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Details

Stereochemistry ABSOLUTE
Molecular Formula C51H64N4O13
Molecular Weight 941.0729
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RIFALAZIL

SMILES

CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c4c5nc6c(O)cc(cc6oc5c(NC(=O)C(C)=C\C=C\[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(=O)c4c(O)c3C)N7CCN(CC(C)C)CC7

InChI

InChIKey=UEFHFKKWYKVLDC-HTQYORAHSA-N
InChI=1S/C51H64N4O13/c1-24(2)23-54-16-18-55(19-17-54)32-21-33(57)39-35(22-32)67-48-40(52-39)36-37-44(60)30(8)47-38(36)49(62)51(10,68-47)65-20-15-34(64-11)27(5)46(66-31(9)56)29(7)43(59)28(6)42(58)25(3)13-12-14-26(4)50(63)53-41(48)45(37)61/h12-15,20-22,24-25,27-29,34,42-43,46,57-60H,16-19,23H2,1-11H3,(H,53,63)/b13-12+,20-15+,26-14-/t25-,27+,28+,29+,34-,42-,43+,46+,51-/m0/s1

HIDE SMILES / InChI
Molecular Formula C51H64N4O13
Molecular Weight 941.0729
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 9 / 9
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Rifalazil (also known as KRM-1648) is a derivative of the antibiotic rifamycin. This orally administered ansamycin is under evaluation for treatment of various bacterial infections. Rifalazil kills bacterial cells by blocking off the β-subunit in RNA polymerase. This drug was originally developed as a therapeutic agent to replace rifampin in the treatment of tuberculosis. It also showed potential to treat indications caused by chlamydia trachomatis and chlamydia pneumoniae. Furthermore, it has been suggested as a potential drug in the treatment of gastric ulcer disease (which is caused by Helicobacter pylori) and antibiotic-associated colitis. Phase II studies evaluated the efficacy and safety of this drug in patients with chlamydia trachomatis and chlamydia seropositive patients. A phase 3 study was initiated including chlamydia seropositive patients. However, the development of rifalazil was terminated in 2013 due to severe side effects.

