Substituted 3,4-dihydropyrido[1,2-a]pyrimidines

A compound of formula I

• 16
• in which
• R1 and R2 independently of each other is H;
• OR10;
• SH;
• SR10;
• C1-12 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, which is saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• heteroaryl, which is unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and is unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted;
• or (C1-6 alkyl)heteroaryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the heteroaryl is unsubstituted or mono- or polysubstituted,
• wherein if one of R1 and R2 is H and the other of R1 and R2 is not H, provided that, if one of R1 and R2 means aryl, the other of R1 and R2 means H or C1-12 alkyl,
• R3 and R4 independently of each other is H;
• C1-12 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, wherein the cycloalkyl is saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• heteroaryl, which is unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted;
• or (C1-6 alkyl)heteroaryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the heteroaryl is unsubstituted or mono- or polysubstituted,
• wherein at least one of R3 and R4 is H, or
• one of R1 or R2, together with one of R3 or R4, forms W,
• wherein W means α′-(CH2)n-β′ where n=3, 4, 5, 6, 7, 8, 9 or 10;
• α′-CH═CH—CH2-β′;
• α′-CH═CH—CH2—CH2-β′;
• α′-CH2—CH═CH—CH2-β′;
• α′-CH2—CH2—CH═CH—CH2—CH2-β′;
• α′-O—(CH2)n-β′ where n=2, 3, 4, 5 or 6;
• 17
• where X═CH2, O or S,
• 18
• and the end of W marked α′ is attached to the α carbon atom of the compound of the general formula I and the end of W marked β′ is attached to the β carbon atom of the compound of formula I,
• the other of R1 and R2 is H or C1-12 alkyl, wherein the alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the other of R3 and R4 is H or C1-12 alkyl, wherein the alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted,
• R5 is C1-12 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• heteroaryl, which is unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)heteroaryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the heteroaryl is unsubstituted or mono- or polysubstituted;
• C(═O)R11;
• CO2H;
• or CO2R12,
• R6, R7, R8 and R9 independently of each other is H, F, Cl, Br, I, CN, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NH((C1-6 alkyl)aryl), N((C1-6 alkyl)aryl)2, NHR13, NO2, OH, SH, O—C1-8 alkyl or S(O)p—C1-8 alkyl, wherein the alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and p is 0, 1 or 2;
• O-aryl or S(O)q-aryl, which is unsubstituted or mono- or polysubstituted, and q is 0, 1 or 2;
• O—(C1-6 alkyl)aryl or S(O)r—(C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, the aryl is unsubstituted or mono- or polysubstituted, and r is 0, 1 or 2;
• CO2H;
• C(═O)R14;
• C1-12 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• CF3;
• C3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• heterocyclyl, which is 3-, 4-, 5-, 6- or 7-membered, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• or heteroaryl, which is unsubstituted or mono- or polysubstituted;
• or R6 and R7 together form Q, wherein Q means γ′-CR15═CR16—CR17═CR18-δ′, the end of Q marked γ′ is attached to the γ carbon atom of the compound of formula I and the end of Q marked δ′ is attached to the δ carbon atom of the compound of formula I, and R8 and R9 are defined as above,
• or R6 and R9 together form T, wherein T means γ′-CR19═CR20—CR21═CR22-ε′ or γ′-N═CR20—CR21═N-ε′, the end of T marked γ′ is attached to the γ carbon atom of the compound of formula I and the end of T marked ε′ is attached to the ε carbon atom of the compound of formula I, and R7 and R8 are defined as above,
• or R8 and R9 together form U, wherein U means η′-CR19═CR20—CR21═CR22-ε′, the end of U marked η′ is attached to the η carbon atom of the compound of formula I and the end of U marked ε′ is attached to the ε carbon atom of the compound of formula I, and R6 and R7 are defined as above,
• R10 is C1-8 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• heteroaryl, which is unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted;
• or (C1-6 alkyl)heteroaryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the heteroaryl is unsubstituted or mono- or polysubstituted,
• R11 means NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NH((C1-6 alkyl)aryl), N((C1-6 alkyl)aryl)2, C1-8 alkyl, wherein the alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• heteroaryl, which is unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted;
• or (C1-6 alkyl)heteroaryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the heteroaryl is unsubstituted or mono- or polysubstituted;
• R12 means C1-8 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted,
• R13 means C(═O)CH3, C(═O)phenyl, C(═O)O-t.-butyl (t-BOC),
• R14 means H, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NH((C1-6 alkyl)aryl), N((C1-6 alkyl)aryl)2, C1-8 alkyl, wherein the alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• C3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• or (C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted;
• OC1-8 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• OC3-8 cycloalkyl, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
• aryl, which is unsubstituted or mono- or polysubstituted;
• or O—(C1-6 alkyl)aryl, wherein the C1-6 alkyl is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted, and the aryl is unsubstituted or mono- or polysubstituted,
• R15, R16, R17 and R18 mutually independently mean H, F, Cl, Br, I, OH, CN;
• C1-8 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• CO2H, and
• R19, R20, R21 and R22 mutually independently mean H, F, Cl, Br, I, CN, OH, C1-8 alkyl, which is linear or branched, saturated or unsaturated, and unsubstituted or mono- or polysubstituted;
• or CO2H,
• or a pharmaceutically acceptable salt thereof,
• provided that the following compounds are excluded:
• 6-chloro-2-(4-nitrophenyl)-4-phenyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 2-(4-nitrophenyl)-4-phenyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 2-(2-nitrophenyl)-4-phenyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 2-(4-nitrophenyl)-4-(4-tolyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 2-(4-chlorophenyl)-4-(4-tolyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 4-ethoxy-2-phenyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 4-ethoxy-2-(2-hydroxyphenyl)-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,
• 4-ethoxy-2-propyl-3,4-dihydro-2H-pyrido[1,2-a]pyrimidine,1
• 4-propyl-2,3,3a,4,5,10a-hexahydro-2H-pyrido[1,2-a]furo[3,2-e]pyrimidine, and
• 4-propyl-2,4,4a,5,6,11 a-hexahydro-2H-pyrido[1,2-a]pyrano[3,2-e]pyrimidine.