Claims (16)
1. Spoj formule (Ia):
ili njegova farmaceutski prihvatljiva sol. 1. Compound of formula (Ia):
or a pharmaceutically acceptable salt thereof.
2. Spoj prema zahtjevu 1, koji je spoj formule (Ib)
ili njegova farmaceutski prihvatljiva sol. 2. Compound according to claim 1, which is a compound of formula (Ib)
or a pharmaceutically acceptable salt thereof.
3. Spoj formule (IIa):
ili njegova farmaceutski prihvatljiva sol. 3. Compound of formula (IIa):
or a pharmaceutically acceptable salt thereof.
4. Spoj prema zahtjevu 3, koji je spoj formule (IIb):
ili njegova farmaceutski prihvatljiva sol. 4. Compound according to claim 3, which is a compound of formula (IIb):
or a pharmaceutically acceptable salt thereof.
5. Farmaceutski sastav koji sadrži terapeutski efikasnu količinu spoja prema bilo kojem od zahtjeva 1-4, ili njegova farmaceutski prihvatljiva sol, i farmaceutski prihvatljiva pomoćna tvar,
spomenuti farmaceutski sastav opcionalno dalje sadrži jedan, dva, tri ili četiri dodatna terapeutska sredstva, opcionalno u kojima su dodatna terapeutska sredstva izabrana iz grupe koju čine kombinirani lijekovi za HIV, drugi lijekovi za liječenje HIV-a, inhibitori HIV proteaze, HIV ne-nukleozidni ili ne-nukleotidni inhibitori reverzne transkriptaze, HIV nukleozidni ili nuklerotidni inhibitori reverzne transkriptaze, inhibitori HIV integraze, inhibitori nekatalitičkog mjesta (ili alosterični) HIV integraze, inhibitori ulaska HIV-a,
inhibitori sazrijevanja HIV-a, sredstva za vraćanje latencije, spojevi koji ciljaju HIV kapsid, imunoterapije, inhibitori fosfatidilinozitol 3-kinaze (PI3K), HIV antitijela, bispecifična antitijela i terapeutski proteini "slični antitijelima", inhibitori HIV p17 matriks proteina, IL-13 antagonisti, modulatori peptidil-prolil cis-trans izomeraze A, inhibitori protein disulfidne izomeraze, antagonisti receptora komplementa C5a , inhibitor DNK metiltransferaze, modulatori HIV vif gena, antagonisti Vif dimerizacije, inhibitori HIV-1 viralnog infekcijskog faktora, inhibitori TAT proteina, modulatori HIV1 Nef, modulatori Hck tirozin kinaze, inhibitori mješovite linijske kinaze-3 (MLK-3), inhibitori HIV-1 spajanja, inhibitori Rev proteina, antagonisti integrina, inhibitori nukleoproteina, modulatori faktora spajanja, modulatori proteina 1 koji sadrži COMM domen, inhibitori HIV ribonukleaze H, modulatori retrociklina, CDK-9 inhibitori, inhibitori dendritnog ICAM-3 hvatajućeg neintegrina 1, inhibitori HIV GAG proteina , inhibitori HIV POL proteina, modulatori komplementarnog faktora H, inhibitori ubikvitin ligaze, inhibitori deoksicitidin kinaze, inhibitori ciklin ovisne kinaze, stimulatori proprotein konvertaze PC9, inhibitori ATP ovisne RNK helikaze DDX3X, inhibitori pripremnog kompleksa reverzne transkriptaze, G6PD i NADH-oksidazni inhibitori, farmakokinetički pojačivači, HIV genetska terapija, i HIV cjepiva, ili bilo koja njihova kombinacija;
opcionalno gdje su dodatna terapeutska sredstva izabrana iz grupe koju čine spojevi koji inhibiraju HIV proteazu, HIV ne-nukleozidni inhibitori reverzne transkriptaze, HIV ne-nukleotidni inhibitori reverzne transkriptaze, HIV nukleozidni inhibitori reverzne transkriptaze, HIV nukleotidni inhibitori reverzne transkriptaze, inhibitori HIV integraze, inhibitori gp41, inhibitori CXCR4, inhibitori gp120, inhibitori CCR5, inhibitori polimerizacije kapsida, farmakokinetički pojačivači, i drugi lijekovi za liječenje HIV, ili bilo koja njihova kombinacija. 5. A pharmaceutical composition containing a therapeutically effective amount of the compound according to any of claims 1-4, or its pharmaceutically acceptable salt, and a pharmaceutically acceptable excipient,
