SK712017A3 - Use of multi-substituted derivatives of hydroxynaphthalenes as antimycobacterial compounds - Google Patents

Use of multi-substituted derivatives of hydroxynaphthalenes as antimycobacterial compounds Download PDF

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SK712017A3
SK712017A3 SK71-2017A SK712017A SK712017A3 SK 712017 A3 SK712017 A3 SK 712017A3 SK 712017 A SK712017 A SK 712017A SK 712017 A3 SK712017 A3 SK 712017A3
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phenyl
fluoro
trifluoromethyl
nmr
yield
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Josef Jampílek
Tomáš Goněc
Jiří Kos
Šárka Pospíšilová
Hana Michnová
Alois Čížek
Aidan Coffey
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Univerzita Komenského v Bratislave
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Abstract

Opísané sú deriváty kyseliny naftalénovej všeobecného vzorca (I), (II) a (III) a farmaceutická kompozícia s ich obsahom. Tieto deriváty sú navrhnuté na použitie ako antimykobakteriálne zlúčeniny. Majú aktivitu nielen proti Mycobacterium tuberculosis, ale aj proti netuberkulóznym mykobaktériám.Described are naphthalene acid derivatives of the general formula (I), (II) and (III) and a pharmaceutical composition thereof. These derivatives are designed for use as antimycobacterial compounds. They have activity not only against Mycobacterium tuberculosis, but also against non-tuberculous mycobacteria.

Description

Oblasť technikyTechnical field

Predmetný vynález sa týka použitia na anilidovom kruhu multisubstituovaných derivátov kyselín hydroxynaftalénových ako antimykobaktenáhych zlúčenín.The present invention relates to the use on the anilide ring of multisubstituted hydroxynaphthalenic acid derivatives as antimycobactene compounds.

Doterajší stav technikyBACKGROUND OF THE INVENTION

Napriek schváleniu niektorých nových protituberkulóznych liekov, ako je bedachilin alebo delamanid [Working Group on New TB Drugs 2016], spomedzi infekčných chorôb tuberkulóza (TBC) zároveň s AIDS zostávajú hlavnou príčinou úmrtí na celom svete [WHO Global Tuberculosis Report 2016], TBC je spôsobovaná patogénom Mycobactenum tuberculosis, tzv. Kochovým bacilom, a aj napriek poklesu jej výskytu od 50. rokov 20. storočia v dôsledku zavedenia nových protituberkulóznych liekov do klinickej praxe, sa morbidita a mortalita od 80. rokov minulého storočia opäť zvýšila; TBC sa opätovne stala hlavnou bakteriálnou príčinou celosvetovej úmrtnosti, a preto zostáva vážnym globálnym problémom Najnovšia správa Svetovej zdravotníckej organizácie [WHO Annual TB Report 2017] uvádza, že v roku 2016 celosvetovo evidovali 10,4 milióna prípadov TBC, pričom zomrelo 1,5 milióna ľudí. V roku 2015 bolo odhadovaných 480 000 nových prípadov multirezistentnej TBC (MDR-TB). Rýchlosť úspešnej liečby tiež klesla v dôsledku výskytu kmeňov s rezistenciou alebo skríženou rezistenciou voči liekom, multrnenstentných, extenzívne alebo dokonca totálne rezistentných kmeňov. Zvýšenie počtu nových infekcií súvisí aj so zníženou imunitou celej populácie. Okrem toho časté výskyty letálnych komplikácií spojených s imunosuprimovanými populáciami zahŕňajú systémové infekcie spôsobené bežnými, pôvodne nepatogénnymi mykobakteriálnymi kmeňmi (napr. M. kansasii, M. avium,M. smegmatis atď.), ktoré spôsobujú ťažko liečiteľné alebo nevyliečiteľné ochorenia. Tieto netuberkulo/ne (atypické) mykobaktérie sú teraz považované za významné ľudské patogény a spôsobujú choroby ako je pľúcne ochorenie, lymfadenitída, ochorenie kože a mäkkých tkanív, gastrointestinálne a skeletálne infekcie, ktoré vedú k významnej chorobnosti často s fatálnym koncom |Ioachimescm O. C.; Tomford, J. W. Nontuberculous mycobacterial disorders. In Disease Management Project, Carey, W., Ed.; Cleveland Chmc-Centre for Continuing Education: Cleveland, OH, USA, 2015],Despite the approval of some new anti-tuberculosis drugs such as bedachillin or delamanide [Working Group on New TB Drugs 2016], among infectious diseases tuberculosis (TB) along with AIDS remain the leading cause of death worldwide [WHO Global Tuberculosis Report 2016], TBC is caused pathogen Mycobactenum tuberculosis, so-called. Koch's bacillus, and despite the decline in its incidence since the 1950s as a result of the introduction of new anti-tuberculosis drugs into clinical practice, morbidity and mortality have increased again since the 1980s; TB has once again become a major bacterial cause of global mortality, and therefore remains a serious global problem The WHO Annual TB Report 2017 reports that 10.4 million TB cases were reported worldwide in 2016, with 1.5 million deaths . In 2015, an estimated 480,000 new cases of multidrug-resistant TB (MDR-TB) were estimated. The rate of successful treatment also decreased due to the occurrence of drug-resistant or cross-drug resistant strains, multrnentent, extensive or even totally resistant strains. An increase in the number of new infections is also associated with reduced immunity of the entire population. In addition, frequent occurrences of lethal complications associated with immunosuppressed populations include systemic infections caused by common, originally non-pathogenic mycobacterial strains (e.g. M. kansasii, M. avium, M. smegmatis, etc.) that cause difficult to treat or incurable diseases. These non-tuberculosis (non-atypical) mycobacteria are now considered to be major human pathogens and cause diseases such as lung disease, lymphadenitis, skin and soft tissue disease, gastrointestinal and skeletal infections, leading to significant morbidity often with fatal outcome. Tomford, J. W. Nontuberculous mycobacterial disorders. In Disease Management Project, Carey, W., Ed .; Cleveland Center for Continuing Education: Cleveland, OH, USA, 2015],

Medzi často používané látky s výrazným biologickým účinkom patria rôzne substituované deriváty naftalénu. Napríklad v dokumente WO 9808797 boli popísané niektoré deriváty naftalénu, potenciálne vhodné pre použitie v terapii postmenopauzálneho syndrómu. V japonskom patente JPH 09183724 boli deriváty naftalén-2-karb orlovej kyseliny popísané ako potenciálne protinádorové lieky. V ďalšom japonskom patente JP 2008120694 boli popísané deriváty naftalén-2,3-diolov ako protinádorové látky. V dokumente WO 2009/068916 boli popísané niektoré diimidove deriváty naftalénu a ich komplexy s DNA. V dokumentoch WO 9621354 a WO 9621355 bolo niekoľko 1,2,3,4-subsúiuovaných derivátov naftalénu popísaných ako antimikróbiálne látky. Okrem toho je možné v literatúre nájsť monosubstituované deriváty naftalénovej kyseliny ako pesticídy [Ganec T. et al. Bioorg. Med. Chem Lett. 2017, 27, 1881; Peško, M. et al. Indián J. Chem B 2015, 54B, 12, 1511] alebo látky so stredne až slabou aktivitou len proti gram-pozitívnym baktériám a aj proti mykobaktériám [Gonéc T. et al. Bioorg. Med. Chem 2013, 21, 6531; Kos J. et al. Bioorg. Med. Chem 2015, 23, 2035; Kos J. et al. Molecules 2013, 18, 7977; Gonec T. et al. Molecules 2013, 18, 9397; ibid. 2014, 19, 10386; ibid. 2015, 20, 9767; ibid. 2016, 21, 1068; ibid. 2016, 21, 1189], V súčasnosti však neexistujú žiadne známe jednoduché deriváty naftalénu a predovšetkým amidové deriváty kyselín hydro^ynaftalénových, ktoré majú výrazmi antimykobakteriálnu účinnosť ako proti M. tuberculosis, tak aj proti tzv. netuberkulóznym (atypickým) mykobaktériám Počas štúdia našich amidových derivátov sme /iutiti výraznú aktivitu proti takýmto druhom/kmeňom mykobakténí.Frequently used substances with significant biological activity include various substituted naphthalene derivatives. For example, some naphthalene derivatives potentially suitable for use in the treatment of postmenopausal syndrome have been described in WO 9808797. In Japanese patent JPH 09183724, naphthalene-2-carbonic acid derivatives have been described as potential anticancer drugs. In another Japanese patent JP 2008120694, naphthalene-2,3-diol derivatives have been described as antitumor agents. WO 2009/068916 describes some of the naphthalene diimide derivatives and their DNA complexes. In WO 9621354 and WO 9621355 several 1,2,3,4-substituted naphthalene derivatives have been described as antimicrobial agents. In addition, monosubstituted naphthalenic acid derivatives as pesticides can be found in the literature [Ganec T. et al. Bioorg. Med. Chem Lett. 2017, 27, 1881; Pesko, M. et al. Indian J. Chem B 2015, 54B, 12, 1511] or substances with moderate to weak activity only against gram-positive bacteria as well as against mycobacteria [Gonéc T. et al. Bioorg. Med. Chem. 2013, 21, 6531; Kos J. et al. Bioorg. Med. Chem. 2015, 23, 2035; Kos J. et al. Molecules 2013, 18, 7977; Gonec T. et al. Molecules 2013, 18, 9397; ibid. 2014, 19, 10386; ibid. 2015, 20, 9767; ibid. 2016, 21, 1068; ibid. 2016, 21, 1189]. However, at present there are no known simple derivatives of naphthalene and in particular amide derivatives of hydro-naphthalenic acids, which have anti-mycobacterial activity against M. tuberculosis and against so-called " non-tuberculous (atypical) mycobacteria During the study of our amide derivatives, we / iutiti have significant activity against such mycobactene species / strains.

Podstata vynálezuSUMMARY OF THE INVENTION

Predmetom vynálezu je použitie zlúčenín so všeobecným vzorcom (I), (II) alebo (III) ako antimykobakteriálnych zlúčenín:The subject of the invention is the use of the compounds of the general formula (I), (II) or (III) as antimycobacterial compounds:

R kde R sú dva až päť substitucntov vybraných zo skupiny: vodík, halogén (fluór, chlór, bróm.jód), alkyl, tiež alkyl substituovaný halogénomalebo halogénmi, alkoxxl majúci 1-3 atómy uhlíka, nitro skupina.Wherein R is two to five substituents selected from the group: hydrogen, halogen (fluoro, chloro, bromo iodo), alkyl, also alkyl substituted by halogen or halogens, alkoxy having 1-3 carbon atoms, nitro group.

Zlúčeniny reprezentované vzorcom (I) alebo (II) alebo (III) majú schopnosť inhibovať rast mykobakténí.The compounds represented by formula (I) or (II) or (III) have the ability to inhibit the growth of mycobactens.

SK 71-2017 A3A3

Zlúčeniny reprezentované vzorcom (I) alebo (II) alebo (III) môžu byť formulované do bežných farmaceutických prípravkov ako sú tablety, kapsuly, prášky, roztoky, suspenzie, injekcie a ďalšie. Ako aktívne látky obsahujú takéto farmaceutické kompozície jednu alebo viac zlúčenín reprezentovaných vzorcom (I) alebo (II) alebo (III), predstavujúcich 0,5 % až 80 % hmotnostných.The compounds represented by formula (I) or (II) or (III) may be formulated into conventional pharmaceutical preparations such as tablets, capsules, powders, solutions, suspensions, injections and others. As active ingredients, such pharmaceutical compositions comprise one or more compounds represented by formula (I) or (II) or (III), representing 0.5% to 80% by weight.

Podrobný popis vynálezuDETAILED DESCRIPTION OF THE INVENTION

Naftalénové jadro patrí medzi často používané subštiuktúry v zlúčeninách s výraznými biologickými účinkami. Predmetom tohto vynálezu je použitie 2-hydr^oxy-A-arylnaftalén-l-karboxam^dov všeobecného štruktúrneho vzorca (I), 3-hydroxy-A-arylnaftalén-2-karboxamidov všeobecného štruktúrneho vzorca (II), 1-hydroxy-A-arylnaftalén-2-karboxamidov všeobecného štruktúrneho vzorca (III), ktoré sú v anilidovej časti di-, tri-, tetra- alebo penta-substituované vodíkom, halogénmi (fluórom, chlórom, brómom, jódom), nitro skupinou, alkylom, tiež alkylom substituovaným halogénom alebo halogénmi, alkoxylom majúcim 1 - 3 atómy uhlíka.The naphthalene nucleus is one of the frequently used substructures in compounds with significant biological effects. The present invention provides the use of 2-hydroxy-A-aryl-naphthalene-1-carboxamides of general structural formula (I), 3-hydroxy-A-aryl-naphthalene-2-carboxamides of general structural formula (II), 1-hydroxy-A -arylnaphthalene-2-carboxamides of the general structural formula (III), which in the anilide part are di-, tri-, tetra- or penta-substituted with hydrogen, halogens (fluorine, chlorine, bromine, iodine), nitro, alkyl, also alkyl substituted halogen or halogens, alkoxy having 1-3 carbon atoms.

Takto substituované zlúčeniny vykazujú výraznú schopnosť inhibovať rast mykobakténí.The compounds thus substituted exhibit a marked ability to inhibit the growth of mycobactens.

Príklady uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION

Príklad 1: Príklady vybraných derivátov naftalénu (I), ktoré sú popísané týmto vynálezomExample 1: Examples of selected naphthalene (I) derivatives described by the present invention

A-(2,6-diehlórfenyl)-2-hydro\ynaftalén-1-karbo\amid (1), výťažok 86 %; teplota topenia 160 - 163 °C; 1H-NMR (DMSO-A), δ: 10,22 (s, 1H); 10,16 (s, 1H); 8,07 (d, 1H, J = 8,1 Hz); 7,86 (d, 1H, J = 8,8 Hz); 7,84 (d, 1H, J = 7,3 Hz); 7,56 - 7,61 (m, 2H); 7,30 - 7,52 (m, 3H); 7,23 (d, 1H, J = 8,8 Hz).N- (2,6-Dichlorophenyl) -2-hydroxy-naphthalene-1-carboxamide (1), 86% yield; mp 160-163 ° C; 1 H-NMR (DMSO-A), δ: 10.22 (s, 1H); 10.16 (s, 1 H); 8.07 (d, 1H, J = 8.1Hz); 7.86 (d, 1H, J = 8.8Hz); 7.84 (d, 1H, J = 7.3Hz); 7.56 - 7.61 (m, 2H); 7.30 - 7.52 (m, 3H); 7.23 (d, 1H, J = 8.8Hz).

W(2,6-difluórfenyl)-2-hydroxynafíalén-1-karbo\amld (2), výťažok 85 %; mp 167 - 169 °C; ’H-NMR (DMSO-A), δ: 10,18 (s, 1H); 10,08 (s, 1H); 7,88 (d, 1H, J = 3,3 Hz); 7,82 - 7,85 (m, 2H); 7,51 (ddd, 1H, J = = 7,0 Hz, J = 3,7 Hz, J = 1,1 Hz); 7,20 - 7,40 (m, 5H).W (2,6-Difluorophenyl) -2-hydroxynaphthalene-1-carboxamide (2), 85% yield; mp 167-169 ° C; 1 H-NMR (DMSO-A), δ: 10.18 (s, 1H); 10.08 (s, 1 H); 7.88 (d, 1H, J = 3.3Hz); 7.82 - 7.85 (m, 2H); 7.51 (ddd, 1H, J = 7.0 Hz, J = 3.7 Hz, J = 1.1 Hz); 7.20-7.40 (m, 5H).

W(2,6-dibróim?enyl)-2-hydro\ynaftalén-1-karbo\amid (3), výťažok 82 %; teplota topenia 185 - 188 °C; 1H-NMR (DMSO-J4 δ: 10,22 (s, 1H); 10,19 (s, 1H); 8,25 (dd, 1H, J = 8,4 Hz, J =1,2 Hz); 7,77 - 7,89 (m, 4H); 7,47 (ddd, 1H, J = 8,3 Hz, J = 7,2 Hz, J = 1,5 Hz); 7,22 - 7,35 (m, 3H).W (2,6-dibróim?) -2-hydroxy \ ynaftalén-1-carbo \ amide (3), yield 82%; mp 185-188 ° C; 1 H-NMR (DMSO-d 6): 10.22 (s, 1H); 10.19 (s, 1H); 8.25 (dd, 1H, J = 8.4 Hz, J = 1.2 Hz); 7.77-7.89 (m, 4H); 7.47 (ddd, 1H, J = 8.3 Hz, J = 7.2 Hz, J = 1.5 Hz); 7.22-7.35 (m, 3 H).

V-|3.5-^lms(tni1lumm2tt^-l)i^^m^'l|-2-lr^'dro\vnafíalém-1-karbo\amid (4), výťažok 57 %; teplota topenia 178 až 179 °C; 1H-NMR (DMSO-Jm. δ: 11,09 (s, 1H); 10,31 (s, 1H); 8,50 (s, 2H); 7,92 (d, 1H, J = 8,4 Hz); 7,89 (s, 1H); 7,84 (d, 1H, J = 5,9 Hz); 7,72 (d, 1H, J = 8,4 Hz); 7,48 (td, 1H, J = 7,6 Hz, J = 1,1 Hz); 7,35 (td, 1H, J = = 8,1 Hz, J = 1,1 Hz); 7,28 (d, 1H, J = 8,8 Hz) [Cliované: Muto S., Itai A., Institute of medicinal molecular design, INC. Therapeutic agent for cancer. WO 03/103655 A1, 05/06/2003].N - (1-carboxymethyl-4-carboxylic amide) (4), yield 57%; mp 178-179 ° C; 1 H-NMR (DMSO-d 6): 11.09 (s, 1H); 10.31 (s, 1H); 8.50 (s, 2H); 7.92 (d, 1H, J = 8.4) Hz) 7.89 (s, 1H) 7.84 (d, 1H, J = 5.9 Hz) 7.72 (d, 1H, J = 8.4 Hz) 7.48 (td, 1H, J = 7.6Hz, J = 1.1Hz) 7.35 (td, 1H, J = 8.1Hz, J = 1.1Hz) 7.28 (d, 1H, J = 8.8 Hz) [Cliated: Muto S., Itai A., Institute of Medicinal Molecular Design, INC. Therapeutic Agent for Cancer, WO 03/103655 A1, 05/06/2003].

A-[2-chlór-5-(trifluórmetyl)fenyr|-2-hydro\ynaftalén-1-karbo\amid (5), výťažok 79 %; teplota topenia 121 až 122 °C; 1H-NMR (DMSO-Ä), δ: 10,53 (br, s, 1H); 10,29 (s, 1H); 8,44 (s, 1H); 8,04 (d, 1H, J = 8,4 Hz); 7,82 - 7,92 (m, 3H); 7,61 (dd, 1H, J = 8,8 Hz, J = 1,3 Hz); 7,51 (td, 1H, J = 7,5 Hz, J = 1,5 Hz); 7,35 (t, 1H, J = 7,3 Hz); 7,26 (d, 1H, J = 9,2 Hz).N- [2-Chloro-5- (trifluoromethyl) phenyl] -2-hydroxy-naphthalene-1-carboxamide (5), 79% yield; mp 121-122 ° C; 1 H-NMR (DMSO-d 6) δ: 10.53 (br, s, 1H); 10.29 (s, 1 H); 8.44 (s, 1 H); 8.04 (d, 1H, J = 8.4Hz); 7.82 - 7.92 (m, 3H); 7.61 (dd, 1H, J = 8.8 Hz, J = 1.3 Hz); 7.51 (td, 1H, J = 7.5Hz, J = 1.5Hz); 7.35 (t, 1H, J = 7.3Hz); 7.26 (d, 1H, J = 9.2Hz).

λ y2.5-dimctvltcmvl)-2-hvdro\vnaftalém-1-karbo\amid (6), výťažok 71 %; teplota topenia 162 - 165 °C; 1H-NMR (DMSO--T), δ: 10,13 (br, s, 1H); 9,71 (s, 1H); 7,83 - 7,87 (m, 3H); 7,50 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,1 Hz); 7,41 (s, 1H); 7,33 (t, 1H, J = 7,5 Hz); 7,24 (d, 1H, J = 9,1 Hz); 7,14 (d, 1H, J = 7,8 Hz); 6,96 (dd, 1H, J = 7,8 Hz, J = 1,1 Hz); 2,32 (s, 3H); 2,28 (s, 3H).[eta] < 5 > -2-dimethyl-naphthalene-1-carboxamide (6), yield 71%; mp 162-165 ° C; 1 H-NMR (DMSO-T), δ: 10.13 (br, s, 1H); 9.71 (s, 1 H); 7.83 - 7.87 (m, 3H); 7.50 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.1 Hz); 7.41 (s, 1 H); 7.33 (t, 1H, J = 7.5Hz); 7.24 (d, 1H, J = 9.1Hz); 7.14 (d, 1H, J = 7.8Hz); 6.96 (dd, 1H, J = 7.8 Hz, J = 1.1 Hz); 2.32 (s, 3H); 2.28 (s, 3H).

A-(3,5-dimetylfenyl)-2-hydrox/nafíalén-1-karbo\amld (7), výťažok 70 %; teplota topenia 181 — 184 °C; 1H-NMR (DMSO-Ä), δ: 10,22 (s, 1H); 10,07 (s, 1H); 7,84 (d, 2H, J = 8,4 Hz); 7,67 (d, 1H, J = 8,4 Hz); 7,49 (td, 1H, J = 7,0 Hz, J = 1,1 Hz); 7,34 (s, 2H); 7,32 (td, 1H, J = 7,0 Hz, J = 1,1 Hz); 7,26 (td, 1H, J = 9,1 Hz, J = 1,3 Hz); 7,34 (s, 1H); 2,27 (s, 6H).N - (3,5-dimethylphenyl) -2-hydroxy / naphthalene-1-carboxamide (7), yield 70%; mp 181-184 ° C; 1 H-NMR (DMSO- d 6), δ: 10.22 (s, 1H); 10.07 (s, 1 H); 7.84 (d, 2H, J = 8.4Hz); 7.67 (d, 1H, J = 8.4Hz); 7.49 (td, 1H, J = 7.0 Hz, J = 1.1 Hz); 7.34 (s, 2 H); 7.32 (td, 1H, J = 7.0 Hz, J = 1.1 Hz); 7.26 (td, 1H, J = 9.1 Hz, J = 1.3 Hz); 7.34 (s, 1 H); 2.27 (s, 6H).

A-(3,5-dimetoχďenyl)-2-hydroxynaftalén-1-karbo\amld (8), výťažok 64 %; teplota topenia 151 — 153 °C; 1H-NMR (DMSO-Ä), δ: 10,31 (s, 1H); 10,12 (s, 1H); 7,86 (d, 2H, J = 8,4 Hz); 7,67 (d, 1H, J = 8,4 Hz); 7,47 (td, 1H, J = 7,3 Hz, J =11 Hz); 7,33 (td, 1H, J = 7,3 Hz, J = 1,1 Hz); 7,25 (d, 1H, J = 8,8 Hz); 7,09 (s, 2H); 6,27 (s, 1H); 3,74 (s, 6H).N - (3,5-dimethoxyphenyl) -2-hydroxynaphthalene-1-carboxamide (8), yield 64%; mp 151-153 ° C; 1 H-NMR (DMSO- d 6), δ: 10.31 (s, 1H); 10.12 (s, 1 H); 7.86 (d, 2H, J = 8.4Hz); 7.67 (d, 1H, J = 8.4Hz); 7.47 (td, 1H, J = 7.3 Hz, J = 11 Hz); 7.33 (td, 1H, J = 7.3 Hz, J = 1.1 Hz); 7.25 (d, 1H, J = 8.8Hz); 7.09 (s, 2 H); 6.27 (s, 1 H); 3.74 (s, 6H).

W(2,4-difluórfenyl)-2-hydroxynafíalén-1-karbo\amld (9), výťažok 83 %; teplota topenia 176 - 180 °C; 1H-NMR (DMSO--T), δ: 10,19 (s, 1H); 10,16 (s, 1H); 7,90 (dd, 1H, J = 8,9 Hz, J = 6,2 Hz); 7,86 (d, 1H, J = 8,9 Hz);W (2,4-difluorophenyl) -2-hydroxynaphthalene-1-carboxamide (9), yield 83%; mp 176-180 ° C; 1 H-NMR (DMSO-T), δ: 10.19 (s, 1H); 10.16 (s, 1 H); 7.90 (dd, 1H, J = 8.9 Hz, J = 6.2 Hz); 7.86 (d, 1H, J = 8.9Hz);

SK 71-2017 A3A3

7,85 (d, 1H, J = 8,2 Hz); 7,82 (d, 1H, J = 8,5 Hz); 7,49 (ddd, 1H, J = 8,5 Hz, J = 6,8 Hz, J = 1,3 Hz); 7,36 (ddd, 1H, J = 10,8 Hz, J = 9,1 Hz, J = 2,9 Hz); 7,34 (ddd, 1H, J = 8,2 Hz, J = 6,8 Hz, J = 1,2 Hz); 7,24 (d, 1H, J = 8,1 Hz); 7,15 (m, 1H).7.85 (d, 1H, J = 8.2Hz); 7.82 (d, 1H, J = 8.5Hz); 7.49 (ddd, 1H, J = 8.5 Hz, J = 6.8 Hz, J = 1.3 Hz); 7.36 (ddd, 1H, J = 10.8 Hz, J = 9.1 Hz, J = 2.9 Hz); 7.34 (ddd, 1H, J = 8.2 Hz, J = 6.8 Hz, J = 1.2 Hz); 7.24 (d, 1H, J = 8.1Hz); 7.15 (m, IH).

AM2.5<dnLioifcm\d)-2-h\HiO\vnaftalen-1-karboxainid (10), výťažok 83 %; teplota topenia 148 - 151 °C; ]H-NMR (DMSO-t/č), δ: 10,36 (s, 1H); 10,29 (s, 1H); 8,03 (ddd, 1H, J = 10,1 Hz, J = 6,1 Hz, J = 3,2 Hz); 7,87 (d, 1H, J = 8,9 Hz); 7,85 (d, 1H, J = 8,2 Hz); 7,83 (d, 1H, J = 8,5 Hz); 7,48 (ddd, 1H, J = 8,5 Hz, J = 6,8 Hz, J = 1,4 Hz); 7,35 (ddd, 1H, J = 10,4 Hz, J = 9,5 Hz, J = 5,1 Hz); 7,34 (ddd, 1H, J = 8,2 Hz, J = 6,8 Hz, J = = 1,2 Hz); 7,24 (d, 1H, J = 8,9 Hz); 7,03 - 7,08 (m, 1H).AM2.5 <RTI ID = 0.0> (d) -2-h-H10 </RTI> naphthalene-1-carboxainide (10), yield 83%; mp 148-151 ° C; 1 H-NMR (DMSO-d6) δ: 10.36 (s, 1H); 10.29 (s, 1 H); 8.03 (ddd, 1H, J = 10.1 Hz, J = 6.1 Hz, J = 3.2 Hz); 7.87 (d, 1H, J = 8.9Hz); 7.85 (d, 1H, J = 8.2Hz); 7.83 (d, 1H, J = 8.5Hz); 7.48 (ddd, 1H, J = 8.5 Hz, J = 6.8 Hz, J = 1.4 Hz); 7.35 (ddd, 1H, J = 10.4 Hz, J = 9.5 Hz, J = 5.1 Hz); 7.34 (ddd, 1H, J = 8.2 Hz, J = 6.8 Hz, J = 1.2 Hz); 7.24 (d, 1H, J = 8.9Hz); 7.03-7.08 (m, 1H).

