FIELD OF THE INVENTION

The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.

BACKGROUND OF THE INVENTION

Flaviviruses, which are transmitted by mosquitoes or ticks, cause life-threatening infections in man, such as encephalitis and hemorrhagic fever. Four distinct, but closely related serotypes of the flavivirus dengue are known (DENV-1 , -2, -3, and -4). Dengue is endemic in most tropical and sub-tropical regions around the world, predominantly in urban and semi-urban areas. According to the World Health Organization (WHO), 2.5 billion people of which 1 billion children are at risk of DENV infection (WHO, 2002). An estimated 50 to 100 million cases of dengue fever [DF], half a million cases of severe dengue disease (i.e. dengue hemorrhagic fever [DHF] and dengue shock syndrome [DSS]), and more than 20,000 deaths occur worldwide each year. DHF has become a leading cause of hospitalization and death amongst children in endemic regions. Altogether, dengue represents the most common cause of arboviral disease. Because of recent large outbreaks in countries situated in Latin America, South-East Asia and the Western Pacific (including Brazil, Puerto Rico, Venezuela, Cambodia, Indonesia, Vietnam, Thailand), numbers of dengue cases have risen dramatically over the past years. Not only is the number of dengue cases increasing as the disease is spreading to new areas, but the outbreaks tend to be more severe.

To prevent and/or control dengue disease, the only available methods at present are mosquito eradication strategies to control the vector. Although progress is being made in the development of vaccines for dengue, many difficulties are encountered. These include the existence of a phenomenon referred to as antibody-dependent enhancement (ADE).

Recovery from an infection by one serotype provides lifelong immunity against that serotype but confers only partial and transient protection against a subsequent infection by one of the other three serotypes. Following infection with another serotype, pre-existing heterologous antibodies form complexes with the newly infecting dengue virus serotype but do not neutralize the pathogen. Instead, virus entry into cells is believed to be facilitated, resulting in uncontrolled virus replication and higher peak viral titres. In both primary and secondary infections, higher viral titres are associated with more severe dengue disease. Since maternal antibodies can easily pass on to infants by breast feeding, this might be one of the reasons that children are more affected by severe dengue disease than adults.

In locations with two or more serotypes circulating simultaneously, also referred to as hyperendemic regions, the risk of serious dengue disease is significantly higher due to an increased risk of experiencing a secondary, more severe infection. Moreover, in a situation of hyper-endemicity, the probability of the emergence of more virulent strains is increased, which in turn augments the probability of dengue hemorrhagic fever (DHF) or dengue shock syndrome.

The mosquitoes that carry dengue, including Aedes aegypti and Aedes albopictus (tiger mosquito), are moving north. According to the United States (US) Centers for Disease Control and Prevention (CDC), both mosquitoes are currently omnipresent in southern Texas. The spread north of dengue-carrying mosquitoes is not confined to the US, but has also been observed in Europe.

Despite large efforts over the past 3 decades, there is currently no vaccine available to protect against dengue virus disease. The main problem is to develop a vaccine that offers protection against all four serotypes (a tetravalent vaccine) to the same extent. Furthermore, today, specific antiviral drugs for the treatment or prevention of dengue fever virus infection are not available. Clearly, there is still a great need for therapeutics for the prevention or treatment of viral infections in animals, more in particular in humans and especially for viral infections caused by Flaviviruses, more in particular Dengue virus. Therapeutics with good potency, no or low levels of less side-effects, a broad spectrum activity against multiple Dengue virus serotypes, a low toxicity and/or good pharmacokinetic or -dynamic properties are very welcome. The present invention provides novel compounds which show activity against Flaviviruses, including Dengue virus. The prior art does not lead a person skilled in the art to the compounds of the present invention, nor to their use as antiviral compounds.

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 a novel class of compounds.

The present invention provides new compounds which have been shown to possess antiviral activity. The present invention furthermore demonstrates that these compounds efficiently inhibit proliferation of viruses, especially Flaviviruses, more specifically Dengue virus (DENV) and Yellow Fever virus (YFV). Therefore, these compounds constitute a useful class of new potent compounds that can be used in the treatment and/or prevention of viral infections in animals, mammals and humans, more specifically for the treatment and/or prevention of infections with viruses belonging to the family of the Flaviviruses, and yet more particularly infections with Dengue viruses or yellow fever virus.

The present invention furthermore relates to the use of such compounds as medicines and to their use for the manufacture of medicaments for treating and/or preventing viral infections, in particular with viruses belonging to the family of the Flaviviruses, and yet more particularly infections with Dengue viruses or yellow fever virus, in animals or mammals, more in particular in humans. The present invention therefore relates to the compounds for use as medicines and to the compounds for use as medicaments for treating and/or preventing viral infections, in particular with viruses belonging to the family of the Flaviviruses, and yet more particularly infections with Dengue viruses or yellow fever virus, in animals or 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 an effective amount.

The present invention also relates to a method of treatment or prevention of viral infections 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. Particularly, the present invention also relates to a method of treatment or prevention of viral infections, especially Flaviviral infections, in humans by the administration of an effective amount of one or more such compounds or a pharmaceutically acceptable salt thereof, optionally in combination with one or more other medicines, to a patient in need thereof. More particularly, the present invention also relates to a method of treatment or prevention of infections by the Dengue virus or yellow fever virus in humans by the administration of an effective amount of one or more such compounds or a pharmaceutically acceptable salt thereof, optionally in combination with one or more other medicines, to a patient in need thereof.

One aspect of the i of formula (A),

wherein,

- cycle A is selected from the group consisting of cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; and heterocycle; wherein said cycloalkyl, cycloalkenyl, cycloalkynyl, aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle C is a monocycle selected from

(a1 ) ; (a2) ; (a3) ;

wherein the wavy line (*ΛΛΛΛ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( iiiiiniiii ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ³ and R ⁹ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; =0; and =S; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-heteroalkyl; heterocycle- heteroalkenyl; heterocycle-heteroalkynyl;

and wherein said cycloalkyi; cycloalkenyl; cycloalkynyl; aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-heteroalkyl, heterocycle- heteroalkenyl and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl;

and wherein said alkyl, cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl, heteroalkenyl, and heteroalkynyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; -

S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, or heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; -

C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

and wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyi; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle- alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ³ is independently selected from hydroxyl; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyi; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyi; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle- heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, - OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

Preferably, the invention provides a compound of formula (A), wherein,

- cycle A is selected from the group consisting of cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; and heterocycle; wherein said cycloalkyi, cycloalkenyl, cycloalkynyl, aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle C is a monocycle selected from

(a1 ) ; (a3) ;

wherein the wavy line wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ⁹ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; =0; and =S; wherein said alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-heteroalkyl; heterocycle- heteroalkenyl; heterocycle-heteroalkynyl;

and wherein said cycloalkyi; cycloalkenyl; cycloalkynyl; aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-heteroalkyl, heterocycle- heteroalkenyl and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl;

and wherein said alkyl, cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi, heteroalkenyl, and heteroalkynyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; - S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, or heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; - C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

and wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle- alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ³ is independently selected from hydroxyl; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle- heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof,

with the proviso that said compound is not

2-anilino-2-(4-tert-butylphenyl)-1 -(2-phenyl-1 -piperidyl)ethanone;

2-anilino-1 -(2-phenyl-1 -piperidyl)-2-[4-(trifluoromethyl)phenyl]ethanone;

2-anilino-2-(4-tert-butylphenyl)-1 -(2-phenylazepan-1 -yl)ethanone.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be described with respect to particular embodiments but the invention is not limited thereto.

Preferred statements (features) and embodiments of the compounds and processes of this invention are set herein. Each statements and embodiments of the invention so defined may be combined with any other statement and/or embodiments unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

Numbered statements of this invention are:

1 . A compound of formula (A)

wherein,

- cycle A is selected from the group consisting of cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; and heterocycle; wherein said cycloalkyi, cycloalkenyl, cycloalkynyl, aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle C is a monocycle selected from

(al ) ; (a2) ; (a3) ;

wherein the wavy line wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ³ and R ⁹ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; =0; and =S; wherein said alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or

NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-heteroalkyl; heterocycle- heteroalkenyl; heterocycle-heteroalkynyl;

and wherein said cycloalkyl; cycloalkenyl; cycloalkynyl; aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-heteroalkyl, heterocycle- heteroalkenyl and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi, heteroalkenyl, and heteroalkynyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; - S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, or heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; -

C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

and wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyi; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle- alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ³ is independently selected from hydroxyl; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyi; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyi; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle- heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ; and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

2. The compound according to statement 1 , wherein cycle C is selected from the following group of cycles

3. The compounds of according to statement 1 or 2, wherein cycle C is selected from the following group of cycles

4. The compounds according to any one of statements 1 to 3, selected from the compounds of formula (C1 ), (C2), (C3), (C4), and (C5),

(C4), (C5).

5. The compounds of according to statement 1 , wherein,

- cycle C is a monocycle selected from

wherein the wavy line ( «ΛΛΛ ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( iiiiiniiii ) indicates the point of attachment to the cycle A of the main formula (A);

- cycle A is selected from aryl; and heterocycle; optionally substituted with one, two, or three substituents (more in particular one or two substituents) selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH , NH ₂ , NH(alkyl), or N(alkyl) ₂ ; more particularly cycle A is selected from

wherein the wavy line ( ·~»~ ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle are optionally substituted with one, two, or three Z ^a ; more particularly cycle B is selected from

wherein the wavy line ( ·~>~ ) indicates the point of attachment to the carbon atom of the main formula (A), and wherein the depicted cycles may be optionally substituted with one, two, or three Z ^a ;

- R is selected from d. ₆ alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ .

₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ .

