SI8911201B - Amino acid derivatives - Google Patents

Amino acid derivatives Download PDF

Info

Publication number
SI8911201B
SI8911201B SI8911201A SI8911201A SI8911201B SI 8911201 B SI8911201 B SI 8911201B SI 8911201 A SI8911201 A SI 8911201A SI 8911201 A SI8911201 A SI 8911201A SI 8911201 B SI8911201 B SI 8911201B
Authority
SI
Slovenia
Prior art keywords
formula
hydroxy
tert
group
butyl
Prior art date
Application number
SI8911201A
Other languages
Slovenian (sl)
Other versions
SI8911201A (en
Inventor
Balraj Krishan Handa
Peter James Machin
Armstrong Joseph Martin
Sally Redshaw
John Gareth Thomas
Original Assignee
F. Hoffmann-La Roche Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB888813940A external-priority patent/GB8813940D0/en
Application filed by F. Hoffmann-La Roche Ag filed Critical F. Hoffmann-La Roche Ag
Priority claimed from YU120189A external-priority patent/YU48068B/en
Publication of SI8911201A publication Critical patent/SI8911201A/en
Publication of SI8911201B publication Critical patent/SI8911201B/en

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Claims (20)

85 PATENTNI ZAHTEVKI 1. Spojine s splošno formulo ,4 1 1 I R—N C O CH R (°) R7T>R •CH2—Nv R 19 8 v kateri n predstavlja število 0 ali 1; Rl predstavlja alkoksikarbonil, aralkoksikarbonil, alkanoil, cikloalkilkarbonil, aralkanoil, aroil, heterociklil-karbonil, alkilsulfonil, arilsulfonil, monoaralkilkarbamoil, cinamoil ali a-aralkoksikarbonil-aminoalkanoil in predstavlja vodik, ali R^ in R7 skupaj z atomom dušika na katerega sta vezana, predstavljata ciklično imidno skupino s formulo OA compound of the general formula, 4 1 1 I R — N C O CH R (°) R7T > R • CH2 — Nv R 19 8 in which n represents the number 0 or 1; R1 represents alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, cycloalkylcarbonyl, aralkanoyl, aroyl, heterocyclylcarbonyl, alkylsulfonyl, arylsulfonyl, monoaralkylcarbamoyl, cinamoyl or α-aralkoxycarbonyl-aminoalkanoyl, together with R and represents a hydrogen and R a cyclic imide group of formula O P^ N— / (a) O v kateri P in Q skupaj predstavljata aromatski sistem; R^ predstavlja alkil, cikloalkil, aril, aralkil, heterociklilalkil, cianoalkil, alkilsulfinilalkil, karbamoilalkil ali alkoksikarbonilalkil, ali kadar n predstavlja število 0, lahko R-* predstavlja alkiltioalkil, ali kadar n označuje število 1, lahko R^ prav tako predstavlja alkilsulfonilalkil; R^ predstavlja alkil, cikloalkil, cikloalkilalkil, aril ali aralkil; R^ predstavlja vodik in R6 predstavlja hidroksi, ali R-^ in R^ skupaj predstavljata okso; R7 in R8 skupaj predstavljata trimetilensko ali tetrametilensko skupino, katera je lahko substituirana s hidroksi, alkoksikarbonilamino ali acilamino, ali v kateri je ena od skupin -CH2- zamenjana z -NH-, -N(alkoksikarbonil)-, -N(acil)- ali -S-, ali katera nosi kondenziran cikloalkan, aromatski ali heteroaromatski obroč; in R^ predstavlja alkoksikarbonil, monoalkilkarbamoil, monoaralkilkarbamoil, monoarilkarbamoil ali skupino s formulo 86P ^ N— / (a) O in which P and Q together represent an aromatic system; R 1 represents alkyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, cyanoalkyl, alkylsulfinylalkyl, carbamoylalkyl or alkoxycarbonylalkyl, or when n represents the number 0, R 1 represents alkylthioalkyl, or when n represents the number 1, R 1 may also represent alkyl; R 1 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; R 1 represents hydrogen and R 6 represents hydroxy, or R 1 and R 6 together represent oxo; R7 and R8 together represent a trimethylene or tetramethylene group which may be substituted by hydroxy, alkoxycarbonylamino or acylamino, or in which one of the groups -CH2- is replaced by -NH-, -N (alkoxycarbonyl) -, -N (acyl) - or -S-, or which carries a fused cycloalkane, aromatic or heteroaromatic ring; and R 1 represents alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of formula 86 v kateri R.10 in vsak posebej predstavlja alkil; in njihove farmacevtsko sprejemljive kislinske adicijske soli.wherein R 10 and each independently represents alkyl; and pharmaceutically acceptable acid addition salts thereof. 