said pharmaceutical composition optionally further contains one, two, three or four additional therapeutic agents, optionally wherein the additional therapeutic agents are selected from the group consisting of HIV combination drugs, other HIV treatment drugs, HIV protease inhibitors, HIV non-nucleoside or non-nucleotide reverse transcriptase inhibitors, HIV nucleoside or nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, non-catalytic site (or allosteric) HIV integrase inhibitors, HIV entry inhibitors,
HIV maturation inhibitors, latency restorers, HIV capsid targeting compounds, immunotherapies, phosphatidylinositol 3-kinase (PI3K) inhibitors, HIV antibodies, bispecific antibodies and "antibody-like" therapeutic proteins, HIV p17 matrix protein inhibitors, IL-13 antagonists, peptidyl-prolyl cis-trans isomerase A modulators, protein disulfide isomerase inhibitors, C5a complement receptor antagonists, DNA methyltransferase inhibitor, HIV vif gene modulators, Vif dimerization antagonists, HIV-1 viral infectious factor inhibitors, TAT protein inhibitors, HIV1 Nef modulators , Hck tyrosine kinase modulators, mixed lineage kinase-3 (MLK-3) inhibitors, HIV-1 splicing inhibitors, Rev protein inhibitors, integrin antagonists, nucleoprotein inhibitors, splicing factor modulators, COMM domain-containing protein 1 modulators, HIV ribonuclease H inhibitors , retrocyclin modulators, CDK-9 inhibitors, inhibitors of dendritic ICAM-3 capturing non-integrin 1, inh HIV GAG protein inhibitors, HIV POL protein inhibitors, complement factor H modulators, ubiquitin ligase inhibitors, deoxycytidine kinase inhibitors, cyclin-dependent kinase inhibitors, PC9 proprotein convertase stimulators, ATP-dependent RNA helicase DDX3X inhibitors, reverse transcriptase preparatory complex inhibitors, G6PD and NADH- oxidase inhibitors, pharmacokinetic enhancers, HIV genetic therapy, and HIV vaccines, or any combination thereof;
optionally, where the additional therapeutic agents are selected from the group consisting of compounds that inhibit HIV protease, HIV non-nucleoside reverse transcriptase inhibitors, HIV non-nucleotide reverse transcriptase inhibitors, HIV nucleoside reverse transcriptase inhibitors, HIV nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, gp41, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, pharmacokinetic enhancers, and other drugs for the treatment of HIV, or any combination thereof.
6. Farmaceutski sastav prema zahtjevu 5, gdje
i) farmaceutski sastav sadrži terapeutski efikasnu količinu spoja prema zahtjevu 1 ili zahtjevu 2 i gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine GS-9131, GS9148, abakavir sulfat, tenofovir, tenofovir dizoproksil, tenofovir dizoproksil fumarat, tenofovir dizoproksil hemifumarat, tenofovir alafenamid, tenofovir alafenamid hemifumarat, 4’-etinil-2-fluoro-2’-deoksiadenozin i biktegravir ili njegova farmaceutski prihvatljiva sol, opcionalno gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine tenofovir alafenamid, tenofovir alafenamid fumarat i tenofovir alafenamid hemifumarat; ili
ii) farmaceutski sastav sadrži terapeutski efikasnu količinu spoja prema zahtjevu 3 ili zahtjevu 4 i gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine GS-9131, GS-9148, 4’-etinil-2-fluoro-2’-deoksiadenozin, biktegravir ili njihova farmaceutski prihvatljiva sol, abakavir sulfat, tenofovir, tenofovir dizoproksil, tenofovir dizoproksil fumarat, tenofovir dizoproksil hemifumarat, tenofovir alafenamid, i tenofovir alafenamid hemifumarat, opcionalno gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine 4’-etinil-2-fluoro-2’-deoksiadenozin, biktegravir ili njegova farmaceutski prihvatljiva sol, tenofovir alafenamid, tenofovir alafenamid fumarat i tenofovir alafenamid hemifumarat. 6. Pharmaceutical composition according to claim 5, where
