AR048691A1 - COMPOUNDS WITH ALQUINO STRUCTURE WITH MCH ANTAGONIST ACTION AND MEDICINES CONTAINING THESE COMPOUNDS - Google Patents

COMPOUNDS WITH ALQUINO STRUCTURE WITH MCH ANTAGONIST ACTION AND MEDICINES CONTAINING THESE COMPOUNDS

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AR048691A1
AR048691A1 ARP050101439A ARP050101439A AR048691A1 AR 048691 A1 AR048691 A1 AR 048691A1 AR P050101439 A ARP050101439 A AR P050101439A AR P050101439 A ARP050101439 A AR P050101439A AR 048691 A1 AR048691 A1 AR 048691A1
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Argentina
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alkyl
group
cycloalkyl
phenyl
atoms
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ARP050101439A
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Spanish (es)
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Dirk Stenkamp
Stephan Georg Mueller
Philipp Lustenberger
Gerald Juergen Roth
Klaus Rudolf
Marcus Schindler
Leo Thomas
Ralf Lotz
Thorsten Lehmann-Lintz
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Boehringer Ingelheim Int
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Application filed by Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of AR048691A1 publication Critical patent/AR048691A1/en

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Abstract

La presente se refiere a compuestos con estructura de alquino de formula general (1), en la que: R1, R2 significan, de modo independiente entre sí, H, alquilo C1-8, cicloalquilo C3-7 o un radical fenilo o piridinilo opcionalmente mono- o polisustituido con radicales R20 iguales o diferentes y/o monosustituido con nitro, donde el grupo alquilo o cicloalquilo puede estar mono- o polisustituido con radicales R11 iguales o diferentes, y donde un grupo -CH2- puede estar reemplazado en la posicion 3 o 4 de un grupo cicloalquilo de 5, 6 o 7 miembros con -O-, -S- o -NR13-; o R1 y R2 forman un puente alquileno C3-8, donde un grupo -CH2- no adyacente al átomo de N del grupo R1R2N puede estar reemplazado por -CH=N-, -CH=CH-, -O-, -S-, - SO, -(SO2)-, -CO-, -C(=CH2)- o -NR13-, donde en el puente alquileno C3-8 antes definido uno o varios átomos de H pueden estar reemplazados por radicales R14 iguales o diferentes, y donde el puente de alquileno antes definido puede estar reemplazados por uno o varios grupos carbocíclicos o heterocíclicos Cy iguales o diferentes de modo tal que el enlace entre el grupo alquileno y el grupo Cy se produzca: a través de un enlace simple o doble; a través de un átomo de C comun, formándose un sistema de anillos espirocíclicos; a través de dos átomos de C y/o N comunes adyacentes, formándose un sistema de anillos bicíclicos condensados; o a través de tres o más átomos de C y/o N, formándose un sistema de anillos en puente; X significa un puente alquileno C1-6 que presenta uno o varios sustituyentes de modo independiente entre sí, seleccionados de fluor, cloro, hidroxi, ciano, CF3, alquilo C1-4, hidroxi-alquilo C1-4, cicloalquilo C3-6 y alcoxi C1-4, donde dos sustituyentes alquilo pueden estar unidos entre sí, formando un grupo cicloalquilo C3-7; o un grupo alquilenoxi C2-4 o alquilenimino C2-4, donde el grupo imino puede estar sustituido con un grupo alquilo C1-4, y donde la unidad de alquileno presenta uno o varios sustituyentes de modo independiente entre sí, seleccionados de fluor, cloro, CF3, hidroxi-alquilo C1-4, alquilo C1-4 y cicloalquilo C3-6, donde dos grupos alquilo pueden estar