Discovery of macrocyclic HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation

Article abstract of DOI:10.1016/j.bmcl.2021.128168

A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified with good enzymatic activity and high selectivity over HDACs 6 and 8. These macrocyclic HDAC inhibitors used an ethyl ketone as the zinc-binding group. Compounds 25 and 26 stood out as leads due to their low double-digit nM EC₅₀s in the 2C4 cell-based HIV latency reactivation assay. The PK profiles of these macrocyclic HDAC inhibitors still needed improvement.

Full text of DOI:10.1016/j.bmcl.2021.128168

Journal Pre-proofs
Discovery of macrocyclic HDACs 1, 2, and 3 selective inhibitors for HIV la‐
tency reactivation
Wensheng Yu, James Fells, Dane Clausen, Jian Liu, Daniel J. Klein, C.
Christine Chung, Robert W. Myers, Jin Wu, Guoxin Wu, Bonnie J. Howell,
Richard J.O. Barnard, Joseph Kozlowski
PII:
S0960-894X(21)00395-4
DOI:
Reference:
https://doi.org/10.1016/j.bmcl.2021.128168
BMCL 128168
To appear in:
Bioorganic & Medicinal Chemistry Letters
Received Date:
Accepted Date:
3 May 2021
28 May 2021
Please cite this article as: Yu, W., Fells, J., Clausen, D., Liu, J., Klein, D.J., Chung, C.C., Myers, R.W., Wu, J.,
Wu, G., Howell, B.J., Barnard, R.J.O., Kozlowski, J., Discovery of macrocyclic HDACs 1, 2, and 3 selective
inhibitors for HIV latency reactivation, Bioorganic & Medicinal Chemistry Letters (2021), doi: https://doi.org/
10.1016/j.bmcl.2021.128168
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Discovery of macrocyclic HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation
Wensheng Yua,*, James Fellsb, Dane Clausena, Jian Liua, Daniel J. Kleinb, Christine C. Chunga, Robert
W. Myersa, Jin Wua, Guoxin Wub, Bonnie J. Howellb, Richard J. O. Barnardb, Joseph Kozlowskia
aMerck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA
bMerck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA
This is where the receipt/accepted dates will go; Received Month XX, 2020; Accepted Month XX, 2021 [BMCL RECEIPT]
Abstract— A series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors were identified with
good enzymatic activity and high selectivity over HDACs 6 and 8. These macrocyclic HDAC inhibitors
used an ethyl ketone as the zinc-binding group. Compounds 25 and 26 stood out as leads due to their low
double-digit nM EC50s in the 2C4 cell-based HIV latency reactivation assay. The PK profiles of these
macrocyclic HDAC inhibitors still needed improvement.
[BMCL ABSTRACT] ©2000 Elsevier Science Ltd. All rights reserved.
*Corresponding author.
E-mail address: wenshengyu@msn.com (W. Yu).

