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, 2-imidazolinyl, pyrazolidinyl imidazolidinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, succinimidyl, 3H-indolyl, indolinyl, isoindolinyl, chromanyl (also known as 3,4-dihydrobenzo[b]pyranyl), 2H-pyrrolyl, 1- pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, 4H-quinolizinyl, 2-oxopiperazinyl, 2-pyrazolinyl, 3-pyrazolinyl, tetrahydro-2H-pyranyl, 2H-pyranyl, 4H-pyranyl, 3,4-dihydro-2H-pyranyl, 3-dioxolanyl, 1,4- dioxanyl, 2,5-dioximidazolidinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, indolinyl, tetrahydrothiophenyl, tetrahydroquinolinyl, tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, thiomorpholin-4-yl, thiomorpholin-4- ylsulfoxide, thiomorpholin-4-ylsulfone, 1,3-dioxolanyl, 1,4-oxathianyl, 1,4-dithianyl, 1,3,5- trioxanyl, 1H-pyrrolizinyl, tetrahydro-1,1-dioxothiophenyl, N- formylpiperazinyl, and morpholin-4- yl. The term “aziridinyl” as used herein includes aziridin-1-yl and aziridin-2-yl. The term “oxyranyl” as used herein includes oxyranyl-2-yl. The term “thiiranyl” as used herein includes thiiran-2-yl. The term “azetidinyl” as used herein includes azetidin-1-yl, azetidin-2-yl and azetidin-3-yl. The term “oxetanyl” as used herein includes oxetan-2-yl and oxetan-3-yl. The term “thietanyl” as used herein includes thietan-2-yl and thietan-3-yl. The term “pyrrolidinyl” as used herein includes pyrrolidin-1-yl, pyrrolidin-2-yl and pyrrolidin-3-yl. The term “tetrahydrofuranyl” as used hereinincludes tetrahydrofuran-2-yl and tetrahydrofuran-3-yl. The term “tetrahydrothiophenyl” as used herein includes tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl. The term “succinimidyl” as used herein includes succinimid-1-yl and succininmid-3-yl. The term “dihydropyrrolyl” as used herein includes 2,3-dihydropyrrol-1-yl, 2,3-dihydro-1H-pyrrol-2-yl, 2,3-dihydro-1H-pyrrol-3-yl, 2,5- dihydropyrrol-1-yl, 2,5-dihydro-1H-pyrrol-3-yl and 2,5-dihydropyrrol-5-yl. The term “2H-pyrrolyl” as used herein includes 2H-pyrrol-2-yl, 2H-pyrrol-3-yl, 2H-pyrrol-4-yl and 2H-pyrrol-5-yl. The term “3H-pyrrolyl” as used herein includes 3H-pyrrol-2-yl, 3H-pyrrol-3-yl, 3H-pyrrol-4-yl and 3H-pyrrol- 5-yl. The term “dihydrofuranyl” as used herein includes 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3- yl, 2,3-dihydrofuran-4-yl, 2,3-dihydrofuran-5-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 2,5- dihydrofuran-4-yl and 2,5-dihydrofuran-5-yl. The term “dihydrothiophenyl” as used herein includes 2,3-dihydrothiophen-2-yl, 2,3-dihydrothiophen-3-yl, 2,3-dihydrothiophen-4-yl, 2,3- dihydrothiophen-5-yl, 2,5-dihydrothiophen-2-yl, 2,5-dihydrothiophen-3-yl, 2,5-dihydrothiophen-4- yl and 2,5-dihydrothiophen-5-yl. The term “imidazolidinyl” as used herein includes imidazolidin-1- yl, imidazolidin-2-yl and imidazolidin-4-yl. The term “pyrazolidinyl” as used herein includes pyrazolidin-1-yl, pyrazolidin-3-yl and pyrazolidin-4-yl. The term “imidazolinyl” as used herein includes imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl and imidazolin-5-yl. The term “pyrazolinyl” as used herein includes 1-pyrazolin-3-yl, 1-pyrazolin-4-yl, 2-pyrazolin-1-yl, 2-pyrazolin-3-yl, 2- pyrazolin-4-yl, 2-pyrazolin-5-yl, 3-pyrazolin-1-yl, 3-pyrazolin-2-yl, 3-pyrazolin-3-yl, 3-pyrazolin-4- yl and 3-pyrazolin-5-yl. The term “dioxolanyl” also known as “1,3-dioxolanyl” as used herein includes dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl. The term “dioxolyl” also known as “1,3- dioxolyl” as used herein includes dioxol-2-yl, dioxol-4-yl and dioxol-5-yl. The term “oxazolidinyl” as used herein includes oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl and oxazolidin-5-yl. The term “isoxazolidinyl” as used herein includes isoxazolidin-2-yl, isoxazolidin-3-yl, isoxazolidin-4-yl and isoxazolidin-5-yl. The term “oxazolinyl” as used herein includes 2-oxazolinyl-2-yl, 2- oxazolinyl-4-yl, 2-oxazolinyl-5-yl, 3-oxazolinyl-2-yl, 3-oxazolinyl-4-yl, 3-oxazolinyl-5-yl, 4- oxazolinyl-2-yl, 4-oxazolinyl-3-yl, 4-oxazolinyl-4-yl and 4-oxazolinyl-5-yl. The term “isoxazolinyl” as used herein includes 2-isoxazolinyl-3-yl, 2-isoxazolinyl-4-yl, 2-isoxazolinyl-5-yl, 3-isoxazolinyl- 3-yl, 3-isoxazolinyl-4-yl, 3-isoxazolinyl-5-yl, 4-isoxazolinyl-2-yl, 4-isoxazolinyl-3-yl, 4-isoxazolinyl- 4-yl and 4-isoxazolinyl-5-yl. The term “thiazolidinyl” as used herein includes thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl and thiazolidin-5-yl. The term “isothiazolidinyl” as used herein includes isothiazolidin-2-yl, isothiazolidin-3-yl, isothiazolidin-4-yl and isothiazolidin-5-yl. The term “thiazolinyl” as used herein includes 2-thiazolinyl-2-yl, 2-thiazolinyl-4-yl, 2-thiazolinyl-5-yl, 3- thiazolinyl-2-yl, 3-thiazolinyl-4-yl, 3-thiazolinyl-5-yl, 4-thiazolinyl-2-yl, 4-thiazolinyl-3-yl, 4- thiazolinyl-4-yl and 4-thiazolinyl-5-yl. The term “isothiazolinyl” as used herein includes 2- isothiazolinyl-3-yl, 2-isothiazolinyl-4-yl, 2-isothiazolinyl-5-yl, 3-isothiazolinyl-3-yl, 3-isothiazolinyl- 4-yl, 3-isothiazolinyl-5-yl, 4-isothiazolinyl-2-yl, 4-isothiazolinyl-3-yl, 4-isothiazolinyl-4-yl and 4- isothiazolinyl-5-yl. The term “piperidyl” also known as “piperidinyl” as used herein includes piperid-1-yl, piperid-2-yl, piperid-3-yl and piperid-4-yl. The term “dihydropyridinyl” as used herein includes 1,2-dihydropyridin-1-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydropyridin-6-yl, 1,4-dihydropyridin-1-yl, 1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 2,3-dihydropyridin-2-yl, 2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl, 2,3-dihydropyridin-5-yl, 2,3-dihydropyridin-6-yl, 2,5-dihydropyridin-2-yl, 2,5-dihydropyridin-3-yl, 2,5-dihydropyridin-4-yl, 2,5-dihydropyridin-5-yl, 2,5-dihydropyridin-6-yl, 3,4-dihydropyridin-2-yl, 3,4-dihydropyridin-3-yl, 3,4-dihydropyridin-4-yl, 3,4-dihydropyridin-5-yl and 3,4-dihydropyridin-6-yl. The term “tetrahydropyridinyl” as used herein includes 1,2,3,4- tetrahydropyridin-1-yl, 1,2,3,4-tetrahydropyridin-2-yl, 1,2,3,4-tetrahydropyridin-3-yl, 1,2,3,4- tetrahydropyridin-4-yl, 1,2,3,4-tetrahydropyridin-5-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,6- tetrahydropyridin-1-yl, 1,2,3,6-tetrahydropyridin-2-yl, 1,2,3,6-tetrahydropyridin-3-yl, 1,2,3,6- tetrahydropyridin-4-yl, 1,2,3,6-tetrahydropyridin-5-yl, 1,2,3,6-tetrahydropyridin-6-yl, 2,3,4,5- tetrahydropyridin-2-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5- tetrahydropyridin-4-yl, 2,3,4,5-tetrahydropyridin-5-yl and 2,3,4,5-tetrahydropyridin-6-yl. The term “tetrahydropyranyl” also known as “oxanyl” or “tetrahydro-2H-pyranyl”, as used herein includes tetrahydropyran-2-yl, tetrahydropyran-3-yl and tetrahydropyran-4-yl. The term “2H-pyranyl” as used herein includes 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl, 2H-pyran-5-yl and 2H-pyran- 6-yl. The term “4H-pyranyl” as used herein includes 4H-pyran-2-yl, 4H-pyran-3-yl and 4H-pyran- 4-yl. The term “3,4-dihydro-2H-pyranyl” as used herein includes 3,4-dihydro-2H-pyran-2-yl, 3,4- dihydro-2H-pyran-3-yl, 3,4-dihydro-2H-pyran-4-yl, 3,4-dihydro-2H-pyran-5-yl and 3,4-dihydro-2H- pyran-6-yl. The term “3,6-dihydro-2H-pyranyl” as used herein includes 3,6-dihydro-2H-pyran-2-yl, 3,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl, 3,6-dihydro-2H-pyran-5-yl and 3,6- dihydro-2H-pyran-6-yl. The term “tetrahydrothiophenyl”, as used herein includes tetrahydrothiophen-2-yl, tetrahydrothiophenyl -3-yl and tetrahydrothiophenyl -4-yl. The term “2H- thiopyranyl” as used herein includes 2H-thiopyran-2-yl, 2H-thiopyran-3-yl, 2H-thiopyran-4-yl, 2H- thiopyran-5-yl and 2H-thiopyran-6-yl. The term “4H-thiopyranyl” as used herein includes 4H- thiopyran-2-yl, 4H-thiopyran-3-yl and 4H-thiopyran-4-yl. The term “3,4-dihydro-2H-thiopyranyl” as used herein includes 3,4-dihydro-2H-thiopyran-2-yl, 3,4-dihydro-2H-thiopyran-3-yl, 3,4-dihydro- 2H-thiopyran-4-yl, 3,4-dihydro-2H-thiopyran-5-yl and 3,4-dihydro-2H-thiopyran-6-yl. The term “3,6-dihydro-2H-thiopyranyl” as used herein includes 3,6-dihydro-2H-thiopyran-2-yl, 3,6-dihydro- 2H-thiopyran-3-yl, 3,6-dihydro-2H-thiopyran-4-yl, 3,6-dihydro-2H-thiopyran-5-yl and 3,6-dihydro- 2H-thiopyran-6-yl. The term “piperazinyl” also known as “piperazidinyl” as used herein includes piperazin-1-yl and piperazin-2-yl. The term “morpholinyl” as used herein includes morpholin-2-yl, morpholin-3-yl and morpholin-4-yl. The term “thiomorpholinyl” as used herein includes thiomorpholin-2-yl, thiomorpholin-3-yl and thiomorpholin-4-yl. The term “dioxanyl” as used herein includes 1,2-dioxan-3-yl, 1,2-dioxan-4-yl, 1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl and 1,4-dioxan-2-yl. The term “dithianyl” as used herein includes 1,2-dithian-3-yl, 1,2-dithian-4-yl, 1,3-dithian-2-yl, 1,3-dithian-4-yl, 1,3-dithian-5-yl and 1,4-dithian-2-yl. The term “oxathianyl” as used herein includes oxathian-2-yl and oxathian-3-yl. The term “trioxanyl” as used herein includes 1,2,3-trioxan-4-yl, 1,2,3-trioxan-5-yl, 1,2,4-trioxan-3-yl, 1,2,4-trioxan-5-yl, 1,2,4-trioxan-6-yl and 1,3,4-trioxan-2-yl. The term “azepanyl” as used herein includes azepan-1-yl, azepan-2-yl, azepan-3-yl and azepan-4-yl. The term “homopiperazinyl” as used herein includes homopiperazin-1-yl, homopiperazin-2-yl, homopiperazin-3-yl and homopiperazin-4-yl. The term “indolinyl” as used herein includes indolin-1-yl, indolin-2-yl, indolin-3-yl, indolin-4-yl, indolin-5-yl, indolin-6-yl, and indolin-7-yl. The term “quinolizinyl” as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl. The term “isoindolinyl” as used herein includes isoindolin-1-yl, isoindolin-2-yl, isoindolin-3-yl, isoindolin-4-yl, isoindolin-5-yl, isoindolin-6- yl, and isoindolin-7-yl. The term “3H-indolyl” as used herein includes 3H-indol-2-yl, 3H-indol-3-yl, 3H-indol-4-yl, 3H-indol-5-yl, 3H-indol-6-yl, and 3H-indol-7-yl. The term “quinolizinyl” as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl. The term “quinolizinyl” as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl. The term “tetrahydroquinolinyl” as used herein includes tetrahydroquinolin-1-yl, tetrahydroquinolin-2-yl, tetrahydroquinolin-3-yl, tetrahydroquinolin-4-yl, tetrahydroquinolin-5-yl, tetrahydroquinolin-6-yl, tetrahydroquinolin-7-yl and tetrahydroquinolin-8-yl. The term “tetrahydroisoquinolinyl” as used herein includes tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, tetrahydroisoquinolin-5-yl, tetrahydroisoquinolin-6-yl, tetrahydroisoquinolin-7-yl and tetrahydroisoquinolin-8-yl. The term “chromanyl” as used herein includes chroman-2-yl, chroman- 3-yl, chroman-4-yl, chroman-5-yl, chroman-6-yl, chroman-7-yl and chroman-8-yl. The term “1H- pyrrolizine” as used herein includes 1H-pyrrolizin-1-yl, 1H-pyrrolizin-2-yl, 1H-pyrrolizin-3-yl, 1H- pyrrolizin-5-yl, 1H-pyrrolizin-6-yl and 1H-pyrrolizin-7-yl. The term “3H-pyrrolizine” as used herein includes 3H-pyrrolizin-1-yl, 3H-pyrrolizin-2-yl, 3H-pyrrolizin-3-yl, 3H-pyrrolizin-5-yl, 3H-pyrrolizin- 6-yl and 3H-pyrrolizin-7-yl. The term “heteroaryl” refers to an aromatic ring system of 5 to 18 atoms including at least one N, O, S, or P, containing 1 or 2 rings which can be fused together or linked covalently, each ring typically containing 5 to 6 atoms; at least one of said rings is aromatic, where the N and S heteroatoms may optionally be oxidized and the N heteroatoms may optionally be quaternized, and wherein at least one carbon atom of said heteroaryl can be oxidized to form at least one C=O. Fused systems of a heteroaryl ring with a cycloalkyl ring, or a cycloalkenyl ring, or a cycloalkynyl ring, are considered as heteroaryl irrespective of the ring that is bound to the core structure. Fused systems of a heteroaryl ring with a heterocycle are considered as heteroaryl irrespective of the ring that is bound to the core structure. Fused systems of a hetero aryl ring with an aryl ring are considered as heteroaryl irrespective of the ring that is bound to the core structure. Non-limiting examples of such heteroaryl, include: triazol-2-yl, pyridinyl, 1H-pyrazol-5-yl, pyrrolyl, furanyl,thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazinyl, dioxinyl, thiazinyl, triazinyl, imidazo[2,1-b][1,3]thiazolyl, thieno[3,2-b]furanyl, thieno[3,2- b]thiophenyl, thieno[2,3-d][1,3]thiazolyl, thieno[2,3-d]imidazolyl, tetrazolo[1,5-a]pyridinyl, indolyl, indolizinyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, isobenzothiophenyl, indazolyl, benzimidazolyl, 1,3-benzoxazolyl, 1,2-benzisoxazolyl, 2,1-benzisoxazolyl, 1,3- benzothiazolyl, 1,2-benzoisothiazolyl, 2,1-benzoisothiazolyl, benzotriazolyl, 1,2,3- benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl, benzo[d]oxazol-2(3H)-one, 2,3-dihydro-benzofuranyl, thienopyridinyl, purinyl, imidazo[1,2- a]pyridinyl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridin-1(2H)-yl, 6-oxo-pyridazin-1(6H)-yl, 2- oxopyridin-1(2H)-yl, 1,3-benzodioxolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl; preferably said heteroaryl group is selected from the group comprising pyridyl, pyrazinyl, pyrimidinyl, pyrazolyl, pyrrolyl, isoxazolyl, thiophenyl, imidazolyl, indolyl, benzimidazolyl, s-triazinyl, oxazolyl, isothiazolyl, furyl, thienyl, triazolyl and thiazolyl ; more preferably, said heteroaryl group is selected from the group comprising pyridyl, pyrazinyl, pyrimidinyl, indolyl and benzimidazolyl. The term “pyrrolyl” (also called azolyl) as used herein includes pyrrol-1-yl, pyrrol-2-yl and pyrrol-3-yl. The term “furanyl” (also called "furyl") as used herein includes furan-2-yl and furan-3- yl (also called furan-2-yl and furan-3-yl). The term “thiophenyl” (also called "thienyl") as used herein includes thiophen-2-yl and thiophen-3-yl (also called thien-2-yl and thien-3-yl). The term “pyrazolyl” (also called 1H-pyrazolyl and 1,2-diazolyl) as used herein includes pyrazol-1-yl, pyrazol-3-yl or 1H-pyrazol-5-yl, pyrazol-4-yl and pyrazol-5-yl. The term “imidazolyl” as used herein includes imidazol-1-yl, imidazol-2-yl, imidazol-4-yl and imidazol-5-yl. The term “oxazolyl” (also called 1,3-oxazolyl) as used herein includes oxazol-2-yl, oxazol-4-yl and oxazol-5-yl. The term “isoxazolyl” (also called 1,2-oxazolyl), as used herein includes isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl. The term “thiazolyl” (also called 1,3-thiazolyl),as used herein includes thiazol-2-yl, thiazol-4-yl and thiazol-5-yl (also called 2-thiazolyl, 4-thiazolyl and 5-thiazolyl). The term “isothiazolyl” (also called 1,2-thiazolyl) as used herein includes isothiazol-3-yl, isothiazol-4-yl, and isothiazol-5-yl. The term “triazolyl” as used herein includes triazol-2-yl, 1H-triazolyl and 4H-1,2,4- triazolyl, “1H-triazolyl” includes 1H-1,2,3-triazol-1-yl, 1H-1,2,3-triazol-4-yl, 1H-1,2,3-triazol-5-yl, 1H-1,2,4-triazol-1-yl, 1H-1,2,4-triazol-3-yl and 1H-1,2,4-triazol-5-yl. “4H-1,2,4-triazolyl” includes 4H-1,2,4-triazol-4-yl, and 4H-1,2,4-triazol-3-yl. The term “oxadiazolyl” as used herein includes 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,5- oxadiazol-3-yl and 1,3,4-oxadiazol-2-yl. The term “thiadiazolyl” as used herein includes 1,2,3- thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,2,5-thiadiazol-3- yl (also called furazan-3-yl) and 1,3,4-thiadiazol-2-yl. The term “tetrazolyl” as used herein includes 1H-tetrazol-1-yl, 1H-tetrazol-5-yl, 2H-tetrazol-2-yl, and 2H-tetrazol-5-yl. The term “oxatriazolyl” asused herein includes 1,2,3,4-oxatriazol-5-yl and 1,2,3,5-oxatriazol-4-yl. The term “thiatriazolyl” as used herein includes 1,2,3,4-thiatriazol-5-yl and 1,2,3,5-thiatriazol-4-yl. The term “pyridinyl” (also called "pyridyl") as used herein includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl (also called 2- pyridyl, 3-pyridyl and 4-pyridyl). The term “pyrimidyl” as used herein includes pyrimid-2-yl, pyrimid- 4-yl, pyrimid-5-yl and pyrimid-6-yl. The term “pyrazinyl” as used herein includes pyrazin-2-yl and pyrazin-3-yl. The term “pyridazinyl as used herein includes pyridazin-3-yl and pyridazin-4-yl. The term “oxazinyl” (also called "1,4-oxazinyl") as used herein includes 1,4-oxazin-4-yl and 1,4- oxazin-5-yl. The term “dioxinyl” (also called "1,4-dioxinyl”) as used herein includes 1,4-dioxin-2-yl and 1,4-dioxin-3-yl. The term “thiazinyl” (also called "1,4-thiazinyl”) as used herein includes 1,4- thiazin-2-yl, 1,4-thiazin-3-yl, 1,4-thiazin-4-yl, 1,4-thiazin-5-yl and 1,4-thiazin-6-yl. The term “triazinyl” as used herein includes 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4- triazin-6-yl, 1,2,3-triazin-4-yl and 1,2,3-triazin-5-yl. The term “imidazo[2,1-b][1,3]thiazolyl” as used herein includes imidazo[2,1-b][1,3]thiazoi-2-yl, imidazo[2,1-b][1,3]thiazol-3-yl, imidazo[2,1- b][1,3]thiazol-5-yl and imidazo[2,1-b][1,3]thiazol-6-yl. The term “thieno[3,2-b]furanyl” as used herein includes thieno[3,2-b]furan-2-yl, thieno[3,2-b]furan-3-yl, thieno[3,2-b]furan-4-yl, and thieno[3,2-b]furan-5-yl. The term “thieno[3,2-b]thiophenyl” as used herein includes