2. Spojine po zahtevku 1, v katerih n označuje 0 (nič), predstavlja alkil, cikloalkil, aril, aralkil, heterociklilalkil, cianoalkil, alkiltioalkil, karbamoilalkil ali alkoksikarbonilalkil in in R^ skupaj predstavljata trimetilensko ali tetrametilensko skupino, v kateri je ena od skupin -CH2- zamenjana z -NH-, ali -S-, ali katera lahko nosi kondenzirani cikloalkanski, aromatski ali heteroaromatski obroč.Compounds according to claim 1, wherein n denotes 0 (zero), represents alkyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, cyanoalkyl, alkylthioalkyl, carbamoylalkyl or alkoxycarbonylalkyl, and and R 1 together represent a trimethylene or tetramethylene group in which is one; groups -CH2- replaced by -NH-, or -S-, or which may carry a fused cycloalkane, aromatic or heteroaromatic ring. 3. Spojine po zahtevku 1 ali 2, v katerih R^ predstavlja alkoksikarbonil, aralkoksikarbonil, alkanoil, cikloalkilkarbonil, aralkanoil, aroil, heterociklil-karbonil ali α-aralkoksikarbonilaminoalkanoil, prednostno benziloksikarbonil, 2-naftoil, 1-hidroksi-2-naftoil, 3-hidroksi-2-naftoil, 3-benziloksi-2-naftoil, 2-kinolilkarbonil ali 3-kinolilkarbonil in R^ predstavlja vodik.Compounds according to claim 1 or 2, wherein R 1 represents alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, cycloalkylcarbonyl, aralkanoyl, aroyl, heterocyclylcarbonyl or α-aralkoxycarbonylaminoalkanoyl, preferably benzyloxycarbonyl, 2-naphthoyl -hydroxy-2-naphthoyl, 3-benzyloxy-2-naphthoyl, 2-quinolylcarbonyl or 3-quinolylcarbonyl and R 1 represents hydrogen. 4. Spojine po kateremkoli od zahtevkov od 1 do 3, v katerih R^ predstavlja alkil, cianolakil, alikiltioalkil ali karbamoilalkil, prednostno cianometil, metiltiometil ali karbamoilmetil.Compounds according to any one of claims 1 to 3, wherein R 1 represents alkyl, cyanolakyl, alkylthioalkyl or carbamoylalkyl, preferably cyanomethyl, methylthiomethyl or carbamoylmethyl. 5. Spojine po kateremkoli od zahtevkov 1 do 4, v katerih R^ predstavlja aralkil, prednostno benzil.Compounds according to any one of claims 1 to 4, in which R 1 represents aralkyl, preferably benzyl. 6. Spojine po kateremkoli izmed zahtevkov 1 do 5, v katerih R^ predstavlja vodik in predstavlja hidroksi.Compounds according to any one of claims 1 to 5, wherein R 1 represents hydrogen and represents hydroxy. 7. Spojine po kateremkoli od zahtevkov 1 do 6, v katerih -N(R7)-CH(R8)(r9) predstavlja eno od naslednjih skupin 12 87 RCompounds according to any one of claims 1 to 6, wherein -N (R 7) -CH (R 8) (r 9) represents one of the following groups 12 87 R R 9 /' N \ / 9 \ N—R 13 / (c) (d) I9 N. (e)R 9 / 'N \ / 9 \ N — R 13 / (c) (d) I9 N. (e) / \ ,// \, / N. R (h) 9N. R (h) 9 II ( i) 88 kjer ima pomen, ki je naveden v zahtevku 1, R.12 predstavlja vodik, hidroksi, alkoksikarbonilamino ali acilamino, R.13 predstavlja vodik, alkoksikarbonil ali acil, m označuje 1 ali 2 in p označuje 1 ali 2, prednostno skupino s formulo (c), v kateri R.12 predstavlja vodik in m označuje 2, ali predstavlja terc.-butoksikarbonilamino in m označuje 1, skupino s formulo (d), v kateri R^ predstavlja terc.-butoksikarbonil, skupino s formulo (e), v kateri m označuje 1, skupino s formulo (f), v kateri m in p oba označujeta 1, ali skupino s formulo (g), (i) ali (j).(i) 88 wherein the meaning given in claim 1, R.12 represents hydrogen, hydroxy, alkoxycarbonylamino or acylamino, R.13 represents hydrogen, alkoxycarbonyl or acyl, m denotes 1 or 2 and p denotes 1 or 2, preferably a group of formula (c) in which R 12 represents hydrogen and m represents 2, or represents tert-butoxycarbonylamino and m represents 1, a group of formula (d) in which R 1 represents tert-butoxycarbonyl, a group of formula (e) wherein m denotes 1, a group of formula (f) wherein m and p both denote 1, or a group of formula (g), (i) or (j). 8. Spojine po kateremkoli izmed zahtevkov od 1 do 7, v katerih R^ predstavlja alkoksikarbonil, monoalkilkarbamoil ali skupino s formulo (b), navedeno v zahtevku 1, prednostno terc.-butoksikarbonil, izobutilkarbamoil, terc.-butilkarbamoil ali skupino s formulo (b), navedeno v zahtevku 1, kjer RlO predstavlja sek.-butil in Ril predstavlja izobutil.Compounds according to any one of claims 1 to 7, wherein R 1 represents alkoxycarbonyl, monoalkylcarbamoyl or a group of formula (b), as claimed in claim 1, preferably tert-butoxycarbonyl, isobutylcarbamoyl, tert-butylcarbamoyl or a group of formula ( b), claimed in claim 1, wherein R 10 represents sec-butyl and R 1 represents isobutyl. 9. Spojine po kateremkoli izmed zahtevkov od 1 do 8, v katerih Rl predstavlja benziloksikarbonil, 2-naftoil, l-hidroksi-2-naftoil, 3-hidroksi-2-naftoil, 3-benziloksi-2-naftoil, 2-kinolilkarboni! ali 3-kinolilkarbonil in R^ predstavlja vodik, R^ predstavlja cianometil, metiltiometil ali karbamoilmetil, R^ predstavlja benzil, R^ predstavlja vodik in R^ predstavlja hidroksi, in -N(R7)-CH(R8)(R9) predstavlja skupino s formulo (c) navedeno v zahtevku 7, kjer Rl2 predstavlja vodik in m označuje 2, ali Rl2 predstavlja terc.-butoksikarbonilamino in m označuje 1, skupino s formulo (d), navedeno v zahtevku 7, kjer Rl3 predstavlja terc.-butoksikarbonil, skupino s formulo (e), dano v zahtevku 7, v kateri m označuje 1, skupino s formulo (f), prikazano v zahtevku 7, v kateri m in p označujeta 1, ali skupino s formulami (g), (i) ali (j), navedenmi v zahtevku 7, in R^ predstavlja terc.