US 12,421,264 B2
Compounds and methods for the treatment of pathogenic Neisseria
Frédéric Veyrier, Montréal (CA); and Annie Castonguay, Montréal (CA)
Assigned to INSTITUT NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Québec (CA)
Appl. No. 17/250,847
Filed by INSTITUT NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Québec (CA)
PCT Filed Sep. 11, 2019, PCT No. PCT/CA2019/051284
§ 371(c)(1), (2) Date Mar. 11, 2021,
PCT Pub. No. WO2020/051701, PCT Pub. Date Mar. 19, 2020.
Claims priority of provisional application 62/730,062, filed on Sep. 12, 2018.
Prior Publication US 2022/0089626 A1, Mar. 24, 2022
Int. Cl. C07F 17/02 (2006.01); C07F 5/02 (2006.01)
CPC C07F 17/02 (2013.01) [C07F 5/02 (2013.01)] 20 Claims
OG exemplary drawing
 
1. A method for treating a pathogenic Neisseria infection in a subject comprising administering an effective amount of a borate compound to said subject, wherein the borate compound is of formula (I):
(Cat+-LK)m—B−—(R1)n(Cat+)p(A−)q  (1)
wherein:
m and n are integers from 0 to 4, with the proviso that m+n=4,
p is an integer and is the larger of 0 and 1-m,
q is an integer and is the larger of 0 and m−1,
each R1 independently represents:
alkyl, alkenyl, alkynyl, alkenynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkenynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heterocycloalkenynyl, aryl, or heteroaryl, all of which being unsubstituted or substituted with one or more of the following:—R2, —OR2, —P(R2)2, —SR2, —O—CO—R2, —CO—O—R2, —CO—R2, —CO—N(R2)2, —N(R2)2, —NR2—CO—R2, —C═NR2, —C≡N, —NO2, —N3, halogen, or -LK-R3,
each R2 independently represents:
alkyl, alkenyl, alkynyl, alkenynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkenynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heterocycloalkenynyl, aryl, or heteroaryl, all of which being unsubstituted or substituted with one or more of the following:—R4, —OR4, —P(R4)2, —SR4, —O—CO—R4, —CO—O—R4, —CO—R4, —CO—N(R4)2, —N(R4)2, —NR4—CO—R4, —C═NR4, —C═N, —NO2, —N3, halogen, or -LK-R3, or
—H, —OH, —P(R4)2, —SH, —O—CO—H, —COOH, —CO—H, —CO—NH2, —NH2, —NH—CO—H, —C═NH, —C═N, —NO2, —N3, halogen, or -LK-R3,
each R3 independently represents is a pharmaceutically acceptable metal-based complex;
each R4 independently represents: H, alkyl, alkenyl, alkynyl, alkenynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, cycloalkenynyl, heterocycloalkyl, heterocycloalkenyl, heterocycloalkynyl, heterocycloalkenynyl, aryl, heteroaryl, —OH, —SH, —O—CO—H, —COOH, —CO—H, —CO—NH2, —NH2, —NH—CO—H, —C═NH, —C≡N, —NO2, —N3, halogen, or -LK-R3,
each -LK- independently represents a covalent bond or one or more of the following, alone or in combination: amide, amine, imine, —C(═O)—, —S—, —S—S—, —O—, ester, alkylene, alkenylene, alkynylene, alkenylnylene, cycloalkylene, cycloalkenylene, cycloalkynylene, cycloalkenynylene, heterocycloalkylene, heterocycloalkenylene, heterocycloalkynylene, heterocycloalkenynylene, arylene, or heteroarylene,
each Cat+ independently represents a pharmaceutically acceptable cation which is:
(i) an alkali metal cation;
(ii) an alkaline earth metal cation;
(iii) a metal cation;
(iv) an inorganic amine cation;
(iv) a cation of an organic base; or
(v) a cationic metal-based complex, and
each A− independently represents a pharmaceutically acceptable anion, which is aceglutamate, acephyllinate, acetamidobenzoate, acetate, acetylasparaginate, acetylaspartate, adipate, aminosalicylate, anhydromethylenecitrate, ascorbate, aspartate, benzoate, benzylate, besylate, bicarbonate, bisulphate, bitartrate, borate, bromide, butylbromide, camphorate, camsylate, carbonate, chloride, chlorophemoxyacetate, citrate, closylate, cromesilate, cyclamate, dehydrochloate, dihydrochloride, dimalonate, edetate, edisylate, estolate, esylate, ethylbromide, ethylsulfate, fendizoate, fluoride, formate, fosfatex, fumarate, gluceptate, gluconate, glucoronate, glutamate, glycerophosphate, glycinate, glycollylarsinilate, glycyrrhizate, hippurate, hemisulphate, hexylresorcinate, hybenzate, hydrobromide, hydrochloride, hydroiodide, hydroxybenzenesulfonate, hydroxybenzoate, iodide, isethionate, lactate, lactobionate, lysine, malate, maleate, mandalate, mesylate, methylbromide, methyliodide, methylnitrate, methylsulphate, monophosadenine, mucate, napadisylate, napsylate, nicotinate, nitrate, oleate, orotate, oxalate, oxoglurate, pamoate, pantothenate, pectinate, phenylethylbarbiturate, phosphate, picrate, policrilix, polistirex, pyridoxylphosphate, polygalacturonate, propionate, saccharinate, salicylate, stearate, stearylsulphate, subacetate, succinate, sulfate, sulfosalicylate, tannate, tartrate, teprosilate, terephthalate, teoclate, thiocyanate, timonaciate, tosylate, triethiodide, undecanoate, and xinafoate,
with the proviso that no more than two R1 are halogen and
with the proviso that the borate compound comprises at least two R1, which are aryl or heteroaryl, both of which being unsubstituted or substituted with one or more of the following:—R2, —OR2, —P(R2)2, —SR2, —O—CO—R2, —CO—O—R2, —CO—R2, —CO—N(R2)2, —N (R2)2, —NR2—CO—R2, —C═NR2, —C≡N, —NO2, —N3, halogen, or -LK-R3.