Claims
- 1. A compound having the following formula (I), (II) or (III),
- 2. The compound of formula (II) or (III) according to claim 1 wherein:
a) X1, X2 and X3 are independently —C(R1)— wherein R1 is hydrogen, halogen, CN, SO3H, NO2, CF3, OR2, SR2, NR2R3, COR2, COOR2, CONR2R3, SO2NR2R3, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl or X—R5;
when said alkyl, alkenyl or alkynyl in the definition of R1 is substituted, said alkyl, alkenyl and alkynyl are independently substituted by one to three halogen, CN, OR2, COOR2, NR6R7, SO2NR6R7 or C(═O)NR6R7; R2 and R3 are independently hydrogen, lower alkyl or lower alkyl substituted with halogen, CN, SO3H, OR6, COOR6, NR6R7, SO2NR6R7 or C(═O)NR6R7; X5 is lower alkylene or a single bond; R5 is phenyl, pyridyl or indolyl; R6 and R7 are taken separately and are independently selected from hydrogen or lower alkyl; or R6 and R7 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, wherein the ring is unsubstituted or substituted with one to three lower alkyl; X5 and R5 are unsubstituted or substituted with one to three Q3, heteroaryl, lower alkyl or lower alkyl substituted with Q3; Q3 is halogen, CN, SO3H, NO2, CF3, OR2′, OC(═O)R2′, C(═O)R2′, C(═O)OR2′, NH—C(═O)R2′, NR3′R4′, SO2NR3′R4′ or C(═O)NR3′R4′; R2′, R3′, and R4′ are taken separately and are independently hydrogen, unsubstituted lower alkyl or lower alkyl substituted with one to three halogen, OR6′, COOR6′ or NR6′R7′; or R3 ′ and R4 ′ are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with a 4- to 8-membered unsubstituted or lower alkyl substituted ring having one or two O, S or N; an unsubstituted lower alkyl or a lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; R6′ and R7′ are taken separately and are independently hydrogen or lower alkyl; or R6′ and R7′ are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with a 4- to 8-membered unsubstituted or lower alkyl substituted ring having one or two O, S or N; an unsubstituted lower alkyl or a lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; X4 is —C(R1′)—
R1′ is hydrogen, halogen, CN, NO2, SO2CH3, SO3H, CH3, CF3, OR2′, SR2′, NR2′R3′, COOR2′, CONR2′R3′ or SO2NR2′R3′; R2′ and R3′ are independently hydrogen or lower alkyl; b) X is NH; c) Y is NH; d) Z1 is NR16R17;
R16 and R17 are taken separately and are independently hydrogen, CN, C(═O)R14, (C═O)NR14R15, OR14, unsubstituted lower alkyl or lower alkyl substituted with one to three OR14 or NR14R15; or R16 and R17 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, said ring being unsubstituted or substituted with lower alkyl; R14 and R15 are taken separately and are independently hydrogen or lower alkyl; or R14 and R15 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, said ring being unsubstituted or substituted with lower alkyl; e) A is 44 wherein:
A1, A2, A3, A4 and A5 are independently CH2; a carbon atom substituted one or two lower alkyl, OH or F or an oxygen atom; and two nonadjacent atoms of A may be linked by a 2,3 or 4 carbon atom chain to form a ring.
- 3. A compound of formula (I) of claim 1.