₆ alkynyl; preferably R is selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, aryl, heterocycle;

and wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, heterocycle-d. ₆ alkyl, heterocycle- C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . 6alkynyl, heterocycle-heterod. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle- heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^b ; preferably said d_ 6alkyl, C _3-7 cycloalkyl, aryl, and heterocycle, are optionally substituted with one, two, or three Z ^{1 b} ;

- R ² is selected from hydrogen, -C(0)Z ³ , C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl; preferably R ² is selected from hydrogen, -C(0)Z ³ , and Ci _-6 alkyl;

and wherein said C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^c ; preferably said d_ ₆ alkyl is optionally substituted with one, two, or three Z ^c ;

- R ³ is selected from hydrogen; C _1-6 alkyl; heteroCi. ₆ alkyl; and =0;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; heteroCi. ₆ alkyl; heteroCi- ₆ alkenyl; and heteroCi. ₆ alkynyl;

- R ⁹ is selected from hydrogen; C _1-6 alkyl; heteroCi. ₆ alkyl; and =0;

- each of R ² , R ⁴ and R ⁶ is independently selected from hydrogen; halogen; trifluoromethyl; cyano; Ci. ₆ alkyl and Ci. ₆ cycloalkyl;

- each R ³ , R ⁵ and R ⁷ is independently selected from hydrogen; C _1-6 alkyl; and Ci _-6 cycloalkyl; - each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ - ₆ alkenyl; C ₂ - ₆ alkynyl; hetero C _1-6 alkyl; heteroC ₂ . ₆ alkenyl; and hetero C ₂ . ₆ alkynyl;

- R ³³ is independently selected from hydrogen and C _1-6 alkyl;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , - NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, C^alkyl, C ₂ _ ₆ alkenyl, C ₂ _ ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci- ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0) ₂ Z ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, C^alkyl, heteroC^alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci- ₆ alkyl;

and wherein said C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci. ₄ alkyl, and -0-Ci _-6 alkyl; preferably said C _1-6 alkyl, heteroCi. ₆ alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , - 0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OC ₁ _ ₆ alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci. ₄ alkyl, morpholinyl, -S(0) ₂ Ci. ₄ alkyl, and -0-Ci. ₆ alkyl; more preferably said Ci. ₆ alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C C OC^alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH- C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, -S(0) ₂ Ci- ₄ alkyl, and -0-d _-6 alkyl;

- each Z ² is independently selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ² is independently selected from Ci _-6 alkyl, aryl, heterocycle, and heterocycle-Ci _-6 alkyl; more preferably Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci _-6 alkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ .

₆ alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi _-6 alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, - C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; preferably said C _1-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -

C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; more preferably said C _{1 -6} alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci _-6 alkyl,

-C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; - each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, heteroCi. ₆ alkyl, heteroC _2-6 alkenyl, heteroC _2-6 alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC _2-6 alkenyl, arylC _2-6 alkynyl, arylheteroCi _-6 alkyl, arylheteroC _2-6 alkenyl, arylheteroC _2-6 alkynyl, heterocycle-Ci_ ₆ alkyl, heterocycle-C _2-6 alkenyl, heterocycle-C _2-6 alkynyl, heterocycle-heteroCi _-6 alkyl, heterocycle- heteroC _2-6 alkenyl, and heterocycle-heteroC _2-6 alkynyl; preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, aryl, and heterocycle; more preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, heteroCi _-6 alkyl, heteroC _2-6 alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC _2-6 alkenyl, arylC _2-6 alkynyl, arylheteroCi _-6 alkyl, arylheteroC _2-6 alkenyl, arylheteroC _2-6 alkynyl, heterocycle-Ci _-6 alkyl, heterocycle-C _2-6 alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heterod. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ - ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ - ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ ; preferably said Ci _-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from d. ₆ alkyl and -N(CH ₃ ) ₂ ; more preferably said Ci. ₆ alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from d_ 6alkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, C ₃ . ₇ cycloalkyl, heterocycle, arylCi.

₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle- heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, aryl, C _3-7 cycloalkyl, and heterocycle; more preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C _3-7 cycloalkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH or -NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which is optionally substituted with C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, or -NH ₂ .

6. The compounds according to any one of statements 1 to 5, wherein

- each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, - NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , d_ ₆ alkyl, heteroCi. ₆ alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl;

and wherein said C _{1 -6} alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C(0)Od_ 6alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-d_ ₄ alkyl; -S(0) ₂ d_ ₄ alkyl, and -0-d_ ₆ alkyl; - each Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _{1 -6} alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-d. ₆ alkyl,

-C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl;

- each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle; wherein said Ci. ₆ alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from d- ₆ alkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C ₃ . ₇ cycloalkyl.

7. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient an effective amount of the compound according to any one of statements 1 to 6 or a pharmaceutically acceptable salt thereof.

8. The compounds according to any one of statements 1 to 6, or a pharmaceutical composition according to statement 7, for use as a medicine.

9. The compounds according to any one of statements 1 to 6, or a pharmaceutical composition according to statement 7, for use in the prevention or treatment of a flavivirus infection in an animal, mammal or human.

10. The compounds according to according to statement 9, or a pharmaceutical composition according to statement 9, wherein the flavivirus infection is an infection with a Dengue virus or a yellow fever virus.

1 1 . A method for the preparation of the compound according to any one of statements 1 to 6 comprising the step of

- reacting an imine with an aldehyde under umpolung conditions in the presence of a thiazolium catalyst to obtain the desired compounds of the invention.

In another embodiment, the invention relates to a method for the preparation of the compounds of the invention, comprising the steps of

- reacting a ketone derivative having a methylene adjacent to the carbonyl under halogenation conditions to obtain an alpha-halogenoketone,

- substitute the previously obtained alpha-halogenoketone with amines to obtain the desired compounds of the invention.

In another embodiment, the invention relates to a method for the preparation of the compounds of the invention, comprising the steps of

- reacting a heterocyclicamine with 2-halogeno-acetic acid halide to obtain an alpha- halogenoamide derivative,

- substitute the previously obtained alpha-halogenoamide with amines to obtain the desired compounds of the invention.

12. A method of treatment or prevention of Flaviviral infections, in humans by the administration of an effective amount of a compound according to any one of statements 1 to 6 or a pharmaceutically acceptable salt thereof, optionally in combination with one or more other medicines, to a patient in need thereof.

13. The method according to statement 12, wherein the Flaviviral infection is an infection by the Dengue virus or yellow fever virus.

14. The compounds according to any one of statements 1 to 10, or a pharmaceutical composition according to any one of statements 7 to 10, wherein,

- cycle A is selected from the group consisting of C ₃ . ₇ cycloalkyl; C ₅ . ₇ cycloalkenyl; C ₅ - ₇ cycloalkynyl; C ₆ -i ₂ aryl; and heterocycle; wherein said C ₃ . ₇ cycloalkyl, C ₅ . ₇ cycloalkenyl, C ₅ . ₇ cycloalkynyl, C ₆ -i ₂ aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₅ . ₇ cycloalkynyl, hetero C _1-6 alkyl, hetero C ₂ . ₆ alkenyl, hetero C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, - SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(Ci _-6 alkyl), or N(C ₁ _ ₆ alkyl) ₂ ; - cycle C is a monocycle selected from

(a1 ) ; (a2) ; (a3) ;

wherein the wavy line wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ³ and R ⁹ is independently selected from hydrogen; d- ₆ alkyl; C ₂ - ₆ alkenyl; C ₂ - ₆ alkynyl; heteroCi- ₆ alkyl; heteroC ₂ - ₆ alkenyl; heteroC ₂ - ₆ alkynyl; =0; and =S; wherein said Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, and heteroC ₂ - ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; d- ₆ alkyl; C ₂ - ₆ alkenyl; C ₂ - ₆ alkynyl; heteroCi- ₆ alkyl; heteroC ₂ - ₆ alkenyl; and heteroC ₂ - ₆ alkynyl; and wherein said Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from C ₃ . ₇ cycloalkyl; C ₅ - ₇ cycloalkenyl; C ₅ - ₇ cycloalkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi- ₆ alkyl; C ₆ -i ₂ arylC ₂ - ₆ alkenyl; C ₆ -i ₂ arylC ₂ - ₆ alkynyl; heterocycle-Ci- ₆ alkyl; heterocycle- C ₂ - ₆ alkenyl; heterocycle-C ₂ - ₆ alkynyl; C ₆ -i ₂ arylheteroCi- ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ - ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ - ₆ alkynyl; heterocycle-heteroCi- ₆ alkyl; heterocycle-heteroC ₂ - ₆ alkenyl; heterocycle-heteroC ₂ - ₆ alkynyl; and wherein said C ₃ . ₇ cycloalkyl; C ₅ . ₇ cycloalkenyl; C ₅ . ₇ cycloalkynyl; C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi- ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle- C ₂ - ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ - ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ - ₆ alkenyl and heterocycle-heteroC ₂ - ₆ alkynyl can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; C _1-6 alkyl; C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; and heteroC ₂ . ₆ alkynyl;

and wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; C _1-6 alkyl; C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl;

wherein said C _{1 -6} alkyl, C _3-7 cycloalkyl, C ₂ . ₆ alkenyl, C _5-7 cycloalkenyl, C ₂ . ₆ alkynyl,

C _5-7 cycloalkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; - S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; Ci _-6 alkyl; C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl;

wherein said C _{1 -6} alkyl, C _3-7 cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, or heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; and heteroC ₂ . ₆ alkynyl; and wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; and heteroC ₂ . ₆ alkynyl; and wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ; - each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; - C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; Ci _-6 alkyl; C _3-7 cycloalkyl; C _2-6 alkenyl; C _5-7 cycloalkenyl; C ₂ _ ₆ alkynyl; C _5-7 cycloalkynyl; heteroCi _-6 alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ _ ₁₂ arylCi_ ₆ alkyl; C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl; heterocycle-Ci. ₆ alkyl; heterocycle- C ₂ . ₆ alkenyl; heterocycle-C ₂ . ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl; or heterocycle-heteroC ₂ . ₆ alkynyl;

and wherein said C _{1 -6} alkyl, C _3-7 cycloalkyl, C ₂ . ₆ alkenyl, C _5-7 cycloalkenyl, C ₂ . ₆ alkynyl,

C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl,

C ₆ -i ₂ arylheteroCi- ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle- alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from C _{1 -6} alkyl; C _3-7 cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi_ ₆ alkyl; C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl;

C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl; heterocycle-Ci. ₆ alkyl; heterocycle-

C ₂ . ₆ alkenyl; heterocycle-C ₂ . ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl; heterocycle-heteroC ₂ . ₆ alkenyl; or heterocycle-heteroC ₂ . ₆ alkynyl;

wherein said C _{1 -6} alkyl, C _3-7 cycloalkyl, C ₂ . ₆ alkenyl, C _5-7 cycloalkenyl, C ₂ . ₆ alkynyl,

