RU2021110751A - ANTIVIRALS FOR THE TREATMENT AND PREVENTION OF HIV INFECTION - Google Patents

Claims (158)

1. Compound of formula I

where R1 is independently selected and is H, CN, CN-CH=CH-, C=O, CH=CH-COOH, substituted or unsubstituted 4-6 membered heterocyclyl containing 1-2 O heteroatoms; aminocarbonyl; _NH2 ; substituted or unsubstituted C _1-6 alkyl; halogen; substituted or unsubstituted C _1-6 alkyloxy; NHR ⁹ ; NR ⁹ R ¹⁰ ; -C(=O)-NHR ⁹ ; -C(=O)-NR ⁹ R ¹⁰ ; -C(=O)-R ⁹ ; -CH=N-NH-C(=O)-R ⁹ ; substituted or unsubstituted C _1-6 alkyloxyC _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl; substituted or unsubstituted C _2-6 alkynyl; -C(=NOR ⁸ )-C _1-4 alkyl; R ⁷ and -Rb-R ⁷ ; X ¹ , X ² are a substituent of the form (CH ₂ ) _n , with n being chosen independently for X ₁ , X ₂ ; Y ¹ is selected independently and represents -O-, -S-, -S(=O)-, -S(=O) ₂ -, or substituents of the form

