US 2024/0182473 A1Published application

Compounds useful in hiv therapy

AssigneesGlaxoSmithKline Intellectual Property Development Limited, ViiV Healthcare Company

InventorsMartha Alicia DE LA ROSA, John F. MILLER, B. Narasimhulu NAIDU, Vicente SAMANO, David TEMELKOFF, Emile Johann VELTHUISEN

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Abstract

The invention relates to compounds of Formula (I), (Ia), (II) or (IIa), salts thereof, pharmaceutical compositions thereof, as well as methods of treating or preventing HIV in subjects.

Claims26

Dependent claims

A compound of formula (I):

wherein:
R1 is:
wherein
X is selected from the group consisting of NH2, F and Cl;
R5 is selected from the group consisting of H and (C1-C14) alkyl;
R6 is selected from the group consisting of H and —(C═O)—(C1-C14) alkyl;
R2 is selected from the group consisting of (C1-C24) alkyl;
(CH2)n1—O—(CH2CH2O)n2—(C1-C14 alkyl) where n1 and n2 are integers independently selected from 1-4 —R7—NH—(C═O)—R8 wherein R7 may be (C1-C14) alkyl and R8 may be independently selected from H and (C1-C14) alkyl;
—R9—(C6-C14) aryl, wherein R9 is a bond or (C1-C6) alkyl;
—R10—(C3-C14) cycloalkyl, wherein R10 is a bond or (C1-C6) alkyl;
—(C1-C20) alkylene-(C═O)—O—R11 wherein R11 may be selected from H and (C1-C20) alkyl;
and
and;
R3 is selected from the group consisting of H, —(C═O)—(C1-C24) alkyl;
—(C═O)—O—(C1-C24) alkyl;
and C3-C14 cycloalkyl or
R2 and R3 join together to form a C3 to C28 cyclic structure;
and
with the proviso that when R2 is (C1-C14 alkyl) at least one of R3, R5 and R6 is not H.

16 more elements

A compound selected from the group consisting of:

Parent Structure
Chemical Name
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan- 2-yl]methyl cyclohexane- carboxylate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9- yl)-2-ethynyl-3- hydroxyoxolan- 2-yl]methyl benzoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 2- phenylacetate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan- 2-yl]methyl (1rs,4rs)-4-tert- butylcyclohexane-1- carboxylate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan- 2-yl]methyl (1rs,4sr)-4- pentylcyclohexane- 1-carboxylate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 2-(2- methoxyethoxy) acetate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 2-[2-(2- methoxyethoxy) ethoxy]acetate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 2-(2- butoxyethoxy)acetate
10-{[(2R,3S,5R)- 5-(6-amino-2- fluoro-9H-purin- 9-yl)-2-ethynyl-3- hydroxyoxolan-2- yl]methoxy}-10- oxodecanoic acid
14-{[(2R,3S,5R)- 5-(6-amino-2- fluoro-9H-purin-9- yl)-2-ethynyl-3- hydroxyoxolan-2- yl]methoxy}-14- oxotetradecanoic acid
20-{[(2R,3S,5R)- 5-(6-amino-2- fluoro-9H-purin-9- yl)-2-ethynyl-3- hydroxyoxolan-2-yl] methoxy}-20- oxoicosanoic acid
1-[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 5-[1,3- bis(heptanoyloxy) propan-2-yl] pentanedioate
1-[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 5-[1,3- bis(tetradecanoyloxy) propan-2-yl] pentanedioate
1-[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl 5- tetradecyl pentanedioate
[(2R,3S,5R)-5-(6- amino-2-fluoro- 9H-purin-9-yl)-3- [(ethoxycarbonyl) oxy]-2- ethynyloxolan- 2-yl]methyl decanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (heptanoyloxy) oxolan-2-yl]methyl heptanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (tetradecanoyloxy) oxolan-2- yl]methyl tetradecanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)-3- (decanoyloxy)-2- ethynyloxolan- 2-yl]methyl decanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- [(pentanoyloxy) methyl]oxolan-3-yl tridecanoate
(2R,3S,5R)-5-(6- amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- [(pentanoyloxy) methyl]oxolan-3-yl heptanoate
(2R,3S,5R)-5-(6- amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- [(pentanoyloxy) methyl]oxolan-3-yl undecanoate
(2R,3S,5R)-5-(6- amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- [(pentanoyloxy) methyl]oxolan-3-yl nonanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (pentanoyloxy) oxolan-2-yl]methyl pentanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (propanoyloxy) oxolan-2-yl]methyl pentanoate
[(2R,3S,5R)-5- (6-butanamido-2- fluoro-9H-purin- 9-yl)-2-ethynyl-3- hydroxyoxolan- 2-yl]methyl pentanoate
[(2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-octanamido-9H- purin-9-yl)-3- hydroxyoxolan- 2-yl]methyl pentanoate
[(2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-tetradecanamido- 9H-purin-9-yl)- 3-hydroxyoxolan- 2-yl]methyl pentanoate
[(2R,3S,5R)-5- (6-dodecanamido-2- fluoro-9H-purin-9- yl)-2-ethynyl-3- hydroxyoxolan- 2-yl]methyl pentanoate
(2R,3S,5R)-5-(6- amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2-{[(2- propylpentanoyl) oxy]methyl}oxolan- 3-yl dodecanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 3-(butanoyloxy)-2- ethynyloxolan-2- yl]methyl 2- propylpentanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)-3- (butanoyloxy)-2- ethynyloxolan- 2-yl]methyl decanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (heptanoyloxy) oxolan-2-yl]methyl benzoate
(2R,3aS,20aR)- 2-(6-amino-2- fluoro-9H-purin-9- yl)-20a-ethynyl- octadecahydro-2H- furo[3,2-b]1,5- dioxacyclo- nonadecane- 5,18-dione
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9- yl)-2-ethynyl-3- hydroxyoxolan-2- yl]methyl 2- heptanamidoacetate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan- 2-yl]methyl 2- tetradecan- amidoacetate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxyoxolan-2- yl]methyl (2S)-2- heptanamido- propanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 3-(butanoyloxy)-2- ethynyloxolan- 2-yl]methyl tetradecanoate
[(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- {[(hexyloxy)carbonyl] oxy}oxolan-2- yl]methyl tetradecanoate
(2R,3S,5R)-5-(6- amino-2-fluoro- 9H-purin-9-yl)-2- ethynyl-2-{[(2- propylpentanoyl)oxy] methyl}oxolan- 3-yl heptanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl tetradecanoyl- L-alaninate
(2R,3S,5R)-2- (acetoxymethyl)-5-(6- amino-2-fluoro- 9H-purin-9-yl)-2- ethynyltetrahy- drofuran-3-yl heptanoate
((2R,3S,5R)-5- (6-decanamido-2- fluoro-9H-purin-9- yl)-2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl heptanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (((hexyloxy)carbonyl) oxy)tetrahydro furan-2-yl)methyl heptanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (((hexyloxy)carbonyl) oxy)tetrahydro furan-2-yl)methyl decanoate
((2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-tetradecanamido- 9H-purin-9-yl)-3- hydroxytetra- hydrofuran- 2-yl)methyl benzoate
((2R,3S,5R)-5- (6-decanamido-2- fluoro-9H-purin-9- yl)-2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl benzoate
((2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-tetradecanamido- 9H-purin-9-yl)-3- hydroxytetra- hydrofuran- 2-yl)methyl heptanoate
((2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-tetradecanamido- 9H-purin-9-yl)-3- hydroxytetra- hydrofuran- 2-yl)methyl decanoate
((2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-tetradecanamido- 9H-purin-9-yl)-3- hydroxytetra- hydrofuran- 2-yl)methyl 2- propylpentanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9- yl)-2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl 3-(2-acetoxy-4,6- dimethylphenyl)- 3-methylbutanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((heptanoyloxy) methyl)tetrahydro- furan-3-yl tetradecanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- (((tridecyloxy) carbonyl) oxy)tetrahy- drofuran-2- yl)methyl heptanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((propionyloxy) methyl) tetrahydro- furan-3-yl stearate
((2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-heptanamido- 9H-purin-9-yl)-3- hydroxytetra- hydrofuran- 2-yl)methyl 2-propylpentanoate
((2R,3S,5R)-2- ethynyl-5-(2-fluoro- 6-tetradecanamido- 9H-purin-9-yl)-3- hydroxytetra- hydrofuran- 2-yl)methyl propionate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)-3- ((ethoxycarbonyl) oxy)-2- ethynyltetra- hydrofuran- 2-yl)methyl tetradecanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl (1,3-bis (isobutyryloxy) propan-2-yl) succinate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)-2- ((dodecanoyloxy) methyl)-2- ethynyltetra- hydrofuran- 3-yl dodecanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((palmitoyloxy) methyl) tetrahydro- furan-3-yl palmitate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((icosanoyloxy) methyl) tetrahydro- furan-3-yl icosanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((undecanoyloxy) methyl)tetrahydro- furan-3-yl undecanoate
(2R,3aS,26aR)- 2-(6-amino-2- fluoro-9H-purin- 9-yl)-26a- ethynyldocosahydro- 2H-furo [3,2-b][1,5] dioxacyclo- pentacosine-5,24- dione
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((hexanoyloxy) methyl) tetrahydro- furan-3-yl hexanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((nonanoyloxy) methyl) tetrahydro- furan-3-yl nonanoate
(2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-2- ((octanoyloxy) methyl) tetrahydro- furan-3-yl octanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl 3-(2,4-dimethyl-6- (pivaloyloxy) phenyl)-3- methylbutanoate
2-(4-(((2R,3S,5R)- 5-(6-amino-2- fluoro-9H- purin-9-yl)- 2-ethynyl-3- hydroxytetra- hydrofuran-2- yl)methoxy)- 2-methyl- 4-oxobutan- 2-yl)-3,5- dimethylphenyl decanoate
((2R,3S,5R)-5- (6-amino-2-fluoro- 9H-purin-9-yl)- 2-ethynyl-3- hydroxytetra- hydrofuran- 2-yl)methyl (1,3-bis (heptanoyloxy) propan-2-yl) succinate
and pharmaceutically acceptable salts thereof.

68 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/508,355Filed 14 Nov 2023
Priority: 6 Mar 2019
Published: 6 Jun 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 473/34
Nitrogen atom: attached in position 6, e.g. adenine
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 31/70
Medicinal preparations containing organic active ingredients: carbohydrates; Sugars; Derivatives thereof
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Application62/814,316Us provisional application · filed 6 Mar 2019
Application16/865,678Continuation · filed 4 May 2020
Application18/508,355Continuation
US 12,240,853 B2Related patent
US 2023/0174534 A1Published application
US 2024/0182473 A1This patent

From the US filing history. Foreign family members aren’t listed.

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