C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle- C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ³ is independently selected from hydroxyl; C _{1 -6} alkyl; C _3-7 cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; aryl; heterocycle; C ₆ _ ₁₂ arylCi_ ₆ alkyl; C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl; heterocycle- Ci_ ₆ alkyl; heterocycle-C ₂ . ₆ alkenyl; heterocycle-C ₂ . ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl; heterocycle-heteroC ₂ . ₆ alkenyl; or heterocycle-heteroC ₂ . ₆ alkynyl;

wherein said C _{1 -6} alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₅ - ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ _i ₂ arylCi_ ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ - ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle- C ₂ - ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; C _1-6 alkyl; C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi. ₆ alkyl; C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl;

C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl; heterocycle-Ci. ₆ alkyl; heterocycle-C ₂ . ₆ alkenyl; heterocycle- C ₂ . ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl; heterocycle-heteroC ₂ . ₆ alkenyl; or heterocycle- heteroC ₂ . ₆ alkynyl;

wherein said C _{1 -6} alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl,

C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle- C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with C _1-6 alkyl, C _3-7 cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₅ . ₇ cycloalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, - OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ;

preferably wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO- O-d-salkyl, -0-Ci _-6 alkyl, -NH-Ci _-6 alkyl, -N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-Ci _-6 alkyl; and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

15. The compounds according to any one of statements 1 to 10, 14, or a pharmaceutical composition according to any one of statements 7 to 10, wherein,

- cycle A is selected from the group consisting of C ₃ . ₇ cycloalkyl; C ₆ -i ₂ aryl; and heterocycle; wherein said C ₃ . ₇ cycloalkyl, C ₆ -i ₂ aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, hetero C _1-6 alkyl, hetero C ₂ . ₆ alkenyl, hetero C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(Ci _-6 alkyl), or N(Ci _-6 alkyl) ₂ ;

- cycle C is a monocycle selected from

(a1 ) ; (a2) ; (a3) ;

wherein the wavy line wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ³ and R ⁹ is independently selected from hydrogen; d- ₆ alkyl; heteroCi- ₆ alkyl; =0; and =S; wherein said Ci- ₆ alkyl, and heteroCi- ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; d- ₆ alkyl; and heteroCi- ₆ alkyl; and wherein said

Ci- ₆ alkyl, heteroCi- ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from C ₃ - ₇ cycloalkyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi- ₆ alkyl; heterocycle- Ci- ₆ alkyl; C ₆ -i ₂ arylheteroCi- ₆ alkyl; heterocycle-heteroCi- ₆ alkyl;

and wherein said C ₃ - ₇ cycloalkyl; C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi- ₆ alkyl, heterocycle- Ci- ₆ alkyl, C ₆ -i ₂ arylheteroCi- ₆ alkyl, and heterocycle-heteroCi- ₆ alkyl, can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; d- ₆ alkyl; C ₃ - ₇ cycloalkyl; and heteroCi- ₆ alkyl;

and wherein said Ci- ₆ alkyl, C ₃ - ₇ cycloalkyl; and heteroCi- ₆ alkyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; d- ₆ alkyl; C ₃ . ₇ cycloalkyl; heteroCi-ealkyl; wherein said d- ₆ alkyl, C ₃ . ₇ cycloalkyl, and heteroCi-ealkyl, can be unsubstituted or substituted with one or more substituents selected from d- ₆ alkyl, heteroCi-ealkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ; - R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; - S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; C^alkyl; C ₃ . ₇ cycloalkyl; heteroCi. ₆ alkyl;

wherein said Ci. ₆ alkyl, C ₃ . ₇ cycloalkyl, heteroCi. ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from Ci. ₆ alkyl, heteroCi. ₆ alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; Ci. ₆ alkyl; and heteroCi. ₆ alkyl; and wherein said Ci- ₆ alkyl, heteroCi. ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; Ci_ ₆ alkyl; and heteroCi. ₆ alkyl; wherein said Ci. ₆ alkyl, heteroCi. ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; - C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; d_ ₆ alkyl; C ₃ _ ₇ cycloalkyl; hetero^alkyl; C ₆ - ₁₂ aryl; heterocycle; C ₆ _ ₁₂ arylCi_ ₆ alkyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; heterocycle-Ci. ₆ alkyl; or heterocycle-heteroCi. ₆ alkyl, and wherein said Ci_ ₆ alkyl, C ₃ . ₇ cycloalkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, heterocycle-Ci. ₆ alkyl, or heterocycle- heteroCi. ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from Ci- ₆ alkyl, heteroCi. ₆ alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from Ci. ₆ alkyl; C ₃ . ₇ cycloalkyl; heteroCi. ₆ alkyl; C ₆ -i ₂ aryl; heterocycle; C ₆ _ ₁₂ arylCi_ ₆ alkyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; heterocycle-Ci. ₆ alkyl; or heterocycle- heteroCi. ₆ alkyl;

wherein said Ci_ ₆ alkyl, C ₃ . ₇ cycloalkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi- ₆ alkyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, heterocycle-Ci. ₆ alkyl, or heterocycle- heteroCi. ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from Ci- ₆ alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ³ is independently selected from hydroxyl; Ci_ ₆ alkyl; C ₃ . ₇ cycloalkyl; heteroCi. ₆ alkyl; aryl; heterocycle; C ₆ -i ₂ arylCi. ₆ alkyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; heterocycle-Ci. ₆ alkyl; or heterocycle- heteroCi. ₆ alkyl;

wherein said Ci. ₆ alkyl, C ₃ . ₇ cycloalkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi- ₆ alkyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, heterocycle-Ci. ₆ alkyl, or heterocycle- heteroCi- ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from Ci- ₆ alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; C _1-6 alkyl; C ₃ . ₇ cycloalkyl; heteroCi. ₆ alkyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi. ₆ alkyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; heterocycle- Ci _-6 alkyl; or heterocycle-heteroCi. ₆ alkyl;

wherein said C _{1 -6} alkyl, C ₃ . ₇ cycloalkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, heterocycle-Ci. ₆ alkyl, or heterocycle- heteroCi. ₆ alkyl, can be unsubstituted or substituted with one or more substituents selected from Ci _-6 alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with C _1-6 alkyl, C _3-7 cycloalkyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ; and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

16. A compound of formula (A)

wherein,

- cycle A is selected from the group consisting of cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; and heterocycle; wherein said cycloalkyi, cycloalkenyl, cycloalkynyl, aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle C is a monocycle selected from

(a1 ) ; (a3) ;

wherein the wavy line ( v wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A); - X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ⁹ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; =0; and =S; wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-heteroalkyl; heterocycle- heteroalkenyl; heterocycle-heteroalkynyl;

and wherein said cycloalkyi; cycloalkenyl; cycloalkynyl; aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-heteroalkyl, heterocycle- heteroalkenyl and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl; heteroalkenyl; and heteroalkynyl;

and wherein said alkyl, cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl, heteroalkenyl, and heteroalkynyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; - S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, or heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; -

C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

and wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle- alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ; - each Z ³ is independently selected from hydroxyl; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle- heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, - OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof,

with the proviso that said compound is not

2-anilino-2-(4-tert-butylphenyl)-1 -(2-phenyl-1 -piperidyl)ethanone;

2-anilino-1 -(2-phenyl-1 -piperidyl)-2-[4-(trifluoromethyl)phenyl]ethanone;

2-anilino-2-(4-tert-butylphenyl)-1 -(2-phenylazepan-1 -yl)ethanone.

17. The compounds according to any one of statements 1 -10, 14-16, or a pharmaceutical composition according to any one of statements 7 to 10, wherein cycle C is selected from the following group of cycles 19. The compounds according to any one of statements 1 -10, 14-18, or a pharmaceutical composition according to any one of statements 7 to 10, selected from the compounds of formula (C1 ), (C2), (C3), and (C5),

(C5).

20. The compounds according to any one of statements 1 -10, 14-19, or a pharmaceutical composition according to any one of statements 7 to 10, wherein,

- cycle C is a monocycle selected from

wherein the wavy line (*ΛΛΛΛ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( iiiiiniiii ) indicates the point of attachment to the cycle A of the main formula (A);

- cycle A is selected from aryl; and heterocycle; optionally substituted with one, two, or three substituents (more in particular one or two substituents) selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH , NH ₂ , NH(alkyl), or N(alkyl) ₂ ; more particularly cycle A is selected from

wherein the wavy line ( ~ ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle are optionally substituted with one, two, or three Z ^a ; more particularly cycle B is selected from

wherein the wavy line ( ·~<~ ) indicates the point of attachment to the carbon atom of the main formula (A), and wherein the depicted cycles may be optionally substituted with one, two, or three Z ^a ;

- R is selected from d. ₆ alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably R is selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, aryl, heterocycle;

and wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, heterocycle-d. ₆ alkyl, heterocycle- C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . 6alkynyl, heterocycle-heterod. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle- heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^b ; preferably said d_ 6alkyl, C _3-7 cycloalkyl, aryl, and heterocycle, are optionally substituted with one, two, or three Z ^{1 b} ;

- R ² is selected from hydrogen, -C(0)Z ³ , C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl; preferably R ² is selected from hydrogen, -C(0)Z ³ , and Ci _-6 alkyl;

and wherein said C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^c ; preferably said d_ 6alkyl is optionally substituted with one, two, or three Z ^c ;

- R ⁹ is selected from hydrogen; C _1-6 alkyl; heteroCi _-6 alkyl; and =0;

- each of R ² , R ⁴ and R ⁶ is independently selected from hydrogen; halogen; trifluoromethyl; cyano; C _1-6 alkyl and d. ₆ cycloalkyl;

- each R ³ , R ⁵ and R ⁷ is independently selected from hydrogen; C _1-6 alkyl; and Ci _-6 cycloalkyl;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; hetero C _1-6 alkyl; heteroC ₂ . ₆ alkenyl; and hetero C ₂ . ₆ alkynyl;

- R ³³ is independently selected from hydrogen and C _1-6 alkyl;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , - NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, d_ ₆ alkyl, C ₂ _ ₆ alkenyl, C ₂ _ ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, aryld. ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ - ₆ alkenyl, arylheteroC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0) ₂ Z ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, C^alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci _-6 alkyl;

and wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci. ₄ alkyl, and -0-Ci _-6 alkyl; preferably said C _1-6 alkyl, heteroCi. 6alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , - 0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci_ ₄ alkyl, and -0-Ci _-6 alkyl; more preferably said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH- C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, -S(0) ₂ Ci- ₄ alkyl, and -0-Ci _-6 alkyl;

- each Z ² is independently selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ² is independently selected from Ci _-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; preferably said Ci _-6 alkyl, aryl, heterocycle, and heterocycle-d. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , -S(=0) ₂ C ₁ _ ₄ alkyl, cyano, nitro, -C(=0)OH, -C(=0)0-d_ 4alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; more preferably said d_ 6alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci _-6 alkyl, -S(=0) ₂ C ₁ _ ₄ alkyl, -C(=0)OH, -C(=0)0-d_ 4alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl;

- each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, aryld. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci_ ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heterod. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, aryl, and heterocycle; more preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, aryld. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-d. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from d. ₆ alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-d_ ₆ alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ ; preferably said Ci _-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from d. ₆ alkyl and -N(CH ₃ ) ₂ ; more preferably said d. ₆ alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from d_ 6alkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, C ₃ . ₇ cycloalkyl, heterocycle, arylCi. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-d. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle- heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, aryl, C ₃ . ₇ cycloalkyl, and heterocycle; more preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C ₃ . ₇ cycloalkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, aryld. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ - ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH or -NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which is optionally substituted with C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, or -NH ₂ .