unidos entre sí, formando un grupo cicloalquilo C3-7 o cicloalquilenimino C4-6; o un puente alquenileno C3-6 o alquinileno C3-6, que es no sustituido o que presenta uno o varios sustituyentes seleccionados, de modo independiente entre sí, de fluor, CF3, hidroxi-alquilo C1-4, alquilo C1-4 y cicloalquilo C3-6, donde dos sustituyentes alquilo pueden estar unidos entre sí, formando un grupo cicloalquilo C3-7 o cicloalquenilo C5-7; y W, Z significan, de modo independiente entre sí, un enlace simple o un puente alquileno C1-2; donde dos átomos de C adyacentes con un puente adicional alquileno C1-4, pueden estar unidos entre sí; y donde uno o dos átomos de C pueden estar sustituidos, de modo independiente entre sí, con uno o dos radicales alquilo C1-3 iguales o diferentes, donde dos radicales alquilo pueden estar unidos entre sí formando un anillo carbocíclico; e Y, A se seleccionan, de modo independiente entre sí, del grupo compuesto por los grupos cíclicos bivalentes fenilo, piridinilo, pirimidinilo, pirazinilo, piridazinilo, naftilo, tetrahidronaftilo, indolilo, dihidroindolilo, quinolinilo, dihidroquinolinilo, tetrahidroquinolinilo, isoquinolinilo, dihidroisoquinolinilo, tetrahidro-isoquinolinilo, benzimidazolilo, benzoxazolilo, cromanilo, cromen-4-onilo, tienilo, furanilo, benzotienilo o benzofuranilo, donde los grupos cíclicos mencionados pueden estar mono- o polisustituidos en uno o varios átomos de C con radicales R20 igual o diferentes, en el caso de un anillo fenilo también monosustituido con nitro, y/o en uno o varios grupos NH con R21; B presenta uno de los significados indicados para Y, A o alquilo C1-6, alquenilo C1-6, alquinoilo C1-6, cicloalquilo C3-7, cicloalquenilo C5-7, cicloalquil C3-7-alquilo C1-3, cicloalquenil C3-7-alquilo C1-3, cicloalquil C3-7-alquenilo C1-3- o cicloalquil C3-7-alquinilo C1-3, donde uno o varios átomos de C de modo independiente entre sí, mono o polisustituidos con halogeno y/o monosustituidos con hidroxi o ciano y/o grupos cíclicos mono- o polisustituidos con radicales R20 iguales o diferentes; Cy es un grupo carbocíclico o heterocíclico seleccionado de uno de los siguientes significados: un grupo carbocíclico saturado de 3 a 7 miembros; un grupo carbocíclico insaturado de 4 a 7 miembros; un grupo fenilo; un grupo heterocíclico saturado de 4 a 7 miembros o insaturado de 5 a 7 miembros con un átomo de N, O o S como heteroátomo; un grupo heterocíclico saturado o insaturado de 5 a 7 miembros con dos o más átomos de N o con uno o dos átomos de N y un átomo de O o S como heteroátomos; un grupo heterocíclico aromático de 5 o 6 miembros con uno o varios heteroátomos iguales o diferentes seleccionados de N, O y/o S; donde los grupos saturados de 6 o 7 miembros antes descritos también pueden estar presentes como sistemas cíclicos en puente con un puente imino, (alquil C1-4)-imino, metileno, (alquil C1-4)-metileno o di-(alquil C1-4)-metileno; y donde los grupos cíclicos antes mencionados mono- o polisustituidos en uno o varios átomos de C pueden estar sustituidos con radicales R20 iguales o diferentes, en el caso de un grupo fenilo también adicionalmente monosustituidos con nitro, y/o uno o varios grupos NH sustituidos con R21; R11 significa halogeno, alquilo C1-6, alquenilo C2-6, alquinoilo C2- 6, R15-O, R15-O-CO-, R15-CO-O-, ciano, R16R17N-, R18R19N-CO- o Cy-, donde en los grupos antes indicados uno o varios átomos de C pueden estar mono- o polisustituidos, de modo independiente