DK2118077T3 - Triazolforbindelser der modulerer hsp90-aktivitet - Google Patents

Triazolforbindelser der modulerer hsp90-aktivitet Download PDF

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DK2118077T3
DK2118077T3 DK08725339T DK08725339T DK2118077T3 DK 2118077 T3 DK2118077 T3 DK 2118077T3 DK 08725339 T DK08725339 T DK 08725339T DK 08725339 T DK08725339 T DK 08725339T DK 2118077 T3 DK2118077 T3 DK 2118077T3
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optionally substituted
nr7c
alkyl
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heteroaryl
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Dinesh U Chimmanamada
Lijun Sun
Shijie Zhang
Zachary Demko
Teresa Przewloka
Weiwen Ying
Joseph A Burlison
David James
Stefan Michael Schweizer
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Synta Pharmaceuticals Corp
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Claims (23)

1. Forbindelse som vist med følgende strukturformel:
(VIII) eller et farmaceutisk acceptabelt salt deraf Y er O eller S; R3 er -OH, -SH, -NR7H, -OR26, -SR26, -0(CH2)m0H, -0(CH2)mSH, -0(CH2)mNR7H, -S(CH2)mOH, -S(CH2)mSH, -S(CH2)mNR7H, -OC(O)NRi0Ru, -SC(0)NRioRu, -NR7C(0)NRioRii, -0C(0)R7, -SC(0)R7, -NR7C(0)R7, -0C(0)0R7, -SC(0)0R7, -NR7C(0)0R7, -0CH2C(0)R7, -SCH2C(0)R7, -NR7CH2C(0)R7, -0CH2C(0)0R7, -SCH2C(0)0R7, -NR7CH2C(0)0R7, -OCH2C(0)NRioRii, -SCH2C(0)NRioRii, -NR7CH2C(O)NRi0Rii, -0S(0)pR7, -SS(0)pR7, -S(0)p0R7, -NR7S(0)pR7, -OS(O)PNRi0Rii, -SS(O)PNRi0Ru, -NR7S(0)pNRioRu, -0S(0)p0R7, -SS(0)p0R7, -NR7S(0)p0R7, -OC(S)R7, -SC(S)R7, -NR7C(S)R7, -OC(S)OR7, -SC(S)OR7, -NR7C(S)OR7, -OC(S)NRioRu, -SC(S)NRioRu, -NR7C(S)NRi0Ru, -OC(NR8)R7, -SC(NR8)R7, -NR7C(NR8)R7, -OC(NR8)OR7, -SC(NR8)OR7, -NR7C(NR8)OR7, -OC(NR8)NRioRu, -SC(NRs)NRioRii, -NR7C(NR8)NRi0Ru, -0P(0)(0R7)2, eller -SP(0)(0R7)2; R5 er -H, -X2oR5o, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eller eventuelt substitueret heteraralkyl; R7 og R8, for hver forekomst, er uafhængigt, -H, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eller eventuelt substitueret heteraralkyl; Rio og Ru, for hver forekomst, er uafhængigt -H, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eller eventuelt substitueret heteraralkyl; eller Ri0 og Ru, sammen med det nitrogenatom til hvilket de er bundet, danner eventuelt substitueret heterocyclyl eller eventuelt substitueret heteroaryl; R26 er C1-C4 alkyl; R35 og R36, for hver forekomst, er uafhængigt -H, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eller eventuelt substitueret heteraralkyl, eller R35 og R36, sammen med N til hvilke de er bundet danner en 5- til 7-leddet heterocyklisk ring; Rso er eventuelt substitueret aryl eller eventuelt substitueret heteroaryl; X20 er C1-C4 alkyl, NR7, C(O), C(S), C(NR8), eller S(0)p; Z, for hver forekomst, er uafhængigt eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eventuelt