- 4. The compound according to claim 3 wherein:
a) X1, X2 and X3 are independently —C(R1)— wherein R1 is hydrogen, halogen, CN, SO3H, NO2, CF3, OR2, SR2, NR2R3, COR2, COOR2, CONR2R3, SO2CH3, SO2NR2R3, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl or X—R5;
when said alkyl, alkenyl or alkynyl in the definition of R1 is substituted, said alkyl, alkenyl and alkynyl are independently substituted by one to three halogen, CN, SO3H, OR2, COOR2, NR6R7, SO2NR6R7 or C(═O)NR6R7; R2 and R3 are independently hydrogen, lower alkyl or lower alkyl substituted with halogen, CN, SO3H, OR6, COOR6, NR6R7, SO2NR6R7 or C(═O)NR6R7; X5 is lower alkylene or a single bond; R5 is phenyl, pyridyl or indolyl; R6 and R7 are taken separately and are independently hydrogen or lower alkyl; or R6 and R7 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with one to three lower alkyl; X5 and R5 are unsubstituted or substituted with one to three Q3, heteroaryl, lower alkyl or lower alkyl substituted with Q3; Q3 is halogen, CN, SO3H, NO2, CF3, OR2′, OC(═O)R2′, C(═O)R2′, C(═O)OR2′, NH—C(═O)R2′, NR3R4′, SO2NR3′R4′, or C(═O)NR3′R4′, R2′, R3′ and R4′ are taken separately and are independently hydrogen, unsubstituted lower alkyl or lower alkyl substituted with one to three halogen, OR6′, COOR6′ or NR6′R7′; or R3′ and R4′ are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with a 4- to 8-membered unsubstituted or lower alkyl substituted ring having one or two O, S or N; an unsubstituted lower alkyl or a lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; R6′ and R7′ are taken separately and are independently hydrogen or lower alkyl; or R6 and R7 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with a 4- to 8-membered unsubstituted or lower alkyl substituted ring having one or two O, S or N; an unsubstituted lower alkyl or a lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; X4 is —C(R1′)—; R1′ is hydrogen, halogen, CN, NO2, SO2CH3, SO3H, CH3, CF3, OR2, SR2, NR2R3, COOR2, CONR2R3 or SO2NR2R3; R2 and R3 are independently hydrogen or lower alkyl; b) X is NH; c) Y is NH; d) Z1 is O, S or NR13;
R13 is hydrogen or CN; e) A is 45 wherein:
A1, A2, A3, A4 and A5 are independently CH2; a carbon atom substituted with one or two lower alkyl, OH or F or an oxygen atom; and two nonadjacent atoms of A may be linked by a 2, 3 or 4 carbon atom chain to form a ring.
- 5. The compound of formula (I), according to claim 1 wherein:
X1, X2, X3 and X4 are independently —C(R1)—;
R1 is Q1, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl or X5R5; when said alkyl, alkenyl or alkynyl in the definition of R1 is substituted, said alkyl, alkenyl and alkynyl are independently substituted by one to three Q2; X5 is a single bond, a lower alkylene or a lower alkylene incorporating one O, S or N;
Q1, Q2 and Q3 are independently hydrogen, halogen, CN, NO2, SO3H, OR2, OC(═O)R2, C(═O)OR2, SR2, S(═O)R2, C(═O)—NH—SO2—CH3, NR3R4, Q—R2, Q—NR3R4, NR2—Q—NR3R4 or NR3—Q—R2; R is hydrogen or lower alkyl.
- 6. The compound of formula (I) according to claim 5 wherein
R1 is Q1; unsubstituted lower alkyl; lower alkyl substituted with 1, 2 or 3 fluorine atoms, OR3, COOR3 or NR3R4; unsubstituted lower alkynyl; lower alkynyl substituted with 1, 2 or 3 fluorine atoms, OR3, COOR3 or NR3R4 or X5—R5; R3 and R4 are taken separately and are independently hydrogen or lower alkyl; or R3 and R4 are taken together with the nitrogen atom to which they are linked to form a 6-membered ring having one or two O or N; X5 is a single bond; R5 is aryl, heteroaryl or a bicyclic group; R5 is unsubstituted or substituted with one, two or three Q3; Q1 and Q3 are independently hydrogen, halogen, CN, lower alkyl, OR2, C(═O)OR2, NR3′R4′, C(═O)NR3′R4′ or SO2NR13′R4′; R2, R3′ and R4′ are taken separately and are independently hydrogen, lower alkyl or Q4-heteroaryl; or R3 and R4 are taken together with the nitrogen atom to which they are linked to form a 4- to 6-membered ring having one or two O or N, the ring being unsubstituted or substituted with a 6-membered ring having one or two O or N and which itself is unsubstituted or substituted with a lower alkyl, a lower alkyl or a lower alkyl substituted with one to three OR′, NR′R″, C(═O)NR′R″ or COOR′; Q4 is lower alkyl incorporating one O, S or N or (CH2)n; Q1 and Q3 are independently unsubstituted or substituted with one or two lower alkyl, CN, SO3H, C(═O)—NH—SO2—CH3, OR6, COOR6 or NR6R7; R6 and R7 are taken separately and are independently selected from hydrogen, unsubstituted lower alkyl, or lower alkyl substituted with one or two groups selected from OR, COOR or NRR8; or R6 and R7 are taken together with the nitrogen atom to which they are linked to form a 4- to 6-membered ring having one or two O or N, the ring being unsubstituted or substituted with a 6-membered ring having one or two O or N and which itself is unsubstituted or substituted with a lower alkyl, a lower alkyl or a lower alkyl substituted with one to three OR′, NR′R″, C(═O)NR′R″ or COOR′; R and R8 are independently hydrogen or lower alkyl.
