HRP20131048T1 - Cikliäśki derivati kao modulatori aktivnosti receptora kemokina - Google Patents

Cikliäśki derivati kao modulatori aktivnosti receptora kemokina Download PDF

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HRP20131048T1
HRP20131048T1 HRP20131048TT HRP20131048T HRP20131048T1 HR P20131048 T1 HRP20131048 T1 HR P20131048T1 HR P20131048T T HRP20131048T T HR P20131048TT HR P20131048 T HRP20131048 T HR P20131048T HR P20131048 T1 HRP20131048 T1 HR P20131048T1
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Croatia
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methyl
amino
isopropyl
tert
oxopyrrolidin
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HRP20131048TT
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Percy H. Carter
Robert J. Cherney
Douglas G. Batt
John V. Duncia
Daniel S. Gardner
Soo S. Ko
Anurag Srivastava
Michael G. Yang
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Bristol-Myers Squibb Company
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Application filed by Bristol-Myers Squibb Company filed Critical Bristol-Myers Squibb Company
Publication of HRP20131048T1 publication Critical patent/HRP20131048T1/hr

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Claims (21)

1. Spoj formule (Ia): [image] ili njegov stereoizomer ili farmaceutski prihvatljiva sol, gdje: Z se izabire između -NR8C(O)- i -NR9-; R1 se izabire između H, R6, C1-6 alkila supstituiranog s 0-3 R6, C2-6 alkenila supstituiranog s 0-3 R6, C2-6 alkinila supstituiranog s 0-3 R6, C6-10 arilne skupine supstituirane s 0-5 R6, i 5-10-eročlanog heteroarilnog sustava koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiranog s 0-3 R6; R2 se izabire između C6-10 arilne skupine supstituirane s 0-5 R7 i 5-10-eročlanog heteroarilnog sustava koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiranog s 0-3 R7; R5 je -NR5aR5a; R5a, pri svakom pojavljivanju, se nezavisno izabire između H, metil, C1-6 alkila supstituiranog s 0-2 R5e gdje se alkil izabire između etil, propil, i-propil, butil, i-butil, pentil, heksil; alila supstituiranog s 0-1 R5e; propinila supstituiranog s 0-1 R5e; i (CH2)r-C3-4 karbocikličkog ostatka supstituiranog s 0-5 R5e, gdje se karbociklički ostatak izabire između ciklopropil, i ciklobutil; R5e, pri svakom pojavljivanju, se izabire između C1-6 alkil, C2-8 alkenil, C2-8 alkinil, C3-6 cikloalkil, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkil, OH, SH, (CH2)rSC1-5 alkil, (CH2)rNR5fR5f, i (CH2)rfenil; R5f, pri svakom pojavljivanju, se izabire između H, C1-6 alkil, i C3-6 cikloalkil; R6, pri svakom pojavljivanju, se izabire između C1-8 alkil, (CH2)rC3-6 cikloalkil, Cl, Br, I, F, NO2, CN, (CR’R’)rNR6aR6a, (CR’R’)rOH, (CR’R’)rO (CR’R’)rR6d, (CR’R’)rSH, (CR’R’)rC (O)H, (CR’R’)rS (CR’R’)rR6d, (CR’R’)rSC (O) (CR’R’)rR6b, (CR’R’)rC (O)OH, (CR’R’)rC (O) (CR’R’)rR6b, (CR’R’)rC (O) NR6aR6a, (CR’R’)rNR6fC (O) (CR’R’)rR6b, (CR’R’)rC (O) O (CR’R’)rR6d, (CR’R’)rOC (O) (CR’R’)rR6b, (CR’R’)rOC (O) NR6a (CR’R’)rR6d, (CR’R’)rNR6aC (O) NR6a (CR’R’)rR6d, (CR’R’)rNR6aC (S) NR6a (CR’R’)rR6d, (CR’R’)rNR6fC (O) O (CR’R’)rR6b, (CR’R’)rC (=NR6f) NR6aR6a, (CR’R’)rNHC (=NR6f) NR6fR6f, -(CR’R’)rS (O)p (CR’R’)rR6b, (CR’R’)rS (O)2NR6aR6a, (CR’R’)rNR6fS (O)2NR6aR6a, (CR’R’)rNR6fS (O)2 (CR’R’)rR6b, C1-6 haloalkil, C2-8 alkenil supstituiran s 0-3 R’, C2-8 alkinil supstituiran s 0-3 R’, (CR’R’)rfenil supstituiran s 0-3 R6e, i (CH2)r-5-6-eročlani heterociklički sustav koji sadrži 1-2 heteroatoma izabrana između N, O, i S, supstituiran s 0-2 R6e; alternativno, dva R6 na susjednim atomima na R1 mogu se spojiti da formiraju ciklički acetal; R6a, pri svakom pojavljivanju, se izabire između H, metila supstituiranog s 0-1 R6g, C2-6 