US 11,807,623 B2
Nucleic acid-binding photoprobes and uses thereof
Gnanasambandam Kumaravel, Lexington, MA (US); Jennifer C. Petter, Stow, MA (US); Jonathan Craig Blain, Melrose, MA (US); Donovan Noel Chin, Lexington, MA (US); Chao Fang, Lexington, MA (US); Herschel Mukherjee, Somerville, MA (US); and Neil Kubica, Swampscott, MA (US)
Assigned to Arrakis Therapeutics, Inc., Waltham, MA (US)
Filed by Arrakis Therapeutics, Inc., Waltham, MA (US)
Filed on Nov. 30, 2018, as Appl. No. 16/207,062.
Claims priority of provisional application 62/593,175, filed on Nov. 30, 2017.
Prior Publication US 2019/0270723 A1, Sep. 5, 2019
Int. Cl. C07H 21/02 (2006.01); C07D 401/14 (2006.01); A61K 47/54 (2017.01); A61K 47/68 (2017.01); A61P 25/28 (2006.01); A61P 43/00 (2006.01); A61K 9/00 (2006.01); C07D 495/04 (2006.01); C12N 15/115 (2010.01); G01N 33/50 (2006.01); C07D 401/12 (2006.01); A61K 31/522 (2006.01); A61K 39/395 (2006.01); C12Q 1/6816 (2018.01); A61K 31/65 (2006.01); C07D 217/26 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0053 (2013.01); A61K 31/522 (2013.01); A61K 31/65 (2013.01); A61K 39/395 (2013.01); A61K 47/545 (2017.08); A61K 47/6809 (2017.08); A61P 25/28 (2018.01); A61P 43/00 (2018.01); C07D 217/26 (2013.01); C07D 401/12 (2013.01); C07D 495/04 (2013.01); C12N 15/115 (2013.01); C12Q 1/6816 (2013.01); G01N 33/5008 (2013.01)] 16 Claims
 
1. A compound of Formula I:

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or a pharmaceutically acceptable salt thereof; wherein:
Ligand is a small molecule RNA binder;
T1 is a bivalent tethering group selected from a C1-20 bivalent straight or branched hydrocarbon chain wherein 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 methylene units of the chain are independently and optionally replaced with a natural or non-natural amino acid, —O—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)—, —C(O)N(R)—, —(R)NC(O)—, —OC(O)N(R)—, —(R)NC(O)O—, —N(R)C(O)N(R)—, —S—, —SO—, —SO2—, —SO2N(R)—, —(R)NSO2—, —C(S)—, —C(S)O—, —OC(S)—, —C(S)N(R)—, —(R)NC(S)—, —(R)NC(S)N(R)—, or -Cy-; and 1-20 of the methylene units of the chain are independently and optionally replaced with —OCH2CH2—;
wherein each -Cy- is independently a bivalent optionally substituted 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, optionally substituted phenylene, an optionally substituted 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an optionally substituted 8-10 membered bicyclic or bridged bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bicyclic or bridged bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and
Rmod is a photoactivatable group selected from

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