It was estimated that 38 million people in the world are infected with Human
Immunodeficiency Virus (HIV).1 The current treatment of combined antiretroviral therapy (cART)
can maintain the virus to undetectable levels, but any disruption will make the virus rebound due
to the existing of the silent HIV-infected memory CD4+ T cells (HIV latency).2 The half-life of
the infected resting memory CD4+ T-cells was estimated to be 44 months,3,4 therefore it would
theoretically take the current cART treatment more than 70 years to eradicate the HIV latency.
Life-long treatment for HIV infection is a big burden to the patients’ health as well as the society.
Acomplete cure of HIV infection is an unmet medical need. Among the current strategies targeting
at a complete cure of HIV infection, the most promising one is known as “shock and kill” strategy.5
In this strategy, a latency-reversing agent (LRA) is used to “shock” the latently infected CD4+ T
cells to induce them produce viral proteins. Once decorated with HIV specific proteins, the infected
memory T-cells can be distinguished and become susceptible to “kill” agents. Reported LRAs are
histone deacetylase inhibitors (HDACi), protein kinase C agonists (PKC), histone methylation
inhibitors (HMTi), DNA methyltransferase inhibitors (DNMTi), bromodomain and extra terminal
(BET) domain proteins (BET) inhibitors, and disulfiram.6
HDAC enzymes are essential for histones deacetylation process which results in a condensed
inactive chromatin structure and shut down the gene expression.7,8 HDAC inhibitors can prevent
this process from happening and keep the chromatin in its active form. HDAC inhibitors have been
used to treat cancers.9,10 Using HDAC inhibitors as LRAs to eradicate HIV latency has been proved
in clinical studies with vorinostat (SAHA), 11 panobinostat, 12 and romidepsin. 13 Significant
increases of HIV mRNA level in resting CD4+ T-cells as well as plasma viraemia were achieved
after administration of HDAC inhibitors.14,15 To ensure the efficacy of the “kick and kill” strategy,
more powerful kick or kill agents would be desired for future clinic studies.16
Early hydroxamic acid based HDAC inhibitors were non-selective and they were active
against HDAC classes I (HDACs 1, 2, 3, 8) and II (HDACs 4, 5, 6, 7, 9, 10) isozymes. Using them
for chronic treatments remains a concern because of their known undesired effects.17 Identification
of selective HDAC inhibitors has become the focus in this research field. Our effort on HDAC
inhibitors used to be focused on oncology purpose.18,19 But our recently effort has shifted to “shock
and kill” strategy for the treatment of HIV latency. To evaluate the cellular potency against HIV
latency, we used the Jurkat model of HIV latency based on 2C4 cells as the latency reactivation
assay. The 2C4 cell assay measures the reactivation of a quiescent HIV provirus by quantification
of the luciferase reporter gene. This cell line was produced based on the same method as Jurkat
HIV T-cell line which used an eGFP reporter gene.20, 21, 22 0.1% Normal human serum (NHS) was
added into the assay to make the Jurkat 2C4 cells live longer. 5% NHS was added to measure the
serum shift of the compounds’ cellular potency. Minimum serum shift in cellular potency is
desirable.
Macrocyclic HDAC inhibitors are known. Romidepsin is a macrocycle with excellent
HDAC potency (Figure 1). Apicidin is another macrocyclic HDAC inhibitor with ethyl ketone as

the zinc-binding group (Figure 1).23 SAR studies based on apicidin scaffold led to the discovery
of 1 and 2 which were HDACs 1, 2, and 3 selective inhibitors (Table 1).24 Both compounds used
an ethyl ketone as the Zinc binding group. However, both 1 and 2 were not as potent as apicidin
against HDACs 1, 2, and 3 (Table 1). Macrocycles could potentially have more interaction with
HDAC 2 enzyme and therefore have better potency. As apicidin had a complex structure,
simplified macrocycles HDAC inhibitors could be derived from 1 and 2. The X-ray structure of 2
co-crystalized with HDAC 2 enzyme was published (access codes for X-ray coordinates in RCSB
Protein Data Bank (PDB) database is 6WBW).25 Docking experiment of 1 into the active site of
HDAC 2 showed that a macrocycle could be formed between the phenyl and the azetidine.
Docking experiments also indicated that a six- or seven-atom linker could fit the active site of
HDAC 2 the best. Therefore macrocycles 3–8 were prepared and their HDAC potency are
summarized in Table 1. Compounds 3 and 4 were diastereomers of the macrocycle with a six-
atom linker between the phenyl and the azetidine, unfortunately, both were not as potent as 1 and
2. Compounds 5 and 6 were diastereomers of the corresponding macrocycle with a seven-atom
linker. Again, neither were as potent as 1 and 2. Replacing the oxygen atom in the linker of 3 and
4 with a carbon led to derivatives 7 and 8, which did not show any improved potency. It seemed
that macrocycles with a linker between the phenyl and azetidine of 1 could not improve the potency
against HDACs 1, 2, and 3. Compound 4 was co-crystalized with HDAC 2 enzyme and its X-ray
structure is shown in Figure 2.
Figure 1. Macrocyclic HDAC inhibitors romidepsin and apicidin
Table 1. Potency data of HDAC inhibitors apicidin and 1–826
HDAC IC50 (nM)
2C4 cell EC50 (nM)
ID
Structures
1
2
3
6
8
0.1% NHS 5% NHS
1.1
9.0
1.7
> 900
134
125
587