-butoksikarbonil, izobutilkarbamoil, terc.-butilkarbamoil, ali skupino s formulo (b), navedeno v zahtevku 1, v kateri RlO predstavlja sek.-butil in R^ predstavlja izobutil.Compounds according to any one of claims 1 to 8, wherein R 1 represents benzyloxycarbonyl, 2-naphthoyl, 1-hydroxy-2-naphthoyl, 3-hydroxy-2-naphthoyl, 3-benzyloxy-2-naphthoyl, 2-quinolylcarbonyl! or 3-quinolylcarbonyl and R 1 represents hydrogen, R 1 represents cyanomethyl, methylthiomethyl or carbamoylmethyl, R 1 represents benzyl, R 1 represents hydrogen and R 1 represents hydroxy, and -N (R 7) -CH (R 8) (R 9) represents a group of formula (c) according to claim 7, wherein R 12 represents hydrogen and m represents 2, or R 12 represents tert-butoxycarbonylamino and m represents 1, a group of formula (d), as claimed in claim 7, wherein R 13 represents tert-butoxycarbonyl , a group of formula (e) given in claim 7, in which m represents 1, a group of formula (f) shown in claim 7, in which m and p represent 1, or a group of formulas (g), (i) or (j) mentioned in claim 7, and R 1 represents tert-butoxycarbonyl, isobutylcarbamoyl, tert-butylcarbamoyl, or a group of formula (b), as claimed in claim 1, in which R 10 represents sec-butyl and R 1. represents isobutyl. 10. N2-[3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2(R ali S)-hidroksi-4-fenilbutil]-Nl-terc.-butiI-L-prolinamid ali N^-[3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2(R ali S)-hidroksi-4-fenilbutil]-Nl-izobutil-L-prolinamid.10. N2- [3 (S) - [[N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2 (R or S) -hydroxy-4-phenylbutyl] -N1-tert-butyl-L-prolinamide or N 1 - [3 (S) - [[N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2 (R or S) -hydroxy-4-phenylbutyl] -N1-isobutyl-L-prolinamide. 11. Spojine po zahtevku 1, izbrane iz skupine, ki jo sestavljajo: N^-[3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2(R )-hidroksi-4-fenilbutil]-Nl-terc.-butil-4(R)-tiazolidin-karboksamid, N-terc.-butil-l-[2(R)-hidroksi-3(S)-[[N-(2-naftoil)-L-asparaginil]amino]-4-fenilbutil]- 2(S)-piperidinkarboksamid, 89 l-[3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2-(R)-hidroksi-4-fenilbutil]-N- terc.-butil-oktahidro-(3aS,6aS)-ciklopenta[b]pirol-2(S)-karboksamid, 1- [3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2-(R)-hidroksi-4-fenilbutil]-N-terc.-butil-2(S)-piperidin-karboksamid, 2- [3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2-(R)-hidroksi-4-fenilbutil]-N-terc.-butil-l,2,3,4-tetrahidropirido[3,4-b]indol-l-karboksamid, N-terc.-butil-3-[2(R)-hidroksi-3(S)-[[N-(2-naftoil)-L-asparaginil]amino]-4-fenilbutil]- 4(R)-tiazolidinkarboksamid, Nl-terc.-butil-N2-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolilkarbonil)-L-asparaginil]amino]-L-proIinamid N^-oksid, l-[3(S)-[[N-(benziloksikarbonil)-3-ciano-L-alanil]amino]-2-(R)-hidroksi-4-fenilbutil- N-terc.-butil-2(S)-piperidinkarboksamid, l-[3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2(R)-hidroksi-4-fenilbutil]-4-(terc.-butoksikarbonil)-N-terc.-butiI-2-(R ali S)-piperazinkarboksamid, l-[3(S)-[[N-(benziloksikarbonil)-3-ciano-L-alanil]amino]-2-(R)-hidroksi-4-fenilbutil]-4-(terc.-butoksikarbonil)-N-terc.-butil-2(R ali S)-piperazinkarboksamid, N^-[3(S)-[[N-(benziloksikarbonil)-L-asparaginil]amino]-2-(R)-hidroksi-4-fenilbutil]-4(R)-(terc.-butoksiformamido)-Nl-terc.-butil-L-prolinamid, l-[3(S)-[[N-(3-benziloksi-2-naftoil)-L-asparaginil]amino]-2-(R)-hidroksi-4-fenilbutil]- N-(terc.-butil-2(S)-piperidin-karboksamid, N-terc.-butil-l-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolilkarbonil)-L-asparaginil]amino]butil]-2-piperidinkarboksamid 1-oksid, N-terc.-butil-l-[3(S)-[[N-(3-hidroksi-2-naftoil)-L-asparaginil]amino]-2(R)-hidroksi-4- fenilbutil]-2(S)-piperidinkarboksamid, trans-2-[3(S)-[[N-benziloksikarbonil)-L-asparaginil]amino]-2-(R)-hidroksi-4- fenilbutil]-N-terc.-butil-dekahidro-(4aR,8aS)-izokinolin-3(S)-karboksamid, 4-(terc.-butoksikarbonil)-N-terc.-butil-l-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2- kinolilkarbonil)-L-asparaginil]amino]butil]'2(R ali S)piperazinkarboksamid, N-terc.-butil-l-[2(R)-hidroksi-3(S)-[[N-(l-hidroksi-2-naftoil)-L-asparaginil]amino]-4- fenilbutil]-2(S)-piperidinkarboksamid, trans-N-terc.-butil-dekahidro-2-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolilkarbonil)-L-asparaginil]amino]butil]-(4aR,8aS)-izokinolin-3(S)-karboksamid in N-terc.-butil-l-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolilkarbonil)-L-cisteinil]amino]butil]-2(S)-piperidinkarboksamid. 