Substituted bicyclic compounds, farmcampsite on their basis and method of inhibiting

 

The present invention relates to compounds of formula (I), where the single dotted line represents a double bond, a double dotted line represents a simple bond, n = 0, Q denotes formula (II), nl, n2 = 0-1, Q - R-substituted aryl or R-substituted heteroaryl, R1, R2denote H, alkyl, foralkyl, littoralis, alkenyl, or they together form =O group, R3denotes H, hydroxy, alkoxy, alkyl, halogen, arylalkyl, hydroxyalkyl, aryl, Het denotes a mono-, bi - or tricyclic heteroaromatic group, R8, R10, R11selected from the group comprising R1, OR1, R9denotes H, HE, alkoxy or halogen, represents -(CH2)3, -CH2-O-, -C(O)NR6, -NR6C(O)-, CIS-or TRANS -(CH2)n4CR12= CR12a(CH2)n5,X is-O-, NR6, Y mean = O, (N,N), (N,HE) (H). The above compounds possess antagonistic activity against thrombin receptor and can therefore be used as active substance in farbkomposition, and the way in which inhibition of thrombin receptors. 3 S. and 9 C.p. f-crystals, 4 PL.

Claims

1. The compound represented by structural formulaor its pharmaceutically acceptable salts, with the single dotted line represents an optional double bond; a double dotted line represents an optional simple bond; n is 0; Q means