- 7. The compound of formula (I) according to claim 5 wherein:
R1 is hydrogen; halogen; OR2; COR2; COOR2; CONR2R3; lower alkyl; lower alkyl substituted with CN, SO3H, OR3′, NR3′R4′, COOR3′ or CONR3′R4′ or X5—R5; R2 and R3 are independently hydrogen; lower alkyl; Q4-aryl; Q4-heteroaryl; Q4-(C3-C7 cycloalkyl) optionally incorporating C(═O) or with one or two O, S or N or Q4-(C3-C7 cycloalkenyl) optionally incorporating C(═O) or with one or two O, S or N; Q4 is (CH2)n; lower alkyl incorporating one O, S or N; lower alkenyl; or lower alkynyl; n is 0, 1, 2 or 3; R3′ and R4′ are taken separately and are independently hydrogen; lower alkyl or lower alkyl substituted with OH, COOH or NH2; or R3′ and R4′ are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with one to three (CH2)m—Q5; COR′; lower alkyl or lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; m is an integer selected from 0, 1, 2 or 3; R′ and R″ are independently hydrogen or lower alkyl; R2 and R3 are unsubstituted or substituted with lower alkyl, CN, OR6, SO3H, C(═O)—NH—SO2—CH3, CONR6R7, COOR6, COR6 or NR6R7; R6 and R7 are taken separately and are independently hydrogen; lower alkyl or lower alkyl substituted with NH2, COOH or OH; or R6 and R7 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S or N, the ring being unsubstituted or substituted with (CH2)m—Q5; COR′; lower alkyl or lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; X5 is a lower alkylene, a lower alkylene substituted with OR3 or COOR3 or a lower alkylene incorporating an O or N; R5 is aryl; heteroaryl; C3-C7 cycloalkyl optionally incorporating C(═O) or one to three O, S or N or C3-C7 cycloalkenyl optionally incorporating C(═O) or one to three O, S or N.
- 8. The compound of formula (I) according to claim 5 wherein:
R1 is hydrogen, halogen or OR2; R2 is hydrogen; lower alkyl ; lower alkyl substituted with CN, C(═O)—NH—SO2—CH3, OR6, SO3H, COOR6 or NR6R7; Q4-oxadiazole; Q4-tetrazole; Q4-morpholine; Q4-furan or Q4-isoxazole; Q4 is lower alkyl incorporating one O, S or N or (CH2)n; n is 1 or 2; R2 is unsubstituted or substituted with CH3, OR6 or COOR6; R6 and R7 are independently hydrogen, lower alkyl or lower alkyl substituted with NH2 or COOH.
- 9. The compound of formula (I) according to claim 5 wherein:
R1 is X5—R5; X5 is a single bond; R5 is phenyl, phenyl substituted with one to three lower alkyl or C(═O)NR3R4, pyridyl or pyridyl substituted with one to three lower alkyl or C(═O)NR3R4; R3 and R4 are taken together with the nitrogen atom to which they are linked to form a 4- to 8-membered ring having one or two O, S, S(═O), SO2 or N; said ring formed from R3 and R4 is unsubstitued or substituted with a 4- to 8-membered ring having one or two O, S or N; unsubstituted lower alkyl or lower alkyl substituted with OR′, NR′R″, C(═O)NR′R″ or COOR′; R5 is optionally further substituted with a lower alkyl.