90Compounds according to claim 1, selected from the group consisting of: N 2 - [3 (S) - [[N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2 (R) -hydroxy-4-phenylbutyl] -N1-tert-butyl-4 (R) -thiazolidinecarboxamide, N-tert-butyl-1- [2 (R) -hydroxy-3 (S) - [[N- (2-naphthoyl) -L -asparaginyl] amino] -4-phenylbutyl] -2 (S) -piperidinecarboxamide, 89 1- [3 (S) - [[N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2- (R) -hydroxy- 4-Phenylbutyl] -N-tert-butyl-octahydro- (3aS, 6aS) -cyclopenta [b] pyrrole-2 (S) -carboxamide, 1- [3 (S) - [[N- (benzyloxycarbonyl) -L -asparaginyl] amino] -2- (R) -hydroxy-4-phenylbutyl] -N-tert-butyl-2 (S) -piperidinecarboxamide, 2- [3 (S) - [[N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2- (R) -hydroxy-4-phenylbutyl] -N-tert-butyl-1,2,3,4-tetrahydropyrido [3,4-b] indole-1-carboxamide, N-tert-butyl-3- [2 (R) -hydroxy-3 (S) - [[N- (2-naphthoyl) -L-asparaginyl] amino] -4-phenylbutyl] -4 (R) -thiazolidinecarboxamide , N1-tert-butyl-N2- [2 (R) -hydroxy-4-phenyl-3 (S) - [[N- (2-quinolylcarbonyl) -L-asparaginyl] amino] -L-pronynamide N 2 - oxide, 1- [3 (S) - [[N- (ben zyloxycarbonyl) -3-cyano-L-alanyl] amino] -2- (R) -hydroxy-4-phenylbutyl-N-tert-butyl-2 (S) -piperidinecarboxamide, 1- [3 (S) - [[ N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2 (R) -hydroxy-4-phenylbutyl] -4- (tert-butoxycarbonyl) -N-tert-butyl-2- (R or S) -piperazinecarboxamide , 1- [3 (S) - [[N- (benzyloxycarbonyl) -3-cyano-L-alanyl] amino] -2- (R) -hydroxy-4-phenylbutyl] -4- (tert-butoxycarbonyl) - N-tert-butyl-2 (R or S) -piperazinecarboxamide, N, N- [3 (S) - [[N- (benzyloxycarbonyl) -L-asparaginyl] amino] -2- (R) -hydroxy-4- phenylbutyl] -4 (R) - (tert-butoxyformamido) -N1-tert-butyl-L-prolinamide, 1- [3 (S) - [[N- (3-benzyloxy-2-naphthoyl) -L- asparaginyl] amino] -2- (R) -hydroxy-4-phenylbutyl] -N- (tert-butyl-2 (S) -piperidinecarboxamide, N-tert-butyl-1- [2 (R) - hydroxy-4-phenyl-3 (S) - [[N- (2-quinolylcarbonyl) -L-asparaginyl] amino] butyl] -2-piperidinecarboxamide 1-oxide, N-tert-butyl-1- [3 ) - [[N- (3-hydroxy-2-naphthoyl) -L-asparaginyl] amino] -2 (R) -hydroxy-4-phenylbutyl] -2 (S) -piperidinecarboxamide, trans-2- [3 ) - [[N-benzyloxycarbonyl) -L -asparaginyl] amino] -2- (R) -hydroxy-4-phenylbutyl] -N-tert-butyl-decahydro- (4aR, 8aS) -isoquinoline-3 (S) -carboxamide, 4- (tert-butoxycarbonyl) ) -N-tert-butyl-1- [2 (R) -hydroxy-4-phenyl-3 (S) - [[N- (2-quinolylcarbonyl) -L-asparaginyl] amino] butyl] '2 (R or S) piperazinecarboxamide, N-tert-butyl-1- [2 (R) -hydroxy-3 (S) - [[N- (1-hydroxy-2-naphthoyl) -L-asparaginyl] amino] -4- phenylbutyl] -2 (S) -piperidinecarboxamide, trans-N-tert-butyl-decahydro-2- [2 (R) -hydroxy-4-phenyl-3 (S) - [[N- (2-quinolylcarbonyl) - L-asparaginyl] amino] butyl] - (4aR, 8aS) -isoquinoline-3 (S) -carboxamide and N-tert-butyl-1- [2 (R) -hydroxy-4-phenyl-3 (S) - [N- (2-quinolylcarbonyl) -L-cysteinyl] amino] butyl] -2 (S) -piperidinecarboxamide. 90 12. N-terc.-butil-l-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolilkarbonil)-L-asparaginil]amino]butil]-2(S)-piperidinkarboksamid.12. N-tert-butyl-1- [2 (R) -hydroxy-4-phenyl-3 (S) - [[N- (2-quinolylcarbonyl) -L-asparaginyl] amino] butyl] -2 (S ) -piperidinecarboxamide. 13. N-terc.-butil-oktahidro-l-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolilkarbonil)-L-asparaginil]amino]butil]-(3aS,6aS)-ciklopenta[b]pirol-2(S)-karboksamid.13. N-tert-butyl-octahydro-1- [2 (R) -hydroxy-4-phenyl-3 (S) - [[N- (2-quinolylcarbonyl) -L-asparaginyl] amino] butyl] - ( 3aS, 6aS) -cyclopenta [b] pyrrole-2 (S) -carboxamide. 14. N-terc.-butil-l,2,3,4-tetrahidro-2-[2(R)-hidroksi-4-fenil-3(S)-[[N-(2-kinolil-karbonil)-L-asparaginil]amino]butil]pirido[3,4-b]indol-l(R ali S)-karboksamid.14. N-tert-butyl-1,2,3,4-tetrahydro-2- [2 (R) -hydroxy-4-phenyl-3 (S) - [[N- (2-quinolyl-carbonyl) - L-asparaginyl] amino] butyl] pyrido [3,4-b] indole-1 (R or S) -carboxamide. 15. Spojine s splošno formulo R15. Compounds of general formula R R A R CH 5R A R CH 5 R 8 v kateri R predstavlja vodik ali skupino CO CH .2 \ R^ predstavlja alkil, cikloalkil, aril, aralkil, heterociklilalkil, cianoalkil, alkiltioalkil, alkilsulfinilalkil, karbamoilalkil ali alkoksikarbonilalkil; R^ predstavlja alkil, cikloalkil, cikloalkilalkil, aril ali aralkil; R^ predstavlja vodik in R^ predstavlja hidroksi, ali R^ in R^ skupaj predstavljata okso; R^ in R^ skupaj predstavljata trimetilensko ali tetrametilensko skupino, katera je lahko substituirana s hidroksi, alkoksikarbonilamino ali acilamino, ali v kateri je ena od skupin -CH2- lahko zamenjana z -NH-, -N(alkoksikarbonil)-, N(acil)- ali -S-, ali katera nosi kondenziran cikloalkanski, aromatski ali heteroaromatski obroč; in R^ predstavlja alkoksikarbonil, monoalkilkarbamoil, mono-aralkilkarbamoil, monoarilkarbamoil ali skupino s formulo NH / —CO . /C°\ CH NH· ,11 (b) ; R 10 VI 91 v kateri vsak izmed R.10 in predstavlja alkil.R 8 in which R represents hydrogen or a CO