1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same

11958,844

17/263333

July 25, 2019

The present invention relates to novel compounds having a histone deacetylase 6 (HDAC6) inhibitory activity, optical isomers thereof or pharmaceutically acceptable salts thereof, a pharmaceutical use thereof, and a method for preparing the same. According to the present invention, the novel compounds, optical isomers thereof or pharmaceutically acceptable salts thereof have the histone deacetylase 6 (HDAC6) inhibitory activity, and are effective in preventing or treating HDAC6-related diseases, comprising infectious diseases; neoplasm; internal secretion; nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; eye and ocular adnexal diseases; circulatory diseases; respiratory diseases; digestive diseases; skin and subcutaneous tissue diseases; musculoskeletal system and connective tissue diseases; and teratosis or deformities, and chromosomal aberration.

Chong Kun Dang Pharmaceutical Corp. (Soul, KR)

Chong Kun Dang Pharmaceutical Corp. (KR)

1. A 1,3,4-oxadiazole derivative compound represented by a following formula I, optical isomer thereof or pharmaceutically acceptable salt thereof: [chemical expression included] wherein, X, Y and Z are each independently CR 3 or N; L is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, —(C═O)—(C 1 -C 4 alkylene)-, —(C═O)O—(C 1 -C 4 alkylene)-, —(C═O)NH—(C 1 -C 4 alkylene)-, —O(C═O)—(C 1 -C 4 alkylene)- or a single bond, wherein at least one H of —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, —(C═O)—(C 1 -C 4 alkylene)-, —(C═O)O—(C 1 -C 4 alkylene)-, —(C═O)NH—(C 1 -C 4 alkylene)- and —O(C═O)—(C 1 -C 4 alkylene)- may be substituted with aryl or heteroaryl; R 1 is hydrogen, —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 3 -C 8 cycloalkyl, heterocycloalkyl, benzyl, aryl, heteroaryl or —NR 4 R 5 , wherein at least one H of aryl or heteroaryl may be substituted with —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, —C 1 -C 6 haloalkyl, —C 1 -C 6 aminoalkyl, —C 1 -C 6 hydroxyalkyl, —C 1 -C 6 alkoxy, hydroxy, cyano, halo, nitro, —CF 2 H, —CF 3 , —NR 6 R 7 , —C(═O)—R 8 or —S(═O) 2 —R 9 ; R 2 is —CF 2 H or —CF 3 ; R 3 is hydrogen, halo or —C 1 -C 6 alkyl; R 4 to R 7 are each independently H or —C 1 -C 6 alkyl; and R 8 and R 9 are each independently H, OH or —C 1 -C 6 alkyl.

2. The 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 1 , wherein: X, Y and Z are each independently CR 3 or N; L is —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, —(C═O)—(C 1 -C 4 alkylene)-, —(C═O)O—(C 1 -C 4 alkylene)-, —(C═O)NH—(C 1 -C 4 alkylene)-, —O(C═O)—(C 1 -C 4 alkylene)- or a single bond, wherein at least one H of —(C 1 -C 6 alkylene)-, —(C 2 -C 6 alkenylene)-, —(C═O)—(C 1 -C 4 alkylene)-, —(C═O)O—(C 1 -C 4 alkylene)-, —(C═O)NH—(C 1 -C 4 alkylene)- and —O(C═O)—(C 1 -C 4 alkylene)- may be substituted with aryl; R 1 is hydrogen, —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, heterocycloalkyl, benzyl, aryl, heteroaryl or —NR 4 R 5 , wherein at least one H of aryl or heteroaryl may be substituted with —C 1 -C 6 alkyl, —C 1 -C 6 alkoxy, halo, nitro, —CF 3 or —S(═O) 2 —R 9 ; R 2 is —CF 2 H or —CF 3 ; R 3 is hydrogen or halo; R 4 to R 5 are each independently —C 1 -C 6 alkyl; and R 9 is each independently —C 1 -C 6 alkyl.