thieno[3,2- b]thien-2-yl, thieno[3,2-b]thien-3-yl, thieno[3,2-b]thien-5-yl and thieno[3,2-b]thien-6-yl. The term “thieno[2,3-d][1,3]thiazolyl” as used herein includes thieno[2,3-d][1,3]thiazol-2-yl, thieno[2,3- d][1,3]thiazol-5-yl and thieno[2,3-d][1,3]thiazol-6-yl. The term “thieno[2,3-d]imidazolyl” as used herein includes thieno[2,3-d]imidazol-2-yl, thieno[2,3-d]imidazol-4-yl and thieno[2,3-d]imidazol-5- yl. The term “tetrazolo[1,5-a]pyridinyl” as used herein includes tetrazolo[1,5-a]pyridine-5-yl, tetrazolo[1,5-a]pyridine-6-yl, tetrazolo[1,5-a]pyridine-7-yl, and tetrazolo[1,5-a]pyridine-8-yl. The term “indolyl” as used herein includes indol-1-yl, indol-2-yl, indol-3-yl,-indol-4-yl, indol-5-yl, indol- 6-yl and indol-7-yl. The term “indolizinyl” as used herein includes indolizin-1-yl, indolizin-2-yl, indolizin-3-yl, indolizin-5-yl, indolizin-6-yl, indolizin-7-yl, and indolizin-8-yl. The term “isoindolyl” as used herein includes isoindol-1-yl, isoindol-2-yl, isoindol-3-yl, isoindol-4-yl, isoindol-5-yl, isoindol- 6-yl and isoindol-7-yl. The term “benzofuranyl” (also called benzo[b]furanyl) as used herein includes benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl and benzofuran-7-yl. The term “isobenzofuranyl” (also called benzo[c]furanyl) as used herein includes isobenzofuran-1-yl, isobenzofuran-3-yl, isobenzofuran-4-yl, isobenzofuran-5-yl, isobenzofuran-6- yl and isobenzofuran-7-yl. The term “benzothiophenyl” (also called benzo[b]thienyl) as used herein includes 2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5- benzo[b]thiophenyl, 6-benzo[b]thiophenyl and -7-benzo[b]thiophenyl (also called benzothien-2-yl, benzothien-3-yl, benzothien-4-yl, benzothien-5-yl, benzothien-6-yl and benzothien-7-yl). The term “isobenzothiophenyl” (also called benzo[c]thienyl) as used herein includes isobenzothien-1-yl, isobenzothien-3-yl, isobenzothien-4-yl, isobenzothien-5-yl, isobenzothien-6-yl and isobenzothien- 7-yl. The term “indazolyl” (also called 1H-indazolyl or 2-azaindolyl) as used herein includes 1H-indazol-1-yl, 1H-indazol-3-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol-7-yl, 2H-indazol-2-yl, 2H-indazol-3-yl, 2H-indazol-4-yl, 2H-indazol-5-yl, 2H-indazol-6-yl, and 2H- indazol-7-yl. The term “benzimidazolyl” as used herein includes benzimidazol-1-yl, benzimidazol- 2-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl and benzimidazol-7-yl. The term “1,3-benzoxazolyl” as used herein includes 1,3-benzoxazol-2-yl, 1,3-benzoxazol-4-yl, 1,3- benzoxazol-5-yl, 1,3-benzoxazol-6-yl and 1,3-benzoxazol-7-yl. The term “1,2-benzisoxazolyl” as used herein includes 1,2-benzisoxazol-3-yl, 1,2-benzisoxazol-4-yl, 1,2-benzisoxazol-5-yl, 1,2- benzisoxazol-6-yl and 1,2-benzisoxazol-7-yl. The term “2,1-benzisoxazolyl” as used herein includes 2,1-benzisoxazol-3-yl, 2,1-benzisoxazol-4-yl, 2,1-benzisoxazol-5-yl, 2,1-benzisoxazol-6- yl and 2,1-benzisoxazol-7-yl. The term “1,3-benzothiazolyl” as used herein includes 1,3- benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl and 1,3- benzothiazol-7-yl. The term “1,2-benzoisothiazolyl” as used herein includes 1,2-benzisothiazol-3- yl, 1,2-benzisothiazol-4-yl, 1,2-benzisothiazol-5-yl, 1,2-benzisothiazol-6-yl and 1,2- benzisothiazol-7-yl. The term “2,1-benzoisothiazolyl” as used herein includes 2,1-benzisothiazol- 3-yl, 2,1-benzisothiazol-4-yl, 2,1-benzisothiazol-5-yl, 2,1-benzisothiazol-6-yl and 2,1- benzisothiazol-7-yl. The term “benzotriazolyl” as used herein includes benzotriazol-1-yl, benzotriazol-4-yl, benzotriazol-5-yl, benzotriazol-6-yl and benzotriazol-7-yl. The term “1,2,3- benzoxadiazolyl” as used herein includes 1,2,3-benzoxadiazol-4-yl, 1,2,3-benzoxadiazol-5-yl, 1,2,3-benzoxadiazol-6-yl and 1,2,3-benzoxadiazol-7-yl. The term “2,1,3-benzoxadiazolyl” as used herein includes 2,1,3-benzoxadiazol-4-yl, 2,1,3-benzoxadiazol-5-yl, 2,1,3-benzoxadiazol-6-yl and 2,1,3-benzoxadiazol-7-yl. The term “1,2,3-benzothiadiazolyl” as used herein includes 1,2,3- benzothiadiazol-4-yl, 1,2,3-benzothiadiazol-5-yl, 1,2,3-benzothiadiazol-6-yl and 1,2,3- benzothiadiazol-7-yl. The term “2,1,3-benzothiadiazolyl” as used herein includes 2,1,3- benzothiadiazol-4-yl, 2,1,3-benzothiadiazol-5-yl, 2,1,3-benzothiadiazol-6-yl and 2,1,3- benzothiadiazol-7-yl. The term “thienopyridinyl” as used herein includes thieno[2,3-b]pyridinyl, thieno[2,3-c]pyridinyl, thieno[3,2-c]pyridinyl and thieno[3,2-b]pyridinyl. The term “purinyl” as used herein includes purin-2-yl, purin-6-yl, purin-7-yl and purin-8-yl. The term “imidazo[1,2-a]pyridinyl”, as used herein includes imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-3-yl, imidazo[1,2- a]pyridin-4-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-6-yl and imidazo[1,2-a]pyridin-7- yl. The term “1,3-benzodioxolyl”, as used herein includes 1,3-benzodioxol-4-yl, 1,3-benzodioxol- 5-yl, 1,3-benzodioxol-6-yl, and 1,3-benzodioxol-7-yl. The term “quinolinyl” as used herein includes quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl and quinolin-8- yl. The term “isoquinolinyl” as used herein includes isoquinolin-1-yl, isoquinolin-3-yl, isoquinolin- 4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl and isoquinolin-8-yl. The term “cinnolinyl” as used herein includes cinnolin-3-yl, cinnolin-4-yl, cinnolin-5-yl, cinnolin-6-yl, cinnolin-7-yl and cinnolin-8-yl. The term “quinazolinyl” as used herein includes quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl and quinazolin-8-yl. The term “quinoxalinyl” asused herein includes quinoxalin-2-yl, quinoxalin-5-yl, and quinoxalin-6-yl. Heteroaryl and heterocycle or heterocyclyl as used herein includes by way of example and not limitation these groups described in Paquette, Leo A. “Principles of Modern Heterocyclic Chemistry” (W.A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; “The Chemistry of Heterocyclic Compounds, A series of Monographs” (John Wiley & Sons, New York, 1950 to present), in particular Volumes 13, 14, 16, 19, and 28; Katritzky, Alan R., Rees, C.W. and Scriven, E. “Comprehensive Heterocyclic Chemistry” (Pergamon Press, 1996); and J. Am. Chem. Soc. (1960) 82:5566. The term “heterocyclyloxy” or “heterocycleoxy”, as a group or part of a group, refers to a group having the formula -O-Riwherein Riis heterocyclyl as defined herein above. The term “heterocyclylalkyloxy” or “heterocycleoxy”, as a group or part of a group, refers to a group having the formula -O-Ra-Riwherein Riis heterocyclyl, and Rais alkyl as defined herein above. The term “heteroaryloxy”, as a group or part of a group, refers to a group having the formula -O-Rkwherein Rkis heteroaryl as defined herein above. The term “heteroarylalkyloxy”, as a group or part of a group, refers to a group having the formula -O-Ra-Riwherein Riis heteroaryl, and Rais alkyl as defined herein above. The term “heterocyclylalkyl” or “heterocycle-alkyl” as a group or part of a group, refers to an alkyl in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with a heterocyclyl. A non-limiting example of a heterocyclylalkyl or heterocycle-alkyl group is 2-piperidinyl-methylene. The heterocyclylalkyl or heterocycle-alkyl group can comprise 6 to 20 atoms, e.g. the alkyl moiety is 1 to 6 carbon atoms and the heterocyclyl moiety is 3 to 14 atoms. The term “heterocyclylalkenyl” or “heterocycle-alkenyl” as a group or part of a group refers to an alkenyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an heterocyclyl. The heterocyclylalkenyl or heterocycle-alkenyl group can comprise 6 to 20 atoms, e.g. the alkenyl moiety is 2 to 6 carbon atoms and the heterocyclyl moiety is 3 to 14 atoms. The term “heterocyclylalkynyl” or “heterocycle-alkynyl” as a group or part of a group refers to an alkynyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with a heterocyclyl. The heterocyclylalkynyl or heterocycle-alkynyl group can comprise 6 to 20 atoms, e.g. the alkynyl moiety can comprise 2 to 6 carbon atoms and the heterocyclyl moiety can comprise 3 to 14 atoms. The term “heterocyclylheteroalkyl” or “heterocycle-heteroalkyl” as a group or part of a group refers to a heteroalkyl in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with a heterocyclyl. The heterocyclylheteroalkyl or heterocycle-heteroalkyl group can comprise 6 to 20 atoms, e.g. the heteroalkyl moiety can comprise 1 to 6 carbon atoms and the heterocyclyl moiety can comprise3 to 14 atoms. In some embodiments heterocyclylheteroalkyl or heterocycle-heteroalkyl is selected from the group comprising heterocyclyl-O-alkyl, heterocyclylalkyl-O-alkyl, heterocyclyl- NH-alkyl, heterocyclyl-N(alkyl)2, heterocyclylalkyl-NH-alkyl, heterocyclylalkyl-N-(alkyl)2, heterocyclyl–S-alkyl, and heterocyclylalkyl-S-alkyl. The term “heterocyclylheteroalkenyl” or “heterocycle-heteroalkenyl” as a group or part of a group refers to a heteroalkenyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with a heterocyclyl. The heterocyclylheteroalkenyl or heterocycle-heteroalkenyl group can comprise 6 to 20 atoms, e.g. the heteroalkenyl moiety can comprise 2 to 6 carbon atoms and the heterocyclyl moiety can comprise 3 to 14 atoms. In some embodiments heterocyclyl- heteroalkenyl or heterocycle-heteroalkenyl is selected from the group comprising heterocyclyl-O- alkenyl, heterocyclylalkyl-O-alkenyl, heterocyclyl-NH-alkenyl, heterocyclyl-N(alkenyl)2, heterocyclylalkyl-NH-alkenyl, heterocyclylalkyl-N-(alkenyl)2, heterocyclyl–S-alkenyl, and heterocyclylalkenyl-S-alkenyl. The term “heterocyclylheteroalkynyl” or “heterocycle-heteroalkynyl” as a group or part of a group refers to a heteroalkynyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with a heterocyclyl. The heterocyclylheteroalkynyl or heterocycle-heteroalkynyl group can comprise 6 to 20 atoms, e.g. the heteroalkynyl moiety can comprise 2 to 6 carbon atoms and the heterocyclyl moiety can comprise 3 to 14 atoms. In some embodiments heterocyclyl- heteroalkynyl is selected from the group comprising heterocyclyl-O-alkynyl, heterocyclylalkynyl- O-alkynyl, heterocyclyl-NH-alkynyl, heterocyclyl-N(alkynyl)2, heterocyclylalkynyl-NH-alkynyl, heterocyclylalkynyl-N-(alkynyl)2, heterocyclyl–S-alkynyl, and heterocyclylalkynyl-S-alkynyl. The term “heteroarylalkyl” as a group or part of a group refers to an alkyl in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3 carbon atom, is replaced with a heteroaryl. An example of a heteroarylalkyl group is 2-pyridyl-methylene. The heteroarylalkyl group can comprise 6 to 20 atoms, e.g. the alkyl moiety of the heteroarylalkyl group can comprise 1 to 6 carbon atoms and the heteroaryl moiety can comprise 5 to 14 atoms. The term “heteroarylalkenyl” as a group or part of a group refers to an alkenyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an heteroaryl. The heteroaryl-alkenyl group can comprise 6 to 20 atoms, e.g. the alkenyl moiety of the heteroaryl- alkenyl group can comprise 2 to 6 carbon atoms and the heteroaryl moiety can comprise 5 to 14 atoms. The term “heteroarylalkynyl” as a group or part of a group as used herein refers to an alkynyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with a heteroaryl. The heteroarylalkynyl group comprises 6 to 20 atoms, e.g. the alkynyl moiety of the heteroaryl-alkynyl group is 2 to 6 carbon atoms and the heteroaryl moiety is 5 to 14 atoms. The term “heteroarylheteroalkyl” as a group or part of a group as used herein refers to a heteroalkyl in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal orsp3 carbon atom, is replaced with a heteroaryl. The heteroarylheteroalkyl group comprises 7 to 20 atoms, e.g. the heteroalkyl moiety of the heteroaryl-heteroalkyl group is 2 to 6 carbon atoms and the heteroaryl moiety is 5 to 14 atoms. In some embodiments heteroaryl-heteroalkyl is selected from the group comprising heteroaryl-O-alkyl, heteroarylalkyl-O-alkyl, heteroaryl-NH- alkyl, heteroaryl-N(alkyl)2, heteroarylalkyl-NH-alkyl, heteroarylalkyl-N-(alkyl)2, heteroaryl–S-alkyl, and heteroarylalkyl-S-alkyl. The term “heteroarylheteroalkenyl” as a group or part of a group as used herein refers to a heteroalkenyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with an heteroaryl. The heteroarylheteroalkenyl group comprises 8 to 20 atoms, e.g. the heteroalkenyl moiety of the heteroarylheteroalkenyl group is 3 to 6 carbon atoms and the heteroaryl moiety is 5 to 14 atoms. In some embodiments heteroarylheteroalkenyl is selected from the group comprising heteroaryl-O-alkenyl, heteroarylalkenyl-O-alkenyl, heteroaryl-NH-alkenyl, heteroaryl-N(alkenyl)2, heteroarylalkenyl-NH-alkenyl, heteroarylalkenyl-N-(alkenyl)2, heteroaryl–S-alkenyl, and heteroarylalkenyl-S-alkenyl. The term “heteroarylheteroalkynyl” as a group or part of a group as used herein refers to a heteroalkynyl in which one of the hydrogen atoms bonded to a carbon atom, is replaced with a heteroaryl. The heteroarylheteroalkynyl group comprises 8 to 20 atoms, e.g. the heteroalkynyl moiety of the heteroarylheteroalkynyl group is 2 to 6 carbon atoms and the heteroaryl moiety is 5 to 14 atoms. In some embodiments heteroarylheteroalkynyl is selected from the group comprising heteroaryl-O-alkynyl, heteroarylalkynyl-O-alkynyl, heteroaryl-NH-alkynyl, heteroaryl-N(alkynyl)2, heteroarylalkynyl-NH-alkynyl, heteroarylalkynyl-N-(alkynyl)2, heteroaryl–S-alkynyl, and heteroarylalkynyl-S-alkynyl. By way of example, carbon bonded heteroaryl or heterocyclic rings (or heterocycles) can be bonded at position 2, 3, 4, 5, or 6 of a pyridine, position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of a pyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiophene, pyrrole or tetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole or thiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine, position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline. Still more typically, carbon bonded heteroaryls and heterocyclyls include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4- pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl. By way of example, nitrogen bonded heterocyclic rings are bonded at position 1 of an aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline, 3- imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole, position 2 of a isoindole, or isoindoline, position 4 of a morpholine, and position 9 of a carbazole, or ß-carboline. Still more typically, nitrogen bonded heteroaryls orheterocyclyls include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl. As used herein and unless otherwise stated, the terms “alkoxy”, “cyclo-alkoxy”, “aryloxy”, “arylalkyloxy”, “heteroaryloxy” “heterocyclyloxy”, “alkylthio”, “cycloalkylthio”, “arylthio”, “arylalkylthio”, “heteroarylthio” and “heterocyclylthio” refer to substituents wherein an alkyl group, respectively a cycloalkyl, aryl, arylalkyl heteroaryl, or heterocyclyl (each of them such as defined herein), are attached to an oxygen atom or a sulfur atom through a single bond, such as but not limited to methoxy, ethoxy, propoxy, butoxy, thioethyl, thiomethyl, phenyloxy, benzyloxy, mercaptobenzyl and the like. The same definitions will apply for alkenyl and alkynyl instead of alkyl. The term “alkylthio", as a group or part of a group, refers to a group having the formula – S-Rbwherein Rbis alkyl as defined herein above. Non-limiting examples of alkylthio groups include methylthio (-SCH3), ethylthio (-SCH2CH3), n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio and the like. The term “alkenylthio", as a group or part of a group, refers to a group having the formula –S-Rdwherein Rdis alkenyl as defined herein above. The term “alkynylthio", as a group or part of a group, refers to a group having the formula –S-Rewherein Reis alkynyl as defined herein above. The term “arylthio", as a group or part of a group, refers to a group having the formula – S-Rgwherein Rgis aryl as defined herein above. The term “arylalkylthio", as a group or part of a group, refers to a group having the formula -S-Ra-Rgwherein Rais alkylene and Rgis aryl as defined herein above. The term “heterocyclylthio", as a group or part of a group, refers to a group having the formula –S-Riwherein Riis heterocyclyl as defined herein above. The term “heteroarylthio", as a group or part of a group, refers to a group having the formula –S-Rkwherein Rkis heteroaryl as defined herein above. The term “heterocyclylalkylthio", as a group or part of a group, refers to a group having the formula -S-Ra-Riwherein Rais alkylene and Riis heterocyclyl as defined herein above. The term “heteroarylalkylthio", as a group or part of a group, refers to a group having the formula -S-Ra-Rkwherein Rais alkylene and Rkis heteroaryl as defined herein above. The term “mono- or di-alkylamino”, as a group or part of a group, refers to a group of formula -N(Ro)(Rb) wherein Rois hydrogen, or alkyl, Rbis alkyl. Thus, alkylamino include mono- alkyl amino group (e.g. mono-alkylamino group such as methylamino and ethylamino), and di- alkylamino