group CH 2 R 2 represents alkyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, cyanoalkyl, alkylthioalkyl, alkylsulfinylalkyl, carbamoylalkyl or alkoxycarbonylalkyl; R 1 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; R 1 represents hydrogen and R 1 represents hydroxy, or R 1 and R 2 together represent oxo; R 1 and R 2 together represent a trimethylene or tetramethylene group which may be substituted by hydroxy, alkoxycarbonylamino or acylamino, or in which one of the groups -CH 2 - may be replaced by -NH-, -N (alkoxycarbonyl) -, N ) - or -S-, or which carries a fused cycloalkane, aromatic or heteroaromatic ring; and R 1 represents alkoxycarbonyl, monoalkylcarbamoyl, mono-aralkylcarbamoyl, monoarylcarbamoyl or a group of formula NH / -CO. Δ C 1 CH NH 3, 11 (b); R 10 VI 91 wherein each of R 10 and represents alkyl. 16. Spojine s splošno formulo VI 91 R Rl“-N\ /C°\ /CH\ . XCH NH .C ψη R7' ,CH_-N R2 \ca/19 8 R v kateri n predstavlja število 0 ali 1; R.1 predstavlja alkoksikarbonil, aralkoksikarbonil, alkanoil, cikloalkilkarbonil, aralkanoil, aroil, heterociklil-karbonil, alkilsulfonil, arilsulfonil, monoaralkilkarbamoil, cinamoil ali a-aralkoksikarbonil-aminoalkanoil in R^ predstavlja vodik, ali in R^ skupaj z atomom dušika na katerega sta vezana, predstavljata ciklično imidno skupino s formulo O (a) N— P I Q O v kateri P in Q skupaj predstavljata aromatski sistem; R^ predstavlja alkil, cikloalkil, aril, aralkil, heterociklilalkil, cianoalkil, alkilsulfinilalkil, karbamoilalkil ali alkoksi-karbonilalkil, ali kadar n predstavlja število 0, R^ lahko tudi predstavlja alkiltioalkil, ali kadar n označuje število 1, R^ prav tako lahko tudi predstavlja alkilsulfonilalkil; R^ predstavlja alkil, cikloalkil, cikloalkilalkil, aril ali aralkil; R^ predstavlja vodik in r6 predstavlja hidroksi ali R^ in R^ skupaj predstavljata okso; R^ in R^ skupaj predstavljata trimetilensko ali tetrametilensko skupino, katera je lahko substituirana z amino; in R^ predstavlja alkoksi-karbonil, monoalkilkarbamoil, monoaralkilkarbamoil, monoarilkarbamoil ali skupino s formulo —coCompounds of general formula VI. XCH NH .C ψη R7 ', CH_-N R2 \ ca / 19 8 R in which n represents the number 0 or 1; R 1 represents alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, cycloalkylcarbonyl, aralkanoyl, aroyl, heterocyclylcarbonyl, alkylsulfonyl, arylsulfonyl, monoaralkylcarbamoyl, cinnamoyl or α-aralkoxycarbonyl-aminoalkanoyl, and R 1 represents an atom and R 1 represents bound, represent a cyclic imide group of formula O (a) N-PIQO in which P and Q together represent an aromatic system; R 1 represents alkyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, cyanoalkyl, alkylsulfinylalkyl, carbamoylalkyl or alkoxycarbonylalkyl, or when n represents the number 0, R 1 may also represent alkylthioalkyl, or when n represents the number 1, R 1 may also represent represents alkylsulfonylalkyl; R 1 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; R 1 represents hydrogen and R 6 represents hydroxy or R 1 and R 6 together represent oxo; R 1 and R 2 together represent a trimethylene or tetramethylene group which may be substituted by amino; and R 1 represents alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of formula -co /“N CH R10 NH-R 11 (b) 92 v kateri vsak izmed RlO in Ril predstavlja alkil./ N N R R 10 NH-R 11 (b) 92 wherein each of R 10 and R 1 represents alkyl. 17. Derivati aminokislin po kateremkoli izmed zahtevkov 1 do 14 za uporabo kot terapevtsko aktivne snovi.Amino acid derivatives according to any one of claims 1 to 14 for use as therapeutically active substances. 18. Derivati aminokislin po kateremkoli izmed zahtevkov 1 do 14 za uporabo pri zdravljenju ali profilaksi virusnih infekcij.Amino acid derivatives according to any one of claims 1 to 14 for use in the treatment or prophylaxis of viral infections. 19. Postopek za proizvodnjo spojine po kateremkoli izmed zahtevkov 1 do 14, označen s tem, da obsega (a) za pripravo spojin s formulo I, v kateri n označuje 0, spojina s splošno formulo H2NProcess for the production of a compound according to any one of claims 1 to 14, characterized in that it comprises (a) for the preparation of compounds of formula I in which n represents 0, a compound of general formula H2N I I v kateri imajo R^, r5? r6; r7? r8 jn r9 v zahtevku 1 navedeni pomen, reagira s kislino s splošno formulo R' R I -N CH-,3 COOH III v kateri imajo Rl, R^ in R^ v zahtevku 1 navedeni pomen, ali z njenim reaktivnim derivatom, ali 93 (b) za pripravo spojine s formulo I, v kateri n označuje 0, predstavlja vodik in predstavlja hidroksi, reduciramo spojino s formulo I, v kateri n označuje 0, in R3 in R^ skupaj predstavljata okso, ali (c) za pripravo spojine s formulo