alkila supstituiranog s 0-2 R6e, C3-8 alkenila supstituiranog s 0-2 R6e, i C3-8 alkinila supstituiranog s 0-2 R6e; R6b, pri svakom pojavljivanju, se izabire između H, C1-6 alkila supstituiranog s 0-2 R6e, C3-8 alkenila supstituiranog s 0-2 R6e, i C3-8 alkinila supstituiranog s 0-2 R6e; R6d, pri svakom pojavljivanju, se izabire između C3-8 alkenila supstituiranog s 0-2 R6e, C3-8 alkinila supstituiranog s 0-2 R6e, metil, CF3, C2-6 alkil supstituiran s 0-3 R6e, i C2-4 haloalkil; R6e, pri svakom pojavljivanju, se izabire između C1-6 alkil, C2-8 alkenil, C2-8 alkinil, (CH2)rC3-6 cikloalkil, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkil, OH, SH, (CH2)rSC1-5 alkil, (CH2)rNR6fR6f, i (CH2)rfenil; R6f, pri svakom pojavljivanju, se izabire između H, C1-5 alkil, i C3-6 cikloalkil, i fenil; R6g se nezavisno izabire između- C (O) R6b, -C (O) OR6d, -C (O) NR6fR6f, i (CH2)rfenil; R7, pri svakom pojavljivanju, se izabire između C1-8 alkil, (CH2)rC3-6 cikloalkil, Cl, Br, I, F, NO2, CN, (CR’R’)rNR7aR7a, (CR’R’)rOH, (CR’R’)rO (CR’R’)rR7d, (CR’R’)rSH, (CR’R’)rC (O) H, (CR’R’)rS (CR’R’)rR7d, (CR’R’)rC (O) OH, (CR’R’)rC (O) (CR’R’)rR7b, (CR’R’)rC (O) NR7aR7a, (CR’R’)rNR7fC (O) (CR’R’)rR7b, (CR’R’)rC (O) O (CR’R’)rR7d, (CR’R’)rOC (O) (CRR’)rR7b, (CR’R’)rOC (O) NR7a (CR’R’)rR7a, (CR’R’)rNR7aC (O) NR7a (CR’R’)rR7a, (CR’R’)rNR7fC (O) O (CR’R’)rR7d, (CR’R’)rC (=NR7f) NR7aR7a, (CR’R’)rNHC (=NR7f) NR7fR7f, (CR’R’)rS (O)p (CR’R’)rR7b, (CR’R’)rS (O)2NR7aR7a, (CR’R’)rNR7aS (O)2NR7aR7a, (CR’R’)rNR7fS (O)2 (CR’R’)rR7b, C1-6 haloalkil, C2-8 alkenil supstituiran s 0-3 R’, C2-8 alkinil supstituiran s 0-3 R’, i (CR’R’)rfenil supstituiran s 0-3 R7e; alternativno, dva R7 na susjednim atomima na R2 mogu se spojiti da formiraju ciklički acetal; R7a, pri svakom pojavljivanju, se nezavisno izabire između H, metila supstituiranog s 0-1 R7g, C2-6 alkila supstituiranog s 0-2 R7e, C3-8 alkenila supstituiranog s 0-2 R7e, C3-8 alkinila supstituiranog s 0-2 R7e, (CH2)r-C3-10 karbocikličkog ostatka supstituiranog s 0-5 R7e, i (CH2)r-5-10-eročlanog heterocikličkog sustava koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiranog s 0-2 R7e; R7b, pri svakom pojavljivanju, se izabire između C1-6 alkila supstituiranog s 0-2 R7e, C3-8 alkenila supstituiranog s 0-2 R7e, C3-8 alkinila supstituiranog s 0-2 R7e, (CH2)rC3-6 karbocikličkog ostatka supstituiranog s 0-3 R7e, i (CH2)r-5-6-eročlanog heterocikličkog sustava koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiranog s 0-2 R7e; R7d, pri svakom pojavljivanju, se izabire između C3-8 alkenila supstituiranog s 0-2 R7e, C3-8 alkinila supstituiranog s 0-2 R7e, metil, CF3, C2-4 haloalkil, C2-6 alkil supstituiran s 0-3 R7e, (CH2)r-C3-10 karbociklički ostatak supstituiran s 0-3 R7e, i (CH2)r-5-6-eročlani heterociklički sustav koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiran s 0-3 R7e; R7e, pri svakom pojavljivanju, se izabire između C1-6 alkil, C2-8 alkenil, C2-8 alkinil, (CH2)rC3-6 cikloalkil, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkil, OH, SH, C (O) OC1-5 alkil, (CH2)rSC1-5 alkil, (CH2)rNR7fR7f, i (CH2)rfenil; R7f, pri svakom pojavljivanju, se izabire između H, C1-5 alkil, i C3-6 cikloalkil, i fenil; R7g se nezavisno izabire između- C (O) R7b, -C (O) OR7d, -C (O) NR7fR7f, i (CH2)rfenil; R’, pri svakom pojavljivanju, se izabire između H, C1-6 alkila supstituiranog s R6e, C2-8 alkenil, C2-8 alkinil, (CH2)rC3-6 cikloalkil; R8 se izabire između H, C1-4 alkil, i C3-4 cikloalkil; R9 se izabire između H, C1-4 alkil, C3-4 cikloalkil, -C (O) H, i - C (O)- C1-4alkil; p, pri svakom pojavljivanju, se nezavisno izabire između 0, 1, i 2; i r, pri svakom pojavljivanju, se nezavisno izabire između 0, 1, 2, 3, i 4.
