HRP20200158T1 - Kombinacije koje sadrže derivate 5-fenoksi-3h-pirimidin-4-ona i njihova uporaba za profilaksu ili liječenje infekcije hiv-om - Google Patents
Kombinacije koje sadrže derivate 5-fenoksi-3h-pirimidin-4-ona i njihova uporaba za profilaksu ili liječenje infekcije hiv-om Download PDFInfo
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- HRP20200158T1 HRP20200158T1 HRP20200158TT HRP20200158T HRP20200158T1 HR P20200158 T1 HRP20200158 T1 HR P20200158T1 HR P20200158T T HRP20200158T T HR P20200158TT HR P20200158 T HRP20200158 T HR P20200158T HR P20200158 T1 HRP20200158 T1 HR P20200158T1
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- alkyl
- haloalkyl
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- 238000011321 prophylaxis Methods 0.000 title claims 3
- PRXCVXCFQYBCQL-UHFFFAOYSA-N 5-phenoxy-1h-pyrimidin-6-one Chemical class OC1=NC=NC=C1OC1=CC=CC=C1 PRXCVXCFQYBCQL-UHFFFAOYSA-N 0.000 title 1
- 208000015181 infectious disease Diseases 0.000 title 1
- 238000011282 treatment Methods 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 45
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 41
- 229910052799 carbon Inorganic materials 0.000 claims 35
- 125000001424 substituent group Chemical group 0.000 claims 30
- 229910052736 halogen Inorganic materials 0.000 claims 12
- 150000002367 halogens Chemical class 0.000 claims 12
- 125000005842 heteroatom Chemical group 0.000 claims 10
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 8
- 101100059444 Mus musculus Ccnb1 gene Proteins 0.000 claims 6
- 229920006395 saturated elastomer Polymers 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 5
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 229940124411 anti-hiv antiviral agent Drugs 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- 208000030507 AIDS Diseases 0.000 claims 3
- 125000003342 alkenyl group Chemical group 0.000 claims 3
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- 125000004122 cyclic group Chemical group 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims 2
- 102100024170 Cyclin-C Human genes 0.000 claims 2
- 208000031886 HIV Infections Diseases 0.000 claims 2
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 claims 2
- 208000037357 HIV infectious disease Diseases 0.000 claims 2
- 101000980770 Homo sapiens Cyclin-C Proteins 0.000 claims 2
- 101100273648 Mus musculus Ccna2 gene Proteins 0.000 claims 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 125000004452 carbocyclyl group Chemical group 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000006574 non-aromatic ring group Chemical group 0.000 claims 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims 1
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims 1
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 claims 1
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 claims 1
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 claims 1
- 229940099797 HIV integrase inhibitor Drugs 0.000 claims 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 claims 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 229960005475 antiinfective agent Drugs 0.000 claims 1
- 239000004599 antimicrobial Substances 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 230000004927 fusion Effects 0.000 claims 1
- 239000002835 hiv fusion inhibitor Substances 0.000 claims 1
- 239000003084 hiv integrase inhibitor Substances 0.000 claims 1