entre sí, por sustituyentes seleccionados de halogeno, OH, CN, CF3, alquilo C1-3, hidroxi-alquilo C1-3; R13 tiene uno de los significados indicados para R17; R14 es halogeno, ciano, alquilo C1-6, alquenilo C2-6, alquinoilo C2-6, R15-O-, R15-O-CO-, R15-CO-, R15-CO-O-, R16R17N-, R18R19N-CO-, R15-O-alquilo C1- 3, R15-O-CO-alquilo C1-3, R15-SO2-NH-, R15-O-CO-NH-alquilo C1-3, R15-SO2-NH-alquilo C1-3, R15-CO-alquilo C1-3, R15-CO-O-alquilo C1-3, R16R17N-alquilo C1-3, R18R19N-CO-alquilo C1-3 o Cy-alquilo C1-3; R15 es H, alquilo C1-4, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-3, fenilo, fenil-alquilo C1-3, piridinilo o piridinil-alquilo C1-3; R16 es H, alquilo C1-6, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-3, cicloalquenilo C4-7, cicloalquenil C4-7-alquilo C1-3, w-hidroxi-alquilo C2-3, w- (alcoxi C1-4)-alquilo C2-3, amino-alquilo C2-6, alquil C1-4-amino-alquilo C2-6, di-(alquil C1-4)-amino-alquilo C2-6 o ciclo-alquilenimino C3-6-alquilo C2-6; R17 tiene uno de los significados indicados para R16 o es fenilo, fenil-alquilo C1-3, piridinilo, alquil C1-4-carbonilo, hidroxicarbonil-alquilo C1-3, alcoxicarbonilo C1-4, alcoxicarbonil C1-4-alquilo C1-3, alquilcarbonilamino C1-4-alquilo C2-3, N-(alquilcarbonil C1-4)-N-(alquil C1-4)-amino-alquilo C2-3, alquilsulfonilo C1-4, alquilsulfonilamino C1-4-alquilo C2-3 o N-(alquilosulfonil C1-4)-N-(alquil C1-4)-amino-alquilo C2-3; R18, R19 son, de modo independiente entre sí, H o alquilo C1-6; R20 es halogeno, hidroxi, ciano, alquilo C1-6, alquenilo C2-6, alquinoilo C2-6, cicloalquilo C3-7, cicloalquil C3-7-alquilo C1-3, hidroxi-alquilo C1-3, R22-alquilo C1-3 o uno de los significados indicados para R22; R21 es alquilo C1-4, w-hidroxi-alquilo C2-6, w-alcoxi C1-4-alquilo C2-6, w-alquil C1-4-amino-alquilo C2-6, w-di- (alquil C1-4)-amino-alquilo C2-6, w-ciclo-alquilenimino C3-6-alquilo C2-6, fenilo, fenil-alquilo C1-3, alquil C1-4-carbonilo, alcoxi C1-4-carbonilo, alquilsulfonilo C1-4, aminosulfonilo, alquilaminosulfonilo C1-4, di-alquilaminosulfonilo C1-4 o ciclo-alquilen C3-6-imino-sulfonilo; R22 es piridinilo, fenilo, fenil-alcoxi C1-3, cicloalquilenimino C3-6-alcoxi C2-4, OHC-, HO-N=HC-, alcoxi C1-4-N=HC-, alcoxi C1-4, alquiltio C1-4, carboxi, alquilcarbonilo C1-4, alcoxicarbonilo C1-4, aminocarbonilo, alquilaminocarbonilo C1-4, di-(alquil C1-4)-aminocarbonilo, cicloalquil C3-6-amino-carbonilo, cicloalquilenimino C3-6-carbonilo, fenilaminocarbonilo, cicloalquilenimino C3-6-alquil C2-4-aminocarbonilo, alquilsulfonilo C1-4, alquilsulfinilo C1-4, alquilsulfonilamino C1-4, amino, alquilamino C1-4, di-(alquil C1-4)-amino, alquil C1-4-carbonil-amino, cicloalquilenimino C3-6, fenil-alquilamino C1-3, N-(alquil C1-4)-fenil-alquilamino C1-3, acetilamino, propionilamino, fenilcarbonilo, fenilcarbonilamino, fenilcarbonilmetilamino, hidroxi-alquilaminocarbonilo C2-3, (4-morfolinil)carbonilo, (1-pirrolidinil)carbo-nilo, (1-piperidinil)carbonilo, (hexahidro-1-azepinil)carbonilo, (4-metil-1-piperazinil)carbonilo, metilendioxi, aminocarbonilamino o alquilaminocarbonilamino C1-4; donde en los grupos y radicales antes mencionados, en especial en W, Z, R13 a R22, uno o varios átomos de C adicionalmente mono o polisustituidos con F y/o uno o dos átomos de C, de modo independiente entre sí, adicionalmente monosustituidos con Cl o Br y/o uno o varios anillos fenilo, de mono independiente entre sí, presentan adicionalmente uno, dos o tres sustituyentes seleccionados del grupo