substitueret heteroaralkyl, halo, cyano, nitro, guanadino, haloalkyl, heteroalkyl, alkoxy, haloalkoxy, -NR10R11, -0R7, -C(0)R7, -C(0)0R7, -C(S)R7, -C(0)SR7, -C(S)SR7, -C(S)OR7, -C(S)NRioRh, -C(NR8)OR7, -C(NR8)R7, -C(NR8)NRioRh, -C(NR8)SR7, -0C(0)R7, -0C(0)0R7, -OC(S)OR7, -OC(NRs)OR7, -SC(0)R7, -SC(0)0R7, -SC(NR8)OR7, -OC(S)R7, -SC(S)R7, -SC(S)OR7, -OC(0)NRioRii, -OC(S)NRioRu, -OC(NR8)NRioRu, -SC(O)NRi0Rh, -SC(NR8)NRi0Rh, -SC(S)NRioRu, -OC(NR8)R7, -SC(NR8)R7, -C(O)NRi0Rh, -NR8C(0)R7, -NR7C(S)R7, -NR7C(S)OR7, -NR7C(NR8)R7, -NR7C(0)0R7, -NR7C(NRs)OR7, -NR7C(0)NRioRh, -NR7C(S)NRioRh, -NR7C(NR8)NRi0Rh, -SR7, -S(0)pR7, -0S(0)pR7, -0S(0)p0R7, -OS(0)pNRioRu, -S(0)P0R7, -NR8S(0)pR7, -NR7S(0)pNRioRii, -NR7S(0)p0R7, -S(0)pNRioRu, -SS(0)PR7, -SS(0)P0R7, -SS(0)pNRioRii, -0P(0)(0R7)2, eller -SP(0)(0R7)2; t er O, 1, 2, 3, eller 4; p, for hver forekomst, er uafhængigt, 1 eller 2; m, for hver forekomst, er uafhængigt 1, 2, 3, eller 4; hvor eventuelle substituenter på alkyl-, alkylen-, alkenyl-, alkynyl-, cycloalkyl-, cycloalkenyl-, heterocyclyl-, aryl-, aralkyl-, heteroaryl-, og heteroarylgrupper er valgt fra alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteraralkyl, haloalkyl, heteroalkyl, alkoxy, -C(0)NR28R29, -C(S)NR28R29, -C(NR32)NR28R29/ -NR33C(0)R3i, -NR33C(S)R3i, -NR33C(NR32)R3i, halo, -OR33, cyano, nitro, haloalkoxy, -C(0)R33, -C(S)R33, -C(NR32)R33, -NR28R29, -C(0)0R33, -C(S)OR33, -C(NR32)OR33, -0C(0)R33, -OC(S)R33, -OC(NR32)R33, -NR3oC(0)NR28R29, -NR33C(S)NR28R29, -NR33C(NR32)NR28R29, -0C(0)NR28R29, -OC(S)NR28R29, -OC(NR32)NR28R29, -NR33C(0)0R31, -NR33C(S)0R31, -NR33C(NR32)OR3i, -S(0)hR33, -0S(0)P’R33, -NR33S(0)P R33, -S(0)P’NR28R29, -0S(0)P NR28R29, eller -NR33S(0)pNR28R29 guanadino, -C(0)SR3i, -C(S)SR3i, -C(NR32)SR3i, -0C(0)0R3i, -OC(S)OR3i, -OC(NR32)OR3i, -SC(0)R33, -SC(0)0R3i, -SC(NR32)OR3), -SC(S)R33, -SC(S)OR3i, -SC(0)NR28R29, -SC(NR32)NR28R28, -SC(S)NR28R29, -SC(NR32)R33, -0S(0)p0R3i, -S(0)POR31, -NR3oS(0)pOR3i, -SS(0)P'R33, -SS(0)P'0R3i, -SS(0)p'NR28R29, -0P(0)(0R3i)2, eller -SP(0)(0R3i)2; R28 og R29, for hver forekomst er uafhængigt, H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl eller heteraralkyl; og R33 og R3i for hver forekomst er uafhængigt, H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl eller heteraralkyl; R32, for hver forekomst er uafhængigt, H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteraralkyl, -C(0)R33, -C(0)NR28R29, -S(0)P'R33, eller -S(0)P'NR28R29; p' er 0, 1 eller 2; h er 0, 1 eller 2; og endvidere, alkyl, cycloalkyl, alkylen, heterocyclyl, og hvilke som helst mættet del af alkenyl-, cycloalkenyl-, alkynyl-, aralkyl-, og heteroaralkylgrupper, kan også erstattes med =0, =S, =N-R32.
2. Forbindelsen ifølge krav 1, hvor R35 og R36, sammen med N til hvilke de er bundet danner en 5- eller 6-leddet heterocyklisk ring.