2-h\uhO\v-AGGÄ44nlliioi1cei\2)naftalen-1-karbo\ainid (11), výťažok 78 %; teplota topenia 164 - 168 °C; ]H-NMR (DMSO-A), δ: 10,39 (s, 1H); 10,23 (s, 1H); 7,87 (d, 1H, J = 8,9 Hz); 7,85 (d, 1H, J = 8,1 Hz); 7,79 (d, 1H, J = 8,5 Hz); 7,66 - 7,70 (m, 1H); 7,49 (ddd, 1H, J = 8,5 Hz, J = 6,8 Hz, J = 1,3 Hz); 7,35 - 7,40 (m, 1H); 7,34 (ddd, 1H, J = 8,1 Hz, J = 6,8 Hz, J = 1,1 Hz); 7,25 (d, 1H, J = 8,9 Hz).2-naphthalene-2-naphthalene-1-carbohydrate (11), yield 78%; mp 164-168 ° C; 1 H-NMR (DMSO-A), δ: 10.39 (s, 1H); 10.23 (s, 1 H); 7.87 (d, 1H, J = 8.9Hz); 7.85 (d, 1H, J = 8.1Hz); 7.79 (d, 1H, J = 8.5Hz); 7.66 - 7.70 (m, 1H); 7.49 (ddd, 1H, J = 8.5 Hz, J = 6.8 Hz, J = 1.3 Hz); 7.35-7.40 (m, 1H); 7.34 (ddd, 1H, J = 8.1 Hz, J = 6.8 Hz, J = 1.1 Hz); 7.25 (d, 1H, J = 8.9Hz).

2-hvdro\^--y-(2.,^.,5-^tiilliu.n1i^^in^-l)iaftalen-1-karbo\amid (12), výťažok 62 %; teplota topenia 152 - 156 °C; ]H-NMR (DMSO-A), δ: 10,37 (s, 1H); 10,25 (s, 1H); 8,15 (ddd, 1H, J = 12,3 Hz, J = 8,8 Hz, J = 7,2 Hz); 7,87 (d, 1H, J = 8,9 Hz); 7,85 (d, 1H, J = 8,2 Hz); 7,81 (d, 1H, J = 8,5 Hz); 7,67 (ddd, 1H, J = 10,6 Hz, J = = 10,6 Hz, J = 7,4 Hz); 7,48 (ddd, 1H, J = 8,5 Hz, J = 6,8 Hz, J = 1,4 Hz); 7,34 (ddd, 1H, J = 8,2 Hz, J = 6,8 Hz, J = 1,2 Hz); 7,24 (d, 1H, J = 8,9 Hz).2-Hydro-4-y- (2 ', 5', 5'-thienyl) -1'-phthalene-1-carboxamide (12), yield 62%; mp 152-156 ° C; 1 H-NMR (DMSO-A), δ: 10.37 (s, 1H); 10.25 (s, 1 H); 8.15 (ddd, 1H, J = 12.3 Hz, J = 8.8 Hz, J = 7.2 Hz); 7.87 (d, 1H, J = 8.9Hz); 7.85 (d, 1H, J = 8.2Hz); 7.81 (d, 1H, J = 8.5Hz); 7.67 (ddd, 1H, J = 10.6 Hz, J = 10.6 Hz, J = 7.4 Hz); 7.48 (ddd, 1H, J = 8.5 Hz, J = 6.8 Hz, J = 1.4 Hz); 7.34 (ddd, 1H, J = 8.2 Hz, J = 6.8 Hz, J = 1.2 Hz); 7.24 (d, 1H, J = 8.9Hz).

2-hvdΓo\λ-y-(2,3.,5.(6tctmtlluírkenvl)nafIalent^ 1-karbo\amid (13), výťažok 76 %; teplota topenia 156 - 159 °C; ]H-NMR (DMSO-de), δ: 10,53 (s, 1H); 10,29 (s, 1H); 7,86 - 7,90 (m, 1H); 7,89 (d, 1H, J = 8,9 Hz); 7,87 (d, 1H, J = 8,1 Hz); 7,79 (d, 1H, J = 8,5 Hz); 7,52 (ddd, 1H, J = 8,5 Hz, .J = 6,8 Hz, J = 1,3 Hz); 7,35 (ddd, 1H, J = 8,1 Hz, J = 6,8 Hz, J = 1,1 Hz); 7,26 (d, 1H, J = 8,9 Hz).2-Hydroxy-γ- (2,3,5,5 (6-trifluoromethyl) naphthalene-4-carboxamide (13), yield 76%; mp 156-159 ° C; 1 H-NMR (DMSO-d6)? δ: 10.53 (s, 1H); 10.29 (s, 1H); 7.86 - 7.90 (m, 1H); 7.89 (d, 1H, J = 8.9 Hz) 7.87 (d, 1H, J = 8.1 Hz); 7.79 (d, 1H, J = 8.5 Hz); 7.52 (ddd, 1H, J = 8.5 Hz, J); = 6.8 Hz, J = 1.3 Hz) 7.35 (ddd, 1H, J = 8.1 Hz, J = 6.8 Hz, J = 1.1 Hz), 7.26 (d, 1 H, J = 8.9 Hz).

2-h\uhΌ\v-λGA3Λ5.(6pceltaΠlιoΓfcnvl)nafIalen-1-kaΓbo\alnld (14), výťažok 69 %; teplota topenia 182 až 186 °C; ]H-NMR (DMSO-dó), δ: 10,52 (s, 1H); 10,30 (s, 1H); 7,90 (d, 1H, J = 8,9 Hz); 7,87 (d, 1H, J = 8,1 Hz); 7,76 (d, 1H, J = 8,5 Hz); 7,52 (ddd, 1H, J = 8,5 Hz, J = 6,8 Hz, J = 1,3 Hz); 7,35 (ddd, 1H, J = 8,1 Hz, J = 6,8 Hz, J = 1,1 Hz); 7,26 (d, 1H, J = 8,9 Hz).2-h-uhΌv-λGA3Λ5 (6pceltaΠlιΓΓfcnvl) naphthalene-1-carboaline (14), yield 69%; mp 182-186 ° C; 1 H-NMR (DMSO-d 6), δ: 10.52 (s, 1H); 10.30 (s, 1 H); 7.90 (d, 1H, J = 8.9Hz); 7.87 (d, 1H, J = 8.1Hz); 7.76 (d, 1H, J = 8.5Hz); 7.52 (ddd, 1H, J = 8.5 Hz, J = 6.8 Hz, J = 1.3 Hz); 7.35 (ddd, 1H, J = 8.1 Hz, J = 6.8 Hz, J = 1.1 Hz); 7.26 (d, 1H, J = 8.9Hz).

At(2,3-dlchlórfenyl)t2-hydro\vnaftalén-1tkarboxamld (15), výťažok 65 %; mp 167 - 168 °C; ]H-NMR (DMSO-dó), δ: 10,42 (s, 1 H); 10,19 (s, 1H); 7,86 - 7,97 (m, 4H); 7,47 - 7,52 (m, 3H); 7,35 (ddd, 1H, J = 8,3 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,25 (d, 1H, J = 8,6 Hz).N, (2,3-dichlorophenyl) -2-hydronaphthalene-1-carboxamide (15), yield 65%; mp 167-168 ° C; 1 H-NMR (DMSO-d 6), δ: 10.42 (s, 1H); 10.19 (s, 1 H); 7.86 - 7.97 (m, 4H); 7.47 - 7.52 (m, 3H); 7.35 (ddd, 1H, J = 8.3 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.25 (d, 1H, J = 8.6Hz).

24ι\Ηιό\\·-N-(2,4+--ποhlórfenyl)naftalén- 1-karbo\^amid (16), výťažok 79 %; teplota topenia 172 - 176 °C; ]H-NMR (DMSO-dô), δ: 10,53 (br.s, 1H); 10,23 (s, 1H); 8,36 (s, 1H); 8,02 (d, 1H, J = 8,4 Hz); 7,96 (s, 1H);N- (2,4 + - (4-fluorophenyl) naphthalene-1-carboxamide) (16), yield 79%; mp 172-176 ° C; 1 H-NMR (DMSO-d 6), δ: 10.53 (br.s, 1H); 10.23 (s, 1 H); 8.36 (s, 1 H); 8.02 (d, 1H, J = 8.4Hz); 7.96 (s, 1 H);

7,90 (d, 1H, J = 9,0 Hz); 7,85 (d, 1H, J =8,1 Hz); 7,47 - 7,53 (m, 1H); 7,32 - 7,38 (im W, 7,25 (d, 1H, J = = 8,8 Hz).7.90 (d, 1H, J = 9.0Hz); 7.85 (d, 1H, J = 8.1Hz); 7.47 - 7.53 (m, 1H); 7.32-7.38 (im W, 7.25 (d, 1H, J = 8.8 Hz).

At[2,4-bls(tπfluórmetyl)fenyΓ|-2-hydro\vnaftalén-1tkarbo\amld (17), výťažok 44 %; teplota topenia 168 až 172 °C; ]H-NMR (DMSO-dô), δ: 10,58 (s, 1H); 10,33 (s, 1H); 8,18 - 8,22 (m, 1H); 8,14 - 8,19 (m, 1H); 8,09 (br, s„ 1H); 7,96 (d, 1H, J = 8,6 Hz); 7,91 (d, 1H, J = 8,9 Hz); 7,86 (d, 1H, J = 8,1 Hz); 7,50 (ddd, 1H, J = 8,6 Hz, J = 6,8 Hz, J = 1,2 Hz); 7,35 (ddd, 1H, J = 8,1 Hz, J = 6,9 Hz, J = 1,0 Hz); 7,26 (d, 1H, J = 8,9 Hz).N, [2,4-bls (trifluoromethyl) phenyl] -2-hydronaphthalene-1-carbamamide (17), yield 44%; mp 168-172 ° C; 1 H-NMR (DMSO-d 6), δ: 10.58 (s, 1H); 10.33 (s, 1 H); 8.18 - 8.22 (m, 1H); 8.14 - 8.19 (m, 1H); 8.09 (br. S, 1H); 7.96 (d, 1H, J = 8.6Hz); 7.91 (d, 1H, J = 8.9Hz); 7.86 (d, 1H, J = 8.1Hz); 7.50 (ddd, 1H, J = 8.6 Hz, J = 6.8 Hz, J = 1.2 Hz); 7.35 (ddd, 1H, J = 8.1 Hz, J = 6.9 Hz, J = 1.0 Hz); 7.26 (d, 1H, J = 8.9Hz).

At[2,5-bls(tπfluórmetyl)fenyΓ|-2-hydro\ynaftalént1tkarbo\amld (18), výťažok 41 %; teplota topenia 141 až 143 °C; 1H-NMR (DMSO-dô), δ: 10,53 (s, 1H); 10,35 (s, 1H); 8,24 (br, s, 1H); 8,06 (d, 1H, J = 7,9 Hz); 7,95 (d, 1H, J = 8,5 Hz); 7,90 (d, 1H, J = 8,9 Hz); 7,87 (d, 1H, J = 7,9 Hz); 7,86 (d, 1H, J = 8,1 Hz); 7,51 (ddd, 1H, J = 8,5 Hz, J = 6,8 Hz, J = 1,1 Hz); 7,35 (ddd, 1H, J = 8,1 Hz, J = 6,8 Hz, J = 0,8 Hz); 7,26 (d, 1H, J = = 8,8 Hz).N, [2,5-bls (trifluoromethyl) phenyl] -2-hydroxy-naphthalene-1-carbo-amide (18), yield 41%; mp 141-143 ° C; 1 H-NMR (DMSO-d 6), δ: 10.53 (s, 1H); 10.35 (s, 1 H); 8.24 (br. S, 1H); 8.06 (d, 1H, J = 7.9Hz); 7.95 (d, 1H, J = 8.5Hz); 7.90 (d, 1H, J = 8.9Hz); 7.87 (d, 1H, J = 7.9Hz); 7.86 (d, 1H, J = 8.1Hz); 7.51 (ddd, 1H, J = 8.5 Hz, J = 6.8 Hz, J = 1.1 Hz); 7.35 (ddd, 1H, J = 8.1 Hz, J = 6.8 Hz, J = 0.8 Hz); 7.26 (d, 1H, J = 8.8 Hz).

At[2-chlórt3,5-bls(trlfluÓInletyl)fenyΓ|-2-hydro\ynaftalént1tkarbo\amld (19), výťažok 97 %; teplota topenia 172 - 176 °C; 1H-NMR (OMSO-de), δ: 10,61 (br, s, 2H); 8,73 (s, 1H); 8,02 (s, 1H); 8,02 (d, 1H, J = 8,4 Hz);At [2-chloro-3,5-bls (trifluoromethyl) phenyl] -2-hydroquinaphthalen-1-carbo-amide (19), yield 97%; mp 172-176 ° C; 1 H-NMR (OMSO-d 6), δ: 10.61 (br, s, 2H); 8.73 (s, 1 H); 8.02 (s, 1 H); 8.02 (d, 1H, J = 8.4Hz);

7,92 (d, 1H, J = 8,8 Hz); 7,86 (d, 1H, J = 8,1 Hz); 7,51 (ddd, 1H, J = 8,4 Hz, J = 6,9 Hz, J = 1,1 Hz); 7,36 (ddd, 1H, J = 8,1 Hz, J = 6,9 Hz, J = 0,9 Hz); 7,26 (d, 1H, J = 8,8 Hz).7.92 (d, 1H, J = 8.8Hz); 7.86 (d, 1H, J = 8.1Hz); 7.51 (ddd, 1H, J = 8.4 Hz, J = 6.9 Hz, J = 1.1 Hz); 7.36 (ddd, 1H, J = 8.1 Hz, J = 6.9 Hz, J = 0.9 Hz); 7.26 (d, 1H, J = 8.8Hz).

At(2-chlórt4-fluÓIr'enyl)-2-hydro\ynaftalént1tkarbo\amld (20), výťažok 81 %; teplota topenia 143 - 146 °C; ]H-NMR (DMSO-d6), δ: 10,30 (br, s, 1H); 10,03 (s, 1H); 7,96 (d, 1H, J = 8,2 Hz); 7,84 - 7,90 (m, 3H); 7,56 (dd, 1H, J = 8,7 Hz, J = 2,7 Hz); 7,47 - 7,52 (m, 1H); 7,29 - 7,36 (m, 2H); 7,25 (d, 1H, J = 8,7 Hz).N - (2-Chloro-4-fluoro-phenyl) -2-hydroxy-naphthalene-1-carbo-amide (20), yield 81%; mp 143-146 ° C; 1 H-NMR (DMSO-d 6), δ: 10.30 (br, s, 1H); 10.03 (s, 1 H); 7.96 (d, 1H, J = 8.2Hz); 7.84 - 7.90 (m, 3H); 7.56 (dd, 1H, J = 8.7 Hz, J = 2.7 Hz); 7.47 - 7.52 (m, 1H); 7.29 - 7.36 (m, 2H); 7.25 (d, 1H, J = 8.7Hz).

SK 71-2017 A3A3

AVM-chlor-2-nLicnfcnvl)-24ivdiO\vnafialcn-1-karéoxainid (21), výťažok 76 %; teplota topenia 157 - 160 °C; 1H-NMR (DMSO-dô), δ: 10,27 (s, 1H); 10,24 (br, s, 1H); 8,03 (t, 1H, J = 8,7 Hz); 7,83 - 7,88 (m, 2H); 7,81 (d, 1H, J = 8,7 Hz); 7,53 (dd, 1H, J = 10,5 Hz, J = 2,3 Hz); 7,48 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,1 Hz); 7,31 - 7,36 (m, 2H); 7,24 (d, 1H, J = 9,1 Hz).AVM-chloro-2-nitro-24-dihydro-naphthalene-1-caroxainide (21), yield 76%; mp 157-160 ° C; 1 H-NMR (DMSO-d 6), δ: 10.27 (s, 1H); 10.24 (br. S, 1H); 8.03 (t, 1H, J = 8.7Hz); 7.83 - 7.88 (m, 2H); 7.81 (d, 1H, J = 8.7Hz); 7.53 (dd, 1H, J = 10.5 Hz, J = 2.3 Hz); 7.48 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.1 Hz); 7.31-7.36 (m, 2H); 7.24 (d, 1H, J = 9.1Hz).

A-(5-chlór-2-ífuórfenyl)-2-hydroxynaftalén---karboxamld (22), výťažok 65 %; teplota topenia 158 - 161 °C; ]H-NMR (DMSO-dô), δ: 10,38 (s, 1H); 10,28 (br, s, 1H); 8,20 (dd, 1H, J = 6,6 Hz, J = 2,5 Hz); 7,87 (d, 1H, J = 9,4 Hz); 7,85 (d, 1H, J = 9,4 Hz); 7,82 (d, 1H, J = 9,1 Hz); 7,49 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,1 Hz);N- (5-chloro-2-fluorophenyl) -2-hydroxynaphthalene-carboxamide (22), yield 65%; mp 158-161 ° C; 1 H-NMR (DMSO-d 6), δ: 10.38 (s, 1H); 10.28 (br. S, 1H); 8.20 (dd, 1H, J = 6.6Hz, J = 2.5Hz); 7.87 (d, 1H, J = 9.4Hz); 7.85 (d, 1H, J = 9.4Hz); 7.82 (d, 1H, J = 9.1Hz); 7.49 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.1 Hz);

7,26 - 7,39 (m, 3H); 7,24 (d, 1H, J = 8,7 Hz).7.26-7.39 (m, 3H); 7.24 (d, 1H, J = 8.7Hz).

V-th-^lbroim^-^-^tlLUHrcin^'lt-h-^lh^'drox^'naftalcn- 1-karboxamid (23), výťažok 63 %; teplota topenia 169 - 172 °C; ]H-NMR (DMSO-dô), δ: 10,61 (br, s, 1H); 9,96 (s, 1H); 8,09 (d, 1H, J = 8,7 Hz); 7,98 (dd, 1H, J = 10,5 Hz, J = 2,3 Hz); 7,91 (d, 1H, J = 8,7 Hz); 7,86 (d, 1H, J = 8,2 Hz); 7,75 (dd, 1H, J = 8,7 Hz, J = 5,9 Hz); 7,50 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,1 Hz); 7,33 - 7,38 (m, 1H); 7,26 (d, 1H, J = 8,7 Hz); 7,08 (td, 1H, J = = 8,5 Hz, J = 2,7 Hz).N-thi-4-bromo-4-di-l-carboxyamide (23), yield 63%; mp 169-172 ° C; 1 H-NMR (DMSO-d 6), δ: 10.61 (br, s, 1H); 9.96 (s, 1 H); 8.09 (d, 1H, J = 8.7Hz); 7.98 (dd, 1H, J = 10.5 Hz, J = 2.3 Hz); 7.91 (d, 1H, J = 8.7Hz); 7.86 (d, 1H, J = 8.2Hz); 7.75 (dd, 1H, J = 8.7 Hz, J = 5.9 Hz); 7.50 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.1 Hz); 7.33-7.38 (m, 1H); 7.26 (d, 1H, J = 8.7Hz); 7.08 (td, 1H, J = 8.5 Hz, J = 2.7 Hz).

AVA-biOin-2-nLicnťcnvl)-2-hvdiO\vnaftalcn-1-karboxamid (24), výťažok 73 %; teplota topenia 186 - 189 °C; ]H-NMR (DMSO-dô), δ: 10,26 (s, 1H); 10,23 (br, s, 1H); 7,98 (t, 1H, J = 8,5 Hz); 7,83 - 7,88 (m, 2H); 7,80 (d, 1H, J = 8,2 Hz); 7,64 (dd, 1H, J = 10,3 Hz, J = 2,1 Hz); 7,45 - 7,50 (m, 2H); 7,33 (t, 1H, J = 7,1 Hz); 7,24 (d, 1H, J = 8,7 Hz).AVA-biolin-2-nitro) -2-hydroxy-naphthalene-1-carboxamide (24), yield 73%; mp 186-189 ° C; 1 H-NMR (DMSO-d 6), δ: 10.26 (s, 1H); 10.23 (br. S, 1H); 7.98 (t, 1H, J = 8.5Hz); 7.83 - 7.88 (m, 2H); 7.80 (d, 1H, J = 8.2Hz); 7.64 (dd, 1H, J = 10.3 Hz, J = 2.1 Hz); 7.45 - 7.50 (m, 2H); 7.33 (t, 1H, J = 7.1Hz); 7.24 (d, 1H, J = 8.7Hz).

A-(5-bróm-2-ífuórfenyl)-2-hydroxynaftalén---karboxamid (25), výťažok 74 %; teplota topenia 173 - 176 °C; ]H-NMR (DMSO-d6), δ: 10,37 (s, 1H); 10,27 (br, s, 1H); 8,32 (dd, 1H, J = 6,9 Hz, J = 2,3 Hz); 7,84 - 7,89 (m 2H); 7,82 (d, 1H, J = 8,7 Hz); 7,49 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,4 Hz); 7,41 (ddd, 1H, J = 8,7 Hz, J = 4,1 Hz, J = 2,7 Hz); 7,28 - 7,36 (m, 2H); 7,24 (d, 1H, J = 9,1 Hz).N- (5-bromo-2-fluorophenyl) -2-hydroxynaphthalene-carboxamide (25), yield 74%; mp 173-176 ° C; 1 H-NMR (DMSO-d 6), δ: 10.37 (s, 1H); 10.27 (br. S, 1H); 8.32 (dd, 1H, J = 6.9 Hz, J = 2.3 Hz); 7.84 - 7.89 (m 2H); 7.82 (d, 1H, J = 8.7Hz); 7.49 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.41 (ddd, 1H, J = 8.7 Hz, J = 4.1 Hz, J = 2.7 Hz); 7.28-7.36 (m, 2H); 7.24 (d, 1H, J = 9.1Hz).

A-(4-bróm-2,3,5,6-tetrafluórfenyl)-2-hydroχynaftalén---karboxamid (26), výťažok 60 %; teplota topenia 188 až 191 °C; ]H-NMR (DMSO-de), δ: 10,61 (s, 1H); 10,31 (s, 1H); 7,90 (d, 1H, J = 8,9 Hz); 8,87 (dd, 1H, J = = 8,0 Hz, J = 1,3 Hz); 7,77 (dd, 1H, J = 8,3 Hz, J = 1,1 Hz); 7,52 (ddd, 1H, J = 8,3 Hz, J = 6,8 Hz, J = 1,3 Hz); 7,35 (ddd, 1H, J = 8,0 Hz, J = 6,8 Hz, J = 1,1 Hz); 7,26 (d, 1H, J = 8,9 Hz).N - (4-bromo-2,3,5,6-tetrafluorophenyl) -2-hydroquinaphthalene-carboxamide (26), yield 60%; mp 188-191 ° C; 1 H-NMR (DMSO-d 6), δ: 10.61 (s, 1H); 10.31 (s, 1 H); 7.90 (d, 1H, J = 8.9Hz); 8.87 (dd, 1H, J = 8.0 Hz, J = 1.3 Hz); 7.77 (dd, 1H, J = 8.3 Hz, J = 1.1 Hz); 7.52 (ddd, 1H, J = 8.3 Hz, J = 6.8 Hz, J = 1.3 Hz); 7.35 (ddd, 1H, J = 8.0 Hz, J = 6.8 Hz, J = 1.1 Hz); 7.26 (d, 1H, J = 8.9Hz).

2-hvdroxy-A-[2-chlór-4-(trrfluórmetyl)fenvl]-naftalén-1-karbo>amid (27), výťažok 55 %; teplota topenia 195 až 198 °C; ]H-NMR (DMSO-d6), δ: 10,59 (br, s, 1H); 10,27 (s, 1H); 8,36 (d, 1H, J = 7,8 Hz); 8,03 (d, 1H, J = 8,2 Hz); 7,97 (s, 1H); 7,91 (d, 1H, J = 8,7 Hz); 7,86 (d, 1H, J = 8,2 Hz); 7,81 (d, 1H, J = 7,8 Hz); 7,48 až2-hydroxy-N- [2-chloro-4- (trifluoromethyl) phenyl] -naphthalene-1-carboxamide (27), yield 55%; mp 195-198 ° C; 1 H-NMR (DMSO-d 6), δ: 10.59 (br, s, 1H); 10.27 (s, 1 H); 8.36 (d, 1H, J = 7.8Hz); 8.03 (d, 1H, J = 8.2Hz); 7.97 (s, 1 H); 7.91 (d, 1H, J = 8.7Hz); 7.86 (d, 1H, J = 8.2Hz); 7.81 (d, 1H, J = 7.8Hz); 7.48 to

7,53 (m, 1H); 7,35 (t, 1H, J = 7,1 Hz); 7,27 (d, 1H, J = 9,1 Hz) [Citované: Needham D., Chen W., Mook R A., Wang J., Ren X., Chen M., Barak L., Lvcrlv H. K., Duke University Durham, Chemical modulators of signaling pathwavs and therapeutic use. WO 2016/210289 A1, 24/06/2016].7.53 (m, IH); 7.35 (t, 1H, J = 7.1Hz); 7.27 (d, 1H, J = 9.1 Hz) [Referred to: Needham D., Chen W., Mook R., Wang J., Ren X., Chen M., Barak L., Lvcrlv HK, Duke University of Durham, Chemical modulators of signaling pathways and therapeutic use. WO 2016/210289 A1, 24/06/2016].

2-hvdroxy-A-[4-chlór-2-(trtfluórmetyl)fenvl]-naftalén-1-karbo>amid (28), výťažok 72 %; teplota topenia 168 až 171 °C; 1H-NMR (DMSO-d6), δ: 10,36 (s, 1H); 10,14 (s, 1H); 7,84 - 7,90 (m, 6H); 7,49 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,1 Hz); 7,32 - 7,36 (m, 1H); 7,25 (d, 1H, J = 8,7 Hz).2-hydroxy-N- [4-chloro-2- (trifluoromethyl) phenyl] -naphthalene-1-carboxamide (28), yield 72%; mp 168-171 ° C; 1 H-NMR (DMSO-d 6), δ: 10.36 (s, 1H); 10.14 (s, 1 H); 7.84 - 7.90 (m, 6H); 7.49 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.1 Hz); 7.32-7.36 (m, 1H); 7.25 (d, 1H, J = 8.7Hz).

