Pnictogen-containing heterocyclic compounds and their use

Patent metadata

Field	Value
Publication number	US-12564636-B2
Application number	US-202318106242-A
Country	US
Kind code	B2
Filing date	Feb 6, 2023
Priority date	Mar 26, 2022
Publication date	Mar 3, 2026
Grant date	Mar 3, 2026

Abstract

Disclosed are pnictogen-containing heterocyclic compounds of Formula (I) Each of R1, the heterocyclic ring H, A+, LG, and X− is defined herein. Also provided are methods of modifying a substrate using such a compound, conjugated biomolecules thus modified, and pharmaceutical compositions containing one of the conjugated biomolecules.

First claim

What is claimed is:

1 . A pnictogen-containing heterocyclic compound of Formula (I):

in which
R 1 is C 1 -C 6 alkyl, C4-C10 cycloalkyl, 5- to 8-membered heterocycloalkyl, aryl, or heteroaryl;

 is a heterocyclic ring;
A + is a cationic quaternary pnictogen atom;
LG is a leaving group selected from the group consisting of halogen, aryloxy, R a O 2 S—, R b O 2 S—O—, R c OS—, R d S(O)(NSO 2 R e )—, and R f S(O)(N + (CH 3 ) 2 )-, each of R a , R b , R c , R d , R e , and R f , independently, being C 1 -C 6 alkyl, aryl, heteroaryl, halogen, alkoxy, or aryloxy;
X − is a counter anion selected from the group consisting of halide, polyhalide anion, perchlorate, hydroxide, peroxide, siloxide, sulfate, hydrogen sulfate, sulfite, disulfite, dithionate, dithionite, halosulfate, thiosulfate, persulfate, disulfate, sulfinate (R′SO 2 − ), sulfonate (R″SO 3 − ), bis(sulfonyl)imide ((R′SO 2 ) 2 N − ), nitrate, nitrite, azide, cyanide, cyanate, thiocyanate, phosphate, metaphosphate, polyphosphate, hydrogen phosphate, dihydrogen phosphate, monohalophosphate, dihalophosphate, hexahalophosphate, organophosphonate (R′P(O)(O − ) 2 or R′P(O)(OR − ) (O − )), organophosphate (R′OP(O)(O) 2 or R′OP(O)(OR″)(O − )), arsenate, alkoxide, alkenoxide, aryloxide, carboxylate, percarboxylate, carbonate, bicarbonate, oxalate, borate, tetrahaloborate, tetraalkylborate, tetraarylborate, carborane, and combinations thereof, each of R′ and R″, independently, being C 1 -C 6 alkyl or aryl; and
the number of net negative charges of X″ equals to that of the net positive charges of

2 . The pnictogen-containing heterocyclic compound of claim 1 , wherein the compound is a compound of Formula (II):

in which
the cationic quaternary pnictogen atom is N + in Formula (II);
R 1 is CH 3 , CH 2 CH 3 or -L-Het + ;
each of R 2 , R 3 , R 4 , R 5 , and R 6 , independently, is H, F, Cl, Br, I, C 1 -C 10 alkoxy, R a O 2 S—, R b O 2 S—O—, R f S(O)(N + (CH 3 ) 2 )—, halogenated aryl, halogenated heteroaryl, Het + , or -L-Het + , in which Het + is

 R 1 ′ is CH 3 or CH 2 CH 3 ; each of R 2 ′, R 3 ′, R 4 ′, R 5 ′, and R 6 ′, independently, is H, NO 2 , F, Cl, Br, I, R a ′O 2 S—, R b ′O 2 S—O—, or R f S(O)(N + (CH 3 ) 2 )—; each of R a ′, R b ′, and R f ′, independently, is C 1 -C 6 alkyl or aryl; and X′ is a counter anion selected from the group consisting of halide, polyhalide anion, perchlorate, hydroxide, peroxide, siloxide, sulfate, hydrogen sulfate, sulfite, disulfite, dithionate, dithionite, halosulfate, thiosulfate, persulfate, disulfate, sulfinate (R′SO 2 − ), sulfonate (R″SO 3 − ), bis(sulfonyl)imide ((R′SO 2 ) 2 N − ), nitrate, nitrite, azide, cyanide, cyanate, thiocyanate, phosphate, metaphosphate, polyphosphate, hydrogen phosphate, dihydrogen phosphate, monohalophosphate, dihalophosphate, hexahalophosphate, organophosphonate (R′P(O)(O − ) 2 or R′P(O)(OR″)(O − )), organophosphate (R′OP(O)(O − ) 2 or R′OP(O)(OR″)(O − )), arsenate, alkoxide, alkenoxide, aryloxide, carboxylate, percarboxylate, carbonate, bicarbonate, oxalate, borate, tetrahaloborate, tetraalkylborate, tetraarylborate, carborane, and combinations thereof, each of R′ and R″, independently, being C 1 -C 6 alkyl or aryl; L is a linker selected from the group consisting of

