Derivatives of triazaspiro[5,5]undecane (variants), pharmaceutical composition and method for control of chemokine/chemokine receptor

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new derivatives of triazaspiro[5,5]undecane of the formula (I):

wherein values of radicals R1-R5 are given in the invention claim, ort o their quaternary ammonium salts, N-oxides or nontoxic salts. Proposed compounds possess inhibitory and regulating activity with respect to chemokine/chemokine receptors and can be useful in prophylaxis and treatment of different inflammatory diseases, such as asthma, atopic dermatitis, nettle rash, allergic diseases, nephritis, hepatitis, arthritis or proliferative arthritis and other similar diseases. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I).

EFFECT: improved control method, valuable medicinal properties of compounds.

9 cl, 5 sch, 36 tbl, 70 ex

 

Description of the invention presented in the graphical part.

1. Derived diazaspiro[5.5]undecane formula (I)

where R1is

(1) hydrogen,

(2) C1-18-alkyl,

(3) (C2-18alkenyl,

(4)2-18-quinil,

(5) -COR6,

(6) -CONR7R8,

(7) -COOR9,

(8) -SO2R10,

(9) -COCOOR11,

(10) -CONR12COR13,

(11) WM 1 or

(12) C1-18-alkyl, C2-18alkenyl or2-18-quinil, substituted by 1-5 substituents, optionally selected from (a) halogen, (b) -CONR7R8, (s) -COOR9, (d) -OR14, (e) -SR15, (f) -NR16R17(g) -NR18COR19(i) -OCOR22(m) Cyc 1, (n) keto,

where each of R6-R9, R11-R19independently represents

(1) hydrogen,

(2) C1-18-alkyl,

(3) (C2-18alkenyl,

(5) WM 1 or

(6) C1-18-alkyl substituted by 1-5 substituents, optionally selected from (a) WM 1, (b) halogen, (s) -OR30, (d) -SR31, (e)-NR32R33and (f),- COOR34,

or

R7and R8taken together, represent

1) With the2-6-alkylen, 2) - (C2-6-alkylene)-O-(C2-6-alkylene)-,

each of R10, R22independent is present

(1) C1-8-alkyl,

(4) WM 1 or

(5) C1-8-alkyl, C2-8alkenyl, substituted WM 1, where each of R30-R34independently represents hydrogen, C1-8-alkyl, WM 1 or C1-8-alkyl, substituted WM 1,

WM 1 represents C3-15mono -, bi-, or tri-(condensed or Spiro)carbocyclic ring or a 3 to 15-membered mono-, bi-(condensed or Spiro)heterocyclic ring containing 1-3 nitrogen atom, 1-3 oxygen atom and/or 1 sulfur atom,

provided that WM 1 can be optionally substituted 1-5 R51,

where R51is

(1) C1-8-alkyl,

(2)2-8alkenyl,

(4) halogen,

(5) nitro,

(6) trifluoromethyl,

(7) triptoreline,

(8) nitrile,

(9) keto,

(10) WM 2,

(11) -OR52,

(12) -SR53,

(13) -NR54R55,

(14) -COOR56,

(15) -CONR57R58,

(16) -NR59COR60,

(17) -SO2NR61R62,

(18) -OCOR63,

(19) -NR64SO2R65,

(20) -NR66COOR67,

(21) -NR68CONR69R70,

(22) -B(OR71)2,

(23) -SO2R72,

(24) - N(SO2R72)2or

(25) C1-8-alkyl, C2-8alkenyl, replaced the s 1-5 substituents, optionally selected from (a) halogen, (b) WM 2, (s) -OR52, (d) -SR53, (e) -NR54R55and (f),- COOR56(g) -CONR57R58, (h) -NR59COR60(i) -SO2NR61R62, (j) -OCOR63, (k) NR64SO2R65, (1) -NR66COOR67(m) -NR68CONR69R70(n) -B(OR71)2, (o) -SO2R72or (R)-N(SO2R72)2,

where each of R52-R62, R64, R66and R68-R71independently represents (1) hydrogen, 2) C1-8-alkyl, 3)2-8alkenyl, 5) WM 2 or 6) C1-8-alkyl, C2-8alkenyl, substituted WM 2 or73, -COOR74or-NR75R76,

or R57and R58, R61and R62, R69and R70taken together, represent 1)2-6-alkylen, 2) - (C2-6-alkylene)-O-(C2-6-alkylen) -; each of R63, R65, R67and R72independently represent 1) C1-8-alkyl, 4) WM 2 or

5) C1-8-alkyl, C2-8alkenyl, substituted WM 2, -OR73, -COOR74or-NR75R76,

where R73-R76independently represent hydrogen, C1-8-alkyl,

WM 2 has the same value as WM 1,

provided that WM 2 may be optionally substituted by 1-5 R77where R77is

(1) C1-8-alkyl,

(2) halogen,

(3) neither the ro,

(4) trifluoromethyl,

(5) triptoreline,

(6) nitrile,

(7) -OR78,

(8) -NR79R80,

(9) -COOR81,

(10) -SR82,

(11) -CONR83R84,

(14) keto,

(17) -SO2NR163R164,

(18) -OCOR165,

(19) -NR166SO2R167,

(22) -SO2R173,

(23) - N(SO2R167)2or

(24) C1-8-alkyl, C2-8alkenyl, substituted by 1-5 substituents, optionally selected from (b) -OR78(s) -NR79R80, (d) -COOR81, (e) -SR82and (f),- CONR83R84(g) keto, (j) -SO2NR163R164, (k) -OCOR165, (1) -NR166SO2R167, (o) -SO2R173or (p) -N (SO2R167)2where each of R78-R84, R161-R164, R166independently represents (a) hydrogen, b) C1-8-alkyl, C)2-8alkenyl, f) C1-8-alkyl, substituted-OR174, -NR176R177or R83and R84, R163and R164, R171and R172taken together, represent

1) With the2-6-alkylen, 2) - (C2-6-alkylene)-O-(C2-6-alkylene)-,

each of R165, R167and R173independently represents

a) C1-8-alkyl, or (e) C1-8-alkyl substituted by-NR176R177,

where each of R174, R176R 177independently represents

1) hydrogen,

2) C1-8-alkyl,

R2is

(1) hydrogen,

(2) C1-8-alkyl,

(3) (C2-8alkenyl,

(4)2-8-quinil,

(5) -OR90,

(6) WM 3 or

(7) C1-8-alkyl substituted by 1-5 substituents, optionally selected from (a) halogen, (b) -OR90, (s) -SR91, (d) -NR92R93, (e) -COOR94(m) Cyc 3,

where each of R90-R94independently represents (1) hydrogen, 2) C1-8-alkyl, 5) WM 3 or 6) C1-8-alkyl, substituted WM 3;

WM 3 has the same value as WM 1,

provided that WM 3 may be optionally substituted by 1-5 R109where R109has the same meaning as R51,

each of R3and R4independently represents

(1) hydrogen,

(2) C1-8-alkyl,

(3) (C2-8alkenyl,

(4)2-8-quinil,

(5) -COOR120,

(6) -CONR121R122,

(7) WM 4 or

(8) C1-8-alkyl substituted by 1-5 substituents, optionally selected from (b) nitrile, (C) WM 4, (d) -COOR120, (e) -CONR121R122, (f) OR123(g) -SR124, (h) -NR125R126(i) -NR127COR128, (j) -SO2NR129R130, (k) -OCOR131, (1) -NR132SO2R133(m) -NR134COOR 135(n) -NR136CONR137R138, (o) -S-SR139(p) -NHC(=NH)other140, (r) -NR145CONR146COR147where each of R120-R128, R132, R134and R136-R138, R145and R146independently represents (1) hydrogen, 2) C1-8-alkyl, 5) WM 4 or 6) C1-8-alkyl, C2-8alkenyl, substituted WM 4, halogen, -OR148, -SR149, -COOR150or-NHCOR141or each of R131, R133, R135, R139and R147independently represents 1) C1-8-alkyl, 2)2-8alkenyl, 3)2-8-quinil, 4) WM 4 or 5) C1-8-alkyl, substituted WM 4, halogen, -OR148, -SR149, -COOR150or-NHCOR141,

R140represents hydrogen or-SO2R143where each of R141and R143independently represents 1) C1-8-alkyl, 4) WM 4 or 5) C1-8-alkyl, substituted WM 4,

each of R148-R150independently represents (1) hydrogen, 2) C1-8-alkyl, 5) WM 4 or 6) C1-8-alkyl, substituted WM 4,

WM 4 has the same meaning as WM 1,

provided that WM 4 may be optionally substituted by 1-5 R144where R144has the same meaning as R51or

R3and R4taken together, represent

where each of R190and R191independently has the same values and R3or R4,

R5is

(1) hydrogen,

(2) C1-8-alkyl,

its pharmaceutically acceptable Quaternary ammonium salts, N-oxides or non-toxic salt.