3. The 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 1 , wherein: X, Y and Z are each independently CR 3 ; L is —(C 1 -C 4 alkylene)-, —(C 2 -C 4 alkenylene)-, —(C═O)—(C 1 -C 2 alkylene)-, —(C═O)O—(C 1 -C 2 alkylene)-, —(C═O)NH—(C 1 -C 2 alkylene)-, —O(C═O)—(C 1 -C 2 alkylene)- or a single bond, wherein at least one H of —(C 1 -C 4 alkylene)-, —(C 2 -C 4 alkenylene)-, —(C═O)—(C 1 -C 2 alkylene)-, —(C═O)O—(C 1 -C 2 alkylene)-, —(C═O)NH—(C 1 -C 2 alkylene)- and —O(C═O)—(C 1 -C 2 alkylene)- may be substituted with aryl; R 1 is —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, [chemical expression included]  benzyl, phenyl, naphthyl, [chemical expression included]  or —NR 4 R 5 , wherein at least one H of phenyl, naphythyl, [chemical expression included] may be substituted with —C 1 -C 6 alkyl, —C 1 -C 6 alkoxy, halo, nitro, —CF 3 or —S(═O) 2 —R 9 ; R 2 is —CF 2 H or —CF 3 ; R 3 is hydrogen; R 4 to R 5 are each independently —C 1 -C 4 alkyl; and R 9 is each independently —C 1 -C 4 alkyl.

4. The 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 1 , wherein: X, Y and Z are each independently CR 3 ; L is —(C 1 -C 4 alkylene)-, —(C 2 -C 4 alkenylene)-, —(C═O)—(C 1 -C 2 alkylene)-, —(C═O)NH—(C 1 -C 2 alkylene)-, —O(C═O)—(C 1 -C 2 alkylene)- or a single bond, wherein at least one H of —(C 1 -C 4 alkylene)-, —(C 2 -C 4 alkenylene)-, —(C═O)—(C 1 -C 2 alkylene)-, —(C═O)NH—(C 1 -C 2 alkylene)- or —O(C═O)—(C 1 -C 2 alkylene)- may be substituted with aryl; R 1 is —C 1 -C 6 alkyl, —C 2 -C 6 alkenyl, [chemical expression included]  phenyl, naphthyl, [chemical expression included]  wherein at least one H of phenyl, naphthyl, [chemical expression included]  may be substituted with —C 1 -C 6 alkoxy, halo, nitro or —CF 3 ; R 2 is —CF 2 H; and R 3 is hydrogen.

5. The 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound represented by the formula I above is selected from the compounds as described in a following table: [table included]

6. The 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 5 , wherein the compound represented by the formula I above is selected from the compounds selected from the group consisting of compounds 1, 2, 3, 5, 7, 8, 9, 10, 13, 14, 15, 20, 21, 24, 25, 26, 28, 29, 43, 44, 45, 50, 51, 52, 53, 55, 56, 57 and 58.

7. A pharmaceutical composition for preventing or treating histone deacetylase 6 activity-related diseases, comprising the 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.

8. The pharmaceutical composition according to claim 7 , wherein histone deacetylase 6 activity-related diseases are at least one selected from the group consisting of infectious diseases; neoplasm; internal secretion; nutritional and metabolic diseases; mental and behavioral disorders; neurological diseases; eye and ocular adnexal diseases; circulatory diseases; respiratory diseases; digestive diseases; skin and subcutaneous tissue diseases; musculoskeletal system and connective tissue diseases; and teratosis or deformities, and chromosomal aberration.

9. A method for treating or preventing histone deacetylase 6 activity-related diseases, comprising administering a therapeutically effective amount of the 1,3,4-oxadiazole derivative compound represented by the formula I, optical isomer thereof or pharmaceutically acceptable salt thereof according to claim 1 .