I, v kateri n označuje 0 in R* predstavlja alkanoil, cikloalkilkarbonil, aralkanoil, aroil, heterociklilkarbonil, alkilsulfonil, arilsulfonil, cinamoil ali a-aralkoksikarbonilaminoalkanoil, in R2 predstavlja vodik, ali Rl in R2 skupaj z atomom dušika s katerim sta vezana, predstavljata ciklično imidno skupino s formulo (a), navedeno v zahtevku 1, spojina s splošno formuloI I in which they have R ^, r5? r6; r7? r8 and r9 as claimed in claim 1 react with an acid of the general formula R 1 R 1 -N CH-, 3 COOH III in which R 1, R 2 and R 2 have the meaning stated in claim 1, or with a reactive derivative thereof, or 93 (b) for the preparation of a compound of formula I in which n represents 0, represents hydrogen and represents hydroxy, reduce a compound of formula I in which n represents 0, and R 3 and R 2 together represent oxo, or (c) for the preparation of a compound of formula I wherein n denotes 0 and R * represents alkanoyl, cycloalkylcarbonyl, aralkanoyl, aroyl, heterocyclylcarbonyl, alkylsulfonyl, arylsulfonyl, cinamoyl or α-aralkoxycarbonylaminoalkanoyl, and R2 represents hydrogen, or R1 and R2 together with the atom , representing a cyclic imide group of formula (a) as claimed in claim 1, a compound of general formula v kateri imajo R3, R4, R5, R6, R7, R8 in R^ v zahtevku 1 prikazani pomen, reagira s sredstvom, ki da skupino alkanoil, cikloalkilkarbonil, aralkanoil, aroil, heterociklilkarbonil, alkilsulfonil, arilsulfonil, cinamoil ali a-aralkoksikarbonil-aminoalkanoil, ali s sredstvom, ki tvori skupino cikličnega imida s formulo (a), ki je prikazana v zahtevku 1, ali (d) za pripravo spojine s formulo I, v kateri n označuje 0 in R3 predstavlja monoaralkilkarbamoil in R2 predstavlja vodik, spojina s prej prikazano formulo IV reagira s spojino s splošno formulo Rl’ -N=C=0 V v kateri R^ predstavlja aralkil, ali (e) za pripravo spojine s formulo I, v kateri R3 predstavlja alikilsulfinilalkil in n označuje 0, oksidiramo spojino s formulo I, v kateri R3 predstavlja alkiltioalkil in n označuje 0, ali 94 (f) za pripravo spojine s formulo I, v kateri n označuje 1, oksidiramo spojino s formulo I, v kateri n označuje 0, ali (g) za pripravo spojine s formulo I, v kateri n označuje 1 in predstavlja aromatsko N-heterociklilkarbonil N-oksidno skupino, in predstavlja vodik, oksidiramo spojino s formulo I, v kateri n označuje 1 in Rl predstavlja aromatsko N-hetero-ciklilkarbonilno skupino in R^ predstavlja vodik, ali (h) za pripravo spojine s formulo I, v kateri n označuje 1 in R^ predstavlja alkilsulfonilalkil, oksidiramo spojino s formulo I, v kateri n označuje 1 in R^ predstavlja alkilsulfinilalkil, ali (i) za pripravo spojine s formulo I, v kateri Rl predstavlja karboksi-substituirani aroil, hidroksi-substituirani aroil ali hidrocinamoil, in R^ predstavlja vodik, katalitsko hidrogeniramo spojino s formulo I, v kateri Rl predstavlja benziloksikarbonil-substituiran aroil, benziloksi-substituiran aroil ali cinamoil in R^ predstavlja vodik, ali (j) za pripravo spojine s formulo I, v kateri R^ predstavlja imidazol-4-il in/ali R^ predstavlja hidroksi-substituirani aril ali hidroksi-substituirani aralkil in/ali R^ in R8 skupaj predstavljata skupino trimetilen ali tetrametilen, v kateri je ena skupina -CH2- zamenjana z -NH-, obdelamo spojino s formulo I, v kateri R^ predstavlja 1-(benziloksikarbonil)-imidazol-4-il in/ali R^ predstavlja terc.-butoksi-substituiran aril ali terc.-butoksi-substituiran aralkil in/ali R^ in R8 skupaj predstavljata skupino trimetilen ali tetrametilen, v kateri je ena skupina -CH2- zamenjana z -N(terc.-butoksikarbonil)- skupino, z močno kislino, ali (k) za pripravo spojine s formulo I, v kateri R^ in R8 skupaj predstavljata skupino trimetilen ali tetrametilen, ki je substituirana z acilamino, ali v kateri je ena skupina -CH2- zamenjana z -N(acil)-, aciliramo spojino s splošno formulo H 2 R 4 CH NH /C» /Ch2 C '°»n R7-l' 'CH' R9 R 8' VI 95 v kateri imajo n, R1, R2, R3, R4, R5, R6 in R9 v zahtevku 1 navedeni pomen in R2 in R^ skupaj predstavljata skupino trimetilen ali tetrametilen, ki je substituirana z amino ali v kateri je ena skupina -CH2- zamenjana z -NH-, in/ali (l) če želimo, ločimo zmes diastereoizomernih racematov na diastereoizomerne racemate ali optično čiste diastereoizomere in/ali (m) če želimo, ločimo zmes diastereoizomerov na optično čiste diastereoizomere in/ali (n) če želimo, dobljene spojine s formulo I prevedemo v farmacevtsko sprejemljive kislinske adicijske soli.in which R 3, R 4, R 5, R 6, R 7, R 8 and R 6 have the meaning shown in claim 1, react with an agent which gives the group alkanoyl, cycloalkylcarbonyl, aralkanoyl, aroyl, heterocyclylcarbonyl, alkylsulfonyl, arylsulfonyl, cinamoyl or α-aralkoxycarbonyl aminoalkanoyl, or