3. Forbindelsen ifølge krav 1, hvor forbindelsen er vist med den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf; hvor: R2 er -OH, -SH, -NR7H, -OR26, -SR25, -0(CH2)mOH, -0(CH2)mSH, -0(CH2)mNR7H, -S(CH2)mOH, -S(CH2)mSH, -S(CH2)mNR7H, -OC(O)NRi0Rn, -SC(0)NRioRu, -NR7C(0)NRioRh, -0C(0)R7, -SC(0)R7, -NR7C(0)R7, -0C(0)0R7, -SC(0)0R7, -NR7C(0)0R7, -0CH2C(0)R7, -SCH2C(0)R7, -NR7CH2C(0)R7, -0CH2C(0)0R7, -SCH2C(0)0R7, -NR7CH2C(0)0R7, -OCH2C(0)NRioRh, -SCH2C(0)NRioRh, -NR7CH2C(O)NRi0Ru, -0S(0)pR7, -SS(0)pR7, -S(0)p0R7, -NR7S(0)pR7, -OS(O)pNRi0Rh, -SS(O)pNRi0Ru, -NR7S(0)pNRioRu, -0S(0)p0R7, -SS(0)p0R7, -NR7S(0)p0R7, -OC(S)R7, -SC(S)R7, -NR7C(S)R7, -OC(S)OR7, -SC(S)OR7, -NR7C(S)OR7, -OC(S)NRioRn, -SC(S)NRioRu, -NR7C(S)NRi0Ru, -OC(NR8)R7, -SC(NR8)R7, -NR7C(NR8)R7, -OC(NR8)OR7, -SC(NR8)OR7, -NR7C(NR8)OR7, -OC(NR8)NRioRu, -SC(NR8)NRioRii, -NR7C(NR8)NRi0Ru, -0P(0)(0R7)2, eller -SP(0)(0R7)2; og n er 0, 1, 2, eller 3.
4. Forbindelsen ifølge krav 3, hvor forbindelsen er vist med den følgende strukturformel: w
eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelsen ifølge krav 4, hvor R2 og R3 er uafhængigt -OH, -SH, eller -NHR7.
6. Forbindelsen ifølge krav 1 eller krav 4, hvor Z er C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkyl sulfanyl eller C3-C6 cycloalkyl.
7. Forbindelsen ifølge krav 1 eller krav 4, hvor R5 er eventuelt substitueret indolyl, eventuelt substitueret benzoimidazolyl, eventuelt substitueret indazolyl, eventuelt substitueret 3H-indazolyl, eventuelt substitueret indolizinyl, eventuelt substitueret quinolinyl, eventuelt substitueret isoquinolinyl, eventuelt substitueret benzoxazolyl, eventuelt substitueret benzo[l,3]dioxolyl, eventuelt substitueret benzofuryl, eventuelt substitueret benzothiazolyl, eventuelt substitueret benzo[d]isoxazolyl, eventuelt substitueret benzo[d]isothiazolyl, eventuelt substitueret thiazolo[4,5-c]pyridinyl, eventuelt substitueret thiazolo[5,4-c]pyridinyl, eventuelt substitueret thiazolo[4,5-b]pyridinyl, eventuelt substitueret thiazolo[5,4-b]pyridinyl, eventuelt substitueret oxazolo[4,5-cjpyridinyl, eventuelt substitueret oxazolo[5,4-c]pyridinyl, eventuelt substitueret oxazolo[4,5-b]pyridinyl, eventuelt substitueret oxazolo[5,4-b]pyridinyl, eventuelt substitueret imidazopyridinyl, eventuelt substitueret benzothiadiazolyl, benzoxadiazolyl, eventuelt substitueret benzotriazolyl, eventuelt substitueret tetrahydroindolyl, eventuelt substitueret azaindolyl, eventuelt substitueret quinazolinyl, eventuelt substitueret purinyl, eventuelt substitueret imidazo[4,5-a]pyridinyl, eventuelt substitueret imidazo[l,2-ajpyridinyl, eventuelt substitueret 3F/-imidazo[4,5-b]pyridinyl, eventuelt substitueret 1H-imidazo[4,5-b]pyridinyl, eventuelt substitueret lfV-imidazo[4,5-c]pyridinyl, eventuelt substitueret 3H-imidazo[4,5-c]pyridinyl, eventuelt substitueret pyridopyrdazinyl, og eventuelt substituted pyridopyrimidinyl, eventuelt substitueret pyrrolo[2,3]pyrimidyl, eventuelt substitueret pyrazolo[3,4]pyrimidyl eventuelt substitueret cyclopentaimidazolyl, eventuelt substitueret cyclopentatriazolyl, eventuelt substitueret pyrrolopyrazolyl, eventuelt substitueret pyrroloimidazolyl, eventuelt substitueret pyrrolotriazolyl, eller eventuelt substitueret benzo(b)thienyl; hvor eventuelle substituenter på aryl, aralkyl, heteroaryl, og heteroarylgrupper er som defineret i krav 1.