2. Derived diazaspiro[5.5]undecane formula (I)

where R1is

(1) hydrogen,

R2is

(1) hydrogen,

(2) C1-8-alkyl,

(3) (C2-8alkenyl,

(4)2-8-quinil,

(5) -OR90,

(6) WM 3 or

(7) C1-8-alkyl substituted by 1-5 substituents, optionally selected from (a) halogen, (b) -OR90, (s) -SR91, (d) -NR92R93, (e) -COOR94(m) Cyc 3,

where each of R90-R94independently represents (1) hydrogen, 2) C1-8-alkyl, 5) WM 3 or 6) C1-8-alkyl, substituted WM 3;

WM 3 has the same value as WM 1,

WM 1 represents C3-15mono -, bi - or tri-(condensed or Spiro)carbocyclic ring or a 3 to 15-membered mono-, bi-(condensed or Spiro)heterocyclic ring containing 1-3 nitrogen atom, 1-3 oxygen atom and/or 1 sulfur atom,

provided that WM 1 can be optionally substituted 1-5 R51,

where R51is

(1) C1-8-alkyl,

(2) the 2-8alkenyl,

(4) halogen,

(5) nitro,

(6) trifluoromethyl,

(7) triptoreline,

(8) nitrile,

(9) keto,

(10) WM 2,

(11) -OR52,

(12) -SR53,

(13) -NR54R55,

(14) -COOR56,

(15) -CONR57R58,

(16) -NR59COR60,

(17) -SO2NR61R62,

(18) -OCOR63,

(19) -NR64SO2R65,

(20) -NR66COOR67,

(21) -NR68CONR69R70,

(22) -B(OR71)2,

(23) -SO2R72,

(24) -N(SO2R72)2or

(25) C1-8-alkyl, C2-8alkenyl, substituted by 1-5 substituents, optionally selected from (a) halogen, (b) WM 2, (s) -OR52, (d) -SR53, (e) -NR54R55and (f),- COOR56(g) -CONR57R58, (h) -NR59COR60(i) -SO2NR61R62, (j) -OCOR63, (k) NR64SO2R65, (1) -NR66COOR67(m) -NR68CONR69R70(n) -B(OR71)2, (o) -SO2R72or (R)-N(SO2R72)2,

where each of R52-R62, R64, R66and R68-R71independently represents (1) hydrogen, 2) C1-8-alkyl, 3)2-8alkenyl, 5) WM 2 or 6) C1-8-alkyl, C2-8alkenyl, substituted WM 2 or73, -COOR74 or-NR75R76,

or R57and R58, R61and R62, R69and R70taken together, represent 1)2-6-alkylen, 2) - (C2-6-alkylene)-O-(C2-6-alkylen) -; each of R63, R65, R67and R72independently represent 1) C1-8-alkyl, 4) WM 2 or

5) C1-8-alkyl, C2-8alkenyl, substituted WM 2, -OR73, -COOR74or-NR75R76;

where R73-R76independently represent hydrogen, C1-8-alkyl,

WM 2 has the same value as WM 1,

provided that WM 2 can be optionally substituted

1-5 R77where R77is

(1) C1-8-alkyl,

(2) halogen,

(3) nitro,

(4) trifluoromethyl,

(5) triptoreline,

(6) nitrile,

(7) -OR78,

(8) -NR79R80,

(9) -COOR81,

(10) -SR82,

(11) -CONR83R84,

(14) keto,

(17) -SO2NR163R164,

(18) -OCOR165,

(19) -NR166SO2R167,

(22) -SO2R173,

(23) -N(SO2R167)2or

(24) C1-8-alkyl, C2-8alkenyl, substituted by 1-5 substituents, optionally selected from (b) -OR78(s) -NR79R80, (d) -COOR81, (e) -SR82and (f),- CONR83 R84(g) keto, (j) -SO2NR163R164, (k) -OCOR165, (1) -NR166SO2R167, (o) -SO2R173or (p) -N (SO2R167)2where each of R78-R84, R161-R164, R166independently represents (a) hydrogen, b) C1-8-alkyl, C2-8alkenyl, f) C1-8-alkyl, substituted-OR174, -NR176R177or

R83and R84, R163and R164, R171and R172taken together, represent

1) With the2-6-alkylen, 2) -(C2-6-alkylene)-O-(C2-6-alkylene)-,

each of R165, R167and R173independently represents

a) C1-8-alkyl, or (e) C1-8-alkyl substituted by-NR176R177,

where each of R174, R176,R177independently represents

1) hydrogen,

2) C1-8-alkyl,

provided that WM 3 may be optionally substituted by 1-5 R109where R109has the same meaning as R51,

each of R3and R4independently represents

(1) hydrogen,

(2) C1-8-alkyl,

(3) (C2-8alkenyl,

(4)2-8-quinil,

(5) -COOR120,

(6) -CONR121R122,

(7) WM 4 or

(8) C1-8-alkyl substituted by 1-5 substituents, optionally selected from (b) nitrile, (C) WM 4, (d) -COO 120, (e) -CONR121R122, (f) OR123(g) -SR124, (h) -NR125R126(i) -NR127COR128, (k) -OCOR131, (1) -NR132SO2R133(m) -NR134COOR135(n) -NR136CONR137R138, (o) -S-SR139(p) -NHC(=NH)other140, (r) -NR145CONR146COR147(where each of R120-R128, R132, R134and R136-R138, R145and R146independently represents (1) hydrogen, 2) C1-8-alkyl, 5) WM 4 or 6) C1-8-alkyl, C2-8alkenyl, substituted WM 4, halogen, -OR148, -SR149, -COOR150or-NHCOR141or

each of R131, R133, R135, R139and R147independently represents 1) C1-8-alkyl, 2)2-8alkenyl, 4) WM 4 or 5) C1-8-alkyl, substituted WM 4, halogen, -OR148, -SR149, -COOR150or-NHCOR141,

R140represents hydrogen or-SO2R143(where each of R141and R143independently represents 1) C1-8-alkyl, 4) WM 4 or 5) C1-8-alkyl, substituted WM 4,

each of R148-R150independently represents (1) hydrogen, 2) C1-8-alkyl, 5) WM 4 or 6) C1-8-alkyl, substituted WM 4,

WM 4 has the same meaning as WM 1,

provided that WM 4 may be optionally substituted by 1-5 R144where R144has the same meaning as R51or

R3and R4taken together, represent

where each of R190and R191independently has the same meaning as R3or R4,

R5is

(1) hydrogen,

(2) C1-8-alkyl,

its pharmaceutically acceptable Quaternary ammonium salts, N-oxides or non-toxic salt.