- 10. The compound of formula (I) according to claim 5 wherein one of X1, X2, X3 and X4 is —C(R1)— in which R1 is hydrogen while the others are independently C—R1 in which R1 is Q1, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkynyl or X5R5.
- 11. The compound of formula (I) according to claim 10 wherein R1 in the definition of X3 is hydrogen.
- 12. The compound of formula (I) according to claim 5 wherein:
R1 in the definition of X3 is hydrogen, halogen or X5—R5; X5 is a single bond; and R5is aryl or heteroaryl, optionally independently substituted with one, two or three halogen, CN, CF3, SO2Me, OR2, COOR2, NR2R3, SO2NR2R3 or CONR2R3; R2 and R3 are independently hydrogen or lower alkyl.
- 13. The compound of formula (I) according to claim 12 wherein R1 in the definition of X3 is hydrogen or halogen.
- 14. The compound of formula (I) according to claim 5 wherein:
R1 in the definition of X4 is hydrogen; halogen; CF3; O-lower alkyl; COOR2; lower alkyl or lower alkyl substituted with OR2, COOR2 or SO2NR2R3; R2 and R3 are independently hydrogen or lower alkyl.
- 15. The compound of formula (I) according to claim 5 wherein X is NH.
- 16. The compound of formula (I) according to claim 5 wherein Y is NH.
- 17. The compound of formula (I) according to claim 5 wherein Z is O or N—CN.
- 18. The compound of formula (I) according to claim 17 wherein Z is O.
- 19. The compound of formula (I) according to claim 5 wherein:
A is cyclohexyl or cycloheptyl, optionally incorporating C(═O) or O; and A is unsubstituted or substituted with CH3, OH or OCH3.
- 20. The compound of formula (I) according to claim 5 wherein A is unsubstituted cyclohexyl or unsubstituted cycloheptyl.
- 21. The compound of formula (I), (II) or (III) according to claim 1 wherein:
X2 is —C(R1)—; R1 is X5—R5; and X5 is not a single bond.
- 22. Spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one;
6′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; spiro[cycloheptane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 7′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-phenylspiro[cycloheptane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 7′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-bromospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-fluorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′,8′-dichlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′,7′-dichlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′,6′-dichlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-phenylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-iodospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-bromospiro[cyclobutane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-bromospiro[cycloheptane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-bromo4-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-bromospiro[bicyclo[3,2,1]octane-2-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′,8′-dichlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-iodospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-phenylspiro[cycloheptane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-phenylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(3-pyridyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(4-pyridyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-(4-carboxyphenyl)-8′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)-quinazolin]-2′(1′H)-one; 6′-(3-carboxyphenyl)-8′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)-quinazolin]-2′(1′H)-one; 8′-chloro-6′-(1H-indol-5yl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)-quinazolin]-2′(1′H)-one; 8′-chloro-6′-(2-pyridyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(3-dimethylamino-prop-1-ynyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)-quinazolin]-2′(1′H)-one; 8′-chloro-6′-(3-methylamino-prop-1-ynyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-methyl-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(3-N-dimethylamino-propylcarboxamide)phenyl]-spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(2-N-dimethylamino-ethylcarboxamide)phenyl]-spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[3-(3-N-dimethylamino-propylcarboxamide)phenyl]-spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[3-(4-methyl-piperazine-1-carbonyl)-phenyl]spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[3-(2-N-dimethylamino-ethylcarboxamide)phenyl]spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-thione; 