LV15002B - Substituted heterocycle [(2-carboxy or -methoxycarbonyl)phenylcarbamoyl-methyl (or trimethylen)]-pyridinium or isoquinolinium bromides as hydroxycarboxylic acid receptor (hca2) family novel class of ligands - Google Patents
Substituted heterocycle [(2-carboxy or -methoxycarbonyl)phenylcarbamoyl-methyl (or trimethylen)]-pyridinium or isoquinolinium bromides as hydroxycarboxylic acid receptor (hca2) family novel class of ligands Download PDFInfo
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Abstract
Description
Izgudrojums attiecas uz bioķīmiju, konkrēti uz heterociklā aizvietotiem [(2-karboksi vai metoksikarbonil)fenilkarbamoil-metil- (vai trimetilēn-)] piridīnija vai izohinolīnija bromīdi kā hidroksikarbonskābju receptoru HCA saimes ligandiem.The invention relates to biochemistry, in particular to heterocyclic-substituted [(2-carboxy or methoxycarbonyl) phenylcarbamoylmethyl (or trimethylene)]] pyridine or isoquinoline bromides as ligands for the HCA family of hydroxycarboxylic acid receptors.
Vielas, kas ietekmē vai modulē šīs saimes receptorus, regulē dažādas svarīgas organisma funkcijas, piemēram, tādas kā lipīdu un cukuru vielmaiņu caur dažādiem mehānismiem. Šī tipa vielas regulē arī organisma pretiekaisuma procesus, organisma masu un holesterīna līmeni. [1, 2], Minētās bioloģiskās funkcijas reflektējas tādās ļoti svarīgās medicīniskās indikācijās kā diabēts, ķermeņa svara regulēšana, holesterīna līmenis asinīs (miokarda infarkts, insults) u.tml.Substances that affect or modulate the receptors in this family regulate various important body functions, such as lipid and sugar metabolism through various mechanisms. These types of substances also regulate the body's anti-inflammatory processes, body weight and cholesterol. [1, 2], These biological functions are reflected in very important medical indications such as diabetes, weight control, blood cholesterol (myocardial infarction, stroke) and so on.
Hidroksikarbonskābju receptoru saimē ietilpst HCAi, HCA2 un HCA3 receptori. Mūsu pētījumi vairāk tika vērsti uz sintezēto savienojumu kā HCA2 receptoru ligandu pētniecību.The hydroxycarboxylic acid receptor family includes the HCA1, HCA2, and HCA3 receptors. Our research focused more on synthesized compounds as ligands for the HCA 2 receptor.
Līdz šim zināmas vairākas HCA2 ligandu ķīmisko struktūru grupas [3]:To date, several groups of chemical structures of HCA 2 ligands are known [3]:
1) nikotīnskābei līdzīgās vielas;1) substances similar to nicotinic acid;
2) pirazoli;2) pyrazoles;
3) acifrāna analogi;3) acifran analogues;
4) antranilskābes atvasinājumi;4) anthranilic acid derivatives;
5) fumārskābes un kanēļskābes atvasinājumi;5) derivatives of fumaric acid and cinnamic acid;
6) piridopirimidīni;6) pyridopyrimidines;
7) pirazolopiridīni.7) pyrazolopyridines.
Tomēr līdz šim praktiski vienīgais līdz klīniskajiem pētījumiem nonākušais savienojums ir pirazola rindas pārstāvis MK0354 [4]. Salīdzinot ar sintezēto potenciālo HCA ligandu daudzumu (kas mērāms tūkstošos), tas ir niecīgs rezultāts. Tāpēc ir būtiski jaunu ligandu struktūru meklējumi.However, to date, practically the only compound that has reached clinical trials is the pyrazole family member MK0354 [4]. Compared to the amount of potential HCA ligands synthesized (measured in thousands), this is a negligible result. Therefore, the search for new ligand structures is essential.
1. TabulaTable 1
Rezultāti attēloti kā vidējais mērījums ± vidējā standartkļūda no 3-5 neatkarīgiem eksperimentiem. Rezultāti atspoguļoti kā forskolīna stimulētā cAMF līmeņa (100%) inhibēšana 50 μΜ liganda (vielas) klātienē.Results are plotted as mean ± standard error of 3-5 independent experiments. Results are shown as inhibition of forskolin-stimulated cAMF level (100%) in the presence of 50 μΜ ligand (substance).