4871753 October 1989 Rorh
8901156 December 2014 Baloglu
8981084 March 2015 Baloglu
9670193 June 2017 Hebach et al.
10464911 November 2019 Lee et al.
10494355 December 2019 Kim et al.
10538498 January 2020 Lee et al.
10584117 February 2020 Lee et al.
10717716 June 2020 Lee et al.
20050288282 December 2005 Delorme et al.
20060058298 March 2006 Delorme et al.
20070293530 December 2007 Smil et al.
20120027874 February 2012 Charrier et al.
20120289495 November 2012 Baloglu et al.
20130059883 March 2013 Baloglu et al.
20140005133 January 2014 Trivedi et al.
20140005164 January 2014 Varrone et al.
20140142105 May 2014 Hebach et al.
20140329825 November 2014 Hebach et al.
20150307497 October 2015 Sugimoto et al.
20160244449 August 2016 Lu et al.
20170015809 January 2017 Hawkins et al.
20170145012 May 2017 Buckmelter et al.
20180215743 August 2018 Lee et al.
20180230113 August 2018 Lee et al.
20180230114 August 2018 Lee et al.
20180251437 September 2018 Lee et al.
20180273495 September 2018 Kim et al.
20190008836 January 2019 Kaieda et al.
20210355089 November 2021 Chern et al.
20230079386 March 2023 Lee et al.
20230092890 March 2023 Lee et al.
101263121 September 2008
102802623 November 2012
103221047 July 2013
103339111 October 2013
104744446 July 2015
103998446 November 2016
108699048 October 2018
201491060 September 2014
0816356 January 1998
3327019 May 2018
3330259 June 2018
H10-059962 March 1998
2005513123 May 2005
2009542752 December 2009
2011008205 January 2011
2011502133 January 2011
2012211149 November 2012
2013517278 May 2013
2013517281 May 2013
2013533279 August 2013
2014513071 May 2014
WO 2014077401 May 2014
2014520794 August 2014
2014524922 September 2014
2014533721 December 2014
2014533734 December 2014
2018511573 April 2018
2018521110 August 2018
2019504821 February 2019
2021532130 November 2021
2022529695 June 2022
2022537904 August 2022
100265385 November 2000
100903743 June 2009
101262870 May 2013
101320198 October 2013
20130112911 October 2013
20140097459 August 2014
20147017436 August 2014
101561860 October 2015
20170013186 February 2017
10-2022-0012243 February 2022
2515611 August 2012
WO 2003028729 April 2003
WO 2007011626 January 2007
WO 2007032445 March 2007
WO 2007093827 August 2007
WO 2007107758 September 2007
WO 2009010479 January 2009
WO 2010109148 September 2010
WO 2010123933 October 2010
WO 2010126002 November 2010
2011011186 January 2011
2011091213 July 2011
WO 2011088181 July 2011
WO 2011088192 July 2011
WO 2011104680 September 2011
WO 2011133888 October 2011
2012011592 January 2012
WO 2012013716 February 2012
WO 2012136492 October 2012
2013008162 January 2013
2013041407 March 2013
2013052110 April 2013
2013066833 May 2013
2013066835 May 2013
2013066838 May 2013
2013066839 May 2013
2013080120 June 2013
2013134467 September 2013
WO 2015033301 March 2015
WO 2015087151 June 2015
WO 2016082930 June 2016
WO 2016134320 August 2016
WO 2017014170 January 2017
2017018804 February 2017
2017023133 February 2017
WO 2017014321 February 2017
WO 2017018803 February 2017
WO 2017018805 February 2017
WO 2017065473 April 2017
2017222951 December 2017
2017222952 December 2017
WO-2017222951 December 2017
WO 2018213364 November 2018
WO 2020022794 January 2020
WO 2020212479 October 2020
WO 2021127643 June 2021