3. The compound according to claim 1, where in formula (I)defined in claim 1, R3and R4represent hydrogen.

4. The compound according to claim 1, where in formula (I)defined in claim 1, R3represents hydrogen, and R4is

(1) C1-8-alkyl,

(2)2-8alkenyl,

(3) C2-8-quinil,

(4) -COOR120,

(5) -CONR121R122,

(6) WM 4 or

(7) C1-8-alkyl substituted by 1-5 substituents, optionally selected from (b) nitrile, (C) WM 4, (d) -COOR120, (e) -CONR121R122, (f) OR123(g) -SR124, (h) -NR125R126(i) -NR127COR128, (k) -OCOR131, (1) -NR132SO2R133(m) -NR134COOR135(n) -NR136CONR137R138, (o) -S-SR139(p) -NHC(=NH)other140, (r) -NR145CONR146COR147(all radicals have the meanings defined in claim 1).

5. The compound according to claim 1, where in formula (I)defined in claim 1, R3and R4each independently submitted the

(1) C1-8-alkyl,

(2)2-8alkenyl,

(3) (C2-8-quinil,

(4) -COOR120,

(5) -CONR121R122,

(6) WM 4 or

(7) C1-8-alkyl substituted by 1-5 substituents, optionally selected from (b) nitrile, (C) WM 4, (d) -COOR120, (e) -CONR121R122, (f) OR123(g) -SR124, (h) -NR125R126(i) -NR127COR128, (j) -SO2NR129R130, (k) -OCOR131, (1) -NR132SO2R133(m) -NR134COOR135(n) -NR136CONR137R138, (o) -S-SR139(p) -NHC(=NH)other140, (r)-NR145CONR146COR147(all radicals have the meanings defined in claim 1).

6. The compound according to claim 1, where in formula (I)defined in claim 1, R3and R4taken together, represent

(all radicals have the meanings defined in claim 1).

Caetanina according to claim 1 or 2, which is a

(1)9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1-propyl-1,4,9-diazaspiro[5.5]undecane,

(2)9-(1,4-benzodioxan-6-ylmethyl)-1-butyl-3-cyclohexylmethyl-2,5-dioxo-1,4,9-diazaspiro[5.5]undecane,

(3)1-butyl-3-cyclohexylmethyl-2,5-dioxo-9-(2-phenylimidazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(4)1-butyl-3-(2-methyl-1-propyl)-2,5-dioxo-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(5)(3S)-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexa)-1-propyl-1,4,9-diazaspiro[5.5]undecane,

(6)(3R)-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexa)-1-propyl-1,4,9-diazaspiro[5.5]undecane,

(7)1-butyl-9-((3,5-dimethyl-1-phenyl)-4-pyrazolyl)methyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-diazaspiro[5.5]undecane,

(8)1-butyl-3-cyclohexylmethyl-2,5-dioxo-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(9)9-(1,4-benzodioxan-6-ylmethyl)-1-butyl-3-(2-methyl-1-propyl) -2,5-dioxo-1,4,9-diazaspiro[5.5]undecane,

(10)9-(4-benzyloxyphenyl)-1-butyl-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-diazaspiro[5.5]undecane,

(11)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenylhexa)-1,4,9-diazaspiro[5.5]undecane,

(12)(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(13)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(14)(3R)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(15)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(3-phenylpropyl) -1,4,9-diazaspiro[5.5]undecane,

(16)(3R)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(3-phenylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(17)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(4-phenylbutyl)-1,4,9-t is azaspiro[5.5]undecane,

(18)(3R)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(4-phenylbutyl)-1,4,9-diazaspiro[5.5]undecane,

(19)(3S)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-diazaspiro[5.5]undecane,

(20)(3R)-1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyl-1,4,9-diazaspiro[5.5]undecane,

(21)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-(2-phenyl-5-methoxazole-4-yl)ethyl)-1,4,9-diazaspiro[5.5]undecane,

(22)(3S)-1-propyl-2,5-dioxo-3-(4-(N-(2-chloroformate)oxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(23)(3S)-1-propyl-2,5-dioxo-3-[3-(3-(2,4,6-trimethylphenylsulfonyl)guanidino)propyl]-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(24)1-propyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(25)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(26)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-allyloxyphenyl)-1,4,9-diazaspiro[5.5]undecane,

(27)(3S)-1-propyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-diazaspiro[5.5]undecane,

(28)(3R)-1-propyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-2,5-dioxo-3-(2-methyl-1-propyl)-1,4,9-diazaspiro[5.5]undecane,

(29)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-phenylmethyl-1,4,9-diazaspiro[5.5]undecane,

(30)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyloxy is of IMT-1,4,9-diazaspiro[5.5]undecane,

(31)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(32)1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(33)1-butyl-2,5-dioxo-3-propyl-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(34)1-butyl-2,5-dioxo-3-methoxymethyl-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(35)1-(1-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(36)1-(2-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(37)1-(2-methylpropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(38)1-(2-dimethylaminoethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(39)1-(2-methoxyethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(40)1-(2-methylthioethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(41)1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(42)1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-benzyloxyphenyl)-1,4,9-diazaspiro[5.5]undecane,

(43)1-benzyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]University is a perfect combination,

(44)1-(3-methylphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(45)1-(3-methylphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane, (46)1-(1-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(47)1-(3-methylbutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(48)1-(2-methoxyphenylacetyl)-2,5-dioxo-3-(2-methylpropyl)-9-((3,5-dimethyl-1-phenyl)-4-pyrazolyl)methyl)-1,4,9-diazaspiro[5.5]undecane,

(49)1-(3-methoxyphenethyl)-2,5-dioxo-3-(2-methylpropyl)-9-((3,5-dimethyl-1-phenyl)-4-pyrazolyl)methyl)-1,4,9-diazaspiro[5.5]undecane,

(50)1-(2-methylphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(51)1-(3-methylphenylethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(52)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-ethylthiophen-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(53)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-ethylfuran-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(54)(3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(55)(3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-Tria is Aspiro[5.5]undecane,

(56)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-allyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(57)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-1,4,9-diazaspiro[5.5]undecane,

(58)1-propyl-2,5-dioxo-3-(2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(59)1-butyl-2,5-dioxo-3-(2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(60)1-butyl-2,5-dioxo-3-cyclohexylmethyl-1,4,9-diazaspiro[5.5]undecane,

(61)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(4-dihydroxybiphenyl)-1,4,9-diazaspiro[5.5]undecane,

(62)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(1,3-benzodioxin-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(63)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-(1,4-benzodioxan-6-yl)ethyl)-1,4,9-diazaspiro[5.5]undecane,

(64)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-(4-phenoxyphenyl)ethyl)-1,4,9-diazaspiro[5.5]undecane,

(65)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1-(1,4-benzodioxan-6-yl)ethyl)-1,4,9-diazaspiro[5.5]undecane,

(66) (3S)-1-propyl-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-allyl-1,4,9-diazaspiro[5.5]undecane,

(67)(3S)-1-propyl-2,5-dioxo-3-(4-aminobutyl)-9-phenylethyl-1,4,9-diazaspiro[5.5]undecane,

(68)(3S)-1-propyl-2,5-dioxo-3-(4-(N-(4-phenyl)phenylcarbamoyl)aminobutyl)-9-phenylethyl-1,4,9-diazaspiro[5.5]undecane,

(69)iodide 1-butyl-2,5-di the CSR-3-cyclohexylmethyl-9-methyl-9-(1-(1,4-benzodioxan-6-yl)ethyl)-1,4-diaza-9-Sonisphere[5.5]undecane,

(70)(3S)-3-(4-(N-benzyloxycarbonyl)aminobutyl)-2,5-dioxo-9-(2-hydroxy-2-phenylethyl)-1-propyl-1,4,9-diazaspiro[5.5]undecane,

(71)(3S)-3-(4-(N-benzyloxycarbonyl)aminobutyl)-2,5-dioxo-9-(2-oxo-2-phenylethyl)-1-propyl-1,4,9-diazaspiro[5.5]undecane,

