Compositions and methods of making expanded hematopoietic stem cells using derivatives of fluorene

A method for expanding hematopoietic stem cells in culture, the method comprising contacting a source of CD34+ cells in culture with an effective amount of a compound of Formula I, thereby expanding hematopoietic stem cells in the culture, wherein the compound of Formula I is

• or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein
• A is a fused cyclic moiety selected from the group consisting of a phenyl, C3-6 cycloalkyl, heterocycloalkyl, and heteroaryl, or is absent,
• wherein the heterocycloalkyl comprises from 3 to 6 ring members having 1 to 3 nitrogen atom ring members, and
• the heteroaryl comprises 5 to 6 ring members having 1 to 3 nitrogen atom ring members;
• R1 is selected from the group consisting of —C(O)—NRb—R1a, —NRb—C(O)—R1a, —NRb—C(O)—R1b, —NRb—X1—C(O)—R1a, —C(O)—X1—NRb—R1a, —X1—C(O)—NRb—R1a, —X1—NRb—C(O)—R1a, —NRb—C(O)—X1—C(O)—R1b, C(O)—NRb—X1—C(O)—R1b, —NRb—C(O)—O—R1a, —O—C(O)—NRb—R1a, —X1—NRb—C(O)—O—R1a, —X1—O—C(O)—NRb—R1a, —NRb—R1a, —C(O)—R1a, —O—C(O)—R1a, halo, and —NO2;
• R1a is selected from the group consisting of H, C1-10 alkyl, and C1-10 haloalkyl;
• R1b is selected from the group consisting of —ORa, —NRaRb, heterocycloalkyl, and phenyl,
• wherein the heterocycloalkyl comprises from 5 to 6 ring members having 1 to 3 heteroatom ring members selected from the group consisting of nitrogen, oxygen, and sulfur, and
• the heterocycloalkyl and the phenyl is unsubstituted or substituted with one to four C1-4 alkyl, —OH, and halo;
• each R2 is independently selected from the group consisting of halogen, —CN, —C1-8 alkyl, —C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, —C1-8 alkoxy, —X1—C1-8 alkoxy, —C(O)—R2a, —NRb—C(O)—R2a, —SRa, —X1—SRa, —ORa, —X1—ORa, —NRaRb, —X1—NRaRb, —S(O)2Ra, —S(O)2NRaRb, —X1—S(O)2Ra, —X1—S(O)2NRaRb, and —O—C(O)—Ra;
• each R3 is independently selected from the group consisting of halogen, CN, —C1-8 alkyl, —C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, —C1-8 alkoxy, —X1—C1-8 alkoxy, —C(O)—R3a, —SRa, —X1—SRa, —ORa, —X1—ORa, —NRaRb, —X1—NRaRb, —S(O)2Ra, —S(O)2NRaRb, —X1—S(O)2Ra, and —X1—S(O)2NRaRb;
• each R2a and R3a is independently selected from the group consisting of H, C1-10 alkyl, C1-10 haloalkyl, —ORa, —X1—ORa, —NRaRb, and —X1—NRaRb;
• R4a is selected from the group consisting of —ORa, —NRaRb, —O—C(O)—Ra, and cyano;
• R4b is H;
• or R4a and R4b are combined to form an oxo or an oxime moiety;
• each Ra and Rb is independently selected from the group consisting of H and C1-4 alkyl;
• each X1 is C1-4 alkylene;
• the subscript n is an integer from 0 to 3;
• and
• the subscript m is an integer from 0 to 2.