IP Library › Granted Patent US 12,441,703
Granted Patent B2
US 12,441,703 · App. 17/421,944 · Granted Oct 14, 2025

Carboxamides as modulators of sodium channels

Inventors: Stephen Andrew Thomson (Del Mar, CA); Nadia Ahmad (Didcot, GB); Corey Anderson (Brighton, MA); Vijayalaksmi Arumugam (San Marcos, CA); Iuliana Luci Asgian (San Diego, CA); Joanne Louise Camp (Didcot, GB); Lev Tyler Dewey Fanning (San Marcos, CA); Sara Sabina Hadida Ruah (La Jolia, CA); Dennis Hurley (San Marcos, CA); Yvonne Schmidt (San Diego, CA); David Shaw (Oxford, GB); Urvi Patel (San Diego, CA); Lidio Marx Carvalho Meireles (San Marcos, CA)
Assignee: VERTEX PHARMACEUTICALS INCORPORATED
C07D401/12A61P3/12C07D213/56C07D213/89C07D239/36C07D405/12
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Quick Facts
Patent No.
US 12,441,703
App. No.
17/421,944
Granted
Oct 14, 2025
Kind
B2
Abstract

Compounds, and pharmaceutically acceptable salts thereof, useful as inhibitors of sodium channels are provided. Also provided are pharmaceutical compositions comprising the compounds or pharmaceutically acceptable salts and methods of using the compounds, pharmaceutically acceptable salts, and pharmaceutical compositions in the treatment of various disorders, including pain.

Claims (56)

1. A compound of formula (I) or (II)

or a pharmaceutically acceptable salt thereof, wherein:

each R is independently H or C 1 -C 6 alkyl;

R 3a is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 4a is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 1b is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 3b is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 4b is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 5 , R 6 , R 7 , and R 8 are defined as follows:

(i) R 5 , R 6 , and R 7 are each independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; and R 8 is C 1 -C 6 alkyl;

(ii) R 5 is W—(CH 2 ) n —R z , C 1 -C 6 alkylsulfanyl, —O—(CH 2 ) p —R w , or —O—(CH 2 ) p —N(C 1 -C 6 alkyl) 2 ; R 6 and R 7 are each independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; and R 8 is H;

(iii) R 5 and R 6 are each independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; R 7 is W—(CH 2 ) n —R z , —C═C—R x , or 3-6 membered cycloalkyl or phenyl, wherein said 3-6 membered cycloalkyl or phenyl is substituted with 1-3 substituents selected from a group consisting of C 1 -C 6 alkoxy, CN, and —C(O)NH 2 ; and R 8 is H; or

(iv) R 5 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; R 6 and R 7 , together with the carbon atoms to which they are attached, form a ring of formula

and R 8 is H;

R 9 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 10 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 11 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 12 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

R 13 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy;

each R 14 is independently H, halo, C 1 -C 4 alkyl, or C 1 -C 4 haloalkyl;

each W is independently O or a single bond;

R x is C 1 -C 6 alkyl or 3-6 membered cycloalkyl, wherein said 3-6 membered cycloalkyl may be unsubstituted or may be substituted with 1-3 substituents selected from a group consisting of halo, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl;

each R w is independently 3-6 membered cycloalkyl, phenyl, or 5-6 membered heteroaryl, wherein said 3-6 membered cycloalkyl, phenyl, or 5-6 membered heteroaryl may be unsubstituted or may be substituted with 1-3 substituents selected from a group consisting of halo, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl;

R z is 3-6 membered heterocyclyl, 7-8 membered cycloalkyl, or 4-8 membered cycloalkenyl, wherein said 3-6 membered heterocyclyl, 7-8 membered cycloalkyl, or 4-8 membered cycloalkenyl may be unsubstituted or may be substituted with 1-3 substituents selected from a group consisting of halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and C 1 -C 6 alkoxy, or wherein 2 substituents together with the atom to which they are attached form a 5-6 membered heterocyclyl ring;

n is 0 or 1; and

p is 2 or 3.

2. The compound of claim 1 , wherein the compound has formula (I)

or a pharmaceutically acceptable salt thereof, wherein R, R 3a , R 4a , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are as defined in claim 1 .

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 3a and R 4a are each H.

4. The compound of claim 1 , wherein the compound has formula (II)

or a pharmaceutically acceptable salt thereof, wherein R, R 1b , R 3b , R 4b , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are as defined in claim 1 .