8. Forbindelsen ifølge krav 1 eller krav 4, hvor R5 er valgt fra gruppen bestående af:
hvor: Xu, for hver forekomst, er uafhængigt CH, CR9, N, N(0), eller N+(Ri7); X12, for hver forekomst, er uafhængigt CH, CR9, N, N(O), N+(Ri7), forudsat at mindst én Xi2-gruppe er uafhængigt valgt fra CH og CRg; X13, for hver forekomst, er uafhængigt O, S, S(0)p, NR7, eller NRi7; R9, for hver forekomst, er uafhængigt en substituent valgt fra gruppen bestående af eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eventuelt substitueret heteraralkyl, halo, cyano, nitro, guanadino, hydroxyalkyl, alkoxyalkyl, haloalkyl, heteroalkyl, -NR10R11, -OR7, -C(0)R7, -C(0)0R7, -0C(0)R7, -C(0)NRioRu, -NR8C(0)R7, -SR7, -S(0)pR7, -0S(0)pR7, -S(0)p0R7, -NR8S(0)pR7, eller -S(O)PNRi0Rn, -S(0)P0R7, -0P(0)(0R7)2, eller -SP(0)(0R7)2, -S(0)p0R7, -0P(0)(0R7)2, eller -SP(0)(0R7)2; eller to Rg-grupper sammen med det carbonatom til hvilket de er bundet danner en kondenseret ring; og Ri7, for hver forekomst, er uafhængigt alkyl eller aralkyl; hvor eventuelle substituenter på alkyl, alkylen, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, aralkyl, heteroaryl, og heteroarylgrupper er som defineret i krav 1.
9. Forbindelsen ifølge krav 1 eller krav 4, hvor R5 er
10. Forbindelsen ifølge krav 1 eller krav 4, hvor R5 er X20R5o, hvor X20 er C1-C4 alkyl og R50 er eventuelt substitueret phenyl.
11. Forbindelsen ifølge krav 1, hvor forbindelsen er vist med den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf X42 er CR44 eller N; R4i er -H, -OH, -SH, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eventuelt substitueret heteraralkyl, halo, cyano, nitro, guanadino, haloalkyl, heteroalkyl, alkoxy eller cycloalkoxy, haloalkoxy, -NR10R11, -0R7, -C(0)R7, -C(0)0R7, -C(S)R7, -C(0)SR7, -C(S)SR7, -C(S)OR7, -C(S)NRioRu, -C(NR8)OR7, -C(NR8)R7, -C(NR8)NRi0Rii, -C(NRs)SR7, -0C(0)R7, -0C(0)0R7, -OC(S)OR7, -OC(NR8)OR7, -SC(0)R7, -SC(0)0R7, -SC(NR8)OR7, -OC(S)R7, -SC(S)R7, -SC(S)OR7, -OC(0)NRioRn, -OC(S)NRioRu, -OC(NR8)NRioRh, -SC(O)NRi0Ru, -SC(NR8)NRi0Rh, -SC(S)NRioRu, -OC(NR8)R7, -SC(NR8)R7, -C(O)NRi0Ru, -NR8C(0)R7, -NR7C(S)R7, -NR7C(S)OR7, -NR7C(NR8)R7, -NR7C(0)0R7, -NR7C(NR8)OR7, -NR7C(0)NRioRu, -NR7C(S)NRioRh, -NR7C(NR8)NRi0Ru, -SR7, -S(0)pR7, -0S(0)pR7, -0S(0)p0R7, -OS(0)pNRioRn, -S(0)p0R7, -NR8S(0)pR7, -NR7S(0)pNRioRii, -NR7S(0)p0R7, -S(O)PNRi0Rn, -SS(0)PR7, -SS(0)p0R7, -SS(0)PNRioRii, -0P(0)(0R7)2, eller -SP(0)(0R7)2; R42 er -H, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eventuelt substitueret