i) the pharmaceutical composition contains a therapeutically effective amount of the compound according to claim 1 or claim 2 and where additional therapeutic agents are selected from the group consisting of GS-9131, GS9148, abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir disoproxil hemifumarate, tenofovir alafenamide , tenofovir alafenamide hemifumarate, 4'-ethynyl-2-fluoro-2'-deoxyadenosine and bictegravir or a pharmaceutically acceptable salt thereof, optionally where additional therapeutic agents are selected from the group consisting of tenofovir alafenamide, tenofovir alafenamide fumarate and tenofovir alafenamide hemifumarate; or
ii) the pharmaceutical composition contains a therapeutically effective amount of the compound according to claim 3 or claim 4 and where additional therapeutic agents are selected from the group consisting of GS-9131, GS-9148, 4'-ethynyl-2-fluoro-2'-deoxyadenosine, bictegravir or a pharmaceutically acceptable salt thereof, abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir disoproxil hemifumarate, tenofovir alafenamide, and tenofovir alafenamide hemifumarate, optionally wherein the additional therapeutic agents are selected from the group consisting of 4'-ethynyl-2-fluoro-2 '-deoxyadenosine, bictegravir or a pharmaceutically acceptable salt thereof, tenofovir alafenamide, tenofovir alafenamide fumarate and tenofovir alafenamide hemifumarate.
7. Spoj prema bilo kojem od zahtjeva 1-4, ili njegova farmaceutski prihvatljiva sol za upotrebu u terapiji. 7. A compound according to any one of claims 1-4, or a pharmaceutically acceptable salt thereof for use in therapy.
8. Spoj prema bilo kojem od zahtjeva 1-4, ili njegova farmaceutski prihvatljiva sol, za upotrebu u postupku liječenja ili prevencije infekcije virusa humane imunodeficijencije (HIV) koja obuhvaća davanje terapeutski efikasne količine spomenutog spoja subjektu kojem je to potrebno. 8. A compound according to any one of claims 1-4, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of human immunodeficiency virus (HIV) infection, which comprises administering a therapeutically effective amount of said compound to a subject in need thereof.
9. Spoj za upotrebu prema zahtjevu 8, gdje spomenuti postupak obuhvaća davanje jedan, dva, tri ili četiri dodatna terapeutska sredstva, opcionalno gdje
i) su dodatna terapeutska sredstva davana simultano sa spojem formule (Ia),(Ib), (IIa) ili (IIb) ili njihovom farmaceutski prihvatljivom soli, opcionalno gdje spoj formule (Ia), (Ib), (IIa) ili (IIb) je kombiniran s dodatnim terapeutskim sredstvima u jediničnom doznom obliku za simultano davanje; ili
ii) spoj formule (Ia), (Ib), (IIa) ili (IIb) je davan i dodatna terapeutska sredstva su davana uzastopno. 9. The compound for use according to claim 8, wherein said method comprises administering one, two, three or four additional therapeutic agents, optionally wherein
i) additional therapeutic agents are administered simultaneously with the compound of formula (Ia), (Ib), (IIa) or (IIb) or a pharmaceutically acceptable salt thereof, optionally where the compound of formula (Ia), (Ib), (IIa) or (IIb) ) is combined with additional therapeutic agents in unit dosage form for simultaneous administration; or
ii) a compound of formula (Ia), (Ib), (IIa) or (IIb) is administered and additional therapeutic agents are administered sequentially.