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1b , R 3b , and R 4b are each H.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R is H.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 , R 6 , and R 7 are each independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; and R 8 is C 1 -C 6 alkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is W—(CH 2 ) n —R z , C 1 -C 6 alkylsulfanyl, —O—(CH 2 ) p —R w , or —O—(CH 2 ) p —N(C 1 -C 6 alkyl) 2 ; R 6 and R 7 are each independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; and R 8 is H.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 and R 6 are each independently H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; R 7 is W—(CH 2 ) n —R z , —C═C—R x , or 3-6 membered cycloalkyl or phenyl, wherein said 3-6 membered cycloalkyl or phenyl is substituted with 1-3 substituents selected from a group consisting of C 1 -C 6 alkoxy, CN, and —C(O)NH 2 ; and R 8 is H.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, F, or CH 3 ; R 6 is H; R 7 is

and R 8 is H.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, or C 1 -C 6 haloalkoxy; R 6 and R 7 , together with the carbon atoms to which they are attached, form a ring of formula

and R 8 is H.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 9 is C 1 -C 6 alkoxy.

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 10 is H.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 10 is F.

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 11 is C 1 -C 6 haloalkoxy.

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 12 is H.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 13 is H.

18. A compound selected from:

or a pharmaceutically acceptable salt thereof.

