US 12,234,228 B2
Nitric oxide donor and anti-oxidant compounds
Suchismita Acharya, Euless, TX (US)
Assigned to UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER, Fort Worth, TX (US)
Appl. No. 17/416,278
Filed by University of North Texas Health Science Center, Fort Worth, TX (US)
PCT Filed Dec. 20, 2019, PCT No. PCT/US2019/067944
§ 371(c)(1), (2) Date Jun. 18, 2021,
PCT Pub. No. WO2020/132496, PCT Pub. Date Jun. 25, 2020.
Claims priority of provisional application 62/783,333, filed on Dec. 21, 2018.
Prior Publication US 2022/0073503 A1, Mar. 10, 2022
Int. Cl. C07D 413/12 (2006.01); A61P 9/10 (2006.01); C07D 409/12 (2006.01)
CPC C07D 413/12 (2013.01) [A61P 9/10 (2018.01); C07D 409/12 (2013.01)] 78 Claims
 
1. A compound of the formula:

OG Complex Work Unit Chemistry
wherein:
n and m are each independently 0, 1, 2, 3, or 4;
Z1 is
a group of the formula:

OG Complex Work Unit Chemistry
wherein:
X1 is ═CRx1— or ═N— wherein,
Rx1 is hydrogen, alkyl(C≤12), or substituted alkyl(C≤12);
X2 is —O—, —S—, —S(O)—, or —S(O)2—;
each instance of R1, R1′, R2, and R2′ is independently hydrogen, hydroxy, amino, nitro, cyano, halo, carboxyl, carbamoyl, mercapto, —S(O)2OH, or —S(O)2NH2; or
alkyl(C≤12), acyl(C≤12), alkoxy(C≤12), alkylamino(C≤12), dialkylamino(C≤12), amido(C≤12), acyloxy(C≤12), or a substituted version of any of these groups; or —C(O)Rb, wherein:
Rb alkoxy(C≤12), alkylamino(C≤12), or dialkylamino(C≤12); or
provided the sum of n and m is 1, 2, 3, 4, 5, or 6; or
a compound of the formula:

OG Complex Work Unit Chemistry
wherein:
Z1 is as defined above;
R3 is alkyl(C2-12), aralkyl(C≤12), heteroaralkyl(C≤12), -alkanediyl(C≤12)-NHC(NH)NH2, or a substituted version of any of these groups;
R3′ is hydrogen; or
R3 and R3′ are taken together and are -alkanediyl(C≤12)-X3—, substituted -alkanediyl(C≤12)-X3—, -alkanediyl(C≤6)-X3-alkanediyl(C≤6)—, or substituted-alkanediyl(C≤6)-X3-alkanediyl(C≤6)—, wherein:
X3 is —O—, —NRa—, —S—, —S(O)—, or —S(O)2—, wherein:
Ra is hydrogen, hydroxy, or oxyl radical; or
alkyl(C≤12), aralkyl(C≤12), acyl(C≤12), or a substituted version of any of these groups; or
a group of the formula:

OG Complex Work Unit Chemistry
wherein:
Rc is hydroxy or oxyl radical; and
Y is —CO2Rd, or —C(O)NRdRe, wherein:
Rd is hydrogen; or
alkyl(C≤12), cycloalkyl(C≤12), heterocycloalkyl(C≤12), aralkyl(C≤12), aryl(C≤12), heteroaralkyl(C≤12), heteroaryl(C≤12), or a substituted version of any of these groups; or
a group of the formula:

OG Complex Work Unit Chemistry
wherein Rc is as defined above; or
a group of the formula:

OG Complex Work Unit Chemistry
Rc is hydrogen, alkyl(C≤12), or substituted alkyl(C≤12); or
a compound of the formula:

OG Complex Work Unit Chemistry
wherein:
n, m, X3, R1, R1′, R2, R2′, and Rc are as defined above; and
L1 is
a group of the formula:

OG Complex Work Unit Chemistry
wherein:
L is a covalent bond; or
a group of the formula:

OG Complex Work Unit Chemistry
wherein:
 Rf is hydrogen, alkyl(C≤12), or substituted alkyl(C≤12);
 R4 is hydrogen; or
 alkyl(C≤12), aralkyl(C≤12), heteroaralkyl(C≤12), -alkanediyl(C≤12)-ONO2, or a substituted version of any of these groups;
provided the sum of n and m is 1, 2, 3, 4, 5, or 6; or
a compound of the formula:

OG Complex Work Unit Chemistry
wherein:
Rc is as defined above;
R5 is —CO2Rg or —C(O)NRhRi, wherein:
Rg is hydrogen; or
alkyl(C≤12), substituted alkyl(C≤12), cycloalkyl(C≤12), or substituted cycloalkyl(C≤12);
Rb and Ri are each independently hydrogen; or
alkyl(C≤12), substituted alkyl(C≤12), cycloalkyl(C≤12), or substituted cycloalkyl(C≤12); and
R5′ is hydrogen; or
alkyl(C≤12), aralkyl(C≤12), heteroaralkyl(C≤12), or a substituted version of any of these groups;
or a pharmaceutically acceptable salt of any of these formulae.