Cycloalkyl Derivatives, compositions containing same and Use thereof for the manufacture of medicaments for inhibiting or antagonizing selectively alfav Beta 3 Integrin beta5 and / or alfav

摘要

Cyclopentane derivatives, including a formula compound (1) or pharmaceutically acceptable formula salt, wherein a ring is a single ring with 4-8 members or a double ring with 7-12 members; the ring may be saturated or unsaturated, This ring can be replaced by one or more selected substitutes, including asphalt, halogen tar, arilo, heteromorph, halogen, ALCOXY, amino, hydroxy, nitro, alcoxi, hydroxy, quinine sulfide, Amin, taxi, arilamino, alkylsulfonamide, acid salt, aminoacyl ammonia, ester, aminomethyl ester, aminoacyl ammonia, aminomethyl ester, aminomethyl ester, alkylmethyl ester, sulfite, allyl ester, allyl ester. Alquenilo, methyldioxy, ethyldioxy, tar, carboxamida,Ciano Y - (CH2) NCO, n is 0-2, R is hydroxi, alcoxi, hydrocarbyl or amine; A1 is a heterocycle consisting of 5-9 members or 7-14 formula members (2), which contains at least one nitrogen atom and 1-4 heteroatoms or groups selected from O, N, s.so2 or Co; optional a. Saturated or unsaturated; or, it can be replaced by one or more rk selected from the group with R as hydroxyl, alcox, hydrocarbon, hydrogen sulfide, halide, cyanogen, aminobenzene, rental Mino, halogenated, amino, amide, sulfamide and cor;Further (2) includes the following heterocyclic ring systems having at least one nitrogen atom. (B2)(B3)(B4)Among them, Za is h, tar, alcoxi, hydroxi, Amina, lease mine, dialamine, carboxilo, alcoxicarbon, hydroxil quilo, halogeno, halogeo, halogeoquile and R1 are h, codilo, alcoxi, acilo, halogeoquilo, alcoxicarbon More specifically, achievements include: Pyridylamine, pyridazole pyridane, morphine Pyridylamine, tetrahydrazine, oxazolilamino, thiazolylamine, Pyridylamine, quinoline, isoquinol, tetrahydroquinol, Pyridylamine, pyridazole Pyridylamine, pyridana or quinolona. The following variants include the ring system described above (Group 3). For heterocycles produced by pyridine derivatives,X4 and X5 are selected from a group consisting of H, asphalt, derivatives, rental, oxygen rental, halogen, hydrogen sulfide, halogen, aminobenzene, alcoxi, ariloxi, alcoxie, hydroxi, cyanogen or hydrazine. In another current situation, X4 and X5 alternatives may be methyl, thyroid, amine, methylamine, trifluoroenzene, dimethylamine, hydroxy, chlorine, bromine, fluorine and cyanogen. X6 can be the most preferential h, tar, halogen, Alcoy, hydroxy and halide. Alternatively, pyridine rings can be combined with 4-8 optional saturated or unsaturated rings. Some examples of these ring systems include tetrahydrazine,Quinine, tetrahydroquinol, azaquinine, morphine pyridine, pidan, etc. Monocyclic ring systems, such as pyridan, thiazole, oxazol, pyrazole, etc., may contain amino substitutes or be rented anywhere in the ring. In another current achievement, when Z1 formula (1) is co or SO2, the a1-z2 link in formula (1) includes the ring system generated by heterocyclic derivatives: pyridine, pyridan, thiazole, oxazol, benzimidazole, pyridan, etc. Other non orthogonal periods of a1-z2 include the following four periods:X4 is the last definition, or A1 is formula (5),Y1 is selected from n-r2, O and s.r2, and H; aspha arilo; hydro; alcoxilo; Alcoy; alquenilo; hydrocarbon; Amido; tar; aricarbonilo; alcoxicarbonilo; arioxicobonilo; arioxicarbonilo; arioxicarbonilo; haloxicarbonilo; hydrocarbon; ariltocbonilo; acuxietobonilo; R2 uptake A 4-12 member isobutylene phenyl cycle is formed together with R7, which can be optionally replaced by one or more substitutes selected from the following compound groups: low pitch, sulfur group, lease, hydroxy group, cetacean, alcoxi, halogen, phenyl, amino group, amino group, carboxy or amino methyl ester, and fusion