19. A compound selected from:

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

21. The compound of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or vehicles.

23. A method of treating or lessening the severity in a subject of chronic pain, gut pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, idiopathic pain, postsurgical pain, visceral pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, pathological cough, or cardiac arrhythmia comprising administering to the subject an effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignments (6)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2025
From: CARVALHO MEIRELES, LIDIO MARX
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 071801/0443 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2025
From: ANDERSON, COREY; ARUMUGAM, VIJAYALAKSMI; ASGIAN, IULIANA LUCI; FANNING, LEV TYLER DEWEY; HADIDA RUAH, SARA SABINA; HURLEY, DENNIS; SCHMIDT, YVONNE; PATEL, URVI
To: VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
Reel/Frame 071801/0622 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2025
From: AHMAD, NADIA; CAMP, JOANNE LOUISE; SHAW, DAVID
To: VERTEX PHARMACEUTICALS (EUROPE) LIMITED
Reel/Frame 071801/0777 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2025
From: VERTEX PHARMACEUTICALS (SAN DIEGO) LLC
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 071801/0873 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2025
From: VERTEX PHARMACEUTICALS (EUROPE) LIMITED
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 071801/0948 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 6, 2021
From: THOMSON, STEPHEN ANDREW
To: VERTEX PHARMACEUTICALS INCORPORATED
Reel/Frame 057102/0560 →
Continuity (3)
Provisional Application 62790897 · Jan 10, 2019
Provisional Application 62791011 · Jan 10, 2019
Related Publication 20230062053A1 · Mar 2, 2023
References Cited (387)
US 2511231A · Weissberger et al. · 1950 [cited by applicant]
US 2657134A · Graham et al. · 1953 [cited by applicant]
US 2688617A · Hein et al. · 1954 [cited by applicant]
US 2694718A · Salminen et al. · 1954 [cited by applicant]
US 2710802A · Parmerter et al. · 1955 [cited by applicant]
US 2710803A · Salminen et al. · 1955 [cited by applicant]
US 2721798A · Loria et al. · 1955 [cited by applicant]
US 2725292A · Graham et al. · 1955 [cited by applicant]
US 2772163A · Tong · 1956 [cited by applicant]
US 4146637A · Metz et al. · 1979 [cited by applicant]
US 4218765A · Kinkade · 1980 [cited by applicant]
US 4639273A · Gilmore et al. · 1987 [cited by applicant]
US 5258407A · Washburn et al. · 1993 [cited by applicant]
US 5304121A · Sahatjian · 1994 [cited by applicant]
US 5310760A · Washburn et al. · 1994 [cited by applicant]
US 5312960A · Kramer et al. · 1994 [cited by applicant]
US 5532235A · Albright et al. · 1996 [cited by applicant]
US 5536718A · Albright et al. · 1996 [cited by applicant]
US 5886026A · Hunter et al. · 1999 [cited by applicant]
US 6099562A · Ding et al. · 2000 [cited by applicant]
US 6211242B1 · Setoi et al. · 2001 [cited by applicant]
US 6235680B1 · Ziemer et al. · 2001 [cited by applicant]
US 6531291B1 · Kabbash et al. · 2003 [cited by applicant]
US 6699994B1 · Babu et al. · 2004 [cited by applicant]
US 6936719B2 · Babu et al. · 2005 [cited by applicant]
US 7056910B2 · Koshio et al. · 2006 [cited by applicant]
US 7374749B2 · Haase et al. · 2008 [cited by applicant]
US 7863280B2 · Paukert et al. · 2011 [cited by applicant]
US 8389734B2 · Chen et al. · 2013 [cited by applicant]
US 8466188B2 · Chafeev et al. · 2013 [cited by applicant]
US 8481479B1 · Mousa · 2013 [cited by applicant]
US 8519137B2 · Joshi et al. · 2013 [cited by applicant]
US 8779197B2 · Chen et al. · 2014 [cited by applicant]
US 8841483B2 · Joshi et al. · 2014 [cited by applicant]
US 8865771B2 · Chen et al. · 2014 [cited by applicant]
US 8883840B2 · Chafeev et al. · 2014 [cited by applicant]
US 9051270B2 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 9108903B2 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 9139529B2 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 9163042B2 · Anderson et al. · 2015 [cited by applicant]
US 9169246B2 · Benazet et al. · 2015 [cited by applicant]
US 9393235B2 · Hadida-Ruah et al. · 2016 [cited by applicant]
US 9421196B2 · Hadida-Ruah et al. · 2016 [cited by applicant]