21 . The compound according to any one of statements 1 -10, 14-20, or a pharmaceutical composition according to any one of statements 7 to 10, wherein

- each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, - NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci _-6 alkyl;

and wherein said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C(0)Od_ 6alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C ₁ _ ₄ alkyl; -S(0) ₂ C ₁ _ ₄ alkyl, and -0-Ci _-6 alkyl;

- each Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _1-6 alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci _-6 alkyl,

-C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl;

- each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said Ci. ₆ alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from d-ealkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C ₃ . ₇ cycloalkyl.

22. The compounds according to any one of statements 16-21 , for use as a medicine.

23. The compounds according to statement 22, for use in the prevention or treatment of a flavivirus infection in an animal, mammal or human.

24. A compounds of formula (A), for use in the prevention or treatment of a flavivirus infection in an animal, mammal or hu

wherein,

- cycle A is selected from the group consisting of cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; and heterocycle; wherein said cycloalkyi, cycloalkenyl, cycloalkynyl, aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle C is a monocycle selected from

(a1 ) ; (a2) ; (a3) ;

wherein the wavy line wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ³ and R ⁹ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; =0; and =S; wherein said alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^a ;

- R is selected from cycloalkyi; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-heteroalkyl; heterocycle- heteroalkenyl; heterocycle-heteroalkynyl;

and wherein said cycloalkyi; cycloalkenyl; cycloalkynyl; aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-heteroalkyl, heterocycle- heteroalkenyl and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z ^b ;

- R ² is selected from hydrogen; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl;

and wherein said alkyl, cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi, heteroalkenyl, and heteroalkynyl, can be unsubstituted or substituted with one or more Z ^c ;

- each R ² , R ⁴ , and R ⁶ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; nitro; amino; cyano; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, and heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- R ³ , R ⁵ , and R ⁷ is independently selected from hydrogen; hydroxyl; sulfhydryl; -S(0)Z ² ; - S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl;

wherein said alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, or heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ³³ is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl; and wherein said alkyl, alkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; -S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; -NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; - C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H; alkyl; cycloalkyi; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

and wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ² is independently selected from alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle- alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle- heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ³ is independently selected from hydroxyl; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle-heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyi, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen; alkyl; cycloalkyl; alkenyl; cycloalkenyl; alkynyl; cycloalkynyl; heteroalkyi; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyi; heterocycle- heteroalkenyl; or heterocycle-heteroalkynyl;

wherein said alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyi, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, arylheteroalkyi, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from alkyl, alkenyl, alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -O-alkyl, -OCF ₃ , cyano, nitro, -C(0)OH or -NH ₂ ;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

25. The compounds according to statement 24, wherein cycle C is selected from the following group of cycles

26. The compounds according to any one of statements 24 or 25, wherein cycle C is selected

(C4) (C5).

28. The compounds according to statement 27 wherein,

- cycle C is a monocycle selected from

wherein the wavy line (*ΛΛΛΛ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( iiiiiniiii ) indicates the point of attachment to the cycle A of the main formula (A);

- cycle A is selected from aryl; and heterocycle; optionally substituted with one, two, or three substituents (more in particular one or two substituents) selected from alkyl, cycloalkyi, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH , NH ₂ , NH(alkyl), or N(alkyl) ₂ ; more particularly cycle A is selected from

wherein the wavy line indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, NH ₂ , NH(alkyl), or N(alkyl) ₂ ;

- cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle are optionally substituted with one, two, or three Z ^a ; more particularly cycle B is selected from

wherein the wavy line ( ·~>~ ) indicates the point of attachment to the carbon atom of the main formula (A), and wherein the depicted cycles may be optionally substituted with one, two, or three Z ^a ;

- R is selected from d- ₆ alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ .

₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ .

₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ .

₆ alkynyl; preferably R is selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, aryl, heterocycle;

and wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle- C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . 6alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle- heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^b ; preferably said d. ₆ alkyl, C ₃ . ₇ cycloalkyl, aryl, and heterocycle, are optionally substituted with one, two, or three

Z ^{1 b} ;

- R ² is selected from hydrogen, -C(0)Z ³ , C _1-6 alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ - ₆ alkenyl, and heteroC ₂ - ₆ alkynyl; preferably R ² is selected from hydrogen, -C(0)Z ³ , and Ci _-6 alkyl;

and wherein said C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^c ; preferably said d. 6alkyl is optionally substituted with one, two, or three Z ^c ;

- R ³ is selected from hydrogen; C _1-6 alkyl; heteroCi _-6 alkyl; and =0;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; heteroCi _-6 alkyl; heteroCi _-6 alkenyl; and heteroCi _-6 alkynyl;

- R ⁹ is selected from hydrogen; C _1-6 alkyl; heteroCi _-6 alkyl; and =0;

- each of R ² , R ⁴ and R ⁶ is independently selected from hydrogen; halogen; trifluoromethyl; cyano; C _1-6 alkyl and Ci _-6 cycloalkyl;

- each R ³ , R ⁵ and R ⁷ is independently selected from hydrogen; C _1-6 alkyl; and Ci _-6 cycloalkyl;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; hetero C _1-6 alkyl; heteroC ₂ . ₆ alkenyl; and hetero C ₂ . ₆ alkynyl;

- R ³³ is independently selected from hydrogen and C _1-6 alkyl;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , - NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, C^alkyl, C ₂ _ ₆ alkenyl, C ₂ _ ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi _-6 alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0) ₂ Z ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, C^alkyl, heteroC^alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl;

and wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi- ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ - ₆ alkynyl, heterocycle-d. ₆ alkyl, heterocycle-C ₂ - ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, heterocycle-heterod. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heterod. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci. ₄ alkyl, and -0-Ci _-6 alkyl; preferably said C _1-6 alkyl, heteroCi. 6alkyl, aryl, heterocycle, and heterocycle-Ci _-6 alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , - 0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci_ ₄ alkyl, and -0-Ci _-6 alkyl; more preferably said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH- C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, -S(0) ₂ Ci- ₄ alkyl, and -0-Ci _-6 alkyl;

- each Z ² is independently selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ² is independently selected from C _1-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; preferably said Ci _-6 alkyl, aryl, heterocycle, and heterocycle-Ci _-6 alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , -S(=0) ₂ C ₁ _ ₄ alkyl, cyano, nitro, -C(=0)OH, -C(=0)0-d_ 4alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; more preferably said d_ 6alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci _-6 alkyl, -S(=0) ₂ C ₁ _ ₄ alkyl, -C(=0)OH, -C(=0)0-d_ 4alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl;

- each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, aryld. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci_ ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ - ₆ alkenyl, and heterocycle-heteroC ₂ - ₆ alkynyl; preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, aryl, and heterocycle; more preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ ; preferably said Ci _-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from d- ₆ alkyl and -N(CH ₃ ) ₂ ; more preferably said Ci_ ₆ alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from d. 6alkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, C ₃ . ₇ cycloalkyl, heterocycle, arylCi. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle- heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, aryl, C _3-7 cycloalkyl, and heterocycle; more preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C _3-7 cycloalkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH or -NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which is optionally substituted with C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, or -NH ₂ .

29. The compound according to any one of statements 24 to 28, wherein

- each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, - NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci _-6 alkyl;

and wherein said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C(0)Od_ 6alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C ₁ _ ₄ alkyl; and -0-Ci _-6 alkyl;

- each Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _1-6 alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci _-6 alkyl,

-C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl;

- each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said C _1-6 alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C _3-7 cycloalkyl.

30. The compounds according to any one of statements 24 to 29, wherein the flavivirus infection is an infection with a Dengue virus or a yellow fever virus.

31 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and as active ingredient an effective amount of the compound according to any one of statements 16 to 29 or a pharmaceutically acceptable salt thereof.

32. A method for the preparation of the compound according to any one of statements 16 to 29 comprising the step of

- reacting an imine with an aldehyde under umpolung conditions in the presence of a thiazolium catalyst to obtain the desired compounds of the invention.

33. A method for the preparation of the compound according to any one of statements 16 to 29 comprising the step of

- reacting a ketone derivative having a methylene adjacent to the carbonyl under halogenation conditions to obtain an alpha-halogenoketone,

- substitute the previously obtained alpha-halogenoketone with amines to obtain the desired compounds of the invention.

34. A method for the preparation of the compound according to any one of statements 16 to 29 comprising the step of

- reacting a heterocyclicamine with 2-halogeno-acetic acid halide to obtain an alpha- halogenoamide derivative,

- substitute the previously obtained alpha-halogenoamide with amines to obtain the desired compounds of the invention.

35. A method of treatment or prevention of Flaviviral infections, in humans by the administration of an effective amount of a compound according to any one of statements 16 to 29 or a pharmaceutically acceptable salt thereof, optionally in combination with one or more other medicines, to a patient in need thereof.

36. The method according to statement 35, wherein the Flaviviral infection is an infection by the Dengue virus or yellow fever virus.

