Title: Antiprotozoal compounds
Inventor : Agnello, Stefano
Adams, Michael
Kaiser, Marcel
Mäser, Pascal
Urban, Alexander
Raguz, Luka
Riedl, Rainer
Patent submitter: Bacoba AG
Issue Date: 11-Jul-2018
Language : English
Subjects : medicinal chemistry; drug discovery
Subject (DDC) : 540: Chemistry
Abstract: The present invention relates to a compound of formula (I) wherein --A-- represents a peptide chain, wherein said peptide chain consists of 5 to 7 amino acids, wherein said amino acids are selected from any amino acid, wherein at least two, preferably at least three of said 5 to 7 amino acids are ±-aminoisobutyric acid (Aib), leucine (Leu) or alanine (Ala); R 1 is wherein X is N or CH; R 5 is selected from H, C 1 -C 16 alkyl, C 1 -C 16 alkenyl, C(O)-C 1 -C 16 alkyl, C(O)-C 1 -C 16 alkenyl, (wherein said C 1 -C 16 alkyl, C 1 -C 16 alkenyl, C(O)-C 1 -C 16 alkyl, C(O)-C 1 -C 16 alkenyl are) independently optionally substituted with halogen, NR 11 R 12 , -[O-C 2 H 4 ] n -OCH 3 wherein n=2-20; C(O)-R 8 , C(O)-C 1 -C 3 alkylene-R 8 , N(H)C(O)-R 8 , or S(O) 2 -R 9 , wherein R 8 is independently at each occurrence selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C 1 -C 4 alkyl, halogen, CF 3 , OR 10 , NR 11 R 12 , C 6 H 5 and C 6 H 5 substituted with halogen, C 1 -C 3 alkyl, OR 10 , NR 11 R 12 ; wherein R 10 , R 11 , R 12 are independently at each occurrence H, C 1 -C 3 alkyl; R 9 is independently at each occurrence selected from C 1 -C 4 alkyl, aryl, heteroaryl, each independently optionally substituted with C 1 -C 4 alkyl, halogen, CF 3 , OR 13 , NR 14 R 15 ; wherein R 13 , R 14, R 15 are independently at each occurrence H, C 1 -C 3 alkyl; R 6, R 7 are independently at each occurrence selected from H, C 1 -C 4 alkyl, C 1 -C 4 alkenyl, C(O)-C 1 -C 3 alkyl, C(O)-C 1 -C 4 alkenyl, (wherein said C 1 -C 4 alkyl, C 1 -C 4 alkenyl, C(O)-C 1 -C 3 alkyl, C(O)-C 1 -C 4 alkenyl are) independently optionally substituted with halogen, NR 11 R 12 ; or R 6 and R 7 together with the X-C to which they are attached form independently at each occurrence an aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally ( further ) substituted with C 1 -C 4 alkyl, halogen, CF 3 , OR 10 , NR 11 R 12 , C 6 H 5 and C 6 H 5 substituted with halogen, C 1 -C 3 alkyl, OR 10 , NR 11 R 12 ; wherein R 10 , R 11 , R 12 are independently at each occurrence H, C 1 -C 3 alkyl; and wherein the arrow indicates the attachment to the NH-moiety depicted in formula (I); R 2 is selected from C 1 -C 14 alkyl, C 2 -C 14 alkyl optionally substituted with OH, C 2 -C 14 alkoxy, C 2 -C 14 alkenyl optionally substituted with OH; C 1 -C 8 alkylene-R 23 , wherein in alkylene one or two -CH 2 - moieties are optionally replaced by -CH(NR 24 R 25 )-,-CH(OH)-, -C(=O)-, -NR 24 R 25 - or -CH(CH 3 )- moieties, wherein there are no adjacent-C(=O)- moieties or adjacent -NR 24 R 25 - moieties, and wherein R 23 is independently at each occurrence selected from hydrogen; aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C 1 -C 4 alkyl, OR 26 , NR 27 R 28 ; wherein R 26 , R 27 , R 28 are independently at each occurrence H, halogen, CF 3 , C 1 -C 3 alkyl; and wherein R 24 and R 25 are independently at each occurrence H, C 1 -C 3 alkyl; with the proviso that R 2 is not -CH 2 CH(CH 3 )CH 2 CH(OH)CH 2 C(O)C 2 H 5 , -CH 2 CH(CH 3 )CH 2 CH=CHC(O)C 2 H 5 , -CH 2 