US 9464102B2 · Anderson et al. · 2016 [cited by applicant]
US 9758483B2 · Hadida-Ruah et al. · 2017 [cited by applicant]
US 9783501B2 · Hadida-Ruah et al. · 2017 [cited by applicant]
US 9828397B2 · Anderson et al. · 2017 [cited by applicant]
US 9951065B2 · Bartlett et al. · 2018 [cited by applicant]
US 10087143B2 · Hadida-Ruah et al. · 2018 [cited by applicant]
US 10253054B2 · Anderson et al. · 2019 [cited by applicant]
US 10647661B2 · Ahmad et al. · 2020 [cited by applicant]
US 10738009B2 · Hadida Ruah et al. · 2020 [cited by applicant]
US 10787472B2 · Anderson et al. · 2020 [cited by applicant]
US 11203571B2 · Hadida-Ruah et al. · 2021 [cited by applicant]
US 20020002183A1 · Zhu et al. · 2002 [cited by applicant]
US 20020032238A1 · Priepke et al. · 2002 [cited by applicant]
US 20020173656A1 · Peyman et al. · 2002 [cited by applicant]
US 20030225158A1 · Auerbach et al. · 2003 [cited by applicant]
US 20040058903A1 · Takasugi et al. · 2004 [cited by applicant]
US 20040132745A1 · Bertinato et al. · 2004 [cited by applicant]
US 20040186148A1 · Shankar et al. · 2004 [cited by applicant]
US 20050038035A1 · Takasugi et al. · 2005 [cited by applicant]
US 20050207972A1 · Friebe et al. · 2005 [cited by applicant]
US 20070237840A1 · Chern et al. · 2007 [cited by applicant]
US 20070238733A1 · Joshi et al. · 2007 [cited by applicant]
US 20080192127A1 · Sakal et al. · 2008 [cited by applicant]
US 20080312235A1 · Lane et al. · 2008 [cited by applicant]
US 20090012091A1 · Yu · 2009 [cited by applicant]
US 20090029994A1 · Nakamura et al. · 2009 [cited by applicant]
US 20090048306A1 · Bagal et al. · 2009 [cited by applicant]
US 20090074884A1 · Chesney et al. · 2009 [cited by applicant]
US 20090099233A1 · Joshi et al. · 2009 [cited by applicant]
US 20090118333A1 · Chen et al. · 2009 [cited by applicant]
US 20090118338A1 · Chen et al. · 2009 [cited by applicant]
US 20090163545A1 · Goldfarb · 2009 [cited by applicant]
US 20090326020A1 · Miller et al. · 2009 [cited by applicant]
US 20100009970A1 · Johansen et al. · 2010 [cited by applicant]
US 20100075948A1 · Ding et al. · 2010 [cited by applicant]
US 20100152190A1 · Bartkovitz et al. · 2010 [cited by applicant]
US 20110046370A1 · Sim et al. · 2011 [cited by applicant]
US 20110178089A1 · Bissantz et al. · 2011 [cited by applicant]
US 20110257196A1 · Lu et al. · 2011 [cited by applicant]
US 20110306607A1 · Hadida-Ruah et al. · 2011 [cited by applicant]
US 20120196869A1 · Hadida Ruah et al. · 2012 [cited by applicant]
US 20120220605A1 · Pajouhesh et al. · 2012 [cited by applicant]
US 20120245136A1 · Hadida-Ruah et al. · 2012 [cited by applicant]
US 20120264749A1 · Hadida-Ruah et al. · 2012 [cited by applicant]
US 20130150339A1 · Boezio et al. · 2013 [cited by applicant]
US 20130231370A1 · Chen et al. · 2013 [cited by applicant]
US 20130274243A1 · Bagal et al. · 2013 [cited by applicant]
US 20130295187A1 · Mousa · 2013 [cited by applicant]
US 20130303535A1 · Tsuboi et al. · 2013 [cited by applicant]
US 20140094457A1 · Gardner et al. · 2014 [cited by applicant]
US 20140187533A1 · Pajouhesh et al. · 2014 [cited by applicant]
US 20140200215A1 · Buckman et al. · 2014 [cited by applicant]
US 20140213616A1 · Hadida-Ruah et al. · 2014 [cited by applicant]
US 20140221435A1 · Hadida-Ruah et al. · 2014 [cited by applicant]
US 20140228371A1 · Hadida-Ruah et al. · 2014 [cited by applicant]
US 20140296313A1 · Bagal et al. · 2014 [cited by applicant]
US 20150005304A1 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 20150166589A1 · Anderson et al. · 2015 [cited by applicant]
US 20150246028A1 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 20150328196A1 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 20150336945A1 · Hadida-Ruah et al. · 2015 [cited by applicant]
US 20160009743A1 · Anderson et al. · 2016 [cited by applicant]
US 20160152561A1 · Hadida-Ruah et al. · 2016 [cited by applicant]
US 20160376295A1 · Anderson et al. · 2016 [cited by applicant]
US 20170037009A1 · Hadida-Ruah et al. · 2017 [cited by applicant]
US 20180016235A1 · Hadida-Ruah et al. · 2018 [cited by applicant]
US 20180044361A1 · Anderson et al. · 2018 [cited by applicant]
US 20190005521A1 · Nobe · 2019 [cited by applicant]
US 20190016671A1 · Ahmad et al. · 2019 [cited by applicant]