or

R ^b is independently selected and is -H, cyano, aminocarbonyl, substituted or unsubstituted -C ₁ -C ₆ -alkyl, substituted or unsubstituted -C 2 -C ₆ -alkenyl, substituted or unsubstituted -C 2 -C ₆ alkynyl, substituted or unsubstituted -C ₃ -C ₆ -aryl, substituted or unsubstituted 4-6-membered heteroaryl containing from 1 to 4 heteroatoms independently selected from N, S and/or O, substituted or unsubstituted -C ₃ -C ₉ -cycloalkyl , a substituted or unsubstituted 4-9 membered heterocyclyl containing from 1 to 4 heteroatoms independently selected from N, S and/or O, R ⁷ or R ⁹ , where Rb can be attached to the rest of the molecule through a linker of the form (CH ₂ ) _n , R ⁷ is a monocyclic, bicyclic or tricyclic, saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic, saturated, partially saturated or aromatic 4-6 membered heterocycle containing from 1 to 4 heteroatoms independently selected from the group S, N and O, where each of the mentioned carbocyclic or heterocyclic fragments may be optionally substituted with one, two, three, four or five substituents, each independently selected from halogen, hydroxy, mercapto, C _1-6 alkyl, hydroxyC _1-6 alkyl , aminoC _1-6 alkyl, mono- and di(C _1-6 alkyl)aminoC _1-6 alkyl, formyl, C _1-6 alkylcarbonyl, C _3-7 cycloalkyl, C _1-6 alkyloxy, C _1-6 alkyloxycarbonyl, C _1-6 alkylthio, cyano, nitro, polyhaloC _1-6 alkyl, polyhaloC _1-6 alkyloxy, aminocarbonyl, -C(=NOR ⁸ ), R ^7a , -Rb-R ^7a , and R ^7a -C _1-4 alkyla ; R ^7a is a monocyclic, bicyclic or tricyclic, saturated, partially saturated or aromatic carbocycle or a monocyclic, bicyclic or tricyclic, saturated, partially saturated or aromatic 4-6 membered heterocycle containing from 1 to 4 heteroatoms independently selected from the group S, N and O, wherein each of said carbocyclic or heterocyclic moieties may be optionally substituted with one, two, three, four or five substituents each independently selected from halo, hydroxy, mercapto, C _1-6 alkyl, hydroxyC _1-6 alkyl , aminoC _1-6 alkyl, mono- or di(C _1-6 alkyl)aminoC _1-6 alkyl, formyl, C _1-6 alkylcarbonyl, C _3-7 cycloalkyl, C _1-6 alkyloxy, C _1-6 alkyloxycarbonyl, C _1-6 alkylthio, cyano, nitro, polyhaloC _1-6 alkyl, polyhaloC _1-6 alkyloxy, aminocarbonyl and -CH(=NOR ⁸ ); R ⁸ is hydrogen, C _1-4 alkyl, aryl or arylC _1-4 alkyl; each of R ⁹ and R ¹⁰ independently represents hydrogen; cyano, aminocarbonyl, hydroxy; C _1-6 alkyl; C _1-6 alkyloxy; C _1-6 alkylcarbonyl; C _1-6 alkyloxycarbonyl; amino; mono- or di(C _1-6 alkyl)amino; mono- or di(C _1-6 alkyl)aminocarbonyl; -CH(=NR ¹¹ ) or R ⁷ , wherein each of the above C _1-6 alkyl groups may optionally be substituted with one or two substituents each independently selected from hydroxy, C _1-6 alkyloxy , hydroxyC _1-6 alkyloxy, carboxyl, C _1-6 alkyloxycarbonyl, cyano, amino, aminocarbonyl, imino, mono- and di(C _1-4 alkyl)amino, polyhalomethyl, polyhalomethyloxy; polyhalomethylthio, -S(=O) _p R ⁸ , -NH-S(=O) _p R ⁸ , -C(=O)R ⁸ , -NHC(=O)H, -C(=O)NHNH ₂ , NHC(=O)R ⁸ , C(=NH)R ⁸ or R ^7, where the substituents R1, Rb are each independently selected from the group consisting of: COO-isobutyl, OH, CN, NH ₂ , C1-4-alkoxy, C1-4alkyl, 4-6-membered heteroaryl containing from 1 to 4 heteroatoms, independently selected from the group S, N and O, wherein said heteroaryl is unsubstituted or substituted with CN, NH ₂ , OH, C1-6 alkyl, O or R ^c ; BOC, COOH, R ^c , C3-6-aryl, optionally substituted with CN, NH2, OH, O or OCH2C≡CH, 4-6 membered heterocyclyl containing 1-3 heteroatoms selected from N, S and O, O, N, S-C1-6-alkyl, halogen, NR ⁹ R ¹⁰ , -C(=O)-NR ⁹ R ¹⁰ , -C(=O)-C _1-6 alkyl; R ^c is NHCOO-C1-6-alkyl; n can take values from 1 to 3; for use as a reverse transcriptase inhibitor. 2. Connection according to claim 1, where R1 is independently selected and is H, CN, CN-CH=CH, C=O, CH=CH-COOH, 4-6 membered heterocyclyl containing 1-2 O heteroatoms; R ^b is chosen independently and is: -H, substituted or unsubstituted -C ₁ -C ₆ -alkyl, substituted or unsubstituted -C ₁ -C ₆ -alkenyl, substituted or unsubstituted -C ₃ -C ₆ -aryl, substituted or unsubstituted -5-6-membered heteroaryl containing from 1 to 4 heteroatoms independently selected from N, S and/or O, substituted or unsubstituted -C ₃ -C ₉ -cycloalkyl, or substituted or unsubstituted 4-9 membered heterocyclyl containing 1 to 4 heteroatoms independently selected from N, S and/or O, wherein said Rb substituents are each independently selected from the group consisting of COO-isobutyl, _NH2 , CN, C1-4-alkoxy, 4-6-membered heteroaryl containing from 1 to 4 heteroatoms independently selected from the group S, N and O, while the specified heteroaryl is unsubstituted or substituted by OH, C1-6-alkyl, O or Rc; WOC; COOH; R ^c ; C3-6-aryl, possibly substituted by OH, O or OCH ₂ C≡CH, 4-6-membered heterocyclyl containing 1-2 heteroatoms selected from N and O, Oh N S-C1-6-alkyl, halogen, The remaining radicals are as defined in paragraph 1. 3. The compound of claim 1 wherein R ¹ is independently selected and is H, -CN, -CH=CH-CN, -C=O, or -CH=CH-COOH. 4. The compound of claim 1 wherein R ¹ is independently selected and is a 4-6 membered heterocyclyl containing 1-2 O heteroatoms. 5. A compound according to claim 3 wherein R ¹ is oxetane, tetrahydrofuran or tetrahydropyran. 6. The compound according to claim 1, wherein Y ¹ is -O-, -S-, -S(=O)- or -S(=O) ₂ -. 7. The compound according to p. 1 in which Y ¹ represents substituents of the form