2-hvdroxy-A-[4-chlór-3-(trtfluórmetyl)fenvl]-naftalén-1-karbo>amid (29), výťažok 77 %; teplota topenia 165 až 168 °C; 1H-NMR (DMSO-de), δ: 10,86 (s, 1H); 10,24 (s, 1H); 8,45 (d, 1H, J = 2,7 Hz); 8,02 (dd, 1H, J = = 8,9 Hz, J = 2,5 Hz); 7,89 (d, 1H, J = 9,1 Hz); 7,86 (d, 1H, J = 8,2 Hz); 7,72 (d, 1H, J = 8,7 Hz); 7,68 (d, 1H, J = 8,2 Hz); 7,47 (ddd, 1H, J = 8,6 Hz, J = 7,0 Hz, J = 1,4 Hz); 7,34 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = = 0,9 Hz); 7,26 (d, 1H, J = 8,9 Hz).2-hydroxy-N- [4-chloro-3- (trifluoromethyl) phenyl] -naphthalene-1-carbamide (29), yield 77%; mp 165-168 ° C; 1 H-NMR (DMSO-d 6), δ: 10.86 (s, 1H); 10.24 (s, 1 H); 8.45 (d, 1H, J = 2.7Hz); 8.02 (dd, 1H, J = 8.9 Hz, J = 2.5 Hz); 7.89 (d, 1H, J = 9.1Hz); 7.86 (d, 1H, J = 8.2Hz); 7.72 (d, 1H, J = 8.7Hz); 7.68 (d, 1H, J = 8.2Hz); 7.47 (ddd, 1H, J = 8.6 Hz, J = 7.0 Hz, J = 1.4 Hz); 7.34 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 0.9 Hz); 7.26 (d, 1H, J = 8.9Hz).

A-[3-fluór-4-(trfuóπnetyl)fenyΓ|-2-hydroxvnaftalén---karbo>amίd (30), výťažok 68 %; teplota topenia 183 až 186 °C; Ή-NMR (DMSO-d6), δ: 10,99 (s, 1H); 10,29 (s, 1H); 8,04 (d, 1H, J = 13,7 Hz); 7,90 (d, 1H, J = = 8,7 Hz); 7,87 (d, 1H, J = 8,2 Hz); 7,75 - 7,80 (m, 1H); 7,65 - 7,70 (m, 2H); 7,47 (t, 1H, J = 7,5 Hz); 7,34 (t, 1H, J = 7,3 Hz); 7,27 (d, 1H, J = 8,7 Hz).N- [3-fluoro-4- (trifluoromethyl) phenyl] -2-hydroxynaphthalene-carbamide (30), yield 68%; mp 183-186 ° C; Δ-NMR (DMSO-d 6), δ: 10.99 (s, 1H); 10.29 (s, 1 H); 8.04 (d, 1H, J = 13.7Hz); 7.90 (d, 1H, J = 8.7 Hz); 7.87 (d, 1H, J = 8.2Hz); 7.75 - 7.80 (m, IH); 7.65 - 7.70 (m, 2H); 7.47 (t, 1H, J = 7.5Hz); 7.34 (t, 1H, J = 7.3Hz); 7.27 (d, 1H, J = 8.7Hz).

A-[3-fluór-5-(trfuóπnetyl)fenyΓ|-2-hydroxvnaftalén---karbo>amίd (31), výťažok 62 %; teplota topenia 163 až 167 °C; 1H-NMR (DMSO-d6), δ: 10,95 (s, 1H); 10,28 (s, 1H); 8,07 (s, 1H); 7,97 (d, 1H, J = 11,0 Hz); 7,90 (d, 1H, J = 9,1 Hz); 7,87 (d, 1H, J = 8,2 Hz); 7,69 (d, 1H, J = 8,2 Hz); 7,45 - 7,50 (m, 1H); 7,41 (d, 1H, J = = 8,7 Hz); 7,35 (t, 1H, J = 7,3 Hz); 7,27 (d, 1H, J = 9,1 Hz).N- [3-fluoro-5- (trifluoromethyl) phenyl] -2-hydroxynaphthalene-carbamide (31), 62% yield; mp 163-167 ° C; 1 H-NMR (DMSO-d 6), δ: 10.95 (s, 1H); 10.28 (s, 1 H); 8.07 (s, 1 H); 7.97 (d, 1H, J = 11.0 Hz); 7.90 (d, 1H, J = 9.1Hz); 7.87 (d, 1H, J = 8.2Hz); 7.69 (d, 1H, J = 8.2Hz); 7.45-7.50 (m, 1H); 7.41 (d, 1H, J = 8.7Hz); 7.35 (t, 1H, J = 7.3Hz); 7.27 (d, 1H, J = 9.1Hz).

A-[4-fluór-2-(trfuóπnetyl)fenyΓ|-2-hydroxvnaftalén---karbo>amίd (32), výťažok 89 %; teplota topenia 158 až 163 °C; 1H-NMR (DMSO-d6), δ: 10,28 (s, 1H); 10,10 (s, 1H); 7,84 - 7,89 (m, 3H); 7,79 (dd, 1H, J = 8,5 Hz,N- [4-fluoro-2- (trifluoromethyl) phenyl] -2-hydroxynaphthalene-carbamide (32), yield 89%; mp 158-163 ° C; 1 H-NMR (DMSO-d 6), δ: 10.28 (s, 1H); 10.10 (s, 1 H); 7.84 - 7.89 (m, 3H); 7.79 (dd, 1H, J = 8.5Hz)

SK 71-2017 A3A3

J = 5,3 Hz); 7,71 (dd, 1H, J = 9,1 Hz, J = 2,7 Hz); 7,67 (td, 1H, J = 8,2 Hz, J = 3,2 Hz); 7,49 (t, 1H, J = = 7,5 Hz); 7,34 (t, 1H, J = 7,5 Hz); 7,25 (d, 1H, J = 9,1 Hz).J = 5.3 Hz); 7.71 (dd, 1H, J = 9.1 Hz, J = 2.7 Hz); 7.67 (td, 1H, J = 8.2 Hz, J = 3.2 Hz); 7.49 (t, 1H, J = 7.5Hz); 7.34 (t, 1H, J = 7.5Hz); 7.25 (d, 1H, J = 9.1Hz).

A’-|4-nLior-3-(4nnLiCHmctvl)fcnvl|-2-hvdiO\ymaftalcn-1-karboyiinid (33), výťažok 68 %; teplota topenia 195 až 198 °C; Ή-NMR (DMSO-dô), δ: 10,78 (s, 1H); 10,22 (s, 1H); 8,38 (dd, 1H, J = 6,4 Hz, J = 2,3 Hz); 7,99 až 8,03 (m, 1H); 7,89 (d, 1H, J = 9,1 Hz); 7,86 (d, 1H, J = 8,2 Hz); 7,69 (d, 1H, J = 8,2 Hz); 7,53 (t, 1H, J = = 9,8 Hz); 7,47 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,4 Hz); 7,37 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 0,9 Hz);N '- | 4-nLior-3- (4nnLiCHmctvl) fcnvl | -2-hvdi0-? Yaftaline-1-carboyiinide (33), 68% yield; mp 195-198 ° C; Δ-NMR (DMSO-d 6), δ: 10.78 (s, 1H); 10.22 (s, 1 H); 8.38 (dd, 1H, J = 6.4 Hz, J = 2.3 Hz); 7.99 to 8.03 (m, 1H); 7.89 (d, 1H, J = 9.1Hz); 7.86 (d, 1H, J = 8.2Hz); 7.69 (d, 1H, J = 8.2Hz); 7.53 (t, 1H, J = 9.8 Hz); 7.47 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.37 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 0.9 Hz);

7,26 (d, 1H, J = 9,1 Hz).7.26 (d, 1H, J = 9.1Hz).

A-[2-fluór-3-(tnfluórmetyl)fenvl]-2-hvdiO\vnaftalén-l-karboxaimíd (34), výťažok 51 %; teplota topenia 133 až 135 °C; Ή-NMR (DMSO-dó), δ: 10,49 (s, 1H); 10,27 (s, 1H); 8,28 (t, 1H, J = 7,3 Hz); 7,85 - 7,89 (m, 2H); 7,81 (d, 1H, J = 8,2 Hz); 7,59 - 7,64 (m, 1H); 7,50 (ddd, 1H, J = 8,5 Hz, J = 7,1 Hz, J = 1,4 Hz); 7,47 (t, 1H, J = 7,8 Hz); 7,32 - 7,37 (m, 1H); 7,26 (d, 1H, J = 8,7 Hz).N- [2-fluoro-3- (trifluoromethyl) phenyl] -2-hydroxy-naphthalene-1-carboxaimide (34), 51% yield; mp 133-135 ° C; Δ-NMR (DMSO-d 6), δ: 10.49 (s, 1H); 10.27 (s, 1 H); 8.28 (t, 1H, J = 7.3Hz); 7.85 - 7.89 (m, 2H); 7.81 (d, 1H, J = 8.2Hz); 7.59 - 7.64 (m, 1H); 7.50 (ddd, 1H, J = 8.5 Hz, J = 7.1 Hz, J = 1.4 Hz); 7.47 (t, 1H, J = 7.8Hz); 7.32-7.37 (m, 1H); 7.26 (d, 1H, J = 8.7Hz).

A-[2-fluór-5-(trlfluórmetyl)fenvl]-2-hvdIΌ\ynaftalén-l-karbo>alΠlld (35), výťažok 71 %; teplota topenia 156 až 158 °C; Ή-NMR (DMSO-dó), δ: 10,55 (s, 1H); 10,31 (bn, s, 1H); 8,54 (dd, 1H, J = 6,9 Hz, J = 1,8 Hz);N- [2-fluoro-5- (trifluoromethyl) phenyl] -2-pyridinaphthalene-1-carbonyl-III (35), yield 71%; mp 156-158 ° C; Δ-NMR (DMSO-d 6), δ: 10.55 (s, 1H); 10.31 (bn, s, 1 H); 8.54 (dd, 1H, J = 6.9 Hz, J = 1.8 Hz);

7.89 (d, 1H, J = 9,1 Hz); 7,86 (d, 1H, J = 8,7 Hz); 7,83 (d, 1H, J = 8,7 Hz); 7,60 - 7,65 (m, 1H); 7,54 - 7,58 (m, 1H); 7,49 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,4 Hz); 7,32 - 7,36 (m, 1H); 7,25 (d, 1H, J = 8,7 Hz).7.89 (d, 1H, J = 9.1Hz); 7.86 (d, 1H, J = 8.7Hz); 7.83 (d, 1H, J = 8.7Hz); 7.60 - 7.65 (m, 1H); 7.54 - 7.58 (m, IH); 7.49 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.32-7.36 (m, 1H); 7.25 (d, 1H, J = 8.7Hz).

A’-p.ň-ditfLioiH-ttntfLiCHinctvl)fcnvl|-2-hvdm\vnaftaléU]-1-karboxainid (36), výťažok 57 %; teplota topenia 164 - 167 °C; 1H-NMR (DMSO-dó), δ: 10,78 (s, 1H); 10,42 (bn, s, 1H); 8,46 (dd, 1H, J = 12,4 Hz, J = 5,9 Hz);N-ditfLioiH-ttntfLiCHinctvl) -2-hvdm \ naphthalene] -1-carboxainide (36), 57% yield; mp 164-167 ° C; 1 H-NMR (DMSO-d 6), δ: 10.78 (s, 1H); 10.42 (bn, s, 1 H); 8.46 (dd, 1H, J = 12.4 Hz, J = 5.9 Hz);

7.90 (d, 1H, J = 9,1 Hz); 7,81 - 7,87 (m, 3H); 7,48 (t, 1H, J = 7,3 Hz); 7,32 - 7,37 (m, 1H); 7,24 (d, 1H, J = = 8,7 Hz).7.90 (d, 1H, J = 9.1Hz); 7.81 - 7.87 (m, 3H); 7.48 (t, 1H, J = 7.3Hz); 7.32-7.37 (m, 1H); 7.24 (d, 1H, J = 8.7 Hz).

A-[4-bnóm-2-(trlΠuÓImetyl)fenyl]-2-hydno\vnaftalén---karbo>aπlld (37), výťažok 68 %; teplota topenia 185 až 188 °C; 1H-NMR (DMSO-dó), δ: 1037 (br, s , 1H); 10,12 (s, 1^; 7,96 - 8,01 (m, 2H); 8,84 - 7,91 (m, 3H); 7,80 (d, 1H, J = 8,2 Hz); 7,49 (t, 1H, J = 7^3 D)) 1,34 1t, 1H, J = 7,3 Hz); 7,25 (d, 1H, J = 9,1 Hz).N- [4-bromo-2- (trifluoromethyl) phenyl] -2-hydnaquinaphthalene-carboaldehyde (37), yield 68%; mp 185-188 ° C; 1 H-NMR (DMSO-d 6), δ: 1037 (br, s, 1H); 10.12 (s, 1H, 7.96-8.01 (m, 2H); 8.84-7.91 (m, 3H); 7.80 (d, 1H, J = 8.2 Hz) 7.49 (t, 1H, J = 7 (3H)) 1.34 (t, 1H, J = 7.3 Hz); 7.25 (d, 1H, J = 9.1Hz).

A-[2-bnóm-5-(tInfluóπnetyl)fenyΓ|-2-hydno\ynaftalén---kanbo\amld (38), výťažok 61 %; teplota topenia 180 až 183 °C; 1H-NMR (DMSO-dó), δ: 1036(1^ 1 , 1HH; 10,17 (s, 1H); 8,37 (s, 1¾ 8,07 (d, 1H, J = 8,7 Hz); 7,98 (d, 1H, J = 8,2 Hz); 7,91 (d, 1H,7 = 9,1 TH); 7,76(d, 1H, J = 8,2 Hz); 7,49 - 7,56 (m, 2H); 7,35 (t, 1H, J = 7,3 Hz); 7,27 (d, 1H, J = 8,7 Hz).N - [2-bromo-5- (trifluoromethyl) phenyl] -2-hydroxy-naphthalene-kanbolamide (38), yield 61%; mp 180-183 ° C; 1 H-NMR (DMSO-d 6), δ: 1036 (1H, 1HH; 10.17 (s, 1H); 8.37 (s, 1H, 8.07 (d, 1H, J = 8.7 Hz)) 7.98 (d, 1H, J = 8.2 Hz); 7.91 (d, 1H, J = 9.1 TH); 7.76 (d, 1H, J = 8.2 Hz); 49-7.56 (m, 2H), 7.35 (t, 1H, J = 7.3 Hz), 7.27 (d, 1H, J = 8.7 Hz).

A-[7-bnóm-5-(tInfluóπnetyl)fenyΓ|-2-hydno\ynaftalén---kanbo\amld (39), výťažok 73 %; teplota topenia 201 až 204 °C; 1H-NMR (DMSO-dó), δ: 10,89 (s, 1H); 10,27 (bn, s, 1H); 8,32 (s, 1H); 8,22 (s, 1H); 7,90 (d, 1H, J = 9,1 Hz); 7,87 (d, 1H, J = 8,2 Hz); 7,68 - 7,72 (m, 2H); 7,45 - 7,50 (m, 1H); 7,32 - 7,37 (m, 1H); 7,26 (d, 1H, J = 8,7 Hz).N - [7-Bromo-5- (trifluoromethyl) phenyl] -2-hydroxy-naphthalene-kanbolamide (39), yield 73%; mp 201-204 ° C; 1 H-NMR (DMSO-d 6), δ: 10.89 (s, 1H); 10.27 (bn, s, 1 H); 8.32 (s, 1 H); 8.22 (s, 1 H); 7.90 (d, 1H, J = 9.1Hz); 7.87 (d, 1H, J = 8.2Hz); 7.68 - 7.72 (m, 2H); 7.45-7.50 (m, 1H); 7.32-7.37 (m, 1H); 7.26 (d, 1H, J = 8.7Hz).

A-[4-bnóm-3-(tInfluóπnetyl)fenyΓ|-2-hydno\ynaftalén---kanbo\amld (40), výťažok 69 %; teplota topenia 155 až 157 °C; 1H-NMR (DMSO-dó), δ: 10,84 (s, 1H); 10,24 (bn, s, 1H); 8,44 (d, 1H, J = 2,3 Hz); 7,95 (dd, 1H, J = 8,9 Hz, J = 2,5 Hz); 7,89 (d, 1H, J = 11,4 Hz); 7,88 (s, 1H); 7,86 (d, 1H, J = 3,2 Hz); 7,68 (d, 1H, J = 8,2 Hz); 7,45 - 7,49 (m, 1H); 7,32 - 7,36 (m, 1H); 7,26 (d, 1H, J = 8,7 Hz).N - [4-bromo-3- (trifluoromethyl) phenyl] -2-hydroxy-naphthalene-kanbolamide (40), yield 69%; mp 155-157 ° C; 1 H-NMR (DMSO-d 6), δ: 10.84 (s, 1H); 10.24 (bn, s, 1 H); 8.44 (d, 1H, J = 2.3Hz); 7.95 (dd, 1H, J = 8.9 Hz, J = 2.5 Hz); 7.89 (d, 1H, J = 11.4Hz); 7.88 (s, 1 H); 7.86 (d, 1H, J = 3.2Hz); 7.68 (d, 1H, J = 8.2Hz); 7.45 - 7.49 (m, 1H); 7.32-7.36 (m, 1H); 7.26 (d, 1H, J = 8.7Hz).

2-hvdno\v-A-[2-metyl-5-(t]nfluórmetyl)fenyΓ|-naftalén---kanbo\amld (41), výťažok 67 %; teplota topenia 143 - 146 °C; 1H-NMR (DMSO-dó), δ: 10,26 (s, 1H); (s, 1H); 8,06 (s, 1H); 7,85 - 7,89 (m, 3H); 7,48 až 7,53 (m, 3H); 7,33 - 7,37 (m, 1H); 7,26 (d, 1H, J = 9,1 Hz); 2,42 (s, 3H).2-Star-N- [2-methyl-5- (trifluoromethyl) phenyl] -naphthalene-kanbolamine (41), yield 67%; mp 143-146 ° C; 1 H-NMR (DMSO-d 6), δ: 10.26 (s, 1H); (s, 1 H); 8.06 (s, 1 H); 7.85 - 7.89 (m, 3H); 7.48 to 7.53 (m, 3H); 7.33-7.37 (m, 1H); 7.26 (d, 1H, J = 9.1Hz); 2.42 (s, 3H).

2-hvdno\v-A-[4-metyl-3-(t]nfluórmctyl)fenyΓ|-naftalén---kanbo\amld (42), výťažok 60 %; teplota topenia 155 - 160 °C; 1H-NMR (DMSO-dó), δ: 10,62 (s, 1H); 10,17 (s, 1H); 8,28 (d, 1H, J = 1,8 Hz); 7,84 - 7,90 (m, 3H); 7,68 (d, 1H, J = 8,2 Hz); 7,44 - 7,48 (m, 1H); 7,42 (d, 1H, J = 8,2 Hz); 7,31 - 7,35 (m, 1H); 7,26 (d, 1H, J = 8,7 Hz); 2,42 (s, 3H).2-Star-N- [4-methyl-3- (trifluoromethyl) phenyl] -naphthalene-kanamide (42), yield 60%; mp 155-160 ° C; 1 H-NMR (DMSO-d 6), δ: 10.62 (s, 1H); 10.17 (s, 1 H); 8.28 (d, 1H, J = 1.8Hz); 7.84 - 7.90 (m, 3H); 7.68 (d, 1H, J = 8.2Hz); 7.44 - 7.48 (m, 1H); 7.42 (d, 1H, J = 8.2Hz); 7.31-7.35 (m, 1H); 7.26 (d, 1H, J = 8.7Hz); 2.42 (s, 3H).

2-hvdno\v-A-[4-nltro-7-(trifluónmetyl)fenvl]-naftalén---karbo>aπlld (43), výťažok 18 %; teplota topenia 157 až 160 °C; 1H-NMR (DMSO-dó), δ: 11,24 (s, 1H); 10,35 (bn, s, 1H); 8,52 (s, 1H); 8,23 - 8,29 (m, 2H); 7,92 (d, 1H, J = 9,1 Hz); 7,88 (d, 1H, J = 8,2 Hz); 7,70 (d, 1H, J = 8,7 Hz); 7,48 (ddd, 1H, J = 8,6 Hz, J = 7,0 Hz, J = 1,4 Hz); 7,33 - 7,38 (m, 1H); 7,28 (d, 1H, J = 9,1 Hz).2-Star-N- [4-nitro-7- (trifluoromethyl) phenyl] -naphthalene-carbonyl (43), 18% yield; mp 157-160 ° C; 1 H-NMR (DMSO-d 6), δ: 11.24 (s, 1H); 10.35 (bn, s, 1 H); 8.52 (s, 1 H); 8.23 - 8.29 (m, 2H); 7.92 (d, 1H, J = 9.1Hz); 7.88 (d, 1H, J = 8.2Hz); 7.70 (d, 1H, J = 8.7Hz); 7.48 (ddd, 1H, J = 8.6 Hz, J = 7.0 Hz, J = 1.4 Hz); 7.33-7.38 (m, 1H); 7.28 (d, 1H, J = 9.1Hz).

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Príklad 2: Príklady vybraných derivátov naftalénu (II), ktoré sú popísané týmto vynálezom λ <3.5<iichkHfcn\d)-34i\xhO\vnaftalen-2-karboxainid (44), výťažok: 70 %; teplota topenia 252 °C; ]H-NMR (DMSO-dó), δ: 7,34 (s, 1H); 7,34 (t, J = 1,7 Hz, 1H); 7,36 (ddd, J =1,1 Hz, J = 6,8 Hz, J = 8,2 Hz, 1H); 7,51 (ddd, J =1,2 Hz, J = 6,8 Hz, J = 8,3 Hz, 1H); 7,77 (d, J = 8,3 Hz, 1H); 7,89 (d, J = 1,7 Hz, 2H); 7,92 (d, J = = 8,2 Hz, 1H); 8,39 (s, 1H); 10,75 (s, NH, 1H); 11,04 (s, OH, 1H).Example 2: Examples of selected naphthalene (II) derivatives described by the present invention λ < 3.5 < 3.5 &gt; [1,3] h-naphthalene-2-carboxainide (44), yield: 70%; mp 252 ° C; 1 H-NMR (DMSO-d 6), δ: 7.34 (s, 1H); 7.34 (t, J = 1.7Hz, 1H); 7.36 (ddd, J = 1.1 Hz, J = 6.8 Hz, J = 8.2 Hz, 1H); 7.51 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.3 Hz, 1H); 7.77 (d, J = 8.3Hz, 1H); 7.89 (d, J = 1.7Hz, 2H); 7.92 (d, J = 8.2Hz, 1H); 8.39 (s, 1 H); 10.75 (s, NH, 1 H); 11.04 (s, OH, 1 H).

A/2.6<hnliorfcn\4)-34i\xhO\vnaftaléaiU-karbo\ainid (44), výťažok 78 %; teplota 19^4 198 OC; ]H-NMR (DMSO-dô), δ: 11,48 (s, 1H); 10,41 (s, 1H); 8,61 (s, 1 1¾ 8,99 (d, 1H J = 8,1 (Hý 8,77 (d 1H J = = 8,1 Hz); 7,54 (t, 1H, J = 7,0 Hz); 7,33 - 7,44 (m, 4H); 7,25 (t, 1H, J = 7,9 Hz).A / 2.6 (pyrrolidin-4) -34i-xhO-naphthalene-carbohydrate (44), yield 78%; temperature 19 ^ C 4198 H; 1 H-NMR (DMSO-d 6), δ: 11.48 (s, 1H); 10.41 (s, 1 H); 8.61 (s, 1H, 8.99 (d, 1H J = 8.1) (H, 8.77 (d 1H J = 8.1 Hz); 7.54 (t, 1H, J = 7.0) Hz), 7.33-7.44 (m, 4H), 7.25 (t, 1H, J = 7.9 Hz).

V-(3,í^-^(^^l^(^]rfe]^^l)-3^^;ydro\ynaftalén^2^^k^ai^bc^xamid (46), výťažok 79 %; teplota topenia 273 - 276 OC; ]H-NMR (DMSO-dô), δ: 11,05 (s, 1H); 10,80 (s, 1H); 8,38 (s, 11H 7,93 (d, 1H, J = 8,0Hz)(7,76 (di 1H, J = 8,4 Hz); 7,51 - 7,62 (m, 3H); 7,38 (t, 1H, J = 7,5 Hz); 7,34 (s, 1H); 6,99 (t, 1H, J = 8,0 Hz). [Citované: Law K. Y., Tamawskyj, I. W. Xerox Corp. Electrophotographic photoconductor containing dtazo compound in photogenerating layer. US 4797337 A, 27/06/1987].N - (3 R, 4 '- (4', 1 '(1') - (1 ') - 3') - 3 ', 4', 4'-naphthalene - 2 ', 4'-hexamide (46), yield 79%; mp 273-276 C;] H-NMR (DMSO-d) δ: 11.05 (s, 1H), 10.80 (s, 1H), 8.38 (s, 11 H 7.93 (d (1H, J = 8.0 Hz) (7.76 (di 1H, J = 8.4 Hz); 7.51-7.62 (m, 3H); 7.38 (t, 1H, J = 7, 5 Hz), 7.34 (s, 1H), 6.99 (t, 1H, J = 8.0 Hz) [Referenced by: Law KY, Tamawsky, IW Xerox Corp. Electrophotographic photoconductor containing dtazo compound in photogenerating layer. US 4797337 A, 27/06/1987].