Mūsu pētāmās vielas ir arī antranilskābes analogi, jo satur šo skābi kā vienojošo fragmentu, kas kopīgs visām mūsu struktūrām (skat. 1. Tabulu, savienojumus 1-7). Tai pašā laikā ir struktūrās dominējošs piridīnija katjonās sāls formelements, kas līdz šim šāda tipa savienojumiem nav minēts ne tikai kā ar G-proteīnu saistīto receptoru ligandu sakarā, bet arī kā ķīmiska struktūra ar attiecīgo sekvenci vispār.The substances under study are also analogues of anthranilic acid because they contain this acid as the unifying moiety common to all our structures (see Table 1, compounds 1-7). At the same time, there is a structure-dominant pyridine cationic salt element, which so far has not been mentioned for this type of compound not only as a G protein-coupled receptor ligand, but also as a chemical structure with the corresponding sequence in general.
Tuvākie analogi mūsus savienojumiem ir antranilāti [5, 6], kuri caur linkeri CH2CH2(C=O)- saistīti ar dažādām kondensētām sistēmām ar sēra, skābekļa vai slāpekļa heteroatomiem. Mūsu gadījumā visbūtiskākā atšķirība ir apstāklī, ka kondensētā sistēma ir aizvietotas ar lādētu piridīnija vai hinolīnija aromātisko sistēmu.The closest analogues of our compounds are anthranilates [5, 6], which are linked via various linker CH 2 CH 2 (C = O) to various condensed systems with sulfur, oxygen or nitrogen heteroatoms. In our case the most important difference is that the condensed system is replaced by a charged pyridine or quinoline aromatic system.
Pēc CA galvenās datu bāzes SciFinder pieejamās informācijas vistuvākās struktūras ir antranilāti caur dažādiem linkeriem (piem. -(C=O)-(C=O)-, -CH2CH2(C=O)u.tml.) saistīti ar dažādām sistēmām ar pārejas tiltu: linkeris—NH-. Būtiskākā atšķirība ir apstāklī, ka mūsu savienojumu 1-7 gadījumā saistība ir caur N+ lādētu un vēl pie tam aromātisku sistēmu NH grupas vietā.According to the information available in CA's main SciFinder database, the closest structures are anthranilates via various linkers (eg - (C = O) - (C = O) -, -CH 2 CH 2 (C = O), etc.) linked to different for bridge systems: linker-NH-. The main difference is that in the case of our compounds 1-7, the bond is via an N + -charged and additionally aromatic system instead of the NH group.
Tādēļ jāsecina, ka savienojumi 1-7 ir jauna GPCR HCA2 receptora ligandu klase, kā arī oriģināli savienojumi.Therefore, it can be concluded that compounds 1-7 are a new class of GPCR HCA 2 receptor ligands as well as the original compounds.
Lādētā aromātiskā sistēma ir būtisks jaunuma elements, jo principiāli atšķiras no neitrālām sistēmām, lādiņš var būtiski ietekmēt polāro receptora virsmu un ievērojami modificēt biopiesaistes un receptoru kā pārvades sistēmas funkcijas.Charged aromatic system is an important element of novelty, as it is fundamentally different from neutral systems, charge can significantly influence the polar receptor surface and significantly modify the functions of bio-binding and receptor as a transmission system.
Tā kā HCA receptoru ligandi veic daļu no fizioloģiskajām funkcijām, inhibējot adenilātciklāzi, tad to funkcionālā aktivitāte tika pārbaudīta ar intracelulārā cAMF līmeņa noteikšanas metodi, izmantojot LANCE™ cAMF kitu. cAMF līmeņa izmaiņas tika mērītas receptorus stabili ekspresējošās cilvēka HCAiR-Flp-ln 293, HCA2R-Flp-In 293 un HCA3R-Flp-In 293 šūnu līnijās 3 μΜ forskolīna klātbūtnē, kas paaugstina šūnu bazālo cAMF līmeni. Ligandi 1-7 uzrāda augstu selektivitāti attiecībā uz cilvēka HCA2 receptoru salīdzinot ar HCAļ un HCA3 receptoriem.Because HCA receptor ligands perform some of the physiological functions by inhibiting adenylate cyclase, their functional activity was tested by the intracellular cAMF assay using the LANCE ™ cAMF kit. cAMP level changes were measured receptors stably expressing human HCAiR-Phil-l n 293, HCA 2 R-Phil-I n 293 and HCA 3 R-Phil-I n 293 cell lines 3 μΜ forskolin in the presence of which increases cell basal cAMP levels. Ligands 1-7 show high selectivity for the human HCA 2 receptor compared to HCA 1 and HCA 3 .