US 20190248745A1 · Hadida Ruah et al. · 2019 [cited by applicant]
US 20190276483A1 · Anderson et al. · 2019 [cited by applicant]
US 20190343817A1 · Agarwal et al. · 2019 [cited by applicant]
US 20210047271A1 · Hadida Ruah et al. · 2021 [cited by applicant]
US 20210052610A1 · Agarwal et al. · 2021 [cited by applicant]
US 20210094906A1 · Ahmad et al. · 2021 [cited by applicant]
US 20210155643A1 · Jiang et al. · 2021 [cited by applicant]
US 20210198241A1 · Durrant · 2021 [cited by applicant]
US 20220110923A1 · Thomson · 2022 [cited by applicant]
BE 854683 · 1977 [cited by applicant]
CA 1091247 · 1980 [cited by applicant]
CA 2109195 · 1993 [cited by applicant]
CA 2512582 · 2004 [cited by applicant]
CA 2851462 · 2004 [cited by applicant]
CN 101838264 · 2010 [cited by applicant]
CN 103012397 · 2013 [cited by applicant]
CN 103961348 · 2014 [cited by applicant]
CN 106317027 · 2017 [cited by applicant]
DE 2623228 · 1977 [cited by applicant]
DE 4023008 · 1991 [cited by applicant]
DE 4019307 · 1991 [cited by applicant]
DE 19523640 · 1997 [cited by applicant]
DE 102004009238 · 2005 [cited by applicant]
DE 102004050196 · 2006 [cited by applicant]
EP 407217 · 1991 [cited by applicant]
EP 569912 · 1993 [cited by applicant]
EP 1217000 · 2002 [cited by applicant]
EP 2573073 · 2013 [cited by applicant]
EP 2606726 · 2013 [cited by applicant]
EP 2997966 · 2016 [cited by applicant]
FR 2628864 · 1989 [cited by applicant]
GB 1555723 · 1979 [cited by applicant]
IT 1349739 · 2008 [cited by applicant]
JP 63182182 · 1988 [cited by applicant]
JP 05313169 · 1993 [cited by applicant]
JP 10191842 · 1998 [cited by applicant]
JP 10213820 · 1998 [cited by applicant]
JP 2003342175 · 2003 [cited by applicant]
JP 2004043456 · 2004 [cited by applicant]
JP 2004175739 · 2004 [cited by applicant]
JP 2004315395 · 2004 [cited by applicant]
JP 2008106017 · 2008 [cited by applicant]
JP 2009108152 · 2009 [cited by applicant]
JP 2009149754 · 2009 [cited by applicant]
JP 2009209090 · 2009 [cited by applicant]
JP 2009242540 · 2009 [cited by applicant]
JP 2010001284 · 2010 [cited by applicant]
JP 2010059131 · 2010 [cited by applicant]
JP 2010066630 · 2010 [cited by applicant]
JP 2010126651 · 2010 [cited by applicant]
JP 2011006360 · 2011 [cited by applicant]
JP 2011162678 · 2011 [cited by applicant]
JP 2011207765 · 2011 [cited by applicant]
JP 2014232188 · 2014 [cited by applicant]
WO WO1993016684 · 1993 [cited by applicant]
WO WO1995029152 · 1995 [cited by applicant]
WO WO1995032943 · 1995 [cited by applicant]
WO WO1996022282 · 1996 [cited by applicant]
WO WO1997001542 · 1997 [cited by applicant]
WO WO1997045016 · 1997 [cited by applicant]
WO WO1997049707 · 1997 [cited by applicant]
WO WO1998047879 · 1998 [cited by applicant]
WO WO1999047529 · 1999 [cited by applicant]
WO WO1999055663 · 1999 [cited by applicant]
WO WO1999065874 · 1999 [cited by applicant]
WO WO2000024707 · 2000 [cited by applicant]
WO WO2000064876 · 2000 [cited by applicant]
WO WO2001007028 · 2001 [cited by applicant]
WO WO2001019788 · 2001 [cited by applicant]
WO WO2001043732 · 2001 [cited by applicant]
WO WO2001056989 · 2001 [cited by applicant]
WO WO2001064642 · 2001 [cited by applicant]
WO WO2001064643 · 2001 [cited by applicant]
WO WO2001066098 · 2001 [cited by applicant]
WO WO2001070671 · 2001 [cited by applicant]
WO WO2001080894 · 2001 [cited by applicant]
WO WO2002004403 · 2002 [cited by applicant]
WO WO2002028835 · 2002 [cited by applicant]
WO WO2002034711 · 2002 [cited by applicant]
WO WO2002042273 · 2002 [cited by applicant]
WO WO2002046159 · 2002 [cited by applicant]
WO WO2002051397 · 2002 [cited by applicant]
WO WO2002054077 · 2002 [cited by applicant]
WO WO2002070483 · 2002 [cited by applicant]
WO WO2002090347 · 2002 [cited by applicant]
WO WO2002098839 · 2002 [cited by applicant]
WO WO2002101007 · 2002 [cited by applicant]
WO WO2003003008 · 2003 [cited by applicant]
WO WO2003003009 · 2003 [cited by applicant]
WO WO2003004020 · 2003 [cited by applicant]
WO WO2003007955 · 2003 [cited by applicant]
WO WO2003013516 · 2003 [cited by applicant]
WO WO2003018536 · 2003 [cited by applicant]
WO WO2003045921 · 2003 [cited by applicant]
WO WO2003055477 · 2003 [cited by applicant]
WO WO2003057205 · 2003 [cited by applicant]
WO WO2003062221 · 2003 [cited by applicant]
WO WO2003072532 · 2003 [cited by applicant]
WO WO2003075907 · 2003 [cited by applicant]