or

8. The compound according to claim 1, in which Y ¹ represents substituents of the form

or

9. The compound of claim 1 wherein Rb is substituted or unsubstituted methyl, ethyl, propyl, n-propyl, isopropyl, butyl, n-butyl, sec-butyl, t-butyl, or pentyl, wherein the substituents are as follows: defined in paragraph 1. 10. The compound of claim 1 wherein Rb is substituted or unsubstituted ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 2-methyl- 2-propenyl, where the substituents are as defined in paragraph 1. 11. The compound of claim 1 wherein Rb is substituted or unsubstituted phenyl, where the substituents are as defined in claim 1. 12. The compound of claim 1 wherein Rb is substituted or unsubstituted thienyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, triazinyl, tetrazolyl, benzo[b]thienyl, isobenzofuranyl, isoindolyl, benzimidazolyl, where the substituents are , as defined in paragraph 1. 13. The compound of claim 1, wherein Rb is substituted or unsubstituted cyclopropyl, cyclopentyl, cyclohexyl, bicyclo[2.2.2]octanyl, spiro[5.5]undecanyl, where the substituents are as defined in claim 1. 14. The compound of claim 1 wherein Rb is a substituted or unsubstituted pyrimidine, piperidine, azetidine, morpholine, piperazine, pyrrolidine, tetrahydropyran, furan, pyrrole, pyrazine, imidazole, or pyrazole. 15. The compound according to claim 1, in which Y ¹ represents substituents of the form

Rb is a substituted or unsubstituted -5÷6-membered heteroaryl or heterocyclyl containing from 1 to 4 heteroatoms independently selected from N, S and/or O, where the substituents are defined in paragraph 1. 16. The compound according to claim 1, in which Y ¹ represents substituents of the form