where n1and n2independently mean 0-1, or when no double bond Q also denotes the R-substituted aryl or R-substituted heteroaryl;
R is from 1 to 3 substituents independently selected from the group including H, C1-C6alkyl, halogen, hydroxy, (C1-C6)alkoxy;
R1and R2independently selected from the group including H, C1-C6alkyl, fluorine(C1-C6)alkyl, debtor(C1-C6)alkyl, C2-C6alkenyl, or R1and R2together form = O group;
R3means H, hydroxy, Ci-C6alkoxy, -C(O)OR17Ci-C6alkyl, halogen, C2-C6alkenyl, aryl(Ci-C6)alkyl, aryl(C2-C6)alkenyl, hydroxy(Ci-C6)alkyl and aryl;
Het denotes a mono-, bi - or tricyclic heteroaromatic group scrappy, consisting of N, O and S, where the ring nitrogen atom may form an N-oxide or a Quaternary group with Ci-C4alkyl group, where the group Het is linked to via a ring carbon atom and where the group Het is substituted by 1-4 substituents, W, independently selected from the group comprising H, Ci-C6alkyl, fluorine(Ci-C6)alkyl, debtor(Ci-C6)alkyl, trifter(Ci-C6)alkyl, C3-C6cycloalkyl,3-C6alkenyl, R21aryl(Ci-C6)alkyl, R21aryl(C2-C6)alkenyl, heteroaryl(Ci-C6)alkyl, heteroaryl(Ci-C6)alkenyl, hydroxy(Ci-C6)alkyl, dihydroxy(Ci-C6)alkyl,
amino(Ci-C6)alkyl, (Ci-C6)alkylamino-(Ci-C6)alkyl, di-((Ci-C6)alkyl)-amino(Ci-C6)alkyl, thio(Ci-C6)alkyl, C2-C6alkoxy, C2-C6alkenylacyl-, halogen, -NR4R5, -CN, -OH, -COOR17, -COR16, -OSO2CF3, -CH2Och2CF3, (Ci-C6)alkylthio-, -C(O)NR4R5, -R6-phenyl, phenoxy-(Ci-C6)alkyl, -NHCOR16, -NHSO2R16, biphenyl, -OC(R6)2COOR7, -OC(R6)alkyl, amino, -OH, -COOR17, -NHCOOR17, -CONR4R5, aryl, aryl substituted by 1-3 substituents, independently selected from the group comprising halogen, -CF3Ci-C6alkyl, Ci-C6alkoxy - and-COOR17; aryl, where adjacent carbon atoms form a ring with methylendioxyphenyl, -C(O)NR4R5and heteroaryl; R21-aryl, aryl, where adjacent carbon atoms form a ring with methylendioxyphenyl, heteroaryl, heteroaryl, substituted by 1-4 substituents selected from the group comprising halogen;
R4and R5independently selected from the group including H, C1-C6alkyl, phenyl, benzyl and C3-C6cycloalkyl, or R4and R5together represent -(CH2)4-, -(CH2)5- or -(CH2)2NR7-(CH2)2- and form a ring with the nitrogen atom to which they relate;
R6independently selected from the group including H, C1-C6alkyl or phenyl;
R7means H or (Ci-C6)alkyl;
R8, R10and R11independently selected from the group comprising R1and-OR1provided that in the presence of optional double bonds10no, but amoxi-, halogen;
In means -(CH2)n3-, -CH2-O-, -C(O)NR6-, -NR6C(O)-,CIS - or TRANS -(CH2)n4CR12= CR12a(CH2)n5orwhere n3means 0 to 5, n4and n5independently 0 to 2, and R12and R12aindependently selected from the group including H, C1-C6alkyl and halogen;
X represents-O - or-NR6- if a double dotted line represents a simple bond, or X is-HE-or-other20if the link is missing;
Y represents = O, (H, H), (H, OH) or (H, C1-C6alkoxy), if a double dotted line represents a simple bond, or, if the connection is absent, Y mean = O, (H, H), (H, OH) or (H1-C6alkoxy);
R15is absent if a double dotted line represents a simple bond, and represents H, C1-C6alkyl or-NR18R19where R18and R19independently denote N or C1-C6alkyl if the bond is absent;
R16means1-C6lower alkyl, phenyl or benzyl;
R17independently selected from the group including H, C1-C6alkyl, phenyl or benzyl;
R20means N or is-CF3, -F3, halogen, -NR2With1-C6alkyl, C1-C6alkoxy, di-((Ci-C6)alkyl)amino, di-((Ci-C6)alkyl)-amino(Ci-C6)alkyl, hydroxy(Ci-C6)alkyl, -COOR17, -COR17, -NHCOR16and-NS2R16, N, CN, -SO2NH2, -SO2(Ci-C6)alkyl, aryl and-NHSO2CH2CF3;
Z denotes-CH2-, -C(O)-, -C(= NOR17or-C(R13R14)-, where R13and R14together with the carbon atom to which they are bound, form spiroheterocyclic group of 3-6 members, including 2 to 5 carbon atoms and 1 to 2 heteroatoms selected from O;
heteroaryl means adnakolava, bicyclic or connected with the benzene ring heteroaromatic group of 5 to 10 atoms, containing 2 to 9 carbon atoms and 1 to 2 heteroatoms, independently selected from the group N, O and S, provided that the rings do not include adjacent oxygen atoms and/or sulfur.

2. Connection on p. 1, where the double dotted line represents a simple bond, X is-O-, a Y mean = O.

3. Connection under item 1 or 2, where each of R2and R8means a hydrogen atom; R3means N or Ci-C6alkyl; R9means H, HE, or Ci-C6

6. The compound according to any one of paragraphs. 1-5, where R is H, fluorine, HE1-C6alkyl or C1-C6alkoxy.

7. The compound according to any one of paragraphs. 1-6, where means-CH= CH-.

8. The compound according to any one of paragraphs. 1-7, where Het means pyridyl, W-substituted pyridyl, chinolin or W-substituted chinosol.

9. Connection on p. 8, where W means1-C6alkyl, aryl, R21-aryl or heteroaryl.

10. Connection on p. 1, selected from the group including














11. Pharmaceutical composition having antagonistic activity against thrombin receptor, comprising an effective amount of the active substance and a pharmaceutically acceptable carrier, is of the thrombin receptor, involving the introduction of a mammal in need of such treatment an effective amount of the compounds on p. 1.

 

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