A-[3,5-bls(trh'luórmetyl)fenyΓ|-3-hydro\ynaftalén-2-karbcxamld (47), výťažok 57 %; teplota topenia 232 až 235 °C; ]H-NMR (DMSO-d6), δ: 11,05 (s, 1H); 10,99 (s, 1H); 8,50 (s, 2H); 8,41 (s, 1H); 7,93 (d, 1H, J = 8,1 Hz);N - [3,5-bls (trifluoromethyl) phenyl] -3-hydroxy-naphthalene-2-carbamethyl (47), 57% yield; mp 232-235 ° C; 1 H-NMR (DMSO-d 6), δ: 11.05 (s, 1H); 10.99 (s, 1 H); 8.50 (s, 2 H); 8.41 (s, 1 H); 7.93 (d, 1H, J = 8.1Hz);

7.84 (s, 1H); 7,78 (d, 1H, J = 8,4 Hz); 7,52 (t, 1H, J = 6,6 Hz); 7,34 - 7,40 (m, 2H). [Chované: Kim S., Lee I. Y., Min H. J., Nam E. H., Kim P., Yun C. S. Korea Research Institute of Bioscience and Biotechnology , Korea Research Institute of Chemical Technology. WO 2013/058613 A2, 19/10/2012],7.84 (s, 1 H); 7.78 (d, 1H, J = 8.4Hz); 7.52 (t, 1H, J = 6.6Hz); 7.34-7.40 (m, 2H). [Breeded: Kim S., Lee I. Y., Min H. J., Nam E. H., Kim P., Yun C. S. Korea Research Institute of Bioscience and Biotechnology, Korea Research Institute of Chemical Technology. WO 2013/058613 A2, 19/10/2012]

3-hydro\y-A-[2-chlór-5-Strlfluómretyl)fenyl]-naltalén-2-karbc)?amld (48), výťažok 60 %; teplota topenia 185 až 188 °C; ]H-NMR (DMSO-d6), δ: 12,09 (s, 1 H); 11,41 (s, 1H); 8,98 (d, 1H, J = 2,2 Hz); 8,72 (s, 1H); 7,99 (d, 1H, J = 8,1 Hz); 7,82 (d, 1H, J = 7,7 Hz); 7,78 (d, 1H, J = 8,1 Hz); 7,50 - 7,57 (m, 2H); 7,33 - 7,41 (m, 2H). [Chované: Porai-Koshits A. E., Porai-Koshits B. A., Eros L. S., Krylova M. I., Livshits D. A., Maryanovskaya K. Y., Aleksandrov I. P., Ulman K. E., Synthesis of some aromatic amines with trifluoromethyl grops and their study as products for cold dyeing. Zhumal Príkladmi Khimii 1955, 28, 967 až 975],3-Hydroxy- [2-chloro-5-trifluoromethyl) phenyl] -naphthalene-2-carbonylamide (48), yield 60%; mp 185-188 ° C; 1 H-NMR (DMSO-d 6), δ: 12.09 (s, 1H); 11.41 (s, 1 H); 8.98 (d, 1H, J = 2.2Hz); 8.72 (s, 1 H); 7.99 (d, 1H, J = 8.1Hz); 7.82 (d, 1H, J = 7.7Hz); 7.78 (d, 1H, J = 8.1Hz); 7.50 - 7.57 (m, 2H); 7.33-7.41 (m, 2H). [Reared: Porai-Koshits AE, Porai-Koshits BA, Eros LS, Krylova MI, Livshits DA, Maryanovskaya KY, Aleksandrov IP, Ulman KE, Synthesis of Some Aromatic Amines with Trifluoromethyl Grops and Their Study for Cold Dyeing Products. Zhumal Examples Khimii 1955, 28, 967-975],

A-S2,6-dlmetylfenyl)-3-hydro\ynaftalén-2-karbc\amld (49), výťažok 83 %; teplota topenia 192 - 196 °C; 1H-NMR (DMSO-d6), δ: 11,73 (s, 1H), 10,24 (s, 1H), 8,63 (s, 1H), 7,92 (d, 1H, J = 7,7 Hz), 7,78 (d, 1H, J = = 8,1 Hz), 7,53 (t, 1H, J = 7,3 Hz), 7,37 (t, 1H, J = 7,3 Hz), 7,34 (s, 1H), 7,16 (s, 3H), 2,25 (s, 6H). [Chované: Lantz R., The special influence of certain substituents on the affinhy of anilides of aromatic o-hydro\y carboxylic acids for cellulose I. Denvatives of 3-hydrow-2-naphthoic acid. Bulletin de la Smiete Chimique de France 1955, 1094 - 1097].N-S2,6-dimethylphenyl) -3-hydroxynaphthalene-2-carbamide (49), yield 83%; mp 192-196 ° C; 1 H-NMR (DMSO-d 6), δ: 11.73 (s, 1H), 10.24 (s, 1H), 8.63 (s, 1H), 7.92 (d, 1H, J = 7, 7 Hz), 7.78 (d, 1H, J = 8.1 Hz), 7.53 (t, 1H, J = 7.3 Hz), 7.37 (t, 1H, J = 7.3 Hz), 7.34 (s, 1H), 7.16 (s, 3H), 2.25 (s, 6H). [Breed: Lantz R., The Special Influence of Certain Substituents on the Affinhy of Anilides of A-Hydrocarboxylic Acids for Cellulose I. Denvatives of 3-Hydrow-2-naphthoic acid. Bulletin de la Smiete Chimique de France 1955, 1094-1097].

A-S3,5-dlmetylfenyl)-3-hydro\ynaftalén-2-karbc\amld (50), výťažok 83 %; teplota topenia 184 - 186 °C; 1H-NMR (DMSO-d6), δ: 11,41 (s, 1H); 10,48 (s, 1H); 8,52 (s, 1H); 7,92 (d, 1H, J = 8,1 Hz); 7,77 (d, 1H, J = = 8,4 Hz); 7,52 (t, 1H, J = 7,1 Hz); 7,40 (s, 2H); 7,36 (t, 1H, J = 7,3 Hz); 7,33 (s, 1H); 6,79 (s, 1H); 2,29 (s, 6H).N-S (3,5-dimethylphenyl) -3-hydroxynaphthalene-2-carbamido (50), yield 83%; mp 184-186 ° C; 1 H-NMR (DMSO-d 6), δ: 11.41 (s, 1H); 10.48 (s, 1 H); 8.52 (s, 1 H); 7.92 (d, 1H, J = 8.1Hz); 7.77 (d, 1H, J = 8.4Hz); 7.52 (t, 1H, J = 7.1Hz); 7.40 (s, 2 H); 7.36 (t, 1H, J = 7.3Hz); 7.33 (s, 1 H); 6.79 (s, 1 H); 2.29 (s, 6H).

A-S3-fluór-5-meto?\ríenyl)-3-hydro\ynaftalén-2-karbo?amld (51), výťažok 59 %; teplota topenia 227 - 230 °C; 1H-NMR (DMSO-d6), δ: 11,12 (s, 1H); 10,64 (s, 1H); 8,41 (s, 1H); 7,93 (d, 1H, J = 8,4 Hz); 7,76 (d, 1H, J = = 8,1 Hz); 7,51 (t, 1H, J = 7,0 Hz); 7,32 - 7,40 (m, 3H); 7,21 (s, 1H); 6,62 (d, 1H J = 11,0 Hz); 3,78 (s, 3H).N-S 3 -fluoro-5-methenylphenyl) -3-hydroxynaphthalene-2-carboxamide (51), 59% yield; mp 227-230 ° C; 1 H-NMR (DMSO-d 6), δ: 11.12 (s, 1H); 10.64 (s, 1 H); 8.41 (s, 1 H); 7.93 (d, 1H, J = 8.4Hz); 7.76 (d, 1H, J = 8.1Hz); 7.51 (t, 1H, J = 7.0 Hz); 7.32-7.40 (m, 3H); 7.21 (s, 1 H); 6.62 (d, 1H, J = 11.0 Hz); 3.78 (s, 3H).

A-S2-fluór-6-meto?\ríenyl)-3-hydro\ynaftalén-2-karbo?amld (52), výťažok 66 %; teplota topenia 138 - 144 °C; 1H-NMR (DMSO-d6), δ: 11,76 (s, 1H); 10,22 (s, 1H); 8,69 (s, 1H); 7,93 (d, 1H, J = 8,8 Hz); 7,78 (d, 1H, J = = 8,4 Hz); 7,54 (t, 1H, J = 7,3 Hz); 7,30 - 7,40 (m, 3H); 6,99 (d, 1H, J = 8,4 Hz); 6,94 (t, 1H, J = 9,0 Hz);N-S2-fluoro-6-methenylphenyl) -3-hydroxynaphthalene-2-carboxamide (52), yield 66%; mp 138-144 ° C; 1 H-NMR (DMSO-d 6), δ: 11.76 (s, 1H); 10.22 (s, 1 H); 8.69 (s, 1 H); 7.93 (d, 1H, J = 8.8Hz); 7.78 (d, 1H, J = 8.4Hz); 7.54 (t, 1H, J = 7.3Hz); 7.30 - 7.40 (m, 3H); 6.99 (d, 1H, J = 8.4Hz); 6.94 (t, 1H, J = 9.0 Hz);

3.84 (s, 3H).3.84 (s, 3 H).

λ4A-Πlιor-2mleto\v fen\4;-3-hydIΌ\ynaftalé'n-2-kaΓboxaInld (53), výťažok 80 %; teplota topenia 198 - 203 °C; 1H-NMR (DMSO-d6, δ: 11,86 (s, 1H); 11,25 (s, 1H); 8,70 (s, 1H); 8,40 (dd, 1H, J = 11,0 Hz, J = 3,3 Hz);λ4A-β-chloro-2-methyl-phenol-3-hydroxy-naphthalene-2-carboxamide (53), 80% yield; mp 198-203 ° C; 1 H-NMR (DMSO-d 6, δ: 11.86 (s, 1H); 11.25 (s, 1H); 8.70 (s, 1H); 8.40 (dd, 1H, J = 11.0) Hz, J = 3.3 Hz);

7,93 (d, 1IH J s-1 Hz); Ί, (d, 1H, J = 8,4 Hz)', Ί5 ((t 1H, J = 7,5 Hz); 7,37 (s, 1H); 7,36 ((t 1H, J = 7,5 Hz); 7,12 (dd, 1H, J = 9,2 Hz, J = 5,1 Hz); 6,92 (td, 1H, J = 8,6 Hz, J = 3,3 Hz); 3,92 (s, 3H).7.93 (d, J 1IH s -1 Hz); Δ, (d, 1H, J = 8.4 Hz),, (5 ((t 1H, J = 7.5 Hz); 7.37 (s, 1H); 7.36 ((t 1H, J = 7) 5 Hz), 7.12 (dd, 1H, J = 9.2 Hz, J = 5.1 Hz), 6.92 (td, 1H, J = 8.6 Hz, J = 3.3 Hz) 3.92 (s, 3H).

A-S4-bróm-3-fluó]:r'enyl)-3-hydro\ynaftalén-2-karbc\amld (54), výťažok 72 %; teplota topenia 255 °C; ]H-NMR (DMSO-d6), δ: 7,33 (s, 1H); 7,36 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,2 Hz, 1H); 7,51 (ddd, J = 1,3 Hz, J = 6,8 Hz, J = 8,3 Hz, 1H); 7,52 (ddd, J = 0,7 Hz, J = 2,4 Hz, J = 8,9 Hz, 1H); 7,69 (dd, J = 8,2 Hz, J = 8,7 Hz,N-S4-bromo-3-fluoro] -phenyl) -3-hydroxy-naphthalene-2-carbamido (54), yield 72%; mp 255 ° C; 1 H-NMR (DMSO-d 6), δ: 7.33 (s, 1H); 7.36 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.2 Hz, 1H); 7.51 (ddd, J = 1.3 Hz, J = 6.8 Hz, J = 8.3 Hz, 1H); 7.52 (ddd, J = 0.7 Hz, J = 2.4 Hz, J = 8.9 Hz, 1H); 7.69 (dd, J = 8.2 Hz, J = 8.7 Hz,

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1H); 7,76 (d, J = 8,3 Hz, 1H); 7,93 (d, J = 8,3 Hz, 1H); 7,95 (dd, J = 2,3 Hz, J = 11,4 Hz, 1H); 8,41 (s, 1H); 10,78 (s, NH, 1H); 11,10 (s, OH, 1H).1H); 7.76 (d, J = 8.3Hz, 1H); 7.93 (d, J = 8.3Hz, 1H); 7.95 (dd, J = 2.3 Hz, J = 11.4 Hz, 1H); 8.41 (s, 1 H); 10.78 (s, NH, 1 H); 11.10 (s, OH, 1 H).

Ai2-biOin-4<Jilcnfcnvl)-3divdiO\\úiaftalcn-2-karbo\ainid (55), výťažok 42 %; teplota topenia 243 °C; 1H-NMR (DMSO-d6), δ: 7,37 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,2 Hz, 1H); 7,38 (s, 1H); 7,53 (ddd, J = 1,2 Hz, J = 6,9 Hz, J = 8,2 Hz, 1H); 7,54 (dd, J = 2,4 Hz, J = 8,9 Hz, 1H); 7,78 (d, J = 8,3 Hz, 1H); 7,87 (d, J = 2,4 Hz, 1H); 7,99 (d, J = 8,2 Hz, 1H); 8,47 (d, J = 8,9 Hz, 1H); 8,71 (s, 1H); 11,07 (s, NH, 1H); 11,97 (s, OH, 1H).Al2-biolin-4 (chlorophenyl) -3-diaminophthalene-2-carbohydrate (55), 42% yield; mp 243 ° C; 1 H-NMR (DMSO-d 6), δ: 7.37 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.2 Hz, 1H); 7.38 (s, 1 H); 7.53 (ddd, J = 1.2 Hz, J = 6.9 Hz, J = 8.2 Hz, 1H); 7.54 (dd, J = 2.4 Hz, J = 8.9 Hz, 1H); 7.78 (d, J = 8.3Hz, 1H); 7.87 (d, J = 2.4Hz, 1H); 7.99 (d, J = 8.2Hz, 1H); 8.47 (d, J = 8.9Hz, 1H); 8.71 (s, 1 H); 11.07 (s, NH, 1 H); 11.97 (s, OH, 1 H).

V-|3-ni^Kór-^l-(tiilfiamn^^tt^T)f(^^iivl|-3-hvdro\vnattailcii-i^-^k^anivxamiid (56), výťažok 61 %; teplota topenia 273 °C; ]H-NMR (DMSO-de), δ: 7,34 (s, 1H); 7,36 (ddd, J =1,2 Hz, J = 6,8 Hz, 8,2 Hz, 1H); 7,51 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,3 Hz, 1H); 7,71 (dd, J = 1,4 Hz, J = 8,7 Hz, 1H); 7,77 (d, J = 8,3 Hz, 1H); 7,78 (t, J = 8,6 Hz, 1H); 7,94 (d, J = 8,2 Hz, 1H); 8,02 (dd, J = 1,4 Hz, 13,5 Hz, 1H); 8,39 (s, 1H); 10,96 (s, HN, 1H); 11,05 (s, OH, 1H).N- (3-nitro) -1- (thiaminoamido) -3- (trifluoromethyl) -3-hydroxymethyl-1,2-dihydroxy (56), yield 61%, m.p. 273 ° C; 1 H-NMR (DMSO-d 6), δ: 7.34 (s, 1H), 7.36 (ddd, J = 1.2 Hz, J = 6.8 Hz, 8.2 Hz, 7.51 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.3 Hz, 1H); 7.71 (dd, J = 1.4 Hz, J = 8, 1H); 7 Hz, 1H) 7.77 (d, J = 8.3 Hz, 1H) 7.78 (t, J = 8.6 Hz, 1H) 7.94 (d, J = 8.2 Hz (1H); 8.02 (dd, J = 1.4 Hz, 13.5 Hz, 1H); 8.39 (s, 1H); 10.96 (s, HN, 1H); 11.05 (s) (OH, 1H).

A’-|4-f|Lioim-(ninLiCHinctvl)fcnvl|-34ivdiO\vnaítalcn-2-karbo\ainid (57), výťažok 72 %; teplota topenia 231 °C; 1H-NMR (DMSO-dô), δ: 7,34 (s, 1H); 7,36 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,2 Hz, 1H); 7,51 (ddd, J = = 1,2 Hz, J = 6,8 Hz, J = 8,3 Hz, 1H); 7,55 (dd, J = 9,0 Hz, J = 10,5 Hz, 1H); 7,77 (d, J = 8,3 Hz, 1H); 7,92 (d, J = 8,2 Hz, 1H); 8,05 (ddd, J = 3,0 Hz, J = 4,2 Hz, J = 8,9 Hz, 1H); 8,29 (dd, J = 2,6 Hz, J = 6,5 Hz, 1H); 8,43 (s, 1H); 10,81 (s, NH, 1H); 11,10 (s, OH, 1H).N '- | 4-f | Lioim- (ninLiCHinctvl) fcnvl | -34ivdiO \ vital-2-carboinin (57), 72% yield; mp 231 ° C; 1 H-NMR (DMSO-d 6), δ: 7.34 (s, 1H); 7.36 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.2 Hz, 1H); 7.51 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.3 Hz, 1H); 7.55 (dd, J = 9.0 Hz, J = 10.5 Hz, 1H); 7.77 (d, J = 8.3Hz, 1H); 7.92 (d, J = 8.2Hz, 1H); 8.05 (ddd, J = 3.0 Hz, J = 4.2 Hz, J = 8.9 Hz, 1H); 8.29 (dd, J = 2.6 Hz, J = 6.5 Hz, 1H); 8.43 (s, 1 H); 10.81 (s, NH, 1 H); 11.10 (s, OH, 1 H).

A’-P-nLioiró--4nnLiCHmctvl)fcnvl|-3-hvdro\vaiaftalcn-2-karbo''aiinid (58), výťažok 77 %; teplota topenia 222 °C; 1H-NMR (DMSO-dô), δ: 7,38 (s, 1H); 7,38 (ddd, J = 1,1 Hz, J = 6,8 Hz, J = 8,2 Hz, 1H); 7,53 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,3 Hz, 1H); 7,57 - 7,62 (m, 2H); 7,78 (d, J = 8,3 Hz, 1H); 7,98 (d, J = 8,2 Hz, 1H); 8,67 (s, 1H); 8,83 (dd, J = 1,6 Hz, J = 7,1 Hz, 1H); 11,16 (s, NH, 1H); 11,92 (s, OH, 1H).[Alpha] -P-n-Lio (4nnLiCHmctvl) fcnvl-3-yl] -valphthalene-2-carboaline (58), yield 77%; mp 222 ° C; 1 H-NMR (DMSO-d 6), δ: 7.38 (s, 1H); 7.38 (ddd, J = 1.1 Hz, J = 6.8 Hz, J = 8.2 Hz, 1H); 7.53 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.3 Hz, 1H); 7.57 - 7.62 (m, 2H); 7.78 (d, J = 8.3Hz, 1H); 7.98 (d, J = 8.2Hz, 1H); 8.67 (s, 1 H); 8.83 (dd, J = 1.6 Hz, J = 7.1 Hz, 1H); 11.16 (s, NH, 1 H); 11.92 (s, OH, 1 H).

A’-|4-biOinm4ninLioimctv|)fcnvl|-34ivdiO\vnaftalcn-2-karbo\ainid (59), výťažok 62 %; teplota topenia 234 °C; 1H-NMR (DMSO-d6), δ: 7,34 (s, 1H); 7,36 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,2 Hz, 1H); 7,51 (ddd, J = 1,2 Hz, J = 6,8 Hz, J = 8,3 Hz, 1H); 7,77 (d, J = 8,3 Hz, 1H); 7,88 (d, J = 8,7 Hz, 1H); 7,92 (d, J = 8,2 Hz, 1H); 7,97 (dd, J = 2,5 Hz, J = 8,7 Hz, 1H); 8,37 (d, J = 2,5 Hz, 1H); 8,42 (s, 1H); 10,86 (s, HN, 1H); 11,07 (s, OH, 1H).’4-biOinm4ninLioimctv |) fcnvl | -34ivdi \ vnaphthal-2-carboinide (59), 62% yield; mp 234 ° C; 1 H-NMR (DMSO-d 6), δ: 7.34 (s, 1H); 7.36 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.2 Hz, 1H); 7.51 (ddd, J = 1.2 Hz, J = 6.8 Hz, J = 8.3 Hz, 1H); 7.77 (d, J = 8.3Hz, 1H); 7.88 (d, J = 8.7Hz, 1H); 7.92 (d, J = 8.2Hz, 1H); 7.97 (dd, J = 2.5 Hz, J = 8.7 Hz, 1H); 8.37 (d, J = 2.5Hz, 1H); 8.42 (s, 1 H); 10.86 (s, HN, 1 H); 11.07 (s, OH, 1 H).

Príklad 3: Príkladv vvbraných derivátov naftaléni (III), ktoré sú popísané týnto vvnálezornExample 3: Examples of selected naphthalene (III) derivatives, which are described in the present invention.

A/A5<lichlcnťcnvl)-1-hvdiO\vnalIalcn-2-kaibo\ainid (60), výťažok 69 %; teplota topenia 194 - 196 °C; 1H-NMR (DMSO-d6), δ: 13,47 (s, 1H); 10,83 (s, 1H); 8,33 (d, 1H, J = 8,6 Hz); 8,05 - 8,10 (n, 1H); 7,95 (d, 1H, J = 2,6 Hz); 7,93 (d, 1H, J = 8,2 Hz); 7,68 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,65 (d, 1H, J = = 8,9 Hz); 7,60 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,2 Hz); 7,51 (d, 1H, J = 8,9 Hz); 7,42 (dd, 1H, J = 8,7 Hz, J = 2,5 Hz).A / <5 (unconventional) -1-hydroxy-2-carboxylic acid (60), yield 69%; mp 194-196 ° C; 1 H-NMR (DMSO-d 6), δ: 13.47 (s, 1H); 10.83 (s, 1 H); 8.33 (d, 1H, J = 8.6Hz); 8.05 - 8.10 (n, 1H); 7.95 (d, 1H, J = 2.6Hz); 7.93 (d, 1H, J = 8.2Hz); 7.68 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.65 (d, 1H, J = 8.9 Hz); 7.60 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.51 (d, 1H, J = 8.9Hz); 7.42 (dd, 1H, J = 8.7 Hz, J = 2.5 Hz).

A/A6<lichlcnťcnvl)-1-hvdiO\vnalIaléa]-2-kabu)\ainid (61), výťažok 59 %; teplota topenia 199 - 202 °C; 1H-NMR (DMSO-d6), δ: 13,85 (s, 1H); 10,76 (s, 1H); 8,28 - 8,33 (n, 1H); 8,11 (d, 1H, J = 8,9 Hz); 7,93 (d, 1H, J = 8,2 Hz); 7,69 (ddd, 1H, J = 8,1 Hz, J = 6,9 Hz, J = 1,2 Hz); 7,65 (d, 2H, J = 8,2 Hz); 7,60 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,0 Hz); 7,50 (d, 1H, J = 8,6 Hz); 7,47 (t, 1H, J = 8,2 Hz).A / <6 (Cyclopentyl) -1-hydroxy-2-carboxylic acid (61), 59% yield; mp 199-202 ° C; 1 H-NMR (DMSO-d 6), δ: 13.85 (s, 1H); 10.76 (s, 1 H); 8.28-8.33 (n, 1H); 8.11 (d, 1H, J = 8.9Hz); 7.93 (d, 1H, J = 8.2Hz); 7.69 (ddd, 1H, J = 8.1 Hz, J = 6.9 Hz, J = 1.2 Hz); 7.65 (d, 2H, J = 8.2Hz); 7.60 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.0 Hz); 7.50 (d, 1H, J = 8.6Hz); 7.47 (t, 1H, J = 8.2Hz).

Aró3.4<lichlcnťcnvl)-1-hvdiO\vnalIaléa]-2-kabu)\ainid (62), výťažok 84 %; teplota topenia 195 - 197 °C; 1H-NMR (DMSO-d6), δ: 13,85 (s, 1H); 10,76 (s, 1H); 8,28 - 8,33 (n, 1H); 8,11 (d, 1H, J = 8,9 Hz); 7,93 (d, 1H, J = 8,2 Hz); 7,69 (ddd, 1H, J = 8,1 Hz, J = 6,9 Hz, J = 1,2 Hz); 7,65 (d, 2H, J = 8,2 Hz); 7,60 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,0 Hz); 7,50 (d, 1H, J = 8,6 Hz); 7,47 (t, 1H, J = 8,2 Hz).Aromo (4-methoxycarbonyl) -1-hydroxy-2-carboxylic acid (62), yield 84%; mp 195-197 ° C; 1 H-NMR (DMSO-d 6), δ: 13.85 (s, 1H); 10.76 (s, 1 H); 8.28-8.33 (n, 1H); 8.11 (d, 1H, J = 8.9Hz); 7.93 (d, 1H, J = 8.2Hz); 7.69 (ddd, 1H, J = 8.1 Hz, J = 6.9 Hz, J = 1.2 Hz); 7.65 (d, 2H, J = 8.2Hz); 7.60 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.0 Hz); 7.50 (d, 1H, J = 8.6Hz); 7.47 (t, 1H, J = 8.2Hz).

Aró3.5<lichlcnťcnvl)-1-hvdiO\vnalIaléa]-2-kabm\ainid (63), výťažok 80 %; teplota topenia 190 - 194 °C; 1H-NMR (DMSO-d6), δ: 13,48 (br, s, 1H); 10,61 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,04 (d, 1H, J = 8,9 Hz);Aromo [eta] < 5 &gt; -hexidazol-2-yl] amino (63), yield 80%; mp 190-194 ° C; 1 H-NMR (DMSO-d 6), δ: 13.48 (br, s, 1H); 10.61 (s, 1 H); 8.31 (d, 1H, J = 8.2Hz); 8.04 (d, 1H, J = 8.9Hz);

7,91 (d, 1H, J = 8,2 Hz); 7,88 (d, 2H, J = 1,6 Hz); 7,68 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,3 Hz); 7,58 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,0 Hz); 7,48 (d, 1H, J = 8,9 Hz); 7,39 (t, 1H, J = 1,8 Hz).7.91 (d, 1H, J = 8.2Hz); 7.88 (d, 2H, J = 1.6Hz); 7.68 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.3 Hz); 7.58 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.0 Hz); 7.48 (d, 1H, J = 8.9Hz); 7.39 (t, 1H, J = 1.8Hz).

A/A6<linLicnťcnvl)-1-hvdiO\vnaítaléai-2-kaibo\ainid (64), výťažok 76 %; teplota topenia 197 - 200 °C; 1H-NMR (DMSO-d6), δ: 13,46 (br, s, 1H); 10,58 (s, 1H); 8,31 (d, 1H, J = 8,1 Hz); 8,09 (d, 1H, J = 8,8 Hz);A / A6 (linear) -1-hydroxy-2-amino-2-carboxylic acid (64), 76% yield; mp 197-200 ° C; 1 H-NMR (DMSO-d 6), δ: 13.46 (br, s, 1H); 10.58 (s, 1 H); 8.31 (d, 1H, J = 8.1Hz); 8.09 (d, 1H, J = 8.8Hz);

7,94 (d, 1H, J = 8,1 Hz); 7,71 (ddd, 1H, J = 8,2 Hz, J = 6,^ Hz, J = 1,,3 Hz); 7,(60 (ddd, 1H, J = 8,3 Hz, J = = 7,0 Hz, J = 1,2 Hz); 7,52 - 7,76 (n, 1H); 7,44 (d, ^H, J = 6,6 Hz); 7,31 (d, ^H, J = 8,1 Hz), 7,29 (t, ^H, J = = 8,1 Hz).7.94 (d, 1H, J = 8.1Hz); 7.71 (ddd, 1H, J = 8.2 Hz, J = 6.6 Hz, J = 1.3 Hz); 7. (60 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.52-7.76 (n, 1H); 7.44 (d) 1 H, J = 6.6 Hz), 7.31 (d, 1 H, J = 8.1 Hz), 7.29 (t, 1 H, J = 8.1 Hz).