2. Spoj prema zahtjevu 1, gdje: R5a, pri svakom pojavljivanju, se nezavisno izabire između H, metil, etil, propil, i-propil, butil, i-butil, pentil, heksil, ciklopropil, i ciklobutil; i r, pri svakom pojavljivanju, se izabire između 0, 1, i 2.
3. Spoj prema zahtjevu 2, gdje: R1 se izabire između H, R6, C1-6 alkila supstituiranog s 0-3 R6, C2-6 alkenila supstituiranog s 0-3 R6, C2-6 alkinila supstituiranog s 0-3 R6, C6-10 arilne skupine supstituirane s 0-5 R6, gdje se arilna skupina izabire između fenil i naftil, i 5-10-eročlani heteroarilni sustav koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiran s 0-3 R6, gdje se heteroaril izabire između indolil, benzimidazolil, benzofuranil, benzotiofuranil, benzoksazolil, benztiazolil, benztriazolil, benztetrazolil, benzizoksazolil, benzizotiazolil, benzimidazalonil, cinolinil, furanil, imidazolil, indazolil, indolil, izonikotinil, izokinolinil izotiazolil, izoksazolinil, izoksazolil, oksazolil, ftalazinil, pikolinil, pirazinil, pirazolil, piridazinil, piridil, piridinil, pirimidinil, pirolil, kinazolinil, kinolinil, tiazolil, tienil, triazinil, i tetrazolil; R2 se izabire između fenila supstituiranog s 0-2 R7, i 5-10-eročlanog heteroarilnog sustava koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiranog s 0-3 R7 gdje se heteroaril izabire između indolil, benzimidazolil, benzofuranil, benzotiofuranil, benzoksazolil, benztiazolil, benztriazolil, benztetrazolil, benzizoksazolil, benzizotiazolil, benzimidazalonil, cinolinil, furanil, imidazolil, indazolil, indolil, izokinolinil izotiazolil, izoksazolil, oksazolil, ftalazinil, pirazinil, pirazolil, piridazinil, piridil, piridinil, pirimidinil, pirolil, pirolotriazinil, kinazolinil, kinolinil, tiazolil, tienil, i tetrazolil; i R8 se izabire između H, metil, etil, propil, i-propil, i ciklopropil.
4. Spoj prema zahtjevu 2 ili 3, gdje: R6, pri svakom pojavljivanju, se izabire između C1-8 alkil, C2-8 alkenil, C2-8 alkinil, (CH2)rC3-6 cikloalkil, Cl, Br, I, F, NO2, CN, (CH2)rNR6a’R6a’, (CH2)rOH, (CH2)rO (CH2)rR6d, (CH2)rSH, (CH2)rC (O) H, (CH2)rS (CH2)rR6d, (CH2)rC(O) OH, (CH2)rC (O) (CH2)rR6b, (CH2)rC (O) NR6aR6a, (CH2)rNR6fC (O) R6b’, (CH2)rC (O) O (CH2)rR6d, (CH2)rNR6aC (O) NR6a’R6d’, (CH2)rNR6aC (S) NR6aR6a, (CH2)rOC (O) (CH2)rR6b, (CH2)rS (O)pR6b’, (CH2)rS(O)2NR6aR6a, (CH2)rNR6fS (O)2 (CH2)rR6b, (CH2)rNR6fS (O)2 NR6aR6a, C1-6 haloalkil, i (CH2)rfenil supstituiran s 0-3 R6e, i (CH2)r- 5-6-eročlani heterociklički sustav koji sadrži 1- 2 heteroatoma izabrana između N, O, i S, supstituiran s 0-2 R6e, gdje se heterociklički sustav izabire između aziridinil, azetidinil, pirolil, piperidinil, i morfolinil; R6a, pri svakom pojavljivanju, se nezavisno izabire između H, metil, etil, propil, i-propil, butil, i-butil, t-butil, pentil, i heksil; R6b, pri svakom pojavljivanju, se izabire između H, metil, etil, propil, i-propil, butil, i-butil, t-butil, pentil, i heksil; R6d, pri svakom pojavljivanju, se izabire između metil, CF3, etil, propil, i-propil, butil, i-butil, t-butil, pentil, i heksil; R6e, pri svakom pojavljivanju, se izabire između C1-6 alkil, C2-8 alkenil, C2-8 alkinil, (CH2)rC3-6 cikloalkil, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkil, OH, SH, (CH2)rSC1-5 alkil, (CH2)rNR6fR6f, C (O) NHR6h, C (O) OC1-5 alkil, (CH2)rOH, C (O) OH, (CH2)rC (O) NHSO2- R6h, NHSO2R6h, (CH2)rtetrazolil, i (CH2)rfenil i (CH2)r-5-6-eročlani heterociklički sustav koji sadrži 1- 4 heteroatoma izabrana između N, O, i S; R6f, pri svakom pojavljivanju, se izabire