(72)(3S)-1-(2-methylpropyl)-2,5-dioxo-3-methyl-9-allyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(73)(3S)-1-(2-methylpropyl)-2,5-dioxo-3-methyl-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(74)(3S)-1-(2-methylpropyl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(75)(3S)-1-(1-benzylpiperidine-4-yl)-2,5-dioxo-3-methyl-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(76)(3S)-1-(1-benzylpiperidine-4-yl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(77)(3S)-1-(2,2-diphenylpropyl)-2,5-dioxo-3-methyl-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(78)(3S)-1-(2,2-diphenylpropyl)-2,5-dioxo-3-(4-(N-benzyloxycarbonyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(79)(3S)-1-propyl-2,5-dioxo-3-(4-benzyloxyphenyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(80)(3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbamoyl)butyl)-9-(2,4,6-trimethoxybenzyl)-1,4,9-diazaspiro[5.5]undecane,

(81)(3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbamoyl)butyl)-9-(2,2-dimethylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(82)(3S)-1-about the Il-2,5-dioxo-3-(4-(benzylcarbamoyl)butyl)-9-(3-phenylpropenoyl)-1,4,9-diazaspiro[5.5]undecane,

(83)(3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbamoyl)butyl)-9-benzazolyl-1,4,9-diazaspiro[5.5]undecane,

(84)(3S)-1-propyl-2,5-dioxo-3-(4-(benzylcarbamoyl)butyl)-9-benzylaminocarbonyl-1,4,9-diazaspiro[5.5]undecane,

(85)(3S)-1-propyl-2,5-dioxo-3-(4-(3-phenylpropenoyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(86)(3S)-1-propyl-2,5-dioxo-3-(4-benzensulfonamidelor)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(87)(3S)-1-propyl-2,5-dioxo-3-(4-(N-benzylcarbamoyl)aminobutyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(88)(3S)-1-butyl-2,5-dioxo-3-(4-methoxyphenethyl)-9-cyclohexylmethyl-1,4,9-diazaspiro[5.5]undecane,

(89)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(4-chlorophenyl)thiophene-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(90)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(4-methoxyphenyl)thiophene-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(91)1-((2E)-2-butenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(92)1-(furan-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(93)1-(thiophene-2-ylmethyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(94)1-cyclopropylmethyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(95)1-(2-performer)-2,5-deok is about-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(96)1-(3-methyl-2-butenyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(97)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(quinoline-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(98)1-butyl-2,5-dioxo-3-(2-benzyloxycarbonylamino)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(99)1-(3-methyl-2-butenyl)-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(100)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-((2E)-3-phenyl-2-propenyl)-1,4,9-diazaspiro[5.5]undecane,

(101)(3S)-1-butyl-2,5-dioxo-3-(1,1-dimethylethyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(102)(3S)-1-butyl-2,5-dioxo-3-(1,1-dimethylethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(103)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methylthiazole-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(104)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-methylthiazole-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(105)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylthiazole-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(106)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-methylthiazole-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(107)(3R)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(108)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-treat the Spiro[5.5]undecane,

(109)(3R)-1-butyl-2,5-dioxo-3-((1R)-1-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(110)(3S)-1-butyl-2,5-dioxo-3-((1S)-1-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(111)1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(112)1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(113)1 pentyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(114)1-(3-methoxyphenethyl)-2,5-dioxo-3-(benzoyloxymethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(115)(3R)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(116)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(117)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(118)1-propyl-2,5-dioxo-3-(cyclohexylmethoxy)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(119)(3S)-1-butyl-2,5-dioxo-3-(1-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(120)(3R)-1-butyl-2,5-dioxo-3-(1-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(121)1-butyl-2,5-dioxo-3-(2-methylp the filing)-9-(5-finaledition-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(122)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-finaledition-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(123)(3R)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(124)(3S)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(125)(3R)-1-(2-butynyl)-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(126)(3S)-1-(2-butynyl)-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(127)1-butyl-2,5-dioxo-3-cycloheptylmethyl-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(128)1-butyl-2,5-dioxo-3-cycloheptylmethyl-9-(2,4,6-trimethoxyphenyl)-1,4,9-diazaspiro[5.5]undecane,

(129)1-butyl-2,5-dioxo-3-(3-cyclohexylprop)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(130)1-butyl-2,5-dioxo-3-(3-cyclohexylprop)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(131)1-butyl-2,5-dioxo-3-(3-cyclohexylprop)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(132)1-butyl-2,5-dioxo-3-(2-hydroxy-2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(133)1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane, (134)1-(2-butynyl)-2,5-dioxo-3-cyclog Kilmer-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(135)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(136)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenoxypyridine-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(137)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-phenoxypyridine-3-ylmethyl) -1,4,9-diazaspiro[5.5]undecane,

(138)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylbenzofuran-7-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(139)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methylbenzofuran-7-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(140)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(N-methyl-N-phenylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(141)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(N-methyl-N-phenylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(142)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(3,5-dimethylpyrazol-1-yl)-5-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(143)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-(3,5-dimethylpyrazol-1-yl)-5-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(144)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-diethyl-1-(4-chlorophenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(145)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-diethyl-1-(4-chlorophenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(146)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-phenoxypyridine-3-ylmethyl) -1,4,9-diazaspiro[5.]undecane,

(147)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-phenoxypyridine-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(148)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,3-benzodioxole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(149)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,3-benzodioxole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(150)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-hydroxy-4-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(151)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylthiophenyl)-1,4,9-diazaspiro[5.5]undecane,

(152)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(N,N-diphenylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(153)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(N,N-diphenylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(154)(3S)-1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(155)(3S)-1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane, (156)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl) -1,4,9-diazaspiro[5.5]undecane,

(157)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-were)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(158)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-were)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(159)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-chlorophenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(160)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-chlorophenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(161)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-triptoreline)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(162)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-triptoreline)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(163)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-diethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(164)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-diethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(165)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-phenylthiazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(166)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenylthiazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(167)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(1,4-benzodioxan-2-yl)thiazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(168)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-trifluoromethyl-2-(morpholine-1-yl)thiazole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(169)1-butyl-2,5-dioxo-3-(tetrahydropyran-4-ylmethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl) -1,4,9-diazaspiro[5.5]undecane,

(170)1-butyl-2,5-dioxo-3-(tetrahydropyran-4-ylmethyl)-9-(1,4-Ben is dioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(171)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-carboxypentyl)-1,4,9-diazaspiro[5.5]undecane,

(172)1-butyl-2,5-dioxo-3-(2-cyclohexylethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(173)1-butyl-2,5-dioxo-3-(2-cyclohexylethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(174)(3R)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(175)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methyl-2-phenylthiazol-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(176)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(thiophene-1-yl)thiazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(177)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-(pyridin-4-yl)thiazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(178)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,4-dimethoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(179)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(180)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(pyridin-2-yl)furan-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(181)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(pyridin-3-yl)furan-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(182)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3,5-dimethylpyrazol-1-yl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(183)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(5-CHL is pyridin-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(184)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrimidine-2-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(185)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridine-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(186)1-(2-butynyl)-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-were)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(187)(3R)-1-(2-butynyl)-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane, (188)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-hydroxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(189)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-2-yl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(190)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-3-yl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(191)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-carboxyphenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(192)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrazin-2-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(193)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-carboxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(194)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridin-4-yl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(195)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyridine-2-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(196)1-butyl-2,5-dioxo-3-cyclohex the methyl-9-(naphthalene-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(197)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-methoxynaphthalene-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(198)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-carboxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(199)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(pyridin-4-yl)furan-2-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(200) 1-butyl-2,5-dioxo-3-cyclopentylmethyl-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(201)(3R)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(202)(3S)-1-butyl-2,5-dioxo-3-(2,2-dimethylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(203)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-nitrophenylamino)-1,4,9-diazaspiro[5.5]undecane,