phenyl;or R2 taken together with R7 forms a 4-12 membered heterocycle containing one or more heteroatoms chosen from O, N and S and is optionally unsaturated; or R2 taken together with R7 forms a five-membered heteroaromatic ring fused with an aryl or heteroaryl ring; R7 (when not taken together with R2) and R8 are chosen independently from the group consisting of H; I rent; alkenyl; alkynyl; aralkyl; Not me; alkylamino; hydroxyl; alkoxy; arylamino; amido, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl; aryloxy; aryloxycarbonyl; haloalkylcarbonyl; haloalkoxycarbonyl; alkylthiocarbonyl; arylthiocarbonyl; acyloxymethoxycarbonyl; cycloalkyl; bicycloalkyl, aryl, acyl,Benzoic acid; or NR7 and R8 are combined to form a single or double ring nitration single ring composed of 4-12 members, which can be replaced by one or more lower hydrocarbon substitutes selected from carbohydrate, arilo or hydroxyl derivatives, and the substitutes are one or more heteroatoms selected from O, N and s groups. R5 is selected from the H and tar groups; or A1 is the formula group (6),Y2 is selected from asphalt group; cyclopropene group; bicycle group; anode group; heterocyclic single cycle group; Z1 is selected from CH2 group; O, N, Co, s, so, Choh and NRK are selected from H or low asphalt group; Z2 is a can of carbon 2-5, which can optionally contain one or more heteroatoms selected from O, s and N groups; otherwise, z1-z2 can also contain a carbon tank, sulfur, sulfur amide, alquenileno, asphalt or acid; In this case, the optional carbon and nitrogen atoms of Z1 and Z2 are replaced by tar, alcoxi, hydrogen sulfide, hydrocarbon, arilo, ALCOXY, hydroxy, rental, heteromorphic and other components,Nitroacylammonium, asphalt, anthrax, halogenated, halogenated tar or acid amide; z2-z1 is associated with formula ring a (1) at the position of X1 substitute or target; n is a whole, 1 or 2; RC is selected from the hydrogen group; tar; halogenated, hydroxy, nitro, oxygen, amino, halogenated tar, arilo, Heteromorphic love, alcoxidiquilo, carbamate, hydroxypropyl, thiopropyl, rental, arimino, arilamino, asphalt, sulfur amide, sulfonamide, acrylonitrile, methylenedioxy, ethoxyl, tar, tar, carbonate, cyanogen, Y - (CH2) NCAR, where n is 0-2, R is selected from hydroxy, hydroxypropyl, hydroxy,Tar and ammonia; X1 from - or-HC, SO2, NRM y (CHRP) Q; RM is h or tar; RP is h, tar; alcoxi or hydroxlo; q is 0 or 1; X2 is selected from CHRE group,CO, SO2, O, NRf and S; wherein Rf is H or alkyl; Re is chosen from the group consisting of H, alkyl, hydroxyl and alkoxy; X or Y are independently selected from the group consisting of -CRg- or -N- wherein Rg is selected from the group consisting of H, alkyl, haloalkyl, fluoro, alkoxyalkyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, alkylsulfone, hydroxyalkyl, hydroxyl, alkoxy and carboxyalkyl; optionally the group X-X2-Y contains a portion chosen from the group consisting of acyl, alkyl, amino, ether, thioether, sulfone and olefin; Cycle B of formula (1) is a 3-8 membered monocyclic ring system; a bicyclic system of 8-11 members;Optional single loop system includes 1-2 heteroatoms selected from n, O and S; optional double loop system includes 1-4 heteroatoms selected from n, O and s, or optionally includes the group as SO2 or Co; Alternatives may be replaced by one or more alternatives selected from the asphalt, halogenated, cyanogenated, carboxy, halogenated, propenyl, propoxyalkyl, asphalt, arilo, isopropene, aralquilo, isopropene or Alcoy groups. RB is x3-rh, where X3 is selected from O, s and Nrj groups, and Rh and RJ are independent of H, asphalt, ACIO and arilo groups.N is o or 1; or O or 1; or O or 1; or O or 1; pharmaceutical compounds containing formula compounds (1), and selectively inhibiting or antagonizing a drug using these derivatives, avb3 and / or avb5 integrity.