između H, metil, etil, propil, i-propil, butil, i-butil, t-butil, pentil, heksil, ciklopropil, i fenil; R7 se izabire između metil, etil, propil, i-propil, butil, i-butil, s-butil, t-butil, pentil, heksil, (CH2)rC3-6 cikloalkil, Cl, Br, I, F, NO2, CN, (CH2)rNR7aR7a, (CH2)rOH, (CH2)rO (CH2)rR7d, (CH2)rSH, (CH2)rC (O) H, (CH2)rS (CH2)rR7d, (CH2)rC (O) OH, (CH2)rC (O) (CH2)rR7b, (CH2)rC (O) NR7aR7a, (CH2)rNR7fC (O) (CH2)rR7b, (CH2)rC (O) O (CH2)rR7d, (CH2)rOC (O) (CH2)rR7b, (CH2)rOC (O) NR7aR7a, (CH2)rNR7aC (O) NR7aR7a, (CH2)rNR7aC (O) O (CH2)rR7d, (CH2)rS (O)p (CH2)rR7b, (CH2)rS (O)2NR7aR7a, (CH2)rNR7fS (O)2 (CH2)rR7b, C1-6 haloalkil, i (CH2)rfenil supstituiran s 0-3 R7e i (CH2)r-5-6-eročlani heterociklički sustav koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiran s 0-3 R7e, gdje se heterociklički sustav izabire između tienil, piridinil, benzotiazolil, i tetrazolil; R7a, pri svakom pojavljivanju, se izabire između H, metil, etil, propil, i-propil, butil, i-butil, t- butil, pentil, heksil, prop-2-enil, 2-metil-2-propenil, ciklopropil, ciklobutil, ciklopentil, cikloheksil, CH2ciklopropil, i benzil; R7b, pri svakom pojavljivanju, se izabire između metil, etil, propil, i-propil, butil, i-butil, t-butil, pentil, heksil, ciklopropil, ciklopentil, CH2-ciklopentil, cikloheksil, CH2- cikloheksil, CF3, pirolidinil, morfolinil, piperizenil supstituiran s 0-1 R7e, i azetidinil; R7d, pri svakom pojavljivanju, se izabire između metil, CF3, CF2CF3, CHF2, CH2F, etil, propil, i-propil, butil, ibutil, t-butil, pentil, heksil, i ciklopropil; R7e, pri svakom pojavljivanju, se izabire između C1-6 alkil, C2-8 alkenil, C2-8 alkinil, (CH2)rC3-6 cikloalkil, Cl, F, Br, I, CN, NO2, (CF2)rCF3, (CH2)rOC1-5 alkil, (CH2)rOH, OH, SH, C (O) OH, C (O) NHR7h, C (O) OC1-5 alkil, (CH2)rSC1-5 alkil, (CH2)rNR7fR7f, (CH2)rC (O) NHSO2- R7h, NHSO2R7h, i (CH2)rfenil, (CH2)rtetrazolil; R7f, pri svakom pojavljivanju, se izabire između H, metil, etil, propil, i-propil, butil, i-butil, t-butil, pentil, heksil, ciklopropil, i fenil; i r je 0 ili 1.
5. Spoj prema zahtjevima 1-4, gdje: R7, pri svakom pojavljivanju, se izabire između metil, etil, propil, i- propil, butil, i- butil, s- butil, t- butil, pentil, heksil, (CH2)rC3-6 cikloalkil, Cl, Br, I, F, NO2, CN, (CH2)rNR7aR7a, (CH2)rOH, (CH2)rOR7d, (CH2)rSH, (CH2)rC(O) H, (CH2)rSR7d, (CH2)rC (O) OH, (CH2)rC (O) R7b, (CH2)rC (O) NR7aR7a, (CH2)rNR7fC (O) R7b, (CH2)rC (O)OR7d, (CH2)rOC (O) R7b, (CH2)rOC (O) NR7aR7a, (CH2)rNR7aC (O) NR7aR7a, (CH2)rNR7fC (O) OR7d, (CH2)rS(O)pR7b, (CH2)rS (O)2NR7aR7a, (CH2)rNR7aS (O)2NR7aR7a, (CH2)rNR7fS (O)2R7b, C1-2 haloalkil, (CH2)rfenil supstituiran s 0-3 R7e, i (CH2)r-5-6-eročlani heterociklički sustav koji sadrži 1- 4 heteroatoma izabrana između N, O, i S, supstituiran s 0-3 R7e, gdje se heterociklički prsten izabire između tiofenil, piridinil, benzotiazolil, i tetrazolil.
6. Spoj prema zahtjevima 1-4, gdje Z se izabire između -NHC(O)-, i -NH-; R1 se izabire između C1-6 alkila supstituiranog od 0-1 R6, i - C (O) O- C1-6 alkil; i R2 se izabire između fenila supstituiranog s 0-2 R7, i 5-10-eročlani heteroarilni sustav koji sadrži 1-4 heteroatoma izabrana između N, O, i S, supstituiran s 0-3 R7 gdje se heteroarilni sustav izabire između kinazolinil, triazinil, pirimidinil, pikolinil, izonikotinil, furanil, indolil, piridinil, pirazolil, pirazinil, tiazolil, tiofenil, i izoksazolil.
7. Spoj prema zahtjevima 1- 4, gdje R1 se izabire između H, C1-6 alkila supstituiranog s 0-1 R6, i - C (O) O- C1-6 alkil.