37. The compound according to any one of statements 1 -10, 14-29, or a pharmaceutical composition according to any one of statements 7 to 10, wherein - cycle C is a monocycle selected from

(a1 ) ; (a2) ; (a3) ;

wherein the wavy line wvr ) indicates the point of attachment to the carbonyl of the main formula (A) and the hashed line ( ) indicates the point of attachment to the cycle A of the main formula (A);

- X ¹ is selected from C; and N;

- X ² is selected from CR ² ; NR ³ ; N; O; and S;

- X ³ is selected from CR ¹⁴ , NR ¹⁵ ; N; O; and S;

- X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; N; O; and S;

- each R ³ and R ⁹ is independently selected from hydrogen; d- ₆ alkyl; C ₂ - ₆ alkenyl; C ₂ - ₆ alkynyl; heteroCi- ₆ alkyl; heteroC ₂ - ₆ alkenyl; heteroC ₂ - ₆ alkynyl; =0; and =S; wherein said Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, and heteroC ₂ - ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; =0; =S; trifluoromethyl; trifluoromethoxy; cyano; d- ₆ alkyl; C ₂ - ₆ alkenyl; C ₂ - ₆ alkynyl; heteroCi- ₆ alkyl; heteroC ₂ - ₆ alkenyl; and heteroC ₂ - ₆ alkynyl; and wherein said Ci- ₆ alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, can be unsubstituted or substituted with one or more substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH or NH ₂ ;

- W is selected from CR ³² R ^32a ; NR ³³ ; O; S; and S0 ₂ ;

- each p and q is independently selected from 1 and 2, whereby p+q is selected from 2 and 3;

- cycle A is selected from the group consisting of C ₃ - ₇ cycloalkyl; C ₅ - ₇ cycloalkenyl; C ₅ - ₇ cycloalkynyl; C ₆ -i ₂ aryl; and heterocycle; wherein said C ₃ - ₇ cycloalkyl, C ₅ - ₇ cycloalkenyl,

C ₅ - ₇ cycloalkynyl, C ₆ -i ₂ aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from Ci- ₆ alkyl, C ₃ . ₇ cycloalkyl, C ₂ - ₆ alkenyl, C ₅ - ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₅ - ₇ cycloalkynyl, hetero Ci- ₆ alkyl, hetero C ₂ - ₆ alkenyl, hetero C ₂ - ₆ alkynyl, hydroxyl, =0, halogen, - SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH^-ealkyl), or N(C ₁ - ₆ alkyl) ₂ ; - cycle B is selected from aryl; and heterocycle; wherein said aryl and heterocycle are optionally substituted with one, two, or three Z ^a ;

- R is selected from Ci- ₆ alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, heterocycle-Ci- ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, arylheteroCi- ₆ alkyl, arylheteroC ₂ - ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-heteroCi- ₆ alkyl, heterocycle-heteroC ₂ - ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably R is selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, aryl, heterocycle; and wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₇ cycloalkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle- C ₂ - ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . 6alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle- heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^b ; preferably said d_ 6alkyl, C ₃ . ₇ cycloalkyl, aryl, and heterocycle, are optionally substituted with one, two, or three Z ^{1 b} ;

- R ² is selected from hydrogen, -C(0)Z ³ , C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl; preferably R ² is selected from hydrogen, -C(0)Z ³ , and

Ci _-6 alkyl;

and wherein said C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, and heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three Z ^c ; preferably said d_ 6alkyl is optionally substituted with one, two, or three Z ^c ;

- R ³ is selected from hydrogen; C _1-6 alkyl; heteroCi _-6 alkyl; and =0;

- each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; heteroCi _-6 alkyl; heteroC ₂ . ₆ alkenyl; and heteroC ₂ . ₆ alkynyl;

- R ⁹ is selected from hydrogen; C _1-6 alkyl; heteroCi. ₆ alkyl; and =0;

- each of R ² , R ⁴ and R ⁶ is independently selected from hydrogen; halogen; trifluoromethyl; cyano; d. ₆ alkyl and d. ₆ cycloalkyl;

- each R ³ , R ⁵ and R ⁷ is independently selected from hydrogen; C _1-6 alkyl; and Ci _-6 cycloalkyl;

- each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; C _1-6 alkyl; C ₂ . ₆ alkenyl; C ₂ . ₆ alkynyl; hetero C _1-6 alkyl; heteroC ₂ . ₆ alkenyl; and heteroC ₂ . ₆ alkynyl;

- R ³³ is independently selected from hydrogen and C _1-6 alkyl;

- each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , - NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, d_ ₆ alkyl, C ₂ _ ₆ alkenyl, C ₂ _ ₆ alkynyl, heterod. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, aryld. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0) ₂ Z ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, d_ ₆ alkyl, heterod_ ₆ alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci- ₆ alkyl;

and wherein said C _1-6 alkyl, C ₂ - ₆ alkenyl, C ₂ - ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci. ₄ alkyl, and -0-Ci _-6 alkyl; preferably said C _1-6 alkyl, heteroCi. 6alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , - 0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0- Ci _-4 alkyl, morpholinyl, -S(0) ₂ Ci_ ₄ alkyl, and -0-Ci _-6 alkyl; more preferably said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH- C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, -S(0) ₂ Ci- ₄ alkyl, and -0-d _-6 alkyl;

- each Z ² is independently selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ² is independently selected from Ci _-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; preferably said Ci _-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , -S(=0) ₂ C ₁ _ ₄ alkyl, cyano, nitro, -C(=0)OH, -C(=0)0-d- 4alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; more preferably said d_ ₆ alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci _-6 alkyl, -S(=0) ₂ C ₁ _ ₄ alkyl, -C(=0)OH, -C(=0)0-d. 4alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl;

- each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, C ₂ - ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci_ ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, aryl, and heterocycle; more preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ ; preferably said Ci _-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from Ci. ₆ alkyl and -N(CH ₃ ) ₂ ; more preferably said Ci_ ₆ alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from Ci_ 6alkyl and -N(CH ₃ ) ₂ ;

- each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, C ₃ . ₇ cycloalkyl, heterocycle, arylCi. ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle- heteroCi- ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, aryl, C _3-7 cycloalkyl, and heterocycle; more preferably each Z ⁴ and Z ⁵ is independently selected from hydrogen, C _1-6 alkyl, and C _3-7 cycloalkyl;

wherein said C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi _-6 alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . 6alkynyl, aryl, heterocycle, arylC _1-6 alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi _-6 alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH or -NH ₂ ;

and wherein Z ⁴ and Z ⁵ can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which is optionally substituted with C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, or -NH ₂ ; preferably wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO-O-C ₁ . ₅ alkyl, -0-Ci _-6 alkyl, -NH-Ci _-6 alkyl, -N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-Ci _-6 alkyl.

38. The compound according to any one of statements 1 -10, 14-29, 37 or a pharmaceutical

and wherein the wavy line (·~~ ) indicates the point of attachment to the carbon atom of the main formula (A), and wherein the depicted cycles may be optionally substituted with one, two, or three Z ^a . 39. The compound according to any one of statements 1 -1 0, 14-29, 37 or a pharmaceutical composition according to any one of statements 7 to 10, wherein B is selected from the group comprising unsubstituted or substituted with one or more Z ^a (for example one, two or three Z ^a ) phenyl, pyrazinyl, pyrazolo[1 ,5-a]pyridinyl; isoxazolyl; 6,8-dihydro-5H- imidazolo[2, 1 -c]1 ,4-oxazinyl; tetrahydropyranyl, thiophenyl, tetrahydrofuranyl, pyrimidinyl, furanyl, imidazo[1 ,2-a]pyridinyl; imidazolyl; quinoxalinyl, pyrazolyl; 1 ,3- dihydrobenzimidazolyl; isoquinolinyl; thiazolyl; indolyl; pyridazinyl; thiazolo[4,5-b]pyrazinyl; 1 H-imidazo[4,5-b]pyridinyl; 1 ,3-benzoxazolyl; 1 ,3-benzothiazolyl; and 4,5,6,7- tetrahydropyrazolo[1 ,5-a]pyrazinyl.

40. The compound according to any one of statements 1 -10, 14-29, 37-39; or a pharmaceutical composition according to any one of statements 7 to 1 0, wherein each Z ^a , is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; - S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; - NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H ; Ci _-6 alkyl; C ₃ . ₇ cycloalkyl; C ₂ - ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi. ₆ alkyl; C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl ; heterocycle-Ci. ₆ alkyl; heterocycle-C ₂ . ₆ alkenyl; heterocycle- C ₂ . ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl; or heterocycle- heteroC ₂ . ₆ alkynyl,

and wherein said Ci _-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle-alkyl, heterocycle- C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH NH ₂ ; or -NZ ⁴ Z ⁵ ;

preferably wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO- O-d-salkyl, -0-Ci _-6 alkyl, -NH-Ci _-6 alkyl, -N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-Ci _-6 alkyl. 41 . The compound according to any one of statements 1 -1 0, 14-29, 37-40; or a pharmaceutical composition according to any one of statements 7 to 10, wherein each Z ^b , is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; - S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; - NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H ; C^alkyl; C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi. ₆ alkyl; C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl ; heterocycle-Ci. ₆ alkyl; heterocycle-C ₂ - ₆ alkenyl; heterocycle- C ₂ - ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ - ₆ alkenyl; or heterocycle- heteroC ₂ . ₆ alkynyl, and wherein said C _{1 -6} alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl,

C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle- alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH NH ₂ ; or -NZ ⁴ Z ⁵ ;

preferably wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO- O-d-salkyl, -0-Ci _-6 alkyl, -NH-Ci _-6 alkyl, -N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-Ci _-6 alkyl. 42. The compound according to any one of statements 1 -1 0, 14-29, 37-41 ; or a pharmaceutical composition according to any one of statements 7 to 10, wherein each Z ^c , is independently selected from the group consisting of halogen; hydroxyl; sulfhydryl; -OZ ² ; =0; -SZ ² ; =S; - S(0)Z ² ; -S(0) ₂ Z ³ ; -S(0) ₂ NZ ⁴ Z ⁵ ; trifluoromethyl; trifluoromethoxy; nitro; -NZ ⁴ Z ⁵ ; -NZ ⁴ S(0) ₂ Z ² ; - NZ ⁴ C(0)Z ² ; -NZ ⁴ C(0)NZ ⁴ Z ⁵ ; cyano; -C(0)Z ³ ; -C(0)OZ ² ; -C(0)NZ ⁴ Z ⁵ ; -C(0)H ; Ci _-6 alkyl; C ₃ . ₇ cycloalkyl; C ₂ . ₆ alkenyl; C ₅ . ₇ cycloalkenyl; C ₂ . ₆ alkynyl; C ₅ . ₇ cycloalkynyl; heteroCi. ₆ alkyl; heteroC ₂ . ₆ alkenyl; heteroC ₂ . ₆ alkynyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi. ₆ alkyl;

