Bis(diazirine) derivatives as photo-crosslinker for treating corneal ectatic disorders

A compound of Formula II

• or a pharmaceutically acceptable salt thereof,
• wherein:
• each of B1 and B2 is independently —Z1—Z2—Z3, wherein:
• Z1 is C1-3 alkylene;
• Z2 is a bond;
• and
• Z3 is H;
• each of E1 and Q1 is C1-C6 alkylene, which is optionally substituted with 1-3 Ra;
• each occurrence of R2 is independently selected from the group consisting of:
• (i) Ra;
• (ii) C1-C6 alkyl, which is substituted with 1-3 Ra;
• (iii) L2-heterocyclyl, wherein the heterocyclyl includes from 3-10 ring atoms, wherein from 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N(Rd), O, and S;
• and wherein one or more of the heterocyclyl ring carbon atoms are optionally substituted with from 1-4 independently selected Rb,
• (iv) L2-C6-C10 aryl, which is optionally substituted with from 1-4 Rc;
• (v) L2-heteroaryl, wherein the heteroaryl includes from 5-10 ring atoms, wherein from 1-4 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(Rd), O, and S, and wherein one or more of the heteroaryl ring carbon atoms are optionally substituted with from 1-4 independently selected Rc;
• and
• (vi) H;
• or
• (vii) R2 and Rd1, in the —C(═O)CH(R2)N(Rd1)— group, combine to form a ring including from 5-8 ring atoms, wherein the ring includes:
• (a) from 3-6 ring carbon atoms (in addition to CH(R2)), each of which is substituted with from 1-2 substituents independently selected from H and C1-3 alkyl;
• and (b) from 0-3 ring heteroatoms (in addition to the nitrogen atom attached to Rd1), which are each independently selected from the group consisting of N(Rd1), O, and S;
• each occurrence of Ra is independently selected from the group consisting of:
• —OH;
• —SH;
• —F;
• —Cl;
• —Br;
• —NReRf;
• C1-4 alkoxy;
• C1-4 haloalkoxy;
• —C(═O)O(C1-4 alkyl);
• —C(═O)(C1-4 alkyl);
• —C(═O)OH;
• —CON(R′)(R″);
• —S(O)1-2(NR′R″);
• —S(O)0-2(C1-4 alkyl);
• cyano;
• —NR′C(═NR′)NR′R″;
• and C3-6 cycloalkyl optionally substituted with from 1-4 independently selected Rb;
• each occurrence of Rb is independently selected from the group consisting of:
• —OH;
• —SH;
• —F;
• —Cl;
• —Br;
• —NReRf;
• C1-4 alkyl;
• C1-4 haloalkyl;
• C1-4 alkoxy;
• C1-4 haloalkoxy;
• —C(═O)O(C1-4 alkyl);
• —C(═O)(C1-4 alkyl);
• —C(═O)OH;
• —CON(R′)(R″);
• oxo;
• —S(O)1-2(NR′R″);
• —S(O)0-2(C1-4 alkyl);
• cyano;
• —NR′C(═NR′)NR′R″;
• and C3-6 cycloalkyl optionally substituted with from 1-4 independently selected C1-4 alkyl;
• each occurrence of Rc is independently selected from the group consisting of:
• —OH;
• —SH;
• —F;
• —Cl;
• —Br;
• —NReRf;
• C1-4 alkyl;
• C1-4 haloalkyl;
• C1-4 alkoxy;
• C1-4 haloalkoxy;
• —C(═O)O(C1-4 alkyl);
• —C(═O)(C1-4 alkyl);
• —C(═O)OH;
• —CON(R′)(R″);
• —S(O)1-2(NR′R″);
• —S(O)0-2(C1-4 alkyl);
• cyano;
• —NR′C(═NR′)NR′R″;
• and C3-6 cycloalkyl optionally substituted with from 1-4 independently selected C1-4 alkyl;
• each occurrence of Rd is selected from the group consisting of:
• H;
• C1-6 alkyl;
• C3-6 cycloalkyl;
• —C(O)(C1-4 alkyl);
• —C(O)O(C1-4 alkyl);
• —CON(R′)(R″);
• —S(O)1-2(NR′R″);
• —S(O)1-2(C1-4 alkyl);
• —OH;
• and C1-4 alkoxy;
• each occurrence of Re and Rf is independently selected from the group consisting of:
• H;
• C1-6 alkyl;
• C3-6 cycloalkyl;
• —C(O)(C1-4 alkyl);
• —C(O)O(C1-4 alkyl);
• —CON(R′)(R″);
• —S(O)1-2(NR′R″);
• —S(O)1-2(C1-4 alkyl);
• —OH;
• and C1-4 alkoxy;
• and
• each occurrence of R′ and R″ is independently selected from the group consisting of:
• H and C1-4 alkyl;
• or R′ and R″ together with the nitrogen atom to which each is attached forms a ring including from 3-8 ring atoms, wherein the ring includes:
• (a) from 1-7 ring carbon atoms, each of which is substituted with from 1-2 substituents independently selected from H and C1-3 alkyl;
• and (b) from 0-3 ring heteroatoms (in addition to the nitrogen atom attached to R′ and R″), which are each independently selected from the group consisting of N(R4), O, and S;
• each occurrence of Rd1 is selected from the group consisting of:
• H, C1-6 alkyl;
• C3-6 cycloalkyl;
• —C(O)(C1-4 alkyl);
• —C(O)O(C1-4 alkyl);
• —CON(R′)(R″);
• —S(O)1-2(NR′R″);
• —S(O)1-2(C1-4 alkyl);
• —OH;
• and C1-4 alkoxy;
• or R2 and Rd1, in the —C(═O)CH(R2)N(Rd1)— group, combine to form a ring including from 5-8 ring atoms as defined above;
• each of L2 in each occurrence is independently a single bond or a C1-C6 alkylene optionally substituted with 1-3 substituents independently selected from oxo and Ra;
• and
• F1 is —N(Rd1)—, —O—, or —S—;
• and
• each of H1, G1, L1, and M1 is independently selected from:
• a bond;
• —N(Rd1)—,
• —O—;
• S(O)p, wherein p is 0, 1, or 2;
• C(═O);
• C(═S);
• CHR2;
• —C(═O)CH(R2)N(Rd1)—;
• and
• —C(═O)CH(R2)CH2N(Rd1)—.