- 239000004030 hiv protease inhibitor Substances 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000002955 immunomodulating agent Substances 0.000 claims 1
- 229940121354 immunomodulator Drugs 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 claims 1
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
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- Animal Behavior & Ethology (AREA)
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- Epidemiology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Enzymes And Modification Thereof (AREA)
Claims (11)
1. Kombinacija koja sadrži (i) spoj formule I:
[image]
ili njegovu farmaceutski prihvatljivu sol i (ii) jedno ili više sredstava protiv HIV-a izabranih od antivirusnih sredstava protiv HIV-a, imunomodulatora i anti-infektivnih sredstava, gdje :
M je CH2, CH2CH2, CH2CH2CH2, CH(CH3), C(CH3)2 ili C(O)N(RA);
Z je izabran iz grupe koja se sastoji od: piridazina, piridazinona, pirimidina, pirimidinona, pirazina, pirazinona, triazina i triazinona, svaki izborno supstituiran sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valencom izabranog od R4 i R5;
svaki R1 je nezavisno izabran iz grupe koja se sastoji od: halogena, CN, NO2, C1-4 alkila, C1-4 haloalkila, C2-4 alkenila, OH, O-C1-4 alkila, O-C1-4 haloalkila, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, SO2RA, SO2N(RA)RB, SO2N(RA)C(O)RB ili C2-4 alkenila supstituiranog sa CN;
R2 je izabran iz grupe koja se sastoji od:
(1) H,
(2) C1-6 alkila,
(3) C1-6 haloalkila,
(4) C1-6 alkila supstituiranog sa od 1 do 3 supstituenta od kojih je svaki nezavisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB ili N(RA)C(O)C(O)N(RA)RB,
(5) O-C1-6 alkila u kome alkil je izborno supstituiran sa 1 do 3 supstituenta nezavisno izabrana od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, ili S(O)2N(RA)RB,
(6) O-C1-6 haloalkila,
(7) halogena,
(8) CN,
(9) NO2,
(10) N(RA)RB,
(11) C(O)N(RA)RB,
(12) C(O)RA,
(13) C(O)-C1-6 haloalkila,
(14) C(O)ORA,
(15) OC(O)RA,
(16) OC(O)N(RA)RB,
(17) SRA,
(18) S(O)RA,
(19) S(O)2RA,
(20) S(O)2N(RA)RB,
(21) N(RA)S(O)2RB,
(22) N(RA)S(O)2N(RA)RB,
(23) N(RA)C(O)RB,
(24) N(RA)C(O)N(RA)RB,
(25) N(RA)C(O)-C(O)N(RA)RB,
(26) N(RA)CO2RB,
(27) N(RC)RD,
(28) C(O)N(RC)RD,
(29) OC(O)N(RC)RD,
(30) S(O)2N(RC)RD,
(31) N(RA)S(O)2N(RC)RD,
(32) N(RA)C(O)N(RC)RD,
(33) N(RA)C(O)-C(O)N(RC)RD,
(34) CycA,
(35) -O-CycA,
(36) ArilA, ili
(37) HetA;
R3 je H, C1-6 alkil, halogen, CN, C1-6 fluoroalkil, OH, O-C1-6 alkil ili O-C1-6 haloalkil;
R4 i R5 su svaki nezavisno izabrani od:
(1) H,
(2) C1-6 alkila, C2-6 alkenila ili C2-6 alkinila, svaki izborno supstituiran sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valencom izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB,
(3) C1-6 haloalkila izborno dodatno supstituiranog sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valencom izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB
(4) O-C1-6 alkila u kome je alkil dio izborno supstituiran sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valencom izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB,
(5) O-C1-6 haloalkila, izborno dodatno supstituiranog sa jednim ili više supstituenata do maksimalnog broja dozvoljenog valencom izabranog od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, N(RA)C(O)C(O)N(RA)RB, CycB, ArilB i HetB,
(6) halogena,
(7) CN,
(8) NO2,
(9) N(RA)RB,
(10) C(O)N(RA)RB,
(11) C(O)RA,
(12) C(O)-C1-6 haloalkila,
(13) C(O)ORA,