F, Cl, Br, I, ciano, alquilo C1- 4, alcoxi C1-4-, difluorometilo, trifluorometilo, hidroxi, amino, alquilamino C1-3, di-(alquil C1-3)-amino, acetilamino, aminocarbonilo, difluorometoxi, trifluorometoxi, amino-alquilo C1-3, alquilamino C1-3-alquilo C1-3 y di-(alquil C1-3)-amino- alquilo C1-3 y/o pueden estar monosustituido con nitro; y el átomo de H de un grupo carboxi existente o un átomo de H unido a un átomo de N puede estar reemplazado por un radical escindible in vivo, sus tautomeros, sus diasteroisomeros, sus enantiomeros, sus mezclas y sus sales; donde los siguientes compuestos no están comprendidos: (1-{5-[5-(4-cloro-fenil)-piridin-2-iletinil]-piridin-2-il}-pirrolidin-3-il)-dimetil-amina; 5'-[5-(4-cloro-fenil)-piridin-2-iletinil]-3-pirrolidin-1-il- 3,4,5,6-tetrahidro-2H-[1,2']bipiridinilo; 1'-{5-[5-(4-cloro-fenil)-piridin-2-iletinil]-piridin-2-il-}-[1,3']bipirrolidinilo; {5-[5-(4-cloro-fenil)-piridin-2-iletinil]-piridThis refers to compounds with an alkyne structure of general formula (1), in which: R1, R2 independently mean each other, H, C1-8 alkyl, C3-7 cycloalkyl or an optionally phenyl or pyridinyl radical mono- or polysubstituted with the same or different R20 radicals and / or monosubstituted with nitro, where the alkyl or cycloalkyl group may be mono- or polysubstituted with the same or different R11 radicals, and where a -CH2- group may be replaced at position 3 or 4 of a cycloalkyl group of 5, 6 or 7 members with -O-, -S- or -NR13-; or R1 and R2 form a C3-8 alkylene bridge, where a group -CH2- not adjacent to the N atom of the group R1R2N can be replaced by -CH = N-, -CH = CH-, -O-, -S- , - SO, - (SO2) -, -CO-, -C (= CH2) - or -NR13-, where in the C3-8 alkylene bridge defined above one or more atoms of H can be replaced by radicals R14 equal or different, and where the alkylene bridge defined above may be replaced by one or more cyclic or heterocyclic groups Cy the same or different such that the bond between the alkylene group and the group Cy occurs: through a single or double bond ; through a common C atom, forming a spirocyclic ring system; through two adjacent common C and / or N atoms, forming a system of condensed bicyclic rings; or through three or more atoms of C and / or N, forming a bridge ring system; X means a C1-6 alkylene bridge having one or more substituents independently of one another, selected from fluorine, chlorine, hydroxy, cyano, CF3, C1-4 alkyl, hydroxy C1-4 alkyl, C3-6 cycloalkyl and alkoxy C1-4, where two alkyl substituents can be linked together, forming a C3-7 cycloalkyl group; or a C2-4 alkyleneoxy or C2-4 alkyleneimino group, where the imino group may be substituted with a C1-4 alkyl group, and where the alkylene unit has one or more substituents independently from each other, selected from fluorine, chlorine , CF3, hydroxyC 1-4 alkyl, C 1-4 alkyl and C 3-6 cycloalkyl, where two alkyl groups may be linked together, forming a C 3-7 cycloalkyl or C 4-6 cycloalkylimino group; or a C3-6 alkenylene or C3-6 alkynylene bridge, which is unsubstituted or having one or more substituents selected, independently from each other, from fluorine, CF3, hydroxyC 1-4 alkyl, C 1-4 alkyl and cycloalkyl C3-6, where two alkyl substituents can be linked together, forming a C3-7 cycloalkyl or C5-7 cycloalkenyl group; and W, Z mean, independently of each other, a single bond or a C1-2 alkylene bridge; where two adjacent C atoms with an additional C1-4 alkylene bridge can be linked