US 12,258,334 B2
Branched sugar alcohol-based compounds, and compositions and methods thereof
Yumei Huang, Lexington, MA (US)
Assigned to CellMosaic Inc., Woburn, MA (US)
Appl. No. 17/045,286
Filed by CellMosaic Inc., Woburn, MA (US)
PCT Filed Apr. 30, 2019, PCT No. PCT/US2019/029854
§ 371(c)(1), (2) Date Oct. 5, 2020,
PCT Pub. No. WO2019/213046, PCT Pub. Date Nov. 7, 2019.
Claims priority of provisional application 62/665,250, filed on May 1, 2018.
Prior Publication US 2021/0170037 A1, Jun. 10, 2021
Int. Cl. C07D 405/14 (2006.01); A61K 47/56 (2017.01); A61K 47/68 (2017.01); C08G 83/00 (2006.01)
CPC C07D 405/14 (2013.01) [A61K 47/56 (2017.08); A61K 47/68033 (2023.08); A61K 47/68037 (2023.08); A61K 47/6809 (2017.08); C08G 83/003 (2013.01)] 19 Claims
 
1. A bifurcated SA monomer having a chemical structure of Formula I:

OG Complex Work Unit Chemistry
wherein
each of Z1, Z2, and Z3 is independently selected from the group consisting of R11,

OG Complex Work Unit Chemistry
 and at least one of Z1, Z2, and Z3 is not R11;
each R11 is independently selected from the group consisting acetyl, acetate, benzoyl, benzyl, beta-methoxyethoxymethyl ether, dimethoxytrityl, methoxymethyl ether, methoxytrityl [(4-methoxyphenyl)diphenylmethyl], p-methoxybenzyl ether, methythiomethyl ether, pivaloyl, tetrahydropyranyl, tetrahydrofuran, tetrahydrothiofuranyl, trityl, silyl ether, C1-C8 alkyl silyl, methyl ethers, and ethoxyethyl ethers;
each R21 is independently selected from the group consisting of hydrogen, acetyl, benzoyl, benzyl, beta-methoxyethoxymethyl ether, dimethoxytrityl, methoxymethyl ether, methoxytrityl [(4-methoxyphenyl)diphenylmethyl], p-methoxybenzyl ether, methythiomethyl ether, pivaloyl, tetrahydropyranyl, tetrahydrofuran, tetrahydrothiofuranyl, trityl, silyl ether, C1-C8 alkyl silyl, methyl ethers, ethoxyethyl ethers, C1-C8 alkyl, cyclic ortho ester, and acetonide of vicinal alcohol;
n is an integer selected from 2 to 8;
m is an integer selected from 1 to 8;
p is an integer selected from 0 to 50;
n1 is an integer selected from 1 to 4;
m1 is an integer selected from 1 to 4;
each L is independently selected from the group consisting of R2 and a structure of —V1—R2—V2—, wherein V1 and V2 are independently selected from the group consisting of a Diels-Alder adduct, a 1,3-dipolar adduct, —C(R4)(═N)—O—, —O—C(R4)(═N)—, —S—CH2—C(═O)—NH—, —NH—C(═O)—CH2—S—, —C(=G2)-G1-, -G1-C(=G2)-, -G3-, -G1-C(=G2)-G1-, —S—S—, —S—(CH2)2—S(O)2—, —S(O)2—(CH2)2—S—, —S(O)2—N(R3)—, —N(R3)—S(O)2—, —C(O)—NH—NH—CH2—, —C(O)—NH—N═CH—, —CH═N—NH—C(O)—, —CH2—NH—NH—C(O)—, —N(R3)—S(O)2—N(R3)—, —C(O)—NH—CH(CH2SH)—, —N═CH—, —NH—CH2—, —NH—C(O)—CH2—C(O)—NH—, —CH═N-G4-, —CH2—NH-G4-, -G4-NH—CH2—, -G4-N═CH—, —C(═NH2+)—NH—, —NH—C(═NH2+)—, —O—P(═O)(O−)—NH—, —NH—P(═O)(O−)—O—, —CH2—CH(NH2)—CH2—S—, —S—CH2—CH(NH2)—CH2—, —O—P(═O)(O−)—O—, —O—P(═O)(S−)—O—, —O—P(═S)(S−)—O—,