SK 71-2017 A3 λ <3J-dinLioifcm\4)-14i\xhO\vnaftalen-2-karboxainid (65), výťažok 85 %; teplota topenia 199 - 200 °C; 1H-NMR (DMSO-dó), δ: 13,51 (s, 1H); 10,66 (s, 1H); 8,30 - 8,33 (m, 1H); 8,05 (d, 1H, J = 8,9 Hz); 7,92 (d, 1H, J = 8,2 Hz); 7,68 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,59 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = = 1,2 Hz); 7,56 (dd, 2H, J = 9,4 Hz, J = 2,1 Hz); 7,49 (d, 1H, J = 8,9 Hz); 7,05 (tt, 1H, J = 9,2 Hz, J = 2,3 Hz).EN 71-2017 A3 λ <3J-dinolio (4) -14i \ xhO \ naphthalene-2-carboxainide (65), 85% yield; mp 199-200 ° C; 1 H-NMR (DMSO-d 6), δ: 13.51 (s, 1H); 10.66 (s, 1 H); 8.30 - 8.33 (m, 1H); 8.05 (d, 1H, J = 8.9Hz); 7.92 (d, 1H, J = 8.2Hz); 7.68 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.59 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.56 (dd, 2H, J = 9.4 Hz, J = 2.1 Hz); 7.49 (d, 1H, J = 8.9Hz); 7.05 (tt, 1H, J = 9.2 Hz, J = 2.3 Hz).

AÚ2/6-bbiOinfcei\4)-1di\xhO\vnaftalen-2-karbo\ainid (66), výťažok 64 %; teplota topenia 212 - 216 °C; ]H-NMR (DMSO-dô), δ: 13,89 (s, 1H); 10,81 (s, 1H); 8,30 (d, 1H, J = 8,6 Hz); 8,11 (d, 1H, J = 8,9 Hz); 7,93 (d, 1H, J = 8,2 Hz); 7,83 (d, 2H, J = 8,2 Hz); 7,69 (ddd, 1H, J = 8,1 Hz, J = 6,9 Hz, J = 1,2 Hz); 7,60 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,0 Hz); 7,50 (d, 1H, J = 8,9 Hz); 7,30 (t, 1H, J = 8,1 Hz).N 2/6-biphenyl (4) -1di-xhO-naphthalene-2-carbohydrate (66), 64% yield; mp 212-216 ° C; 1 H-NMR (DMSO-d 6), δ: 13.89 (s, 1H); 10.81 (s, 1 H); 8.30 (d, 1H, J = 8.6Hz); 8.11 (d, 1H, J = 8.9Hz); 7.93 (d, 1H, J = 8.2Hz); 7.83 (d, 2H, J = 8.2Hz); 7.69 (ddd, 1H, J = 8.1 Hz, J = 6.9 Hz, J = 1.2 Hz); 7.60 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.0 Hz); 7.50 (d, 1H, J = 8.9Hz); 7.30 (t, 1H, J = 8.1Hz).

A'-|3.54bs(Oaniionncá\4)fai\4|-1-hvdro\vnaftalen-2-karbo\amid (67), výťažok 84 %; teplota topenia 183 až 186 °C; H-NMR (DMSO-de), δ: 13,36 (bn, s, 1H); 10,89 (s, 1H); 8,50 (s, 2H); 8,31 (d, 1H, J = 8,2 Hz); 8,07 (d, 1H, J = 8,9 Hz); 7,91 (d, 1H, J = 8,2 Hz); 7,88 (s, 1H); 7,68 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,59 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,0 Hz); 7,50 (d, 1H, J = 8,9 Hz). [Citované: Kang S., Min H. J., Kang M. S., Jung M. G., Kim S. Discoveny of novel 2-hydno\ydianylamtde denvatives as TMPRSS4 tnhibitons. Bioong. Med. Chem Lett. 2013, 23, 1748 - 1751; Muto S., Itai A. Institute of medicinal moleculan design. INC. Thenapeutic agent fon cancer. WO 03/103655 A1, 05/06/2003; Muto S., Itai A. Institute of medicinal moleculan design. INC. Inhibitons against the activation of AP-1 andNFAT. EP 1512396 A1, 05/06/2003].N-3.54bs (NH 4) fai-4 -1 -1-naphthalene-2-carboamide (67), yield 84%; mp 183-186 ° C; H-NMR (DMSO-d6), [delta]: 13.36 (bn, s, 1H); 10.89 (s, 1 H); 8.50 (s, 2 H); 8.31 (d, 1H, J = 8.2Hz); 8.07 (d, 1H, J = 8.9Hz); 7.91 (d, 1H, J = 8.2Hz); 7.88 (s, 1 H); 7.68 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.59 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.0 Hz); 7.50 (d, 1H, J = 8.9Hz). [Cited by: Kang S., Min H. J., Kang M. S., Jung M. G., Kim S. Discoveny of novel 2-Hydroxylamide denvatives as TMPRSS4 compounds. Bioong. Med. Chem Lett. 2013, 23, 1748-1751; Muto S., Itai A. Institute of Medicinal Molecular Design. INC. Therapeutic agent fon cancer. WO 03/103655 A1, 05/06/2003; Muto S., Itai A. Institute of Medicinal Molecular Design. INC. Inhibitons against the activation of AP-1 andNFAT. EP 1512396 A1, 05/06/2003].

A-1-hydnoxy-[2-chlón-5-(tnfluónmetyl)fenyl]-naftalén-2-kanboxamtd (68), výťažok 67 %; teplota topenia 182 až 183 °C; H-NMR (DMSO-de), δ: 13,59 (bn, s, 1H); 10,96 (s, 1H); 8,34 (d, 1H, J = 7,7 Hz); 8,25 (s, 1H); 8,09 (d, 1H, J = 8,8 Hz); 7,93 (d, 1H, J = 8,1 Hz); 7,87 (d, 1H, J = 8,4 Hz); 7,70 (d, 1H, J = 7,2 Hz); 7,68 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,57 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,2 Hz); 7,51 (d, 1H, J = 7,8 Hz).N-1-Hydroxy- [2-chloro-5- (trifluoromethyl) phenyl] -naphthalene-2-carboxamide (68), yield 67%; mp 182-183 ° C; 1 H-NMR (DMSO-d 6), δ: 13.59 (bn, s, 1H); 10.96 (s, 1 H); 8.34 (d, 1H, J = 7.7Hz); 8.25 (s, 1 H); 8.09 (d, 1H, J = 8.8Hz); 7.93 (d, 1H, J = 8.1Hz); 7.87 (d, 1H, J = 8.4Hz); 7.70 (d, 1H, J = 7.2Hz); 7.68 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.57 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.51 (d, 1H, J = 7.8Hz).

y-(3,5-^-dim2tt^-líc^^ir^-])-k^lh^-dno\vnaftalén-2-kanbo\^imid (69), výťažok 69 %; teplota topenia 88 - 90 °C; 1H-NMR (DMSO-dô), δ: 14,10 (bn, s, 1H); 10,33 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,12 (d, 1H, J = 8,9 Hz);γ- (3,5-dimethylaminocarbonyl) -2-naphthalene-2-kanboimide (69), yield 69%; mp 88-90 ° C; 1 H-NMR (DMSO-d 6), δ: 14.10 (bn, s, 1H); 10.33 (s, 1 H); 8.31 (d, 1H, J = 8.2Hz); 8.12 (d, 1H, J = 8.9Hz);

7.91 (d, 1H, J = 8,2 Hz); 7,67 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,58 (ddd, 1H, J = 8,2 Hz, J = = 6,9 Hz, J = 1,3 Hz); 7,45 (d, 1H, J = 8,9 Hz); 7,37 (s, 2H); 6,84 (s, 1H); 2,30 (s, 6H).7.91 (d, 1H, J = 8.2Hz); 7.67 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.58 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.45 (d, 1H, J = 8.9Hz); 7.37 (s, 2 H); 6.84 (s, 1 H); 2.30 (s, 6H).

A-(2,5-dlmeto?\,ďenyl)-1-hydnoxynaftalén-2-kanbo\amtd (70), výťažok 75 %; teplota topenia 116 - 119 °C; H-NMR (DMSO-dó), δ: 13,66 (s, 1H); 10,34 (s, 1H); 8,33 (dd, 1H, J = 7,7 Hz, J = 1,3 Hz); 8,07 (d, 1H, J = = 8,6 Hz); 7,91 (d, 1H, J = 8,1 Hz); 7,67 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,59 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,2 Hz); 7,53 (d, 1H, J = 8,8 Hz); 7,43 (d, 1H, J = 2,9 Hz); 7,06 (d, 1H, J = 8,8 Hz); 6,81 (dd, 1H, J = 8,8 Hz, J = 2,9 Hz); 3,82 (s, 3H); 3,74 (s, 3H).N - (2,5-dimethoxyphenyl) -1-hydroxy-naphthalene-2-kanamido (70), yield 75%; mp 116-119 ° C; H-NMR (DMSO-d6), [delta]: 13.66 (s, 1H); 10.34 (s, 1 H); 8.33 (dd, 1H, J = 7.7Hz, J = 1.3Hz); 8.07 (d, 1H, J = 8.6Hz); 7.91 (d, 1H, J = 8.1Hz); 7.67 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.59 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.53 (d, 1H, J = 8.8Hz); 7.43 (d, 1H, J = 2.9Hz); 7.06 (d, 1H, J = 8.8Hz); 6.81 (dd, 1H, J = 8.8 Hz, J = 2.9 Hz); 3.82 (s, 3H); 3.74 (s, 3H).

A-(3,5-dlmeto?\,ďenyl)-1-hydnoxynaftalén-2-kanbo\amtd (71), výťažok 83 %; teplota topenia 118 - 121 °C; H-NMR (DMSO-dó), δ: 13,93 (s, 1H); 10,35 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,11 (d, 1H, J = 9,2 Hz); 7,91 (d, 1H, J = 8,2 Hz); 7,67 (ddd, 1H, J = 8,0 Hz, J = 6,8 Hz, J = 1,3 Hz); 7,58 (ddd, 1H, J = 8,3 Hz, J = 7,0 Hz, J = 1,2 Hz); 7,47 (d, 1H, J = 8,9 Hz); 7,05 (d, 2H, J = 2,3 Hz); 6,36 (t, 1H, J = 2,3 Hz); 3,77 (s, 6H).N - (3,5-dimethoxyphenyl) -1-hydroxy-naphthalene-2-kanamido (71), yield 83%; mp 118-121 ° C; H-NMR (DMSO-d6), [delta]: 13.93 (s, 1H); 10.35 (s, 1 H); 8.31 (d, 1H, J = 8.2Hz); 8.11 (d, 1H, J = 9.2Hz); 7.91 (d, 1H, J = 8.2Hz); 7.67 (ddd, 1H, J = 8.0 Hz, J = 6.8 Hz, J = 1.3 Hz); 7.58 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.47 (d, 1H, J = 8.9Hz); 7.05 (d, 2H, J = 2.3Hz); 6.36 (t, 1H, J = 2.3Hz); 3.77 (s, 6H).

A-(3-fluón-5-metoxffenyl)-1-hydnoxvnaftalén-2-karbo?αιmld (72), výťažok 54 %; teplota topenia 95 - 98 °C; H-NMR (DMSO-de), δ: 13,66 (bn, s, 1H); 10,51 (s, 1H); 8,34 (d, 1H, J = 8,2 Hz); 8,08 (d, 1H, J = 8,8 Hz);N - (3-Fluoro-5-methoxyphenyl) -1-hydroxy-naphthalene-2-carboxylamide (72), yield 54%; mp 95-98 ° C; H-NMR (DMSO-d6), [delta]: 13.66 (bn, s, 1H); 10.51 (s, 1 H); 8.34 (d, 1H, J = 8.2Hz); 8.08 (d, 1H, J = 8.8Hz);

7.92 (d, 1H, J = 8,2 Hz); 7,69 (ddd, 1H, J = 8,0 Hz, J = 6,8 Hz, J = 1,3 Hz); 7,59 (ddd, 1H, J = 8,3 Hz, J = = 7,0 Hz, J = 1,2 Hz); 7,48 (d, 1H, J = 8,8 Hz); 7,34 (dt, 1H, J =1^ 1,0 Hz, J = 1,2 Hz); 7,25 (t, 1H, J = 1,2 Hz); 6,67 (dt, 1H, J = 11,0 Hz, J = 1,2 Hz); 3,80 (s, 3H).7.92 (d, 1H, J = 8.2Hz); 7.69 (ddd, 1H, J = 8.0 Hz, J = 6.8 Hz, J = 1.3 Hz); 7.59 (ddd, 1H, J = 8.3 Hz, J = 7.0 Hz, J = 1.2 Hz); 7.48 (d, 1H, J = 8.8Hz); 7.34 (dt, 1H, J = 1, 1.0 Hz, J = 1.2 Hz); 7.25 (t, 1H, J = 1.2Hz); 6.67 (dt, 1H, J = 11.0 Hz, J = 1.2 Hz); 3.80 (s, 3H).

Y-(2.,^-^-dilLuôn^^^iivk)-k^lh^-dnownaftalén^2-karbo\amid (73), výťažok 70 %; teplota topenia 185 - 187 °C; 1H-NMR (DMSO-de), δ: 13,86 (s, 1H); 10,57 (s, 1H); 8,31 (d, 1H, J = 8,6 Hz); 8,06 (d, 1H, J = 8,9 Hz); 7,92 (d, 1H, J = 8,2 Hz); 7,68 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,0 Hz); 7,57 - 7,64 (m, 2H); 7,48 (d, 1H, J = = 8,9 Hz); 7,43 (ddd, 1H, J = 10,4 Hz, J = 9,1 Hz, J = 2,8 Hz); 7,16 - 7,20 (m, 1H).Y- (2, 4, 4-Difluoro-4-carboxylic acid) -cyclohexanediophthalene-2-carbo-amide (73), yield 70%; mp 185-187 ° C; 1 H-NMR (DMSO-d 6), δ: 13.86 (s, 1H); 10.57 (s, 1 H); 8.31 (d, 1H, J = 8.6Hz); 8.06 (d, 1H, J = 8.9Hz); 7.92 (d, 1H, J = 8.2Hz); 7.68 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 1.0 Hz); 7.57 - 7.64 (m, 2H); 7.48 (d, 1H, J = 8.9 Hz); 7.43 (ddd, 1H, J = 10.4 Hz, J = 9.1 Hz, J = 2.8 Hz); 7.16 - 7.20 (m, 1H).

y-(3,-^-^-dilLuôI^^^nvk)-d^lh^’dnownaftalén^2-karbo\amid (74), výťažok 65 %; teplota topenia 153 - 156 °C; H-NMR (DMSO-dá), δ: 13,73 (s, 1H); 10,59 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,07 (d, 1H, J = 8,9 Hz); 7,87 ažγ- (3 ', 4', 4'-dichloro-2'-di-naphthalene-2-carbo-amide (74), yield 65%); mp 153-156 ° C; H-NMR (DMSO-d6), [delta]: 13.73 (s, 1H); 10.59 (s, 1 H); 8.31 (d, 1H, J = 8.2Hz); 8.07 (d, 1H, J = 8.9Hz); 7.87 to

7.92 (m, 2H); !£! (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 1,,2 Hz); 7,55 - 7,60 (m 2H); 7,-45 - 7,50 (m, 2H).7.92 (m. 2H); ! £! (ddd, 1H, J = 8.1Hz, J = 7.0Hz, J = 1.2Hz); 7.55 - 7.60 (m 2H); 7.45-7.50 (m, 2H).

y-(2,5-^-dilLuôn^^^nvk)-d^lh^-dnownaftalén^2-karbo\amid (75), výťažok 72 %; teplota topenia 153 - 155 °C; H-NMR (DMSO-d6), δ: 13,58 (bn, s, 1H); 10,70 (s, 1H); 8,33 (d, 1H, J = 8,6 Hz); 8,07 (d, 1H, J = 8,9 Hz);γ- (2,5-4-Difluoro-2,4-di) -d-1H-di-naphthalene-2-carbo-amide (75), yield 72%; mp 153-155 ° C; H-NMR (DMSO-d6), [delta]: 13.58 (bn, s, 1H); 10.70 (s, 1H); 8.33 (d, 1H, J = 8.6Hz); 8.07 (d, 1H, J = 8.9Hz);

SK 71-2017 A3A3

7,93 (d, 1H, J = 8,2 Hz); 7,68 1H J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,58 - 7,64 (im 2¾ 7,49 (<^, 1H,7.93 (d, 1H, J = 8.2Hz); 7.68 1H J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.58 - 7.64 (im 2¾ 7.49 (<^, 1H,

J = 8,9 Hz); 7,42 (td, 1H, J = 9,5 Hz, J = 4,9 Hz); 7,18 - 7,22 (m, 1H).J = 8.9 Hz); 7.42 (td, 1H, J = 9.5 Hz, J = 4.9 Hz); 7.18-7.22 (m, 1H).

divdiO\\'-Ä 42A64nnLioifcnvl)naftalcn-2-kadm\ainid (76), výťažok 74 %; teplota topenia 180 - 184 °C; ]H-NMR (DMSO-d,), δ: 13,70 (s, 1H); 10,54 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,06 (d, 1H, J = 9,2 Hz); 7,93 (d, 1H, J = 8,2 Hz); 7,68 - 7,72 (m, 1H); 7,58 - 7,62 (m, 1H); 7,50 (d, 1H, J = 8,7 Hz); 7,38 - 7,45 (m, 2H).DivdiO (42 (64) (Li-phenylamino) naphthalene-2-cadminine (76), 74% yield); mp 180-184 ° C; 1 H-NMR (DMSO-d 6) δ: 13.70 (s, 1H); 10.54 (s, 1 H); 8.31 (d, 1H, J = 8.2Hz); 8.06 (d, 1H, J = 9.2Hz); 7.93 (d, 1H, J = 8.2Hz); 7.68-7.72 (m, 1H); 7.58 - 7.62 (m, 1H); 7.50 (d, 1H, J = 8.7Hz); 7.38-7.45 (m, 2H).

divdm\v-A 42.3.44nlliioifcnvl)naftalcn-2-kadnmainid (77), výťažok 75 %; teplota topenia 173 - 175 °C; ]H-NMR (DMSO-de), δ: 13,69 (br, s, 1H); 10,74 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,05 (d, 1H, J = 9,2 Hz);divdmin (42.3.44 (lithium) naphthalene-2-cadminine (77), 75% yield; mp 173-175 ° C; 1 H-NMR (DMSO-d 6), δ: 13.69 (br, s, 1H); 10.74 (s, 1 H); 8.31 (d, 1H, J = 8.2Hz); 8.05 (d, 1H, J = 9.2Hz);

7,93 (d, 1H, J = 8,2 Hz); 7,69 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,3 Hz); 7,60 (ddd, 1H, J = 8,4 Hz, J = = 7,0 Hz, J = 1,1 Hz); 7,49 (d, 1H, J = 8,7 Hz); 7,38 - 7,46 (m, 2H).7.93 (d, 1H, J = 8.2Hz); 7.69 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.3 Hz); 7.60 (ddd, 1H, J = 8.4 Hz, J = 7.0 Hz, J = 1.1 Hz); 7.49 (d, 1H, J = 8.7Hz); 7.38-7.46 (m, 2H).

k^lr^'dro\A'-V-(2.,,^..:^-^tirllmircin^'kniaftalcn-2-karbo\amid (78), výťažok 73 %; teplota topenia 201 - 204 °C; ]H-NMR (DMSO-dó), δ: 13,64 (br, s, 1H); 10,67 (s, 1H); 8,31 (d, 1H, J = 8,2 Hz); 8,05 (d, 1H, J = 9,2 Hz); 7,92 (d, 1H, J = 8,2 Hz); 7,79 - 7,87 (m, 1H); 7,75 (td, 1H, J = 10,5 Hz, J = 7,3 Hz); 7,66 - 7,71 (m, 1H); 7,57 - 7,62 (m, 1H); 7,49 (d, 1H, J = 8,7 Hz).m.p. 201-204 ° C; m.p. A-N- (2 ', 4'-trifluoromethyl-4'-thiazolidine-2-carboxamide (78), yield 73%; mp 201-204 ° C); 1 H-NMR (DMSO-d 6) δ: 13.64 (br, s, 1H); 10.67 (s, 1H); 8.31 (d, 1H, J = 8.2 Hz); 05 (d, 1H, J = 9.2Hz); 7.92 (d, 1H, J = 8.2Hz); 7.79-7.87 (m, 1H); 7.75 (td, 1H); J = 10.5 Hz, J = 7.3 Hz), 7.66-7.71 (m, 1H), 7.57-7.62 (m, 1H), 7.49 (d, 1H, J = 8.7 Hz).

k^tΓ^dro\λtYt(3 .^_.;^.^tIΊllLUIrceΓ^kΠlaftalcnt2tkarbo\amld (79), výťažok 76 %; teplota topenia 242 - 247 °C; ]H-NMR (OMSO-dô), δ: 13,49 (s, 1H); 10,62 (s, 1H); 8,29 (d, 1H, J = 8,2 Hz); 8,01 (d, 1H, J = 9,2 Hz); 7,90 (d, 1H, J = 8,2 Hz); 7,65 - 7,75 (m, 3H); 7,58 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,4 Hz); 7,47 (d, 1H, J = = 9,2 Hz).m.p. 242-147 ° C; @ 1 H-NMR (OMSO-d6) .delta. 13.49 (s, 1H), 10.62 (s, 1H), 8.29 (d, 1H, J = 8.2 Hz), 8.01 (d, 1H, J = 9.2 Hz); 7.90 (d, 1H, J = 8.2 Hz), 7.65-7.75 (m, 3H), 7.58 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz) J = 1.4 Hz) 7.47 (d, 1H, J = 9.2 Hz).

1-hydro\ytΛtI2,3,5,6-tetraluórfenyl)tnaftalén-2tkarbo\amtd (80), výťažok 69 %; teplota topenia 160 - 163 °C; ]H-NMR (DMSO-dó), δ: 13,42 (br, s, 1H); 10,91 (s, 1¾ 8,32 (d, 1¾ J = 8,2 Hz); 8,07 (d, 1H, J = 8,7 Hz);1-Hydroxy-1,2,3,5,6-tetraluorophenyl) -naphthalene-2-carbamate (80), yield 69%; mp 160-163 ° C; 1 H-NMR (DMSO-d 6), δ: 13.42 (br, s, 1H); 10.91 (s, 1H, 8.32 (d, 1H, 8.2 Hz), 8.07 (d, 1H, J = 8.7 Hz);

7.92 - 8,03 (m, 2H); 7,68 - 7,73 (m, 1H); 7,58 - 7,63 (m, 1H); 7,52 (d, H J = 9,2 Hz).7.92 - 8.03 (m, 2H); 7.68 - 7.73 (m, 1H); 7.58 - 7.63 (m, 1H); 7.52 (d, H J = 9.2 Hz).

ΛtI2,4-dlchlórfenyl)t1-hydro\ynaf(alén-2tkarbo\amtd (81ý výťažok 76 %; teplota topenia 1811 — 184 °C;(12,4-dichlorophenyl) -1-hydroxyanaphthalen-2-carbo-amtd (81% yield, 76%; mp 1811-184 ° C;

]H-NMR (OMSO-dô), δ: 13,67 (br, s, 1H); 10,74 (s, W, 8,32 {d, 1¾ J = 8,2 Hz); 8,08 (d, 1H, J = 8,7 Hz); 1 H-NMR (OMSO-d 6), δ: 13.67 (br, s, 1H); 10.74 (s, W, 8.32 (d, 1H) = 8.2 Hz); 8.08 (d, 1H, J = 8.7Hz);

7.93 (d, 1H, J = 8,2 Hz); 7,79 (d, 1H, J = 2,3 Hz); 7,75 (d, 1H, J = 8,7 Hz); 7,68 (ddd, 1H, J = 8,1 Hz, J = 7,0 Hz, J = 0,9 Hz); 7,59 (ddd, 1H, J = 8,2 Hz, J = 6,9 Hz, J = 1,4 Hz); 7,52 (dd, 1H, J = 8,7 Hz, J = 2,3 Hz); 7,49 (d, 1H, J = 8,7 Hz). [Citované: Dubey S. K. Singh A. K., Smgh H., Sharma S., Iyer R. N. Synthesis of substituted 1-hydroxy-2-naphthanlltdes as potential cestodicidal agents. J. Med. Chem 1978, 21, 1178 až 1181],7.93 (d, 1H, J = 8.2Hz); 7.79 (d, 1H, J = 2.3Hz); 7.75 (d, 1H, J = 8.7Hz); 7.68 (ddd, 1H, J = 8.1 Hz, J = 7.0 Hz, J = 0.9 Hz); 7.59 (ddd, 1H, J = 8.2 Hz, J = 6.9 Hz, J = 1.4 Hz); 7.52 (dd, 1H, J = 8.7 Hz, J = 2.3 Hz); 7.49 (d, 1H, J = 8.7Hz). [Cited by: Dubey, S.K. Singh, A.K., Smgh, H., Sharma, S., Iyer, R.N. Synthesis of substituted 1-hydroxy-2-naphthaniltdes as potential cestodicidal agents. J. Med. Chem. 1978, 21, 1178-1181],

Λt[2,4-blsItrlfluórmetyl)fenyΓ|-1-hydro\ynaftalént2tkarbo\amld (82), výťažok 42 %; teplota topenia 166 až 169 °C; ]H-NMR (OMSO-dó), δ: 13,42 (br, s, 1H); 10,99 (s, 1H); 8,33 (d, J = 8,3 Hz, 1H); 8,20 (d, J = 8,6 Hz, 1H); 8,07 (s, 1H), 8,09 (d, J = 9,1 Hz, 1¾ 8,06 (d, J = 9,1 Hz, 1H) 1 7,94 (d, J = 8,1 HL·, 1Hý 7,70 (, 1 J = = 7,5 Hz, 1H); 7,58 - 7,63 (m, 1H); 7,52 (d, J= 8,88 Dz 1H).[T [2,4-bis (trifluoromethyl) phenyl] -1-hydronaphthalene-2-carboamide (82), yield 42%; mp 166-169 ° C; 1 H-NMR (OMSO-d 6), δ: 13.42 (br, s, 1H); 10.99 (s, 1 H); 8.33 (d, J = 8.3Hz, 1H); 8.20 (d, J = 8.6Hz, 1H); 8.07 (s, 1H), 8.09 (d, J = 9.1 Hz, 11¾ 8.06 (d, J = 9.1 Hz, 1H) 17.94 (d, J = 8.1) HL ·, 1 H = 7.70 (, 1 J = 7.5 Hz, 1H); 7.58-7.63 (m, 1H); 7.52 (d, J = 8.88 Dz 1H).