(14) OC(O)RA,
(15) OC(O)N(RA)RB,
(16) SRA,
(17) S(O)RA,
(18) S(O)2RA,
(19) S(O)2N(RA)RB,
(20) N(RA)S(O)2RB,
(21) N(RA)S(O)2N(RA)RB,
(22) N(RA)C(O)RB,
(23) N(RA)C(O)N(RA)RB,
(24) N(RA)C(O)-C(O)N(RA)RB,
(25) N(RA)CO2RB,
(26) N(RC)RD,
(27) C(O)N(RC)RD,
(28) OC(O)N(RC)RD,
(29) S(O)2N(RC)RD,
(30) N(RA)S(O)2N(RC)RD,
(31) N(RA)C(O)N(RC)RD,
(32) N(RA)C(O)-C(O)N(RC)RD,
(33) OH,
(34) CycB,
(35) ArilB,
(36) HetB,
(37) -J-CycB,
(38) -J-ArilB, i
(39) -J-HetB,
ili R4 i R5 na susjednim atomima mogu biti spojeni zajedno sa atomima za koje su vezani tako da formiraju fuzionirani CycC, ArilC ili HetC;
CycA, CycB i CycC su nezavisno karbociklil koji je C3-8 cikloalkil, C5-8 cikloalkenil ili C7-12 bicikličan, zasićeni ili nezasićeni, nearomatičan sustav prstena u kome je jedan prsten fuzioniran za ili premošćen drugim prstenom; pri čemu je karbociklil izborno supstituiran s ukupno od 1 do 6 supstituenata, pri čemu:
(i) od nula do 6 supstituenata su svaki nezavisno:
(1) halogen,
(2) CN,
(3) C1-6 alkil,
(4) OH,
(5) O-C1-6 alkil,
(6) C1-6 haloalkil,
(7) O-C1-6 haloalkil,
(8) C1-6 alkenil, ili
(9) C1-6 alkenil supstituiran sa CN, andi
(ii) od nula do 2 supstituenta su svaki nezavisno:
(1) CycQ,
(2) AriQ,
(3) HetQ,
(4) HetR,
(5) J-CycQ,
(6) J-AriQ,
(7) J-HetQ,
(8) J-HetR,
(9) C1-6 alkil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR,
(10) C2-6 alkenil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR, ili
(11) C2-6 alkinil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR;
ArilA, ArilB i ArilC su nezavisno aril koji je izborno supstituiran sa ukupno od 1 do 8 supstituenata, pri čemu:
(i) od nula do 8 supstituenata su svaki nezavisno:
(1) C1-6 alkil,
(2) C1-6 haloalkil, koji je izborno supstituiran sa 1 do 3 dodatna supstituenta od kojih je svaki nezavisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(3) C1-6 alkila supstituiranog sa od 1 do 3 supstituenta od kojih je svaki nezavisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(4) C2-6 alkenil,
(5) C2-6 alkenil supstituiran sa od 1 do 3 supstituenta od kojih je svaki nezavisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(6) C2-6 alkinil,
(7) C2-6 alkinil supstituiran sa od 1 do 3 supstituenta od kojih je svaki nezavisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(8) O-C1-6 alkil,
(9) O-C1-6 haloalkil,
(10) OH,
(11) halogen,
(12) CN,
(13) NO2,
(14) N(RA)RB,
(15) C(O)N(RA)RB,
(16) C(O)RA,
(17) C(O)-C1-6 haloalkil,
(18) C(O)ORA,
(19) OC(O)N(RA)RB,
(20) SRA,
(21) S(O)RA,
(22) S(O)2RA,
(23) S(O)2N(RA)RB,
(24) N(RA)S(O)2RB,
(25) N(RA)S(O)2N(RA)RB,
(26) N(RA)C(O)RB,
(27) N(RA)C(O)N(RA)RB,
(28) N(RA)C(O)-C(O)N(RA)RB, ili
(29) N(RA)CO2RB, i
(ii) od nula do 2 supstituenta su svaki nezavisno:
(1) CycQ,
(2) AriQ,
(3) HetQ,
(4) HetR,
(5) J-CycQ,
(6) J-AriQ,
(7) J-HetQ,
(8) J-HetR,
(9) C1-6 alkil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR,
(10) C2-6 alkenil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR, ili
(11) C2-6 alkinil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR;
HetA, HetB i HetC su nezavisno heterociklil ili heteroaril koji je izborno supstituiran sa ukupno od 1 do 8 supstituenata, gdje :
(i) od nula do 8 supstituenata su svaki nezavisno:
(1) C1-6 alkil,
(2) C1-6 haloalkil, koji je izborno supstituiran sa 1 do 3 dodatna supstituenta od kojih je svaki nezavisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(3) C1-6 alkil supstituiran sa od 1 do 3 supstituenta od kojih je svaki nezavisno izabran od OH, O-C1-6 alkila, O-C1-6 haloalkila, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(4) C2-6 alkenil,