C ₆ -i ₂ arylC ₂ . ₆ alkenyl; C ₆ -i ₂ arylC ₂ . ₆ alkynyl; C ₆ -i ₂ arylheteroCi. ₆ alkyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl; C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl ; heterocycle-Ci. ₆ alkyl; heterocycle-C ₂ . ₆ alkenyl; heterocycle- C ₂ . ₆ alkynyl; heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl; or heterocycle- heteroC ₂ . ₆ alkynyl, and wherein said C _{1 -6} alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₅ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylC ₂ . ₆ alkenyl, C ₆ -i ₂ arylC ₂ . ₆ alkynyl,

C ₆ -i ₂ arylheteroCi. ₆ alkyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkenyl, C ₆ -i ₂ arylheteroC ₂ . ₆ alkynyl, heterocycle- alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, or heterocycle-heteroC ₂ . ₆ alkynyl can be unsubstituted or substituted with one or more substituents selected from C _{1 -6} alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH NH ₂ ; or -NZ ⁴ Z ⁵ ;

preferably wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO- O-d-salkyl, -0-Ci _-6 alkyl, -NH-Ci _-6 alkyl, -N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-Ci _-6 alkyl. 43. The compound according to any one of statements 1 -1 0, 14-29, 37-42; or a pharmaceutical composition according to any one of statements 7 to 1 0, wherein, cycle A is selected from the group consisting of C ₃ . ₇ cycloalkyl; C ₅ . ₇ cycloalkenyl; C ₅ . ₇ cycloalkynyl; C ₆ -i ₂ aryl; and heterocycle; wherein said C ₃ . ₇ cycloalkyl, C ₅ . ₇ cycloalkenyl, C ₅ . ₇ cycloalkynyl, C ₆ -i ₂ aryl and heterocycle, can be unsubstituted or substituted with one or more substituents selected from Ci _-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ - ₆ alkenyl, C ₅ . ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₅ . ₇ cycloalkynyl, hetero Ci _-6 alkyl, hetero C ₂ - ₆ alkenyl, hetero C ₂ - ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, -NH ₂ , NH(Ci _-6 alkyl), or N(C ₁ _ ₆ alkyl) ₂ ; preferably wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO- O-d-salkyl, -0-Ci _-6 alkyl, -NH-Ci _-6 alkyl, -N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-Ci _-6 alkyl. The compound according to any one of statements 1 -10, 14-29, 37-43; or a pharmaceutical composition according to any one of statements 7 to 10, wherein cycle A is selected from

wherein the wavy line ( ·~>~ ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, - OCF ₃ , cyano, nitro, -C(0)OH, NH ₂ , NH(alkyl), or N(alkyl) ₂ ; preferably wherein said heteroCi- ₆ alkyl as a group or part of a group is selected from -CO-0-Ci- ₅ alkyl, -0-Ci- ₆ alkyl, -NH-C ₁ - ₆ alkyl, -N(C ₁ - ₆ alkyl) ₂ , -S(=0) ₂ C ₁ - ₆ alkyl, and -S-Ci _-6 alkyl.

45. The compound according to any one of statements 1 -10, 14-29, 37-43; or a pharmaceutical composition according to any one of statements 7 to 10, wherein cycle A is selected from the group comprising unsubstituted or substituted with one or more substituents (for example one, two or three substituents) phenyl; pyrazolyl; pyrimidinyl; pyridinyl; thiophenyl; isoxazolyl; benzothiazolyl; furanyl; 1 ,3-benzoxazolyl; pyrazinyl; 2,3-dihydrobenzo[b]furanyl; indolyl; cyclopropyl; cyclopentyl; cyclohexyl; piperidinyl; tetrahydropyranyl; wherein said substituent can be each independently selected from d- ₆ alkyl, C ₃ - ₇ cycloalkyl, C ₂ - ₆ alkenyl, C ₅ - ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₅ - ₇ cycloalkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, - C(0)OH, -NH ₂ , NH(alkyl), or N(alkyl) ₂ ; preferably wherein said heteroCi- ₆ alkyl as a group or part of a group is selected from -CO-0-Ci- ₅ alkyl, -0-Ci- ₆ alkyl, -NH-Ci- ₆ alkyl, -N(C ₁ - ₆ alkyl) ₂ , - S(=0) ₂ C ₁ - ₆ alkyl, and -S-Ci _-6 alkyl.

46. The compound according to any one of statements 1 -10, 14-29, 37-45; or a pharmaceutical composition according to any one of statements 7 to 10, wherein

- R is selected from C ₃ - ₇ cycloalkyl; C ₆ -i ₂ aryl; heterocycle; C ₆ -i ₂ arylCi- ₆ alkyl; heterocycle- Ci- ₆ alkyl; C ₆ -i ₂ arylheteroCi- ₆ alkyl; heterocycle-heteroCi- ₆ alkyl;

and wherein said C ₃ - ₇ cycloalkyl; C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi- ₆ alkyl, heterocycle- Ci- ₆ alkyl, C ₆ -i ₂ arylheteroCi- ₆ alkyl, heterocycle-heteroCi- ₆ alkyl, can be unsubstituted or substituted with one or more Z ^b ;

- each Z ^b is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, - OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, Ci _-6 alkyl, heteroCi _-6 alkyl, C ₆ - ₁₂ aryl, heterocycle, C ₆ -i ₂ arylCi- ₆ alkyl, C ₆ -i ₂ arylheteroCi- ₆ alkyl, heterocycle-Ci- ₆ alkyl, and heterocycle- heteroCi- ₆ alkyl, preferably each Z ^b is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , - S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , - NZ ⁴ C(=0) ₂ Z ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, Ci _-6 alkyl, heteroCi- ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably each Z ^b is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, C ₆ - ₁₂ aryl, heterocycle, and heterocycle-Ci. ₆ alkyl;

and wherein said C _{1 -6} alkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl, C ₆ -i ₂ arylheteroCi. ₆ alkyl, heterocycle-Ci. ₆ alkyl, and heterocycle-heteroCi. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, heteroCi _-6 alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, - C(0)OC ₁ _ ₆ alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, -S(0) ₂ Ci. 4alkyl, and -0-Ci _-6 alkyl; preferably said C _{1 -6} alkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, - C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C^alkyl, morpholinyl, - S(0) ₂ Ci- ₄ alkyl, and -0-Ci _-6 alkyl; more preferably said C _1-6 alkyl, C ₆ -i ₂ aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, - 0-C(0)Me, cyano, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-d. 4alkyl, morpholinyl, -S(0) ₂ Ci_ ₄ alkyl, and -0-Ci _-6 alkyl.

47. The compound according to any one of statements 1 -10, 14-29, 37-46; or a pharmaceutical composition according to any one of statements 7 to 10, wherein

- R is selected from C ₃ . ₇ cycloalkyl; C ₆ -i ₂ aryl; heterocycle; C ₆ _ ₁₂ arylCi_ ₆ alkyl; heterocycle- Ci- ₆ alkyl; C ₆ -i ₂ aryl-0-Ci. ₆ alkyl-; heterocycle-0-Ci. _s alkyl-;

and wherein said C ₃ . ₇ cycloalkyl; C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ arylCi. ₆ alkyl-, heterocycle- Ci- ₆ alkyl-, C ₆ -i ₂ aryl-0-Ci. ₆ alkyl-, heterocycle-0-Ci. _s alkyl-, can be unsubstituted or substituted with one or more Z ^b ;

- each Z ^b is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, - OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, C^alkyl, heteroCi _-6 alkyl, C ₆ _ ₁₂ aryl, heterocycle, C ₆ _ ₁₂ arylCi_ ₆ alkyl, C ₆ -i ₂ arylO-Ci. ₆ alkyl-, heterocycle-Ci. ₆ alkyl, and heterocycle-0-Ci_ ₆ alkyl-, preferably each Z ^b is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0) ₂ Z ² , - NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, Ci _-6 alkyl, heteroCi _-6 alkyl, C ₆ -i ₂ aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably each Z ^b is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, -S(=0) ₂ Z ³ , - S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, - C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, C ₆ - ₁₂ aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; and wherein said C _1-6 alkyl, heterod. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, C ₆ -i ₂ aryld- ₆ alkyl, C ₆ -i ₂ aryl- 0-Ci. ₆ alkyl-, heterocycle-Ci. ₆ alkyl, and heterocycle-0-Ci. ₆ alkyl-, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, heteroCi. ₆ alkyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)Od_ 6alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, -S(0) ₂ C ₁ _ ₄ alkyl, and -O- Ci_ ₆ alkyl; preferably said Ci_ ₆ alkyl, heteroCi. ₆ alkyl, C ₆ -i ₂ aryl, heterocycle, and heterocycle-Ci_ 6alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)Od_ 6alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-d_ ₄ alkyl, morpholinyl, -S(0) ₂ Ci _-4 alkyl, and -O- Ci_ ₆ alkyl; more preferably said Ci_ ₆ alkyl, C ₆ -i ₂ aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, - C(0)OH, -C(0)Od_ ₆ alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-d_ ₄ alkyl, morpholinyl, - S(0) ₂ C ₁ _ ₄ alkyl, and -0-d_ ₆ alkyl.

48. The compound according to any one of statements 1 -10, 14-29, 37-47; or a pharmaceutical composition according to any one of statements 7 to 10, wherein said heteroalkyi as a group or part of a group is selected from -CO-O-alkyl, -O-alkyl, -NH-alkyl, -N(alkyl) ₂ , -S(=0) ₂ alkyl, and -S-alkyl.