or

Rb is substituted or unsubstituted -C ₃ -C ₆ -aryl or substituted or unsubstituted -C ₃ -C ₉ -cycloalkyl, where the substituents are defined in paragraph 1. 17. The compound according to claim 1, selected from: 4-((4-(2,6-dimethylphenoxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)amino)-benzonitrile 4-(2,6-dimethylphenoxy)-N-(piperidin-4-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine 4-(((6-benzyl-4-(4-cyano-2,6-dimethylphenoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)amino)methyl ethyl ester ) benzoic acid 4-(((6-Benzyl-4-(2,6-dimethylphenoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)amino)methyl)benzoic acid ethyl ester 4-(((7-Benzyl-4-(2,6-dimethylphenoxy)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)amino)methyl)benzonitrile N-(1-benzylpiperidin-4-yl)-4-(2,6-dimethylphenoxy)-5,6,7,8-tetrahydroquinazolin-2-amine N-(1-benzylpiperidin-4-yl)-4-(2,6-dimethylphenoxy)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-amine 4-((2-((4-cyanophenyl)amino)-7-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile 4-((4-(4-Formyl-2,6-dimethylphenoxy)-7-methyl-5,6,7,8-tetrahydro[3,4-d]pyrimidin-2-yl)amino)benzonitrile tert-Butyl 4-(4-(1,3-dioxalan-2-yl)-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-8,9-dihydro-5H-pyrimido[4, 5-d]azepine-7(6Н)-carboxylate tert-Butyl 2-((4-cyanophenyl)amino)-4-(4-formyl-2,6-dimethylphenioxy)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H) -carboxylate tert-Butyl 4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate 4-((2-((4-Cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(methylsulfonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)-3,5- dimethylbenzonitiryl ethyl 4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate (E)-3-(4-((7-(tert-Butoxycarbonyl)-2-((4-cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d] azepin-4-yl)oxy)-3,5-dimethylphenyl)acrylic acid tert-Butyl 4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7(6H) -carboxylate 4-((2-((4-Cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)oxy)-3,5-dimethylbenzonitrile tert-Butyl 2-((4-cyanophenyl)amino)-4-(4-(2-cyanovinyl)-2,6-dimethylphenoxy)-8,9-dihydro-5H-pyrimido[4,5-d]azepin- 7(6H)-carboxylate 4-((2-((4-Cyanophenyl)amino)-7-picolinoyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)oxy)-3, 5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-isonicotinoyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)oxy)-3, 5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-nicotinoyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)oxy)-3, 5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(pyridin-2-ylmethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl )hydroxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(pyridin-3-ylmethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl )hydroxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(pyridin-4-ylmethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl )hydroxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl)oxy)-3,5-d imethyl benzonitrile tert-Butyl 4-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-gyrimido[4,5-d ]azein-7-carbonyl)piperidine-1-carboxylate 4-((2-((4-Cyanophenyl)amino)-7-(piperidine-4-carbonyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl )hydroxy)-3,5-dimethylbenzonitrile tert-Butyl 4-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-8,9-dihydro-5H-pyrimido[4,5-d]azepine-7 (6H)-yl)piperidine-1-carboxylate 4-((2-((4-Cyanophenyl)amino)-7-(piperidin-4-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-yl )hydroxy)-3,5-dimethylbenzonitrile 4-((6-(2-Aminoacetyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl-)oxy)-3 ,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(2-(3-hydroxyazetidin-1-yl)acetyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine- 4-yl)oxy)-3,5-dimethylbenzonitrile 4-({2-[(4-cyanophenyl)amino]-6-[2-(morpholin-4-yl)acetyl]-5H,6H,7H,8H-pyrido[4,3-d]pyrimidine-4- yl}oxy)-3,5-dimethylbenzonitrile 4-({2-[(4-cyanophenyl)amino]-6-[2-(4,4-difluoropiperidin-1-yl)acetyl]-5H,6H,7H,8H-pyrido[4,3-d] pyrimidin-4-yl}oxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(cyclopropanecarbonyl)-5,6,7,8-tetrahydro-[4,3-d]pyrimidin-4-yl)oxy)-3.5 -dimethylbenzonitrile 4-({2-[(4-cyanophenyl)amino]-6-(morpholine-4-carbonyl)-5H,6H,7H,8H-pyrido[4,3-d]pyrimidin-4-yl}oxy)- 