(204)(3R)-1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-(4-phenylbutyl)-1,4,9-diazaspiro[5.5]undecane,

(205)(3S)-1-(tetrahydrofuran-2-ylmethyl)-2,5-dioxo-3-phenylmethyl-9-(4-phenylbutyl)-1,4,9-diazaspiro[5.5]undecane,

(206)(3S)-1-propyl-2,5-dioxo-3-(3-(benzyloxycarbonylamino)propyl)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(207)1-butyl-2,5-dioxo-3-(carboxymethyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(208)1-(3-hydroxybutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(209)1-(3-hydroxypropyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenyloxy animetal)-1,4,9-diazaspiro[5.5]undecane,

(210)1-(2-hydroxybutyl)-2,5-dioxo-3-(2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(211)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-aminophenethyl)-1,4,9-diazaspiro[5.5]undecane,

(212)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenylcarbonylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(213)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-((4-(were)sulfonylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(214)(3S)-1-butyl-2,5-dioxo-3-benzoyloxymethyl-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(215)(3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(216)(3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-1,4,9-diazaspiro[5.5]undecane, (217)(3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(218)(3S)-1-butyl-2,5-dioxo-3-hydroxymethyl-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(219)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-cyclopentylacetyl)-1,4,9-diazaspiro[5.5]undecane,

(220)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-diethylaminoethoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(221)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-dimethylaminoethoxy) phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(222)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-proproxyphene)-1,4,9-Tr is azaspiro[5.5]undecane,

(223)1-(thiophene-2-ylmethyl)-2,5-dioxo-3-cyclohexylmethyl-9-(4-cyclopropylacetylene)-1,4,9-diazaspiro[5.5]undecane,

(224)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-cyclopropylacetylene)-1,4,9-diazaspiro[5.5]undecane,

(225)1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-cyclopropylacetylene)-1,4,9-diazaspiro[5.5]undecane,

(226)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(dimethylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(227)1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(diethylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(228)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(229)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(230)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(5-(3-methyl-4-chlorophenyl)-1-(4-methylphenylethyl)pyrazole-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(231)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-dimethylaminophenyl)-1,4,9-diazaspiro[5.5]undecane,

(232)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-diethylaminophenyl)-1,4,9-diazaspiro[5.5]undecane,

(233)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-cyclohexenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(234)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(235)(3S)-1-butyl-2,5-dioxo-3-(2-methylprop the l)-9-(4-(4-methoxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(236)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-butylphenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(237)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-methylpropyl)phenylmethyl) -1,4,9-diazaspiro[5.5]undecane,

(238)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-torpedolike)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(239)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-hydroxy-4-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(240)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-performer)-1,4,9-diazaspiro[5.5]undecane,

(241)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-performer)-1,4,9-diazaspiro[5.5]undecane,

(242)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-performer)-1,4,9-diazaspiro[5.5]undecane,

(243)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-chloroformate)-1,4,9-diazaspiro[5.5]undecane,

(244)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-chloroformate)-1,4,9-diazaspiro[5.5]undecane,

(245)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-chloroformate)-1,4,9-diazaspiro[5.5]undecane,

(246)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methyl-4-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(247)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(7-methoxy-1,3-benzodioxole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(248)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylthiomethyl)-1,4,9-diazaspiro[5.5]undecane,

(249)(3S)-1-butyl-2,5-di the CSR-3-(2-methylpropyl)-9-(2-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(250)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(251)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(252)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1-methylethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(253)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-fluoro-4-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(254)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-hydroxyethyloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(255)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-hydroxy-3-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(256)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-triftormetilfosfinov)-1,4,9-diazaspiro[5.5]undecane,

(257)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-methyl-5-chloro-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(258)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(6-vinylpyridin-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(259)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylsulfonylmethane)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(260)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylsulfonylamino)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(261)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(5-methylpyridin-2-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(262)(3S)-1-b the Teal-2,5-dioxo-3-(2-methylpropyl)-9-(4-(6-methylpyridin-1-oxide-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(263)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1-(2-methylpropionitrile)indole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(264)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2-phenyl-5-methoxazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(265)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(266)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(6-methylpyridin-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(267)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-forfinal)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(268)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(pyridine-2-yl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(269)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl}-9-(3,5-dimethyl-1-(4-hydroxyphenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(270)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-carboxyethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(271)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(dimethylaminomethyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(272)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(5-methylpyridin-1-oxide-2-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(273)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(2-carboxy-1-ethynyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(274)(3S)-1-butyl-2,5-dioxo-(2-methylpropyl)-9-(4-(4-(2-carboxy-1-ethynyl)phenyloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(275)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-aminosulphonylphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(276)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-aminosulphonylphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(277)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-benzylphenol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(278)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(2,4-differenl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(279)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(pyrrolidin-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(280)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(morpholine-4-ylsulphonyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(281)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(methylaminomethyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(282)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-cyanovinylene)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(283)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(dimethylaminomethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(284)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(2-dimethylbenzenesulfonyl)phenyl)-pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(285)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-(4-hydroxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undec is h,

(286)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-methoxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(287)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(cinoxacin-2-yl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(288)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenylcarbonylamino)-1,4,9-diazaspiro[5.5]undecane,

(289)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(N-(2-hydroxyethyl)-N-methylaminomethyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(290)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(2-phenylethyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(291)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(1,3,5-trimethylpyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(292)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(morpholine-4-ylmethyl)phenylmethyl) -1,4,9-diazaspiro[5.5]undecane,

(293)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylpiperazin-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(294)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-phenolsulfonephthalein)-1,4,9-diazaspiro[5.5]undecane,

(295)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-cyclohexylprop-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(296)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-carboxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(297)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)9-(4-(piperidine-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(298)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(pyrrolidin-1-ylsulphonyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(299)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(2,3-dihydrobenzofuran-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(300)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3,5-dimethyl-1-(4-(2-hydroxyethylaminomethyl)phenyl)-pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(301)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(carboxymethoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(302)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1-phenyl-1-hydroxymethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(303)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-hydroxypiperidine-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(304)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(3-carboxypolymethylene)phenylmethyl) -1,4,9-diazaspiro[5.5]undecane,

(305)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(bis(methylsulphonyl)amino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(306)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(1,4-benzodioxan-6-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(307)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-(3-hydroxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(308)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(methylsulfonylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(309)(3S)-1-Buti is -2,5-dioxo-3-(2-methylpropyl)-9-(6-(4-methoxybenzyloxy)pyridine-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(310)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylaminoacenaphthylene)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(311)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-chlorphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(312)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(3-(4-carboxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(313)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(phenylenecarbonyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(314)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-methylthiophenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(315)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-(4-(2-diethylaminoethylamine)phenyloxy)-phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(316)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-aminocarbonylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(317)(3S)-1-butyl-2,5-dioxo-3-(2-methylpropyl)-9-(4-dimethylaminocarbonylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(318)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(319)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-1,4,9-diazaspiro[5.5]undecane,

(320)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylphenoxy)phenylmethyl}-1,4,9-diazaspiro[5.5]undecane,

(321)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methoxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(322)(3)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-performer)-1,4,9-diazaspiro[5.5]undecane,

(323)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-performer)-1,4,9-diazaspiro[5.5]undecane,

(324)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-performer)-1,4,9-diazaspiro[5.5]undecane,

(325)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-chloroformate)-1,4,9-diazaspiro[5.5]undecane,

(326)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-cyclohexenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(327)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methoxy-3-hydroxyphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(328)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-chloroformate)-1,4,9-diazaspiro[5.5]undecane,

(329)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(330)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(331)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(332)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenylthiomethyl)-1,4,9-diazaspiro[5.5]undecane,