 n is an integer from 0 to 20; R g is C 1 -C 6 alkyl; and Ar is aryl;
at least one of R 2 , R 3 , R 4 , R 5 , and R 6 is the leaving group that is F, Cl, Br, I, R a O 2 S—, or R b O 2 S—O—;
when R 2 is F, (i) R 4 is F, Cl, Br, I, C 1 -C 10 alkoxy, R a O 2 S—, or R b O 2 S—O—, (ii) R 5 is NO 2 , or (iii) one and only one of R 3 , R 4 , R 5 , and R 6 is Het + ;
when R 2 is Cl, R 5 is H or Het + ; and
when R 4 is-SO 2 CH 3 , (i) R 2 is F, Cl, Br, I, C 1 -C 10 alkoxy, R a O 2 S—, or R b O 2 S—O—, or (ii) one and only one of R 2 , R 3 , R 5 , and R 6 is Het + .

3 . The pnictogen-containing heterocyclic compound of claim 2 , wherein at least one of R 2 , R 4 , and R 6 is the leaving group.

4 . The pnictogen-containing heterocyclic compound of claim 3 , wherein the leaving group is F or CH 3 O 2 S—.

5 . The pnictogen-containing heterocyclic compound of claim 2 , wherein R 2 , being the leaving group, is CH 3 O 2 S—, and R 4 is H, C 1 -C 10 alkoxy, or Het + .

6 . The pnictogen-containing heterocyclic compound of claim 2 , wherein R 1 is methyl or ethyl.

7 . The pnictogen-containing heterocyclic compound of claim 2 , wherein R 3 or R 5 is NO 2 .

8 . The pnictogen-containing heterocyclic compound of claim 2 , wherein the compound is a compound of Formula (III):

in which
one and only one of B, D, and E is N + CH 3 or N + CH 2 CH 3 ;
one and only one of B, D, and E is CR 2 , R 2 being F, Cl, Br, I, R a O 2 S—, or R b O 2 S—O—;
one and only one of B, D, and E is CR 11 , R 11 being C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl amino, C 4 -C 10 cycloalkyl, C 4 -C 10 cycloalkoxy, 5- to 8-membered heterocycloalkyl, 5- to 8-membered heterocycloalkoxy, aryl, aryloxy, heteroaryl, or heteroaryloxy;
one and only one of B′, D′, and E′ is N + CH 3 or N + CH 2 CH 3 ;
one and only one of B′, D′, and E′ is CR 2 ′, R 2 ′ being F, Cl, Br, I, R a ′O 2 S—, or R b ′O 2 S—O—;
one and only one of B′, D′, and E′ is CR 11 ′, R 11 ′ being C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyl amino, C 4 -C 10 cycloalkyl, C 4 -C 10 cycloalkoxy, 5- to 8-membered heterocycloalkyl, 5- to 8-membered heterocycloalkoxy, aryl, aryloxy, heteroaryl, or heteroaryloxy; and
X′ − is a counter anion selected from the group consisting of halide, polyhalide anion, perchlorate, hydroxide, peroxide, siloxide, sulfate, hydrogen sulfate, sulfite, disulfite, dithionate, dithionite, halosulfate, thiosulfate, persulfate, disulfate, sulfinate (R′SO 2 − ), sulfonate (R″SO 3 − ), bis(sulfonyl)imide ((R′SO 2 ) 2 N − ), nitrate, nitrite, azide, cyanide, cyanate, thiocyanate, phosphate, metaphosphate, polyphosphate, hydrogen phosphate, dihydrogen phosphate, monohalophosphate, dihalophosphate, hexahalophosphate, organophosphonate (R′P(O)(O − ) 2 or R′P(O)(OR″)(O − )), organophosphate (R′OP(O)(O − ) 2 or R′OP(O)(OR″)(O − )), arsenate, alkoxide, alkenoxide, aryloxide, carboxylate, percarboxylate, carbonate, bicarbonate, oxalate, borate, tetrahaloborate, tetraalkylborate, tetraarylborate, carborane, and combinations thereof, each of R′ and R″, independently, being C 1 -C 6 alkyl or aryl.

9 . The pnictogen-containing heterocyclic compound of claim 8 , wherein each of R 2 and R 2 ′, independently, is F or CH 3 O 2 S—.

10 . The pnictogen-containing heterocyclic compound of claim 1 , wherein the compound is a compound of Formula (IV):

Assignees

• Univ Of Rhode Island Board Of Trustees
• Colgate Univ

Inventors

• Wang Fang
• Goldberg Jacob M
• Lipka Bradley M
• Honeycutt Daniel S

Classifications

• C07D277/62

  Benzothiazoles · CPC title

• C07D239/30

  Halogen atoms or nitro radicals · CPC title

• C07D237/12

  Halogen atoms or nitro radicals · CPC title

• C07D235/28

  Sulfur atoms · CPC title

• C07D235/24

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2 · CPC title