Back to results
US 2026/0076918 A1Published application
Heterotelechelic compounds
AssigneeKawasaki Institute of Industrial Promotion
InventorsJoachim VAN GUYSE, Saed ABBASI, Kazunori KATAOKA, Satoshi UCHIDA
Life of this patent
Estimating the term…
Abstract
The present invention relates to biocompatible polymers suitable for drugs and gene delivery, and producing methods thereof. The present invention also enables the creation of compounds with diverse structures by a concise method. The present invention relates to polycyclic iminoether compounds having different functional groups in both sides, such as a pentafluorophenyl group at one end and an azide group at the other end, derivatives thereof and producing methods thereof.
Claims28
A compound of formula (I)
- wherein X is halogen, —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, —N3, —C≡C—R2, —NHOR2, —ONR2R3, heteroaryl which may be substituted, a group which can form lipid based nano-particle (e.g., a formulation containing a lipid nano-particle (LNP), liposome, or lipoplex) or micelle including polycationic group, polyanionic group, or lipid soluble groups such as groups derived from fatty acid, preferably F, —SR2, —OR2, —CN, —NHR2, —N3,
- Y is SR2, —OR2 (provided that when X is F, it is not —OH), —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, —N3, or heteroaryl which may be substituted, preferably —SR2, —OR2 (provided that when X is F, it is not —OH), —NHR2, —NR2 R3, —N3, or
- more preferably —SR2, —OR2 (provided that when X is F, it is not —OH), —NHR2, or
- wherein repeating unit
- is independent of each occurrence and may be identical or different;
- R1 is selected from the group consisting of alkyl group having 1-40 carbon atoms which may be substituted, alkenyl group having 2-40 carbon atoms which may be substituted, alkynyl group having 2-40 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, sugar derivatives, and repeating unit or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted, preferably —CH2CH(ORC)CH2ORC,
- RA, RAA and RAAA are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, alkenyl group having 2-20 carbon atoms which may be substituted, and alkynyl group having 2-20 carbon atoms which may be substituted, or RA and RAA may be linked together to form ring, such as carbocycle, heterocycle, aryl, heterocyclyl, lactone, or lactam, and RA, RAA and/or RAAA may be further linked to functional molecules such as labels, or biofunctional molecules including proteins, nucleic acid, etc.;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, lipid soluble groups such as alkyl group having 1-20 carbon atoms which may be substituted, alkenyl group having 2-20 carbon atoms which may be substituted, and alkynyl group having 2-20 carbon atoms which may be substituted, and oxygen protective groups including acyl groups such as acetyl, ether groups such as methoxymethyl etc.;
- said alkyl, alkenyl and alkynyl is straight chain, branched chain or cyclic chain;
- m is integer from 1 to 3;
- and
- n is integer from 1 to 2000,
- or a pharmaceutically acceptable salt thereof.
12 more elements
A compound of formula (II)
- wherein repeating unit
- is independent of each occurrence and may be identical or different;
- R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, and —N3, —NHOR2, -and —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case that R5 is —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted, preferably —CH2CH(ORC)CH2ORC;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, or alkenyl group having 2-20 carbon atoms which may be substituted;
- said alkyl, and alkenyl are straight chain;
- m is integer from 1 to 3;
- and
- n is integer from 2 to 2000.
8 more elements
A method for producing a compound of Formula (III),
- wherein repeating unit is independent of each occurrence and may be identical or different;
- R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of halogen, —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, —N3, —NHOR2, -and —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, or alkenyl group having 2-20 carbon atoms which may be substituted;
- said alkyl, and alkenyl are straight chain;
- and
- n is integer from 2 to 2000,
- comprising the following steps;
- (a) a compound of Formula (IV)
- wherein L is a leaving group;
- is reacted with a compound of Formula (V)
- wherein R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- in the presence of base to obtain a compound of Formula (II)
- (b) a compound of Formula (II) is reacted with an azide reagent to obtain a compound of Formula (III).