Office Action for Korean Appln, No. 10-2020-0065508, dated Mar. 2, 2022, 15 pages (with Machine Translation). cited by applicant
Cancer [online], “Cancer,” Jun. 27, 2007, retrieved on Jul. 6, 2007, retrieved from URL , 10 pages. cited by applicant
CAS No. 904635-69-4, “4-Morpholinecarboxamide, N-[4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl],” STN Easy, dated Aug. 25, 2006, 1 page. cited by applicant
CAS No. 904652-71-7, “4-Morpholinecarboxamide, N-[4-[5-(dichloromethyl)-1,3,4-oxadiazol-2-yl]phenyl],” STN Easy, dated Aug. 25, 2006, 1 page. cited by applicant
CAS No. 904653-13-0, “4-Morpholinecarboxamide, N-[4-[5-(trichloromethyl)-1, 3,4-oxadiazol-2-yl]phenyl],” STN Easy, dated Aug. 25, 2006, 1 page. cited by applicant
Chemical Abstract compound RN No. 1355844-43-7, STN Express, dated Feb. 8, 2012, 1 page. cited by applicant
Chemical Abstract compound RN No. 1384673-31-7, STN Express, dated Jul. 27, 2012, 1 page. cited by applicant
Chemical Abstract compound RN No. 1436149-02-8, STN Express, dated Jun. 9, 2013, 1 page. cited by applicant
Chemical Abstract compound RN No. 1708354-35-1, STN Express, dated May 20, 2015, 1 page. cited by applicant
Chemical Abstract compound RN No. 1790675-44-3, STN Express, dated Jun. 29, 2015, 1 page. cited by applicant
Chemical Abstract compound RN No. 1798074-73-3, STN Express, dated Jul. 9, 2015, 1 page. cited by applicant
Chemical Abstract compound RN No. 904653-15-2, STN Express, dated Aug. 25. 2006, 1 page. cited by applicant
Chemical Abstract compound RN No. 904653-17-4, STN Express, Aug. 25, 2006, 1 page. cited by applicant
Chemical Abstract compound RN No. 904653-20-9, STN Express, dated Aug. 25, 2006, 2 pages. cited by applicant
Chemical Abstract compound RN No. 904653-21-0, STN Express, dated Aug. 25, 2006, 1 page. cited by applicant
Chemical Abstract compound RN No. 904653-22-1, STN Express, dated Aug. 25, 2006, 1 page. cited by applicant
Chen et al., “Computational exploration of zinc binding groups for HDAC inhibition,” J. Org. Chem., May 2013, 78(10):5051-5055. cited by applicant
Chen et al., “Discovery of 2-methylpyridine-based biaryl amides as y-secretase modulators for the treatment of Alzheimer's disease, ”Bioorg. Med. Chem, 2013, 23(23):6447-6454. cited by applicant
Decision to Grant in Russian Appln. No. 2021104625, dated Dec. 3, 2021, 29 pages (with English Translation). cited by applicant
El-Din et al., “Synthesis and in vitro antiproliferative activity of new 1,3,4-oxadiazole derivatives possessing sulfonamide moiety,” Eur. J. Med. Chem, Jan. 2015, 90:45-52. cited by applicant
Extended European Search Report in European Appln. No. 16830836.9, dated Dec. 19, 2018, 7 pages. cited by applicant
Extended European Search Report in European Appln. No. 16830837.7, dated Dec. 17, 2018, 9 pages. cited by applicant
Extended European Search Report in European Appln. No. 16830838.5, dated Nov. 19, 2018, 7 pages. cited by applicant
Extended European Search Report in European Appln. No. 16833369.8, dated Apr. 1, 2019, 6 pages. cited by applicant
Golub et al., “Molecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring,” Science, Oct. 1991, 286:531-537. cited by applicant
International Preliminary Report on Patentability and Written Opinion for International Appln. No. PCT/KR2016/008214, dated Jan. 30, 2018, 8 pages. cited by applicant
International Preliminary Report on Patentability and Written Opinion for International Appln. No. PCT/KR2016/008216, dated Jan. 30, 2018, 9 pages. cited by applicant
International Preliminary Report on Patentability and Written Opinion for International Appln. No. PCT/KR2016/008218, dated Jan. 30, 2018, 8 pages. cited by applicant
International Preliminary Report on Patentability and Written Opinion for International Appln. No. PCT/KR2016/008622, dated Feb. 6, 2018, 8 pages. cited by applicant
International Preliminary Report on Patentability and Written Opinion for International Appln. No. PCT/KR2016/011355, dated Apr. 17, 2018, 6 pages. cited by applicant