8. Spoj prema zahtjevu 1 koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol.
9. Spoj prema zahtjevu 1 koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol.
10. Spoj prema zahtjevu 1 koji ima strukturu: [image] ili njegova farmaceutski prihvatljiva sol.
11. Spoj prema zahtjevu 1 koji ima strukturu Cis-(3S)-1-(4-(tert- butilamino)cikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2-on, trans-(3S)-1-(4-(tert- butilamino)cikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, Cis-(3S)-1-(4-(tert- butilamino)cikloheksil)-3-(6-tert-butilpirolo[1,2-f][1,2,4] triazin-4- ilamino) pirolidin-2- on, trans-(3S)-1-(4-(tert- butilamino)cikloheksil)-3-(6- tert- butilpirolo [1,2-f][1,2,4] triazin-4- ilamino) pirolidin-2- on, cis-(3S)-3- tert- butil- N-(1-(4-(tert- butilamino) cikloheksil)-2- oksopirolidin-3- il)-4- hidroksibenzamid, trans-(3S)-3- tert- butil- N-(1-(4-(tert- butilamino) cikloheksil)-2- oksopirolidin-3- il)-4- hidroksibenzamid, Cis- i trans-(3S)-4- tert- butil- N-(1-(4-(tert- butilamino) cikloheksil)-2- oksopirolidin-3- il)- 1H- pirol-2-karboksamid, Cis- i trans-(3S)-4- tert- butil- N-(1-(4-(tert- butilamino) cikloheksil)-2- oksopirolidin-3- il)-1- metil- 1Hpirol-2- karboksamid, N- {(3S)-1-[(1S, 2R, 4R)-4-(Izopropil- metil- amino)-2- propil- cikloheksil]-2- okso- pirolidin-3- il}-2-(3-izopropil- ureido)- 5- trifluorometil- benzamid, 1- {2-[((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il) karbamoil]-4-(trifluorometil) fenil}-3- etilurea, 1-(2-(((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il) karbamoil)-4-(trifluorometil) fenil)-3- ciklopropilurea, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil)benzamid, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)benzamid, 2- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)pirimidin-4- karboksamid, 3- tert- butil-4- hidroksi- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il) benzamid, 6- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)pikolinamid, 2- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)izonikotinamid, (S)-1-[(1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil]-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-3-(6-(trifluorometoksi) kinazolin-4-ilamino) pirolidin-2- on, (S)-3-(6- klorokinazolin-4- ilamino)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)pirolidin-2- on, (S)-3-(6- fluorokinazolin-4- ilamino)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil) pirolidin-2- on, (S)-3-(6- tert- butilpirimido [5, 4- d] pirimidin-4- ilamino)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-propilcikloheksil) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-3-(6-(2- metoksifenil) kinazolin-4-ilamino) pirolidin-2- on, 3-(4-((S)-1-((lS, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- ilamino) kinazolin-6- il) benzonitril, (S)-3-(6- klorokinazolin-4- ilamino)-1-((1S, 2R, 4R)-4-(izopropilamino)-2- propilcikloheksil) pirolidin-2- on, (S)-3-(6- klorokinazolin-4- ilamino)-1-((1S, 2R, 4S)-4-(etil (izopropil) amino)-2- propilcikloheksil) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(tert- butilamino)-2- propilcikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino)pirolidin-2- on, (S)-1-((1S, 2R, 4S)-4-(tert- butilamino)-2- propilcikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino)pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino)pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-3-(6-(trifluorometoksi) kinazolin-4- ilamino)pirolidin-2- on, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-4- hidroksibenzamid, N-((S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-2-(trifluorometil) pirimidin-4- karboksamid, (S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-3-(6-(2- metoksifenil) kinazolin-4- ilamino)pirolidin-2- on, 6- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il) pikolinamid, 5-(4- klorofenil)- N-((S)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il) furan-2- karboksamid, (S)-3-(6- tert- butilpirimido [5, 4- d] pirimidin-4- ilamino)-1-((1S, 2R, 4R)-4-(dimetilamino)-2- propilcikloheksil)pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(dietilamino)-2- propilcikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(dietilamino)-2- propilcikloheksil)-3-(6-(trifluorometoksi) kinazolin-4- ilamino)pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-4-(dietilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, 2- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(dietilamino)-2- propilcikloheksil)-2- oksopirolidin-3- il) pirimidin-4-karboksamid, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-3-(6-(trifluorometil) kinolin-4- ilamino)pirolidin-2- on, (R)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-3-(6-(trifluorometil) kinolin-4- ilamino)pirolidin-2- on, 4- hidroksi- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-3-fenil- benzamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-3- fenilbenzamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-2- fenilizonikotinamid N- oksid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-1- metil- 1Hindol-3- karboksamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-1- metil- 1Hindol-2- karboksamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-2-(metilsulfonamido)-5-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)- 5-(trifluorometil)-2-(trifluorometilsulfonamido) benzamid, 5- izopropil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)-2-(trifluorometilsulfonamido) benzamid, 2- kloro- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il)- 5-(trifluorometil) benzamid, metil 3-(((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il) karbamoil)-5- tert- butilbenzoat, 3-(((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il) karbamoil)- 5-tert- butilbenzojeva