RIFALAZIL

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 Search

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
Sources: https://www.drugbank.ca/drugs/DB04934 | https://www.ncbi.nlm.nih.gov/pubmed/12556219 | https://www.sciencedirect.com/science/article/pii/S1472979208700234?via%3Dihub | https://clinicaltrials.gov/ct2/show/NCT01631201 | https://medkoo.com/products/20148

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

PubMed

Title	Date	PubMed
[In vitro activities of new rifamycin derivatives against Mycobacterium tuberculosis and M. avium complex].	1990 Dec	2127615
Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.	1993 Apr	7684214
Synthesis and biological activity of 3'-hydroxy-5'-aminobenzoxazinorifamycin derivatives.	1993 Jan	8448815
In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method.	1993 Jan	8431020
Activity of KRM 1648 alone or in combination with ethambutol or clarithromycin against Mycobacterium avium in beige mouse model of disseminated infection.	1994 Aug	7986018
Activities of the benzoxazinorifamycin KRM 1648 and ethambutol against Mycobacterium avium complex in vitro and in macrophages.	1994 Aug	7986017
In vitro and in vivo antibacterial activities of KRM-1648 and KRM-1657, new rifamycin derivatives.	1994 May	8067748
[New drugs against tuberculosis and nontuberculous mycobacterial infections: a review].	1994 Nov	7837725
Activity of KRM-1648, a new benzoxazinorifamycin, against Mycobacterium tuberculosis in a murine model.	1994 Oct	7840552
In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli.	1995 Feb	7726512
Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648.	1995 Jul	7492091
In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.	1995 Oct	8619585
New drugs for tuberculosis.	1995 Sep	8590571
Low-dose aerosol infection model for testing drugs for efficacy against Mycobacterium tuberculosis.	1996 Dec	9124846
Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages.	1996 Jun	8726023
Evaluation of in vivo therapeutic efficacy of a new benzoxazinorifamycin, KRM-1648, in SCID mouse model for disseminated Mycobacterium avium complex infection.	1998 Apr	9624545
Contribution of rpoB mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis.	1998 Jul	9661035
Relationship between antimycobacterial activities of rifampicin, rifabutin and KRM-1648 and rpoB mutations of Mycobacterium tuberculosis.	1998 Nov	9848446
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	9925533
Effects of Yokuinin on the therapeutic efficacy of a new benzoxazinorifamycin KRM-1648 against Mycobacterium avium infection.	1999 Jan	10075281
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	10223590
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	10049260
Evaluation of rifapentine in long-term treatment regimens for tuberculosis in mice.	1999 Oct	10508006
Evaluation of rifalazil in a combination treatment regimen as an alternative to isoniazid-rifampin therapy in a mouse tuberculosis model.	2000 Nov	11036043
Antimicrobial activities of clarithromycin, gatifloxacin and sitafloxacin, in combination with various antimycobacterial drugs against extracellular and intramacrophage Mycobacterium avium complex.	2002 Feb	11850167

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:03:24 GMT 2023` Edited by `admin` on `Sat Dec 16 16:03:24 GMT 2023`
Record UNII	S1976TE8QK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

RIFALAZIL

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