10. Spoj za upotrebu prema zahtjevu 9, gdje je spoj spoj prema zahtjevu 1 ili zahtjevu 2 i gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine kombinirani lijekovi za HIV, drugi lijekovi za liječenje HIV-a, HIV proteazni inhibitori, HIV ne-nukleozidni ili ne-nukleotidni inhibitori reverzne transkriptaze, HIV nukleozidni ili neukeotidni inhibitori reverzne transkriptaze, inhibitori HIV integraze, inhibitori nekatalitičkog mjesta (ili alosterični) HIV integraze, inhibitori ulaska HIV-a , inhibitori sazrijevanja HIV-a, sredstva za vraćanje latencije, spojevi koja ciljaju HIV kapsid, imunoterapije, inhibitori fosfatidilinozitol 3-kinaze (PI3K), HIV antitijela, bispecifična antitijela i terapeutski proteini "slični antitijelima", inhibitori HIV p17 matriks proteina, IL-13 antagonisti, modulatori peptidil-prolil cis-trans izomeraze A , inhibitori protein disulfidne izomeraze, antagonisti receptora komplementa C5a , inhibitor DNK metiltransferaze, modulatori HIV vif gena, antagonisti Vif dimerizacije , inhibitori HIV-1 viralnog infekcijskog faktora , inhibitori TAT proteina , modulatori HIV1 Nef, modulatori Hck tirozin kinaze, inhibitori mješovite linijske kinaze-3 (MLK-3) , inhibitori HIV-1 spajanja, inhibitori Rev proteina, antagonisti integrina, inhibitori nukleoproteina, modulatori faktora spajanja, modulatori proteina 1 koji sadrži COMM domen, inhibitori HIV ribonukleaze H, modulatori retrociklina, CDK-9 inhibitori, inhibitori dendritnog ICAM-3 hvatajućeg neintegrina 1, inhibitori HIV GAG proteina, inhibitori HIV POL proteina, modulatori komplementarnog faktora H, inhibitori ubihitin ligaze, inhibitori deoksicitidin kinaze, inhibitori ciklin zavisne kinaze, stimulatori proprotein konvertaze PC9, inhibitori ATP zavisne RNK helikaze DDX3X, inhibitori pripremnog kompleksa reverzne transkriptaze, G6PD i NADH-oksidazni inhibitori, farmakokinetički pojačivači, HIV genetska terapija, i HIV cjepiva, ili bilo koja njihova kombinacija; opcionalno gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine spojevi koja inhibiraju HIV protezu, HIV ne-nukleozidni inhibitori reverzne transkriptaze, HIV ne-nukleotidni inhibitori reverzne transkriptaze, HIV nukleozidni inhibitori reverzne transkriptaze, HIV nukleotidni inhibitori reverzne transkriptaze, inhibitori HIV integraze, inhibitori gp41, inhibitori CXCR4, inhibitori gp120, inhibitori CCR5, inhibitori polimerizacije kapsida, farmakokinetički pojačivači, i drugi lijekovi za liječenje HIV, ili bilo koja njihova kombinacija, opcionalno kada se spomenuti spoj kombinira sa
i) abakavir sulfatom, tenofovir, tenofovir dizoproksilom, tenofovir dizoproksil fumaratom, tenofovir dizoproksil hemifumaratom, tenofovir alafenamidom, ili tenofovir alafenamid hemifumaratom; ili
ii) 4’-etinil-2-fluoro-2’-deoksiadenozinom, biktegravirom, ili njihovom farmaceutski prihvatljivom soli; ili
iii) tenofovir alafenamidom, tenofovir alafenamid fumaratom ili tenofovir alafenamid hemifumaratom; ili
iv) tenofovir dizoproksilom, tenofovir dizoproksil hemifumaratom ili tenofovir dizoproksil fumaratom; ili
v) prvim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine abakavir sulfat, tenofovir, tenofovir dizoproksil, tenofovir dizoproksil fumarat, tenofovir alafenamid, i tenofovir alafenamid hemifumarat, i drugim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine emtricitabin i lamivudin; ili
vi) prvim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine tenofovir alafenamid fumaratom, tenofovir alafenamidom, i tenofovir alafenamid hemifumaratom, i drugim dodatnim terapeutskim sredstvom, gdje je drugo dodatno terapeutsko sredstvo emtricitabin; ili