3,5-dimethylbenzonitrile 4-({2-[(4-cyanophenyl)amino]-6-(4-methylpiperazin-1-carbonyl)-5H,6H,7H,8H-pyrido[4,3-d]pyrimidin-4-yl}oxy )-3,5-dimethylbenzonitrile tert-Butyl 2-(4-(4-Cyano-2,6-dimethylphenoxy)-2-((cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepine -7-carbonyl)pyrrolidine-1-carboxylate (R)-tert-Butyl 2-(4-(4-Cyano-2,6-dimethylphenoxy)-2-((cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,3 -d]azepine-7-carbonyl)pyrrolidine-1-carboxylate (S)-tert-Butyl 2-(4-(4-Cyano-2,6-dimethylphenoxy)-2-((cyanophenyl)amino)-6,7,8,9-tetrahydro-5Н-pyrimido[4,3 -d]azepine-7-carbonyl)pyrrolidine-1-carboxylate 4-((2-((4-Cyanophenyl)amino)-7-(tetrahydro-2H-pyran-4-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine -4-yl)oxy)-3,5-dimethylbenzonitrile Synthesis of 4-((2-((4-Cyanophenyl)amino)-7-(5-methylfuran-2-yl)methyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d] azepin-4-yl)oxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(1-methyl-1H-pyrrol-2-yl)methyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,3 -d]azepin-4-yl)oxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(4-hydroxybenzyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepin-4-yl)oxy )-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(1-methoxypropan-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepine-4 -yl)oxy)-3,5-dimethylbenzonitrile tert-Butyl 2-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6 -carbonyl)pyrrolidine-1-carboxylate 4-((2-((4-Cyanophenyl)amino)-6-(pyrrolidin-2-carbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)- 3,5-dimethylbenzonitrile 4-((6-(Azetidine-3-carbonyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)- 3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(pyrazine-2-carbonyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)- 3,5-dimethylbenzonitrile (S)-tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine- 6(5Н)-yl)-1-oxopropan-2-yl)carbamate (S)-4-((6-(2-Aminopropanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy )-3,5-dimethylbenzonitrile (S)-tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine- 6(5Н)-yl)-1-oxo-3-phenylpropan-2-yl)carbamate (S)-4-((6-(2-Amino-3-phenylpropanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyri1iidine-4 -yl)oxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(2-morpholinoethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepin-4-yl)oxy )-3,5-dimethylbenzonitrile (R)-tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine- 6(5Н)-yl)-3-hydroxy-1-oxopropan-2-yl)carbamate tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H) -yl)-4-(methylthio)-1-oxobutan-2-yl)carbamate 4-({6-[2-amino-3-(1H-imidazol-5-yl)propanoyl]-2-[(4-cyanophenyl)amino]-5H,6H,7H,8H-pyrido[4,3- d]pyrimidin-4-yl}oxy)-3,5-dimethylbenzonitrile 4-((6-(2-Amino-3-(1H-pyrazol-4-yl)propanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3- d]pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile tert-Butyl 4-(2-((tert-butoxycarbonyl)amino)-3-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido [4,3-d]pyrimidin-6(5H)-yl)-3-oxopropyl)-1 H-pyrazole-1-carboxylate (R)-4-((6-(2-Amino-3-hydroxypropanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-4 -yl)oxy)-3,5-dimethylbenzonitrile (S)-tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine- 6(5Н)-yl)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)carbamate (S)-4-((6-(2-Amino-3-(4-hydroxyphenyl)propanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3- d]pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile (R)-tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine- 6(5Н)-yl)-3-methyl-1-oxobutan-2-yl)carbamate (R)-4-((6-(2-Amino-3-methylbutanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-4 -yl)oxy)-3,5-dimethylbenzonitrile (S)-tert-Butyl (1-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d]pyrimidine- 6(5Н)-yl)-4-methyl-1-oxopentan-2-yl)carbamate (S)-4-((6-(2-Amino-4-methylpentanoyl)-2-((4-cyanophenyl)amino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-4 -yl)oxy)-3,5-dimethylbenzonitrile (S)-Di-tert-butyl (6-(4-(4-cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-7,8-dihydropyrido[4,3-d] pyrimidin-6(5H)-yl)-6-oxohexane-1,5-diyl)dicarbamate (S)-4-((2-((4-Cyanophenyl)amino)-6-(2,6-diaminohexanoyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl )hydroxy)-3,5-dimethylbenzonitrile 