49. The compound according to any one of statements 1 -10, 14-29, 37-48; or a pharmaceutical composition according to any one of statements 7 to 10, wherein said heteroCi. ₆ alkyl as a group or part of a group is selected from -CO-0-Ci. ₅ alkyl, -0-Ci. ₆ alkyl, -NH-Ci. ₆ alkyl, - N(C ₁ _ ₆ alkyl) ₂ , -S(=0) ₂ C ₁ _ ₆ alkyl, and -S-d_ ₆ alkyl.

A particular embodiment of the invention is the provision of new compounds of formula

(B1 ), (B2), and (B3),

(B1 ) (B2) (B3)

wherein each of X ¹ , X ² , X ³ , X ⁴ , cycle A, cycle B, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁹ , W ¹ , p and q are as described herein for formula (A) and particular embodiments described herein;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

In another particular embodiment, the compounds have a structure according to formula

(A), wherein cycle C is selected from the following group of cycles

wherein each of cycle A, cycle B, R\ R ² , R ³ , R ⁴ , R ⁵ , R ⁹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ³² , R ^32a and R ³³ are as described for formula (A) and particular embodiments described herein;

and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

In still another particular embodiment, the compounds have a structure according to formula (A), wherein cycle C is selected from the following group of cycles

wherein each of cycle A, cycle B, R\ R ² , R ³ , R ⁴ , R ⁵ , R ⁹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ³² , R ^32a and R ³³ are as described for formula (A) and particular embodiments described herein; and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

In another embodiment, X ¹ is C.

In another particular embodiment, X ² is selected from CR ² ; NR ³ ; and N.

In a particular embodiment, R ² is selected from hydrogen; halogen; trifluoromethyl; cyano; alkyl and cycloalkyl. In a more particular embodiment, R ² is selected from hydrogen; halogen; trifluoromethyl; cyano; d- ₆ alkyl and C ₃ - ₇ cycloalkyl. In a more particular embodiment, R ² is selected from hydrogen; F; CI; trifluoromethyl; cyano; and Ci- ₃ alkyl.

In a particular embodiment, R ³ is selected from hydrogen; alkyl; and cycloalkyl. In a more particular embodiment, R ³ is selected from hydrogen; d- ₆ alkyl and C ₃ - ₇ cycloalkyl. In a more particular embodiment, R ³ is selected from hydrogen; and d- ₃ alkyl; more in particular hydrogen and methyl.

In another particular embodiment, X ³ is selected from CR ¹⁴ , NR ¹⁵ ; and N.

In a particular embodiment, R ⁴ is selected from hydrogen; halogen; trifluoromethyl; cyano; alkyl and cycloalkyl. In a more particular embodiment, R ⁴ is selected from hydrogen; halogen; trifluoromethyl; cyano; d- ₆ alkyl and C ₃ - ₇ cycloalkyl. In a more particular embodiment, R ⁴ is selected from hydrogen; F; CI; trifluoromethyl; cyano; and Ci- ₃ alkyl.

In a particular embodiment, R ⁵ is selected from hydrogen; alkyl; and cycloalkyl. In a more particular embodiment, R ⁵ is selected from hydrogen; d- ₆ alkyl and C ₃ - ₇ cycloalkyl. In a more particular embodiment, R ⁵ is selected from hydrogen; and Ci- ₃ alkyl; more in particular selected from hydrogen and methyl.

In another particular embodiment, X ⁴ is selected from CR ¹⁶ , NR ¹⁷ ; and N.

In a particular embodiment, R ⁶ is selected from hydrogen; halogen; trifluoromethyl; cyano; alkyl and cycloalkyl. In a more particular embodiment, R ⁶ is selected from hydrogen; halogen; trifluoromethyl; cyano; d- ₆ alkyl and C ₃ - ₇ cycloalkyl. In a more particular embodiment, R ⁶ is selected from hydrogen; F; CI; trifluoromethyl; cyano; and Ci- ₃ alkyl.

In a particular embodiment, R ⁷ is selected from hydrogen; alkyl; and cycloalkyl. In a more particular embodiment, R ⁷ is selected from hydrogen; d- ₆ alkyl and C ₃ - ₇ cycloalkyl. In a more particular embodiment, R ⁷ is selected from hydrogen; and C _1-3 alkyl; more in particular selected from hydrogen and methyl.

In a particular embodiment, R ³ is selected from hydrogen; alkyl; heteroalkyi; and =0. In a more particular embodiment, R ³ is selected from hydrogen and alkyl; more in particular from hydrogen and C _1-6 alkyl; yet more in particular from hydrogen and C _1-3 alkyl; yet more in particular from hydrogen and methyl. In a particular embodiment, R ³ is selected from hydrogen; C _1-4 alkyl; Ci _-4 alkoxycarbonyl; aminocarbonyl; Ci _-4 alkylaminocarbonyl; di(Ci _-4 alkyl)aminocarbonyl; or hydroxymethyl.

In a particular embodiment, each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl. In a more particular embodiment, each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; and alkyl. In a more particular embodiment, each R ⁴ and R ⁵ is independently selected from hydrogen; F; CI; and C _1-6 alkyl (more in particular

Ci _-3 alkyl, more in particular methyl). In a more particular embodiment, at least one of R ⁴ and R ⁵ is hydrogen. In a particular embodiment, each R ⁴ and R ⁵ is independently selected from hydrogen; halogen; C ₁ _ ₄ alkyl; C _1-4 alkoxy; cyano; hydroxy; C _{1 4} alkylthio; trifluoromethyl; amino;

Ci _-4 alkylamino; di(Ci _-4 alkyl)amino; carboxy; Ci _-4 alkoxycarbonyl; C _1-4 alkylsulfonyl; d.

₄ alkoxycarbonylamino; trifluoromethanesulfonyl; trifluoromethoxy; and hydroxyCi _-4 alkyl; provided that one of R ⁴ and R ⁵ is hydrogen.

In a particular embodiment, R ⁹ is selected from hydrogen; alkyl; heteroalkyi; and =0. In a more particular embodiment, R ⁹ is selected from hydrogen and alkyl; more in particular from hydrogen and C _1-6 alkyl; yet more in particular from hydrogen and C _1-3 alkyl; yet more in particular from hydrogen and methyl.

In a particular embodiment, W is selected from CR ³² R ^32a and NR ³³ . In another particular embodiment, W is selected from CHR ^32a and NR ³³ . In another particular embodiment, W is selected from CH ₂ and NH.

In a particular embodiment, each R ³² and R ^32a is independently selected from hydrogen; halogen; hydroxyl; sulfhydryl; trifluoromethyl; trifluoromethoxy; cyano; alkyl; alkenyl; alkynyl; heteroalkyi; heteroalkenyl; and heteroalkynyl. In a particular embodiment, it is provided that one of R ³² or R ^32a is hydrogen, except that both R ³² or R ^32a can be alkyl at the same time. In a more particular embodiment, each R ³² and R ^32a is independently selected from hydrogen; halogen; and alkyl. In a more particular embodiment, each R ³² and R ^32a is independently selected from hydrogen; F; CI; and C _1-6 alkyl (more in particular C _1-3 alkyl, more in particular methyl). In a more particular embodiment, at least one of R ³² and R ^32a is hydrogen.

In a particular embodiment, R ³³ is independently selected from hydrogen and alkyl. In a particular embodiment, R ³³ is independently selected from hydrogen and C _1-6 alkyl (more in particular C _1-3 alkyl, more in particular methyl).

In a particular embodiment, p and q are 1 .

In still another particular embodiment, the compounds have a structure according to ormula (C1 ), (C2), (C3), (C4), and (C5),

(C4) (C5)

wherein each of cycle A, cycle B, R , R ² , R ³ , R ⁹ , and R ⁵ , are as described for formula (A) and particular embodiments described herein; and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

In still another particular embodiment, the compounds have a structure according to formula (D1 ), (D2), (D3), (D4), and (D5),

(D4) (D5)

wherein each of cycle A, cycle B, R , R ² , R ³ , R ⁹ , and R ⁵ , are as described for formula (A) and particular embodiments described herein; and isomers (in particular stereo-isomers or tautomers), solvates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof.

In a particular embodiment, cycle A is selected from the group consisting of cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; and heterocycle; wherein said cycloalkyl, cycloalkenyl, cycloalkynyl, aryl and heterocycle, can be unsubstituted or substituted with one, two or three substituents (more in particular one or two substituents) selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH , NH ₂ , NH(alkyl), or N(alkyl) ₂ . In another particular embodiment, cycle A is selected from the group consisting of aryl; and heterocycle (more in particular heteroaryl); wherein said aryl and heterocycle (more in particular heteroaryl), can be unsubstituted or substituted with one, two or three substituents (more in particular one or two substituents) selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH , NH ₂ , NH(alkyl), or N(alkyl) ₂ . In another particular embodiment, cycle A is selected from aryl; and heterocycle selected from

wherein the wavy line ( ·~>~ ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, , NH ₂ , NH(alkyl), or N(alkyl) ₂ . In another particular embodiment, cycle A is selected from aryl; and heteroaryl selected from

wherein the wavy line ( ·~»~ ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, , NH ₂ , NH(alkyl), or N(alkyl) ₂ . In another particular embodiment, cycle A is selected from

wherein the wavy line (■™~ ) indicates the point of attachment to the atom of cycle C, and wherein the depicted cycles may be optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, , NH ₂ , NH(alkyl), or N(alkyl) ₂ . In yet another particular embodiment, cycle A is selected from phenyl optionally substituted with one, two, or three substituents selected from alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH, NH ₂ , NH(alkyl), or N(alkyl) ₂ . In yet another particular embodiment, cycle A is phenyl optionally substituted with one, two, or three substituents selected from alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, halogen, -SH, trifluoromethyl, -OCF ₃ , cyano, nitro, - C(0)OH, NH ₂ , NH(alkyl), or N(alkyl) ₂ . In yet another particular embodiment, cycle A is phenyl optionally substituted with one, two, or three substituents selected from alkyl, alkoxy, halogen, trifluoromethyl, -OCF ₃ , or cyano. In a particular embodiment, the cycles encompassed by cycle A are unsubstituted or substituted one, two or three substituents (more in particular one or two substituents) selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₃ . ₆ alkynyl, C ₃ . ₇ cycloalkynyl, d- ₆ heteroalkyl, C ₂ . ₆ heteroalkenyl, C ₃ . ₆ heteroalkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , cyano, nitro, -C(0)OH , NH ₂ , NH(alkyl), or N(alkyl) ₂ .