with an agent forming a cyclic imide group of formula (a) as claimed in claim 1, or (d) for the preparation of a compound of formula I in which n represents 0 and R 3 represents monoaralkylcarbamoyl and R 2 represents hydrogen, a compound with the above formula IV is reacted with a compound of general formula R 1 '-N = C = 0 V in which R 1 represents aralkyl, or (e) to prepare a compound of formula I in which R 3 represents alkylsulfinylalkyl and n represents 0, oxidize the compound of formula I in which R3 represents alkylthioalkyl and n represents 0, or 94 (f) for the preparation of a compound of formula I in which n represents 1 is oxidized to a compound of formula I in which n represents 0, or (g) for the preparation compounds of formula I in which n denotes 1 and represents a flavor N-heterocyclylcarbonyl N-oxide group, and represents hydrogen, oxidize a compound of formula I in which n represents 1 and R1 represents an aromatic N-heterocyclylcarbonyl group and R1 represents hydrogen, or (h) to prepare a compound of formula I , wherein n represents 1 and R 1 represents alkylsulfonylalkyl, oxidizing a compound of formula I in which n represents 1 and R 1 represents alkylsulfinylalkyl, or (i) to prepare a compound of formula I in which R 1 represents carboxy-substituted aroyl, hydroxy -substituted aroyl or hydrocinnamoyl, and R 1 represents hydrogen, catalytically hydrogenated a compound of formula I in which R 1 represents benzyloxycarbonyl-substituted aroyl, benzyloxy-substituted aroyl or cinamoyl and R 1 represents hydrogen, or (j) for the preparation of a compound of formula I , wherein R 1 represents imidazol-4-yl and / or R 1 represents hydroxy-substituted aryl or hydroxy-substituted aralkyl and / or R 1 and R 8 together represent a trimethylene or tetramethylene group in which one group -CH2- replaced by -NH-, is treated with a compound of formula I in which R 1 represents 1- (benzyloxycarbonyl) -imidazol-4-yl and / or R 1 represents tert-butoxy-substituted aryl or tert- butoxy-substituted aralkyl and / or R 1 and R 8 together represent a trimethylene or tetramethylene group in which one -CH 2 - group is replaced by an -N (tert-butoxycarbonyl) - group, with a strong acid, or (k) for the preparation of a compound of formula I, in which R 1 and R 8 together represent an acylamino-substituted trimethylene or tetramethylene group, or in which one -CH 2 - group is replaced by -N (acyl) -, a compound of general formula H 2 R 4 is acylated CH NH / C »/ Ch2 C '°» n R7-1' 'CH' R9 R 8 'VI 95 in which n, R1, R2, R3, R4, R5, R6 and R9 have the meaning given in claim 1 and R2 and R 1 together represent a group of trimethylene or tetramethylene substituted with amino or in which one group -CH 2 - is replaced by -NH-, and / or (l) if desired, separate the mixture of diastereoisomeric racemates to diast ereoisomeric racemates or optically pure diastereoisomers and / or (m) if desired, separating the mixture of diastereoisomers into optically pure diastereoisomers and / or (n) if desired, converting the obtained compounds of formula I into pharmaceutically acceptable acid addition salts. 20. Postopek po zahtevku 19, označen s tem, da spojine s formulo I, v kateri n označuje 0, R3 predstavlja alkil, cikloalkil, aril, aralkil, heterociklilalkil, cianoalkil, alkiltioalkil, karbamoilalkil ali alkoksikarbonilalkil in R2 in R^ skupaj predstavljata skupino trimetilen ali tetrametilen, v kateri je ena skupina -CH2- lahko zamenjana z -NH- ali -S-, ali katera lahko nosi kondenzirani cikloalkanski, aromatski ali heteroaromatski obroč, in njihove farmacevtsko sprejemljive kislinske adicijske soli pripravimo na osnovi izvedb (a), (b), (c), (d) in/ali (n) postopka. Za: F.HOFFMANN-LA ROCHE AG 4 VRELI J A G 4.Process according to Claim 19, characterized in that the compounds of the formula I in which n represents 0, R 3 represents alkyl, cycloalkyl, aryl, aralkyl, heterocyclylalkyl, cyanoalkyl, alkylthioalkyl, carbamoylalkyl or alkoxycarbonylalkyl and R 2 and R 2 together represent a group trimethylene or tetramethylene, in which one group -CH2- may be replaced by -NH- or -S-, or which may bear a fused cycloalkane, aromatic or heteroaromatic ring, and their pharmaceutically acceptable acid addition salts are prepared on the basis of embodiments (a), (b), (c), (d) and / or (n) of the procedure. For: F.HOFFMANN-LA ROCHE AG 4 VRELI J A G 4.
SI8911201A 1988-06-13 1989-06-12 Amino acid derivatives SI8911201B (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB888813940A GB8813940D0 (en) 1988-06-13 1988-06-13 Amino acid derivatives
GB898908035A GB8908035D0 (en) 1988-06-13 1989-04-10 Amino acid derivatives
YU120189A YU48068B (en) 1988-06-13 1989-06-12 DERIVATIVES OF AMINO ACIDS