viii) prvim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine tenofovir dizoproksil fumarat, tenofovir dizoproksil, i tenofovir dizoproksil hemifumarat, i drugim dodatnim terapeutskim sredstvom, gdje je drugo dodatno terapeutsko sredstvo emtricitabin. 10. A compound for use according to claim 9, wherein the compound is a compound according to claim 1 or claim 2 and wherein the additional therapeutic agents are selected from the group consisting of combination HIV drugs, other HIV treatment drugs, HIV protease inhibitors, HIV non- nucleoside or non-nucleotide reverse transcriptase inhibitors, HIV nucleoside or non-nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, non-catalytic site (or allosteric) HIV integrase inhibitors, HIV entry inhibitors, HIV maturation inhibitors, latency restorers, compounds that targeting the HIV capsid, immunotherapies, phosphatidylinositol 3-kinase (PI3K) inhibitors, HIV antibodies, bispecific antibodies and "antibody-like" therapeutic proteins, HIV p17 matrix protein inhibitors, IL-13 antagonists, peptidyl-prolyl cis-trans isomerase A modulators, inhibitors disulfide isomerase protein, complement C5a receptor antagonists, DNA methyltransferase inhibitor, HIV vif gene modulators, antagonist same Vif dimerization, HIV-1 viral infection factor inhibitors, TAT protein inhibitors, HIV1 Nef modulators, Hck tyrosine kinase modulators, mixed line kinase-3 (MLK-3) inhibitors, HIV-1 splicing inhibitors, Rev protein inhibitors, integrin antagonists, nucleoprotein inhibitors, splicing factor modulators, COMM domain-containing protein 1 modulators, HIV ribonuclease H inhibitors, retrocyclin modulators, CDK-9 inhibitors, dendritic ICAM-3 binding non-integrin 1 inhibitors, HIV GAG protein inhibitors, HIV POL protein inhibitors, complement factor modulators H, ubiquitin ligase inhibitors, deoxycytidine kinase inhibitors, cyclin-dependent kinase inhibitors, PC9 proprotein convertase stimulators, DDX3X ATP-dependent RNA helicase inhibitors, reverse transcriptase preparatory complex inhibitors, G6PD and NADH-oxidase inhibitors, pharmacokinetic enhancers, HIV genetic therapy, and HIV vaccines , or any combination thereof; optionally, where the additional therapeutic agents are selected from the group consisting of compounds that inhibit HIV protease, HIV non-nucleoside reverse transcriptase inhibitors, HIV non-nucleotide reverse transcriptase inhibitors, HIV nucleoside reverse transcriptase inhibitors, HIV nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, gp41, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, pharmacokinetic enhancers, and other drugs for the treatment of HIV, or any combination thereof, optionally when said compound is combined with
i) abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir disoproxil hemifumarate, tenofovir alafenamide, or tenofovir alafenamide hemifumarate; or
ii) 4'-ethynyl-2-fluoro-2'-deoxyadenosine, bictegravir, or their pharmaceutically acceptable salt; or
iii) tenofovir alafenamide, tenofovir alafenamide fumarate or tenofovir alafenamide hemifumarate; or
iv) tenofovir disoproxil, tenofovir disoproxil hemifumarate or tenofovir disoproxil fumarate; or
v) the first additional therapeutic agent selected from the group consisting of abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir alafenamide, and tenofovir alafenamide hemifumarate, and the second additional therapeutic agent selected from the group consisting of emtricitabine and lamivudine; or
vi) a first additional therapeutic agent selected from the group consisting of tenofovir alafenamide fumarate, tenofovir alafenamide, and tenofovir alafenamide hemifumarate, and a second additional therapeutic agent, where the second additional therapeutic agent is emtricitabine; or
viii) a first additional therapeutic agent selected from the group consisting of tenofovir disoproxil fumarate, tenofovir disoproxil, and tenofovir disoproxil hemifumarate, and a second additional therapeutic agent, where the second additional therapeutic agent is emtricitabine.
