# US 2017/0283433 A1 · Pharmaceutical formulations containing 3-(4-cinnamyl-l-piperazinyl) amino derivatives of 3-formylrifamycin sv and 3-formylrifamycin s and a process of their preparation

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- Number: US 2017/0283433 A1
- Document ID: US20170283433A1
- Status: Published application
- Kind: A1
- Application number: 15/622,880
- Filed: 2017-06-14
- Published: 2017-10-05
- Earliest claimed: 2012-08-13
- Assignees: Adipharm EAD; Bozhidar Lyubenov Fudlov; Lyibomir Bozhidarov Fudlov; Kiril Asenov Ninov; Velichka Ilieva Apostolova-Dimova; Evtimia Ivanova Stefanova; Rossen Krumov Koychev; Ditchev Consulting OOD
- Applicants: Adipharm EAD; Ditchev Consulting OOD
- Inventors: Kiril Asenov Ninov; Velichka Ilieva Apostolova-Dimova; Evtimia Ivanova Stefanova; Rossen Krumov Koytchev; Rumyana Gueorguieva Konstantinova
- Web page: https://patentgrep.com/patent/US20170283433A1

## CPC

- C07D 498/08: Bridged systems
- A61K 9/4866: {Organic macromolecular compounds}
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61P 31/04: Antibacterial agents
- A61P 31/06: for tuberculosis
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention related to a process of preparation of pharmaceutically acceptable formulations containing as active substance 3-(4-cinnamy-1-piperazinyl)-amino derivatives of 3-formylrifamycine SV and 3-formylrifamycine S, which possess high activity against Gram-positive and Gram-negative microorganisms, as well as against tuberculous micobacteria (including atypical and rifamycin resistant), and to a method for the preparation of 3-(4-cinnamyl-1-piperazinyl)-amino derivatives of 3-formylrifamycine SV and 3-formylrifamycine S. The method for the preparation of pharmaceutical compositions is readily feasible, and does not require special equipment for its implementation. The process for preparing the compounds is characterized by high yield and purity, using an environmental clean solvent—ethanol and water in the preparation and isolation of substances, and the absence of residual organic solvents in the final product.

## Claims

### Claim at position 1

1-5. (canceled)

### Claim 6

A process for the preparation of 3-(4-cinnamyl-1-piperazinyl)-iminomethyl rifamycin SV by reacting 3-formylrifamycin SV with N1-cinnamyl-N4-aminopiperazin, characterized by the fact that to an ethanol solution of N1-cinnamyl-N4-aminopiperazin in the presence of small amounts of acetic acid and a temperature of 20-30° C. 3-formylrifamycin SV is added apart, the reaction mixture is diluted with equal volume of water, filtered and the precipitate is washed with water.

### Claim 7 (depends on 6)

A process for preparing a sodium salt of the compound according to claim 6, characterized by the fact that the 3-(4-cinnamyl-1-piperazinyl) iminomethyl rifamycin SV is reacted with an equimolar amount of sodium methoxide in ethanol, at temperature of 20-30° C., followed by distilling off the ethanol, the residue is dissolved in water in the presence of sodium ascorbate, and the aqueous solution is lyophilized

### Claim at position 4

8-15. (canceled)