Publications (2)

Publication Number Publication Date
SI8911201A SI8911201A (en) 1997-10-31
SI8911201B true SI8911201B (en) 2002-06-30

Family

ID=27263947

Family Applications (1)

Application Number Title Priority Date Filing Date
SI8911201A SI8911201B (en) 1988-06-13 1989-06-12 Amino acid derivatives

Country Status (2)

Country Link
HR (1) HRP930443B1 (en)
SI (1) SI8911201B (en)

Also Published As

Publication number Publication date
HRP930443B1 (en) 1999-04-30
SI8911201A (en) 1997-10-31
HRP930443A2 (en) 1996-12-31

Similar Documents

Publication Publication Date Title
EP0346847A3 (en) Amino acid derivatives
EP0228893A3 (en) Arylalkyl-heterocyclic amines, n-substituted by aryloxyalkyl group in allergy treatment
NO2005016I2 (en) Solifenacin and / or a pharmaceutical acid addition salt thereof
NO933450D0 (en) ANTI-RHYTHMIC AND CARDI-PROTECTIVE SUBSTITUTED 1 (2H) ISOQINOLINES, PROCEDURES FOR THEIR PREPARATION, MEDICINES CONTAINING THESE AND USE THEREOF FOR THE PREPARATION OF A MEDICINE FOR EFFECTIVE EFFECT
ES2164889T3 (en) SEMICARBAZONAS WITH ACTIVITY ON THE SNC AND PHARMACEUTICAL PREPARATIONS BASED ON THE SAME.
EP0632036A3 (en) Amide and urea derivatives having anti-hypercholesteremic activity, their preparation and their therapeutic uses
DE69312243D1 (en) Phenoxy- or phenoxyalkyl-piperidines as antiviral agents
ES2082024T3 (en) AZABICICLIC AND AZACICLIC OXIMES AND AMINES USEFUL AS CHOLINERGIC AGENTS AND THEIR PHARMACEUTICALLY ACCEPTABLE SALTS.
WO2001070733A3 (en) Di-substituted iminoheterocyclic compounds
DE68923151D1 (en) Use of trifluoromethylphenyl tetrahydropyridines for the manufacture of medicaments for the treatment of anxio-depressive disorders.
ATE19397T1 (en) (+)-2-(1-(2,6-DICHLORPHENOXY)-ETHY1)-1,3DIAZACYCLOPENT-2-EN,ITS PRODUCTION AND ITS USE IN PHARMACEUTICAL PREPARATIONS.
HU9201033D0 (en) Tiazolidinone- and oxazolidinone derivatives, process for their production, and for the production of medical preparations containing them as active agents
SI8911201B (en) Amino acid derivatives
DE3673468D1 (en) N-ALKYL-2,6-DIMETHYLMORPHOLINIO-CARBONIC ACID AMIDE SALTS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS FUNGICIDES.
DE68925173D1 (en) 4-methyl and 4-ethyl substituted pyrrolidin-2-ones
IL74800A (en) Esters of 4-aryl-1,4,5,7-tetrahydro-5-oxothieno(3,4-b)-pyridine-3-carboxylic acid derivatives,their preparation and pharmaceutical compositions containing them
ATE74138T1 (en) HEPTANOYL-GLU-ASP-ALA-AMINO ACID IMMUNOGANTS.
NO167286C (en) PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE BENZOTIAZEPINE DERIVATIVES.
DE59108026D1 (en) Phenylalkylaminoalkyl compounds and processes for their preparation and medicaments containing these compounds
EP0192393A3 (en) Alkylaminofuranone derivatives
FI891807A0 (en) Process for the preparation of therapeutically active octahydropyrrolo-pyrazino / 2,1-i / indol-2-one derivatives
DE3675431D1 (en) 1,3-OXATHIAN DERIVATIVES.
SE8305362D0 (en) NOVEL SUBSTITUTED PHENYLAZACYCLOALKANES, PROCESSES FOR PREPARATION AND PHARMACEUTICAL PREPARATIONS FOR SUCH COMPOUNDS

Legal Events

Date Code Title Description
IF Valid on the prs date