(333)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-(2-methylpropyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(334)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-butylphenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(335)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-isopropylphenyl)-1,4,9-diazaspiro[5.5]undecane,

(336)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-methoxy-3-performer)-1,4,9-diazaspiro[5.5]undecane,

(337)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-hydroxyethoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(338)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2-hydroxy-3-methylphenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(339)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-chloroformate)-1,4,9-diazaspiro[5.5]undecane,

(340)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(7-methoxy-1,3-benzodioxole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(341)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-methyl-4-methoxyphenethyl)-1,4,9-diazaspiro[5.5]undecane,

(342)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-torpedolike)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(343)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-cryptomaterial)-1,4,9-diazaspiro[5.5]undecane,

(344)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-methyl-5-chloro-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(345)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2,3-dimethyl-5-oxo-1-phenylpyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(346)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1-(2-methylpropionitrile)indole-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(347)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(5-methyl-2-phenyloxazol-4-ylmethyl)-1,4,9-triazene what about[5.5]undecane,

(348)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-methylsulfonylamino)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(349)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylsulfonylmethane)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(350)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(6-methylpyridin-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(351)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(6-methylpyridin-1-oxide-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(352)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(353)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-vinylpyridin-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(354)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-forfinal)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(355)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(pyridine-2-yl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(356)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-hydroxyphenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(357)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-carboxyethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(358)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-hydroxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

p num="596"> (359)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-carboxyphenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(360)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(dimethylaminomethyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(361)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(5-methylpyridin-1-oxide-2-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(362)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(2-carboxy-1-ethinyl) phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(363)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-((1E)-2-carboxy-1-ethinyl)phenyloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(364)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-aminosulphonylphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(365)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-aminosulphonylphenyl)phenylmethyl))-1,4,9-diazaspiro[5.5]undecane,

(366)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-benzylphenol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(367)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(2,4-differenl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(368)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(pyrrolidin-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(369)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(morpholine-4-ylsulphonyl)phenyl)piraso the-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(370)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-cyanovinylene)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(371)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(N-(2-hydroxyethyl)-N-methylaminomethyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(372)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(2-phenylethyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(373)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-dimethylaminomethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(374)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-(4-hydroxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(375)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(cinoxacin-2-yl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(376)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenylcarbamoyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(377)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-methylaminoethanol)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(378)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(1,3,5-trimethylpyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(379)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(morpholine-4-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(380)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(3-methoxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(381)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylpiperazin-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(382)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(pyridine-1-oxide-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(383)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-phenolsulfonephthalein)-1,4,9-diazaspiro[5.5]undecane,

(384)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-cyclohexylprop-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(385)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(3-carboxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(386)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(piperidine-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(387)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(pyrrolidin-1-ylsulphonyl)phenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(388)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(2,3-dihydrobenzofuran-5-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(389)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-carboxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(390)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(2-hydroxyethylaminomethyl)phenyl)-pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(391)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3,5-dimethyl-1-(4-(2-dimethylbenzenesulfonyl)phenyl)-pyrazole-4-yl is ethyl)-1,4,9-diazaspiro[5.5]undecane,

(392)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(1-hydroxy-1-phenylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(393)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-carboxymethoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(394)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-hydroxypiperidine-1-ylmethyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(395)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(3-carboxypolymethylene)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(396)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(1,4-benzodioxan-6-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(397)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(3-(3-hydroxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(398)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(methylsulfonylamino)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(399)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(6-(4-methoxyphenyl)pyridine-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(400)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylaminoacenaphthylene)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(401)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-chlorphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(402)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-bis(methylsulphonyl)aminophenethyl)-1,4,9-diazaspiro[5.5]undecane, (403)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl--(3-(4-carboxyphenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(404)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(phenylenecarbonyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(405)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-methylthiophenyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(406)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-(4-(2-diethylaminoethylamine)phenyloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(407)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-aminocarbonylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(408)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-dimethylaminobenzoyl)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(409)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(410)1-butyl-2,5-dioxo-3-(1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(411)(Z)-1-butyl-2,5-dioxo-3-(2-methylpiperidin)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(412)(3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxyethyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(413)(Z)-1-butyl-2,5-dioxo-3-ethylidene-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(414)(Z)-1-butyl-2,5-dioxo-3-(2-methylpiperidin)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(415)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

p num="652"> (416)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(417)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(418)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(419)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(6-phenoxypyridine-3-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(420)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(421)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-cyclohexenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(422)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-tetrahydropyran-4-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(423)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-pyridine-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(424)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-isopropylphenyl)-1,4,9-diazaspiro[5.5]undecane,

(425)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(4-were)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(426)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3-methyl-5-chloro-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(427)(R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(4-carboxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(428)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(pyridine-2-yl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(429)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(4-carboxyphenyl)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(430)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-benzyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(431)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(432)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(433)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(434)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-isopropylphenyl)-1,4,9-diazaspiro[5.5]undecane,

(435)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(6-methylpyridin-3-yloxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(436)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-(4-forfinal)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(437)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-methoxyphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(438)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-4-torpedolike)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(439)(3R*)-1-butyl-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-methylsulfonylmethane)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(440)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-allyloxycarbonyl-1,4,9-diazaspiro[5.5]undecane,

(441)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-diazaspiro[5.5]undecane, (442) (3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(443)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-(4-were)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(444)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-isopropylphenyl)-1,4,9-diazaspiro[5.5]undecane,

(445)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(446)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-methylphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(447)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-1-cyclohexylmethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(448)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(449)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-(4-methylphen is)pyrazole-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(450)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylphenoxy)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(451)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(452)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-isopropylphenyl)-1,4,9-diazaspiro[5.5]undecane,

(453)(3R*)-1-(2-butynyl)-2,5-dioxo-3-((1R*)-1-hydroxy-2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(454)(3R*)-1-butyl-2,5-dioxo-3-((1S*)-1-hydroxy-1-cyclohexylmethyl)-9-benzyl-1,4,9-diazaspiro[5.5]undecane,

(455)(3R*)-1-butyl-2,5-dioxo-3-((1S*)-1-hydroxy-1-cyclohexylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(456)(3R*)-1-butyl-2,5-dioxo-3-((1S*)-1-hydroxy-1-cyclohexylmethyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(457)(3R*)-1-butyl-2,5-dioxo-3-((1S*)-1-hydroxy-1-cyclohexylmethyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(458)(3R*)-1-butyl-2,5-dioxo-3-((1S*)-1-hydroxy-1-cyclohexylmethyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(459)(3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(460)(3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(461)(3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylp the filing)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5]undecane,

(462)(3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(463)(3S)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylmethane)-phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(464)(3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(465)(3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(466)(3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-vinyloxymethyl)-1,4,9-diazaspiro[5.5] undecane,

(467)(3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(468)(3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylmethane)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(469)(3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(470)(3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(471)(3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(472)(3R)-1-butyl-2,5-dioxo-3-((1S)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylmethane)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(473)(3S)-1-butyl-2,5-dio is co-3-((1H)-1-hydroxy-2-methylpropyl)-1,4,9-diazaspiro[5.5]undecane,

(474)(3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(3,5-dimethyl-1-phenylpyrazol-4-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(475)(3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(1,4-benzodioxan-6-ylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(476)(3S)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-2-methylpropyl)-9-(4-(4-methylsulfonylmethane)phenylmethyl)-1,4,9-diazaspiro[5.5]undecane,

(477)(3S)-2,5-dioxo-3-(3-benzyloxycarbonylamino)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane,

(478)(3S)-1-methyl-2,5-dioxo-3-(3-benzyloxycarbonylamino)-9-(2-phenylethyl)-1,4,9-diazaspiro[5.5]undecane or

(479)(3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-9-(4-vinyloxymethyl)-9-oxide-1,4,9-diazaspiro[5.5]undecane,

or its Quaternary ammonium salt, N-oxide or a non-toxic salt.