37
13
249
18
12
12
5,749 14,950
2,468
110
2,363
477
1
2
680
>10,000
ND
2,558 8,617
791
91
NDa
ND
3,168
ND
ND
5,086
ND
3
4
5
216
682
911
5,394 21,460
2,828
242
ND
ND
218
668
105
5,549
8,419
1,569
3,019
6
2,940 5,951 1,224
355 1,140 188
ND
ND
ND
ND
ND
ND
ND
ND
7
8
aNot determined.
Figure 2. X-ray structure of 4 in HDAC 2 (access codes for X-ray coordinates in RCSB Protein
Data Bank (PDB) database is 7MOS)
During our continued SAR studies in HDAC inhibitors, compounds 9 and 10 were
discovered with improved potency against HDACs 1, 2, and 3 (Table 2).27 Compound 10 had a
spiro-cyclopropyl-piperidine in the amide region and it was 3- to 5-fold more potent against
HDACs 1, 2, and 3 than 9. The X-ray structure of 9 co-crystalized with HDAC 2 enzyme is shown
in Figure 3. The primary amide in the imidazole core of 9 or 10 offered a good opportunity to
form a macrocycle with the phenyl group. Docking experiments of such macrocycles with different
ring sizes indicated that a five-carbon linker between the amide and phenyl group was optimal for
the HDAC potency. Macrocycles 11–13 were prepared, and their data are summarized in Table 2.
Compound 11 had a cis double bond in the linker, and it was significantly less potent than 10.
Compound 12 was the trans isomer of 11. Although it was more potent than 9 against HDACs 1,

2, and 3, it was still significantly less potent than 10. When the double bond in the linker of 11 or
12 was reduced to alkane (13), its HDAC potency was not improved. It seemed that the
macrocycles formed by linking the amide and the phenyl group were not able to improve the
potency against HDACs 1, 2, and 3.
Figure 3. X-ray structure of 9 in HDAC 2 (access codes for X-ray coordinates in RCSB PDB
database is 7MOT)
Table 2. Potency data of HDAC inhibitors 9–1326
HDAC IC50 (nM)
2C4 cell EC50 (nM)
ID
Structures
1
2
3
6
8
0.1% NHS 5% NHS
1.9
18
2.5
9,829 5,422
294
269
9
0.4
133
21
5.0
0.7 17,460 6,364
193
1,464
5,235
>40000
165
10
11
12
13
572 113 >900
90
2,875
1,9340
12,000
223
18
>900
>900
>900
109 >900 103 >900

Compounds 14 was another selective HDACs 1, 2, and 3 inhibitor we identified (Table 3).
It had 1,2,3,4-tetrahydro-1,4-methanonaphthalene attached to the imidazole core, and showed
good potency against HDACs 1, 2, and 3 as well as in the 2C4 cell latency reactivation assay. The
X-ray structure of 14 co-crystalized with HDAC 2 enzyme is shown in Figure 4. It seemed that
the 1,2,3,4-tetrahydro-1,4-methanonaphthalene offered a good attaching point to form a
macrocycle with the spiro-cyclopropyl-piperidine nitrogen. Docking experiments of such
macrocycles with different ring sizes indicated that a four-carbon linker between the 1,2,3,4-
tetrahydro-1,4-methanonaphthalene and spiro-cyclopropyl-piperidine nitrogen fit the active site of
HDAC 2 the best. Therefore 15 and 16 were prepared and their HDAC potency are summarized
in Table 3. Compound 15 had a four-carbon linker with a trans double bond. To our delight, it
showed better enzymatic and cellular potency than 14. This is the first time we proved that forming
a macrocycle from a HDAC inhibitor could improve its potency. Reducing the double bond in the
linker of 15 hurt its potency and 16 was not as potent as 14. Compound 17 was a regio-isomer of
16 with less potency.
Figure 4. X-ray structure of 14 in HDAC 2 (access codes for X-ray coordinates in RCSB PDB
database is 7MOX)
Table 3. Potency data of HDAC inhibitors 14–1726
HDAC IC50 (nM)
2C4 cell EC50 (nM)
1
2
3
6
8
0.1% NHS 5% NHS
8.2
36
3.7
7847 4527
351
73
376
76
14
15
2.7
7.0
0.86 >900 >900

