Substituted pyrazolo[1,5-α]pyrimidines as CRF receptor antagonists

A compound of Formula (I):

• or a pharmaceutically acceptable salt or stereoisomer thereof,
• wherein:
• R1 is H or C1-6 alkyl;
• R2 is C3-10 cycloalkyl, 4- to 14-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl;
• wherein the C3-10 cycloalkyl, 4- to 14-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-Cy, C2-6 alkenyl, C2-6 alkynyl, C(NRe)NRcRd, C(O)Rb, C(O)NRcRd, C(O)ORa, NRcRd, NRcC(Ne)NRcRd, NRcC(O)Rb, NRcC(O)NRcRd, NRcC(O)ORa, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, ORa, OC(O)Rb, OC(O)NRcRd, SRa, S(O)Rb, S(O)NRcRd, S(O)2Rb, S(O)2NRcRd, and Cy;
• and
• wherein each C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl substituent is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, NO2, C1-6 haloalkyl, C(NRe)NRcRd, C(O)Rb, C(O)NRcRd, C(O)ORa, NRcRd, NRcC(Re)NRcRd, NRcC(O)Rb, NRcC(O)NRcRd, NRcC(O)ORa, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, ORa,
• OC(O)Rb, OC(O)NRcRd, SRa, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd;
• each Cy is independently C3-10 cycloalkyl, 4- to 14-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl, wherein each C3-10 cycloalkyl, 4- to 14-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C(NRe1)NRc1Rd1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1, NRc1C(NRe1)NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)NRc1Rd1, NRc1C(O)ORa1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, ORa1, OC(O)Rb1, OC(O)NRc1Rd1, SRa1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, and S(O)2NRc1Rd1;
• each Ra is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Rb is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Rc is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Rd is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• or
• any Rc and Rd, taken together with the nitrogen atom to which they are attached, independently forms a 4- to 7-membered heterocycloalkyl, wherein each 4- to 7-membered heterocycloalkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Ra1 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Rb1 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Rc1 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Rd1 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, C6-10 aryl, 4- to 10-membered heterocycloalkyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRe2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• or
• any Rc1 and Rd1, taken together with the nitrogen atom to which they are attached, independently forms a 4- to 7-membered heterocycloalkyl, wherein each 4- to 7-membered heterocycloalkyl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, C1-4 alkyl, C1-4 haloalkyl, C(NRe2)NRc2Rd2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(NRc2)NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)NRc2Rd2, NRc2C(O)ORa2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2 ORa2, OC(O)Rb2, OC(O)NRc2Rd2, SRa2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• each Ra2 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, C1-6 alkyl, C1-6 haloalkyl, NH2, OH, OC1-6 alkyl, and OC1-6 haloalkyl;
• each Rb2 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, C1-6 alkyl, C1-6 haloalkyl, NH2, OH, OC1-6 alkyl, and OC1-6 haloalkyl;
• each Rc2 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, C1-6 alkyl, C1-6 haloalkyl, NH2, OH, OC1-6 alkyl, and OC1-6 haloalkyl;
• each Rd2 is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, or 5- to 10-membered heteroaryl, wherein each C1-6 alkyl, C1-6 haloalkyl, C1-4 alkylene-C3-7 cycloalkyl, C1-4 alkylene-4- to 10-membered heterocycloalkyl, C1-4 alkylene-C6-10 aryl, C1-4 alkylene-5- to 10-membered heteroaryl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, and 5- to 10-membered heteroaryl is optionally and independently substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, CN, C1-6 alkyl, C1-6 haloalkyl, NH2, OH, OC1-6 alkyl, and OC1-6 haloalkyl;
• each Re is independently H, CN, or C1-4 alkyl;
• each Re1 is independently H, CN, or C1-4 alkyl;
• and
• each Re2 is independently H, CN, or C1-4 alkyl;
• with the provisos that:
• (1) any ring-forming carbon atom or any ring-forming nitrogen atom of any aforementioned heterocycloalkyl is optionally and independently substituted with one ═O substituent;
• and
• (2) any ring-forming sulfur atom of any aforementioned heterocycloalkyl is optionally and independently substituted with one or two ═O substituents.