8. Pharmaceutical composition having regulatory activity in relation to the chemokine/receptor of the chemokine, comprising as an active ingredient derived diazaspiro[5.5]undecane formula (I) according to claim 1 or its Quaternary ammonium salt, N-oxide or a non-toxic salt.

9. The method of regulation of chemokine/receptor of the chemokine, including the introduction as an active ingredient derived diazaspiro[5.5]undecane formula (I) according to claim 1 or its Quaternary ammonium salt, N-oxide or a non-toxic salt.

10. The way warned of the I and/or treatment of asthma, atopic dermatitis, urticaria, allergic aspergillosis of the bronchi and lungs, allergic eosinophilic gastroenteritis, nephritis, nephropathy, hepatitis, arthritis, rheumatoid arthritis, psoriasis, rhinitis, conjunctivitis, damage, ischemic reperfusion injury, multiple sclerosis, ulcerative colitis, acute respiratory distress syndrome adults, cytotoxic shock, diabetes, autoimmune diseases, failure of many organs, immunosuppression, cancer metastasis and acquired immune deficiency syndrome, including the introduction as an active ingredient derived diazaspiro[5.5]undecane formula (I) according to claim 1 or its Quaternary ammonium salt, N-oxide or a non-toxic salt.

Priority points and features:

03.12.1999, 27.01.2000 and 04.02.2000 equally - according to claims 1,3-7, which are compounds where R1is2-C10alkyl, substituted WM 1 WM 1 represents C3-C10carbocyclic ring or3-C10heterocyclic ring, optionally substituted 1-41-C4the alkyl, C1-C4alkoxy; R2represents C1-C8alkyl; R3represents C1-C8alkyl or C3-C7cycloalkyl1-C4alkyl; R4is hydrogen; R5represents vodor the d or C 1-C8alkyl, and their non-toxic salts;

on item 8, which relates to pharmaceutical compositions using these compounds

on PP,10, which relate to methods of using these compounds;

19.05.2000 - claims 1 to 7, which apply to all compounds and their pharmaceutically acceptable Quaternary ammonium salts, N-oxides and non-toxic salts, excluding the compounds in which R7and R8taken together represent - (C2-C6alkylene) -O- (C2-C6alkylene) -; R51is-N(SO2R72)2With2-C8alkenyl, substituted by 1-5 substituents

-N (SO2R72)2,each of R52-R62,R64,R66and R68-R71is2-C8alkenyl, R57and R5S, R61and R62, R69and R70taken together, represent -(C2-C6alkylene) -O- (C2-C6alkylene) -; each of R63, R65, R67and R72independently represent2-C8alkenyl, R77is (14) keto, (17)-SO2NR163R164, (18)-OCOR165, (19)-NR166SO2R167, (22)-SO2R173, (23)-N(SO2R167)2or (24)C1-8-alkyl, C2-8alkenyl, substituted by 1-5 substituents, optionally selected from b-OR 78with)NR79R80, (d) -COOR81, (e) -SR82and (f),-CONR83R84, g)keto, (j)SO2NR163R164k)-OCOR165l)-NR166SO2R167about)-SO2R173or (p) - N(SO2R167)2where each of R78-R84, R161-R164, R166independently represents C2-8alkenyl,C1-8-alkyl, substituted-OR174, -NR176R177or R83and R84, R163and R164, R171and R172taken together, represent 1)2-C6alkylene -(C2-C6alkylene) -O- (C2-C6alkylene) -; each of R165, R167, R173independently is a)C1-8-alkyl or (e) C1-8-alkyl, substituted NR176,R177(where each of R174, R176, R174independently represents (1) hydrogen, 2) C1-8-alkyl, each of R131, R133, R135, R139and R147independently is-COOR150or

-NHCOR141, R3and R4taken together, represent

where each of R190and R191independently has the same meaning as R3or R4) , and their pharmaceutically acceptable Quaternary ammonium salts, N-oxides and non-toxic salts,

on item 8, which relates to pharmaceutical compositions using pointed to by the x connections

and p,10, which relate to methods of using such compounds.



 

Same patents:

The invention relates to (DL)-1-hydroxy-3,7,7,9,9-pentamethyl-1,4,8-diazaspiro[4.5]decane-2-ONU formula (1)

The invention relates to new spirochetes formula I

< / BR>
where Ar is phenyl, substituted phenyl where the substituents are: alkoxy, alkyl, alkoxyalkyl, phenoxy, halogen, pyridyloxy, alkoxyalkane, halogenfree; R1- H; R2- H1-C4alkyl; W represents O or one or more1-C4alkyl fragments; Y is independently one or more members of the group consisting of H2, SR3, alkoxy; R3- H, alkyl; Z is a carbocyclic or heterocyclic Spiro-fragment with a 3-7 member ring system, where the heterocyclic fragment includes 2 oxygen atom or sulfur, or one nitrogen atom and spirits may be unsubstituted or substituted by hydroxy, C1-C4the alkyl, benzyloxy; n=1-3; optical isomers, diastereomers or enantiomers or pharmaceutically acceptable salts

The invention relates to nitrogen-containing compounds that may constitute the active ingredient of the pharmaceutical composition active as an antagonist neirokinina, and more particularly to a derivative of arylpyrimidines and pharmaceutical compositions containing these compounds

The invention relates to new derivatives of pyrrolidinone possessing biological activity, in particular derivatives of 1H-3-aryl-pyrrolidin-2,4-dione

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new nitrogen-containing aromatic derivatives of the general formula:

wherein Ag represents (1) group of the formula:

; (2) group represented by the formula:

or ; (3) group represented by the formula:

; Xg represents -O-, -S-, C1-6-alkylene group or -N(Rg3)- (wherein Rg3 represents hydrogen atom); Yg represents optionally substituted C6-14-aryl group, optionally substituted 5-14-membered heterocyclic group including at least one heteroatom, such as nitrogen atom or sulfur atom, optionally substituted C1-8-alkyl group; Tg1 means (1) group represented by the following general formula:

; (2) group represented by the following general formula: . Other radical values are given in cl. 1 of the invention claim. Also, invention relates to a medicinal agent, pharmaceutical composition, angiogenesis inhibitor, method for treatment based on these compounds and to using these compounds. Invention provides preparing new compounds and medicinal agents based on thereof in aims for prophylaxis or treatment of diseases wherein inhibition of angiogenesis is effective.

EFFECT: improved treatment method, valuable medicinal properties of compounds and agents.

40 cl, 51 tbl, 741 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention concerns a new oral formulation of the galenic preparation molsidomine with prolonged releasing an active substance and designated in treatment of stenocardia attack in all its variations (stress stenocardia, spastic stenocardia, nonstable stenocardia). This novel formulation of galenic preparation comprises the therapeutically effective dose of molsidomine or one of its active metabolites and shows the following dissolving rate values in vitro [measured by spectrophotometry method at wavelength 286 or 311 nm according to a method reported in Pharmacopee Europeene, 3-d edition (or U. S. P. XXIV) at 50 rev./min in 500 ml of medium consisting of 0.1 N HCl at 37°C]: 15-25% of molsidomine released in 1 h; 20-35% of molsidomine released in 2 h; 50-65% of molsidomine released in 6 h; 75-95% of molsidomine released in 12 h; >85% of molsidomine released in 18 h, and >90% of molsidomine released in 24 h wherein the maximal blood plasma concentration of molsidomine in vivo appears in 2.5-5 h but preferably in 3-4 h after intake of abovementioned formulation and has value from 25 to 50 ng/ml of blood plasma. Invention provides reducing amount of doses of drug per a day that is more suitable for a patient.

EFFECT: improved and valuable pharmaceutical properties of preparation.