kiselina, 2- tert- butil-1- okso- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- propilcikloheksil)-2- oksopirolidin-3- il) pirimidin-4- karboksamid, (S)-1-((1S, 2S, 4R)-2- izopropil-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, (S)-1-((1S, 2S, 4S)-2- izopropil-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, (S)-1-((1S, 2S, 4R)-2- izopropil-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometoksi) kinazolin-4- ilamino) pirolidin-2- on, (S)-3-(6- klorokinazolin-4- ilamino)-1-((1S, 2S, 4R)-2- izopropil-4-(izopropil (metil) amino) cikloheksil)pirolidin-2- on, 6- tert- butil- N-((S)-1-((1S, 2S, 4R)-2- izopropil-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3-il) pikolinamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- metilcikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil)benzamid, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- metilcikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- metilcikloheksil)-3-(6-(trifluorometoksi) kinazolin-4-ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-2- etil-4-(izopropil (metil) amino)- cikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metoksimetil) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, 1-(2-(((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metoksimetil) cikloheksil)-2- oksopirolidin-3- il)karbamoil)-4-(trifluorometil) fenil)-3- etilurea, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metoksimetil) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, (S)-3-(6- klorokinazolin-4- ilamino)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metoksimetil) cikloheksil)pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metoksimetil) cikloheksil)-3-(6-(trifluorometoksi) kinazolin-4- ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metoksimetil) cikloheksil)-3-(6-(2- metoksifenil)kinazolin-4- ilamino) pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-2-(etoksimetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, (S)-1-((1S, 2R, 4R)-2-(etoksimetil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, 1-(2-(((S)-1-((1S, 2R, 4R)-2-(etoksimetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)karbamoil)-4-(trifluorometil) fenil)-3- etilurea, N-((S)-1-((1S, 2S, 4R)-4-(izopropil (metil) amino)-2-(2- metoksietil) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, (S)-1-((1S, 2S, 4R)-4-(izopropil (metil) amino)-2-(2- metoksietil) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, 1-(2-(((S)-1-((1S, 2S, 4R)-4-(izopropil (metil) amino)-2-(2- metoksietil) cikloheksil)-2- oksopirolidin-3- il)karbamoil)-4-(trifluorometil) fenil)-3- etilurea, 1-((1S, 2R, 4R)-2-(1- hidroksipropil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, 1-((1S, 2R, 4R)-2-(1- hidroksipropil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, N-(1-((1S, 2R, 4R)-2-(1- hidroksipropil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, N-(1-((1S, 2R, 4R)-2-(1- hidroksipropil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-2-(tertbutil)pirimidin-4- karboksamid, 5-(4- klorofenil)- N-(1-((1S, 2R, 4R)-2-(1- hidroksipropil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il) furan-2- karboksamid, 1-((1S, 2R, 4R)-2-(1- hidroksietil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, N-(1-((1S, 2R, 4R)-2-(1-hidroksietil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, 1-((1S, 2R, 4R)-2-(hidroksimetil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-2- on, 1-((1S, 2R, 4R)-2-(2- hidroksipropan-2- il)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-2-(2- hidroksipropan-2- il)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, 6- tert- butil- N-((S)-1-((1S, 2R, 4R)-2-(2- hidroksipropan-2- il)-4-(izopropil (metil) amino) cikloheksil)-2-oksopirolidin-3- il) pikolinamid, ((1R, 2S, 5R)- 5-(izopropil (metil) amino)-2-(2- okso-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-1- il) cikloheksil) metil izobutirat, ((1R, 2S, 5R)- 5-(izopropil (metil) amino)-2-(2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il) cikloheksil)metil izobutirat, ((1R, 2S, 5R)-2-(3-(3- tert- butil-1- metil- 1H- pirazol- 5- karboksamido)-2- oksopirolidin-1- il)- 5-(izopropil(metil) amino) cikloheksil) metil izobutirat, ((1R, 2S, 5R)- 5-(dimetilamino)-2-(2- okso-3-(6-(trifluorometil) kinazolin-4- karboksamido) pirolidin-1- il)cikloheksil) metil izobutirat, ((1R, 2S, 5R)- 5-(dimetilamino)-2-(2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il) cikloheksil) metil izobutirat, ((1R, 2S, 5R)-2-(3-(3- tert- butil-1- metil- 1H- pirazol- 5- karboksamido)-2- oksopirolidin-1- il)- 5-(dimetilamino)cikloheksil) metil izobutirat, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)-3-(trifluorometil) benzamid, 2- amino- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il)- 5-(trifluorometoksi) benzamid, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il)-1- metil- 1H- pirazol- 5- karboksamid, 6- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il) pikolinamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)- 6-(trifluorometil) pikolinamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)- 6- fenilpikolinamid, N-((S)-1-((1S, 2R, 4R)-4-(etil (izopropil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-2-(metilsulfonilmetil)-4-(neopentilamino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)-4- metil-3-(trifluorometil) benzamid, 4- kloro- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il) benzamid, 3- fenil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il) benzamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)- 6- fenilpirazin-2- karboksamid, 3- fluoro- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il)- 