(5) C2-6 alkenil supstituiran sa od 1 do 3 supstituenta od kojih je svaki nezavisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(6) C2-6 alkinil,
(7) C2-6 alkinil supstituiran sa od 1 do 3 supstituenta od kojih je svaki nezavisno OH, O-C1-6 alkil, O-C1-6 haloalkil, CN, NO2, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, S(O)2RA, S(O)2N(RA)RB, N(RA)C(O)RB, N(RA)CO2RB, N(RA)S(O)2RB, N(RA)S(O)2N(RA)RB, OC(O)N(RA)RB, N(RA)C(O)N(RA)RB, ili N(RA)C(O)C(O)N(RA)RB,
(8) O-C1-6 alkil,
(9) O-C1-6 haloalkil,
(10) OH,
(11) okso,
(12) halogen,
(13) CN,
(14) NO2,
(15) N(RA)RB,
(16) C(O)N(RA)RB,
(17) C(O)RA,
(18) C(O)-C1-6 haloalkil,
(19) C(O)ORA,
(20) OC(O)N(RA)RB,
(21) SRA,
(22) S(O)RA,
(23) S(O)2RA,
(24) S(O)2N(RA)RB,
(25) N(RA)S(O)2RB,
(26) N(RA)S(O)2N(RA)RB,
(27) N(RA)C(O)RB,
(28) N(RA)C(O)N(RA)RB,
(29) N(RA)C(O)-C(O)N(RA)RB, or
(30) N(RA)CO2RB, i
(ii) od nula do 2 supstituenta su svaki nezavisno:
(1) CycQ,
(2) AriQ,
(3) HetQ,
(4) HetR,
(5) J-CycQ,
(6) J-AriQ,
(7) J-HetQ,
(8) J-HetR,
(9) C1-6 alkil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR,
(10) C2-6 alkenil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR, ili
(11) C2-6 alkinil supstituiran sa CycQ, AriQ, HetQ, HetR, J-CycQ, J-AriQ, J-HetQ, ili J-HetR;
svaki CycQ je nezavisno C3-8 cikloalkil ili C5-8 cikloalkenil, pri čemu cikloalkil ili cikloalkenil je izborno supstituiran sa od 1 do 4 supstituenta, od kojih je svaki nezavisno halogen, C1-6 alkil, OH, O-C1-6 alkil, C1-6 haloalkil ili O-C1-6 haloalkil;
svaki AriQ je nezavisno fenil ili naftil, gdje je fenil ili naftil izborno supstituiran sa od 1 do 5 supstituenata od kojih je svaki nezavisno halogen, CN, NO2, C1-6 alkil, C1-6 haloalkil, OH, O-C1-6 alkil, O-C1-6 haloalkil, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SRA, S(O)RA, SO2RA, SO2N(RA)RB ili SO2N(RA)C(O)RB;
svaki HetQ je nezavisno heteroaril koji je izborno supstituiran sa od 1 do 4 supstituenta od kojih je svaki nezavisno halogen, C1-6 alkil, C1-6 haloalkil, OH, O-C1-6 alkil, O-C1-6 haloalkil, N(RA)RB, C(O)N(RA)RB, C(O)RA, CO2RA, SO2RA, N(RA)C(O)N(RA)RB ili N(RA)CO2RB;
svaki HetR je nezavisno 4- do 7-člani, zasićeni ili nezasićeni, nearomatični heterociklični prsten koji sadrži najmanje jedan atom ugljika i od 1 do 4 heteroatoma nezavisno izabrana od N, O i S, gdje je svaki S izborno oksidovan do S(O) ili S(O)2, i gdje je zasićeni ili nezasićeni heterociklični prsten izborno supstituiran sa od 1 do 4 supstituenta od kojih je svaki nezavisno halogen, CN, C1-6 alkil, OH, okso, O-C1-6 alkil, C1-6 haloalkil, O-C1-6 haloalkil, C(O)N(RA)RB, C(O)RA, CO2RA, ili SO2RA;
svaki J je nezavisno:
(i) O,
(ii) S,
(iii) S(O),
(iv) S(O)2,
(v) O-C1-6 alkilen,
(vi) S-C1-6 alkilen,
(vii) S(O)-C1-6 alkilen,
(viii) S(O)2-C1-6 alkilen,
(ix) N(RA), ili
(x) N(RA)-C1-6 alkilen;
svaki RA, RB, RC i RD su nezavisno izabrani od H, C1-6 alkila i C3-6cikloalkila, pri čemu su navedeni C1-6 alkil i C3-6cikloalkil izborno supstituirani jednim ili više supstituenata do maksimalnog broja dozvoljenog valencom izabranog iz grupe koja se sastoji od: halogena, OH, CN, C1-4alkoksi, C3-6cikloalkila i fenila;