OG Complex Work Unit Chemistry
wherein
each G1 is independently selected from NR3, O, and S;
each G2 is independently O or S;
each G3 is independently selected from S, O, NR3, and SO2;
each G4 is independently O or NR3;
each R2 is independently selected from a bond, C1-C12 alkyl, —(CH2CH2O)1-10—, —(CH2CH2O)1-10—CH2—, —CH2—(CHOH)1-6—, —(CHOH)1-6—CH2—, —(CHOH)1-6—, optionally substituted alicyclyl, heteroalicyclyl, aryl, a peptide, p-aminobenzylcarbonyl spacer, a peptide with p-aminobenzylcarbonyl spacer, a dipeptide with p-aminobenzylcarbonyl spacer, and a peptidomimetic oligomer;
each R3 is independently selected from hydrogen, C1-C8 alkyl, —(OCH2CH2)1-3, optionally substituted alicyclyl, and optionally substituted heteroalicyclyl,
each R4 is independently selected from C1-C16 alkyl,
each X is independently selected from —OH, -J, —R5J, —C(═O)-J, —C(═O)—CH2-J, —NH—C(═O)—CH2-J, —OR5, —OR6, —OR7, —O-mesyl, —O-tosyl, —NH—C(═O)—CH2—O-mesyl, —NH—C(═O)—CH2—O-tosyl, —SH, —S—S-t-butyl, —SR7, —SR5, —S—S—R8, —NH—C(═O)—R9—S—S—R8, —NH—C(═O)—CH2—SH, —S(═O)2-J, —NH—C(═O)—R9—S—C(═O) R5, —NH2, —NHR5, —N(R5) R5, —NHR7, —NH-Fmoc, —NH-Boc, N-(phthalimidyl), —C(═O) H, —C(═O)—R5, NH—C(═O)—R9—C(═O)—R5, —C(═O)OH, NH—C(═O)—R9—C(═O)OH, —N═C═S, —N═C—O, —C≡C—R5, —N═N+=N−, —O—NH2, —O—NH-Fmoc, —O—NH-Boc, —O—N-(Boc)2, —O—N(-phthalimidyl), —NH—C(═O)—R9—O—NH-Boc, —NH—C(═O)—R9—O—N-(Boc)2, NH—C(═O)—R9—O—N(-phthalimidyl), —NH—NH2, —C(═O)—NH—NH2, —NH—C(═O)—NH—NH2, —NH—C(═S)—NH—NH2, -toluenesulfonylhydrazide, —R5—NH—C(═NH2+)—NH2, —NH—C(═NH2+)—CH2CH2CH2—SH,

OG Complex Work Unit Chemistry
 a benzophenone, an aryl diazonium, a diazoalkane, a diazoacetyl, an anthraquinone, a diazirine, an optionally substituted trifluoromethylphenyldiazirine, a diene, a dienophile, a 1,3-dipole, a dipolarophile, an alkene, a ketene, an alkene with allylic hydrogen, a dicarbonyl group, an epoxide, an oxirane, an organosilane, a phosphonium group, an ester, an anhydride, a carbonate group, a glyoxal, —C(═N+H2)—O—R5, a hydroxymethyl phosphine, an ethyl vinyl, a maleimide, a vinylsulfone, an allyl sulfone, a thioester, a cisplatin, an aziridine, and an acryloyl group,
wherein
each R5 is independently selected from optionally substituted C1-C8 alkyl, alicyclyl, heteroalicyclyl, benzyl, and aryl, wherein any ring in R5 is optionally substituted;
each R6 is independently selected from benzoyl, acetyl, benzyl, C1-C8 alkyl silyl, tetrahydropyranyl, tetrahydrofuranyl, and tetrahydrothiofuranyl;
each R7 is independently selected from trityl, MMT, and DMT;
each R8 is independently selected from 2-pyridyl, 4-pyridyl, 5-nitro-2-pyridyl, 5-nitro-4-pyridyl, 2-nitrophenyl, 4-nitrophenyl, 3-carboxy-4-nitrophenyl, and 2,4-dinitrophenyl;
each R9 is independently selected from C1-C16 alkyl; and
each J is independently selected from Cl, Br and I.