US 12,358,919 B2
Antibacterial compounds
Federico Corelli, Siena (IT); Antonella Brizzi, Siena (IT); Claudia Mugnaini, Siena (IT); Jean-Denis Docquier, Siena (IT); and Filomena Sannio, Siena (IT)
Assigned to Universita' degli Studi di Siena, Siena (IT)
Appl. No. 17/614,388
Filed by Universita' degli Studi di Siena, Siena (IT)
PCT Filed Jun. 4, 2020, PCT No. PCT/IB2020/055270
§ 371(c)(1), (2) Date Nov. 26, 2021,
PCT Pub. No. WO2020/245759, PCT Pub. Date Dec. 10, 2020.
Claims priority of application No. 102019000008151 (IT), filed on Jun. 5, 2019.
Prior Publication US 2022/0235059 A1, Jul. 28, 2022
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 6 Claims
 
1. A Compound of formula (I)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1, R5 are selected independently from the group consisting of:
H;
linear or branched C1-C10 alkyl optionally containing 1-3 multiple bonds, carboxy, hydroxy, acyloxy, amino, halide, C1-C3 alkylamino, C1-C3 dialkylamino;
C3-C7 cycloalkyl optionally containing heteroatoms such as N, O, S; aryl, arylalkyl, arylalkenyl optionally containing heterocyclic rings and substituted on the aromatic ring with halogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 alkylthio, trifluoromethyl, and methylenedioxy;
R2, R3 are selected independently from the group consisting of:
H;
linear or branched C1-C6 alkyl;
C3-C12 cycloalkyl optionally substituted with halogen, hydroxy, carboxy, amino;
aryl, arylalkyl, optionally containing heterocyclic rings and substituted on the aromatic ring with halogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 alkylthio, trifluoromethyl, and methylenedioxy;
alternatively, R2, R3, form, together with the nitrogen atom to which they are bonded, a 5- to 7-membered heteroalicyclic ring; and
R4 is selected from the group consisting of:
H;
Na+, K+, Cs+, NMe4+;
Me, Et, n-Pr;
P(O)(OH)2, P(O)(OMe)2, P(O)(OEt)2, P(O)(OPh)2, P(O)(OCH2Ph)2, S(O)2OH, S(O)2NH2, S(O)2NMe2, C(O)H, C(O)Me, C(O)Et, C(O)Pr, C(O)CH(Me)2, C(O)C(Me)3, C(O)Ph, C(O)CH2Ph, CO2Me, CO2Et, CO2CH2Ph, C(O)NHMe, C(O)NMe2, C(O)NHEt, C(O)NEt2, C(O)NHPh, C(O)NHCH2Ph;
acyl residues of C4-C10 carboxylic acids optionally containing 1-3 multiple bonds;
acyl residues of the amino acids glycine, alanine, valine, leucine, isoleucine, serine, threonine, cysteine, methionine, proline, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, histidine, phenylalanine, tyrosine, and tryptophan,
wherein said compound is selected from the group consisting of:
N-(adamantan-1-yl)-4-(1-butyl)-4,5-dihydro-7-hydroxy-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4-(1-butyl)-4,5-dihydro-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-4-(4-fluoro-1-butyl)-7-hydroxy-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4,5-dihydro-4-(4-fluoro-1-butyl)-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-2-methyl-5-oxo-4-(1-pentyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4-(4-acetoxy-1-butyl)-N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4-(1-butyl)-4,5-dihydro-7-hydroxy-1-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4-(1-butyl)-4,5-dihydro-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-1-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-4-(4-fluoro-1-butyl)-7-hydroxy-1-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4,5-dihydro-4-(4-fluoro-1-butyl)-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-1-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-1-methyl-5-oxo-4-(1-pentyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-2-(2-hydroxyethyl)-5-oxo-4-(1-propyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4-(1-butyl)-4,5-dihydro-7-hydroxy-2-(2-hydroxyethyl)-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-2-(2-hydroxyethyl)-5-oxo-4-(1-pentyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4,5-dihydro-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-2-(2-hydroxyethyl)-5-oxo-4-(1-pentyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4-(1-butyl)-4,5-dihydro-7-hydroxy-1-(2-hydroxyethyl)-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-4-(4-hydroxy-1-butyl)-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
2-(2-acetoxyethyl)-N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-5-oxo-4-(1-propyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4,5-dihydro-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-1-methyl-5-oxo-4-(3-propenyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4-(1-butyl)-4,5-dihydro-2-ethyl-7-hydroxy-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
4,5-dihydro-7-hydroxy-N-(1-hydroxyadamantan-3-yl)-2-methyl-5-oxo-4-(2-propyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-hydroxy-2-methyl-5-oxo-4-(2-propyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-7-methoxy-2-methyl-5-oxo-4-(1-pentyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
7-acetoxy-N-(adamantan-1-yl)-4,5-dihydro-2-methyl-5-oxo-4-(1-propyl)-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-4-(4-fluoro-1-butyl)-7-(3-ethoxycarbonyl-1-oxopropoxy)-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide,
N-(adamantan-1-yl)-4,5-dihydro-4-(4-fluoro-1-butyl)-7-(3-carboxy-1-oxopropoxy)-2-methyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide sodium salt,
N-(adamantan-1-yl)-4-(1-butyl)-7-dibenzylphosphoryloxy-4,5-dihydro-2-ethyl-5-oxo-2H-pyrazolo [4,3-b]pyridin-6-carboxamide, and
N-(adamantan-1-yl)-4-(1-butyl)-4,5-dihydro-2-ethyl-5-oxo-7-phosphoryloxy-2H-pyrazolo [4,3-b]pyridin-6-carboxamide disodium salt.