ili alternativno svaki par RC i RD zajedno sa azotom za koji su oba vezani formiraju 4- do 7-člani zasićeni ili mono-nezasićeni prsten koji izborno sadrži heteroatom pored N za koji su RC i RD vezani, pri čemu je dodatni heteroatom izabran od N, O i S; pri čemu je prsten izborno supstituiran sa 1 ili 2 supstituenta od kojih je svaki nezavisno C1-6 alkil, C(O)RA, C(O)ORA, C(O)N(RA)RB ili S(O)2RA; i pri čemu je izborni S u prstenu izborno u obliku S(O) ili S(O)2
svaki aril je nezavisno (i) fenil, (ii) 9- ili 10-člani biciklični, fuzionirani karbociklični sustav prstena u kome je najmanje jedan prsten aromatičan, ili (iii) 11- do 14-člani tricikličan, fuzioniran karbocikličan sistem prstena u kome je najmanje jedan prsten aromatičan;
svaki heterociklil je nezavisno (i) 4- do 8-člani, zasićeni ili nezasićeni monociklični prsten, (ii) 7- do 12-člani biciklični sistem prstena, ili (iii) 10- do 18-člani tricikličan sistem prstena, gdje je svaki prsten u (ii) ili (iii) nezavistan od, fuzionisan sa ili premošćen sa drugim prstenom ili prstenovima i svaki prsten je zasićen ili nezasićen;gdje monocikličan prsten sadrži od 1 do 4 heteroatoma i ravnotežu atoma ugljenika; bicikličan sistem prstena ili tricikličan sistem prstena sadrži od 1 do 8 heteroatoma i ravnotežu atoma ugljenika, gdje jedan ili više od prstenova sadrže jedan ili više od heteroatoma; gdje su heteroatomi izabrani od N, O i S; i gdje su bilo koji ili više od heteroatoma azota i sumpora izborno oksidovani, i bilo koji ili više od heteroatoma azota je izborno kvaternizovan;
svaki heteroaril je nezavisno (i) 5- ili 6-člani heteroaromatični prsten koji sadrži od 1 do 4 heteroatoma nezavisno izabrana od N, O i S, gdje je svaki N izborno u obliku oksida, ili (ii) 9- ili 10-člani heterobicikličan, fuzioniran sustav prstena koji sadrži od 1 do 6 heteroatoma nezavisno izabrana od N, O i S, gdje bilo koji ili oba prstena sadrže jedan ili više od heteroatoma, najmanje jedan prsten je aromatičan, svaki N je izborno u obliku oksida i svaki S u prstenu koji nije aromatičan je izborno S(O) ili S(O)2.
2. Kombinacija prema patentnom zahtjevu 1, naznačena time što spoj formule I je izabrano od:
[image]
i
[image]
ili njegove farmaceutski prihvatljive soli.
3. Kombinacija prema patentnom zahtjevu 1 ili patentnom zahtjevu 2, naznačena time što jedno ili više sredstava protiv HIV-a je antivirusno sredstvo izabrano od inhibitora HIV proteaze, nukleozidnih inhibitora HIV reverzne transkriptaze, nenukleozidnih inhibitora HIV reverzne transkriptaze, inhibitora HIV integraze, inhibitora fuzije HIV-a i inhibitora ulaska HIV-a.
4. Kombinacija prema patentnom zahtjevu 1 ili patentnom zahtjevu 2, naznačena time što su jedan ili više sredstava protiv HIV-a izabrani od:
[image]
5. Farmaceutska kompozicija koja sadrži kombinaciju prema bilo kojem od patentnih zahtjeva 1-4 i farmaceutski prihvatljiv nosač.
6. Kombinacija prema bilo kojem od patentnih zahtjeva 1-4, za uporabu u inhibiciji HIV reverzne transkriptaze kod subjekta.
7. Kombinacija prema bilo kojem od patentnih zahtjeva 1-4, za uporabu u profilaksi infekcije HIV-om ili profilaksi SIDA-e kod subjekta.
8. Kombinacija prema bilo kojem od patentnih zahtjeva 1-4, za uporabu u liječenju infekcije HIV-om, liječenju SIDA-e, ili odlaganju početka SIDA-e kod subjekta.
9. Kombinacija za uporabu prema patentnom zahtjevu 6, naznačena time što je subjekt čovjek.
10. Kombinacija za uporabu prema patentnom zahtjevu 7, naznačena time što je subjekt čovjek.
11. Kombinacija za uporabu prema patentnom zahtjevu 8, naznačena time što je subjekt čovjek.
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