8′-chloro-2′-cyanoiminospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazoline; 8′-chloro-2′-methoxyiminospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazoline; 8′-chloro-2′-dimethylaminospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazoline]; 8′-chloro-1′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-1′-(ethoxycarbonylmethyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)-quinazolin]-2′(1′H)-one; 8′-chloro-3′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-pyrimidin-2-yl-piperazine-1-carbonyl)phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-(2-morpholin-4-yl-ethyl)-piperazine-1-carbonyl)-phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazine-1carbonyl)-phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-(2-hydroxy-ethoxy)-ethyl)-piperazine-1-carbonyl)-phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 9′-chlorospiro[cyclohexane-1-5′-(5′,10′-dihydro)]-imidazo[2,1-b]quinazoline; 9′-chlorospiro[cyclohexane-1-5′-(5′,10′-dihydro)]-[1,2,4]triazolo[3,4-b]quinazoline; 9′-chlorospiro[cyclohexane-1-5′-(4′,5′-dihydro)]-[1,2,4]triazolo[4,3a]quinazoline; spiro[cyclohexane-1-9′-(8′,9′-dihydro)-pyrazolo[4′,3′-f]quinazolin]-7′(6′H)-one; 8′-chloro-5′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′,8′-difluorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(morpholin-4-yl)methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-hydroxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-hydroxy-6′-iodo-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-iodo-5′-methoxy-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-cyano-5′-methoxy-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1 ′H)-one; 8′-chloro-5′-[2-(4-morpholino)ethoxy]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1H)-one; 8′-chloro-5′-[2-dimethylaminoethoxy]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1H)-one; 8′-chloro-5′-(2-aminoethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[2-(methylamino)ethoxy]-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1H)-one; 8′-chloro-5′-[2-(2-aminoethoxy)ethoxy]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[3-dimethylaminopropoxy]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1H)-one; 8′-chloro-5′-ethoxycarbonylmethoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′-carboxymethoxy-8′-chloro-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′-carboxypropoxy-8′-chloro-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(3-sulphopropoxy)-spiro[cyclohexane-1-4′(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(2-hydroxy-ethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(5-ethoxycarbonyl-furan-2-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(5-carboxy-furan-2-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-cyanomethoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(1H-tetrazol-5-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(5-hydroxy-[1,2,4]oxadiazol-3-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-iodo-5′-[2-dimethylamino-ethoxy]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazoline]-2′(1′H)-one; 6′-(4-carboxyphenyl)-8′-chloro-5′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-(3-carboxyphenyl)-8′-chloro-5′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[2-(4-methyl-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[2-methyl4-(4-methyl-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinzaolin]-2′(1′H)-one; 8′-chloro-6′-[4-carbamoyl-phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1H)-one; 8′-chloro-6′-[4-((1-methyl-piperidin-4-yl)-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-methoxy-6′-[4-(4-methyl-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8-chloro-5-methoxyspiro[4H-benzo[d][1,3]oxazin-2-ylamine-4-4′-(tetrahydro-pyran-4′-yl)]; 8′-trifluoromethylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-cyanomethylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(3-dimethylamino-2-hydroxy-propoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(3-methylamino-2-hydroxy-propoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[2-(ethoxycarbonylmethyl-amino)-ethoxy]-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[2-(carboxymethyl-amino)-ethoxy]-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one hydrochloride; 8′-chloro-5′-(2-methanesulfonylamino-2-oxo-ethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one or 8′-chloro-5′-(2-[(5-methyl-isoxazol-3-ylmethyl)-amino]ethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one.