11. Spoj za upotrebu prema zahtjevu 9, gdje je spoj spoj prema zahtjevu 3 ili zahtjevu 4, i gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine kombinacija lijekova za HIV, drugi lijekovi za liječenje HIV-a, inhibitori HIV proteaze, HIV ne-nukleozidni ili ne-nukleotidni inhibitori reverzne transkriptaze, HIV nukleozidni ili nukleotidni inhibitori reverzne transkriptaze, inhibitori HIV integraze, inhibitori nekatalitičkog mjesta (ili alosterični) HIV integraze, inhibitori ulaska HIV-a, inhibitori sazrijevanja HIV-a, sredstva za vraćanje latencije, spojevi koja ciljaju HIV kapsid, imunoterapije, inhibitori fosfatidilinozitol 3-kinaze (PI3K), HIV antitijela, bispecifična antitijela i terapeutski proteini "slični antitijelima", inhibitori HIV p17 matriks proteina, IL-13 antagonisti, modulatori peptidil-prolil cis-trans izomeraze A, inhibitori protein disulfidne izomeraze, antagonisti receptora komplementa C5a, inhibitor DNK metiltransferaze, modulatori HIV vif gena, antagonisti Vif dimerizacije, inhibitori HIV-1 viralnog infektivnog faktora, inhibitori TAT proteina, modulatori HIV-1 Nef, modulatori Hck tirozin kinaze, inhibitori mješovite linijske kinaze-3 (MLK-3), inhibitori HIV-1 spajanja, inhibitori Rev proteina, antagonisti integrina, inhibitori nukleoproteina, modulatori faktora spajanja, modulatori proteina 1 koji sadrži COMM domen, inhibitori HIV ribonukleaze H, modulatori retrociklina, CDK-9 inhibitori, inhibitori dendritnog ICAM-3 hvatajućeg neintegrina 1, inhibitori HIV GAG proteina, inhibitori HIV POL proteina, modulatori komplementarnog faktora H, inhibitori ubihitin ligaze, inhibitori deoksicitidin kinaze, inhibitori ciklin ovisne kinaze, stimulatori proprotein konvertaze PC9, inhibitori ATP ovisne RNK helikaze DDX3X, inhibitori pripremnog kompleksa reverzne transkriptaze, G6PD i NADH-oksidazni inhibitori, farmakokinetički pojačivači, HIV genetska terapija, i HIV cjepiva, ili bilo koja njihova kombinacija; opcionalno gdje dodatna terapeutska sredstva su izabrana iz grupe koju čine spojevi koja inhibiraju HIV proteazu, HIV ne-nukleozidni inhibitori reverzne transkriptaze, HIV ne-nukleotidni inhibitori reverzne transkriptaze, HIV nukleozidni inhibitori reverzne transkriptaze, HIV nukleotidni inhibitori reverzne transkriptaze, inhibitori HIV integraze, inhibitori gp41, inhibitori CXCR4, inhibitori gp120 , inhibitori CCR5, inhibitori polimerizacije kapsida, farmakokinetički pojačivači, i drugi lijekovi za liječenje HIV, ili bilo koja njihova kombinacija, opcionalno kad je spomenuti spoj kombiniran sa
i) 4’-etinil-2-fluoro-2’-deoksiadenozinom, biktegravirom ili njegovom farmaceutski prihvatljivom soli, abakavir sulfatom, tenofovirom, tenofovir dizoproksilom, tenofovir disolproksil fumaratom, tenofovir dizoproksil hemifumaratom, tenofovir alafenamidom, ili tenofovir alafenamid hemifumaratom; ili
ii) 4’-etinil-2-fluoro-2’-deoksiadenozinom, biktegravirom ili njegovom farmaceutski prihvatljivom soli, tenofovir alafenamidom, tenofovir alafenamid fumaratom ili tenofovir alafenamid hemifumaratom; ili
iii) 4’-etinil-2-fluoro-2’-deoksiadenozinom, biktegravirom ili njegovom farmaceutski prihvatljivom soli, tenofovir dizoproksilom, tenofovir dizoproksil hemifumaratom ili tenofovir dizoproksil fumaratom; ili
iv) prvim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine 4’-etinil-2-fluoro-2’-deoksiadenozin, abakavir sulfat, tenofovir, tenofovir dizoproksil, tenofovir dizoproksil fumarat, tenofovir alafenamid, i tenofovir alafenamid hemifumarat, i drugim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine emtricitabin i lamivudin; ili
v) prvim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine 4’-etinil-2-fluoro-2’-deoksiadenozin, tenofovir alafenamid fumarat, tenofovir alafenamid, i tenofovir alafenamid hemifumarat, i drugim dodatnim terapeutskim sredstvom, gdje je drugo dodatno terapeutsko sredsto emtricitabin; ili