International Search Report for International Appln. No. PCT/KR2016/008214, dated Nov. 24, 2016, 5 pages. cited by applicant
International Search Report for International Appln. No. PCT/KR2016/008216, dated Nov. 21, 2016, 12 pages (with English Translation). cited by applicant
International Search Report for International Appln. No. PCT/KR2016/008218, dated Nov. 21, 2016, 5 pages. cited by applicant
International Search Report for International Appln. No. PCT/KR2016/008622, dated Feb. 17, 2017, 5 pages. cited by applicant
International Search Report for International Appln. No. PCT/KR2016/011355, dated Jan. 26, 2017, 5 pages. cited by applicant
Lala et al., “Role of nitric oxide in tumor progression: Lessons from experimental tumors,” Cancer Metastasis Rev., 1998, 17(1):91-106. cited by applicant
Manku, et al., “Synthesis and evaluation of lysine derived sulfamides as histone deacetylase inhibitors,” Bioorg. Med. Chem. Lett., Feb. 2009, 19:1866-1870. cited by applicant
Murphy et al., “Regulation of the Dynamics of hsp90 Action on the Glucocorticoid Receptor by Acetylation/Deacetylation of the Chaperone,” J. Biol. Chem., Oct. 2005, 280(40):33792-33799. cited by applicant
Office Action for Australian Appln. No. 2016299484, dated Aug. 28, 2018, 6 pages. cited by applicant
Office Action for Australian Appln. No. 2016299484, dated Dec. 18, 2018, 3 pages. cited by applicant
Office Action for Australian Appln. No. 2016299485, dated Sep. 13, 2018, 7 pages. cited by applicant
Office Action for Australian Appln. No. 2016299486, dated Jul. 21, 2018, 5 pages. cited by applicant
Office Action for Australian Appln. No. 2016303891, dated Nov. 16, 2018, 7 pages. cited by applicant
Office Action for Canadian Appln. No. 2987570, dated Oct. 18, 2018, 5 pages. cited by applicant
Office Action for Canadian Appln. No. 2993918, dated Dec. 4, 2018, 5 pages. cited by applicant
Office Action for Canadian Appln. No. 2993929, dated Dec. 4, 2018, 4 pages. cited by applicant
Office Action for Indian Appln. No. 201727037873, dated May 21, 2019, 7 pages. cited by applicant
Office Action for Indian Appln. No. 201817006324, dated Jun. 27, 2019, 6 pages. cited by applicant
Office Action for Japanese Appln. No. 2018-503804, dated Feb. 15, 2019, 4 pages (with English Translation). cited by applicant
Office Action for Japanese Appln. No. 2018-504096, dated Jan. 8, 2019, 5 pages (with English Translation). cited by applicant
Office Action for Japanese Appln. No. 2018-504720, dated Jan. 8, 2019, 19 pages (with English Translation). cited by applicant
Office Action for Japanese Appln. No. 2018-505725, dated Sep. 12, 2018, 3 pages. cited by applicant
Office Action for Japanese Appln. No. 2021-503874, dated Feb. 8, 2022, 7 pages (with English Translation). cited by applicant
Office Action for Korean Appln, No. 10-2016-0095332, dated May 9, 2017, 15 pages. cited by applicant
Office Action for Korean Appln, No. 10-2016-0095334, dated May 9, 2017, 17 pages. cited by applicant
Office Action for Korean Appln, No. 10-2016-0099508, dated May 9, 2017. 20 pages. cited by applicant
Office Action for Korean Appln, No. 10-2016-0131245, dated May 9, 2017, 7 pages. cited by applicant
Office Action for New Zealand Appln. No. 739211, dated Jun. 14, 2018, 3 pages. cited by applicant
Office Action for Russian Appln. No. 2018106877, dated Oct. 18, 2018, 16 pages (with English translation). cited by applicant
Office Action for Russian Appln. No. 2018106904, dated Sep. 20, 2018, 14 pages (with English translation). cited by applicant
Office Action for Russian Appln. No. 2018106914, dated Nov. 15, 2018, 14 pages (with English translation). cited by applicant
Office Action for Taiwanese Appln. No. 105132939, dated Nov. 2, 2017, 8 pages (with English translation). cited by applicant
Othman et al., “1,3,4-Oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives as potential antibacterial agents,” Arab. J. Chem., 2014:1-16. cited by applicant