19
45
147
176
49
24
>900 >900
>900 >900
844
867
16
17
6,267
9,059
Compound 18 was potent HDAC inhibitor we discovered recently (Table 4).28 Compound
19 was a close analog of 18 and showed even better potency. Compound 19 was co-crystallized
with HDAC 2 enzyme and its X-ray structure is shown in Figure 5. The two ethyl substituents
offered two proper attachment points to form a macrocyclic ring. Based on docking experiments,
macrocyclic HDAC inhibitors 20–26 were prepared and their potency data are listed in Table 4.
Compound 20 was a macrocycle with a five-atom linker between the isoquinolin-1(2H)-one and
spiro-cyclopropylpiperidine moieties. It showed good potency against HDAC 1, 2, and 3. However,
it lost potency in the 2C4 cell assay. Compound 21 is the quinolin-2(1H)-one analog of 14 with a
five-carbon linker and an oxazole core. It was not as potent as 20 against HDAC 1, 2, and 3.
Compound 22 is a close analog of 20 with five carbons and an oxygen in the linker. It was more
potent against HDACs 1 and 3 than 20. However, it still did not show activity in the 2C4 cell assay.
Compound 23 was the O-alkylation product obtained during the synthesis of 21. It had a different
attaching point and different ring size than 21. It was similar in potency as 21 except 3-fold less
potent against HDAC 3. The better potency of 22 against HDAC 1 and 3 than 20 hinted that a
bigger ring size might be beneficial to HDAC potency. Therefore, a macrocyclic analog with a
linker containing six carbons and an oxygen was prepared (24), and it showed improved potency
against HDACs 2 and 3 than 22. It also showed improved potency, still pretty weak, in the 2C4
cell assay. Very interestingly, compound 25, which had a linker of eight carbons and no oxygen,
showed low double-digit nM EC50 values in the 2C4 cell assay. It showed 20-fold improvement in
potency against HDAC 2 than 24. Its selectivity against HDAC 6 and 8 was above 2000X, and its
serum shift in the cellular activity between 0.1% and 5% NHS was only 1.1X. Introduction of a
methoxy group to the first phenyl ring of the isoquinolin-1(2H)-one was discovered previously to
be able to improve cellular potency. The corresponding methoxy analog of 25 was prepared to
give 26. But it was similar in potency to 25 with reduced selectivity over HDAC 6. Compound 27
is a macrocycle without the spiro-cyclopropylpiperidine moiety which could offer the macrocycle
ring more flexibility. However, it only showed moderate potency against HDAC 1, 2, and 3.
Compound 25 was co-crystalized with HDAC 2 and its X-ray structure is shown in Figure 6.
Compound 25 fit the active site of HDAC 2 pretty well with the macrocycle fixed its configuration.
That could explain the improved potency of 25 against HDAC 2.

Figure 5. X-ray structure of 19 in HDAC 2 (access codes for X-ray coordinates in RCSB PDB
database is 7MOY)
Table 4. Potency data of HDAC inhibitors 18–2726
HDAC IC50 (nM)
2C4 cell EC50 (nM)
1
2
3
6
8
0.1% NHS 5% NHS
<0.3
1.6
<0.3 2,000 5,600
100
52
130
56
18
19
<1.5 <1.5 <1.5 2,977 6,261
0.61
16
35
7.1
56
>900 >900
>40000
5,147
>40000
4,734
20
21
260
858
>900
0.11
24
22
335
8.5
2.6
>900 >900
>40000
>40000
1,788
>40000
>40000
1,985
22
23
24
150 >900 >900
0.33
0.32 >900
808