vi) prvim dodatnim terapeutskim sredstvom izabranim iz grupe koju čine 4’-etinil-2-fluoro-2’-deoksiadenozin, tenofovir dizoproksil fumarat, tenofovir dizoproksil, i tenofovir dizoproksil hemifumarat, i drugim dodatnim terapeutskim sredstvom, gdje je drugo dodatno terapeutsko sredstvo emtricitabin. 11. A compound for use according to claim 9, wherein the compound is a compound according to claim 3 or claim 4, and wherein the additional therapeutic agents are selected from the group consisting of a combination of HIV drugs, other HIV treatment drugs, HIV protease inhibitors, HIV non -nucleoside or non-nucleotide reverse transcriptase inhibitors, HIV nucleoside or nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, non-catalytic site (or allosteric) HIV integrase inhibitors, HIV entry inhibitors, HIV maturation inhibitors, latency restorers, compounds that target the HIV capsid, immunotherapies, phosphatidylinositol 3-kinase (PI3K) inhibitors, HIV antibodies, bispecific antibodies and "antibody-like" therapeutic proteins, HIV p17 matrix protein inhibitors, IL-13 antagonists, peptidyl-prolyl cis-trans isomerase A modulators, protein disulfide isomerase inhibitors, complement C5a receptor antagonists, DNA methyltransferase inhibitor, HIV vif gene modulators, antagonist and Vif dimerization, HIV-1 viral infectivity factor inhibitors, TAT protein inhibitors, HIV-1 Nef modulators, Hck tyrosine kinase modulators, mixed lineage kinase-3 (MLK-3) inhibitors, HIV-1 splicing inhibitors, Rev protein inhibitors, antagonists integrins, nucleoprotein inhibitors, splicing factor modulators, COMM domain-containing protein 1 modulators, HIV ribonuclease H inhibitors, retrocyclin modulators, CDK-9 inhibitors, dendritic ICAM-3 binding non-integrin 1 inhibitors, HIV GAG protein inhibitors, HIV POL protein inhibitors, modulators complement factor H, ubiquitin ligase inhibitors, deoxycytidine kinase inhibitors, cyclin-dependent kinase inhibitors, proprotein convertase PC9 stimulators, ATP-dependent RNA helicase DDX3X inhibitors, reverse transcriptase preparatory complex inhibitors, G6PD and NADH-oxidase inhibitors, pharmacokinetic enhancers, HIV genetic therapy, and HIV vaccines, or any combination thereof; optionally, where the additional therapeutic agents are selected from the group consisting of compounds that inhibit HIV protease, HIV non-nucleoside reverse transcriptase inhibitors, HIV non-nucleotide reverse transcriptase inhibitors, HIV nucleoside reverse transcriptase inhibitors, HIV nucleotide reverse transcriptase inhibitors, HIV integrase inhibitors, gp41, CXCR4 inhibitors, gp120 inhibitors, CCR5 inhibitors, capsid polymerization inhibitors, pharmacokinetic enhancers, and other drugs for the treatment of HIV, or any combination thereof, optionally when said compound is combined with
i) 4'-ethynyl-2-fluoro-2'-deoxyadenosine, bictegravir or its pharmaceutically acceptable salt, abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir disoproxil hemifumarate, tenofovir alafenamide, or tenofovir alafenamide hemifumarate; or
ii) 4'-ethynyl-2-fluoro-2'-deoxyadenosine, bictegravir or its pharmaceutically acceptable salt, tenofovir alafenamide, tenofovir alafenamide fumarate or tenofovir alafenamide hemifumarate; or
iii) 4'-ethynyl-2-fluoro-2'-deoxyadenosine, bictegravir or its pharmaceutically acceptable salt, tenofovir disoproxil, tenofovir disoproxil hemifumarate or tenofovir disoproxil fumarate; or
iv) the first additional therapeutic agent selected from the group consisting of 4'-ethynyl-2-fluoro-2'-deoxyadenosine, abacavir sulfate, tenofovir, tenofovir disoproxil, tenofovir disoproxil fumarate, tenofovir alafenamide, and tenofovir alafenamide hemifumarate, and another additional therapeutic agent selected from the group consisting of emtricitabine and lamivudine; or
v) a first additional therapeutic agent selected from the group consisting of 4'-ethynyl-2-fluoro-2'-deoxyadenosine, tenofovir alafenamide fumarate, tenofovir alafenamide, and tenofovir alafenamide hemifumarate, and a second additional therapeutic agent, where the second additional therapeutic agent is emtricitabine ; or
vi) a first additional therapeutic agent selected from the group consisting of 4'-ethynyl-2-fluoro-2'-deoxyadenosine, tenofovir disoproxil fumarate, tenofovir disoproxil, and tenofovir disoproxil hemifumarate, and a second additional therapeutic agent, where the second additional therapeutic agent is emtricitabine .