group (e.g. di-alkylamino group such as dimethylamino and diethylamino). Non- limiting examples of suitable mono- or di-alkylamino groups include n-propylamino, isopropylamino, n-butylamino, i-butylamino, sec-butylamino, t-butylamino, pentylamino, n- hexylamino, di-n-propylamino, di-i-propylamino, ethylmethylamino, methyl-n-propylamino, methyl-i-propylamino, n-butylmethylamino, i-butylmethylamino, t-butylmethylamino, ethyl-n-propylamino, ethyl-i-propylamino, n-butylethylamino, i-butylethylamino, t-butylethylamino, di-n- butylamino, di-i-butylamino, methylpentylamino, methylhexylamino, ethylpentylamino, ethylhexylamino, propylpentylamino, propylhexylamino, and the like. The term “mono- or di-arylamino”, as a group or part of a group, refers to a group of formula -N(Rq)(Rr) wherein Rqand Rrare each independently selected from hydrogen, aryl, or alkyl, wherein at least one of Rqor Rris aryl. The term “mono- or di-heteroarylamino”, as a group or part of a group, refers to a group of formula -N(Ru)(Rv) wherein Ruand Rvare each independently selected from hydrogen, heteroaryl, or alkyl, wherein at least one of Ruor Rvis heteroaryl as defined herein. The term “mono- or di-heterocyclylamino”, as a group or part of a group, refers to a group of formula -N(Rw)(Rx) wherein Rwand Rxare each independently selected from hydrogen, heterocyclyl, or alkyl, wherein at least one of Rwor Rxis heterocyclyl as defined herein. As used herein and unless otherwise stated, the term halogen means any atom selected from the group consisting of fluorine (F), chlorine (Cl), bromine (Br) and iodine (I). The terminology regarding a chemical group “which optionally includes one or more heteroatoms, said heteroatoms being selected from the atoms consisting of O, S, and N” as used herein, refers to a group where one or more carbon atoms are replaced by an oxygen, nitrogen or sulphur atom and thus includes, depending on the group to which is referred, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloheteroalkyl, cycloheteroalkenyl, cycloheteroalkynyl, heteroaryl, arylheteroalkyl, heteroarylalkyl, heteroarylheteroalkyl, arylheteroalkenyl, heteroarylalkenyl, heteroarylheteroalkenyl, heteroarylheteroalkenyl, arylheteroalkynyl, heteroarylalkynyl, heteroarylheteroalkynyl, among others. This term therefore comprises, depending on the group to which is referred, as an example alkoxy, alkenyloxy, alkynyloxy, alkyl-O-alkylene, alkenyl-O-alkylene, arylalkoxy, benzyloxy, heteroarylheteroalkyl, heterocyclylheteroalkyl, heteroaryl-alkoxy, heterocyclyl-alkoxy, among others. As an example, the terminology “alkyl which optionally includes one or more heteroatoms, said heteroatoms being selected from the atoms consisting of O, S, and N” therefore refers to heteroalkyl, meaning an alkyl which comprises one or more heteroatoms in the hydrocarbon chain, whereas the heteroatoms may be positioned at the beginning of the hydrocarbon chain, in the hydrocarbon chain or at the end of the hydrocarbon chain. Examples of heteroalkyl include methoxy, methylthio, ethoxy, propoxy, CH3-O-CH2-, CH3-S-CH2-, CH3-CH2-O-CH2-, CH3-NH-, (CH3)2-N-, (CH3)2-CH2-NH-CH2-CH2-, among many other examples. As an example, the terminology “arylalkylene which optionally includes one or more heteroatoms in the alkylene chain, said heteroatoms being selected from the atoms consisting of O, S, and N” therefore refers to arylheteroalkylene, meaning an arylalkylene which comprises one or more heteroatoms in the hydrocarbon chain, whereas the heteroatoms may be positioned at the beginning of the hydrocarbon chain, in the hydrocarbon chain or at the end of the hydrocarbon chain.“Arylheteroalkylene” thus includes aryloxy, arylalkoxy, aryl-alkyl-NH- and the like and examples are phenyloxy, benzyloxy, aryl-CH2-S-CH2-, aryl-CH2-O-CH2-, aryl-NH-CH2- among many other examples. The same counts for “heteroalkenylene”, “heteroalkynylene”, and other terms used herein when referred to “which optionally includes one or more heteroatoms, said heteroatoms being selected from the atoms consisting of O, S, and N”. The terminology regarding a chemical group “wherein optionally two or more hydrogen atoms on a carbon atom or heteroatom of said group can be taken together to form a =O or =S” as used herein, refers to a group where two or more hydrogen atoms on a carbon atom or heteroatom of said group are taken together to form =O or =S. As an example, the terminology refers to “an alkyl wherein optionally two or more hydrogen atoms on a carbon atom or heteroatom of said alkyl can be taken together to form a =O or =S”, includes among other examples CH3- C(O)-CH2-, CH3-C(O)-, CH3-C(S)-CH2-, CH3-S(O)2-CH2- and (CH3)2-CH2-C(O)-CH2-CH2-. The combination for a group “which optionally includes one or more heteroatoms, said heteroatoms being selected from the atoms consisting of O, S, and N” and “wherein optionally two or more hydrogen atoms on a carbon atom or heteroatom of said group can be taken together to form a =O or =S” can combine the two aspects described herein above and includes, if the group referred to is alkyl, among other examples CH3-C(O)O-, CH3-C(O)O-CH2-, CH3-NH-C(O)-, CH3-C(O)-NH- CH3-NH-C(O)-CH2-, CH3-NH-C(S)-CH2-, CH3-NH-C(S)-NH-CH2-, CH3-NH-S(O)2- and CH3-NH-S(O)2-NH-CH2-. The term “single bond” as used herein for a linking group i.e. in a way that a certain linking group is selected from a single bond, etc. in the formulas herein, refers to a molecule wherein the linking group is not present and therefore refers to compounds with a direct linkage via a single bond between the two moieties being linked by the linking group. As used herein with respect to a substituting group, and unless otherwise stated, the terms “substituted” such as in “substituted alkyl”, “substituted alkenyl”, substituted alkynyl”, “substituted aryl”, “substituted heteroaryl”, “substituted heterocyclyl”, “substituted arylalkyl”, “substituted heteroaryl-alkyl”, “substituted heterocyclylalkyl” and the like refer to the chemical structures defined herein, and wherein the said alkyl, alkenyl, alkynyl, group and / or the said aryl, heteroaryl, or heterocyclyl may be optionally substituted with one or more substituents (preferable 1, 2, 3, 4, 5 or 6), meaning that one or more hydrogen atoms are each independently replaced with at least one substituent. Typical substituents include, but are not limited to and in a particular embodiment said substituents are being independently selected from the group consisting of halogen, amino, hydroxyl, sulfhydryl, alkyl, alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocyclyl, arylalkyl, arylalkenyl, arylalkynyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heteroarylalkyl, heterocyclylalkyl, heteroarylalkenyl, heterocyclylalkenyl and heteroarylalkynyl, heterocyclylalkynyl, -X, -Z, -O-, -OZ, =O, -SZ, -S-, =S, -NZ2, -N+Z3, =NZ, =N-OZ, -CX3(e.g.trifluoromethyl), -CN, -OCN, -SCN, -N=C=O, -N=C=S, -NO, -NO2, =N2, -N3, -NZC(O)Z, -NZC(S)Z, -NZC(O)O-, -NZC(O)OZ, -NZC(S)OZ, -NZC(O)NZZ, NZC(NZ)Z, NZC(NZ)NZZ, -C(O)NZZ, - C(NZ)Z, -S(O)2O-, -S(O)2OZ, -S(O)2Z, -OS(O)2OZ, -OS(O)2Z, -OS(O)2O-, -S(O)2NZZ, -S(O)(NZ)Z, -S(O)Z, -OP(O)(OZ)2, -P(O)(OZ)2, -P(O)(O-)2, -P(O)(OZ)(O-), -P(O)(OH)2, -C(O)Z, -C(O)X, - C(S)Z, -C(O)OZ, -C(O)O-, -C(S)OZ, -C(O)SZ, -C(S)SZ, -C(O)NZZ, -C(S)NZZ, -C(NZ)NZZ, - OC(O)Z, -OC(S)Z, -OC(O)O-, -OC(O)OZ, -OC(S)OZ, wherein each X is independently a halogen selected from F, Cl, Br, or I; and each Z is independently –H, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocyclyl, cycloalkyl, protecting group or prodrug moiety, while two Z bonded to a nitrogen atom can be taken together with the nitrogen atom to which they are bonded to form a heteroaryl, or heterocyclyl. Alkyl(ene), alkenyl(ene), and alkynyl(ene) groups may also be similarly substituted. Any substituent designation that is found in more than one site in a compound of this invention shall be independently selected. Substituents optionally are designated with or without bonds. Regardless of bond indications, if a substituent is polyvalent (based on its position in the structure referred to), then any and all possible orientations of the substituent are intended. As used herein and unless otherwise stated, the term “solvate” includes any combination which may be formed by a derivative of this invention with a suitable inorganic solvent (e.g. hydrates) or organic solvent, such as but not limited to alcohols, ketones, esters, ethers, nitriles and the like. The term “heteroatom(s)” as used herein means an atom selected from nitrogen, which can be quaternized; oxygen; and sulfur, including sulfoxide and sulfone. The term “hydroxy” as used herein means -OH. The term “carbonyl” as used herein means carbon atom bonded to oxygen with a double bond, i.e., C═O. The term “amino” as used herein means the -NH2 group. The present invention provides novel compounds which have been shown to possess PTPN2 and / or PTPN1 inhibitory activity. Therefore, these compounds constitute a useful class of new potent compounds that can be used in the treatment and / or prevention of PTPN2 and / or PTPN1 mediated diseases in subjects, more specifically for the treatment and / or prevention of cancer and metabolic diseases, among other diseases. The present invention furthermore relates to the compounds for use as medicines and to their use for the manufacture of medicaments for treating and / or preventing cancer or metabolic diseases. The present invention relates to the compounds for use as medicines for treating and / or preventing PTPN2 and / or PTPN1 mediated diseases such as cancer or metabolic diseases in animals, mammals, more in particular in humans. The invention also relates to methods for the preparation of all such compounds and to pharmaceutical compositions comprising them in aneffective amount. The present invention also relates to a method of treatment or prevention of cancer or metabolic diseases in humans by the administration of one or more such compounds, optionally in combination with one or more other medicines, to a patient in need thereof. The present invention also relates to the compounds for veterinary use and to their use as medicines for the prevention or treatment of diseases in a non-human mammal, such as cancer and metabolic diseases in non-human mammals. More particularly, the compounds of the invention are compounds of formula (I) and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, polymorph and / or prodrug thereof,wherein: - represents a double bond () or a triple bond ( ); - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl; or a 4-, 5-, 6-, or 7-membered heterocycle; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl;heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. It is clear from the description of the invention that in formula (I) and other relevant formulas and embodiments herein, R1can be unsubstituted or substituted with one or more R4and that in formula (I) and other relevant formulas and embodiments herein when is a double bond, R2is selected from hydrogen; alkyl and halogen, or R2can be taken together with R1to form a 3- , 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6- , or 7-membered cycloalkynyl; or a 4-, 5-, 6-, or 7-membered heterocycle;wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl, or a 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4, meaning that one or more hydrogen atoms on one or more carbon atoms or heteroatoms such as nitrogen atom, are each independently replaced with one or more R4substituents; wherein - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3- , 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl. Preferred or particular statements (features) and embodiments of the compounds of this invention are set herein below. Each statement, aspect and embodiment of the invention so defined may be combined with any other statement, aspect and / or embodiment, unless clearly indicated to the contrary. In particular, any feature indicated as being preferred, particular or advantageous may be combined with any other features or statements indicated as being preferred, particular or advantageous. Hereto, the present invention is in particular captured by any one or any combination of one or more of the below numbered statements and embodiments,with any other statement, aspect and / or embodiment (which are not numbered). A1. A compound of formula (I), a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), a solvate, a hydrate, a polymorph, an isotope, and / or a prodrug thereof,wherein: - represents a double bond ( ) or a triple bond ( ); - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4;alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl;heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; heterocyclylheteroalkynyl; alkyl-oxy-alkyl; (mono or di)alkylamino; (mono or di-)alkyl-amino-alkyl; alkylthio; and alkyl-thio-alkyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, heterocyclylheteroalkynyl, alkyl-oxy-alkyl, (mono or di)alkylamino, (mono or di-)alkyl-amino-alkyl, alkylthio, and alkyl-thio-alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3- , 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl;heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2; preferably wherein “heteroalkyl” as a group or part of a group is selected from the group comprising alkyloxy, alkyl-oxy-alkyl, (mono or di)alkylamino, (mono or di-)alkyl-amino-alkyl, alkylthio, and alkyl-thio-alkyl; preferably wherein “heteroalkenyl” as a group or part of a group is selected from the group comprising alkenyloxy, alkenyl-oxy-alkenyl, alkyl-oxy-alkenyl, alkenyl-oxy-alkyl, (mono ordi)alkenylamino, (alkyl)(alkenyl)amino, (mono or di-)alkenyl-amino-alkenyl, (mono or di-)alkyl- amino-alkenyl, (mono or di-)alkenyl-amino-alkyl, (alkyl)(alkenyl)amino-alkenyl, (alkyl)(alkenyl)amino-alkyl, alkenylthio, alkenyl-thio-alkyl, alkyl-thio-alkenyl, and alkenyl-thio- alkenyl; preferably wherein “heteroalkynyl” as a group or part of a group is selected from the group comprising alkynyloxy, alkynyl-oxy-alkynyl, alkyl-oxy-alkynyl, alkynyl-oxy-alkyl, (mono or di)alkynylamino, (alkyl)(alkynyl)amino, (mono or di-)alkynyl-amino-alkynyl, (mono or di-)alkyl- amino-alkynyl, (mono or di-)alkynyl-amino-alkyl, (alkyl)(alkynyl)amino-alkynyl, (alkyl)(alkynyl)amino-alkyl, alkynylthio, alkynyl-thio-alkyl, alkyl-thio-alkynyl, and alkynyl-thio- alkynyl; In some preferred embodiments: - R1is selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C3-9cycloalkylC1-6alkyl; C5- 10cycloalkenylC1-6alkyl; C7-10cycloalkynylC1-6alkyl; C3-9cycloalkylC1-6heteroalkyl; C5- 10cycloalkenylC1-6heteroalkyl; C7-10cycloalkynylC1-6heteroalkyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; heteroarylC1-6alkyl; heterocyclylC1-6alkyl; C6-10arylC1-6heteroalkyl; heteroarylC1- 6heteroalkyl; and heterocyclylC1-6heteroalkyl; whereby each of said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C3-9cycloalkylC1-6alkyl; C5- 10cycloalkenylC1-6alkyl; C7-10cycloalkynylC1-6alkyl; C3-9cycloalkylC1-6heteroalkyl; C5- 10cycloalkenylC1-6heteroalkyl; C7-10cycloalkynylC1-6heteroalkyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; heteroarylC1-6alkyl; heterocyclylC1-6alkyl; C6-10arylC1-6heteroalkyl; heteroarylC1-6heteroalkyl; and heterocyclylC1-6heteroalkyl is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; C1-9alkyl and halogen; - R3is selected from hydrogen and C1-9alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; - CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; - NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-9alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; arylC1-6heteroalkyl; arylC2-6heteroalkenyl; arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl;heterocyclylC2-6heteroalkynyl; C1-6alkyl-oxy-C1-6alkyl; (mono or di)C1-6alkylamino; (mono or di-)C1- 6alkyl-amino-C1-6alkyl; C1-9alkylthio; and C1-6alkyl-thio-C1-6alkyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-9alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; arylC1-6heteroalkyl; arylC2-6heteroalkenyl; arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2- 6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; heterocyclylC2-6heteroalkynyl; C1- 6alkyl-oxy-C1-6alkyl; (mono or di)C1-6alkylamino; (mono or di-)C1-6alkyl-amino-C1-6alkyl; C1- 9alkylthio; and C1-6alkyl-thio-C1-6alkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, - NHC1-6alkyl, -N(C1-6alkyl)2, -S(O)2C1-6alkyl, and -NHS(O)2C1-6alkyl; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, -N(C1-6alkyl)2, -S(O)2C1-6alkyl, and -NHS(O)2C1-6alkyl; - each Z1is independently selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2- 6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3- 9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6- 10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC1-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2- 