WO WO2004000820 · 2003 [cited by applicant]
WO WO2004014844 · 2004 [cited by applicant]
WO WO2004018428 · 2004 [cited by applicant]
WO WO2004052837 · 2004 [cited by applicant]
WO WO2004056777 · 2004 [cited by applicant]
WO WO2004062601 · 2004 [cited by applicant]
WO WO2005000309 · 2005 [cited by applicant]
WO WO2005023761 · 2005 [cited by applicant]
WO WO2005033079 · 2005 [cited by applicant]
WO WO2005040135 · 2005 [cited by applicant]
WO WO2005073165 · 2005 [cited by applicant]
WO WO2005085202 · 2005 [cited by applicant]
WO WO2006007864 · 2006 [cited by applicant]
WO WO2006011050 · 2006 [cited by applicant]
WO WO2006058905 · 2006 [cited by applicant]
WO WO2006067445 · 2006 [cited by applicant]
WO WO2006068199 · 2006 [cited by applicant]
WO WO2006137376 · 2006 [cited by applicant]
WO WO2007008627 · 2007 [cited by applicant]
WO WO2007013332 · 2007 [cited by applicant]
WO WO2007030567 · 2007 [cited by applicant]
WO WO2007052843 · 2007 [cited by applicant]
WO WO2007056143 · 2007 [cited by applicant]
WO WO2007071632 · 2007 [cited by applicant]
WO WO2007088996 · 2007 [cited by applicant]
WO WO2008044767 · 2008 [cited by applicant]
WO WO2008073670 · 2008 [cited by applicant]
WO WO2008074997 · 2008 [cited by applicant]
WO WO2008104994 · 2008 [cited by applicant]
WO WO2008135826 · 2008 [cited by applicant]
WO WO2008140810 · 2008 [cited by applicant]
WO WO2009000413 · 2008 [cited by applicant]
WO WO2009047105 · 2009 [cited by applicant]
WO WO2009047151 · 2009 [cited by applicant]
WO WO2009049180 · 2009 [cited by applicant]
WO WO2009049181 · 2009 [cited by applicant]
WO WO2009049183 · 2009 [cited by applicant]
WO WO2009070533 · 2009 [cited by applicant]
WO WO2010027746 · 2010 [cited by applicant]
WO WO2010031713 · 2010 [cited by applicant]
WO WO2010048149 · 2010 [cited by applicant]
WO WO2010133312 · 2010 [cited by applicant]
WO WO2010133748 · 2010 [cited by applicant]
WO WO2010138901 · 2010 [cited by applicant]
WO WO2011026240 · 2011 [cited by applicant]
WO WO2011032169 · 2011 [cited by applicant]
WO WO2011109059 · 2011 [cited by applicant]
WO WO2011133729 · 2011 [cited by applicant]
WO WO2011139765 · 2011 [cited by applicant]
WO WO2011140425 · 2011 [cited by applicant]
WO WO2012016133 · 2012 [cited by applicant]
WO WO2012026931 · 2012 [cited by applicant]
WO WO2012027392 · 2012 [cited by applicant]
WO WO2012106499 · 2012 [cited by applicant]
WO WO2012080729 · 2012 [cited by applicant]
WO WO2012112743 · 2012 [cited by applicant]
WO WO2012116440 · 2012 [cited by applicant]
WO WO2012125613 · 2012 [cited by applicant]
WO WO2012129562 · 2012 [cited by applicant]
WO WO2012166951 · 2012 [cited by applicant]
WO WO2012177668 · 2012 [cited by applicant]
WO WO2013003112 · 2013 [cited by applicant]
WO WO2013045400 · 2013 [cited by applicant]
WO WO2013061205 · 2013 [cited by applicant]
WO WO2013072502 · 2013 [cited by applicant]
WO WO2013092350 · 2013 [cited by applicant]
WO WO2013096060 · 2013 [cited by applicant]
WO WO2013109521 · 2013 [cited by applicant]
WO WO2013114250 · 2013 [cited by applicant]
WO WO2013131018 · 2013 [cited by applicant]
WO WO2014041125 · 2014 [cited by applicant]
WO WO2014055634 · 2014 [cited by applicant]
WO WO2014120808 · 2014 [cited by applicant]
WO WO2014120815 · 2014 [cited by applicant]
WO WO2014120820 · 2014 [cited by applicant]
WO WO2014134127 · 2014 [cited by applicant]
WO WO2014149207 · 2014 [cited by applicant]
WO WO2014157267 · 2014 [cited by applicant]
WO WO2014192681 · 2014 [cited by applicant]
WO WO2014204831 · 2014 [cited by applicant]
WO WO2015003816 · 2015 [cited by applicant]
WO WO2015010065 · 2015 [cited by applicant]
WO WO2015011284 · 2015 [cited by applicant]
WO WO2015014900 · 2015 [cited by applicant]
WO WO2015030898 · 2015 [cited by applicant]
WO WO2015046827 · 2015 [cited by applicant]
WO WO2015085238 · 2015 [cited by applicant]
WO WO2015089361 · 2015 [cited by applicant]
WO WO2015196072 · 2015 [cited by applicant]
WO WO2016022626 · 2016 [cited by applicant]
WO WO2016040449 · 2016 [cited by applicant]
WO WO2017040982 · 2017 [cited by applicant]
WO WO2017062751 · 2017 [cited by applicant]
WO WO2017066705 · 2017 [cited by applicant]
WO WO2017161028 · 2017 [cited by applicant]
WO WO2018060110 · 2018 [cited by applicant]
WO WO2018064119 · 2018 [cited by applicant]