together; and where one or two C atoms can be substituted, independently of one another, with one or two identical or different C1-3 alkyl radicals, where two alkyl radicals can be linked together forming a carbocyclic ring; and Y, A are selected independently of each other, from the group consisting of the bivalent cyclic groups phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, naphthyl, tetrahydronaphthyl, indolyl, dihydroindolyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl, tetrahydro -isoquinolinyl, benzimidazolyl, benzoxazolyl, chromanyl, chromen-4-onyl, thienyl, furanyl, benzothienyl or benzofuranyl, where the aforementioned cyclic groups may be mono- or polysubstituted in one or more C atoms with the same or different R20 radicals, in the case of a phenyl ring also monosubstituted with nitro, and / or in one or more NH groups with R21; B has one of the meanings indicated for Y, A or C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, C3-7 cycloalkyl, C5-7 cycloalkenyl, C3-7 cycloalkyl-C1-3 alkyl, C3- cycloalkenyl 7-C1-3 alkyl, C3-7 cycloalkyl C1-3- or C3-7 cycloalkyl-C1-3 alkynyl, where one or more C atoms independently of one another, mono or polysubstituted with halogen and / or monosubstituted with hydroxy or cyano and / or mono- or polysubstituted cyclic groups with the same or different R20 radicals; Cy is a carbocyclic or heterocyclic group selected from one of the following meanings: a saturated carbocyclic group of 3 to 7 members; an unsaturated carbocyclic group of 4 to 7 members; a phenyl group; a saturated heterocyclic group of 4 to 7 members or unsaturated of 5 to 7 members with an atom of N, O or S as a heteroatom; a saturated or unsaturated 5- to 7-membered heterocyclic group with two or more N atoms or with one or two N atoms and an O or S atom as heteroatoms; a 5- or 6-membered aromatic heterocyclic group with one or more same or different heteroatoms selected from N, O and / or S; where the 6 or 7-member saturated groups described above may also be present as cyclic bridging systems with an imino bridge, (C1-4 alkyl) -imino, methylene, (C1-4 alkyl) -methylene or di- (C1 alkyl -4) -methylene; and where the above-mentioned cyclic groups mono- or polysubstituted in one or more C atoms may be substituted with the same or different R20 radicals, in the case of a phenyl group also additionally monosubstituted with nitro, and / or one or more NH groups substituted with R21; R11 means halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, R15-O, R15-O-CO-, R15-CO-O-, cyano, R16R17N-, R18R19N-CO- or Cy-, where in the above-mentioned groups one or more C atoms may be mono- or polysubstituted, independently from each other, by substituents selected from halogen, OH, CN, CF3, C1-3 alkyl, hydroxy-C1-3 alkyl; R13 has one of the meanings indicated for R17; R14 is halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, R15-O-, R15-O-CO-, R15-CO-, R15-CO-O-, R16R17N-, R18R19N- CO-, R15-O-C1-3 alkyl, R15-O-CO-C1-3 alkyl, R15-SO2-NH-, R15-O-CO-NH-C1-3 alkyl, R15-SO2-NH-alkyl C1-3, R15-CO-C1-3 alkyl, R15-CO-O-C1-3 alkyl, R16R17N-C1-3 alkyl, R18R19N-CO-C1-3 alkyl or Cy-C1-3 alkyl; R15 is H, C1-4 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkyl, phenyl, phenyl-C1-3 alkyl, pyridinyl or pyridinyl-C1-3 alkyl; R16 is H, C1-6 alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkyl, C4-7 cycloalkenyl, C4-7 cycloalkenyl-C1-3 alkyl, w-hydroxy-C2-3 alkyl, w- (C1-4 alkoxy) -C2-3 