5-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)-3-(trifluorometoksi) benzamid, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, (S)-3-(6- klorokinazolin-4- ilamino)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil)cikloheksil) pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2- oksopirolidin-3-il)- 3, 5- bis (trifluorometil) benzamid, 3, 5- dikloro- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(metilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il) benzamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-4- fluoro-3-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)- 6-(trifluorometil) pikolinamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, 6- tert- butil- N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2-oksopirolidin-3- il) pikolinamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometoksi) benzamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3- fluoro- 5-(trifluorometil) benzamid, 2- amino- N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2-oksopirolidin-3- il)- 5-(trifluorometoksi) benzamid, 3- amino- N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2-oksopirolidin-3- il)- 5-(trifluorometil) benzamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)- 5- fenilnikotinamid N- oksid, (S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-3-(6- klorokinazolin-4- ilamino) pirolidin-2- on, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2-oksopirolidin-3- il)-4- hidroksibenzamid, N-((S)-1-((1S, 2R, 4R)-2-(tert- butilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)- 5- fenilnikotinamid, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il)-1- metil- 1H- pirazol- 5- karboksamid, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il) benzamid, (S)-1-((1S, 2R, 4R)-4-(etil (izopropil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(etil (izopropil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il) benzamid, 3- tert- butil- N-((S)-1-((1S, 2R, 4R)-4-(izopropil (propil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-2-oksopirolidin-3- il) benzamid, (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-3-(6-(trifluorometoksi)kinazolin-4- ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(etil (izopropil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-3-(6-(trifluorometoksi)kinazolin-4- ilamino) pirolidin-2- on, (S)-1-((1S, 2R, 4R)-4-(etil (izopropil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2-(izopropilsulfonilmetil) cikloheksil)-2- oksopirolidin-3- il)-1- metil- 1H- indol-2- karboksamid, N-((S)-1-((1S, 2R, 4R)-2-(etilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(trifluorometil) benzamid, (S)-1-((1S, 2R, 4R)-2-(etilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-3-(6-(trifluorometil)kinazolin-4- ilamino) pirolidin-2- on, N-((S)-1-((1S, 2R, 4R)-2-(etilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)-3-(fenil) benzamid, 3-(((S)-1-((1S, 2R, 4R)-2-(etilsulfonilmetil)-4-(izopropil (metil) amino) cikloheksil)-2- oksopirolidin-3- il)karbamoil)- 5- tert- butilbenzojeva kiselina, (1R, 2S, 5R)- metil 5-(izopropil (metil) amino)-2-((S)-2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butil (metil) amino)-2-((S)-2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(izopropil (metil) amino)-2-((S)-2- okso-3-(6-(trifluorometil) kinazolin-4- ilamino)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(izopropil (metil) amino)-2-((S)-2- okso-3-(6-(trifluorometoksi) kinazolin-4- ilamino)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 2-((S)-3-(3- tert- butil-4- hidroksibenzamido)-2- oksopirolidin-1- il)- 5-(izopropil (metil)amino)- cikloheksankarboksilat, (1R, 2S, 5R)- metil 2-((S)-3-(3- fluoro- 5-(trifluorometil) benzamido)-2- oksopirolidin-1- il)- 5-(izopropil(metil) amino)- cikloheksankarboksilat, (1R, 2S, 5R)- metil 2-((S)-3-(2- tert- butilpikolinamido)-2- oksopirolidin-1- il)- 5-(izopropil (metil) amino)-cikloheksankarboksilat, (1R, 2S, 5R)- metil 2-((S)-3-(3- tert- butil-4- hidroksibenzamido)-2- oksopirolidin-1- il)- 5-(tert- butilamino)cikloheksankarboksilat, (1R, 2S, 5R)- metil 2-((S)-3-(3- tert- butilbenzamido)-2- oksopirolidin-1- il)- 5-(tert- butilamino) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2- tert- butilpirimidin-4- karboksamido)-2- oksopirolidin-1-il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2- tert- butilpikolinamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(3- fenilbenzamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2- fenilpirazin- 6- karboksamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(4- fluoro-3-(trifluorometil)- benzamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butil (metil) amino)-2-((S)-3-(2-(4- klorofenil) furan- 5- karboksamido)-2-oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butil (metil) amino)-2-((S)-2- okso-3-(6-(trifluorometoksi) kinazolin-4- ilamino)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butil (metil) amino)-2-((S)-2- okso-3-(6-(trifluorometil) kinazolin-4- ilamino)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(4-(perfluoroetil) tiazol-2- karboksamido) pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(4- tert- butiltiazol-2- karboksamido)-2- oksopirolidin-1-il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(4-(3-(trifluorometil)- fenil) tiazol-2- karboksamido)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(4- feniltiazol-2- karboksamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(4-(4- klorofenil) tiazol-2- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2- feniltiazol-4- karboksamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(4- klorofenil) tiazol-4- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 2-((S)-3-(2- tert- butil- 5- metilfuran-4- karboksamido)-2- oksopirolidin-1- il)- 5-(tertbutilamino)cikloheksan- karboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2-(trifluorometil) furan- 