Pal et al., “Hydroxamic acid—A novel molecule for anticancer therapy,” J. Adv. Pharm. Technol. Res., 2012, 3(2):92-99. cited by applicant
Rajak et al., “2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: Design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors,” Bioorg. Med. Chem. Lett., Aug. 2011, 21:5735-5738. cited by applicant
Rossi et al., “4-N-Hydroxy-4-[ 1-( sulfony1 )piperidin-4-y1 ]-butyramides as HDAC inhibitors,” Bioorg. Med. Chem. Lett., Sep. 2011, 21:6767-6769. cited by applicant
International Search Report for PCT/KR2019/009228, dated Nov. 11, 2019. 4 pages. cited by applicant
Hassig et al., Nuclear histone acetylases and deacetylases and transcriptional regulation: HATs off to HDACs' Current Opinion in Chemical Biology 1997, 1, pp. 300-308. cited by applicant
Warrell et al, Therapeutic Targeting of Transcription in Acute Promyelocytic Leukemia by Use of an Inhibitor of Histone Deacetylase, Journal of the National Cancer Institute, vol. 90, No. 21, Nov. 4, 1998, pp. 1621-1625. cited by applicant
Bolden et al., “Anticancer activities of histone deacetylase inhibitors”, National Reviews, Drug Discovery, vol. 5, Sep. 2006, pp. 769-784. cited by applicant
Piekarz et al., “Clinical Toxicities of Histone Deacetylase Inhibitors”, Pharmaceuticals 2010, 3, pp. 2751-2767. cited by applicant
Witt et al., “HDAC family: What are the cancer relevant targets”?, Cancer Letters 277, 2009, 2, pp. 8-21. cited by applicant
Matthias et al., “Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally”, Molecular and Cellular Biology, Mar. 2008, pp. 1688-1701. cited by applicant
Yao et al., “HDAC6 Regulates Hsp90 Acetylation and Chaperone-Dependent Activation of Glucocorticoid Receptor”, Molecular Cell, vol. 18, May 27, 2006, pp. 601-607. cited by applicant
Santo et al., “Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma”, Blood, Mar. 15, 2012, vol. 119, No. 11, pp. 2579-2590. cited by applicant
Vishwakarma et al., “Tubastatin, a selective histone deacetylase 6 inhibitor shows anti-inflammatory and anti-rheumatic effects”, International Immunopharmacology 2013, 16, pp. 72-78. cited by applicant
Hlu et al., “HDAC6 α-tubulin deacetylase: A potential therapeutic target in neurodegenerative diseases”, Journal of the Neurological Sciences 304, 2011, pp. 1-8. cited by applicant
Wiest et al., “Computational Exploration of Zinc Binding Groups for HDAC Inhibition”, J. Org. Chem. , May 17, 2013 78: pp. 5051-5055. cited by applicant
Methot et al., Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2), Bioorganic & Medicinal Chemistry Letters 18 (2008), pp. 973-978. cited by applicant
Woster et al., “Discovery of a new class of histone deacetylase inhibitors with a novel zinc binding group”, Med. Chem. Commun. 2015, online publication, 6 pages. cited by applicant
Baijuka, et al., “Synthesis and Biological Activities of 1, 3, 4-Oxadiazole Derivatives: a Review of Literature”, Int. J. Adv. Res, [Published] Jan. 2018, vol. 6, No. 1, pp. 1114-1122. cited by applicant
Extended European Search Report in European Appln. No. 20814548.2, dated Nov. 8, 2022, 5 pages. cited by applicant
Extended European Search Report in European Appln. No. 20815468.2, dated May 4, 2023, 13 pages. cited by applicant
Notice of Allowance in Australian Appln. No. 2020284167, dated May 1, 2023, 3 pages. cited by applicant
Notice of Allowance in Korean Appln. No. 2020-0065507, dated Nov. 10, 2022, 10 pages (with English translation). cited by applicant
Office Action for Australian Appln. No. 2020284167, dated Nov. 3, 2022, 3 pages. cited by applicant
Office Action for Australian Appln. No. 2020284606, dated Aug. 11, 2022, 8 pages. cited by applicant
Office Action for Canadian Appln. No. 3136223, dated Nov. 30, 2022, 4 pages. cited by applicant
Office Action for Canadian Appln. No. 3139026, dated Dec. 14, 2022, 6 pages. cited by applicant
Office Action for Indian Appln. No. 202137058528, dated Jul. 6, 2022, 5 pages. cited by applicant