Λt[2,5-blsItrlfluórmetyl)fenyΓ|-1-hydro\ynaftalént2tkarbo\amld (83), výťažok 41 %; teplota topenia 139 až 142 °C; ]H-NMR (OMSO-dó), δ: 13,49 (br, s, 1H) ; 10,91 (s> 1H); 8,32 (d 1 J = 8,,3 Hz, 1H); 8,25 (s, 1H); 8,11 (d, J = 8,3 Hz, 1H); 8,05 (d, J = 8,8 Hz, 1H); 7,97 (d, J = 8,3 Hz, 1H; 1 8,94 (d, J = 81¾ 1H)1 7,69 t, 1 J = = 7,5 Hz, 1H); 7,58 - 7,63 (m, 1H); 7,51 (d, J = 8,8 Hz, 1H).[T [2,5-bis (trifluoromethyl) phenyl] -1-hydronaphthalene-2-carbo-amide (83), yield 41%; mp 139-142 ° C; 1 H-NMR (OMSO-d 6), δ: 13.49 (br, s, 1H); 10.91 (s>1H); 8.32 (d, J = 8.3 Hz, 1H); 8.25 (s, 1 H); 8.11 (d, J = 8.3Hz, 1H); 8.05 (d, J = 8.8 Hz, 1 H); 7.97 (d, J = 8.3 Hz, 1H; 18.94 (d, J = 81 1 H) 1 7.69 t, 1 J = 7.5 Hz, 1H); 7.58 - 7.63 (m, 1H); 7.51 (d, J = 8.8 Hz, 1 H).

Λthydroxynaftalén-[2-chlór-3,5tbls((nfluórme(yl)fenyΓ|-2tkarbo\amld (84), výťažok 37 %; teplota topenia 192 - 193 °C; 1H-NMR (OMSO-dó), δ: 13,26 (br, s, 1H); 11,18 (s, 1H); 8,65 (s, 1H); 8,35 (d, J = 8,1 Hz, 1H); 8,11 (s, 1H); 8,08 (d, J = 9,1 Hz, 1H); 7,94 (d, J = 7,8 Hz, 1H); 7,70 (t, J = 7,1 Hz, 1H); 7,58 - 7,63 (m, 1H); 7,53 (d, J = 8,3 Hz, 1H).Yd thydroxynaphthalene- [2-chloro-3,5tbls ((trifluoromethyl) phenyl] -2-carbamido (84), yield 37%; mp 192-193 ° C; 1 H-NMR (OMSO-d 6), δ: 13.26 (br, s, 1H); 11.18 (s, 1H); 8.65 (s, 1H); 8.35 (d, J = 8.1 Hz, 1H); 8.11 (s) 8.08 (d, J = 9.1 Hz, 1H); 7.94 (d, J = 7.8 Hz, 1H); 7.70 (t, J = 7.1 Hz, 1H); 7.58-7.63 (m, 1H) 7.53 (d, J = 8.3 Hz, 1H).

1-hydro\ytΛt(3,4,5-trImeto?tyfenyl)naf(alént2tkarbo\amtd (85), výťažok 66 %; teplota topenia 177 - 180 °C; ]H-NMR (OMSO-dô), δ: 14,01 (s, 1H); 10,36 (s, 1H); 8,31 (d, J = 8,1 Hz, 1H); 8,11 (d, J = 8,8 Hz, 1H); 7,92 (d, J = 8,1 Hz, 1H); 7,68 (t, J = 7,2 Hz, 1H); 7,56 - 7,61 (m, 1H); 7,47 (d, J = 8,8 Hz, 1H); 7,17 (s, 2H); 3,81 (s, 6H); 3,67 (s, 3H).1-Hydroxy (3,4,5-trimethylphenyl) naphthalene (alkene-2-carbo-amtd (85), yield 66%; mp 177-180 ° C; 1 H-NMR (OMSO-d 6), δ: 14 1.01 (s, 1H); 10.36 (s, 1H); 8.31 (d, J = 8.1 Hz, 1H); 8.11 (d, J = 8.8 Hz, 1H); 92 (d, J = 8.1 Hz, 1H) 7.68 (t, J = 7.2 Hz, 1H) 7.56-7.61 (m, 1H) 7.47 (d, J = 8.8 Hz, 1H), 7.17 (s, 2H), 3.81 (s, 6H), 3.67 (s, 3H).

lthydro\ytΛt(2,4,6-trImetylfenyl)naf(alént2tkarbo\amtd (86), výťažok 52 %; teplota topenia 160 - 163 °C; ]H-NMR (OMSO-dô), δ: 14,40 (s, 1H); 10,15 (s, 1H); 8,29 (d, J = 8,1 Hz, 1H); 8,12 (d, J = 8,8 Hz, 1H); 7,91 (d, J = 8,3 Hz, 1H); 7,67 (t, J = 7,5 Hz, 1H); 7,55 - 7,60 (m, 1H); 7,45 (d, J = 8,8 Hz, 1H); 6,98 (s, 2H); 2,28 (s, 3H); 2,17 (s, 6H).(2,4,6-trimethylphenyl) naphthyl (2,4-trimethylphenyl) naphthalenol (86), yield 52%; mp 160-163 ° C; 1 H-NMR (OMSO-d 6), δ: 14.40 (s (1H); 10.15 (s, 1H); 8.29 (d, J = 8.1 Hz, 1H); 8.12 (d, J = 8.8 Hz, 1H); 7.91 (d) J = 8.3 Hz, 1H) 7.67 (t, J = 7.5 Hz, 1H) 7.55-7.60 (m, 1H) 7.45 (d, J = 8 8 Hz, 1H), 6.98 (s, 2H), 2.28 (s, 3H), 2.17 (s, 6H).

1-hydro\ytΛt(5-metoxy-2-metylfenyl)naftalén-2tkarboxamtd (87), výťažok 60 %; teplota topenia 128 až 130°C; ]H-^MR (DMSO-dó), δ: 14,18 (s, 1H); 10,36 (s, 1H); 8,30 (d, J = 8,3 Hz, 1H); 8,09 (d, J = 8,8 Hz,1-Hydroxy (5-methoxy-2-methylphenyl) naphthalene-2-carboxamide (87), yield 60%; mp 128-130 ° C; 1 H-NMR (DMSO-d 6), δ: 14.18 (s, 1H); 10.36 (s, 1 H); 8.30 (d, J = 8.3Hz, 1H); 8.09 (d, J = 8.8Hz,

SK 71-2017 A3A3

1H); 7,92 (d, J = 8,1 Hz, 1H); 7,67 (t, J = 7,5 Hz, 1H); 7,56 - 7,61 (m, 1H); 7,46 (d, J = 8,6 Hz, 1H); 7,23 (d, J = 8,6 Hz, 1H); 6,98 (d, J = 2,5 Hz, 1H); 6,84 (dd, J = 8,3, 2,5 Hz, 1H); 3,76 (s, 3H); 2,18 (s, 3H).1H); 7.92 (d, J = 8.1Hz, 1H); 7.67 (t, J = 7.5Hz, 1H); 7.56 - 7.61 (m, 1H); 7.46 (d, J = 8.6Hz, 1H); 7.23 (d, J = 8.6Hz, 1H); 6.98 (d, J = 2.5Hz, 1H); 6.84 (dd, J = 8.3, 2.5 Hz, 1H); 3.76 (s, 3H); 2.18 (s, 3H).

1-h\AhO\\’-AM2-incno\\’-5-incUvlfenvl)naftalén-2-karboxainid (88), výťažok 74 %; teplota topenia 106 - 108 °C; 1H-NMR (DMSO-dó), δ: 13,92 (s, 1H); 10,23 (s, 1H); 8,31 (d, J = 8,1 Hz, 1H); 8,07 (d, J = 8,8 Hz, 1H); 7,91 (d, J = 8,3 Hz, 1H); 7,66 (ddd, J = 8,2, 6,9, 1,4 Hz, 1H); 7,56 - 7,60 (m, 1H); 7,49 (d, J = 1,8 Hz, 1H); 7,46 (d, J = 8,8 Hz, 1H); 7,01 - 7,08 (m, 2H); 3,82 (s, 3H); 2,29 (s, 3H).1-h-Ah2-incno-5-incvvlfenvl) naphthalene-2-carboxainide (88), 74% yield; mp 106-108 ° C; 1 H-NMR (DMSO-d 6), δ: 13.92 (s, 1H); 10.23 (s, 1 H); 8.31 (d, J = 8.1Hz, 1H); 8.07 (d, J = 8.8 Hz, 1 H); 7.91 (d, J = 8.3Hz, 1H); 7.66 (ddd, J = 8.2, 6.9, 1.4 Hz, 1H); 7.56 - 7.60 (m, IH); 7.49 (d, J = 1.8Hz, 1H); 7.46 (d, J = 8.8 Hz, 1 H); 7.01-7.08 (m, 2H); 3.82 (s, 3H); 2.29 (s, 3H).

1-hydro\v-A-(2-meto\y-6-meeyLfenyΓ|-naftalén-2-karboxamid (89), výťažok 58 %; teplota topenia 177 - 179 °C; 1H-NMR (DMSO-dó), δ: 14,40 (s, 1H); 10,07 (s, 1H); 8,29 (d, J = 8,2 Hz, 1H); 8,12 (d, J = 8,8 Hz, 1H); 7,91 (d, J = 8,3 Hz, 1H); 7,65 - 7,69 (m, 1H); 7,55 - 7,60 (m, 1H); 7,45 (d, J = 8,8 Hz, 1H); 7,25 (t, J = 8,0 Hz, 1H); 6,97 (d, J = 8,1 Hz, 1H); 6,92 (d, J = 7,6 Hz, 1H); 3,77 (s, 3H); 2,20 (s, 3H).1-Hydroxy- (2-methyl-6-methylphenyl) -naphthalene-2-carboxamide (89), 58% yield; mp 177-179 ° C; 1 H-NMR (DMSO-d 6) δ: 14.40 (s, 1H); 10.07 (s, 1H); 8.29 (d, J = 8.2 Hz, 1H); 8.12 (d, J = 8.8 Hz, 1H); 7.91 (d, J = 8.3 Hz, 1H), 7.65-7.69 (m, 1H), 7.55-7.60 (m, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.25 (t, J = 8.0 Hz, 1H), 6.97 (d, J = 8.1 Hz, 1H), 6.92 (d, J = 7, 6 Hz, 1H) 3.77 (s, 3H), 2.20 (s, 3H).

1-hydro\v-A-(3-chlór-2-fluórfenvl)-naftalén-2-karbo^amid (90), výťažok 60 %; teplota topenia 172 - 174 °C; 1H-NMR (DMSO-dó), δ: 13,70 (s, 1H); 10,73 (s, 1H); 8,32 (d, J = 8,1 Hz, 1H); 8,06 (d, J = 8,8 Hz, 1H); 7,93 (d, J = 7,8 Hz, 1H); 7,69 (t, J = 7,0 Hz, 1H); 7,53 - 7,62 (m, 3H); 7,49 (d, J = 8,8 Hz, 1H); 7,31 (t, J = 7,6 Hz, 1H).1-Hydro- N - (3-chloro-2-fluorophenyl) -naphthalene-2-carboxamide (90), yield 60%; mp 172-174 ° C; 1 H-NMR (DMSO-d 6), δ: 13.70 (s, 1H); 10.73 (s, 1 H); 8.32 (d, J = 8.1Hz, 1H); 8.06 (d, J = 8.8 Hz, 1 H); 7.93 (d, J = 7.8Hz, 1H); 7.69 (t, J = 7.0Hz, 1H); 7.53 - 7.62 (m, 3H); 7.49 (d, J = 8.8 Hz, 1 H); 7.31 (t, J = 7.6Hz, 1H).

1-hydro\v-A-(3-chlór-4-fluórfenvl)-naftalén-2-karbo^amid (91), výťažok 71 %; teplota topenia 202 - 204 °C; 1H-NMR (DMSO-d6), δ: 13,72 (s, 1H); 10,59 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,07 (d, J = 8,8 Hz, 1H); 8,02 (d, J = 6,1 Hz, 1H); 7,92 (d, J = 7,8 Hz, 1H); 7,65 - 7,75 (m, 2H); 7,56 - 7,61 (m, 1H); 7,44 - 7,50 (m, 2H).1-hydro- N - (3-chloro-4-fluorophenyl) -naphthalene-2-carboxamide (91), yield 71%; mp 202-204 ° C; 1 H-NMR (DMSO-d 6), δ: 13.72 (s, 1H); 10.59 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.07 (d, J = 8.8 Hz, 1 H); 8.02 (d, J = 6.1Hz, 1H); 7.92 (d, J = 7.8Hz, 1H); 7.65 - 7.75 (m, 2H); 7.56 - 7.61 (m, 1H); 7.44-7.50 (m, 2H).

1-hydro\v-A-(4-chlór-2-fluórfenvl)-naftalén-2-karbo?αmid (92), výťažok 63 %; teplota topenia 163 - 165 °C; 1H-NMR (DMSO-d6), δ: 13,73 (s, 1H); 10,64 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,06 (d, J = 8,8 Hz, 1H); 7,92 (d, J = 8,1 Hz, 1H); 7,57 - 7,71 (m, 4H); 7,48 (d, J = 8,6 Hz, 1H); 7,38 (d, J = 8,3 Hz, 1H).1-hydro- N - (4-chloro-2-fluorophenyl) -naphthalene-2-carboxamide (92), 63% yield; mp 163-165 ° C; 1 H-NMR (DMSO-d 6), δ: 13.73 (s, 1H); 10.64 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.06 (d, J = 8.8 Hz, 1 H); 7.92 (d, J = 8.1Hz, 1H); 7.57 - 7.71 (m, 4H); 7.48 (d, J = 8.6Hz, 1H); 7.38 (d, J = 8.3Hz, 1H).

1-hydro\v-A-(5-chlór-2-fluórfenvl)-naftalén-2-karbo?αmid (93), výťažok 67 %; teplota topenia 169 - 171 °C; 1H-NMR (DMSO-d6), δ: 13,58 (br, s, 1H); 10,69 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,05 (d, J = 8,8 Hz, 1H);1-Hydro- N - (5-chloro-2-fluorophenyl) -naphthalene-2-carboxamide (93), yield 67%; mp 169-171 ° C; 1 H-NMR (DMSO-d 6), δ: 13.58 (br, s, 1H); 10.69 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.05 (d, J = 8.8 Hz, 1 H);

7,93 («d, J = 8,1 Hz, 1H); 7,78 - 7,81 (m, 1H); 7,6(6 - 7,71 (m, 1H); 7,57 - 7,62 (m, 1H); 7,49 (t, J = 8,8 Hz, 1H); 7,40 - 7,44 (m, 2H).7.93 (d, J = 8.1 Hz, 1H); 7.78-7.81 (m, 1H); 7.6 (6-7.71 (m, 1H); 7.57-7.62 (m, 1H); 7.49 (t, J = 8.8 Hz, 1H); 7.40-7, 44 (m. 2H).

V-(2-bróm-5-fluórfenyl)-1-hydro\ynaftalén-2-karbo\amid (94), výťažok 61 %; teplota topenia 187 - 190 °C; 1H-NMR (DMSO-d6), δ: 13,53 (br, s, 1H); 10,78 (s, 1H); 8,34 (d, J = 8,3 Hz, 1H); 8,08 (d, J = 8,8 Hz, 1H);N - (2-Bromo-5-fluorophenyl) -1-hydronaphthalene-2-carboxamide (94), 61% yield; mp 187-190 ° C; 1 H-NMR (DMSO-d 6), δ: 13.53 (br, s, 1H); 10.78 (s, 1 H); 8.34 (d, J = 8.3Hz, 1H); 8.08 (d, J = 8.8 Hz, 1 H);

7,93 (d, J = 8,1 Hz, 1H); 7,81 (dd, J = 8,8 Hz, 5,8 Hz, 1H); 7,74 (dd, J = 10,0 Hz, 2,9 Hz, 1H); 7,69 (t, J = = 7,5 Hz, 1H); 7,58 - 7,62 (m, 1H); 7,51 (d, J = 8,8 Hz, 1H); 7,19 (td, J = 8,5, 2,8 Hz, 1H).7.93 (d, J = 8.1Hz, 1H); 7.81 (dd, J = 8.8 Hz, 5.8 Hz, 1H); 7.74 (dd, J = 10.0 Hz, 2.9 Hz, 1H); 7.69 (t, J = 7.5Hz, 1H); 7.58 - 7.62 (m, 1H); 7.51 (d, J = 8.8Hz, 1H); 7.19 (td, J = 8.5, 2.8 Hz, 1H).

V-(4-bróm-2-fluórfenyl)-1-hydro\ynaftalén-2-karbo\amid (95), výťažok 74 %; teplota topenia 172 - 174 °C; 1H-NMR (DMSO-d6), δ: 13,72 (s, 1H); 10,63 (s, 1H); 8,31 (d, J = 8,1 Hz, 1H); 8,06 (d, J = 8,8 Hz, 1H); 7,92 (d, J = 8,1 Hz, 1H); 7,66 - 7,74 (m, 2H); 7,57 - 7,62 (m, 2H); 7,47 - 7,52 (m, 2H).N - (4-Bromo-2-fluorophenyl) -1-hydronaphthalene-2-carboxamide (95), 74% yield; mp 172-174 ° C; 1 H-NMR (DMSO-d 6), δ: 13.72 (s, 1H); 10.63 (s, 1 H); 8.31 (d, J = 8.1Hz, 1H); 8.06 (d, J = 8.8 Hz, 1 H); 7.92 (d, J = 8.1Hz, 1H); 7.66 - 7.74 (m, 2H); 7.57 - 7.62 (m, 2H); 7.47 - 7.52 (m, 2H).

V-(4-bróm-3-fluórfenyl)-1-hydro\ynaftalén-2-karbo\amid (96), výťažok 58 %; teplota topenia 199 - 202 °C; 1H-NMR (DMSO-d6), δ: 13,62 (s, 1H); 10,66 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,08 (d, J = 8,8 Hz, 1H); 7,92 (d, J = 8,3 Hz, 1H); 7,88 (dd, J = 11,2, 2,1 Hz, 1H); 7,74 (t, J = 8,3 Hz, 1H); 7,69 (t, J = 7,5 Hz, 1H); 7,56 až 7,62 (m, 2H); 7¾ (d, J = 8,:8 Hz, 1H).N - (4-Bromo-3-fluorophenyl) -1-hydronaphthalene-2-carboxamide (96), 58% yield; mp 199-202 ° C; 1 H-NMR (DMSO-d 6), δ: 13.62 (s, 1H); 10.66 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.08 (d, J = 8.8 Hz, 1 H); 7.92 (d, J = 8.3Hz, 1H); 7.88 (dd, J = 11.2, 2.1 Hz, 1H); 7.74 (t, J = 8.3Hz, 1H); 7.69 (t, J = 7.5Hz, 1H); 7.56-7.62 (m, 2H); 7.1 (d, J = 8.1 Hz: 1H).

V-(5-bróm-2-fluórfenyl)-1-hydro\ynaftalén-2-karbo\amid (97), výťažok 60 %; teplota topenia 174 - 177 °C; 1H-NMR (DMSO-d6), δ: 13,59 (s, 1H); 10,69 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,05 (d, J = 8,8 Hz, 1H); 7,90 až 7,94 (m, 2H); 7,69 (t, J = 7,5 Hz, 1H); 7,57 - 7,62 (m, 1H); 7,52 - 7,56 (m, 1H); 7,49 (d, J = 8,8 Hz, 1H); 7,37 (t, J = 9,5 Hz, 1H).N - (5-Bromo-2-fluorophenyl) -1-hydroxy-naphthalene-2-carboxamide (97), yield 60%; mp 174-177 ° C; 1 H-NMR (DMSO-d 6), δ: 13.59 (s, 1H); 10.69 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.05 (d, J = 8.8 Hz, 1 H); 7.90 to 7.94 (m, 2H); 7.69 (t, J = 7.5Hz, 1H); 7.57 - 7.62 (m, 1H); 7.52-7.56 (m, 1H); 7.49 (d, J = 8.8 Hz, 1 H); 7.37 (t, J = 9.5Hz, 1H).

V-(4-bróm-3-chlórfenyl)-1-hydro\ynaftalén-2-karbo\amid (98), výťažok 58 %; teplota topenia 203 - 205 °C; 1H-NMR (DMSO-d6), δ: 13,61 (s, 1H); 10,67 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,12 (d, J = 2,3 Hz, 1H); 8,07 (d, J = 9,1 Hz, 1H); 7,91 (d, J = 8,1 Hz, 1H); 7,80 (d, J = 8,8 Hz, 1H); 7,66 - 7,72 (m, 2H); 7,56 - 7,61 (m, 1H); 7,48 (d, J = 8,8 Hz, 1H).N - (4-Bromo-3-chlorophenyl) -1-hydroxynaphthalene-2-carboxamide (98), 58% yield; mp 203-205 ° C; 1 H-NMR (DMSO-d 6), δ: 13.61 (s, 1H); 10.67 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.12 (d, J = 2.3Hz, 1H); 8.07 (d, J = 9.1Hz, 1H); 7.91 (d, J = 8.1Hz, 1H); 7.80 (d, J = 8.8 Hz, 1 H); 7.66 - 7.72 (m, 2H); 7.56 - 7.61 (m, 1H); 7.48 (d, J = 8.8 Hz, 1 H).

V-(4-bróm-2,3,5,6-teerafluórfenyl)-1-hydro\vnaftalén-2-karbo\amid (99), výťažok 24 %; teplota topenia 220 až 223 °C; ]H-NMR (DMSO-d6), δ: 13,35 (br, s, 1H); 10,96 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,07 (d, J = 8,8 Hz, 1H); 7,94 (d, J = 8,1 Hz, 1H); 7,71 (t, J = 7,5 Hz, 1H); 7,59 - 7,64 (m, 1H); 7,52 (d, J = 9,1 Hz, ^H).N - (4-bromo-2,3,5,6-tertafluorophenyl) -1-hydronaphthalene-2-carboxamide (99), 24% yield; mp 220-223 ° C; 1 H-NMR (DMSO-d 6), δ: 13.35 (br, s, 1H); 10.96 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.07 (d, J = 8.8 Hz, 1 H); 7.94 (d, J = 8.1Hz, 1H); 7.71 (t, J = 7.5Hz, 1H); 7.59 - 7.64 (m, 1H); 7.52 (d, J = 9.1 Hz, 1H).

SK 71-2017 A3A3

Mi\xhO\vA'-|2s2hkHH-UnnLionnm\T)fcnvl|-naftalen-2_karboxainid (100), výťažok 32 %; teplota topenia 158 - 160 °C; 1H-NMR (DMSO-dó), δ: 13,33 (br, s, 1H); 11,02 (s, 1H); 8,35 (d, J = 8,3 Hz, 1H); 8,13 (d, J = = 8,3 Hz, 1H); 8,09 (d, J = 8,8 Hz, 1H); 8,05 (s, 1H); 7,94 (d, J = 8,1 Hz, 1H); 7,83 (d, J = 8,3 Hz, 1H); 7,67 až 7,72 (m, 1H); 7,58 - 7,64 (m, 1H); 7,53 (d, J = 8,8 Hz, 1H).Mi-xyl-1,2-2H-NH2-unionic-1-naphthalene-2-carboxainide (100), 32% yield; mp 158-160 ° C; 1 H-NMR (DMSO-d 6), δ: 13.33 (br, s, 1H); 11.02 (s, 1 H); 8.35 (d, J = 8.3Hz, 1H); 8.13 (d, J = 8.3Hz, 1H); 8.09 (d, J = 8.8 Hz, 1 H); 8.05 (s, 1 H); 7.94 (d, J = 8.1Hz, 1H); 7.83 (d, J = 8.3Hz, 1H); 7.67 to 7.72 (m, 1H); 7.58 - 7.64 (m, 1H); 7.53 (d, J = 8.8 Hz, 1 H).

MixxhOxv-A^ld-chlon^-UnniiiOincUxďfcnvlI-naftalen^-karboxainid (101), výťažok 21 %; teplota topenia 157 - 160 °C; ]H-NMR (DMSO-dó), δ: 13,69 (s, 1H); 10,72 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,04 (d, J = 8,8 Hz, 1H); 7,87 - 7,95 (m, 3H); 7,75 (d, J = 8,3 Hz, 1H); 7,69 (t, J = 7,5 Hz, 1H); 7,57 - 7,62 (m, 1H); 7,49 (d, J = 8,8 Hz, 1H).Mixxhex-N, 4'-chloro-4'-amine-4'-naphthalene-4-naphthalene-4-carboxainide (101), 21% yield; mp 157-160 ° C; 1 H-NMR (DMSO-d 6), δ: 13.69 (s, 1H); 10.72 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.04 (d, J = 8.8 Hz, 1 H); 7.87-7.95 (m, 3H); 7.75 (d, J = 8.3Hz, 1H); 7.69 (t, J = 7.5Hz, 1H); 7.57 - 7.62 (m, 1H); 7.49 (d, J = 8.8 Hz, 1 H).

MixxhOxv-A^ld-chloim-UnniionmUxďfcnvlI-naftalen-Ž-karboxainid (102), výťažok 59 %; teplota topenia 173 - 175 °C; ]H-NMR (DMSO-dó), δ: 13,56 (s, 1H); 10,76 (s, 1H); 8,30 - 8,33 (m, 2H); 8,12 (dd, J = 8,8, 1,8 Hz, 1H); 8,08 (d, J = 9,1 Hz, 1H); 7,92 (d, J = 8,1 Hz, 1H); 7,77 (d, J = 8,8 Hz, 1H); 7,69 (t, J = 7,5 Hz, 1H); 7,57 - 7,62 (m, 1H); 7,50 (d, J = 8,8 Hz, 1H).Mixxhex-N, N-chloim-Unionic N-methyl-naphthalene-2-carboxainide (102), 59% yield; mp 173-175 ° C; 1 H-NMR (DMSO-d 6), δ: 13.56 (s, 1H); 10.76 (s, 1 H); 8.30 - 8.33 (m, 2H); 8.12 (dd, J = 8.8, 1.8 Hz, 1H); 8.08 (d, J = 9.1Hz, 1H); 7.92 (d, J = 8.1Hz, 1H); 7.77 (d, J = 8.8 Hz, 1 H); 7.69 (t, J = 7.5Hz, 1H); 7.57 - 7.62 (m, 1H); 7.50 (d, J = 8.8 Hz, 1 H).

y-|2.(6^i^iii^likôn-^-^(tinlliuunm'tt^’l)f^^Ilvl|’1^-h^’dnownaftalen-2-karbo\amid (103), výťažok 16 %; teplota topenia 191 - 194 °C; ]H-NMR (DMSO-dó), δ: 13,61 (s, 1H); 10,97 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,15 (s, 2H); 8,10 (d, J = 9,1 Hz, 1H); 7,95 (d, J = 8,1 Hz, 1H); 7,71 (t, J = 7,3 Hz, 1H); 7,59 - 7,64 (m, 1H); 7,53 (d, J = = 8,8 Hz, 1H).y | second (6 ^ i ^ iii ^ Likon - ^^ (^ tinlliuunm'tt l) f ^^ Ilv l | '1 ^ H ^' dnownaftalen-2-carbo \ amide (103), yield 16%; mp 191-194 ° C; 1 H-NMR (DMSO-d 6), δ: 13.61 (s, 1H); 10.97 (s, 1H); 8.31 (d, J = 8) 3 Hz, 1H); 8.15 (s, 2H); 8.10 (d, J = 9.1 Hz, 1H); 7.95 (d, J = 8.1 Hz, 1H); 71 (t, J = 7.3 Hz, 1H), 7.59-7.64 (m, 1H), 7.53 (d, J = 8.8 Hz, 1H).