heteraralkyl, hydroxyalkyl, alkoxyalkyl, haloalkyl, heteroalkyl, -C(0)R7, -(CH2)mC(0)0R7, -C(0)0R7, -0C(0)R7, -C(0)NRioRu, -S(0)PR7, -S(0)P0R7, eller -S(O)PNRi0Rn; R43 og R44 er, uafhængigt, -H, -OH, eventuelt substitueret alkyl, eventuelt substitueret alkenyl, eventuelt substitueret alkynyl, eventuelt substitueret cycloalkyl, eventuelt substitueret cycloalkenyl, eventuelt substitueret heterocyclyl, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret aralkyl, eventuelt substitueret heteraralkyl, hydroxyalkyl, alkoxyalkyl, halo, cyano, nitro, guanadino, haloalkyl, heteroalkyl, -C(0)R7, -C(0)0R7, -0C(0)R7, -C(0)NRioRu, -NR8C(0)R7, -SR7, -S(0)pR7, -0S(0)pR7, -S(0)P0R7, -NR8S(0)pR7, -S(0)pNRioRn, eller R43 og R44 sammen med det carbonatom til hvilket de er bundet danner eventuelt substitueret cycloalkenyl, eventuelt substitueret aryl, eventuelt substitueret heterocyclyl, eller eventuelt substitueret heteroaryl; og R45 er -H, -OH, -SH, -NR7H, -OR26, -SR26, -NHR26, -0(CH2)m0H, -0(CH2)mSH, -0(CH2)mNR7H, -S(CH2)mOH, -S(CH2)mSH, -S(CH2)mNR7H, -OC(0)NRioRu, -SC(0)NRioRu, -NR7C(O)NRi0Ru, -0C(0)R7, -SC(0)R7, -NR7C(0)R7, -0C(0)0R7, -SC(0)0R7, -NR7C(0)0R7, -0CH2C(0)R7, -SCH2C(0)R7, -NR7CH2C(0)R7, -0CH2C(0)0R7, -SCH2C(0)0R7, -NR7CH2C(0)0R7, -OCH2C(0)NRioRu, -SCH2C(0)NRioRu, -NR7CH2C(0)NRioRii, -0S(0)pR7, -SS(0)PR7, -NR7S(0)pR7, -OS(O)PNRi0Ru, -SS(0)PNRioRii, -NR7S(0)PNRioRii, -0S(0)P0R7, -SS(0)P0R7, -NR7S(0)p0R7, -OC(S)R7, -SC(S)R7, -NR7C(S)R7, -OC(S)OR7, -SC(S)OR7, -NR7C(S)OR7, -OC(S)NRioRh, -SC(S)NRi0Ru, -NR7C(S)NRioRu, -OC(NRs)R7, -SC(NRs)R7, -NR7C(NR8)R7, -OC(NRs)OR7, -SC(NR8)OR7, -NR7C(NRs)OR7, -OC(NRs)NRioRu, -SC(NR8)NRioRh, eller -NR7C(NR8)NRioRii; hvor eventuelle substituenter på alkyl, alkylen, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, aralkyl, heteroaryl, og heteroarylgrupper er som defineret i krav 1.
12. Forbindelsen ifølge krav 11, hvor X42 er CR44, og R43 og R44 er, uafhængigt, valgt fra gruppen bestående af -H, methyl, ethyl, propyl, isopropyl, cyclopropyl.
13. Forbindelsen ifølge krav 11, hvor X42 er N.
14. Forbindelsen ifølge krav 11, hvor forbindelsen er vist med den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf.
15. Forbindelsen ifølge krav 14, hvor R41 er valgt fra gruppen bestående af -H, methyl, ethyl, propyl, isopropyl, cyclopropyl, methoxy, ethoxy, propoxy, og cyclopropoxy.
16. Forbindelsen ifølge krav 15, hvor R42 er -Fl eller eventuelt substitueret C1-C4 alkyl, hvor eventuelle substituenter på alkylgrupperne er som defineret i krav 1.