12. Farmaceutski sastav prema bilo kojem od zahtjeva 5-6, gdje je sastav za oralnu fomulaciju ili parenteralnu formulaciju, opcionalno gdje je parenteralna formulacija davana potkožno ili međumišićno subjektu kojem je to potrebno. 12. A pharmaceutical composition according to any of claims 5-6, wherein the composition is for oral formulation or parenteral formulation, optionally wherein the parenteral formulation is administered subcutaneously or intramuscularly to a subject in need thereof.
13. Spoj izabran iz grupe koju čine: 13. A compound selected from the group consisting of:
14. Potkožna formulacija prema zahtjevu 12, gdje formulacija sadrži
i) fiziološku otopinu i opcionalno sadrži još poloksamer, opcionalno gdje je spomenuti poloksamer poloksamer 338 ili poloksamer 188, opcionalno gdje je spomenuti poloksamer poloksamer 188, koncentracija poloksamera 188 u fiziološkoj otopini je oko 1% do oko 10%, opcionalno oko 1% do oko 3%, opcionalno oko 2%; ili
ii) N-metil-2-pirolidon, opcionalno gdje se formulacija sastoji esencijalno od N-metil-2-pirolidona; ili
iii) dimetil sulfoksid, opcionalno gdje se formulacija sastoji esencijalno od dimetil sulfoksida; ili
iv) vodu i/ili alkohol, opcionalno gdje je spomenuti alkohol etanol, i/ili polietilen glikol, opcionalno gdje polietilen glikol ima srednju molekularnu masu od oko 200 g/mol, i/ili neorgansku bazu, opcionalno gdje je spomenuta anorganska baza natrijev hidroksid. 14. Subcutaneous formulation according to claim 12, wherein the formulation contains
i) physiological solution and optionally also contains poloxamer, optionally where said poloxamer is poloxamer 338 or poloxamer 188, optionally where said poloxamer is poloxamer 188, the concentration of poloxamer 188 in physiological solution is about 1% to about 10%, optionally about 1% to about 3%, optional about 2%; or
ii) N-methyl-2-pyrrolidone, optionally where the formulation consists essentially of N-methyl-2-pyrrolidone; or
iii) dimethyl sulfoxide, optionally where the formulation consists essentially of dimethyl sulfoxide; or
iv) water and/or alcohol, optionally where said alcohol is ethanol, and/or polyethylene glycol, optionally where polyethylene glycol has an average molecular weight of about 200 g/mol, and/or an inorganic base, optionally where said inorganic base is sodium hydroxide .
15. Potkožna formulacija prema zahtjevima 12 i 14, dio iv), gdje formulacija sadrži oko 5% do oko 20% etanola, oko 5% do oko 20% vode, i oko 60% do oko 90% polietilen glikola 200; opcionalno sadrži oko 10% do oko 15% etanola, oko 10% do oko 15% vode, i oko 70% do oko 80% polietilen glikola 200; opcionalno sadrži oko 10% etanola, oko 12% vode, i oko 78% polietilen glikola 200. 15. The subcutaneous formulation according to claims 12 and 14, part iv), wherein the formulation contains about 5% to about 20% ethanol, about 5% to about 20% water, and about 60% to about 90% polyethylene glycol 200; optionally contains about 10% to about 15% ethanol, about 10% to about 15% water, and about 70% to about 80% polyethylene glycol 200; optionally contains about 10% ethanol, about 12% water, and about 78% polyethylene glycol 200.
16. Formulacija prema bilo kojem od zahtjeva 12, 14 i 16, gdje je spoj prisutan kao natrijeva sol.16. A formulation according to any one of claims 12, 14 and 16, wherein the compound is present as the sodium salt.