A-[3-fluór-4-(tInfluónΏetyl)fenyΓ|-1-hydIΌ\vnaftalén-2-karbo?almld (104), výťažok 40 %; teplota topenia 185 až 187 °C; 1H-NMR (DMSO-dó), δ: 13,41 (bn, s, 1H); 10,83 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,09 (d, J = 8,8 Hz, 1H); 7,99 (d, J = 13,4 Hz, 1H); 7,93 (d, J = 8,1 Hz, 1H); 7,78 - 7,85 (m, 2H); 7,69 (t, J = 7,5 Hz, 1H); 7,57 až 7,62 (m, 1H); 7,50 (d, J = 8,8 Hz, 1H).N - [3-Fluoro-4- (trifluoromethyl) phenyl] -1-hydroxy-naphthalene-2-carbamidine (104), 40% yield; mp 185-187 ° C; 1 H-NMR (DMSO-d 6), δ: 13.41 (bn, s, 1H); 10.83 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.09 (d, J = 8.8 Hz, 1 H); 7.99 (d, J = 13.4 Hz, 1 H); 7.93 (d, J = 8.1Hz, 1H); 7.78-7.85 (m, 2H); 7.69 (t, J = 7.5Hz, 1H); 7.57 to 7.62 (m, 1H); 7.50 (d, J = 8.8 Hz, 1 H).

A-[3-fluór-5-(tInfluóπnetyl)fenyΓ|-1-hydIΌ\vnaftalén-2-karbo?almld (105), výťažok 48 %; teplota topenia 165 až 167 °C; ]H-NMR (DMSO-dó), δ: 13,43 (s, 1H); 10,81 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,07 (d, J = 9,1 Hz, 1H); 8,01 - 8,06 (m, 2H); 7,93 (d, J = 8,1 Hz, 1H); 7,70 (t, J = 7,5 Hz, 1H); 7,58 - 7,63 (m, 1H); 7,48 až 7,53 (m, 2H).N - [3-Fluoro-5- (trifluoromethyl) phenyl] -1-hydroxy-naphthalene-2-carbamyl (105), yield 48%; mp 165-167 ° C; 1 H-NMR (DMSO-d 6), δ: 13.43 (s, 1H); 10.81 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.07 (d, J = 9.1Hz, 1H); 8.01 - 8.06 (m, 2H); 7.93 (d, J = 8.1Hz, 1H); 7.70 (t, J = 7.5Hz, 1H); 7.58 - 7.63 (m, 1H); 7.48 to 7.53 (m, 2H).

A-[4-fluór-2-(trifluóimetyl)fenyr|-1-hydno\vnaftalén-2-karbo?aimid (106), výťažok 24 %; teplota topenia 135 až 137 °C; ]H-NMR (DMSO-dó), δ: 13,80 (s, 1H); 10,64 (s, 1H); 8,30 (d, J = 8,3 Hz, 1H); 8,05 (d, J = 8,8 Hz, 1H); 7,92 (d, J = 8,3 Hz, 1H); 7,78 (dd, J = 8,8 Hz, 2,5 Hz, 1H); 7,65 - 7,76 (m, 3H); 7,57 - 7,62 (m, 1H); 7,49 (d, J = 8,6 Hz, 1H).N- [4-fluoro-2- (trifluoromethyl) phenyl] -1-hydna-naphthalene-2-carbamide (106), yield 24%; mp 135-137 ° C; 1 H-NMR (DMSO-d 6) δ: 13.80 (s, 1H); 10.64 (s, 1 H); 8.30 (d, J = 8.3Hz, 1H); 8.05 (d, J = 8.8 Hz, 1 H); 7.92 (d, J = 8.3Hz, 1H); 7.78 (dd, J = 8.8 Hz, 2.5 Hz, 1H); 7.65 - 7.76 (m, 3H); 7.57 - 7.62 (m, 1H); 7.49 (d, J = 8.6Hz, 1H).

A-[4-fluór-3-(tπfluónnetyl)fenyl]-1-hydno\vnaftalén-2-kanbo\amld (107), výťažok 53 %; teplota topenia 164 až 166 °C; ]H-NMR (DMSO-dó), δ: 13,65 (s, 1H); 10,71 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,20 (dd, J = 6,3 Hz, 2,3 Hz, 1H); 8,06 - 8,13 (m, 2H); 7,92 (d, J = 8,1 Hz, 1H); 7,68 (t, J = 7,5 Hz, 1H); 7,55 - 7,61 (m, 2H); 7,49 (d, J = 9,1 Hz, 1H).N - [4-fluoro-3- (trifluoromethyl) phenyl] -1-hydna-naphthalene-2-kanbolamide (107), yield 53%; mp 164-166 ° C; 1 H-NMR (DMSO-d 6), δ: 13.65 (s, 1H); 10.71 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.20 (dd, J = 6.3 Hz, 2.3 Hz, 1H); 8.06 - 8.13 (m, 2H); 7.92 (d, J = 8.1Hz, 1H); 7.68 (t, J = 7.5Hz, 1H); 7.55 - 7.61 (m, 2H); 7.49 (d, J = 9.1Hz, 1H).

A-[2-fluór-3-(tInfluóπnetyl)fenyΓ|-1-hydIΌ\vnaftalén-2-karbo?almld (108), výťažok 45 %; teplota topenia 174 až 175 °C; 1H-NMR (DMSO-d·.), δ: 13,61 (bn, s, 1H); 10,79 (s, 1H); 8,32 (d, J = 8,3 Hz, 1H); 8,07 (d, J = 8,8 Hz, 1H); 7,97 (t, J = 7,6 Hz, 1H); 7,94 (d, J = 8,6 Hz, 1H); 7,74 (t, J = 7,2 Hz, 1H); 7,67 - 7,72 (m, 1H); 7,58 až 7,63 (m, 1H); 7,48 - 7,53 (m, 2H).N- [2-fluoro-3- (trifluoromethyl) phenyl] -1-hydroxy-naphthalene-2-carbamyl (108), yield 45%; mp 174-175 ° C; 1 H-NMR (DMSO-d 6), δ: 13.61 (bn, s, 1H); 10.79 (s, 1 H); 8.32 (d, J = 8.3Hz, 1H); 8.07 (d, J = 8.8 Hz, 1 H); 7.97 (t, J = 7.6Hz, 1H); 7.94 (d, J = 8.6Hz, 1H); 7.74 (t, J = 7.2Hz, 1H); 7.67 - 7.72 (m, 1H); 7.58 to 7.63 (m, 1H); 7.48-7.53 (m, 2H).

y-|2,5-^i^iiilluôr-^-^(4inillUôm'tt^-]);^^i]vl|-14ivdro\^’nabalen-2^-^k^aib^ox^ímiid (109), výťažok 38 %; teplota topenia 229 - 231 °C; ]H-NMR (DMSO-dó), δ: 13,14 (bn, s, 1H); 11,05 (s, 1H); 8,35 (d, J = 8,3 Hz, 1H); 8,10 (dd, J = 11,8, 6,0 Hz, 1H); 8,06 (d, J = 9,1 Hz, 1H); 7,90 - 7,96 (m, 2H); 7,70 (t, J = 7,3 Hz, 1H); 7,58 - 7,64 (m, 1H); 7,52 (d, J = 8,8 Hz, 1H).γ- | 2,5- [1,2-difluoro-4- (4-trifluoromethyl) -1- (1,4-naphthalen-2-yl) -benzenesulfonamide (109); ), yield 38%; mp 229-231 ° C; 1 H-NMR (DMSO-d 6), δ: 13.14 (bn, s, 1H); 11.05 (s, 1 H); 8.35 (d, J = 8.3Hz, 1H); 8.10 (dd, J = 11.8, 6.0 Hz, 1H); 8.06 (d, J = 9.1Hz, 1H); 7.90 - 7.96 (m, 2H); 7.70 (t, J = 7.3Hz, 1H); 7.58 - 7.64 (m, 1H); 7.52 (d, J = 8.8 Hz, 1 H).

A-[2-bnóm-5-(tπfluóπnetyl)fenyΓ|-1-hydno\ynaftalén-·2-kanbo\amld (110), výťažok 41 %; teplota topenia 190 - 193 °C; ]H-NMR (DMSO-dó), δ: 13,50 (bn, s, 1H); 10,89 (s, 1H); 8,33 (d, J = 8,3 Hz, 1H); 8,17 (s, 1H); 8,08 (d, J = 8,8 Hz, 1H); 8,03 (d, J = 8,3 Hz, 1H); 7,94 (d, J = 8,1 Hz, 1H); 7,69 (t, J = 7,5 Hz, 1H); 7,58 - 7,66 (m, 2H); 7,52 (d, J = 8,8 Hz, 1H).N - [2-Bromo-5- (trifluoromethyl) phenyl] -1-hydroxy-naphthalene-2-kanbolamide (110), 41% yield; mp 190-193 ° C; 1 H-NMR (DMSO-d 6) δ: 13.50 (bn, s, 1H); 10.89 (s, 1 H); 8.33 (d, J = 8.3Hz, 1H); 8.17 (s, 1 H); 8.08 (d, J = 8.8 Hz, 1 H); 8.03 (d, J = 8.3Hz, 1H); 7.94 (d, J = 8.1Hz, 1H); 7.69 (t, J = 7.5Hz, 1H); 7.58 - 7.66 (m, 2H); 7.52 (d, J = 8.8 Hz, 1 H).

A-P-bnóm^-On fluónmetyl)fenyl]-1-hydno\vnaftalén-2-karbo?αmld (111), výťažok 57 %; teplota topenia 154 - 156 °C; ]H-NMR (DMSO-dó), δ: 13,43 (bn, s, 1H); 10,75 (s, 1H); 8,35 (s, 1H); 8,31 (d, J = 8,2 Hz, 1H); 8,19 (s, 1H); 8,06 (d, J = 8,7 Hz, 1H); 7,91 (d, J = 8,2 Hz, 1H); 7,75 (s, 1H); 7,68 (t, J = 7,5 Hz, 1H); 7,56 - 7,61 (m, 1H); 7,49 (d, J = 8,7 Hz, 1H).AP-Bromo-4-fluoromethyl) phenyl] -1-hydna-naphthalene-2-carbamido (111), 57% yield; mp 154-156 ° C; 1 H-NMR (DMSO-d 6), δ: 13.43 (bn, s, 1H); 10.75 (s, 1 H); 8.35 (s, 1 H); 8.31 (d, J = 8.2Hz, 1H); 8.19 (s, 1 H); 8.06 (d, J = 8.7Hz, 1H); 7.91 (d, J = 8.2Hz, 1H); 7.75 (s, 1 H); 7.68 (t, J = 7.5Hz, 1H); 7.56 - 7.61 (m, 1H); 7.49 (d, J = 8.7Hz, 1H).

SK 71-2017 A3 λ'-|24πΌΐη-4-(4πΠίΐοηη^ν1 )fcaivl|-1-hvdiO\vnaftalen-2-karboxainid (112), výťažok 37 %; teplota topenia 168 - 170 °C; ]H-NMR (DMSO-d6), δ: 13,43 (s, 1H); 10,93 (s, 1H); 8,34 (d, J = 8,1 Hz, 1H); 8,17 (s, 1H); 8,09 (d, J = 8,8 Hz, 1H); 8,05 (d, J = 8,3 Hz, 1H); 7,94 (d, J = 8,3 Hz, 1H); 7,87 (d, J = 8,3 Hz, 1H); 7,67 až 7,72 (m, 1H); 7,58 - 7,63 (m, 1H); 7,52 (d, J = 8,8 Hz, 1H).SK 71-2017 A3 λ'- 24πΌΐη-4- (4πΠίΐοηη 1) fcaivl-1-HvdiO-naphthalene-2-carboxainide (112), yield 37%; mp 168-170 ° C; 1 H-NMR (DMSO-d 6), δ: 13.43 (s, 1H); 10.93 (s, 1 H); 8.34 (d, J = 8.1Hz, 1H); 8.17 (s, 1 H); 8.09 (d, J = 8.8 Hz, 1 H); 8.05 (d, J = 8.3Hz, 1H); 7.94 (d, J = 8.3Hz, 1H); 7.87 (d, J = 8.3Hz, 1H); 7.67 to 7.72 (m, 1H); 7.58 - 7.63 (m, 1H); 7.52 (d, J = 8.8 Hz, 1 H).

λl·|4-brom-3-^rlΠlιomlctvl )fcnvl|l1-hvdrc\ynaftalen-2-karboxamld (113), výťažok 33 %; teplota topenia 172 - 173 °C; ]H-NMR (DMSO-dó), δ: 13,55 (s, 1H); 10,75 (s, 1H); 8,32 (d, J = 8,1 Hz, 1H); 8,31 (s, 1H); 8,08 (d, J = 9,1 Hz, 1H); 8,04 (dd, J = 8,8 Hz, 2,0 Hz, 1H); 7,92 (d, J = 8,1 Hz, 2H); 7,69 (t, J = 7,6 Hz, 1H); 7,57 - 7,62 (m, 1H); 7,50 (d, J = 8,8 Hz, 1H).λ · L | 4-bromo-3- ^ rlΠlιomlctvl) Phenyl | l1-hvdrc \ ynaftalen-2-carboxamide A (113), yield 33%; mp 172-173 ° C; 1 H-NMR (DMSO-d 6), δ: 13.55 (s, 1H); 10.75 (s, 1 H); 8.32 (d, J = 8.1Hz, 1H); 8.31 (s, 1 H); 8.08 (d, J = 9.1Hz, 1H); 8.04 (dd, J = 8.8 Hz, 2.0 Hz, 1H); 7.92 (d, J = 8.1Hz, 2H); 7.69 (t, J = 7.6Hz, 1H); 7.57 - 7.62 (m, 1H); 7.50 (d, J = 8.8 Hz, 1 H).

Al[2,6-dlbróm-4-(ttrΠuórmetyl)fenyΓ|-1-hydrc\vnaΠtalén-2-karbc?αmlld (114), výťažok 21 %; teplota topenia 183 - 186 °C; ]H-NMR (DMSO-dó), δ: 13,68 (s, 1H); 11,00 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,27 (s, 2H);Al [2,6-dibromo-4- (trifluoromethyl) phenyl] -1-hydronaphthalene-2-carbonylmethyl (114), 21% yield; mp 183-186 ° C; 1 H-NMR (DMSO-d 6), δ: 13.68 (s, 1H); 11.00 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.27 (s, 2 H);

8,11 (d, J = 8,8 Hz, 1H); 7,94 (d, J = 8,3 Hz, 1H); 7,71 (t, J = 7,5 Hz, 1H); 7,58 - 7,63 (m, 1H); 7,52 (d, J = = 8,8 Hz, 1H).8.11 (d, J = 8.8 Hz, 1 H); 7.94 (d, J = 8.3Hz, 1H); 7.71 (t, J = 7.5Hz, 1H); 7.58 - 7.63 (m, 1H); 7.52 (d, J = 8.8 Hz, 1 H).

1-hydrc\v-Al[2-metyl-5-(trlΠuórmetyl)fenyΓ|-naΠtalénl2lkarbc\amld (115), výťažok 24 %; teplota topenia 140 - 143 °C; ]H-NMR (DMSO-de), δ: 13,87 (s, 1H); 10,54 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,09 (d, J = 8,8 Hz, 1H); 7,93 (d, J = 8,1 Hz, 1H); 7,80 (s, 1H); 7,68 (t, J = 7,5 Hz, 1H); 7,56 - 7,62 (m, 3H); 7,49 (d, J = 8,8 Hz, 1H); 2,36 (s, 3H).1-Hydroxy-Al [2-methyl-5- (trifluoromethyl) phenyl] -naphthalen-21-carbamide (115), 24% yield; mp 140-143 ° C; 1 H-NMR (DMSO-d 6), δ: 13.87 (s, 1H); 10.54 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.09 (d, J = 8.8 Hz, 1 H); 7.93 (d, J = 8.1Hz, 1H); 7.80 (s, 1 H); 7.68 (t, J = 7.5Hz, 1H); 7.56 - 7.62 (m, 3H); 7.49 (d, J = 8.8 Hz, 1 H); 2.36 (s, 3H).

1-hvdIΌ\λ-λl·P-IntIΌ-4-ΠnΠlιonηcnvl·Πcnvl|-naftalen-2-kaΓbo\aIηld (116), výťažok 53 %; teplota topenia 222 - 224 °C; ]H-NMR (DMSO-dó), δ: 13,01 (br, s, 1H); 11,57 (s, 1H); 8,43 (s, 1H); 8,35 (d, J = 8,1 Hz, 1H); 8,18 - 8,25 (m, 2H); 8,02 (d, J = 8,8 Hz, 1H); 7,95 (d, J = 8,1 Hz, 1H); 7,71 (t, J = 7,5 Hz, 1H); 7,59 až 7,64 (m 1H); 7,55 (d, J = 8,8 Hz, 1H).1-hvdIΌ \ λ-λ l · β-IntIΌ-4-β-ω-naphthalene-2-naphthalene-2-carboxylic acid (116), yield 53%; mp 222-224 ° C; 1 H-NMR (DMSO-d 6), δ: 13.01 (br, s, 1H); 11.57 (s, 1 H); 8.43 (s, 1 H); 8.35 (d, J = 8.1Hz, 1H); 8.18 - 8.25 (m, 2H); 8.02 (d, J = 8.8 Hz, 1 H); 7.95 (d, J = 8.1Hz, 1H); 7.71 (t, J = 7.5Hz, 1H); 7.59 to 7.64 (m 1H); 7.55 (d, J = 8.8 Hz, 1 H).

1-hvdIΌ\λ-λl·|4-IntIΌ-2-ΠnΠLlonηcnvl·Πcalvl|-naftalen-2-karbo\aIηld (117), výťažok 36 %; teplota topenia 193 - 197 °C; ]H-NMR (DMSO-de), δ: 13,15 (br, s, 1H); 11,23 (s, 1H); 8,61 (dd, J = 8,8 Hz, 1,8 Hz, 1H); 8,55 (d, J = 1,8 Hz, 1H); 8,36 (d, J = 8,1 Hz, 1H); 8,31 (d, J = 9,1 Hz, 1H); 8,06 (d, J = 8,8 Hz, 1H); 7,94 (d, J = 8,1 Hz, 1H); 7,70 (t, J = 7,2 Hz, 1H); 7,59 - 7,64 (m, 1H); 7,54 (d, J = 8,8 Hz, 1H).1-hvdIΌ-λ-λ l · 4-IntiΌ-2-β-α-α-naphthalene-2-carboxylic acid (117), yield 36%; mp 193-197 ° C; 1 H-NMR (DMSO-d 6), δ: 13.15 (br, s, 1H); 11.23 (s, 1 H); 8.61 (dd, J = 8.8 Hz, 1.8 Hz, 1H); 8.55 (d, J = 1.8Hz, 1H); 8.36 (d, J = 8.1Hz, 1H); 8.31 (d, J = 9.1Hz, 1H); 8.06 (d, J = 8.8 Hz, 1 H); 7.94 (d, J = 8.1Hz, 1H); 7.70 (t, J = 7.2Hz, 1H); 7.59 - 7.64 (m, 1H); 7.54 (d, J = 8.8 Hz, 1 H).

1-hvdrc\λ-λl·|4mltrCl3-ΠrlΠlιonηctvlΠcnvl|lnaftalen-2-karbo\amld (118), výťažok 35 %; teplota topenia 193 - 196 °C; ]H-NMR (DMSO-de), δ: 13,24 (br, s, 1H); 11,03 (s, 1H); 8,46 (d, J = 1,4 Hz, 1H); 8,37 (dd, J = 9,1 Hz, J =1,6 Hz, 1H); 8,33 (d, J = 8,3 Hz, 1H); 8,28 (d, J = 8,8 Hz, 1H); 8,08 (d, J = 8,8 Hz, 1H); 7,93 (d, J = 8,1 Hz, 1H); 7,70 (t, J = 7,5 Hz, 1H); 7,58 - 7,63 (m, 1H); 7,52 (d, J = 8,8 Hz, 1H).1-hvdrc-λ-λ 1 · 4mltrCl 3 -PrlPl-3-acyl-lnaphthalene-2-carboxamide (118), yield 35%; mp 193-196 ° C; 1 H-NMR (DMSO-d 6), δ: 13.24 (br, s, 1H); 11.03 (s, 1 H); 8.46 (d, J = 1.4Hz, 1H); 8.37 (dd, J = 9.1 Hz, J = 1.6 Hz, 1H); 8.33 (d, J = 8.3Hz, 1H); 8.28 (d, J = 8.8 Hz, 1 H); 8.08 (d, J = 8.8 Hz, 1 H); 7.93 (d, J = 8.1Hz, 1H); 7.70 (t, J = 7.5Hz, 1H); 7.58 - 7.63 (m, 1H); 7.52 (d, J = 8.8 Hz, 1 H).

L^l^;vdro\v-A-[2-^^t^o\V-5-^(t^]rifl^(^n^^t^;vl)^^^1^iVl]_naftalén^-^2^-k^ai^bc^\amid (119), výťažok 72 %; teplota topenia 158 - 160 °C; ]H-NMR (DMSO-d6), δ: 13,35 (br, s, 1H); 10,58 (s, 1H); 8,34 (d, J = 8,3 Hz, 1H); 8,22 (s, 1H); 8,08 (d, J = 8,8 Hz, 1H); 7,93 (d, J = 8,1 Hz, 1H); 7,68 (t, J = 7,5 Hz, 1H); 7,57 - 7,64 (m, 2H); 7,50 (d, J = 8,8 Hz, 1H); 7,34 (d, J = 8,8 Hz, 1H); 3,97 (s, 3H).L ^ 1 ^; v A - [2 - ^^ t ^ o \ V-5 - ^ (t ^] rifl ^ (^ n ^^ t ^; vl) ^^^ 1 ^ iVl] _on ft a ln (119), 72% yield; mp 158-160 ° C; 1 H-NMR (DMSO-d 6), δ: 13.35 (br, s, 1H); 10.58 (s, 1H); 8.34 (d, J = 8.3 Hz, 1H); 8.22 (s, 1H); 8.08 (d, J = 8.8 Hz, 1H); 1H); 7.93 (d, J = 8.1 Hz, 1H); 7.68 (t, J = 7.5 Hz, 1H); 7.57-7.64 (m, 2H); 50 (d, J = 8.8 Hz, 1H) 7.34 (d, J = 8.8 Hz, 1H) 3.97 (s, 3H).

1-hydrc\v-Al[4-meto\y-3-(tr]lΠuórmetyl)fenyΓ|-naftalén·-2lkarbc\amld (120), výťažok 74 %; teplota topenia 183 - 186 °C; ]H-NMR (DMSO-d6), δ: 13,90 (s, 1H); 10,56 (s, 1H); 8,31 (d, J = 8,3 Hz, 1H); 8,09 (d, J = 8,8 Hz, 1H); 8,03 (s, 1H); 8,00 (d, J = 9,1 Hz, 1H); 7,92 (d, J = 8,1 Hz, 1H); 7,68 (t, J = 7,2 Hz, 1H); 7,56 - 7,61 (m, 1H); 7,48 (d, J = 8,8 Hz, 1H); 7,33 (d, J = 9,1 Hz, 1H); 3,91 (s, 3H).1-hydroxy-N- [4-methyl-3- (tr) trifluoromethyl) phenyl] -naphthalene-2-carbonyl-amide (120), yield 74%; mp 183-186 ° C; 1 H-NMR (DMSO-d 6), δ: 13.90 (s, 1H); 10.56 (s, 1 H); 8.31 (d, J = 8.3Hz, 1H); 8.09 (d, J = 8.8 Hz, 1 H); 8.03 (s, 1 H); 8.00 (d, J = 9.1Hz, 1H); 7.92 (d, J = 8.1Hz, 1H); 7.68 (t, J = 7.2Hz, 1H); 7.56 - 7.61 (m, 1H); 7.48 (d, J = 8.8 Hz, 1 H); 7.33 (d, J = 9.1Hz, 1H); 3.91 (s, 3H).

Príklad 4: Metodika testovania antim^kobaktenálnej účinnosti.Example 4: Methodology for testing antimicobacterial efficacy.

Aktivita pripravených zlúčenín sa testovala in vitro proti Mycobacterium tuberculosis H37Ra ATCC 25177, M. smegmatis ATCC 700084, M. kansasii DSM 44162 a M. marinum CAMP 5644.The activity of the prepared compounds was tested in vitro against Mycobacterium tuberculosis H37Rα ATCC 25177, M. smegmatis ATCC 700084, M. kansasii DSM 44162, and M. marinum CAMP 5644.