Izgudrojuma izpildes piemēriExamples of Execution of the Invention
5-Aminoizohinolīnija bromīdu 1-3 sintēzes vispārējais apraksts. 5-Aminoizohinolīnu (3.5 mmol) suspendē acetonitrilā vai butān-2-onā (5ml), maisot pievieno ekvimolāru daudzumu alkilējošā aģenta un turpina maisīt, kamēr novēro izejvielu izšķīšanu un produkta izgulsnēšanos. Produktu filtrē un uz filtra mazgā ar acetonitrilu vai butān-2-onu.General description of the synthesis of 5-aminoisoquinoline bromides 1-3. Suspend 5-aminoisoquinoline (3.5 mmol) in acetonitrile or butan-2-one (5 ml) with stirring, add an equimolar amount of the alkylating agent and continue stirring until dissolution of the starting materials and product precipitation are observed. The product is filtered and washed with acetonitrile or butan-2-one on the filter.
1. Piemērs. 5-Amino-2-{2-[(2-karboksifenil)amino]-2-oksoetil}izohinolīnija bromīdu (1) iegūst no 2-(2-bromacetilamino)benzoskābes ar 56% iznākumu. K.t. 226 °C. 1H KMR (400 MHz, DMSO-de) δ: 5,71 (s, 2H), 6,66 (s, 2H), 6,97 (m, 1H), 7,24 (m, 2H), 7,60 (m, 1H), 7,77 (m, 1H), 7,96 (m, 2H), 8,33 (m, 1H), 8,63 (s, 2H), 9,83 (s, 1H) m.d. LC-MS (ESI+), m/z; 322 ([M-Brf, 84).1. Example. 5-Amino-2- {2 - [(2-carboxyphenyl) amino] -2-oxoethyl} isoquinoline bromide (1) is obtained from 2- (2-bromoacetylamino) benzoic acid in 56% yield. Mp 226 ° C. 1 H NMR (400 MHz, DMSO-d 6) δ: 5.71 (s, 2H), 6.66 (s, 2H), 6.97 (m, 1H), 7.24 (m, 2H), 7 , 60 (m, 1H), 7.77 (m, 1H), 7.96 (m, 2H), 8.33 (m, 1H), 8.63 (s, 2H), 9.83 (s, 1H) md LC-MS (ESI +), m / z; 322 ([M-Brf, 84).
2. Piemērs. 5-Amino-2-{2-[2-(2-metoksikarbonilfenil)amino]-2-oksoetil}izohinoiīnija bromīdu (2) iegūst no 2-(2-bromacetilamino)benzoskābes metilestera ar 93% iznākumu. K.t. 237-239 °C. 1H KMR (400 MHz, DMSO-d6) δ: 3,87 (s, 3H), 5,79 (s, 2H), 6,69 (s, 2H), 7,31 (m, 2H), 7,64 (m, 2H), 7,78 (m, 1H), 7,96 (m, 2H), 8,63 (m, 2H), 9,82 (s, 1H), 10,97 (s, 1H) m.d. LC-MS (ESI+), m/z; 336 ([M-Brf, 100).2. Example. 5-Amino-2- {2- [2- (2-methoxycarbonylphenyl) amino] -2-oxoethyl} isoquinolinium bromide (2) is obtained from 93% yield of 2- (2-bromoacetylamino) benzoic acid methyl ester. Mp 237-239 ° C. 1 H NMR (400 MHz, DMSO-d 6 ) δ: 3.87 (s, 3H), 5.79 (s, 2H), 6.69 (s, 2H), 7.31 (m, 2H), 7.64 (m, 2H), 7.78 (m, 1H), 7.96 (m, 2H), 8.63 (m, 2H), 9.82 (s, 1H), 10.97 (s) , 1H) md LC-MS (ESI +), m / z; 336 ([M-Brf, 100).
