US 11,807,631 B2
Herboxidiene derivatives and uses thereof
Arun K. Ghosh, West Lafayette, IN (US); and Melissa Jurica, Santa Cruz, CA (US)
Assigned to Purdue Research Foundation, West Lafayette, IN (US); and The Regents of the University of California, Oakland, CA (US)
Appl. No. 16/633,953
Filed by Purdue Research Foundation, West Lafayette, IN (US); and The Regents of the University of California, Oakland, CA (US)
PCT Filed Jul. 26, 2018, PCT No. PCT/US2018/043894
§ 371(c)(1), (2) Date Jan. 24, 2020,
PCT Pub. No. WO2019/023450, PCT Pub. Date Jan. 31, 2019.
Claims priority of provisional application 62/537,129, filed on Jul. 26, 2017.
Prior Publication US 2020/0207746 A1, Jul. 2, 2020
Int. Cl. C07D 405/14 (2006.01); C07D 407/06 (2006.01); C07D 413/14 (2006.01)
CPC C07D 405/14 (2013.01) [C07D 407/06 (2013.01); C07D 413/14 (2013.01)] 11 Claims
 
1. A compound of the formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, crystalline form, non crystalline form, hydrate, or solvate thereof wherein:
Y is alkoxy or:
(a) a group of the formula:

OG Complex Work Unit Chemistry
wherein: X6 is O or N, it being understood that R14 is absent if X5 is O; Y1 is an amino acid side chain; L1 is the group CH(Y1)NHC(O)CH(Y1), wherein each Y1 is, independently, an amino acid side chain; R14 is H, alkyl or a nitrogen protecting group; R15 is or (CH2)p—R16, wherein R16 is N3, —C≡C—CN, NHR14, or a maleimide group and p is an integer from 0 to 6; X7 is NHR14, OR17 or —O(CH2CH2O)g(CH2)h(CH2CH2O)gR17, wherein R17 is H or alkyl, each g is an integer from 0 to 5 and h is an integer from 0 to 5; X8 is O, CH2 or NR14, it being understood that R14 is absent and X8 is CH when the group C(O)X7 or CH2X7 is attached to X8; m is an integer from 0 to 2;
(b) a group of the formula:

OG Complex Work Unit Chemistry
wherein X, R14, m, X7, and X8 are as defined herein; or
(c) a group of the formula:

OG Complex Work Unit Chemistry
X is O; X1 is CH2; R1, R3, R4, and R5 are each H; R2, R6, R7, R8, and R11 are each alkyl; R9 is alkoxy; R10 is hydroxy; X5 is O; and X6 is CH;
the dashed lines in the ring comprising X2-X4 each independently a single or a double bond;
X2, X3 and X4 are each independently O, NR12 or C(R12)2, wherein R12 is alkyl, alkenyl, alkoxy, alkoxyalkyl or (CH2)n—N3, wherein n is an integer from 1 to 6, or, in the case of C(R12)2, two R12 groups, together with the atom to which they are attached, form a cycloalkyl group.