M. tuberculosis sa pestuje v bujóne Middlebrook (MB), doplnenom o prídavok OADC (Becton, Dickinson & Comp., Franklin Lakes, NJ, USA) a mykobaktín J (2 pg/ml). Pri logaritmickej rastovej fáze sa vzorka kultúry (10 ml) centnfugovala pri 15.000 ot/min celkovo 20 min pomocou centrifúgy (Model CR 4-12, Jouan Inc., Winchester, VA, USA). Po odstránení supernatantu sa zvyšok premyl v čerstvom bujóne Middlebrook 7H9GC a resuspendoval sa v čerstvom MB doplnenom ODAC (10 ml). Zá kal sa upravil tak, aby vyhovoval norme McFarland č. 1 (3x108 cfu) s MB bujónom Potom sa uskutočnilo ďalšie riedenie kultúry 1 : 20 v MB bujóne. Antimikrobiálna citlivosť M. tuberculosis sa skúmala v 96-jamkovej platničke. V týchto experimentoch sa do všetkých jamiek vonkajšieho obvodu dosiek pridala sterilná deionizovaná voda (300 pl), aby sa minimalizovalo odparovanie média v jamkách počas inkubácie. Každá hodnotená zlúčenina (100 pl) sa nakukovala s M. tuberculosis (100 pl). Zriedenia každej zlúčeniny sa pripravili dvojmo. Pre všetky syntetizované zlúčeniny boli konečné koncentrácie v rozmedzí od 1000 pg/ml do 8 pg/ml. Všetky zlúčen iny sa rozpustili v DMSO (Sigma-Aldrich) (jeho konečná koncentrácia nepresiahla 2,5 %) a následné riedenia sa vykonaliM. tuberculosis is grown in Middlebrook (MB) broth supplemented with the addition of OADC (Becton, Dickinson & Comp., Franklin Lakes, NJ, USA) and mycobactin J (2 pg / ml). In the logarithmic growth phase, a culture sample (10 mL) was centrifuged at 15,000 rpm for a total of 20 min using a centrifuge (Model CR 4-12, Jouan Inc., Winchester, VA, USA). After removal of the supernatant, the residue was washed in fresh Middlebrook 7H9GC broth and resuspended in fresh MB supplemented with ODAC (10 mL). The Base was modified to comply with McFarland standard no. 1 (3x10 8 cfu) with MB broth A further 1: 20 dilution of culture in MB broth was then performed. The antimicrobial susceptibility of M. tuberculosis was examined in a 96-well plate. In these experiments, sterile deionized water (300 µl) was added to all wells of the outer perimeter of the plates to minimize evaporation of the medium in the wells during incubation. Each test compound (100 µl) was pumped with M. tuberculosis (100 µl). Dilutions of each compound were prepared in duplicate. For all synthesized compounds, final concentrations ranged from 1000 pg / ml to 8 pg / ml. All compounds were dissolved in DMSO (Sigma-Aldrich) (its final concentration did not exceed 2.5%) and subsequent dilutions were performed

SK71-2017A3 s použitím doplneného MB. Platne sa uzatvorili parafilmom a inkubovali sa pri 37 °C počas 7 dní. Po inkubácii sa do každej jamky pridalo 10 % alamarBlue (AbD Serotec, Kidlmgton, UK) a merili sa absorbancie pri 570 nm a 600 nm; najskôr pre odčítanie pozadia a následne po 24 h re-inkubácii. Odčítanie pozadia je potrebné pre šibe sfarbené zlúčeniny, kde farba môže narušiť interpretáciu akejkoľvek zmeny farby. Pre neinterferujúce zlúčeniny sa modrá farba v jamke interpretovala ako neprítomnosť rastu a ružová farba sa zaznamenala ako rast.SK71-2017A3 using the added MB. Plates were sealed with parafilm and incubated at 37 ° C for 7 days. After incubation, 10% alamarBlue (AbD Serotec, Kidlmgton, UK) was added to each well and absorbances were measured at 570 nm and 600 nm; first for background reading and after 24 h re-incubation. Background subtraction is required for vividly colored compounds where color may interfere with the interpretation of any color change. For non-interfering compounds, the blue color in the well was interpreted as the absence of growth, and the pink color was recorded as growth.

M. smegmatis, M. kansasii a M. marinum sa kultivovali v médiu Middlebrook 7H9 (DIFC, Lawrence, KS, USA) s prídavkom ADC (Becton, Dickinson & Comp., San Diego, CA, USA). Zlúčeniny sa rozpustili v DMSO (Sigma-Aldrich) a jeho konečná koncentrácia nepresiahla 2,5 % z celkového zloženia roztoku. Konečné koncentrácie hodnotených zlúčenín v rozmedzí od 256 pg/ml do 0,125 pg/ml sa pripravili dvojnásobným sériovým riedením zásobného roztoku v mikrotitračnej doštičke sterilným médiom. Bakteriálne inokulá sa pripravili prenesením kolónií z kultúry do sterilnej vody. Hustota buniek sa upravila na 0,5 McFarland jednotiek denzitometrom (Denso-La-Meter, LIAP, Riga, Lotyšsko). Konečné inokulum sa pripravilo riedením suspenzie v pomere 1 : 1000 sterilnou vodou. Do testovania sa zahrnuli aj kontroly bez lieku, kontroly sterility a kontroly zahŕňajúce médium a samotný DMSO. Stanovenie výsledkov sa vykonalo vizuálne po 3 dňoch statickej inkubácie v tme pn 37 °C v aeróbnom prostredí pre M. smegmatis a po 7 dňoch statickej inkubácie v tme pri 37 °C v aeróbnom prostredí pre M. kansasii a po 21 dňoch statickej inkubácie v tme pn 28 °C v aeróbnom prostredí pre AT. marinum.M. smegmatis, M. kansasii and M. marinum were cultured in Middlebrook 7H9 medium (DIFC, Lawrence, KS, USA) with the addition of ADC (Becton, Dickinson & Comp., San Diego, CA, USA). Compounds were dissolved in DMSO (Sigma-Aldrich) and its final concentration did not exceed 2.5% of the total solution composition. Final concentrations of test compounds ranging from 256 pg / ml to 0.125 pg / ml were prepared by two-fold serial dilutions of the stock solution in the microtiter plate with sterile medium. Bacterial inocula were prepared by transferring colonies from the culture to sterile water. The cell density was adjusted to 0.5 McFarland units with a densitometer (Denso-La-Meter, LIAP, Riga, Latvia). The final inoculum was prepared by diluting the suspension 1: 1000 with sterile water. Drug-free controls, sterility controls, and controls including medium and DMSO alone were also included in the testing. The results were determined visually after 3 days of static incubation at 37 ° C in an aerobic environment for M. smegmatis and after 7 days of static incubation at 37 ° C in an aerobic environment for M. kansasii and after 21 days of static incubation in the dark. pn 28 ° C in aerobic environment for AT. marinum.

Minimálne inhibičné koncentrácie (MIC) látok sa definovali ako najnižšie koncentrácie látok, pri ktorých sa nepozoroval rast mykobakténí. Pre mykobaktérie sa MIC definuje ako 90 % alebo väčšie (IC90) zníženie rastu v porovnaní s kontrolou. Hodnota MIC/IC90 sa rutinne a rozšírené používa v baktenálnych testoch a je štandardným detekčným limiiom podľa „Clinical and Laboratory Standards Inštitúte“ (CLSI, www.clsi.org). Ako štandard sa použil klinicky používaný antimykobaktenálne liečivo izoniazid (Sigma-Aldnch). Výsledky (hodnoty MIC) sú uvedené v Tabuľke 1 (deriváty naftalénu I), Tabuľke 2 (deriváty naftalénu II), Tabuľke 3 (deriváty naftalénu III).Minimum inhibitory concentrations (MICs) of substances were defined as the lowest concentrations of substances at which no growth of mycobactins was observed. For mycobacteria, MIC is defined as a 90% or greater (IC 90) reduction in growth compared to control. The MIC / IC90 value is routinely and widely used in bacterial assays and is the standard detection limit of the Clinical and Laboratory Standards Institute (CLSI, www.clsi.org). The clinically used antifungal agent isoniazid (Sigma-Aldnch) was used as a standard. The results (MIC values) are shown in Table 1 (naphthalene derivatives I), Table 2 (naphthalene derivatives II), Table 3 (naphthalene derivatives III).

Tabuľka 1. Aktivita zlúčenín všeobecného štruktúrneho vzorca (I) proti mvkobaktenáin.Table 1. Activity of compounds of general structural formula (I) against mycobactenain.

Zlúčenina compound MIC [pg/ml] MIC [pg / ml] R R M. tuberculosisH37Ra ATCC 25177 M. tuberculosisH37Ra ATCC 25177 M. smegmatis ATCC 700084 M. smegmatis ATCC 700084 M. kansasii DSM 44162 M. Kansasii DSM 44162 M. marinum CAMP 5644 M. marinum CAMP 5644 1 1 2,6-Cl 2,6-Cl 64 64 64 64 32 32 64 64 2 2 2,6-F 2,6-F 64 64 64 64 32 32 128 128 3 3 2,6-Br 2,6-Br 64 64 64 64 64 64 64 64 4 4 3,5-CFs 3,5--CF 16 16 16 16 4 4 8 8 5 5 2-Cľ-5-CFs 2-Cl-5--CF 16 16 16 16 2 2 8 8 6 6 2,5-Me 2,5-Me >128 > 128 64 64 32 32 32 32 7 7 3,5-Me 3,5-Me 16 16 64 64 32 32 32 32 8 8 3,5-MeO 3,5-MeO 128 128 128 128 32 32 64 64 9 9 2,4-F 2,4-F 128 128 128 128 32 32 64 64 10 10 2,5-F 2,5-F 32 32 32 32 16 16 16 16 11 11 2,3,4-F 2,3,4-F 32 32 16 16 32 32 16 16 12 12 2,4,5-F 2,4,5-F 16 16 4 4 16 16 8 8 13 13 2,3,5,6-F 2,3,5,6-F 64 64 32 32 16 16 64 64 14 14 2,3,4,5,6-F 2,3,4,5,6-F 128 128 >256 > 256 16 16 32 32 15 15 2,3-Cl 2,3-Cl 32 32 32 32 8 8 32 32 16 16 2,4,5-Cl 2,4,5-Cl 8 8 2 2 2 2 1 1 17 17 2,4-CFs 2,4--CF 8 8 16 16 8 8 16 16 18 18 2,5-CFs 2,5--CF 32 32 8 8 8 8 8 8 19 19 3,5-CF3-2-Cl 3,5-CF3-2-Cl 16 16 4 4 1 1 1 1 20 20 2-C1-4-F 2-C1-4-F 32 32 32 32 32 32 64 64 21 21 4-C1-2-F 4-C1-2-F 32 32 16 16 16 16 32 32 22 22 5-C1-2-F 5-C1-2-F 16 16 16 16 16 16 16 16 23 23 2-Br-5-F 2-Br-5-F 32 32 >256 > 256 16 16 32 32 24 24 4-Br-2-F 4-Br-2-F 32 32 32 32 32 32 32 32 25 25 5-Br-2-F 5-Br-2-F 32 32 16 16 8 8 16 16 26 26 2,3,5,6-F-4-Br 2,3,5,6-F-4-Br 64 64 32 32 32 32 32 32 27 27 2-CH-CF3 -CH 2 -CF 3 64 64 64 64 64 64 64 64 28 28 4-Cl-2-CF3 4-Cl-2-CF3 32 32 32 32 32 32 32 32 29 29 4-Cl-3-CF3 4-Cl-3-CF 3 32 32 32 32 32 32 32 32

SK 71-2017 A3A3

Zlúčenina compound MIC [pg/ml] MIC [pg / ml] R R M. tuberculosisH37Ra ATCC 25177 M. tuberculosisH37Ra ATCC 25177 M. smegmatis ATCC 700084 M. smegmatis ATCC 700084 M. kansasii DSM 44162 M. Kansasii DSM 44162 M. marinum CAMP 5644 M. marinum CAMP 5644 30 30 3-F-4-CF3 3-F-4-CF 3 16 16 8 8 16 16 8 8 31 31 3-F-5-CF3 3-F-5-CF 3 8 8 8 8 8 8 8 8 32 32 4-F-2-CF3 4-F-2-CF3 64 64 256 256 256 256 64 64 33 33 4-F-3-CF3 4-F-3-CF 3 64 64 64 64 64 64 64 64 34 34 2-F-3-CF3 2-F-3-CF 3 16 16 16 16 8 8 8 8 35 35 2-F-5-CF3 2-F-5-CF 3 32 32 4 4 4 4 8 8 36 36 2,5-F-4-CF3 2,5-F-4-CF 3 8 8 <2 <2 <2 <2 <2 <2 37 37 4-Br-2-CF3 4-Br-2-CF3 64 64 32 32 32 32 32 32 38 38 2-Br-5-CF3 2-Br-5-CF 3 32 32 4 4 4 4 8 8 39 39 3-Br-5-CF3 3-Br-5-CF 3 32 32 16 16 8 8 16 16 40 40 4-Br-3-CF3 4-Br-3-CF 3 32 32 16 16 16 16 32 32 41 41 2-Me-5-CF3 2-Me-5-CF 3 16 16 8 8 16 16 32 32 42 42 4-Me-3-CF3 4-Me-3-CF 3 16 16 16 16 16 16 16 16 43 43 4-NO2-3-CF34-NO 2 -3-CF 3 32 32 8 8 8 8 16 16 izoniazid isoniazid 8 8 32 32 32 32 64 64

Tabuľka 2. Aktivita zlúčenín všeobecného štruktúrneho vzorca (II) proti mykobakténámTable 2. Activity of compounds of general structural formula (II) against mycobactens

Zlúčeniny compounds MIC [pg/ml] MIC [pg / ml] R R M. tuberculosisH37Ra ATCC 25177 M. tuberculosisH37Ra ATCC 25177 M. smegmatis ATCC 700084 M. smegmatis ATCC 700084 M. kansasii DSM 44162 M. Kansasii DSM 44162 M. marinum CAMP 5644 M. marinum CAMP 5644 44 44 3,5-Cl 3,5-Cl <2 <2 4 4 2 2 2 2 45 45 2,6-F 2,6-F 32 32 128 128 64 64 64 64 46 46 3,5-F 3,5-F 16 16 >256 > 256 32 32 >256 > 256 47 47 3,5-CF3 3,5-CF3 <4 <4 <4 <4 <4 <4 <4 <4 48 48 2-C1-5-CFs 2-C1-5--CF 4 4 32 32 16 16 16 16 49 49 2,6-Me 2,6-Me 16 16 256 256 8 8 64 64 50 50 3,5-Me 3,5-Me 32 32 256 256 16 16 64 64 51 51 3-F-5-MeO 3-F-5-MeO 32 32 >256 > 256 256 256 >256 > 256 52 52 2-F-6-MeO 2-F-6-MeO 8 8 >256 > 256 64 64 16 16 53 53 2-MeO-5-F 2-MeO-5-F 8 8 >256 > 256 >256 > 256 >256 > 256 54 54 3-F-4-Br 3-F-4-Br <2 <2 128 128 32 32 16 16 55 55 2-Br-U1 2-Br-U1 8 8 128 128 64 64 16 16 56 56 3-F-4-CF3 3-F-4-CF 3 <2 <2 2 2 2 2 2 2 57 57 3-CF3-4-F3 3-CF 3-4-F 3 <2 <2 2 2 2 2 2 2 58 58 2-F-5-CF3 2-F-5-CF 3 <2 <2 2 2 2 2 2 2 59 59 4-Br-3-CF3 4-Br-3-CF 3 <2 <2 2 2 2 2 2 2 izoniazid isoniazid 8 8 32 32 32 32 64 64

Tabuľka 3. Aktivita zlúčenín všeobecného štruktúrneho vzorca (III) proti mykobakténám.Table 3. Activity of compounds of general structural formula (III) against mycobactens.

Zlúčeniny compounds MIC [pg/ml] MIC [pg / ml] R R M. kansasii DSM 44162 M. kansasii DSM 44162 M. marinum CAMP 5644 M. marinum CAMP 5644 60 60 2,5-C1 2,5-C1 4 4 64 64 61 61 2,6-C1 2,6-C1 8 8 64 64 62 62 3,4-C1 3,4-C1 8 8 16 16 63 63 3,5-Cl 3,5-Cl 0,5 0.5 <4 <4 64 64 2,6-F 2,6-F 8 8 4 4 65 65 3,5-F 3,5-F 4 4 8 8 66 66 2,6-Br 2,6-Br 8 8 64 64 67 67 3,5-CF3 3,5-CF3 1 1 32 32 68 68 2-C1-5-CF3 2-C1-5-CF3 4 4 <4 <4 69 69 3,5-Me 3,5-Me 8 8 16 16 70 70 2,5-MeO 2,5-MeO 8 8 16 16 71 71 3,5-MeO 3,5-MeO 8 8 32 32 72 72 3-F-5-MeO 3-F-5-MeO 4 4 128 128

SK 71-2017 A3A3

Zlúčeniny compounds MIC [pg/ml] MIC [pg / ml] R R M. kansasii DSM 44162 M. kansasii DSM 44162 M. marinum CAMP 5644 M. marinum CAMP 5644 73 73 2,4-F 2,4-F 16 16 16 16 74 74 3,4-F 3,4-F 8 8 64 64 75 75 2,5-F 2,5-F 16 16 32 32 76 76 2,4,6-F 2,4,6-F 8 8 32 32 77 77 2,3,4-F 2,3,4-F >256 > 256 32 32 78 78 2,4,5-F 2,4,5-F >256 > 256 64 64 79 79 3,4,5-F 3,4,5-F 256 256 128 128 80 80 2,3,5,6-F 2,3,5,6-F 32 32 64 64 81 81 2,4-Cl 2,4-Cl 32 32 64 64 82 82 2,4-CFs 2,4--CF 16 16 8 8 83 83 2,5-CFs 2,5--CF 32 32 64 64 84 84 2-C1-3,5-CFs 2-C1-3,5--CF 16 16 32 32 85 85 3,4,5-MeO 3,4,5-MeO 32 32 16 16 86 86 2,4,6-Me 2,4,6-Me 32 32 64 64 87 87 2-Me-5-MeO 2-Me-5-MeO 32 32 32 32 88 88 2-MeO-5-Me 2-MeO-5-Me 16 16 64 64 89 89 2-MeO-6-Me 2-MeO-6-Me 32 32 64 64 90 90 2-F-3-C1 2-F-3-C1 32 32 64 64 91 91 3-C1-4-F 3-C1-4-F 32 32 64 64 92 92 2-F-4-C1 2-F-4-C1 16 16 64 64 93 93 2-F-S-C1- 2-F-S-C1 16 16 64 64 94 94 2-Br-5-F 2-Br-5-F 32 32 64 64 95 95 2-F-4-Br 2-F-4-Br 32 32 64 64 96 96 3-F-4-Br 3-F-4-Br 8 8 8 8 97 97 2-F-5-Br 2-F-5-Br 16 16 32 32 98 98 3-C1-4-Br 3-C1-4-Br 32 32 32 32 99 99 2,3,5,6-F-4-Br 2,3,5,6-F-4-Br 16 16 32 32 100 100 2-CM-CF3 2-CF3-CM 16 16 16 16 101 101 4-C1-2-CF3 4-C1-2-CF 3 64 64 64 64 102 102 4-C1-3-CF3 4-C1-3-CF 3 16 16 16 16 103 103 2,6-C1-4-CFs 2,6-C1-4--CF 16 16 16 16 104 104 3-F-4-CF3 3-F-4-CF 3 8 8 8 8 105 105 3-F-5-CF3 3-F-5-CF 3 16 16 64 64 106 106 4-F-2-CF3 4-F-2-CF3 32 32 64 64 107 107 4-F-3-CF3 4-F-3-CF 3 16 16 16 16 108 108 2-F-3-CF3 2-F-3-CF 3 64 64 64 64 109 109 2,5-F-4-CF3 2,5-F-4-CF 3 32 32 64 64 110 110 2-Br-5-CF3 2-Br-5-CF 3 8 8 16 16 111 111 3-Br-5-CF3 3-Br-5-CF 3 8 8 8 8 112 112 2-Br-4-CF3 2-Br-4-CF3 16 16 8 8 113 113 4-Br-3-CF3 4-Br-3-CF 3 32 32 32 32 114 114 2,6-Br-4-CF3 2,6-Br-4-CF3 16 16 64 64 115 115 2-Me-5-CF3 2-Me-5-CF 3 32 32 32 32 116 116 2-NO2-4-CF3 2-NO2-4-CF3 8 8 8 8 117 117 4-NO2-2-CF3 4-NO2-2-CF3 16 16 16 16 118 118 4-NO2-3-CF3 4-NO2-3-CF3 8 8 8 8 119 119 2-MeO-5-CF3 2-MeO-5-CF 3 8 8 8 8 120 120 4-MeO-3-CF3 4-MeO-3-CF 3 32 32 32 32 izoniazid isoniazid 32 32 64 64

Claims (6)

PATENTOVÉ NÁROKYPATENT CLAIMS 1. Zlúčeniny podľa vzorca (I) (2-hydrorw.\'-aiy· lnaffalérl---kns0rxamidy j, lén-2-karboxamidy) alebo (III) (l-hydroxy -Λ'-aiylnaftalcn-2-karboxamidv).Compounds according to formula (I) (2-Hydroxy-1'-amino-naphthalene-2-carboxamides), (l'-2-carboxamides) or (III) (1-hydroxy-4'-allynaphthalene-2-carboxamides). (II) (S-^^ydrox^-V-aryhiafta- /(II) (S - (-) - hydroxy-N-aryhiapha-) // kde R sú dva až päť substituentov vybraných zo skupiny: vodík, halogén (fluór, chlór, bróm, jód), alkyl, tiež alkyl substituovaný halogénom alebo halogénmi, alkoxyl s 1 - 3 atómami uhlíka, nitro skupina, na použitie na liečbu f^berk^lózv a ďalších mykobakteriálnych ochorení.// wherein R is two to five substituents selected from the group: hydrogen, halogen (fluorine, chlorine, bromine, iodine), alkyl, also alkyl substituted with halogen or halogens, alkoxy of 1 to 3 carbon atoms, nitro group, for use in therapy fibrosis and other mycobacterial diseases. 2. Zlúčeniny podľa nároku 1 na použitie podľanároku 1, pričom sa potlačírast mykobakténí.Compounds according to claim 1 for use according to claim 1, wherein the growth of mycobactens is suppressed. 3. Farmaceutická kompozícia obsahujúca zlúčeninu podľa nároku 1 v množstve od 0,5 % do 80 % hmotnostných na použitie pre liečbu, kde dochádza k potlačeniu rastu my kobakténí.A pharmaceutical composition comprising the compound of claim 1 in an amount of from 0.5% to 80% by weight for use in a treatment wherein the growth inhibition of my cobactens occurs. 4. Farmaceutická kompozícia podľa nároku 3 vo forme tabliet, kapsúl, práškov, roztokov, suspenzií a injekcií.The pharmaceutical composition of claim 3 in the form of tablets, capsules, powders, solutions, suspensions and injections. 5. Zlúčenina podľa vzorca (I) (2-hydroxy--V-amlmtaftalén-S-karbo?xlmidy), /Compound according to formula (I) (2-hydroxy-N-amtaphthalene-S-carboxamide), kde R je 2,6-dichlórfenyľ, 2,6-fluóraenyľ, 2,6-dibrómfenvl; 2-chlór-5-(tnfluónmetyl)-fenyľ, 2,5-dimctylaenvl·, 3,5-dlmetyaenvľ, .3,5--dmcto\vfen\l·, 2,4-difluórfenyľ, 2,5-dialuórfenyľ, 2,3,4-tnaluóraenvľ, 2,4,5-tnfluórfenyl; 2,3,5,6--etrafluórfenyl; 2,3,4,5,6-pentafluórfenyľ, 2,3-dichlórfenyľ, 2,4,5-trichlórfenvľ, 2,4-bis(tnfluórmetvl)-fenvl; 2,5-biu(tπfluónmetyl)fenyľ, 2-chlór-3,5-bis(trialuórmetyl)fenyľ, 2-chlór-4-fluór-fenyľ, 4-chlór-2 -fluórfcnv ľ, 5-chlór-2-fluóraenyľ, 2-bróm-5-fluórfenyľ, 4-bróm-2-ftuór-fenyľ, 5-bróm-2-aluórfenyľ, 4-bróm-2,3,5,6--e tra-fluórfenyl; 4-chlór-2-(tnfluónmetyl)-fenyľ, 4-chlór-3-(trifluórmetyl)fenyľ, 3sfluórs4s(fπaluórme tyl)fenyl; 3-fluór-5-(tnfluór-InetylJfenvľ, 4-fluór-2-(trialuónmetyl)fenyľ, 4-fluór-3-(tnfluónmetyl)fenyľ, 2-flu ór-3-(tnfluónmetyl)fenyľ, 2-fluór-5-(trifluórmetyl)-fenyľ, 2,5-difluór-4-(tπaluónnetyl)fenvľ, 4sbr0m^-2s(fπalu órmety lfeny 1; 2-bróm-5-(tnfluónmetv lfeny 1; 3 sbróms5s(trialuórmefv lXeny 1; 4sbróms3s(tπfluórmety lfeny 1; 2-metyl-5-(trifluórmetyl)fenyľ, 4-metyl-3-StπSluórrmetyltfenyl a 4-mtro-3-(trifluór-metyl)fenyl.wherein R is 2,6-dichlorophenyl, 2,6-fluoro-phenyl, 2,6-dibromophenyl; 2-chloro-5- (trifluoromethyl) phenyl, 2,5-dimethylamino, 3,5-dimethylamino, 3,5-dimethoxyphenyl, 2,4-difluorophenyl, 2,5-dialfluorophenyl, 2,3,4-trifluoro-phenyl, 2,4,5-trifluorophenyl; 2,3,5,6 - etrafluórfenyl; 2,3,4,5,6-pentafluorophenyl, 2,3-dichlorophenyl, 2,4,5-trichlorophenyl, 2,4-bis (trifluoromethyl) phenyl; 2,5-biu (trifluoromethyl) phenyl, 2-chloro-3,5-bis (trialuoromethyl) phenyl, 2-chloro-4-fluoro-phenyl, 4-chloro-2-fluoro-phenyl, 5-chloro-2-fluoro-phenyl 2-bromo-5-fluorophenyl, 4-bromo-2-fluorophenyl, 5-bromo-2-fluorophenyl, 4-bromo-2,3,5,6-trifluorophenyl; 4-chloro-2- (trifluoromethyl) -phenyl, 4-chloro-3- (trifluoromethyl) phenyl, 3-fluoro-4- (phthalomethyl) phenyl; 3-Fluoro-5- (trifluoromethyl) phenyl, 4-Fluoro-2- (trialuonomethyl) phenyl, 4-Fluoro-3- (trifluoromethyl) phenyl, 2-Fluoro-3- (trifluoromethyl) phenyl, 2-Fluoro-5 - (trifluoromethyl) phenyl, 2,5-difluoro-4- (phthalomethyl) phenyl, 4bromo-2s (phthalomethylphenyl); 2-bromo-5- (trifluoromethylphenyl); trifluoromethylphenyl; 2-methyl-5- (trifluoromethyl) phenyl, 4-methyl-3-trifluoromethylphenyl and 4-methyl-3- (trifluoromethyl) phenyl. 6. Zlúčenina podľa vzorca (II) (3-hydroxvsV-arylnaftalén-2-karboxamidy), Compound of formula (II) (3-hydroxy-N-arylnaphthalene-2-carboxamides), II kde R je 3,5-dichlórfenyľ, 2,6-dialuórfenyľ, 3,5-diInct\|acn\|; 3-fluórr5-metoxy feny l; 2-fluórr6-metoxy feny l; 5-fluór-2-metoxy-fenvľ, 4-bróm-3-aluórfenyľ, 2-bróm-4-chlórfenyľ, 3-fluór-4-(trialuórmetyl)fenvľ, 4sfluórs3s -(tnfluórmetylXenyl; 2-fluór-5-(tπSauórmetyl)fenyl a 4-bróm-3-(1^r^uórmetyl)feny^.II wherein R is 3,5-dichlorophenyl, 2,6-dialfluorophenyl, 3,5-di-ethynyl; 3-fluoro-5-methoxyphenyl; 2-fluoro-6-methoxyphenyl; 5-fluoro-2-methoxyphenyl, 4-bromo-3-fluorophenyl, 2-bromo-4-chlorophenyl, 3-fluoro-4- (trialuoromethyl) phenyl, 4-fluoro-3- (trifluoromethylXenyl), 2-fluoro-5- (trifluoromethyl) phenyl and 4-bromo-3- (1-fluoromethyl) phenyl.
SK71-2017A 2017-07-28 2017-07-28 Use of multi-substituted derivatives of hydroxynaphthalenes as antimycobacterial compounds SK712017A3 (en)

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