3. Piemērs. 5-Amino-2-{4-[2-(2-metoksikarbonilfenil)amino]-4-oksobutil}izohinolīnija bromīdu (3) iegūst no 2-(4-brombutānamīdo)benzoskābes metilestera ar 38% iznākumu. K.t. 218-220 °C. 1H KMR (400 MHz, DMSO-d6) δ: 2,36 (t, J = 6,6 Hz, 2H), 2,54 (m, 2H), 3,85 (s, 3H), 4,72 (t, J = 6,6 Hz, 2H), 6,62 (s, 2H), 7,24 (m, 2H), 7,54 (m, 2H), 7,71 (m, 1H), 7,87 (m, 1H), 8,04 (m, 2H), 8,63 (m, 2H), 9,85 (s, 1H), 10,53 (s, 1H) m.d. LC-MS (ESI-*-), m/z; 364 ([M-Brf, 100).Example 3. 5-Amino-2- {4- [2- (2-methoxycarbonylphenyl) amino] -4-oxobutyl} isoquinolinium bromide (3) is prepared from 2- (4-bromobutanamide) benzoic acid methyl ester in 38% yield. Mp 218-220 ° C. 1 H NMR (400 MHz, DMSO-d 6 ) δ: 2.36 (t, J = 6.6 Hz, 2H), 2.54 (m, 2H), 3.85 (s, 3H), 4, 72 (t, J = 6.6 Hz, 2H), 6.62 (s, 2H), 7.24 (m, 2H), 7.54 (m, 2H), 7.71 (m, 1H), 7.87 (m, 1H), 8.04 (m, 2H), 8.63 (m, 2H), 9.85 (s, 1H), 10.53 (s, 1H) md LC-MS (ESI) - * -), m / z; 364 ([M-Brf, 100).
3-Karboksi- vai 3-etoksikarbonilpiridīnija bromīdu 4-6 sintēzes vispārējais aprakstsGeneral Description of Synthesis of 3-Carboxy- or 3-Ethoxycarbonylpyridinium Bromides 4-6
Nikotīnskābi vai tās etilesteri (2 mmol) un alkilējošo aģentu (2 mmol) 24 stundas maisa ar 2 ml DMF ampulā argona atmosfērā 50 °C temperatūrā. Reakcijas maisījumu ietvaicē pazeminātā spiedienā, atlikumu saberž ar sausu acetonu. Filtrē, kristalizē no acetona/etilspirta maisījuma.Nicotinic acid or its ethyl ester (2 mmol) and alkylating agent (2 mmol) are stirred for 24 hours in a 2 ml ampoule of DMF at 50 ° C under argon. The reaction mixture is evaporated under reduced pressure and the residue is triturated with dry acetone. Filter, crystallize from acetone / ethyl alcohol.
4. Piemērs. 3-Karboksi-1-[(2-metoksikarbonil-fenilkarbamoil)-metil]-piridīnija bromīdu (4) iegūst no nikotīnskābes un 2-(2-bromacetilamino)benzoskābes metilestera ar 83% iznākumu. K.t. 217 °C (sad.). 1H KMR (400 MHz, DMSO-d6): 3,86 (s, 3H); 5,89 (s, 2H); 7,29 (t, J = 7,2 Hz, 1H); 7,64 (t, J = 7,2 Hz, 1H); 7,91 (d, J = 8,0 Hz, 1H); 7,97 (d, J = 8,0 Hz, 1H); 8,34-8,38 (m, 1H); 9,07 (d, J = 8,4 Hz, 1H); 9,25 (d, J = 6,0 Hz, 1H); 9,62 (s, 1H); 10,96 (s, 1H) m.d. LC-MS (ESI+), m/z; 301 ([Mf, 100).4. Example. 3-Carboxy-1 - [(2-methoxycarbonyl-phenylcarbamoyl) -methyl] -pyridinium bromide (4) is obtained from nicotinic acid and 2- (2-bromoacetylamino) benzoic acid methyl ester in 83% yield. Mp 217 ° C (sat). 1 H NMR (400 MHz, DMSO-d 6 ): 3.86 (s, 3H); 5.89 (s, 2H); 7.29 (t, J = 7.2 Hz, 1H); 7.64 (t, J = 7.2 Hz, 1H); 7.91 (d, J = 8.0 Hz, 1H); 7.97 (d, J = 8.0 Hz, 1H); 8.34-8.38 (m, 1H); 9.07 (d, J = 8.4 Hz, 1H); 9.25 (d, J = 6.0 Hz, 1H); 9.62 (s, 1H); 10.96 (s, 1H) md LC-MS (ESI +), m / z; 301 ([Mf, 100).
