Polyene macrolide derivative

Patent metadata

Field	Value
Publication number	US-2017190729-A1
Application number	US-201515315646-A
Country	US
Kind code	A1
Filing date	Jun 12, 2015
Priority date	Jun 12, 2014
Publication date	Jul 6, 2017
Grant date	—

Abstract

The present invention is the following Amphotericin B derivative:

wherein each symbol is defined in description. The compound of the present invention has 16th position (X) is urea structure, cyclic structure, hydroxyalkyl or substituted monoalkylcarbamoyl. The compound of the present invention has antifungal activity.

First claim

1 . A compound represented by formula (I):

wherein X is a group of formula:

—N(R F )—CO—X 1 , hydroxyalkyl or a group of formula: —CO—NH(R X )
wherein R X is substituted or unsubstituted non-aromatic heterocyclyloxyalkyl;
Ring C is substituted or unsubstituted aromatic carbocycle, substituted or unsubstituted non-aromatic carbocycle, substituted or unsubstituted aromatic heterocycle or substituted or unsubstituted non-aromatic heterocycle;
R F is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl; and
X 1 is any one of following groups:

L, J 1 and V 1 are each independently hydrogen, halogen, hydroxy, substituted or unsubstituted amino or substituted or unsubstituted alkyloxy;
J 2 and V 2 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl;

or J 1 and J 2 and/or V 1 and V 2 may be taken together to form oxo;
R a1 and R b1 are each independently, hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted amino, formyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, sulfo, cyano, substituted or unsubstituted ureido, guanidino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkyl carbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkyl ammonium, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted alkylphosphonyl, substituted or unsubstituted dialkynylphosphonyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkynylcarbonyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl or substituted or unsubstituted non-aromatic heterocyclyl sulfonyl;
R a2 and R b2 are each independently hydrogen, halogen, hydroxy, carboxy, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkynylcarbonyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxyalkyl, substituted or unsubstituted non-aromatic heterocyclyloxyalkenyl or substituted or unsubstituted non-aromatic heterocyclyloxyalkynyl;
R a3 and R b3 are each independently, hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted non-aromatic heterocyclyl oxyalkyl, substituted or unsubstituted non-aromatic heterocyclyloxyalkenyl or substituted or unsubstituted non-aromatic heterocyclyloxyalkynyl;

or R a2 and R a3 and/or R b2 and R b3 are each independently may be taken together to form oxo, substituted or unsubstituted imino or thioxo, or may be taken together with neighboring atoms to form substituted or unsubstituted non-aromatic carbocycle or substituted or unsubstituted non-aromatic heterocycle;
R a4 , R b4 and R c4 are each independently, hydrogen, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl or substituted or unsubstituted non-aromatic carbocyclyl;
R b5 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl;
Ring A and Ring B are each independently, substituted or unsubstituted nitrogen-containing aromatic heterocycle or substituted or unsubstituted nitrogen-containing non-aromatic heterocycle;
T is a bond, —N(R a5 )— or —O—;
R a5 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl or substituted or unsubstituted alkynylcarbonyl;
m and n are each independently an integer of 0 to 10;
Y is any one of following groups

R A is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl;
R B and R C are each independently hydrogen, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or substituted or unsubstituted alkynyl;

or R B and R C may be taken together to form oxo, substituted or unsubstituted imino or thioxo, or may be taken together with neighboring atoms to form substituted or unsubstituted non-aromatic carbocycle or substituted or unsubstituted non-aromatic heterocycle;
R D is hydrogen, hydroxy, carboxy, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted guanidino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl or substituted or unsubstituted non-aromatic heterocyclyl;
R E is hydrogen, hydroxy or substituted or unsubstituted amino;
q is an integer of 0 to 10;

provided that the following compounds are

Assignees

• Shionogi & Co

Inventors

• Miyazaki Keisuke
• Takaya Kenji
• Ohara Takafumi
• Sugimoto Hideki
• Fujitani Manabu
• Ogata Yuki
• Suzuki Naoyuki

Classifications

• A61P31/10

  Antimycotics · CPC title

• C07H17/08 Primary

  Hetero rings containing eight or more ring members, e.g. erythromycins · CPC title

• C07H23/00

  Compounds containing boron, silicon or a metal, e.g. chelates or vitamin B12 (esters with inorganic acids C07H11/00) · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title