6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3- 10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1- 6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2- 6heteroalkenyl; heteroarylC1-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and - N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S,-CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and - N(C1-6alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; preferably wherein “C1-12heteroalkyl” as a group or part of a group is selected from the group comprising C1-12alkyloxy, C1-6alkyl-oxy-C1-6alkyl, (mono or di)C1-6alkylamino, (mono or di-)C1- 6alkyl-amino-C1-6alkyl, C1-12alkylthio, and C1-6alkyl-thio-C1-6alkyl; preferably wherein “C2-12heteroalkenyl” as a group or part of a group is selected from the group comprising C2-12alkenyloxy, C2-6alkenyl-oxy-C2-6alkenyl, C1-6alkyl-oxy-C2-6alkenyl, C2-6alkenyl- oxy-C1-6alkyl, (mono or di)C2-6alkenylamino, (C1-6alkyl)(C2-6alkenyl)amino, (mono or di-)C2- 6alkenyl-amino-C2-6alkenyl, (mono or di-)C1-6alkyl-amino-C2-6alkenyl, (mono or di-)C2-6alkenyl- amino-C1-6alkyl, (C1-6alkyl)(C2-6alkenyl)amino-C2-6alkenyl, (C1-6alkyl)(C2-6alkenyl)amino-C1-6alkyl, C2-12alkenylthio, C2-6alkenyl-thio-C1-6alkyl, C1-6alkyl-thio-C2-6alkenyl, and C2-6alkenyl-thio-C2- 6alkenyl; preferably wherein “C2-12heteroalkynyl” as a group or part of a group is selected from the group comprising C2-12alkynyloxy, C2-6alkynyl-oxy-C2-6alkynyl, C1-6alkyl-oxy-C2-6alkynyl, C2-6alkynyl-oxy- C1-6alkyl, (mono or di)C2-6alkynylamino, (C1-6alkyl)(C2-6alkynyl)amino, (mono or di-)C2-6alkynyl- amino-C2-6alkynyl, (mono or di-)C1-6alkyl-amino-C2-6alkynyl, (mono or di-)C2-6alkynyl-amino-C1-6alkyl, (C1-6alkyl)(C2-6alkynyl)amino-C2-6alkynyl, (C1-6alkyl)(C2-6alkynyl)amino-C1-6alkyl, C2-12alkynylthio, C2-6alkynyl-thio-C1-6alkyl, C1-6alkyl-thio-C2-6alkynyl, and C2-6alkynyl-thio-C2-6alkynyl; preferably each heteroaryl is 5 to 20 membered heteroaryl, more in particular is a 6 to 14 membered heteroaryl; yet more in particular is a 6 to 10 membered heteroaryl; including when such heteroaryl is linked to alkyl, alkenyl or alkynyl such as in heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl; preferably each heterocycle is 5 to 20 membered heterocycle, more in particular is a 6 to 14 membered heterocycle; yet more in particular is a 6 to 10 membered heterocycle; including when such heterocycle is linked to alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl as in heterocyclealkyl, heterocyclealkenyl, heterocyclealkynyl, heterocycleheteroalkyl, heterocycleheteroalkenyl and heterocycleheteroalkynyl. A2. In some embodiments of the compound according to statement A1, with a structure of formula (II)wherein: - cycle A is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; preferably cycle A is selected from C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle; and - n is selected from 0; 1; 2; 3; 4; and 5. A3. In some embodiments of the compound according to statement 2, n is selected from 1; 2; 3 and 4. A4. In some embodiments of the compound according to any one of statements A1 to A3, represents a double bond ( ). A5. In some embodiments of the compound according to any one of statements A1 to A3, represents a triple bondA6. In some embodiments of the compound according to statement A1, said compound has a structure of formula (Ib) or (Ia)A7. In some embodiments of the compound according to any one of statements A1, A5, A6, said compound has a structure of formula (Ib)wherein: - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; preferably R1is selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1- 12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7- 10cycloalkynyl; C3-9cycloalkylC1-6alkyl; C5-10cycloalkenylC1-6alkyl; C7-10cycloalkynylC1-6alkyl; C3- 9cycloalkylC1-6heteroalkyl; C5-10cycloalkenylC1-6heteroalkyl; C7-10cycloalkynylC1-6heteroalkyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; heteroarylC1-6alkyl; heterocyclylC1-6alkyl; C6-10arylC1-6heteroalkyl; heteroarylC1-6heteroalkyl; and heterocyclylC1-6heteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4; preferably whereby each of said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C3-9cycloalkylC1-6alkyl; C5-10cycloalkenylC1-6alkyl; C7-10cycloalkynylC1-6alkyl; C3-9cycloalkylC1-6heteroalkyl; C5-10cycloalkenylC1-6heteroalkyl; C7-10cycloalkynylC1-6heteroalkyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; heteroarylC1-6alkyl; heterocyclylC1-6alkyl; C6-10arylC1-6heteroalkyl; heteroarylC1-6heteroalkyl; and heterocyclylC1-6heteroalkyl is unsubstituted or is substituted with one or more R4; - R3is selected from hydrogen and alkyl; preferably R3is selected from hydrogen and C1-9alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl;heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; preferably each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - - C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; - P(O)Z3Z4; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-9alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; arylC1-6heteroalkyl; arylC2- 6heteroalkenyl; arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2- 6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; preferably wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3- 9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; C6- 10arylC1-9alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; arylC1-6heteroalkyl; arylC2-6heteroalkenyl; arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, - CF3, -O-C1-6alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, - N(C1-6alkyl)2, -S(O)2C1-6alkyl, and -NHS(O)2C1-6alkyl; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl;arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; preferably each Z1is independently selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1- 6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2- 6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2- 6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, - CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and - N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl;heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; preferably - each Z2is independently selected from hydroxyl; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6- 10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6- 10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC1-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably wherein said C1- 9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1- 12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6- 10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC1-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2- 6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2- 6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, - CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and - N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; preferably each Z3and Z4is independently selected from hydrogen; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6- 10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6- 10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably wherein said C1- 9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1- 12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6- 10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6- 10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2- 6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, - CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and - N(C1-6alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, - OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2. A8. In some embodiments of the compound according to any one of statements A1-A3, A5-A7, said compound has a structure of formula (IIa):cycle A is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; and R3, n, each R4, have the same meaning as that defined in any one of statements A1-A3, A5-A7; preferably cycle A is selected from C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle; and R3, n, each R4, have the same meaning as that defined in any one of statements A1-A3, A5-A7. A9. In some embodiments of the compound according to any one of statements A1-A8, R1or cycle A is selected from the group comprisingwherein each cycle A1 and cycle A2 is independently selected from 5-, 6-, or 7--membered heterocycle; 5-, 6-, or 7-membered cycloalkyl; and n, each R4, have the same meaning as that defined in any one of statements A1-A8. A10. In some embodiments of the compound according to any one of statements A1-A9, R1or cycle A is selected from the group comprising. A11. In some embodiments of the compound according to any one of statements A1-A9, R1or cycle A is selected from the group comprising. A12. In some embodiments of the compound according to any one of statements A1-A9, R1or cycle A is selected from the group comprising.A13. In some embodiments of the compound according to any one of statements A1 to A12, R3is hydrogen. A14. In some embodiments of the compound according to any one of statements A1 to A12, R3is alkyl, preferably R3is C1-6alkyl, A15. In some embodiments of the compound according to any one of statements A1-A14, each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; - NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle, and heterocyclylalkyl; preferably each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; - OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; C1- 9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3- 9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; and heteroarylC1-6alkyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle and heterocyclylalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; preferably wherein each of said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2- 12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6- 10aryl; heteroaryl; heterocycle; and heteroarylC1-6alkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, -N(C1-6alkyl)2, -S(O)2C1-6alkyl, and -NHS(O)2C1-6alkyl. A16. In some embodiments of the compound according to any one of statements A1 to A15, - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3Z4; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; preferably each R4is independently selectedfrom halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - NZ3Z4; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1- 12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7- 10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably wherein each of said C1-9alkyl; C2- 9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3- 9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3- 9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, - OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1-6alkyl)2. A17. In some embodiments of the compound according to any one of statements A1 to A16, each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; =O; -CF3; - OCF3; -CHF2; -OCHF2; cyano; -OZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -C(O)H; -C(O)Z2; - C(O)OH; -C(O)OZ1; -NZ3Z4; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; heteroalkyl; aryl; heteroaryl; and heterocycle; preferably each R4is independently selected from C1-9alkyl; C3- 9cycloalkyl; halogen; hydroxyl; =O; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -S(O)Z1; - S(O)2Z2; -S(O)2NZ3Z4; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3Z4; -NZ3S(O)2Z1; - NZ3C(O)OZ1; -NZ3C(O)Z1; C1-9heteroalkyl; C6-10aryl; heteroaryl; and heterocycle; wherein said alkyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably wherein each of said C1-9alkyl; C1-12heteroalkyl; C3-9cycloalkyl; C6-10aryl; heteroaryl; and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1-6alkyl)2. A18. In some embodiments of the compound according to any one of statements A1 to A17, - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl,alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z1is independently selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3- 10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; and C2-12heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; - NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl, heterocycle; and arylalkyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, heterocycle; and arylalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z2is independently selected from hydroxyl; C1- 9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1- 12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; heterocycle; and C6-10arylC1-6alkyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3- 10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; heterocycle; and C6-10arylC1-6alkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3 and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z3and Z4is independently selected from hydrogen; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; and C2-12heteroalkynyl is unsubstituted oris substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2, and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2- 9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2. A19. In some embodiments of the compound according to any one of statements A1 to A18, - each Z1is independently selected from alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z1is independently selected from C1-9alkyl; and C3-9cycloalkyl; wherein said C1-9alkyl; and C3- 9cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1- 9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1- 6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z2is independently selected from hydroxyl; C1-9alkyl; and C3-9cycloalkyl; wherein said C1-9alkyl; and C3-9cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z3and Z4is independently selected from hydrogen; C1-9alkyl; and C3-9cycloalkyl; wherein said C1-9alkyl; and C3-9cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, - O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2. A20. In some embodiments of the compound according to any one of statements A1-A19, said compound is selected from the group comprising Cpd001, Cpd002, Cpd003, Cpd004, Cpd005, Cpd006, Cpd007, Cpd008, Cpd009, Cpd010, Cpd011, Cpd012, Cpd013, Cpd014, Cpd015, Cpd016, Cpd017, Cpd018, Cpd019, Cpd020, Cpd021, Cpd022, Cpd023, Cpd024, Cpd025, Cpd026, Cpd027, Cpd028, Cpd029, Cpd030, Cpd031, Cpd032, Cpd033, Cpd034, Cpd035, Cpd036, Cpd040, Cpd041, Cpd042, Cpd043, Cpd044, Cpd045, Cpd049, Cpd050, Cpd051, Cpd052, Cpd053, Cpd054, Cpd055, Cpd056, Cpd057, Cpd058, Cpd059, Cpd060, Cpd061, Cpd062, Cpd063, Cpd064, Cpd065, Cpd066, Cpd067, Cpd068, Cpd069, Cpd070, Cpd071, Cpd072, Cpd073, Cpd074, Cpd075, Cpd076, Cpd077, Cpd078, Cpd079, Cpd080, Cpd081, Cpd082, Cpd083, Cpd084, Cpd085, Cpd086, Cpd087, Cpd088, Cpd089, Cpd090, Cpd091, Cpd092, Cpd093, Cpd094, Cpd097, Cpd098, Cpd099, Cpd100, Cpd101, Cpd102, Cpd103, Cpd104, Cpd105, Cpd106, Cpd107, Cpd108, Cpd109, Cpd110, Cpd111, Cpd112, Cpd113, Cpd080-en1, Cpd080-en2, Cpd116, Cpd117, Cpd118, Cpd119, Cpd120, Cpd121, Cpd122, Cpd123, Cpd124-en1, Cpd124-en2, Cpd125-en1, Cpd125-en2, Cpd126-en1, Cpd126-en2, Cpd127, Cpd128, Cpd129, Cpd134, Cpd135, Cpd136, Cpd137, Cpd138, Cpd140, Cpd141, Cpd142-en1, Cpd142-en2, Cpd148, Cpd149-en1, Cpd149-en2, Cpd150, Cpd151, Cpd152, Cpd153, Cpd154, Cpd155, Cpd161, and Cpd166. A21. A method for the preparation of compounds according to any one of statements A1-A20, comprising the steps of: - coupling a halogen-containing compound of formula (A1) with an alkyne derivative and further removing PG (if different than H) thereby obtaining a compound of formula (A2), wherein R1and R3have the same meaning as defined in any one of statements A1-A20, PG is a protecting group or a hydrogen and X is a halogen; or- coupling a halogen-containing compound of formula (A1) with a silylated-acetylene derivative ; in a next step, performing concomitant in situ silyl deprotection with a fluoride source and coupling with a R1-X halogen derivative, and further removing PG, if different than H, thereby obtaining a compound of formula (A2), wherein R1and R3have the same meaning as definedin any one of statements A1-A20, PG is a protecting group or a hydrogen and X is a halogen; or- coupling a halogen-containing compound of formula (A1) with an alkenyl boronic derivative and further removing PG, if different than H, thereby obtaining compound of formula (A3), wherein R1, R2and R3have the same meaning as defined in any one of statements A1-A20, PG is a protecting group or a hydrogen and X is a halogen, or a:lternatively, the alkenyl boronic derivative can be replaced by a terminal alkene, an alkenyl zinc reagent or an alkenyl stannane reagent. B1.A compound of formula (III), a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, hydrate, polymorph, isotope, and / or prodrug thereof,wherein: - cycle B is selected from heterocycle; cycloalkyl; cycloalkenyl; and cycloalkynyl; - m is selected from 0; 1; 2; 3; 4; and 5. - R3is selected from hydrogen and alkyl;- each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; - S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - - C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; - NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, hydroxyl, cycloalkyl, alkenyl, alkynyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl isunsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituentsselected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O- alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably wherein “heteroalkyl” as a group or part of a group is selected from the group comprising alkyloxy, alkyl-oxy-alkyl, (mono or di)alkylamino, (mono or di-)alkyl-amino-alkyl, alkylthio, and alkyl-thio-alkyl; preferably wherein “heteroalkenyl” as a group or part of a group is selected from the group comprising alkenyloxy, alkenyl-oxy-alkenyl, alkyl-oxy-alkenyl, alkenyl-oxy-alkyl, (mono or di)alkenylamino, (alkyl)(alkenyl)amino, (mono or di-)alkenyl-amino-alkenyl, (mono or di-)alkyl- amino-alkenyl, (mono or di-)alkenyl-amino-alkyl, (alkyl)(alkenyl)amino-alkenyl, (alkyl)(alkenyl)amino-alkyl, alkenylthio, alkenyl-thio-alkyl, alkyl-thio-alkenyl, and alkenyl-thio- alkenyl; preferably wherein “heteroalkynyl” as a group or part of a group is selected from the group comprising alkynyloxy, alkynyl-oxy-alkynyl, alkyl-oxy-alkynyl, alkynyl-oxy-alkyl, (mono or di)alkynylamino, (alkyl)(alkynyl)amino, (mono or di-)alkynyl-amino-alkynyl, (mono or di-)alkyl- amino-alkynyl, (mono or di-)alkynyl-amino-alkyl, (alkyl)(alkynyl)amino-alkynyl, (alkyl)(alkynyl)amino-alkyl, alkynylthio, alkynyl-thio-alkyl, alkyl-thio-alkynyl, and alkynyl-thio- alkynyl; In some preferred embodiments: - R3is selected from hydrogen and C1-9alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; - CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; - NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5- 10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-9alkyl; C6-10arylC2- 6alkenyl; C6-10arylC2-6alkynyl; arylC1-6heteroalkyl; arylC2-6heteroalkenyl; arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3-9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-9alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; arylC1-6heteroalkyl; arylC2-6heteroalkenyl; arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; andheterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1-6alkyl)2; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z1is independently selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3- 10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1- 6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2- 6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3- 10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6- 10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2- 9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC1-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6- 10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1- 6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC1-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2- 9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6- 10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2- 6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3- 10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C6-10aryl; heteroaryl; heterocycle; C6-10arylC1-6alkyl; C6-10arylC2-6alkenyl; C6-10arylC2-6alkynyl; C6-10arylC1-6heteroalkyl; C6-10arylC2-6heteroalkenyl; C6-10arylC2-6heteroalkynyl; heteroarylC1-6alkyl; heteroarylC2-6alkenyl; heteroarylC2-6alkynyl; heteroarylC1-6heteroalkyl; heteroarylC2-6heteroalkenyl; heteroarylC2-6heteroalkynyl; heterocyclylC1-6alkyl; heterocyclylC2-6alkenyl; heterocyclylC2-6alkynyl; heterocyclylC1-6heteroalkyl; heterocyclylC2-6heteroalkenyl; and heterocyclylC2-6heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, - CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; preferably wherein “C1-12heteroalkyl” as a group or part of a group is selected from the group comprising C1-12alkyloxy, C1-6alkyl-oxy-C1-6alkyl, (mono or di)C1-6alkylamino, (mono or di-)C1-6alkyl-amino-C1-6alkyl, C1-12alkylthio, and C1-6alkyl-thio-C1-6alkyl;preferably wherein “C2-12heteroalkenyl” as a group or part of a group is selected from the group comprising C2-12alkenyloxy, C2-6alkenyl-oxy-C2-6alkenyl, C1-6alkyl-oxy-C2-6alkenyl, C2- 6alkenyl-oxy-C1-6alkyl, (mono or di)C2-6alkenylamino, (C1-6alkyl)(C2-6alkenyl)amino, (mono or di- )C2-6alkenyl-amino-C2-6alkenyl, (mono or di-)C1-6alkyl-amino-C2-6alkenyl, (mono or di-)C2-6alkenyl- amino-C1-6alkyl, (C1-6alkyl)(C2-6alkenyl)amino-C2-6alkenyl, (C1-6alkyl)(C2-6alkenyl)amino-C1-6alkyl, C2-12alkenylthio, C2-6alkenyl-thio-C1-6alkyl, C1-6alkyl-thio-C2-6alkenyl, and C2-6alkenyl-thio-C2-6alkenyl; preferably wherein “C2-12heteroalkynyl” as a group or part of a group is selected from the group comprising C2-12alkynyloxy, C2-6alkynyl-oxy-C2-6alkynyl, C1-6alkyl-oxy-C2-6alkynyl, C2- 6alkynyl-oxy-C1-6alkyl, (mono or di)C2-6alkynylamino, (C1-6alkyl)(C2-6alkynyl)amino, (mono or di- )C2-6alkynyl-amino-C2-6alkynyl, (mono or di-)C1-6alkyl-amino-C2-6alkynyl, (mono or di-)C2-6alkynyl- amino-C1-6alkyl, (C1-6alkyl)(C2-6alkynyl)amino-C2-6alkynyl, (C1-6alkyl)(C2-6alkynyl)amino-C1-6alkyl, C2-12alkynylthio, C2-6alkynyl-thio-C1-6alkyl, C1-6alkyl-thio-C2-6alkynyl, and C2-6alkynyl-thio-C2- 6alkynyl; preferably each heteroaryl is 5 to 20 membered heteroaryl, more in particular is a 6 to 14 membered heteroaryl; yet more in particular is a 6 to 10 membered heteroaryl; including when such heteroaryl is linked to alkyl, alkenyl or alkynyl such as in heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl; preferably each heterocycle is 5 to 20 membered heterocycle, more in particular is a 6 to 14 membered heterocycle; yet more in particular is a 6 to 10 membered heterocycle; including when such heterocycle is linked to alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl as in heterocyclealkyl, heterocyclealkenyl, heterocyclealkynyl, heterocycleheteroalkyl, heterocycleheteroalkenyl and heterocycleheteroalkynyl. B2.In some embodiments of the compound according to statement B1, wherein cycle B is selected from 4-, 5-, 6-, 7-, 8-, 9-, 10-, or 11-membered heterocycle; 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, or 11-membered cycloalkyl; 4-, 5-, 6-, 7-, 8-, 9-, 10-, or 11-membered cycloalkenyl; and 7-, 8-, 9-, 10-, or 11-membered cycloalkynyl. B3.In some embodiments of the compound according to any one of statements B1-B2, wherein cycle B is selected from 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered heterocycle; 3-, 4-, 5-, 6-, or 7-, 8-, 9-, or 10-membered cycloalkyl; 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered cycloalkenyl; and 7-, 8-, 9-, or 10-membered cycloalkynyl. B4.In some embodiments of the compound according to any one of statements B1-B3, cycle B is selected from the group comprising 4-, 5-, 6-, or 7-membered heterocycle; 3-, 4-, 5-, 6-, or 7- membered cycloalkyl; 5-, 6-, or 7-membered cycloalkenyl; and 7-membered cycloalkynyl. B5.In some embodiments of the compound according to any one of statements B1-B4, m is selected from 0; 1; 2; and 3, preferably m is 0, 1 or 2, for example m is 0, or m is 1 or m is 2.B6. In some embodiments of the compound according to any one of statements B1-B5, R3is hydrogen. B7. In some embodiments of the compound according to any one of statements B1-B5, R3is alkyl, for example R3is C1-6alkyl. B8. In some embodiments of the compound according to any one of statements B1-B7, each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; - NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; preferably each R4is independently selected from C1-9alkyl; C3-9cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; - NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2- 12heteroalkenyl; C2-12heteroalkynyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle; wherein said alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably wherein each of said C1-9alkyl; C3-9cycloalkyl; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3- 9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, - OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1-6alkyl)2. B9. In some embodiments of the compound according to any one of statements B1 to B8, - each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; - C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; preferably each R4is independently selected from C1-9alkyl; C3-9cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; - -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3Z4; - NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; C2-9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle; wherein said alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably wherein each of said C1-9alkyl; C2- 9alkenyl; C2-9alkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; C3- 9cycloalkyl; C5-10cycloalkenyl; C7-10cycloalkynyl; C6-10aryl; heteroaryl; and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3- 9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, - OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1-6alkyl)2. B10. In some embodiments of the compound according to any one of statements B1 to B9, each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; =O; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -S(O)Z1; -S(O)2Z2; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; heteroalkyl; aryl; heteroaryl; and heterocycle; preferably each R4is independently selected from C1-9alkyl; C3-9cycloalkyl; halogen; hydroxyl; =O; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -C(O)H; - C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3Z4; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; C1- 9heteroalkyl; C6-10aryl; heteroaryl; and heterocycle; wherein said alkyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; preferably wherein each of said C1-9alkyl; C1-12heteroalkyl; C3-9cycloalkyl; C6-10aryl; heteroaryl; and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2- 9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2; - OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1-6alkyl)2. B11. In some embodiments of the compound according to any one of statements B1 to B10, - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z1is independently selected from C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; wherein said C1-9alkyl;C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; and C2-12heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; - NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z2is independently selected from hydroxyl; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3- 10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl; heterocycle; and C6-10arylC1-6alkyl; wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3- 9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2- 12heteroalkynyl; heterocycle; and C6-10arylC1-6alkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z3and Z4is independently selected from hydrogen; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; C2-12heteroalkynyl wherein said C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C3-9cycloalkyl; C3-10cycloalkenyl; C3-10cycloalkynyl; C1-12heteroalkyl; C2-12heteroalkenyl; and C2-12heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2, and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstitutedor is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2- 9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2. B12. In some embodiments of the compound according to any one of statements B1 to B11, - each Z1is independently selected from alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z1is independently selected from C1-9alkyl; and C3-9cycloalkyl; wherein said C1-9alkyl; and C3-9cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3- 9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2;preferably each Z2is independently selected from hydroxyl; C1-9alkyl; and C3-9cycloalkyl; wherein said C1-9alkyl; and C3-9cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1- 6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF , -OCHF , cyano, nitro, -C(O)OH; NH ; -NHalkyl, and -N(alkyl) ; a 3 2 2 2 2 nd wherein each Z and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z3and Z4is independently selected from hydrogen; C1-9alkyl; and C3-9cycloalkyl; wherein said C1-9alkyl; and C3-9cycloalkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, - O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2.B13. In some embodiments of the compound according to any one of statements B1-B12, - each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -C(O)Z2; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; and aryl; preferably each R4is independently selected from C1-9alkyl; C3-9cycloalkyl; halogen; hydroxyl; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -C(O)Z2; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; and C6-10aryl; wherein said alkyl, cycloalkyl, and aryl is unsubstituted or is substituted with one or more substituents selected from alkyl, hydroxyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, - NHalkyl, and -N(alkyl)2; preferably wherein each of said C1-9alkyl; C3-9cycloalkyl; and C6- 10aryl is unsubstituted or is substituted with one or more substituents selected from C1- 9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1- 6alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHC1-6alkyl, and -N(C1- 6alkyl)2 - each Z1is independently selected from alkyl; wherein said alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, - C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z1is independently selected from C1- 9alkyl; wherein said C1-9alkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z2is independently selected from hydroxyl; and alkyl; wherein said alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, - OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; preferably each Z2is independently selected from hydroxyl; and C1-9alkyl; wherein said C1-9alkyl is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-C1-6alkyl, - OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHC1-6alkyl, and -N(C1-6alkyl)2; - each Z3and Z4is hydrogen. B14. In some embodiments of the compound according to any one of statements B1-B13, cycle B is selected from 4-, 5-, or 6-, or 7-membered heterocycle, preferably cycle B is selected from the group comprising pyrrolidinyl; azetidinyl; oxetanyl; tetrahydrofuranyl; piperidinyl; tetrahydro-2H-pyranyl; and azepanyl; preferably cycle B is selected from the group comprising pyrrolidinyl; azetidinyl; and piperidinyl.B15. In some embodiments of the compound according to any one of statements B1-B13, cycle B is selected 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, preferably cycle B is selected from the group comprising cyclobutyl; cyclopentyl; cyclohexyl; and cycloheptyl. B16. In some embodiments of the compound according to any one of statements B1-B14, said compound is a compound of formula (IIIa), (IIIb) or (IIIc)wherein R3, R4and m have the same meaning as that defined in any one of statements B1- B14. B17. In some embodiments of the compound according to any one of statements B1-B16, said compound is selected from the group comprising Cpd037, Cpd038, Cpd039, Cpd046, Cpd047, Cpd048, Cpd095, Cpd096, Cpd114, Cpd115, Cpd130, Cpd131, Cpd132, Cpd133, Cpd139, Cpd143, Cpd144, Cpd145, Cpd146, Cpd147, Cpd156, Cpd156-en1, Cpd156-en2, Cpd157, Cpd158, Cpd158-en1, Cpd158-en2, Cpd159, Cpd160, Cpd162, Cpd163, Cpd164, Cpd165, Cpd167 and Cpd168. B18. The present invention also encompasses a pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient, an effective amount of a compound according to any one of statements A1 to A20, B1 to B17. B19. The present invention also encompasses a compound according to any one of statements A1 to A20, B1 to B17, or a pharmaceutical composition according to statement B18, for use as a medicine. B20. The present invention also encompasses a compound according to any one of statements A1 to A20, B1 to B17, or a pharmaceutical composition according to statement B18, for use in the prevention or treatment of a PTPN2 and / or PTPN1 mediated disorder in an animal, mammal or human.B21. In some embodiments of the compound for use according to statement B20, or the pharmaceutical composition for use according to statement B20, the PTPN2 and / or PTPN1 mediated disorders is selected from the group comprising cancer and metabolic diseases. B22. In some embodiments of the compound for use according to any one of statements B20, B21, or the pharmaceutical composition for use according to any of any one of statements B20, B21, the PTPN2 and / or PTPN1 mediated disorders is selected from lung cancer, breast cancer, head and neck cancer, oesophageal cancer, kidney cancer, bladder cancer, colon cancer, ovarian cancer, cervical cancer, endometrial cancer, liver cancer, skin cancer, pancreatic cancer, gastric cancer, brain cancer and prostate cancer. B23. The present invention also encompasses a method for the prevention or treatment of a PTPN2 and / or PTPN1 activation mediated disorders in an animal, mammal or human comprising administering to said animal, mammal or human in need for such prevention or treatment an effective dose of at least one compound according to any one of statements A1 to A20, B1 to B17. B24. In some embodiments of the method of treatment or prevention of PTPN2 and / or PTPN1 activation mediated disorder according to statement B23 comprising administering to a patient in need for such prevention or treatment an effective dose of at least one compound according to any one of statements A1 to A20, B1 to B17, in combination with one or more other anti- cancer agents, more specifically immunotherapeutic agents. 