alkyl, amino C2-6 alkyl, C1-4 alkyl-C2-6 alkyl, di- (C1-4 alkyl) -amino-C2-6 alkyl or cyclo-alkyleneimino C3-6-C2-6 alkyl; R17 has one of the meanings indicated for R16 or is phenyl, phenyl-C 1-3 alkyl, pyridinyl, C 1-4 alkylcarbonyl, hydroxycarbonylC 1-3 alkyl, C 1-4 alkoxycarbonyl, C 1-4 alkoxycarbonyl , C1-4 alkylcarbonylamino-C2-3 alkyl, N- (C1-4 alkylcarbonyl) -N- (C1-4 alkyl) -amino-C2-3 alkyl, C1-4 alkylsulfonyl, C1-4 alkylsulfonylamino-C2-3 alkyl or N- (C1-4 alkylsulfonyl) -N- (C1-4 alkyl) -amino-C2-3 alkyl; R18, R19 are, independently of each other, H or C1-6 alkyl; R20 is halogen, hydroxy, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-3 alkyl, hydroxy-C1-3 alkyl, R22-C1-alkyl 3 or one of the meanings indicated for R22; R21 is C1-4 alkyl, w-hydroxyC2-6 alkyl, w-C1-4 alkoxy-C2-6 alkyl, w-C1-4 alkyl-C2-6 alkyl, w-di- (C1- alkyl 4) -amino-C2-6 alkyl, w-cyclo-C3-6 alkyleneimino-C2-6 alkyl, phenyl, phenyl-C1-3 alkyl, C1-4 alkylcarbonyl, C1-4 alkoxycarbonyl, C1-alkylsulfonyl 4, aminosulfonyl, C 1-4 alkylaminosulfonyl, C 1-4 di-alkylaminosulfonyl or C 3-6 cyclo-alkylene sulfonyl; R22 is pyridinyl, phenyl, C1-3 phenyl-alkoxy, C3-6 cycloalkyliminoC2-4, OHC-, HO-N = HC-, C1-4-N-alkoxy = HC-, C1-4 alkoxy, C1-alkylthio -4, carboxy, C1-4 alkylcarbonyl, C1-4 alkoxycarbonyl, aminocarbonyl, C1-4 alkylaminocarbonyl, di- (C1-4 alkyl) -aminocarbonyl, C3-6-amino-carbonyl cycloalkyl, C3-6-cycloalkyliminocarbonyl, phenylaminocarbonyl , C3-6 cycloalkylimino-C2-4-alkylcarbonyl, C1-4 alkylsulfonyl, C1-4 alkylsulfinyl, C1-4 alkylsulfonylamino, amino, C1-4 alkylamino, di- (C1-4 alkyl) -amino, C1-4 alkyl -carbonyl-amino, C3-6 cycloalkyleneimino, phenyl-C1-3alkylamino, N- (C1-4alkyl) -phenyl-C1-3alkylamino, acetylamino, propionylamino, phenylcarbonyl, phenylcarbonylamino, phenylcarbonylmethylamino, hydroxy-C2-3 alkylaminocarbonyl, (4-morpholinyl) carbonyl, (1-pyrrolidinyl) carbo-nyl, (1-piperidinyl) carbonyl, (hexahydro-1-azepinyl) carbonyl, (4-methyl-1-piperazinyl) carbonyl, methylenedioxy, aminocarbonylamino or C1-alkylaminocarbonylamino 4; where in the aforementioned groups and radicals, especially in W, Z, R13 to R22, one or more C atoms additionally mono or polysubstituted with F and / or one or two C atoms, independently of each other, additionally monosubstituted with Cl or Br and / or one or several phenyl rings, of mono independent from each other, additionally have one, two or three substituents selected from the group F, Cl, Br, I, cyano, C1-4 alkyl, C1-4 alkoxy , difluoromethyl, trifluoromethyl, hydroxy, amino, C1-3 alkylamino, di- (C1-3 alkyl) -amino, acetylamino, aminocarbonyl, difluoromethoxy, trifluoromethoxy, amino C1-3 alkyl, C1-3 alkylamino-C1-3 alkyl and di- (C1-3 alkyl) -amino-C1-3 alkyl and / or may be monosubstituted with nitro; and the H atom of an existing carboxy group or an H atom attached to an N atom can be replaced by an in vivo cleavable radical, its tautomers, its diasteroisomers, its enantiomers, mixtures and salts thereof; wherein the following compounds are not included: (1- {5- [5- (4-Chloro-phenyl) -pyridin-2-iletinyl] -pyridin-2-yl} -pyrrolidin-3-yl) -dimethyl-amine; 5 '- [5- (4-Chloro-phenyl) -pyridin-2-iletinyl] -3-pyrrolidin-1-yl-3,4,5,6-tetrahydro-2H- [1,2'] bipyridinyl; 1 '- {5- [5- (4-chloro-phenyl) -pyridin-2-yletinyl] -pyridin-2-yl -} - [1,3'] bipyrrolidinyl; {5- [5- (4-Chloro-phenyl) -pyridin-2-iletinyl] -pyrid

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