WO WO2018161033 · 2018 [cited by applicant]
WO WO2018195439 · 2018 [cited by applicant]
WO WO2018202681 · 2018 [cited by applicant]
WO WO2019014352 · 2019 [cited by applicant]
WO WO2019018119 · 2019 [cited by applicant]
WO WO2019036657 · 2019 [cited by applicant]
WO WO2019150220 · 2019 [cited by applicant]
WO WO2019206925 · 2019 [cited by applicant]
WO WO2019207081 · 2019 [cited by applicant]
WO WO2019241787 · 2019 [cited by applicant]
WO WO2020051207 · 2020 [cited by applicant]
WO WO2020081572 · 2020 [cited by applicant]
WO WO2020123675 · 2020 [cited by applicant]
WO WO2020139748 · 2020 [cited by applicant]
WO WO2020146612 · 2020 [cited by applicant]
WO WO2020146682 · 2020 [cited by applicant]
WO WO2020152079 · 2020 [cited by applicant]
WO WO2020159576 · 2020 [cited by applicant]
WO WO2020176763 · 2020 [cited by applicant]
WO WO2020190774 · 2020 [cited by applicant]
WO WO2020198712 · 2020 [cited by applicant]
WO WO2020219867 · 2020 [cited by applicant]
WO WO2020221677 · 2020 [cited by applicant]
WO WO2020251974 · 2020 [cited by applicant]
ZA 9704663 · 1997 [cited by applicant]
Akopian, A.N., L. Sivilotti, and J.N. Wood, A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. [cited by applicant]
Balasegaram, T. et al., “Structure-Activity Relations. Part 9. The Biological Activity and Mode of Action of Substituted 2-Phenoxy-N′phenyl-pyridine-3-carboxamides,” J. Chem. Research (S), (1991), pp. 234. [cited by applicant]
Berge, S.M., et al. describe pharmaceutically acceptable salts in detail in [cited by applicant]
Black, J.A., et al., Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas. [cited by applicant]
Blair, N.T. and B.P. Bean, Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na [cited by applicant]
Bolton et al., “Discovery of nonbenzamidine factor VIIa inhibitors using a biaryl acid scaffold,” Bioorganic & Medicinal Chemistry Letters, vol. 23, Iss. 18, (Sep. 15, 2013), pp. 5239-5243. [cited by applicant]
Catterall, W. A., Goldin, A. L., and Waxman, S. G., International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. [cited by applicant]
Chahine, M., Chatelier, A., Babich, O., and Krupp, J. J., Voltage-gated sodium channels in neurological disorders. [cited by applicant]
Cheney et al., “Discovery of Novel P1 Groups for Coagulation Factor VIIa Inhibition Using Fragment-Based Screening,” J. med. Chem., (2015), 58, 6, pp. 2799-2808. [cited by applicant]
Choi, J.S. and S.G. Waxman, Physiological interactions between Na [cited by applicant]
Coward, K., et al., Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states. [cited by applicant]
Deak HL, et al., “N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR.” Bioorg. Med. Chem. Lett., (Feb. 1, 2008); 18(3); pp. 1172-1176. [cited by applicant]
Dieleman, J.P., et al., Incidence rates and treatment of neuropathic pain conditions in the general population. [cited by applicant]
Dong, X.W., et al., Small interfering RNA-mediated selective knockdown of Na( [cited by applicant]
England, S., Voltage-gated sodium channels: the search for subtype-selective analgesics. [cited by applicant]
Harbeson, S.L., and Tung, [cited by applicant]
Huang, H.L., et al., Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper-excitable nerves. [cited by applicant]
Jarvis, M.F., et al., A-803467, a potent and selective Na [cited by applicant]
Joshi, S.K., et al., Involvement of the TTX-resistant sodium channel Nav1.8 in inflammatory and neuropathic, but not post-operative, pain states. [cited by applicant]
Kassah, E.A. et al., “Synthesis and behavior of a static benzoxazinone derivative towards nitrogen and sulphur nucleophieles,” Egyptian Journal of Chemistry, 44, (2001); pp. 169-180. [cited by applicant]
Krafte, D. S. and Bannon, A. W., Sodium channels and nociception: recent concepts and therapeutic opportunities. [cited by applicant]
Lai, J., et al., Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, Na [cited by applicant]
Lambeng et al., “Arylsulfonamides as a new class of cannabinoid CB [cited by applicant]
Li, J., et al., “Discovery of potent and orally active MTP inhibitors as potential anti-obesity agents,” Bioorganic & Medicinal Chemistry Letters, vol. 16, Iss. 11, 16 (Jun. 2006), pp. 3039-3042. [cited by applicant]
Liew et al., “SVM Model for Virtual Screening of Lck Inhibitors,” J. Chem. Inf. Model. (2009), 44, 4, pp. 877-885. [cited by applicant]