17. Forbindelsen ifølge et hvilket som helst af kravene 1, 4 og 16, hvor en af R35 eller R36 er -H.
18. Forbindelse ifølge krav 1 som vist med den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf.
19. Forbindelse ifølge krav 1 som vist med den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf.
20. Forbindelse ifølge krav 1 som vist med den følgende strukturformel:
eller et farmaceutisk acceptabelt salt deraf.
21. Forbindelse ifølge et hvilket som helst af kravene 1 til 20 til anvendelse i: (a) behandling eller inhibering af angiogenese; (b) behandling eller forebyggelse afen proliferativ forstyrrelse; (c) tilstopning, okkludering, eller på anden måde afbrydelse af blodstrømningen i neovaskulatur; (d) behandling af ikke-Flodgkin's lymfom; (e) behandling eller forebyggelse af en svampe-, bakterie-, virus- eller parasitinfektion; (f) behandle eller forebygge en inflammatorisk lidelse eller en immunforstyrrelse; (g) undertrykke immunsystemet hos et individ med behov derfor; eller (h) behandle en sygdom valgt fra: cancer; infektionssygdomme; autoimmune forstyrrelser; benigne tumorer; arteroskleriske plaks; okulære angiogene sygdomme; rheumatoid arthritis; psoriasis; vorter; allergisk dermatitis; blistsygdomme; Karposi sarcom; forsinket sårheling; endometriose; livmoderblødning; ovariecyster; ovarie-hyperstimulation; vasculogenese; granulationer; hypertrofe ar (keloider); nonunion frakturer; scleroderma; trachoma; vaskulære adhæsioner; vaskulære malfunktioner; DiGeorge syndrom; HHT; transplantations- arteriopati; restinose; fedme; myokardial angiogenese; koronar kollateral; cerebral kollateral; arteriovenøse malfunktioner; iskæmisk lem-angiogenese; primær pulmonær hypertension; astma; næsepolypper; inflammatorisk tarmsygdom; periodontal sygdom; ascites; peritoneale adhæsioner; Osler-Webber Syndrom; plak-neovaskularisering; telangiectasi; hæmofilisamlinger; synovitis; osteomyelitis; osteophytdannelse; angiofibrom; fibromuskulær dysplasi; sårgranulering; Crohn's sygdom; og aterosklerose.
22. Anvendelse af en forbindelse ifølge et hvilket som helst af kravene 1 til 20 til fremstillingen af et medikament til: (a) behandlingen eller inhibition of angiogenese; (b) behandlingen eller forebyggelse afen proliferativ forstyrrelse; (c) tilstopning, okkludering, eller på anden måde afbrydelse af blodstrømningen i neovaskulatur; (d) behandlingen et en ikke-Hodgkin's lymfom; (e) behandlingen eller forebyggelse af en svampe-, bakterie-, virus- eller parasitinfektion; (f) behandlingen eller forebyggelse af en inflammatorisk lidelse eller en immunforstyrrelse; (g) undertrykkelse af immunsystemet hos et individ med behov derfor; eller (h) behandlingen af en sygdom valgt fra : cancer; infektionssygdomme; autoimmune forstyrrelser; benigne tumorer; arteroskleriske plaks; okulære angiogene sygdomme; rheumatoid arthritis; psoriasis; vorter; allergisk dermatitis; blist-sygdomme; Karposi sarcoma; forsinket sårheling; endometriosis; livmoderblødning; ovariecyster; ovarie-hyperstimulering; vasculogenese; granulationer; hypertrofiske ar (keloider); nonunion frakturer; scleroderma; trachoma; vaskulære adhæsioner; vaskulære malfunktioner; DiGeorge syndrom; HHT; transplantations-arteriopati; restinose; fedme; myokardial angiogenese; koronar kollateral; cerebral kollateral; arteriovenøse malfunktioner; iskæmisk lem-angiogenese; primær pulmonær hypertension; astma; næsepolypper; inflammatorisk tarmsygdom; periodontal sygdom; ascites; peritoneale adhæsioner; Osler-Webber Syndrom; plak-neovaskularisering; telangiectasi; hæmofilisamlinger; synovitis; osteomyelitis; osteophyt-dannelse; angiofibrom; fibromuskulær dysplasi; sår-granulering; Crohn's sygdom; og aterosklerose.
23. Farmaceutisk sammensætning, omfattende en farmaceutisk acceptabel bærer og forbindelse ifølge et hvilket som helst af kravene 1 til 20.
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