CH(CH 3 )CH 2 CH 2 CH 2 C(O)C 2 H 5 , -CH 2 CH(CH 3 )(CH 2 ) 3 CH(OH)C 2 H 5 , -CH 2 CH(CH 3 )CH 2 CH(OCH 3 )CH 2 C(O)C 2 H 5 ; R 3 is selected from C 2 -C 12 alkyl optionally substituted with OH, C 2 -C 12 alkoxy, C 2 -C 12 alkenyl optionally substituted with OH, C 1 -C 8 alkylene-R 29 , wherein in alkylene one or two -CH 2 - moieties are optionally replaced by -CH(NR 30 R 31 )-, -CH(OH)-, -C(=O)-, -NR 30 R 31 - or -CH(CH 3 )- moieties, wherein there are no adjacent -C(=O)- moieties or adjacent -NR 30 R 31 - moieties, and wherein R 29 is independently at each occurrence selected from hydrogen; aryl, heteroaryl, cycloalkyl, heterocyclyl, each independently optionally substituted with C 1 -C 4 alkyl, OR 32 , NR 33 R 34 ; wherein R 32 , R 33 , R 34 are independently at each occurrence H, halogen, CF 3 , C 1 -C 3 alkyl; and wherein R 30 and R 31 are independently at each occurrence H, C 1 -C 3 alkyl; R 4 is wherein R 35 is independently selected from hydrogen and C 1 -C 3 -alkyl; R 36 is independently at each occurrence selected from -cycloalkyl-NR 41 R 42 , wherein said cycloalkyl moiety is optionally substituted by C 1 -C 4 alkyl, hydroxyl, halogen, OR 43 ; -C 3 -C 6 alkylene-NR 41 R 42 , wherein said C 3 -C 6 alkylene moiety is optionally substituted by hydroxyl, OR 43 , halogen; cycloalkyl optionally substituted with C 1 -C 4 alkyl, halogen, OR 43 ; or wherein R 35 and R 36 together with the nitrogen atom to which they are attached form independently at each occurrence a heteroaryl, a heterocyclyl or a heterocyclic spiranyl, each independently optionally substituted with C 1 -C 4 alkyl, halogen, OR 43 , NR 44 R 45 , wherein R 43 , R 44 , R 45 are independently at each occurrence H, C 1 -C 4 alkyl; and wherein R 37 , R 38 , R 39 and R 40 are independently at each occurrence H or C 1 -C 3 alkyl, preferably H or methyl, or independently at each occurrence two of said R 37 , R 38 , R 39 and R 40 together with the carbon atom to which they are attached form a carbocyclic or heterocyclic ring, preferably a carbocyclic ring, and wherein R 41 and R 42 are independently of each other H or C 1 -C 4 alkyl optionally substituted with halogen, hydroxyl or C 3 -C 6 cycloalkyl; or together with the nitrogen atoms to which they are attached form independently at each occurrence a heteroaryl or a heterocyclyl, each independently optionally substituted with halogen, C 1 -C 4 alkyl, OR 43 , NR 44 R 45 ; wherein the arrow indicates the attachment to the C(O)-moiety depicted in formula (I); and pharmaceutically acceptable salts of said compound of formula (I). The present invention further relates to pharmaceutical compositions comprising said compounds and to the use of said compounds in a method of treatment of a protozoan disease, wherein preferably said protozoan disease is selected from malaria, human African trypanosomiasis, Chagas disease or leishmaniasis.
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Patent
Patentnumber : EP3345917
metadata.zhaw.publication.code: A1
URI: https://register.epo.org/espacenet/regviewer?AP=17150353&CY=EP&LG=en&DB=REG
https://digitalcollection.zhaw.ch/handle/11475/17354
Published as part of the ZHAW project : New antileishmanial and antitrypanosomal drugs
Appears in Collections:Patente Life Sciences und Facility Management

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