Approval Year

Unknown
149124
PubMed

PubMed

TitleDatePubMed
Fluoroquinolones: an important class of antibiotics against tuberculosis.
2006
Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.
2002-02
Safety and bactericidal activity of rifalazil in patients with pulmonary tuberculosis.
2001-07
In vitro activity of KRM-1648, either singly or in combination with ofloxacin, against Mycobacterium ulcerans.
2001-01
Evaluation of rifalazil in a combination treatment regimen as an alternative to isoniazid-rifampin therapy in a mouse tuberculosis model.
2000-11
Antimicrobial activities of levofloxacin, clarithromycin, and KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium complex replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines.
2000-09
Identification of enzymes responsible for rifalazil metabolism in human liver microsomes.
2000-06
Accumulation of KRM-1648 by Mycobacterium aurum and Mycobacterium tuberculosis.
2000-05
Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex.
2000-02
Evaluation of rifapentine in long-term treatment regimens for tuberculosis in mice.
1999-10
[MICs and MBCs of levofloxacin, clarithromycin, and KRM-1648 for Mycobacterium tuberculosis and M. avium complex residing in MONO-MAC-6 human macrophage-like cell and A-549 human type II alveolar epithelial cell lines].
1999-07
Antimicrobial activities of benzoxazinorifamycin (KRM-1648) and clarithromycin against Mycobacterium avium-intracellulare complex within murine peritoneal macrophages, human macrophage-like cells and human alveolar epithelial cells.
1999-03
Effects of the Chinese traditional medicine mao-bushi-saishin-to on therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, against Mycobacterium avium infection in mice.
1999-03
Therapeutic effects of benzoxazinorifamycin KRM-1648 administered alone or in combination with a half-sized secretory leukocyte protease inhibitor or the nonsteroidal anti-inflammatory drug diclofenac sodium against Mycobacterium avium complex infection in mice.
1999-02
Effects of Yokuinin on the therapeutic efficacy of a new benzoxazinorifamycin KRM-1648 against Mycobacterium avium infection.
1999-01
Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.
1998-11
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis.
1998-07
Evaluation of in vivo therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, in SCID mouse model for disseminated Mycobacterium avium complex infection.
1998-04
[Therapeutic efficacy of benzoxazinorifamycin KRM-1648 against experimental murine tuberculosis: (1). A study on the efficacy of short course treatment with the intratracheal and intravenous infection model].
1998-02
Antimicrobial activities of benzoxazinorifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages.
1998-01
[In vivo activities of benzoxazinorifamycin KRM-1648, clarithromycin, and levofloxacin, or combination of KRM-1648 with diclofenac sodium against Mycobacterium avium infection induced in mice].
1997-08
Effect of Mycobacterium avium infection on the influx, accumulation, and efflux of KRM-1648 by human macrophages.
1997
Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.
1996-12
Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations.
1996-11
[Preclinical study of therapeutic agents used against Mycobacterium avium complex infections--with special reference to new macrolides and new quinolones].
1996-09
Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages.
1996-06
Chemotherapeutic activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium tuberculosis in C57BL/6 mice.
1996-04
How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?
1996-02
Activity of KRM-1648 alone or in combination with both ethambutol and kanamycin or clarithromycin against Mycobacterium intracellulare infections in beige mice.
1996-02
In vitro bactericidal and in vivo therapeutic activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis.
1996-02
Activity of KRM-1648 in combination with isoniazid against Mycobacterium tuberculosis in a murine model.
1996-02
In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.
1995-10
New drugs for tuberculosis.
1995-09
Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648.
1995-07
In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli.
1995-02
[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review].
1994-11
Activity of KRM-1648, a new benzoxazinorifamycin, against Mycobacterium tuberculosis in a murine model.
1994-10
Activity of KRM 1648 alone or in combination with ethambutol or clarithromycin against Mycobacterium avium in beige mouse model of disseminated infection.
1994-08
Activities of the benzoxazinorifamycin KRM 1648 and ethambutol against Mycobacterium avium complex in vitro and in macrophages.
1994-08
In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives.
1994-05
Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.
1993-04
Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.
1993-01
In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method.
1993-01
Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice.
1992-02
In vitro antimycobacterial activities of newly synthesized benzoxazinorifamycins.
1991-03
[In vivo activities of new rifamycin derivatives against mycobacteria].
1991-01
[In vitro activities of new rifamycin derivatives against Mycobacterium tuberculosis and M. avium complex].
1990-12
Substance Class Chemical
Created
by admin
on Wed Apr 02 07:04:42 GMT 2025
Edited
by admin
on Wed Apr 02 07:04:42 GMT 2025
Record UNII
S1976TE8QK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
1',4-DIDEHYDRO-1-DEOXY-1,4-DIHYDRO-3'-HYDROXY-5'-(4-(2-METHYLPROPYL)-1-PIPERAZINYL)-1-OXORIFAMYCIN VIII
Preferred Name English
RIFALAZIL
INN   MI   USAN  
INN   USAN  
Official Name English
KRM-1648
Code English
(2S,16Z,18E,20S,21S,22R,23R,24R,25S,26R,27S,28E)-5,12,21,23,25-PENTAHYDROXY-10-(4-ISOBUTYL-1-PIPERAZINYL)-27-METHOXY-2,4,16,20,22,24,26-HEPTAMETHYL-2,7-(EPOXYPENTADECA(1,11,13)TRIENIMINO)-6H-BENZOFURO(4,5-A)PHENOXAZINE-1(2H),6,15-TRIONE 25-ACETATE
Common Name English
3'-HYDROXY-5'-(4-ISOBUTYL-1-PIPERAZINYL)BENZOXAZINORIFAMYCIN
Common Name English
RIFALAZIL [MI]
Common Name English
rifalazil [INN]
Common Name English
RIFALAZIL [USAN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 122699
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
NCI_THESAURUS C258
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C152213
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
DRUG BANK
DB04934
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
MERCK INDEX
m9609
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY Merck Index
INN
7674
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
EPA CompTox
DTXSID301030497
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
USAN
II-70
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
WIKIPEDIA
RIFALAZIL
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
EVMPD
SUB10305MIG
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
FDA UNII
S1976TE8QK
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
ChEMBL
CHEMBL236297
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
CAS
129791-92-0
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
SMS_ID
100000080559
Created by admin on Wed Apr 02 07:04:42 GMT 2025 , Edited by admin on Wed Apr 02 07:04:42 GMT 2025
PRIMARY
Related Record Type Details
Structure of Rifamycin
PARENT -> DERIVATIVE
CHLAMYDIA TRACHOMATIS
TARGET ORGANISM->INHIBITOR
Clostridioides difficile
TARGET ORGANISM->INHIBITOR
Helicobacter pylori
TARGET ORGANISM->INHIBITOR
Related Record Type Details
Structure of RIFALAZIL
ACTIVE MOIETY
NIH
NCATS
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