1. A compound of formula (I), or an isomer (preferably a stereo-isomer or a tautomer), a solvate, a salt (preferably a pharmaceutically acceptable salt) or a prodrug thereof, preferably a pharmaceutically acceptable salt, solvate, hydrate, polymorph, tautomer, stereoisomer, or prodrug thereof,wherein: - represents a double bond ( ) or a triple bond ( ); - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl,cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl; or a 4-, 5-, 6-, or 7-membered heterocycle; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O- alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; wherein said alkyl, alkenyl and alkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; and alkynyl; wherein said alkyl, alkenyl and alkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; and alkynyl; wherein said alkyl, alkenyl and alkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. In some embodiment, it is clear from the description of the invention that when isa double bond, R2is selected from hydrogen; alkyl and halogen, or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl; or a 4-, 5-, 6-, or 7-membered heterocycle; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl, or a 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4. 2. A compound of formula (I), or an isomer (preferably a stereo-isomer or a tautomer), a solvate, a salt (preferably a pharmaceutically acceptable salt) or a prodrug thereof, preferably a pharmaceutically acceptable salt, solvate, hydrate, polymorph, tautomer, stereoisomer, or prodrug thereof,wherein: - represents a double bond ( ) or a triple bond ( ); - R1is selected from alkyl; alkenyl; heteroalkyl; cycloalkyl; aryl; heteroaryl; heterocycle; whereby each of said alkyl, alkenyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more R4; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; and alkyl, or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; or a 4-, 5-, 6-, or 7-membered heterocycle; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; -CF3; -OCF3; -CHF2; - OCHF2; cyano; -OZ1; -C(O)Z2; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; - NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; alkyl; and aryl; wherein said alkyl and aryl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O- alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; wherein said alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2;- each Z2is independently selected from hydroxyl; and alkyl; wherein said alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, - OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is hydrogen. For further specification of this embodiment, when is a double bond, R2is selected from hydrogen; alkyl and halogen, or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; or a 4-, 5-, 6-, or 7-membered heterocycle; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, or 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4. In a specific embodiment of the present invention, the compounds have a structure according to formula I described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to any one of statements A1, A2, 1, and 2 herein, whereby represents a double bond (). In another specific embodiment of the present invention, the compounds have a structure according to formula I described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to any one of statements A1, A2, 1, and 2 herein, whereby represents a triple bond3. A compound of formula (Ia), or an isomer (preferably a stereo-isomer or a tautomer), a solvate, a salt (preferably a pharmaceutically acceptable salt) or a prodrug thereof, preferably a pharmaceutically acceptable salt, solvate, hydrate, polymorph, tautomer, stereoisomer, or prodrug thereof,wherein: - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl;whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4; - R2is selected from hydrogen; alkyl and halogen, or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl; or a 4-, 5-, 6-, or 7-membered heterocycle; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl,arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2,-OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. For further specification of this embodiment, R2is selected from hydrogen; alkyl and halogen, or R2can be taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl; or a 4-, 5- , 6-, or 7-membered heterocycle; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl, 3-, 4-, 5-, 6-, or 7-membered cycloalkynyl, or 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4. 4. A compound of formula (Ib), or an isomer (preferably a stereo-isomer or a tautomer), a solvate, a salt (preferably a pharmaceutically acceptable salt) or a prodrug thereof, preferably a pharmaceutically acceptable salt, solvate, hydrate, polymorph, tautomer, stereoisomer, or prodrug thereof,wherein: - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted withone or more R4; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl;cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. In a specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc), described herein, more inparticular according to the other formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1-A20, B1-B17, 1, 2, 3, 4, 5, 6, and 7 herein, whereby: - each alkyl is C1-C18 membered alkyl, more in particular is a C1-C12 membered alkyl; yet more in particular is a C1-C9 membered alkyl; still more in particular is a C1-C6 membered alkyl; including when such alkyl is linked for example to aryl, heteroaryl or heterocycle as for example in arylalkyl, heteroarylalkyl and heterocycle-alkyl; - each alkenyl is C2-C18 membered alkenyl, more in particular is a C2-C12 membered alkenyl; yet more in particular is a C2-C9 membered alkenyl; still more in particular is a C2-C6 membered alkenyl; including when such alkenyl is linked to for example aryl, heteroaryl or heterocycle as for example in arylalkenyl, heteroarylalkenyl and heterocycle-alkenyl; - each alkynyl is C2-C18 membered alkynyl, more in particular is a C2-C12 membered alkynyl; yet more in particular is a C2-C9 membered alkynyl; still more in particular is a C2-C6 membered alkynyl; including when such alkynyl is linked to for example aryl, heteroaryl or heterocycle as for example in arylalkynyl, heteroarylalkynyl and heterocycle-alkynyl; - each heteroalkyl is C1-C18 membered heteroalkyl, more in particular is a C1-C12 membered heteroalkyl; yet more in particular is a C1-C9 membered heteroalkyl; still more in particular is a C1- C6 membered heteroalkyl; including when such heteroalkyl is linked for example to aryl, heteroaryl or heterocycle as for example in arylheteroalkyl, heteroarylheteroalkyl and heterocycle- heteroalkyl; - each heteroalkenyl is C2-C18membered heteroalkenyl, more in particular is a C2-C12membered heteroalkenyl; yet more in particular is a C2-C9membered heteroalkenyl; still more in particular is a C2-C6membered heteroalkenyl; including when such heteroalkenyl is linked to for example aryl, heteroaryl or heterocycle as for example in arylheteroalkenyl, heteroarylheteroalkenyl and heterocycle-heteroalkenyl; and - each heteroalkynyl is C2-C18 membered heteroalkynyl, more in particular is a C2-C12 membered heteroalkynyl; yet more in particular is a C2-C9membered heteroalkynyl; still more in particular is a C2-C6membered heteroalkynyl; including when such alkenyl is linked to for example aryl, heteroaryl or heterocycle as for example in arylheteroalkynyl, heteroarylheteroalkynyl and heterocycle-heteroalkynyl. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc), described herein, more in particular according to the other formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1-A20, B1-B17, 1, 2, 3, 4, 5, 6 and 7 herein, whereby: - each cycloalkyl is C3-C18membered cycloalkyl, more in particular is a C3-C12membered cycloalkyl; yet more in particular is a C3-C9membered cycloalkyl; still more in particular is a C3-C6 membered cycloalkyl; - each cycloalkenyl is C5-C18 membered cycloalkenyl, more in particular is a C5-C12 membered cycloalkenyl; yet more in particular is a C5-C9 membered cycloalkenyl; still more in particular is a C5-C6 membered cycloalkenyl; - each cycloalkynyl is C5-C18 membered cycloalkynyl, more in particular is a C5-C12 membered cycloalkynyl; yet more in particular is a C5-C9membered cycloalkynyl; still more in particular is a C5-C6 membered cycloalkynyl; In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc), described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1-A20, B1-B17, 1, 2, 3, 4, 5, 6, and 7 herein, whereby: - each aryl is C6-C20 membered aryl, more in particular is a C6-C14 membered aryl; yet more in particular is a C6-C10 membered aryl; including when such aryl is linked to alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl or heteroalkynyl, as in arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl; - each heteroaryl is 5 to 20 membered heteroaryl, more in particular is a 6 to 14 membered heteroaryl; yet more in particular is a 6 to 10 membered heteroaryl; including when such heteroaryl is linked to alkyl, alkenyl or alkynyl such as in heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl; - each heterocycle is 5 to 20 membered heterocycle, more in particular is a 6 to 14 membered heterocycle; yet more in particular is a 6 to 10 membered heterocycle; including when such heterocycle is linked to alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl as in heterocyclealkyl, heterocyclealkenyl, heterocyclealkynyl, heterocycleheteroalkyl, heterocycleheteroalkenyl and heterocycleheteroalkynyl. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia) and (Ib) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1, A6, A7, 1, 2, 3 and 4 herein, whereby - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more R4; or - R1is selected from alkyl; alkenyl; heteroalkyl; heteroalkenyl; cycloalkyl; cycloalkenyl; aryl; heteroaryl; and heterocycle; whereby each of said alkyl, alkenyl, heteroalkyl, heteroalkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more R4; or - R1is selected from alkyl; alkenyl; heteroalkyl; cycloalkyl; aryl; heteroaryl; and heterocycle;whereby each of said alkyl, alkenyl, heteroalkyl, cycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more R4; or - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl is unsubstituted or is substituted with one or more R4; or - R1is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; whereby each of said cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more R4; or - R1is selected from aryl; and heteroaryl; whereby each of said aryl and heteroaryl is unsubstituted or is substituted with one or more R4. In yet more particular embodiments of the present invention, the compounds have a structure according to formula (I), (Ia) and (Ib) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1, A6, A7, 1, 2, 3 and 4 herein, whereby: - R1is selected from C1-C6 alkyl; yet more specifically whereby R1is selected from methyl, ethyl, propyl; butyl; pentyl and hexyl; or - R1is selected from C1-C6 heteroalkyl; or - R1is selected from C3-C6 cycloalkyl; yet more specifically whereby R1is selected from cyclopropyl; cyclobutyl; cyclopentyl and cyclohexyl; or - R1 is selected from C1-C6 alkyl; and C3-C6 cycloalkyl; yet more specifically whereby R1is selected from methyl, ethyl, propyl; butyl; pentyl; hexyl; cyclopropyl; cyclobutyl; cyclopentyl and cyclohexyl; or - more in particular R1is selected from aryl; yet more specifically whereby R1is phenyl; or - more in particular R1is selected from heteroaryl; yet more specifically whereby R1is selected from pyrazolyl; isoxazolyl; pyridyl; and thiazolyl; or - more in particular R1is selected from heterocycle; yet more specifically whereby R1is selected from azetidinyl; oxetanyl; pyrrolidinyl; tetrahydrofuranyl; piperidinyl; tetrahydro-2H-pyranyl; and azepanyl. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia) and (Ib) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1, A6, A7, 1, 2, 3 and 4 herein, whereby - R1is selected from C1-C6alkyl; yet more specifically whereby R1is selected from methyl, ethyl, propyl; butyl; pentyl and hexyl; and is unsubstituted or substituted with one or more R4; or - R1is selected from C1-C6heteroalkyl and is unsubstituted or is substituted with one or more R4; or - R1is selected from C3-C4cycloalkyl; yet more specifically whereby R1is selected fromcyclopropyl and cyclobutyl; or R1is selected from C cycloalkyl; yet more specifically w 1 3 hereby R is cyclopropyl; and for each of said R1, R1is unsubstituted or is substituted with one or more R4. In another specific embodiment of the present invention, the compounds have a structure according to formula (I) and (Ia) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements 1, 2 and 3 herein, whereby - R2is selected from hydrogen; and alkyl; yet more in particular R2is hydrogen; still more in particular R2is alkyl; or - R2is taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 3-, 4-, 5-, 6-, or 7-membered cycloalkenyl; or a 4-, 5-, 6-, or 7-membered heterocycle; - yet more in particular R2is taken together with R1to form a 4-, 5-, 6-, or 7-membered cycloalkyl; or a 4-, 5-, 6-, or 7-membered heterocycle. In another specific embodiment of the present invention, the compounds have a structure according to formula (I) and (Ia) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements 1, 2 and 3 herein, whereby - R2is selected from hydrogen; and alkyl; yet more in particular R2is hydrogen; still more in particular R2is alkyl; or - R2is taken together with R1to form a 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; a 5-, 6-, or 7- membered cycloalkenyl; or a 4-, 5-, 6-, or 7-membered heterocycle; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, 5-, 6-, or 7- membered cycloalkenyl, or 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4; - yet more in particular R2is taken together with R1to form a 4-, 5-, 6-, or 7-membered cycloalkyl; or a 4-, 5-, 6-, or 7-membered heterocycle; wherein said 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, or a 4-, 5-, 6-, or 7-membered heterocycle is unsubstituted or substituted with one or more R4. In yet more particular embodiments of the present invention, the compounds have a structure according to formula (I) and (Ia) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements 1, 2 and 3 herein, whereby: - R2is selected from C1-C6alkyl; yet more specifically whereby R2is selected from methyl; ethyl; propyl; butyl; pentyl and hexyl; or - R2is taken together with R1to form a 4-, 5-, 6-, or 7-membered cycloalkyl; yet more in particular to form cyclobutyl; cyclopentyl; cyclohexyl; or cycloheptyl; or - R2is taken together with R1to form a 4-, 5-, 6-, or 7-membered heterocycle; yet more in particular to form azetidinyl; oxetanyl; pyrrolidinyl; tetrahydrofuranyl; piperidinyl; tetrahydro-2H-pyranyl; and azepanyl; still more in particular to form azetidinyl; pyrrolidinyl; and piperidinyl.In yet more particular embodiments of the present invention, the compounds have a structure according to formula (I) and (Ia) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements 1, 2 and 3 herein, whereby: - R2is selected from C1-C6 alkyl; yet more specifically whereby R2is selected from methyl; ethyl; propyl; butyl; pentyl and hexyl; or - R2is taken together with R1to form a 4-, 5-, 6-, or 7-membered cycloalkyl unsubstituted or substituted with one or more R4; yet more in particular to form cyclobutyl; cyclopentyl; cyclohexyl; or cycloheptyl; wherein said cyclobutyl, cyclopentyl, cyclohexyl, or cycloheptyl is unsubstituted or substituted with one or more R4; or - R2is taken together with R1to form a 4-, 5-, 6-, or 7-membered heterocycle unsubstituted or substituted with one or more R4; yet more in particular to form azetidinyl; oxetanyl; pyrrolidinyl; tetrahydrofuranyl; piperidinyl; tetrahydro-2H-pyranyl; and azepanyl; wherein said azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, tetrahydro-2H-pyranyl, and azepanyl is unsubstituted or substituted with one or more R4; still more in particular to form azetidinyl; pyrrolidinyl; and piperidinyl; wherein said azetidinyl, pyrrolidinyl, and piperidinyl is unsubstituted or substituted with one or more R4. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia) and (Ib) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to any one of statements A1-A20, B1-B17, 1, 2, 3 and 4 herein, whereby - R3is hydrogen; or - R3is C1-C6alkyl; yet more specifically R3is selected from methyl; ethyl; propyl; butyl; pentyl and hexyl; still more in particular R3is selected from methyl, ethyl, and propyl; 5. More particularly, the compounds of the invention are compounds of formula (II) and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, polymorph and / or prodrug thereof,wherein:- represents a double bond ( ) or a triple bond ( ); - cycle A is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; - when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; - R3is selected from hydrogen and alkyl; - n is selected from 0, 1, 2, 3, 4 and 5; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl isunsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH,=S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. In another specific embodiment of the present invention, the compounds have a structure according to formula (IIa) described herein, more in particular according to the statements, embodiments and aspects described herein:wherein cycle A, R3, n, each R4, each Z1, each Z2, each Z3and each Z4are independently according to the formulas, statements, aspects and embodiments described herein, such as for formula (II). In another specific embodiment of the present invention, the compounds have a structure according to formulas, statements, embodiments and aspects described herein whereby: R1is cycle A selected from cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; - at least one R4substituent is present on cycle A, more in particular such substituent is positioned in the meta-position. In a more particular embodiment, the compounds have a structure according to formulas, statements, embodiments and aspects described herein whereby R1or cycle A is unsubstituted or substituted with one or more R4, and is selected from the following structures:. In another more particular embodiment, the compounds have a structure according to formulas, statements, embodiments and aspects described herein whereby R1or cycle A unsubstituted or substituted with one or more R4and is selected from the following structures:. In yet another more particular embodiment, the compounds have a structure according to formulas, statements, embodiments and aspects described herein whereby R1or cycle A unsubstituted or substituted with one or more R4and is selected from the following structures:. 6. More particularly, the compounds of the invention are compounds of formula (III) and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, polymorph and / or prodrug thereof,wherein: - cycle B is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; and heterocycle; - m is selected from 0; 1; 2; 3; 4; and 5; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl,=O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl;heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. 7. More particularly, the compounds of the invention are compounds of formula (IIIa), (IIIb) and (IIIc) and any subgroup thereof as described herein, a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, polymorph and / or prodrug thereof,wherein: - m is selected from 0; 1; 2; 3; 4 and 5; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3;-OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl;heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; or heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements A1, A3-A7, 1, 2, 3, 4, 5, 6 and 7 herein, whereby R1is substituted with 1, 2, 3, 4, 5 or 6 R4; or more specifically, R1is substituted with 1, 2, 3, 4 or 5 R4;or more specifically, R1is substituted with 1, 2, 3 or 4 R4; still more in particular, R1is substituted with 1, 2 or 3 R4; yet more in particular, R1is substituted with 1 or 2 R4; still more in particular, R1is substituted with 1 R4; or in another embodiment, R1is unsubstituted. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements 1, 2, 3, 4, 5, 6 and 7 herein, whereby R1taken together with R2is substituted with 1, 2, 3, 4, 5 or 6 R4; or more specifically, R1taken together with R2is substituted with 1, 2, 3, 4 or 5 R4; or more specifically, R1taken together with R2is substituted with 1, 2, 3 or 4 R4; still more in particular, R1taken together with R2is substituted with 1, 2 or 3 R4; yet more in particular, R1taken together with R2is substituted with 1 or 2 R4; still more in particular, R1taken together with R2is substituted with 1 R4; or in another embodiment, R1taken together with R2is unsubstituted. In another embodiment, the compounds are according to any one of statements A2, A8- A12, 5, wherein n is selected from 1, 2, 3, 4, 5 and 6. In another embodiment, the compounds are according to any one of statements A2, A8-A12, 5, wherein n is selected from 1, 2, 3, 4 and 5.In another embodiment, the compounds are according to any one of statements A2, A8-A12, 5, wherein n is selected from 1, 2, 3 and 4. In another embodiment, the compounds are according to any one of statements A2, A8-A12, 5, wherein n is selected from 1, 2 and 3. In another embodiment, the compounds are according to any one of statements A2, A8-A12, 5, wherein n is selected from 1 and 2. In another embodiment, the compounds are according to any one of statements A2, A8-A12, 5, wherein n is not 0. In yet another embodiment, the compounds are according to any one of statements B1- B17, 6, wherein m is selected from 1, 2, 3, 4, 5 and 6. In another embodiment, the compounds are according to any one of statements B1-B17, 6, wherein m is selected from 1, 2, 3, 4 and 5. In another embodiment, the compounds are according to any one of statements B1-B17, 6, wherein m is selected from 1, 2, 3 and 4. In another embodiment, the compounds are according to any one of statements B1-B17, 6 and 7, wherein m is selected from 1, 2 and 3. In another embodiment, the compounds are according to any one of statements B1-B17, 6 and 7, wherein m is selected from 1 and 2. In another embodiment, the compounds are according to any one of statements B1-B17, 6 and 7, wherein m is not 0. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to any one of statements A1-A20, B1-B17, 1, 2, 3, 4, 5 and 6 and 7 herein, whereby:- each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; or - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -C(O)H; -C(O)Z2; -C(O)OH; - C(O)OZ1; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; or - each R4is independently selected from halogen; hydroxyl; =O; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -S(O)Z1; -S(O)2Z2; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3S(O)2Z1; - NZ3C(O)OZ1; -NZ3C(O)Z1; alkyl; heteroalkyl; cycloalkyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, heteroalkylcycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to any one of statements A1-A20, B1-B17, 1, 2, 3, 4, 5 and 6 and 7 herein, whereby: - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1-9heteroalkyl; C2-9heteroalkenyl; C2-9heteroalkynyl; C3-9cycloalkyl; C5-9cycloalkenyl; C5- 9cycloalkynyl; aryl; heteroaryl; and heterocycle; wherein said C1-9alkyl, C2-9alkenyl, C2-9alkynyl, C1-9heteroalkyl, C2-9heteroalkenyl, C2- 9heteroalkynyl, C3-9cycloalkyl, C5-9cycloalkenyl, C5-9cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O- alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; or - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -C(O)H; -C(O)Z2; -C(O)OH; - C(O)OZ1; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; C1-9alkyl; C2-9alkenyl; C2-9alkynyl; C1- 9heteroalkyl; C2-9heteroalkenyl; C2-9heteroalkynyl; C3-9cycloalkyl; C5-9cycloalkenyl; C5- 9cycloalkynyl; aryl; heteroaryl; and heterocycle; wherein said C1-9alkyl, C2-9alkenyl, C2-9alkynyl, C1-9heteroalkyl, C2-9heteroalkenyl, C2- 9heteroalkynyl, C3-9cycloalkyl, C5-9cycloalkenyl, C5-9cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from C1-9alkyl, C3-9cycloalkyl, C2-9alkenyl, C2-9alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O- alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; or - each R4is independently selected from halogen; hydroxyl; =O; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -S(O)Z1; -S(O)2Z2; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3S(O)2Z1; - NZ3C(O)OZ1; -NZ3C(O)Z1; C1-9alkyl; C1-9heteroalkyl; C3-9cycloalkyl; aryl; heteroaryl; and heterocycle; wherein said C1-9alkyl, C1-9heteroalkyl, C3-9cycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to statements any one of A1-A20, B1-B17, 1, 2, 3, 4, 5 and 6 and 7 herein, whereby: - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; alkoxy; and alkyl; wherein said alkoxy and alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, - NH2, -NHalkyl, and -N(alkyl)2; or more specifically - each R4is independently selected from halogen; hydroxyl; CF3; -OCF3; -CHF2; -OCHF2; cyano; alkoxy; and alkyl; wherein said alkoxy and alkyl is unsubstituted or is substituted with one or moresubstituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, - CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; or more specifically - each R4is independently selected from halogen; hydroxyl; CF3; -OCF3; alkoxy; and alkyl; or more specifically - each R4is independently selected from F; Cl; hydroxyl; CF3; -OCF3; alkoxy; and alkyl. In another specific embodiment of the present invention, the compounds have a structure according to formula (I), (Ia), (Ib), (II), (IIa), (III), (IIIa), (IIIb) and (IIIc) described herein, more in particular according to the formulas, statements, embodiments and aspects described herein, yet more in particular according to any one of statements A1-A20, B1-B17, 1, 2, 3, 4, 5 and 6 and 7 herein, whereby: - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2. In another more particular embodiment, - each Z1is independently selected from alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano,nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2. In a particular embodiment, the compounds of the invention are selected from the compounds listed in Table 1 and as described with their chemical name below. Cpd001: 5-(3-(cyclopentylethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd002: 5-(3-(3,3-dimethylbut-1-yn-1-yl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd003: 5-(3-((3-chlorophenyl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd004: 5-(2-fluoro-3-((3-fluorophenyl)ethynyl)-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd005: 5-(2-fluoro-6-hydroxy-3-(pyridin-2-ylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd006: 5-(2-fluoro-6-hydroxy-3-(pyridin-3-ylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd007: 5-(2-fluoro-6-hydroxy-3-(3-(methylamino)prop-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd008: 5-(2-fluoro-6-hydroxy-3-(phenylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd009: 5-(3-(cyclopropylethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd010: 5-(2-fluoro-6-hydroxy-3-((1-(methylsulfonyl)pyrrolidin-3-yl)ethynyl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd011: 5-(2-fluoro-6-hydroxy-3-(4-methylpent-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd012: 5-(3-((2,5-difluorophenyl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one1,1-dioxide; Cpd013: 5-(2-fluoro-6-hydroxy-3-((2-methylthiazol-4-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd014: 5-(2-fluoro-6-hydroxy-3-((5-methylisoxazol-3-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd015: 5-(2-fluoro-6-hydroxy-3-((5-methylthiazol-2-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd016: 5-(2-fluoro-6-hydroxy-3-((3-(trifluoromethyl)phenyl)ethynyl)phenyl)-1,2,5-thiadiazolidin- 3-one 1,1-dioxide; Cpd017: 5-(3-((3,4-dichlorophenyl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd018: 5-(3-((1H-pyrazol-5-yl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd019: 5-(3-(azetidin-3-ylethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd020: 5-(2-fluoro-6-hydroxy-3-(pyrrolidin-2-ylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd021: 5-(3-((1-acetylazetidin-3-yl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd022: 5-(2-fluoro-6-hydroxy-3-(pyrrolidin-3-ylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd023: 5-(3-(cyclohexylethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd024: 5-(2-fluoro-6-hydroxy-3-(piperidin-4-ylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd025: 5-(3-(but-1-yn-1-yl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd026: 5-(2-fluoro-6-hydroxy-3-(3-methoxy-3-methylbut-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin- 3-one 1,1-dioxide; Cpd027: 5-(2-fluoro-6-hydroxy-3-(3-methylbut-3-en-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd028: N-(4-(3-(1,1-dioxido-4-oxo-1,2,5-thiadiazolidin-2-yl)-2-fluoro-4-hydroxyphenyl)-2- methylenebut-3-yn-1-yl)methanesulfonamide; Cpd029: 5-(2-fluoro-6-hydroxy-3-((3-methoxyphenyl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd030: 5-(2-fluoro-6-hydroxy-3-((3-hydroxyoxetan-3-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd031: 5-(2-fluoro-6-hydroxy-3-((3-methoxyoxetan-3-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd032: 5-(2-fluoro-6-hydroxy-3-((1-phenylcyclopropyl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd033: 5-(2-fluoro-6-hydroxy-3-((4-methoxyphenyl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd034: 5-(3-((3-chloro-4-methoxyphenyl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd035: 5-(2-fluoro-6-hydroxy-3-(prop-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd036: 5-(2-fluoro-6-hydroxy-4-methyl-3-(phenylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd037: (E)-5-(2-fluoro-6-hydroxy-3-(pyrrolidin-3-ylidenemethyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd038: (Z)-5-(2-fluoro-6-hydroxy-3-(pyrrolidin-3-ylidenemethyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd039: 5-(3-(azetidin-3-ylidenemethyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd040: (E)-5-(2-fluoro-3-(3-fluorostyryl)-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd041: (E)-5-(3-(2-cyclopropylvinyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd042: (E)-5-(3-(3,3-dimethylbut-1-en-1-yl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd043: 5-(2-fluoro-6-hydroxy-3-(2-methylprop-1-en-1-yl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd044: (E)-5-(3-(2-cyclohexylvinyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd045: (E)-5-(2-fluoro-6-hydroxy-3-styrylphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd046: 5-(2-fluoro-6-hydroxy-3-(piperidin-4-ylidenemethyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd047: 5-(3-(cyclopentylidenemethyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd048: 5-(2-fluoro-6-hydroxy-3-((1-propylpiperidin-4-ylidene)methyl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd049: N-(4-(3-(1,1-dioxido-4-oxo-1,2,5-thiadiazolidin-2-yl)-2-fluoro-4-hydroxyphenyl)-2- methylbut-3-yn-2-yl)methanesulfonamide; Cpd050: 5-(2-fluoro-6-hydroxy-3-(pyrimidin-5-ylethynyl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide;Cpd051: 5-(3-((2,3-difluorophenyl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd052: 5-(2-fluoro-6-hydroxy-3-(imidazo[1,2-b]pyridazin-3-ylethynyl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd053: 5-(2-fluoro-6-hydroxy-3-((1-(methylsulfonyl)piperidin-4-yl)ethynyl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd054: 5-(2-fluoro-6-hydroxy-3-((1-(methylsulfonyl)piperidin-3-yl)ethynyl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd055: 5-(2-fluoro-6-hydroxy-3-(3-methoxyprop-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd056: 5-(3-((1H-pyrazol-4-yl)ethynyl)-2-fluoro-6-hydroxyphenyl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide; Cpd057: 5-(2-fluoro-6-hydroxy-3-(3-methylbut-1-yn-1-yl)phenyl)-1,2,5-thiadiazolidin-3-one 1,1- dioxide; Cpd058: 5-(2-fluoro-6-hydroxy-3-((5-methoxypyridin-3-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd059: 5-(2-fluoro-6-hydroxy-3-((6-methylpyridin-3-yl)ethynyl)phenyl)-1,2,5-thiadiazolidin-3- one 1,1-dioxide; Cpd060: 5-(2-fluoro-6-hydroxy-3-((1-(hydroxymethyl)cyclopropyl)ethynyl)phenyl)-1,2,5- thiadiazolidin-3-one 1,1-dioxide; Cpd061: 5-(2...