5. Piemērs. 3-Etoksikarbonil-1 -[(2-metoksikarbonilfenilkarbamoil)-metil]-piridīnija bromīdu (5) iegūst no nikotīnskābes etilestera un 2-(2-bromacetilamino)benzoskābes metilestera ar 66% iznākumu. K.t. 173 °C. 1H KMR (400 MHz, DMSO-d6): 1,38 (t, J =7,2 Hz, 3H); 3,87 (s, 3H); 4,45 (k, J =7,2 Hz, 2H); 5,90 (s, 2H); 7,30 (t, J =7,6 Hz, 2H); 7,627,66 (m, 1H); 7,91 (d, J = 7,6 Hz, 1H); 7,97 (d, J = 7,6 Hz, 1H); 8,37-8,41 (m, 1H); 9,10 (d, J = 8,4 Hz,1H); 9,28 (d, J = 6,4 Hz, 1H); 9,66 (s,1H); 10,97 (s, 1H) m.d. LC-MS (ESI+), m/z; 343 ([Mf, 100).5. Example. 3-Ethoxycarbonyl-1 - [(2-methoxycarbonylphenylcarbamoyl) -methyl] -pyridinium bromide (5) is obtained from ethyl ester of nicotinic acid and methyl ester of 2- (2-bromoacetylamino) benzoic acid in 66% yield. Mp 173 ° C. 1 H NMR (400 MHz, DMSO-d 6 ): 1.38 (t, J = 7.2 Hz, 3H); 3.87 (s, 3H); 4.45 (k, J = 7.2 Hz, 2H); 5.90 (s, 2H); 7.30 (t, J = 7.6 Hz, 2H); 7.627.66 (m, 1H); 7.91 (d, J = 7.6 Hz, 1H); 7.97 (d, J = 7.6 Hz, 1H); 8.37-8.41 (m, 1H); 9.10 (d, J = 8.4 Hz, 1H); 9.28 (d, J = 6.4 Hz, 1H); 9.66 (s, 1H); 10.97 (s, 1H) md LC-MS (ESI +), m / z; 343 ([MH], 100).
6. Piemērs. 3-Karboksi-1-[(2-karboksi-fenilkarbamoil)-metil]piridīnija bromīdu (6) iegūst no nikotīnskābes un 2-(2-bromacetilamino)benzoskābes ar 92% iznākumu. K.t. 205-210 °C (sad.). 1H KMR (400 MHz, DMSO-d6): 3,86 (s, 3H), 5,89 (s, 2H), 7,29 (t, J = 7,2 Hz, 1H), 7,64 (t, J = 7,2 Hz, 1H), 7,91 (d, J = 8,0 Hz, 1H), 7,97 (d, J = 8,0 Hz, 1H), 8,34-8,34 (m, 1H), 9,07 (d, J = 8,4 Hz, 1H), 9,25 (d, J = 6,0 Hz, 1H), 9,62 (s, 1H), 10,96 (s, 1H) m.d. LC-MS (ESI+), m/z: 301 ([M]+, 100).6. Example. 3-Carboxy-1 - [(2-carboxy-phenylcarbamoyl) -methyl] -pyridinium bromide (6) is obtained from nicotinic acid and 2- (2-bromoacetylamino) benzoic acid in 92% yield. Mp 205-210 ° C (sat.). 1 H NMR (400 MHz, DMSO-d 6 ): 3.86 (s, 3H), 5.89 (s, 2H), 7.29 (t, J = 7.2 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 8.34-8 , 34 (m, 1H), 9.07 (d, J = 8.4 Hz, 1H), 9.25 (d, J = 6.0 Hz, 1H), 9.62 (s, 1H), 10 , 96 (s, 1H) md LC-MS (ESI +), m / z: 301 ([M] + , 100).
