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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)OC3=C(C2=O)C4=C(C(=O)C(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)=C5OC6=C(N=C45)C(O)=CC(=C6)N7CCN(CC(C)C)CC7)C(O)=C3C

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
139594
PubMed

PubMed

TitleDatePubMed
Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.
1993 Apr
Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.
1993 Jan
Activity of KRM 1648 alone or in combination with ethambutol or clarithromycin against Mycobacterium avium in beige mouse model of disseminated infection.
1994 Aug
Activities of the benzoxazinorifamycin KRM 1648 and ethambutol against Mycobacterium avium complex in vitro and in macrophages.
1994 Aug
In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives.
1994 May
[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review].
1994 Nov
In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli.
1995 Feb
Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648.
1995 Jul
New drugs for tuberculosis.
1995 Sep
Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.
1996 Dec
How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?
1996 Feb
Activity of KRM-1648 alone or in combination with both ethambutol and kanamycin or clarithromycin against Mycobacterium intracellulare infections in beige mice.
1996 Feb
In vitro bactericidal and in vivo therapeutic activities of a new rifamycin derivative, KRM-1648, against Mycobacterium tuberculosis.
1996 Feb
Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages.
1996 Jun
Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations.
1996 Nov
[Preclinical study of therapeutic agents used against Mycobacterium avium complex infections--with special reference to new macrolides and new quinolones].
1996 Sep
[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 Aug
Effect of Mycobacterium avium infection on the influx, accumulation, and efflux of KRM-1648 by human macrophages.
1997 Fall
Evaluation of in vivo therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, in SCID mouse model for disseminated Mycobacterium avium complex infection.
1998 Apr
[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 Feb
Antimicrobial activities of benzoxazinorifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages.
1998 Jan
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis.
1998 Jul
Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.
1998 Nov
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 Feb
Effects of Yokuinin on the therapeutic efficacy of a new benzoxazinorifamycin KRM-1648 against Mycobacterium avium infection.
1999 Jan
[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 Jul
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 Mar
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 Mar
Evaluation of rifapentine in long-term treatment regimens for tuberculosis in mice.
1999 Oct
Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex.
2000 Feb
Identification of enzymes responsible for rifalazil metabolism in human liver microsomes.
2000 Jun
Accumulation of KRM-1648 by Mycobacterium aurum and Mycobacterium tuberculosis.
2000 May
Evaluation of rifalazil in a combination treatment regimen as an alternative to isoniazid-rifampin therapy in a mouse tuberculosis model.
2000 Nov
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 Sep
In vitro activity of KRM-1648, either singly or in combination with ofloxacin, against Mycobacterium ulcerans.
2001 Jan
Safety and bactericidal activity of rifalazil in patients with pulmonary tuberculosis.
2001 Jul
Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.
2002 Feb
Fluoroquinolones: an important class of antibiotics against tuberculosis.
2006
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:03:24 UTC 2023
Edited
by admin
on Sat Dec 16 16:03:24 UTC 2023
Record UNII
S1976TE8QK
Record Status Validated (UNII)
Record Version
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Name Type Language
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
1',4-DIDEHYDRO-1-DEOXY-1,4-DIHYDRO-3'-HYDROXY-5'-(4-(2-METHYLPROPYL)-1-PIPERAZINYL)-1-OXORIFAMYCIN VIII
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 Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
NCI_THESAURUS C258
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C152213
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
DRUG BANK
DB04934
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
MERCK INDEX
m9609
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY Merck Index
INN
7674
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
EPA CompTox
DTXSID301030497
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
USAN
II-70
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
WIKIPEDIA
RIFALAZIL
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
EVMPD
SUB10305MIG
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
FDA UNII
S1976TE8QK
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
ChEMBL
CHEMBL236297
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
CAS
129791-92-0
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
SMS_ID
100000080559
Created by admin on Sat Dec 16 16:03:24 UTC 2023 , Edited by admin on Sat Dec 16 16:03:24 UTC 2023
PRIMARY
Related Record Type Details
Structure of RIFAMYCIN
PARENT -> DERIVATIVE
CHLAMYDIA TRACHOMATIS
TARGET ORGANISM->INHIBITOR
CLOSTRIDIUM DIFFICILE
TARGET ORGANISM->INHIBITOR
Helicobacter pylori
TARGET ORGANISM->INHIBITOR
Related Record Type Details
Structure of RIFALAZIL
ACTIVE MOIETY
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