13 more elements
A method for producing the compound of formula (III),
- wherein repeating unit is independent of each occurrence and may be identical or different;
- R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of halogen, —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, and —N3, —NHOR2, —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, or alkenyl group having 2-20 carbon atoms which may be substituted;
- said alkyl, and alkenyl are straight chain;
- and
- n is integer from 2 to 2000,
- comprising the following steps;
- (a) a compound of Formula (IIIa)
- wherein R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- n is integer from 2 to 2000,
- is reacted with a nucleophile to obtain a compound of Formula (III)
- wherein R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of halogen, —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, and —N3, —NHOR2, and —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted;
- RC is selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, or alkenyl group having 2-20 carbon atoms which may be substituted;
- said alkyl, and alkenyl are straight chain;
- and
- n is integer from 2 to 2000.
18 more elements
The method for producing the compound of formula (VI),
- wherein repeating unit is independent of each occurrence and may be identical or different;
- R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of halogen, —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, —N3, —NHOR2, and —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, or alkenyl group having 2-20 carbon atoms which may be substituted;
- said alkyl, and alkenyl are straight chain;
- and
- n is integer from 2 to 100,
- in which a compound of formula (IIa)
- wherein R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- n is integer from 2 to 2000,
- is reacted with nucleophile to obtain the compound of Formula (VI).
10 more elements
A method for producing the compound of Formula (Ia)
- wherein repeating unit is independent of each occurrence and may be identical or different;
- R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of —SR2, —OR2, —CN, —NHR2, —NR2R3, —NHNHR2, —N═NR2, —N3, —NHOR2, and —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted, preferably —CH2CH(ORC)CH2ORC;
- RA and RAA are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, alkenyl group having 2-20 carbon atoms which may be substituted, and alkynyl group having 2-20 carbon atoms which may be substituted, or RA and RAA may be linked together to form ring, such as carbocycle, heterocycle, aryl, heterocyclyl, lactone, or lactam, and RA and/or RAA may be further linked to functional molecules such as labels, biofunctional molecules including proteins, nucleic acid, etc.;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, lipid soluble groups such as alkyl group having 1-20 carbon atoms which may be substituted, alkenyl group having 2-20 carbon atoms which may be substituted, and alkynyl group having 2-20 carbon atoms which may be substituted, or oxygen protective groups including acyl groups such as acetyl, ether groups such as methoxymethyl etc.;
- said alkyl, alkenyl and alkynyl is straight chain, branched chain or cyclic chain;
- and
- n is integer from 1 to 2000,
- wherein the compound of Formula (III)
- wherein repeating unit is independent of each occurrence and may be identical or different;
- R4 is selected from the group consisting of alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, aryl which may be substituted, heteroaryl which may be substituted;
- R5 is selected from the group consisting of halogen, —SR2, —OR2, —CN, —NHR2, —NR2 R3, —NHNHR2, —N═NR2, and —N3, —NHOR2, —ONR2R3;
- R2 and R3 are, independent of each other, selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted, carbocyclyl which may be substituted, heterocyclyl which may be substituted, aryl which may be substituted, heteroaryl which may be substituted, —C(═O)RB, —C(═O)ORB, —C(═O)N(RB)2, —S(═O)RB, —S(═O)2RB, —CH2CH(ORC)CH2ORC, and sugar derivatives, or in the case of —NR2 R3, R2 and R3 may be linked together to form heterocyclyl which may be substituted;
- RB is selected from the group consisting of hydrogen, alkyl group having 1-6 carbon atoms which may be substituted, alkenyl group having 2-6 carbon atoms which may be substituted, and alkynyl group having 2-6 carbon atoms which may be substituted;
- RC is selected from the group consisting of hydrogen, alkyl group having 1-20 carbon atoms which may be substituted, or alkenyl group having 2-20 carbon atoms which may be substituted;
- said alkyl, and alkenyl are straight chain;
- and
- n is integer from 2 to 2000
- is reacted with formula (VII)
- wherein RA and RAA are as shown above,
- to obtain the compound of Formula (Ia).
20 more elements
Dependencies are inferred from the claim text.