US 12,258,680 B2
Solid support
Frederic Berst, Altkirch (FR); and Yves Ruff, Strasbourg (FR)
Assigned to NOVARTIS AG, Basel (CH)
Appl. No. 17/055,733
Filed by NOVARTIS AG, Basel (CH)
PCT Filed May 17, 2019, PCT No. PCT/IB2019/054094
§ 371(c)(1), (2) Date Nov. 16, 2020,
PCT Pub. No. WO2019/220406, PCT Pub. Date Nov. 21, 2019.
Claims priority of application No. 18173182 (EP), filed on May 18, 2018.
Prior Publication US 2021/0207288 A1, Jul. 8, 2021
Int. Cl. C40B 50/14 (2006.01); C07C 237/12 (2006.01); G01N 33/545 (2006.01)
CPC C40B 50/14 (2013.01) [C07C 237/12 (2013.01); G01N 33/545 (2013.01); C07B 2200/11 (2013.01); C07C 2601/14 (2017.05)] 13 Claims
OG exemplary drawing
 
1. A solid support for use in non-aqueous DNA-conjugated molecule reactions, wherein the support comprises a solid body formed from a plurality of polyethylene glycol units, wherein the solid body includes at least one cationic moiety, wherein the cationic moiety includes a quaternary ammonium group or a guanidinium group, and wherein the cationic moiety is a compound according to Formula I:

OG Complex Work Unit Chemistry
wherein:
Body is the solid support formed from a plurality of polyethylene glycol units;
R is hydrogen; C1-C8 alkyl optionally substituted by hydroxy, phenyl, C3-C8 cycloalkyl, 5 to 10 membered heterocyclic ring or —OC1-C8 alkyl; C3-C8 cycloalkyl; —C(O)C1-C8 alkyl; or a 5 to 10 membered heterocyclic ring;
X is X1 or X2, wherein
X1 is a C1-C20 alkylene chain, wherein the chain is straight or branched and is optionally substituted by one or more substituents selected from halogen, —OH, C1-C8 alkoxy, nitro, cyano, —COOH, carbamoyl, —N(R4)R5, C3-C6 cycloalkyl, 3 to 7 membered heterocyclic ring, phenyl, 5 or 6 membered heteroaryl, or C1-C4 alkyl-phenyl;
X2 is —Z—X1—
wherein Z is selected from —(CH2)a—Rx—(CH2)a—NH—C(═O)—; —(CH2)a—CH((CH2)a—Rx1)NH—C(═O)—; —(CH2)a—(O)0-1—Rx2—CH(Rx3)NH—C(═O)—; and —(CH2)b—(O)0-1—(CH2)b—NH—C(═O)—;
a is an integer from 0 to 6;
b is an integer from 1 to 6;
Rx is selected from phenyl; C3-C8 cycloalkylene; —C(H)2-x((C1-C6alkyl)x)-; naphthyl; and anthracyl,
which phenyl, C3-C8 cycloalkylene, C1-C6alkyl, naphthyl or anthracyl are optionally substituted 1, 2, 3 or 4 times independently with C1-C6alkyl, C1-C6alkoxy, C1-C6 haloalkyl or halo;
Rx1 is selected from phenyl; C3-C8 cycloalkyl; naphthyl; and anthracyl,
which phenyl, C3-C8 cycloalkyl, naphthyl or anthracyl are optionally substituted 1, 2, 3 or 4 times independently with C1-C6alkyl, C1-C6alkoxy, C1-C6 haloalkyl or halo;
Rx2 is selected from phenyl; C3-C8 cycloalkylene; naphthyl; and anthracyl,
which phenyl, C3-C8 cycloalkylene, naphthyl or anthracyl are optionally substituted 1, 2, 3 or 4 times independently with C1-C6alkyl, C1-C6alkoxy, C1-C6 haloalkyl or halo;
Rx3 is selected from hydrogen; phenyl; and C3-C6cycloalkyl,
which phenyl or C3-C6cycloalkyl are optionally substituted 1, 2, 3 or 4 times independently with C1-C6alkyl; C1-C6alkoxy; C1-C6 haloalkyl or halo;
x is an integer from 0 to 2;
Y is C(O); and
R1, R2, R3 are each independently selected from hydroxy; C1-C8 alkyl optionally substituted by hydroxy, phenyl, C3-C8 cycloalkyl, 5 to 10 membered heterocyclic ring or —OC1-C8 alkyl; C3-C8 cycloalkyl; —C(O)C1-C8 alkyl; or a 5 to 10 membered heterocyclic ring;
R4 and R5 are each independently selected from hydrogen; hydroxy; C1-C8 alkyl optionally substituted by hydroxy, phenyl, C3-C8 cycloalkyl, 5 to 10 membered heterocyclic ring or —OC1-C8 alkyl; C3-C8 cycloalkyl; —C(O)C1-C8 alkyl; or a 5 to 10 membered heterocyclic ring.