Claims

CLAIMS 1. A compound of formula (III), a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), solvate, hydrate, polymorph, isotope, and / or prodrug thereof,wherein: - cycle B is selected from heterocycle; cycloalkyl; cycloalkenyl; and cycloalkynyl; - m is selected from 0; 1; 2; 3; 4; and 5. - R3is selected from hydrogen and alkyl; - each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; - S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - - C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; -NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; - NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, hydroxyl, cycloalkyl, alkenyl, alkynyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle ora 3-, 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; and -NHalkyl, -N(alkyl)2; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl;heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O- alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2.

2. The compound according to claim 1, wherein cycle B is selected from 4-, 5-, 6-, 7-, 8-, 9-, 10- , or 11-membered heterocycle; 3-, 4-, 5-, 6-, 7-, 8-, 9-, 10-, or 11-membered cycloalkyl; 4-, 5- , 6-, 7-, 8-, 9-, 10-, or 11-membered cycloalkenyl; and 7-, 8-, 9-, 10-, or 11-membered cycloalkynyl.

3. The compound according to any one of claims 1-2, wherein cycle B is selected from 4-, 5-, 6- , 7-, 8-, 9-, or 10-membered heterocycle; 3-, 4-, 5-, 6-, 7-, 8-, 9-, or 10 membered cycloalkyl; 4-, 5-, 6-, 7-, 8-, 9- or 10-membered cycloalkenyl; and 7-, 8-, 9- or 10-membered cycloalkynyl.

4. The compound according to any one of claims 1-3, wherein cycle B is selected from 4-, 5-, 6- , or 7-membered heterocycle; 3-, 4-, 5-, 6-, or 7-membered cycloalkyl; 5-, 6-, or 7-membered cycloalkenyl; and 7-membered cycloalkynyl.

5. The compound according to any one of claims 1-4, wherein m is selected from 0; 1; 2; and 3, preferably m is 0, 1 or 2.

6. The compound according to any one of claims 1-5, wherein R3is hydrogen.

7. The compound according to any one of claims 1-5, wherein R3is alkyl.

8. The compound according to any one of claims 1-7, wherein each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; -S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2.

9. The compound according to any one of claims 1 to 8, wherein - each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; - C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3S(O)2Z1; -NZ3C(O)OZ1; -NZ3C(O)Z1; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, cycloalkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, - C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2.

10. The compound according to any one of claims 1 to 9, wherein each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; =O; -CF3; -OCF3; -CHF2; -OCHF2; cyano; - OZ1; -S(O)Z1; -S(O)2Z2; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; -NZ3S(O)2Z1; -NZ3C(O)OZ1; - NZ3C(O)Z1; heteroalkyl; aryl; heteroaryl; and heterocycle; wherein said alkyl, heteroalkylcycloalkyl, aryl, heteroaryl and heterocycle is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, and -N(alkyl)2.

11. The compound according to any one of claims 1 to 7, wherein two R4can be taken together in order to form a 4-, 5-, or 6-membered heterocycle or a 3-, 4-, 5-, or 6-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, hydroxyl, =O, halogen, -SH, =S, -CF3, - O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2.

12. The compound according to any one of claims 1 to 11, wherein - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl,alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, - CHF , -OCHF , cyano, nitro, -C(O)OH; NH ; -NHalkyl, 3 2 2 2 and -N(alkyl)2; and wherein each Z and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2.

13. The compound according to any one of claims 1 to 12, wherein - each Z1is independently selected from alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, - OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; and cycloalkyl; wherein said alkyl and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3 and Z4can be taken together in order to form a (4-, 5-, 6-, or 7-membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2.

14. The compound according to any one of claims 1-13, wherein - each R4is independently selected from alkyl; cycloalkyl; halogen; hydroxyl; sulfhydryl; -CF3; -OCF3; -CHF2; -OCHF2; cyano; -OZ1; -C(O)Z2; -C(O)OZ1; -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; and aryl; wherein said alkyl, cycloalkyl, and aryl is unsubstituted or is substituted with one or more substituents selected from alkyl, hydroxyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, - NHalkyl, and -N(alkyl)2; - each Z1is independently selected from alkyl; wherein said alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, - C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; and alkyl; wherein said alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, - OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is hydrogen.

15. The compound according to any one of claims 1-14, wherein cycle B is selected from 4-, 5-, 6-, or 7-membered heterocycle, preferably cycle B is selected from the group comprising pyrrolidinyl; azetidinyl; oxetanyl; tetrahydrofuranyl; piperidinyl; tetrahydro-2H-pyranyl; and azepanyl; preferably cycle B is selected from the group comprising pyrrolidinyl; azetidinyl; and piperidinyl.

16. The compound according to any one of claims 1-14, wherein cycle B is selected 4-, 5-, 6-, or 7-membered cycloalkyl, preferably cycle B is selected from the group comprising cyclobutyl; cyclopentyl; cyclohexyl; and cycloheptyl.

17. The compound according to any one of claims 1-16, wherein said compound is a compound of formula (IIIa), (IIIb), or (IIIc)wherein R3, R4and m have the same meaning as that defined in any one of claims 1-16.

18. A compound selected from the group comprising Cpd037, Cpd038, Cpd039, Cpd046, Cpd047, Cpd048, Cpd095, Cpd096, Cpd114, Cpd115, Cpd130, Cpd131, Cpd132, Cpd133, Cpd139, Cpd143, Cpd144, Cpd145, Cpd146, Cpd147, Cpd156, Cpd156-en1, Cpd156-en2, Cpd157, Cpd158, Cpd158-en1, Cpd158-en2, Cpd159, Cpd160, Cpd162, Cpd163, Cpd164, Cpd165, Cpd167 and Cpd168.

19. A compound of formula (I), a stereo-isomeric form, a tautomer, a salt (in particular a pharmaceutically acceptable salt), a solvate, a hydrate, a polymorph, an isotope, and / or a prodrug thereof,wherein: - represents a double bond () or a triple bond ( ); - R1is selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; cycloalkylalkyl; cycloalkenylalkyl; cycloalkynylalkyl; cycloalkylheteroalkyl; cycloalkenylheteroalkyl; cycloalkynylheteroalkyl; aryl; heteroaryl; heterocycle; arylalkyl; heteroarylalkyl; heterocyclylalkyl; arylheteroalkyl; heteroarylheteroalkyl; and heterocyclylheteroalkyl; whereby each of said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkylalkyl, cycloalkenylalkyl, cycloalkynylalkyl, cycloalkylheteroalkyl, cycloalkenylheteroalkyl, cycloalkynylheteroalkyl, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclylalkyl, arylheteroalkyl, heteroarylheteroalkyl, and heterocyclylheteroalkyl is unsubstituted or is substituted with one or more R4;- when is a triple bond, then R2is not present; when is a double bond, then R2is selected from hydrogen; alkyl and halogen; - R3is selected from hydrogen and alkyl; - each R4is independently selected from halogen; hydroxyl; sulfhydryl; =O; =S; -SCF3; -SF5; -CF3; -OCF3; -CHF2; -OCHF2; cyano; nitro; -OZ1; -SZ1; -S(O)Z1; -S(O)2Z2; -S(O)2NZ3Z4; -S(O)(NZ3)Z1; - S(NZ3)(NZ3)Z1; -C(O)H; -C(O)Z2; -C(O)OH; -C(O)OZ1; - -C(O)NZ3Z4; -NZ3Z4; -NZ3S(O)2Z1; - NZ3S(O)2NZ3Z4; -NZ3C(O)OZ1; -NZ3C(O)Z1; -NZ3C(O)NZ3Z4; -P(O)Z3Z4; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; heterocyclylheteroalkynyl; alkyl-oxy-alkyl; (mono or di)alkylamino; (mono or di-)alkyl-amino-alkyl; alkylthio; and alkyl-thio-alkyl; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, heterocyclylheteroalkynyl, alkyl-oxy-alkyl, (mono or di)alkylamino, (mono or di-)alkyl-amino-alkyl, alkylthio, and alkyl-thio-alkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2; -OCHF2, cyano, nitro, -C(O)OH, -NH2, -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - or two R4can be taken together in order to form a 4-, 5-, 6-, or 7-membered heterocycle or a 3- , 4-, 5-, 6-, or 7-membered cycloalkyl, wherein said heterocycle and cycloalkyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, -N(alkyl)2, -S(O)2alkyl, and -NHS(O)2alkyl; - each Z1is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclylheteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl,arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z2is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; - each Z3and Z4is independently selected from hydrogen; alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heteroaryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heteroarylalkyl; heteroarylalkenyl; heteroarylalkynyl; heteroarylheteroalkyl; heteroarylheteroalkenyl; heteroarylheteroalkynyl; heterocyclylalkyl; heterocyclylalkenyl; heterocyclylalkynyl; heterocyclylheteroalkyl; heterocyclylheteroalkenyl; and heterocyclyl heteroalkynyl; wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, heteroarylheteroalkyl, heteroarylheteroalkenyl, heteroarylheteroalkynyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, heterocyclylheteroalkyl, heterocyclylheteroalkenyl, and heterocyclylheteroalkynyl is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2,-OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and -N(alkyl)2; and wherein each Z3and Z4can be taken together in order to form a (4-, 5-, 6-, or 7- membered) heterocycle which is unsubstituted or is substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, alkynyl, hydroxyl, =O, halogen, -SH, =S, -CF3, -O-alkyl, -OCF3, -CHF2, -OCHF2, cyano, nitro, -C(O)OH; NH2; -NHalkyl, and - N(alkyl)2.

20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient, an effective amount of a compound according to any one of claims 1-19.

21. The compound according to any one of claims 1-19, or a pharmaceutical composition according to claim 20, for use as a medicine.

22. The compound according to any one of claims 1-19, or a pharmaceutical composition according to claim 20, for use in the prevention or treatment of a PTPN2 and / or PTPN1 mediated disorder in an animal, mammal or human.

23. The compound for use according to claim 22, or a pharmaceutical composition for use according to claim 22, wherein the PTPN2 and / or PTPN1 mediated disorders is selected from the group comprising cancer and metabolic diseases.

24. The compound for use according to any of claims 22, 23 or a pharmaceutical composition for use according to any of claims 22, 23 wherein the PTPN2 and / or PTPN1 mediated disorders is selected from the group comprising lung cancer, breast cancer, head and neck cancer, oesophageal cancer, kidney cancer, bladder cancer, colon cancer, ovarian cancer, cervical cancer, endometrial cancer, liver cancer, skin cancer, pancreatic cancer, gastric cancer, brain cancer and prostate cancer.

25. A method for the prevention or treatment of a PTPN2 and / or PTPN1 activation mediated disorders in an animal, mammal or human comprising administering to said animal, mammal or human in need for such prevention or treatment an effective dose of a compound according to any one of claims 1-19.

26. A method of treatment or prevention of PTPN2 and / or PTPN1 activation mediated disorder according to claim 25 comprising administering to a patient in need thereof an effective dose of a compound according to any one of claims 1-19, in combination with one or more other anti-cancer agents, more specifically immunotherapeutic agents.

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