0.20 0.43 0.06 >900 >900
14
11
16
12
25
26
27
0.11 0.31 0.13
218
>900
28
595
247 >900 >900
2,500
3,513
Figure 6. X-ray structure of 25 in HDAC 2 (access codes for X-ray coordinates in RCSB PDB
database is 7MOZ)
Selected macrocyclic HDAC inhibitors were tested in rat PK studies. The data are
summarized in Table 5. Compound 20 showed good clearance and reasonable T1/2, but its
bioavailability was low. Compound 25 showed high clearance. Compound 26 showed moderate
clearance and long T1/2, but its bioavailability was still low. The PK profiles of these compounds
still needed improvement.
Table 5. Pharmacokinetic profiles of HDAC inhibitors 20, 25, 26 in rata
IV
PO
ID
Dose
(mpk)
2
T1/2
CL
Dose
(mpk)
10
AUC
(μM.h)
0.11
Tmax
(h)
C24h
(μM)
0.001
ND
Cmax
(μM)
0.062
ND
F%
(h) (mL/min/Kg)
3.9
2.8
14
3.9
312
96
0.25
ND
3
0.15
ND
2.9
20
25
26
0.05
2
NDb
ND
10
0.04
0.013
0
a Winstar Han rats were used. Compounds were dosed at indicated doses in IV in DMSO/PEG400/H2O (20/60/20) as well as in P.O. in 10%
TWEEN. bNot determined.
The preparations of 3 and 4 are demonstrated in Scheme 1. Compound 28 was prepared
based on published method.25 HATU mediated coupling reaction of 28 with 1-(tert-
butoxycarbonyl)azetidine-2-carboxylic acid led to 29 which was converted to 30 via a Suzuki

coupling reaction with (2-hydroxyphenyl)boronic acid. Alkylation of phenol 27 with 1-bromo-5-
chloropentane afforded 31. The Boc group on the azetidine moiety was removed and the
macrocycle was closed via an intra-molecular SN2 alkylation. The two diastereomers were
separated by silica gel chromatography to give 3a and 4a. The SEM group was removed and the
3 and 4 were obtained in good yields. Compound 5 and 6 were prepared in the same method with
1-bromo-6-chlorohexane.
Scheme 1. Reagents and conditions: i) 1-(tert-butoxycarbonyl)azetidine-2-carboxylic acid, HATU, TEA, DMF, rt, 18
h, 64%; ii) (2-hydroxyphenyl)boronic acid, PdCl2(dppf), Na2CO3, 100 oC, 30 min, 62%; iii) 1-bromo-5-chloropentane,
CH3CN, K2CO3, 100 oC, 21 h, 83%; iv) HCl, MeOH, rt, 2 h, 91%; v) NaI, DIPEA, 80 oC, 24 h, SiO2 chromatography,
35% for 3a, 32% for 4a; vi) 3a or 4a, HCl, MeOH, rt, 18 h, 67% for 3, 68% for 4.
Compounds 7 and 8 were prepared in a similar manner as 3 and 4. The key intermediate
37 was prepared by the chemistry outlined in Scheme 2. Sonagashira reaction between 32 and
hex-5-yn-1-ol afforded alkyne 33 which was converted to borate 34. Suzuki coupling reaction of
34 and 29 gave 35 which was reduced to alkane 36. The primary alcohol of 36 was converted to a
bromide to afford 37. Compounds 7 and 8 were prepared from 37 by the same chemistry of step v
and vi in Scheme 1.

Scheme 2. Reagents and conditions: i) hex-5-yn-1-ol, PdCl2(PPh3)2, CuI, TEA, DMF, rt, 12 h, 72%; ii)
4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane), PdCl2(dppf), KOAc, dioxane, 80 °C, 12 h, 91%; iii) 26,
PdCl2(dppf), K2CO3, 80 °C, 12 h, 71%; iv) H2, Pd/C, rt, 2 h; v) CBr4, PPh3, DCM, rt, 2 h, 36%.
The preparation of 13 is outlined in Scheme 3. Compound 38 was prepared based on
published method.27 Amide coupling reaction of 38 with pent-4-en-1-amine gave 39 which
underwent a Suzuki coupling reaction with (3-vinylphenyl)boronic acid afforded 40. Ring closure
metathesis of 40 gave 41 as a mixture of Z and E isomers. After the sulfonamide group was taken
off, the Z (42) and E (43) isomers were separated. Hydrogenation of 42 led to 44 which was
converted to 13 by a HATU mediated amide coupling reaction with (S)-6-ethyl-6-
azaspiro[2.5]octane-1-carboxylic acid.27 Compounds 11 and 12 were prepared from 42 and 43,
respectively, based the same method as step vi in Scheme 3.
Scheme 3. Reagents and conditions: i) pent-4-en-1-amine, PyBOP, DIPEA, rt, 1 h, ii) (3-vinylphenyl)boronic acid,
Pd(PPh3)4, K3PO4, 24 for two steps; iii) Zhan 1B, DCM, 50 oC, 2 h, 44%; iv) HCl, MeOH, rt, 2 h, 57% for 42, 26%
for 43; v) 42, Pd/C, H2 (1 atm), MeOH, rt, 1 h; vi) (S)-6-ethyl-6-azaspiro[2.5]octane-1-carboxylic acid, HATU, DIPEA,
DMF, rt, 1 h, 78% for two steps.
The preparations of 15 and 16 are demonstrated in Scheme 4. Iridium catalyzed C-H
activation of 45 led to two regio-isomers (46a and 46b). Suzuki coupling reaction of 46a with 50
afforded 47. Both Boc groups of 47 were removed and two allyl groups were introduced to give
48. Ring-closure metathesis of 48 led to macrocycle 15. Reduction of the double bond of 15 gave
16 in moderate yield. Compound 17 was prepared from 46b based on the same method as 16.
Compound 27 was prepared based on the same method as described in Scheme 1 with N-(tert-
butoxycarbonyl)-N-methylglycine.