14 cl, 5 dwg, 2 tbl, 7 ex

FIELD: medicine, phytotherapy, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to using Belamcanda chinensis extract for preparing organ-selective medicinal preparation without uterotropic effect or with minimal such effect that is used as estrogen-like preparation. This preparation is used in selective treatment and/or prophylaxis of cardiovascular diseases, in particular, atherosclerosis and osteoporosis, climacteric disturbances, especially for prophylaxis or softening congestions of blood. Extract is used in manufacturing a medicinal preparation in ready formulation for selective treatment and/or prophylaxis of cardiovascular diseases, in particular atherosclerosis, and for selective treatment and/or prophylaxis of osteoporosis, climacteric disturbances, especially for prophylaxis and softening congestions of blood. Extract promotes to effective prophylaxis and/or treatment of cardiovascular diseases, in particular, atherosclerosis, climacteric disturbances, especially for prophylaxis and softening congestions of blood.

EFFECT: valuable medicinal properties of extract.

4 cl, 4 ex

FIELD: medicine, neurology.

SUBSTANCE: the present innovation deals with treating cerebral vascular diseases accompanied with psychic disorders. For this purpose one should introduce homeopathic preparations named Cerebrum compositum and Hepar compositum per 2.2 ml every other day for 20 d intramuscularly, and beginning since the 11th d one should additionally prescribe Vertigohel preparation per 10 drops thrice daily for 10 d. The innovation suggested provides decreased different psychotic and unpsychotic depressive syndromes that considerably improves quality of life in this category of patients.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine, cardiology, pharmacy.

SUBSTANCE: invention proposes applying moxonidine as an active component in preparing pharmaceutical compositions designated for treatment of injuries of heart muscle caused by infarction. Indicated compositions promote to prophylaxis in the infarction progression and to treatment of its complications also.

EFFECT: valuable medicinal properties of composition.

3 cl, 1 tbl, 1 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention describes 2-phenyl-substituted imidazotriazinones of the general formula (I): wherein R1 and R2 mean independently linear (C1-C4)-alkyl; R3 and R4 are similar or distinct and represent hydrogen atom or linear or branched (C1-C4)-alkenyl or (C1-C4)-alkoxy-group, linear or branched (C1-C6)-alkyl chain that can be broken by oxygen atom, and/or it can comprise from to some similar or different the following substitutes: methoxy-, hydroxy-, carboxyl, linear or branched (C1-C4)-alkoxycarbonyl, and/or residues of formulae -SO3H, -(A)a-NR7R8, -O-CO-NR7'R8', and/or wherein A means a number 0 or 1; A means residue -CO or -SO2; R7 and R8 mean hydrogen atom (H), cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl or pyridyl that can be substituted with different substitutes, methoxy-, (C1-C6)-alkyl and others; R7' and R8' mean (C1-C6)-alkyl. Also, other values of radicals R3 and R4 are given, a method for their preparing and a pharmaceutical composition. Described compounds are inhibitors of phosphodiesterases and can be used in manufacturing agents showing an anti-thrombosis, anti-proliferative, anti-vasospastic and vasodilating effect.

EFFECT: improved preparing method, valuable biochemical and medicinal properties.

10 cl, 6 tbl, 337 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to new substituted derivatives of norbornylamine with exo-configuration of nitrogen atom and endo-anellated 5-6-membered cycles of the formula (I) and with exo-configuration of nitrogen atom and exo-anellated 5-6-membered cycles of the formula (Ia) , and their pharmaceutically acceptable salts or trifluoroacetates also. In compounds of the formula (I) or (Ia) A means (C1-C4)-alkylene; S1 means optionally (C1-C4)-alkyl; S2 means (C1-C4)-alkyl or hydrogen atom (H) being if S1 and S2 mean alkyl then X in the group [-N+(S1S2)-X-] corresponds to pharmacologically acceptable anion or trifluoroacetate; B means saturated or unsaturated carbon 5- or 6-membered cycle; R1, R2, R3, R4 and R5 have values given in the description. Also, invention relates to a method for preparing these compounds and to a medicinal agent. These compounds can be used for preparing medicinal agents useful for treatment or prophylaxis in breathing impulse disturbance, in particular, in breathing disturbance caused by sleep, transient breathing stop during sleep, snore, for treatment or prophylaxis of acute and chronic renal diseases, in particular, acute and chronic renal insufficiency and, disturbance in intestine, gallbladder, ischemic states of peripheral and central nervous system disturbances, severe attacks and others symptoms. Compounds are inhibitors of sodium-proton exchange, show effect on serum lipoprotein and therefore they can be used in prophylaxis and regression of atherosclerotic alterations.

EFFECT: improved preparing method, valuable medicinal properties of compounds.

21 cl, 70 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a medicinal formulation consisting of a core and the stomach-dissolving envelope. The core comprises trimetazidine dihydrochloride as an active component, and starch, mannitol, povidone, magnesium stearate, croscarmelose and microcrystalline cellulose as accessory substances. The envelope comprises hydroxypropylmethylcellulose, polyethylene glycol, titanium dioxide, magnesium stearate and acid red as a dye. Also, invention describes a method for making the trimetazidine medicinal formulation. Trimetazidine tablets show high mechanical strength in the low pressing strength (3.5-5 kH). The composition of the medicinal formulation provides releasing 80% of trimetazidine for 30 min.

EFFECT: improved and valuable properties of formulation.

3 cl, 1 tbl, 1 ex

FIELD: organic chemistry, chemical technology, biochemistry.

SUBSTANCE: invention relates to new substituted 6-sulfo-2-oxo-1,2-dihydroquinoline 4-carboxylic acids and their derivatives of the general formula (1):

eliciting physiological activity, in particular, capacity to inhibit activity of protein kinase, and also to intermediate compounds for their preparing and to the focused library, for search compound-leaders and medicinal candidates obtaining on the basis of screening combinatory libraries. In compounds of the general formula (1) R1 represents hydrogen atom or electrophilic substitute; R2 represents hydrogen atom or inert substitute; R3 represents optionally substituted hydroxyl group, optionally substituted amino-group and optionally substituted azaheterocycle; R4 represents optionally substituted amino-group and optionally substituted azaheterocycle. Also, invention relates to compounds of the general formula (1.1):

wherein R1, R2 and R3 have above given values; R5 represents hydroxyl or chlorine atom, and to their applying for preparing compounds of the general formula (1.2):

and (1.3):

wherein R1, R2 and R4 have above given values.

EFFECT: valuable medicinal and biochemical properties of compounds.

6 cl, 4 tbl, 5 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to applying compounds of the general formula (1):

as inhibitors of caspase-3 that allows their applying as "molecular tools" and as active medicinal substances inhibiting selectively the scheduling cellular death (apoptosis). Also, invention relates to pharmaceutical compositions based on compounds of the formula (1), to a method for their preparing and a method for treatment or prophylaxis of diseases associated with enhanced activation of apoptosis. Also, invention relates to new groups of compounds of the formula 91), in particular, to compounds of the formulae (1.1):

and (1.2):

. In indicated structural formulae R1 represents inert substitute; R2, R3 and R4 represent independently of one another hydrogen atom, fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J). CF3, inert substitute, nitro-group (NO2), CN, COOH, optionally substituted sulfamoyl group, optionally substituted carbamide group, optionally substituted carboxy-(C1-C6)-alkyl group; R5 represents oxygen atom or carbon atom included in optionally condensed, optionally substituted and optionally comprising one or some heteroatoms; R6 represents hydrogen atom or inert substitute; X represents sulfur atom or oxygen atom.

EFFECT: improved preparing and applying methods, valuable medicinal and biochemical properties of compounds.

3 cl, 1 dwg, 2 tbl, 1 sch, 8 ex

FIELD: medicine.

SUBSTANCE: method involves introducing effective quantity of imidazole derivative of formula 1.

EFFECT: enhanced effectiveness of treatment.

14 cl, 2 dwg, 1 tbl

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