List of Registry Compounds from CAS STN® Registry Database, with dates of entry in database. [cited by applicant]
Mehta et al., “Synthesis, characterization and antimicrobial activity of 1, 3, 4,-oxadiazoles derivatives of benzimidazoles,” Chem. Sci. Rev. & Lett., 2014, 3(11), pp. 522-528. [cited by applicant]
Mehta et al., “Synthesis, characterization and antimicrobial evaluation of some novel benzenesulfonylhydrazone derivatives of benzimidazole,” Der ChemicaSinica, 2015, 6(2): pp. 29-34. [cited by applicant]
Micronized amino-substituted hydroxyphenylbenzophenone derivatives IP.com Journal (Feb. 24, 2006) IP134143D. [cited by applicant]
Miura et al., “Design, synthesis and biological activity of selective and orally available TF/FVIIa complex inhibitors containing non-amidine P1 ligands,” Bioorg. Med. Chem. (Jan. 1, 2007); 15(1): pp. 160-173. [cited by applicant]
Miura et la., “Potent and selective TF/FVIIa inhibitors containing a neutral P1 ligand,” Bioorg. Med. Chem. (Dec. 1, 2006); 14(23): pp. 7688-7705. [cited by applicant]
Naruto et al., “Synthesis of yokonoside and its related compounds,” Yakugaku Zassh (Aug. 1976); 96(8): pp. 945-951. [cited by applicant]
Nielsen et la., “2-(4-Methoxyphenoxy)-5-nitro-N-(4-sulfamoylphenyl)benzamide activates Kir6.2/SUR1 KATP channels,” Bioorg. Med. Chem. Lett. (Dec. 6, 2004); 14(23): pp. 5727-5730. [cited by applicant]
Preparation of amino substituted hydroxyl phenyl benzophenone derivatives and their uses as UV filters in sunscreen formulations, IP.com Journal (Aug. 4, 2003) IP 18721D. [cited by applicant]
Qiu, F., et al., Increased expression of tetrodotoxin-resistant sodium channels Na [cited by applicant]
Renganathan, M., T.R. Cummins, and S.G. Waxman, Contribution of Na( [cited by applicant]
Roza, C., et al., The tetrodotoxin-resistant Na [cited by applicant]
Ruangsri, S., et al., Relationship of axonal voltage-gated sodium channel 1.8 (Na [cited by applicant]
Rush, A.M. and T.R. Cummins, [cited by applicant]
Rush, A.M., et al., A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons. [cited by applicant]
Shirley, V.S., & Lederer, C.M., Isotopes Project, Nuclear Science Division, Lawrence Berkeley Laboratory, Table of Nuclides (Jan. 1980). [cited by applicant]
Soderpalm, B., Anticonvulsants: aspects of their mechanisms of action. [cited by applicant]
Strickland, I.T., et al., Changes in the expression of NaV1.7, Na [cited by applicant]
Sun, W., et al., Reduced conduction failure of the main axon of polymodal nociceptive C-fibers contributes to painful diabetic neuropathy in rats. [cited by applicant]
Use of amino hydroxy benzophenone derivatives for protecting human hair and skin, IP.com Journal (Aug. 10, 2006) IP 138915D. [cited by applicant]
Use of aminohydroxybenzophenone derivatives in sunscreen preparations, IP.com Journal (Aug. 24, 2006) IP139425D. [cited by applicant]
Vertex Announces Treatment with the NaV1.8 Inhibitor VX-150 Showed Significant Relief of Acute Pain in Phase 2 Study (Feb. 14, 2018). [cited by applicant]
Wang et al., “Kinetics of extractable residue, bound residue and mineralization of a novel herbicide, ZJ0273, in aerobic soils,” Chemosphere, vol. 76, Iss. 8, (Aug. 2009), pp. 1036-1040. [cited by applicant]
Wang et al., “Studies on the anoxic dissipation and metabolism of pyribambenz propyl (ZJ0273) in soils using position-specific radiolabeling,” Science of the Total Environment 472, (2014), pp. 582-589. [cited by applicant]
Wang et al., “Transformation of 14C-pyrimidynyloxybenzoic herbicide ZJ0273 in aerobic soils,” Science of The Total Environment, vol. 408, Iss. 10, (Apr. 15, 2010); pp. 2239-2244. [cited by applicant]
Wang, G. K., Mitchell, J., and Wang, S. Y., Block of persistent late Na [cited by applicant]
Written Opinion of the International Searching Authority and International Search Report for PCT/US2018/041649 dated Oct. 17, 2018. [cited by applicant]
Yiangou, Y., et al., SNS/PN3 and SNS2/NaN sodium channel-like immunoreactivity in human adulty and neonate injured sensory nerves. [cited by applicant]
Yue et al., “The metabolism of a novel herbicide ZJ0273 in oilseed rape and crickweed,” Pesticide Biochemistry and Physiology, vol. 104, Iss.3, (Sep. 2012), pp. 44-49. [cited by applicant]