In another particular embodiment, cycle B is selected from unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ) phenyl; pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, furyl, thienyl, pyrrolyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridinimidazolyl, pyridinpyrolyl, pyrazolepyridinyl, benzpyrolyl, triazinyl, purinyl, quinoxalinyl, quinazolinyl, dihydroimidazooxazinyl and pteridinyl. In yet another particular embodiment, cycle B is selected from unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ) phenyl; and pyridyl. In another particular embodiment, cycle B is a heterocycle which can be unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ). In another particular embodiment, cycle B is selected from unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ) aryl and heteroaryl. In a more particular embodiment cycle B is a heteroaryl which can be unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ). In a yet more particular embodiment, cycle B is selected from unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ) pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, oxazolyl, imidazolyl, thiazolyl, isoxazolyl, pyrazolyl, isothiazolyl, furyl, thienyl, pyrrolyl, benzofuranyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridinimidazolyl, pyridinpyrolyl, pyrazolepyridinyl, benzpyrolyl, triazinyl, purinyl, quinoxalinyl, quinazolinyl, and pteridinyl. In a still more particular embodiment, cycle B is selected from unsubstituted or substituted with one or more Z ^a (in particular one, two or three Z ^a ) pyridyl, pyrazinyl, pyrimidyl, imidazolyl, isoxazolyl, pyrazolyl, furyl, thienyl, isoquinolinyl, benzimidazolyl, pyridinimidazolyl, benzopyrolyl, pyrazolepyridinyl and quinoxalinyl. In a particular embodiment, cycle B is not an unsubstituted phenyl.

In a particular embodiment, cycle B is selected from aryl and heterocycle, wherein said aryl and heterocycle are optionally substituted with one, two, or three Z ^a ; preferably cycle B is selected from

indicates the point of attachment to the carbon atom of the main formula (A), and wherein the depicted cycles may be optionally substituted with one, two, or three Z ^a .

In another embodiment, R ² is selected from hydrogen and unsubstituted or substituted with one or more Z ^c (in particular one or two Z ^c ) alkyl. In another particular embodiment, R ² is selected from hydrogen and alkyl (more in particular d- ₃ alkyl). In yet another particular embodiment, R ² is selected from hydrogen, methyl, ethyl, and propyl.

In another embodiment, R is selected from aryl; heterocycle; arylalkyi; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; heterocycle-heteroalkynyl; and wherein said aryl, heterocycle, arylalkyi, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl and heterocycle- heteroalkynyl can be unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ). In another embodiment, R is selected from aryl; heterocycle; W-aryl; and W- heterocycle; wherein said aryl, heterocycle, W-aryl, and W-heterocycle can be unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ); and wherein W is selected from Ci- ₃ alkyl, d- ₃ alkenyl, Ci. ₃ alkynyl, Ci _-3 heteroalkyl, Ci _-3 heteroalkenyl and Ci _-3 heteroalkynyl. In another particular embodiment, R is selected from aryl; heterocycle; W-aryl; and W-heterocycle; wherein said aryl, heterocycle, W-aryl, and W-heterocycle can be unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ); and wherein W is selected from C _1-3 alkyl. In yet another particular embodiment, R is selected from aryl; heterocycle; -CH ₂ -aryl; and -CH ₂ -heterocycle; wherein said aryl, heterocycle, -CH ₂ -aryl and -CH ₂ -heterocycle can be unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ). In another embodiment, R is selected from aryl; and heterocycle; wherein said aryl and heterocycle can be unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ). In yet a more particular embodiment, R is selected from phenyl and pyridyl, unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ). In still a more particular embodiment, R is selected from phenyl and , unsubstituted or substituted with one or more Z ^b (in particular one, two or three Z ^b ).

In a particular embodiment, each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , - NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , - C(=0)H, Ci- ₆ alkyl, C ₃ - ₇ cycloalkyl, C ₂ - ₆ alkenyl, C ₃ - ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₃ - ₇ cycloalkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, aryl, heterocycle, arylCi- ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ - ₆ alkynyl, arylheteroCi- ₆ alkyl, arylheteroC ₂ - ₆ alkenyl, arylheteroC ₂ - ₆ alkynyl, heterocycle-Ci- ₆ alkyl, heterocycle-C ₂ - ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, heterocycle-heterod- ₆ alkyl, heterocycle-heteroC ₂ - ₆ alkenyl, and heterocycle-heteroC ₂ - ₆ alkynyl; preferably each Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, sulfhydryl, -OZ ² , -0-C(=0)Z ³ , =0, -SZ ² , =S, -S(=0)Z ² , -S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, nitro, -NZ ⁴ Z ⁵ , -NZ ⁴ S(=0) ₂ Z ² , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0) ₂ Z ² , -NZ ⁴ C(=0)NZ ⁴ Z ⁵ , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , -C(=0)H, Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci- ₆ alkyl; more preferably each Z Z ^a , Z ^b , and Z ^c is independently selected from the group consisting of halogen, hydroxyl, -OZ ² , -0-C(=0)Z ³ , =0, - S(=0) ₂ Z ³ , -S(=0) ₂ NZ ⁴ Z ⁵ , trifluoromethyl, trifluoromethoxy, -NZ ⁴ Z ⁵ , -NZ ⁴ C(=0)Z ² , -NZ ⁴ C(=0)-OZ ² , cyano, -C(=0)Z ³ , -C(=0)OZ ² , -C(=0)NZ ⁴ Z ⁵ , Ci _-6 alkyl, heteroCi _-6 alkyl, aryl, heterocycle, and heterocycle-Ci- ₆ alkyl;

and wherein said Ci_ ₆ alkyl, C ₃ - ₇ cycloalkyl, C ₂ - ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₃ . ₇ cycloalkynyl, heteroCi- ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, aryl, heterocycle, aryld- ₆ alkyl, arylC ₂ - ₆ alkenyl, arylC ₂ - ₆ alkynyl, arylheteroCi- ₆ alkyl, arylheteroC ₂ - ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ - ₆ alkynyl, heterocycle- heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ - ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₃ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C ₁ _ ₄ alkyl, morpholinyl, - S(0) ₂ Ci_ ₄ alkyl, and -0-Ci _-6 alkyl; preferably said C _1-6 alkyl, heteroCi. ₆ alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -OCF ₃ , -0-C(0)Me, cyano, nitro, -C(0)OH, -C(0)OCi _-6 alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ ,

and -0-Ci- ₆ alkyl; more preferably said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, -0-C(0)Me, cyano, -C(0)OH, - C(0)OC ₁ _ ₆ alkyl, -NH ₂ , -NHCH ₃ ; -N(CH ₃ ) ₂ , -NH-C(=0)0-C^alkyl, morpholinyl, -S(0) ₂ C ₁ _ ₄ alkyl, and -0-Ci _-6 alkyl.

In a particular embodiment, each Z ² is independently selected from C _1-6 alkyl, C ₃ .

₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₃ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi- ₆ alkyl, arylheteroCi. ₆ alkenyl, arylheteroCi. ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ² is independently selected from Ci _-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl; more preferably Z ² is independently selected from C _1-6 alkyl, aryl, and heterocycle-Ci. ₆ alkyl;

wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₃ . 7cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi. 6alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . 6alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle- heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, - OCF ₃ , -S(=0) ₂ C ₁ _ ₄ alkyl, cyano, nitro, -C(=0)OH, -C(=0)0-C^alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; preferably said C _1-6 alkyl, aryl, heterocycle, and heterocycle-Ci. ₆ alkyl, are optionally substituted with one, two, or three substituents selected from hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, difluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , - S(=0) ₂ C ₁ _ ₄ alkyl, cyano, nitro, -C(=0)OH, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl; more preferably said C _1-6 alkyl, and aryl, are optionally substituted with one, two, or three substituents selected from hydroxyl, halogen, difluoromethyl, -0-Ci_ 6alkyl, -S(=0) ₂ C ₁ _ ₄ alkyl, -C(=0)OH, -C(=0)0-C^alkyl, -NH ₂ , -N(CH ₃ ) ₂ , pyrrolidinyl, piperidinyl, and piperazinyl.

In a particular embodiment, each Z ³ is independently selected from hydroxyl, C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₂ - ₆ alkynyl, C ₃ . ₇ cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ - ₆ alkenyl, heteroC ₂ - ₆ alkynyl, aryl, heterocycle, arylCi_ ₆ alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . ₆ alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle-heteroCi. ₆ alkyl, heterocycle- heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl; preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, aryl, and heterocycle; more preferably Z ³ is independently selected from hydroxyl, C _1-6 alkyl, and heterocycle;

wherein said C _1-6 alkyl, C ₃ . ₇ cycloalkyl, C ₂ . ₆ alkenyl, C ₃ . ₇ cycloalkenyl, C ₂ . ₆ alkynyl, C ₃ . 7cycloalkynyl, heteroCi. ₆ alkyl, heteroC ₂ . ₆ alkenyl, heteroC ₂ . ₆ alkynyl, aryl, heterocycle, arylCi. 6alkyl, arylC ₂ . ₆ alkenyl, arylC ₂ . ₆ alkynyl, arylheteroCi. ₆ alkyl, arylheteroC ₂ . ₆ alkenyl, arylheteroC ₂ . 6alkynyl, heterocycle-Ci. ₆ alkyl, heterocycle-C ₂ . ₆ alkenyl, heterocycle-C ₂ . ₆ alkynyl, heterocycle- heteroCi. ₆ alkyl, heterocycle-heteroC ₂ . ₆ alkenyl, and heterocycle-heteroC ₂ . ₆ alkynyl, are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl, C ₂ . ₆ alkenyl, C ₂ . ₆ alkynyl, hydroxyl, =0, halogen, -SH, =S, trifluoromethyl, -0-Ci _-6 alkyl, -OCF ₃ , cyano, nitro, -C(=0)OH, -NH ₂ , and -N(CH ₃ ) ₂ ; preferably said C _1-6 alkyl, aryl, and heterocycle are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl and -N(CH ₃ ) ₂ ; more preferably said C _1-6 alkyl and heterocycle are optionally substituted with one, two, or three substituents selected from C _1-6 alkyl and -N(CH ₃ ) ₂ .