Scheme 4. Reagents and conditions: i) 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane), (1,5-
cyclooctadiene)(methoxy)iridium(I) dimer, hexane, 90 oC, 16 h, 36% for 46a, 20% for 46b; ii) 41a, 50,
PdCl2(DTBPF), K2CO3, THF, 65 oC, 16 h, 82%; iii) HCl, MeOH, 25 oC, 1 h, 93%; iv) 3-bromoprop-1-ene, DIPEA,
CH3CN, 25 oC, 2 h; 53%; v) Grubbs II, DCE, 50 oC, 18 h, 16%; vi) Pd/C, H2 (1 atm), MeOH, 25 oC, 1 h; 33%.
Compound 25 was prepared based on the chemistry outlined in Scheme 5. Intermediate 49
was prepared based on published method.28 Suzuki coupling of 49 and 50 led to 51 which was
converted to 52 via a SN2 alkylation with 1,8-dibromooctane. The Boc group of 52 was removed
and the macrocycle was closed by an intra-molecular SN2 alkylation to afford 25.

o
Scheme 5. Reagents and conditions: i) PdCl2(DTBPF), K3PO4, 75 C, 3 h, 73%; ii) 1,8-dibromooctane, Cs2CO3,
CH3CN, 75 oC, 2 h, 56%; iii) HCl, MeOH, 20 oC, 4 h, 72%; iv) NaI, DIPEA, CH3CN, 37%; v) TFA, DCM, 20 oC, 18
h, 59%.
In summary, a series of unique macrocyclic HDACs 1, 2, and 3 selective inhibitors with
ethyl ketone as the zinc-binding group were discovered. Different types of macrocycles with
different ring sizes were explored. Some of these macrocyclic HDAC inhibitors, such as 15, 25,
and 26, had improved potency than their corresponding non-macrocyclic precursors. Compounds
25 and 26 showed sub-nM IC50s against HDACs 1, 2, and 3, and low double-digit nM EC50s in the 2C4
cell HIV latency reactivation assay. Their selectivity over HDACs 6 and 8 was above 1000X, and their
serum shift in the cellular activity between 0.1% and 5% NHS was both 1.1X. Unfortunately, both 25 and
26 showed high clearance and low bioavailability in rat PK studies. Their PK profiles in rat still need to be
improved.
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26
All compounds tested in this publication had purity > 95% determined by LCMS or HPLC, and
their structures were fully characterized by LCMS and 1H-NMR spectra. All reported values were
the mean of two assay measurements or greater. Standard deviation was within three-fold of the
reported value for all compounds. For HDAC enzymatic and 2C4 cell-based HIV reactivation
assay methods, see reference 28.
27
Clausen, D. J.; Liu, J.; Yu, W.; Duffy, J.; Chang, C. C.; Myers, R. W.; Klein, D. J.; Fells, J.;
Holloway, K.; Wu, J.; Wu, G.; Howell, B. J.; Barnard, R. J. O.; Kozlowski, J. Development of a
selective HDAC inhibitor aimed at reactivating the HIV latent reservoir. Bioorg. Med. Chem.
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Chang, C. C.; Myers, R. W.; Klein, D. J.; Fells, J.; Holloway, K.; Wu, J.; Wu, G.; Howell, B. J.;
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