- 23. 8′-Bromospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one;
5′,8′-dichlorospiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-bromospiro[cycloheptane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-phenylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(3-pyridyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(4-pyridyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-(4-carboxyphenyl)-8′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro) -quinazolin]-2′(1′H)-one; 6′-(3-carboxyphenyl)-8′-chlorospiro[cyclohexane-1-4′-(3′,4′-dihydro) -quinazolin]-2′(1′H)-one; 8′-chloro-6′-(1H-indol-5yl)spiro[cyclohexane-1-4′-(3′,4′-dihydro) -quinazolin]-2′(1H)-one; 8′-chloro-6′-(2-pyridyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(3-dimethylamino-prop-1-ynyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-(3-methylamino-prop-1-ynyl)spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-methyl-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(3-N-dimethylamino-propylcarboxamide)phenyl]-spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(2-N-dimethylamino-ethylcarboxamide)phenyl]-spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[3-(3-N-dimethylamino-propylcarboxamide)phenyl]-spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[3-(4-methyl-piperazine-1-carbonyl)-phenyl]spiro-[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[3-(2-N-dimethylamino-ethylcarboxamide)phenyl]spiro-[cyclohexane-4-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-pyrimidin-2-yl-piperazine-1-carbonyl)phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-(2-morpholin-4-yl-ethyl)-piperazine-1-carbonyl)-phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazine-1-carbonyl)-phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(4-(2-hydroxy-ethoxy)-ethyl)-piperazine-1-carbonyl)-phenyl]spiro[-cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-methylspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-hydroxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-cyano-5′-methoxy-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[2-(4-morpholino)ethoxy]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]2′(1′H)-one; 5′-carboxymethoxy-8′-chloro-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 5′-carboxypropoxy-8′-chloro-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′)-one 8′-chloro-5′-(3-sulphopropoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(2-hydroxy-ethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(5-ethoxycarbonyl-furan-2-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(5-carboxy-furan-2-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-cyanomethoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(1H-tetrazol-5-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-(5-hydroxy-[1,2,4]oxadiazol-3-ylmethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-(4-carboxyphenyl)-8′-chloro-5′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 6′-(3-carboxyphenyl)-8′-chloro-5′-methoxyspiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[2-methyl-4-(4-methyl-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-(piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-6′-[4-carbamoyl-phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1H)-one; 8′-chloro-6′-[4-((1-methyl-piperidin-4-yl)-piperazine-1-carbonyl)phenyl]spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one; 8′-chloro-5′-[2-(carboxymethyl-amino)-ethoxy]-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one hydrochloride; 8′-chloro-5′-(2-methanesulfonylamino-2-oxo-ethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one or 8′-chloro-5′-(2-[(5-methyl-isoxazol-3-ylmethyl)-amino]ethoxy)-spiro[cyclohexane-1-4′-(3′,4′-dihydro)quinazolin]-2′(1′H)-one.
- 24. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
- 25. A method of treating a disorder mediated by the inhibition of PDE7 in a mammal, said method comprising administering to said mammal in need thereof a therapeutically effective amount of a compound according to claim 1 or a pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
- 26. The method according to claim 25, wherein the disorder is a T-cell-related disease, an autoimmune disease, osteoarthritis, multiple sclerosis, osteoporosis, chronic obstructive pulmonary disease, asthma, cancer, acquired immune deficiency syndrome, allergy or inflammatory bowel disease.
- 27. A process for preparing a compound of formula (I) according to claim 1 in which Y is N—R12, X is N—R9 and Z is O, said process comprising:
reacting a substituted urea of formula 46with a cyclic ketone of formula 47to form the compound of formula (I); and isolating the compound of formula (I).
- 28. A process for preparing a compound of formula (I) according to claim 1 in which Y is O, S or NH, said process comprising:
(1) reacting a compound (2a) 48with a compound P-LG, wherein P is a protecting group and LG is a leaving group, to form compound (2b) 49(2) reacting compound (2b) with R—Li, wherein R is lower alkyl, and, subsequently with a ketone of formula 50to form compound (2c) 51(3) removing the protecting group P under reductive conditions, acidic condition or basic condition to form compound (2d) 52(4) reacting compound (2d) with a compound O═C═N—R9 to form compound (2e) 53(5) reacting compound (2e) with an acid to form the compound of formula (I); and (6) isolating the compound of formula (I).
Priority Claims (1)
Number |
Date |
Country |
Kind |
PCT/EP01/03355 |
Mar 2001 |
WO |
|
CROSS REFERENCE TO RELATED APPLICATION
[0001] This is a continuation of U.S. patent application Ser. No. 10/101,996, filed on Mar. 19, 2002, which claims the benefit of priority from PCT International Application Number PCT/EP01/03355, filed Mar. 21, 2001.
Continuations (1)
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Number |
Date |
Country |
Parent |
10101996 |
Mar 2002 |
US |
Child |
10852404 |
May 2004 |
US |