5- karboksamido) pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(4- klorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2-(3-(trifluorometil) fenil) furan- 5- karboksamido)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(2- kloro- 5-(trifluorometil) fenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(2, 5- diklorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(4- izopropilfenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(4- fluorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2- fenilfuran- 5- karboksamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(3- fluorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(3- cijanofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(3- metoksifenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(4- cijanofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(3, 4- difluorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2-(4-(trifluorometil) fenil) furan- 5- karboksamido)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(3-(4- metoksifenil) furan- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(3-(4-(trifluorometil) fenil) furan- 5- karboksamido)pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(3- fenilfuran- 5- karboksamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(3- feniltiofen- 5- karboksamido) pirolidin-1-il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(2- feniltiofen- 5- karboksamido) pirolidin-1-il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(2-(4- metoksifenil) tiofen- 5- karboksamido)-2- oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(1- metil-3- fenil- 1H- pirazol- 5- karboksamido)-2-oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(3- fenilizoksazol- 5- karboksamido) pirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(6-(trifluorometil) kinazolin-4- ilamino) pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(6- tert- butilpirimido [5, 4- d] pirimidin-4- ilamino)-2-oksopirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-3-(6- klorokinazolin-4- ilamino)-2- oksopirolidin-1- il)cikloheksankarboksilat, (1R, 2S, 5R)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(6-(trifluorometoksi)- kinazolin-4- ilamino) pirolidin-1- il) cikloheksankarboksilat, (1R, 2S, 5S)- metil 5-(tert- butilamino)-2-((S)-2- okso-3-(3-(trifluorometil)- benzamido) pirolidin-1- il)cikloheksankarboksilat, (1S, 2S, 5R)- metil 5-(izopropil (metil) amino)-2-((S)-2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1-il) cikloheksankarboksilat, (1S, 2S, 5R)- metil 2-((S)-3-(2-(4- klorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il)- 5-(izopropil(metil) amino) cikloheksankarboksilat, (1S, 2S, 5R)- metil 2-((S)-3-(3- tert- butil-4- hidroksibenzamido)-2- oksopirolidin-1- il)- 5-(izopropil (metil)amino) cikloheksankarboksilat, (1S, 2S, 5R)- etil 2-((S)-3-(2-(4- klorofenil) furan- 5- karboksamido)-2- oksopirolidin-1- il)- 5-(izopropil(metil) amino) cikloheksankarboksilat, etil 3-((1S, 2S, 5R)- 5-(izopropil (metil) amino)-2-((S)-2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il) cikloheksil) propanoat, 3-((1S, 2S, 5R)- 5-(izopropil (metil) amino)-2-((S)-2- okso-3-(3-(trifluorometil) benzamido) pirolidin-1- il)cikloheksil) propan kiselina, (S)-1-((1R, 2S, 4S)-4-(izopropil (metil) amino)-2- metoksicikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on, ili (S)-1-((1S, 2R, 4R)-4-(izopropil (metil) amino)-2- metoksicikloheksil)-3-(6-(trifluorometil) kinazolin-4-ilamino) pirolidin-2- on.
12. Spoj prema bilo kojem od zahtjeva 1-11, za uporabu u liječenju.
13. Farmaceutska smjesa, sadrži farmaceutski prihvatljivi nosač i terapijski učinkovitu količinu spoja prema zahtjevima 1-11.
14. Spoj prema bilo kojem od zahtjeva 1-11 za uporabu u liječenju poremećaja izabranog između osteoartritisa, aneurizme, vrućice, kardiovaskularnih učinaka, Crohnove bolesti, kongestivnog zatajenja srca, autoimunih bolesti, HIV-infekcije, HIV-povezane demencije, psorijaze, idiopatske plućne fibroze, transplantacijske arterioskleroze, fizički ili kemijski inducirane traume mozga, upalne bolesti crijeva, alveolitisa, kolitisa, sistemskog lupus eritematosus, nefrotoksičnog serumskog nefritisa, glomerulonefritisa, astme, multiple skleroze, ateroskleroze, reumatoidnog artritisa, restenoze, transplantacije organa i raka.
15. Uporaba spoja prema bilo kojem od zahtjeva 1 do 11 u pripremi lijeka za modulaciju aktivnosti receptora kemokina u bolesnika kojemu je to potrebno.
16. Uporaba spoja prema bilo kojem od zahtjeva 1 do 11 u pripremi lijeka za modulaciju MCP-1, MCP-2, MCP-3, MCP-4, i MCP-5 aktivnosti u bolesnika kojemu je to potrebno.
17. Uporaba spoja prema bilo kojem od zahtjeva 1 do 11 u pripremi lijeka za modulaciju MCP-1 aktivnosti u bolesnika kojemu je to potrebno.
18. Uporaba spoja prema bilo kojem od zahtjeva 1 do 11 u pripremi lijeka za modulaciju MIP-1β i RANTES aktivnosti koja je posredovana CCR5 receptorom u bolesnika kojemu je to potrebno.
19. Uporaba spoja prema bilo kojem od zahtjeva 1 do u pripremi lijeka za inhibiciju CCR2 i CCR5 aktivnosti u bolesnika kojemu je to potrebno.
20. Spoj prema bilo kojem od zahtjeva 1-11, za uporabu u liječenju poremećaja izabranog između alveolitisa, kolitisa, sistemskog lupus eritematosus, nefrotoksičnog serumskog nefritisa, glomerulonefritisa, astme, multiple skleroze, ateroskleroze, reumatoidnog artritisa, restenoze, transplantacije organa i raka.
21. Spoj prema bilo kojem od zahtjeva 1-11, za uporabu u liječenju poremećaja izabranog između astme, multiple skleroze, ateroskleroze, i reumatoidnog artritisa.
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US7829571B2 (en) 2010-11-09
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