Office Action for Indian Appln. No. 202137061193, dated Jul. 7, 2022, 6 pages. cited by applicant
Office Action for Japanese Appln. No. 2021-571486, dated Jan. 10, 2023, 12 pages (with English Translation). cited by applicant
Office Action for Japanese Appln. No. 2021-571498, dated Nov. 8, 2022, 12 pages (with English Translation). cited by applicant
Office Action for Malaysian Appln. No. PI2021006507, dated May 22, 2023, 4 pages. cited by applicant
Office Action for Russian Appln. No. 2021139516, dated Aug. 11, 2022, 20 pages (with English Translation). cited by applicant
Office Action for Russian Appln. No. 2021139540, dated Aug. 17, 2022, 32 pages (with English Translation). cited by applicant
U.S. Appl. No. 17/615,363, filed Nov. 30, 2021, Chang Sik Lee. cited by applicant
U.S. Appl. No. 17/614,967, filed Nov. 29, 2021, Chang Sik Lee. cited by applicant
ACS RN 904653-05-0, “Benzamide, 3-methoxy-N-[4-[5-(trichloromethyl)-1,3,4-oxadiazol-2-yl]phenyl]”, STN-Registry, dated Aug. 25, 2006, 1 page. cited by applicant
ACS RN 904568-68-9, “Benz amide, 3,4,5-trimethoxy-N-[4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]” STN-Registry, Aug. 25, 2006, 1 page. cited by applicant
Office Action and Search Report for Chinese Application No. 201680044430.0, dated Aug. 21, 2020, 9 pages (with English translation). cited by applicant
Office Action and Search Report for Chinese Application No. 201680053218.0 dated Nov. 4, 2020, 14 pages (with English translation). cited by applicant
Office Action and Search Report for Chinese Application No. 201680058155.8, dated Jan. 6, 2021, 13 pages (with English translation). cited by applicant
Office Action and Search Report for Chinese Application No. 201680072029.8, dated Oct. 26, 2020, 12 pages (with English translation). cited by applicant
PCT International Preliminary Report on Patentability in International Appln. No. PCT/KR2019/009228, dated Feb. 4, 2021, 6 pages. cited by applicant
Notice of Allowance in Korean Appln. No. 2018-0087455, dated Oct. 7, 2021, 4 pages (with English translation). cited by applicant
Office Action in Russian Appln. No. 2021104625, dated Jul. 23, 2021, 22 pages (with English translation). cited by applicant
Action for TW108126316 dated Oct. 22, 2020 and English translation. 7 pages. cited by applicant
Baijika, et al., “Synthesis and biological activities of 1, 3, 4-oxadiazole derivatives: A Review of Literature”, Int. J. Adv. Res, [Published] Jan. 2018, vol. 6, No. 1, pp. 1114-1122. cited by applicant
Office Action for TW109118219, dated Mar. 19, 2021 and English translation, 9 pages. cited by applicant
Office Action for TW109118221, dated Apr. 15, 2021 and English translation, 9 pages. cited by applicant
PCT International Search Report and Written Opinion in International Application No. PCT/1B2020/055109, dated Sep. 4, 2020, 10 pages. cited by applicant
PCT International Search Report and Written Opinion in International Application No. PCT/IB2020/055110, dated Sep. 4, 2020, 12 pages. cited by applicant
PCT International Search Report and Written Opinion in International Application No. PCT/KR2019/009228, dated Nov. 11, 2019, 8 pages. cited by applicant
Office Action in Chinese Appln. No. 201980049375.8, dated Sep. 20, 2023, 13 pages (with English translation). cited by applicant
Office Action in Malaysia Appln. No. PI2021000199, dated Dec. 1, 2023, 2 pages (with English translation). cited by applicant
Office Action in Mexico Appln. No. MX/a/2021/000737, dated Jun. 15, 2023, 8 pages (with English translation). cited by applicant
Office Action in New Zealand Appln. No. 771899, dated Aug. 22, 2023, 4 pages. cited by applicant
Office Action in Vietnam Appln. No. 51472w/SHTT-SC, dated Aug. 23, 2023, 4 pages (with English translation). cited by applicant
Silverman, “The Organic Chemistry of Drug Design and Drug Action,” Second Edition, 2008, pp. 17-23. cited by applicant

edspgr.11958844