4-((7-(2-Chloroacetyl)-2-((4-cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepin-4-yl)oxy )-3,5-dimethylbenzonitrile methyl 4-(4-cyano-2,6-dimethylphenoxy)-2-((4-4-cyanophenyl)amino)-8,9-dihydro-5H-pyrimido[4,3-d]azepine-7(6H) -carboxylate 4-((2-((4-Cyanophenyl)amino)-7-(methylsulfonyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepin-4-yl)oxy)- 3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(pyridin-4-ylmethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)- 3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(pyridin-3-ylmethyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)- 3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(2-hydroxybenzyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)oxy)-3, 5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-6-(2-(prop-2-yn-1-yloxy)benzyl)-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidin-4-yl)oxy)-3,5-dimethylbenzonitrile 3-(4-(4-Cyano-2,6-dimethylphenoxy)-2-((4-cyanophenyl)amino)-8,9-dihydro-5H-pyrimido[4,3-d]azepine-7(6H) -yl) propanoic acid 4-((7-Allyl-2-((4-cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepin-4-yl)oxy)-3, 5-dimethylbenzonitrile 4-((7-Acetyl-2-((4-cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,3-d]azepin-4-yl)oxy)-3, 5-dimethylbenzonitrile 4-((7-(2-(1H-Imidazol-1-yl)acetyl)-2-((4-cyanophenyl)amino)-6,7,8,9-tetrahydro-5H-pyrimido[4,3- d]azepin-4-yl)oxy)-3,5-dimethylbenzonitrile 4-((2-((4-Cyanophenyl)amino)-7-(2-(methyl-1H-imidazol-1-yl)acetyl)-6,7,8,9-tetrahydro-5H-pyrimido[4, 3-d]azepin-4-yl)oxy)-3,5-dimethylbenzonitrile 4-(4-cyano-2,6-dimethylphenoxy)-2-[(4-cyanophenyl)amino]-5Н,6Н,7Н,8Н-pyrido[4,3-d]pyrimidine-6-sulfonamide methyl 2-{2-[(4-cyanophenyl)amino]-4-(4-formyl-2,6-dimethylphenoxy)-5H,6H,7H,8H,9H-pyrimido [4,5-d]azepine-7 -yl}-2-oxoacetate 4-(4-cyano-2,6-dimethylphenoxy)-2-[(4-cyanophenyl)amino]-N-(oxan-4-yl)-4аН,5Н,6Н,7Н,8Н,8аН-pyrido [4 ,3-d]pyrimidine-6-carboxamide. 18. Connection according to any of the square. 1-17, which includes at least one isotope. 19. Connection according to any one of paragraphs. 1-17 in the form of a free base or a pharmaceutically acceptable salt selected from the group consisting of salts of the amino group formed with inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric and perchloric acids, or formed with organic acids such as acetic, oxalic, maleic, tartaric, succinic or malonic acids, or pharmaceutically acceptable salts: adipinate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentane propionate, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanate , hexanate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3- phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanate, valeriate, or a pharmaceutically acceptable salt containing alkali and/or alkaline earth metals or non-toxic ammonium, quaternary ammonium and amine cations, or a pharmaceutically acceptable salt derived from counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates and aryl sulfonates. 20. Connection according to any one of paragraphs. 1-19, where reverse transcriptase is HIV reverse transcriptase. 21. Pharmaceutical composition having inhibitory activity against reverse transcriptase, comprising a compound according to paragraphs. 1-20 in a therapeutically effective amount and at least one carrier, excipient or diluent. 22. The pharmaceutical composition of claim 21 further comprising at least one compound selected from the group consisting of HIV protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, CCR5 antagonists, and inhibitors of viral cell entry, wherein the reverse transcriptase is HIV reverse transcriptase. 23. The pharmaceutical composition of claim 21, wherein the HIV reverse transcriptase contains at least one mutation compared to wild-type HIV. 24. The pharmaceutical composition according to claim 21, wherein the HIV reverse transcriptase has a reduced sensitivity to the drugs efavirenz, nevirapine, doravirine or delavirdine. 25. The use of a composition according to any one of paragraphs. 21-24 to obtain an agent for the treatment or prevention of HIV. 26. A method of inhibiting HIV reverse transcriptase in the body of a subject infected with HIV, which consists in the fact that a subject in need of treatment is administered a therapeutically effective amount of a compound according to any one of paragraphs. 1-20.