7. Piemērs. 3-{2,6-Dimetil-3,5-bis[(1-etoksikarbonil-1-metil)etoksikarbonil]-1,4-dihidropiridīn-4-il}-1-[(2-karboksifenil)karbamoilmetil]piridīnija bromīdu (7) iegūst ar 74% iznākumu no 4-(3-piridil)-2,6-dimetii-3,5-bis[(1 -etoksikarbonil-1 -metil)etoksikarbonil]-1,4dihidropiridīna (1 mmol) un 2-(2-bromacetilamino)benzoskābes (1mmol), tos izšķīdinot 15 ml acetona un dzidro šķīdumu 24 stundas maisot 40 °C temperatūrā. Reakcijas maisījumu atdzesē 2 stundas ledus skapī un filtrē bāli dzeltenās nogulsnes, kuras mazgā ar aukstu acetonu un dietilēteri. K.t. 174-176 °C. 1H KMR (400 MHz, DMSO-d6): 0,92 (t, J = 7,0 Hz, 6H); 1,36 (s, 6H); 1,44 (s, 6H); 2,29 (s, 6H); 3,90-4,01 (kv, J = 7,0 Hz , 4H); 4,99 (s, 1H); 5,87 (s, 2H); 7,21-7,25 (m, 1H); 7,60-7,64 (m, 1H); 8,01-8,04 (m, 1H); 8,16-8,19 (m, 1H); 8,29-8,31 (m, 1H); 8,46-8,49 (m, 1H); 8,37 (s, 1H); 8,87-8,89 (m, 1H); 11,46 (s, 1H) m.d. LC-MS (ESI+), m/z: 680 ([Mf, 100).7. Example. 3- {2,6-Dimethyl-3,5-bis [(1-ethoxycarbonyl-1-methyl) ethoxycarbonyl] -1,4-dihydropyridin-4-yl} -1 - [(2-carboxyphenyl) carbamoylmethyl] pyridinium bromide (7) obtained in 74% yield from 4- (3-pyridyl) -2,6-dimethyl-3,5-bis [(1-ethoxycarbonyl-1-methyl) ethoxycarbonyl] -1,4-dihydropyridine (1 mmol) and 2 - (2-Bromoacetylamino) benzoic acid (1 mmol) by dissolving them in 15 ml of acetone and stirring the solution at 40 ° C for 24 hours. The reaction mixture is cooled in a refrigerator for 2 hours and filtered off with a pale yellow precipitate which is washed with cold acetone and diethyl ether. Mp 174-176 ° C. 1 H NMR (400 MHz, DMSO-d 6 ): 0.92 (t, J = 7.0 Hz, 6H); 1.36 (s, 6H); 1.44 (s, 6H); 2.29 (s, 6H); 3.90-4.01 (kv, J = 7.0 Hz, 4H); 4.99 (s, 1H); 5.87 (s, 2H); 7.21-7.25 (m, 1H); 7.60-7.64 (m, 1H); 8.01 - 8.04 (m, 1H); 8.16-8.19 (m, 1H); 8.29-8.31 (m, 1H); 8.46-8.49 (m, 1H); 8.37 (s, 1H); 8.87-8.89 (m, 1H); 11.46 (s, 1H) md LC-MS (ESI +), m / z: 680 ([M] +, 100).
Rezultāti un secinājumiResults and conclusions
1. Heterociklā aizvietoti [(2-karboksi vai metoksikarbonil)fenilkarbamoil-metil- (vai trimetilēn-)] piridīnija vai izohinolīnija bromīdi 1-7 ir ne tikai oriģināli savienojumi, bet arī jauna HCA2 receptora ligandu klase.1. Heterocyclic-substituted [(2-carboxy or methoxycarbonyl) phenylcarbamoylmethyl (or trimethylene)] pyridine or isoquinoline bromides 1-7 are not only the original compounds, but also a novel class of HCA 2 receptor ligands.
2. Savienojumi 1-7 kā ligandi neiedarbojas vai iedarbojas vāji uz HCA3 receptoru, kas liecina par selektivitāti. Tas var būt būtisks faktors medicīnas preparātu pētniecībai.2. Compounds 1-7 as ligands have no or little effect on the HCA 3 receptor, indicating selectivity. This can be an important factor in medical drug research.
3. Savienojums satur linkera-lādēta aromātiska heterocikliska sistēmu — , kas nodrošina ne tikai bioloģisko selektivitāti attiecībā uz HCA2 receptoru, bet arī kā struktūr elements nodrošina savienojumus 1-7 kā jaunas HCA2 ligandu grupas novitāti.3. The compound contains a linker-charged aromatic heterocyclic system that not only provides biological selectivity for the HCA 2 receptor but also, as a structural element, provides compounds 1-7 as a novelty of a novel group of HCA 2 ligands.
LiteratūraLiterature
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