# US 2013/0158028 A1 · Use of stimulators and activators of soluble guanylate cyclase for treating sickle-cell anemia and conserving blood substitutes

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- Number: US 2013/0158028 A1
- Document ID: US20130158028A1
- Status: Published application
- Kind: A1
- Application number: 13/806,270
- Filed: 2011-06-21
- Published: 2013-06-20
- Earliest claimed: 2010-06-25
- Assignees: Bayer Intellectual Property GmbH
- Inventors: Johannes-Peter Stasch; Eva-Maria Becker; Hubert Trübel; Herbert Himmel
- Web page: https://patentgrep.com/patent/US20130158028A1

## CPC

- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205)
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/426: 1,3-Thiazoles
- A61K 31/427: not condensed and containing further heterocyclic rings
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/06: Antianaemics
- 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 relates to the novel use of stimulators and activators of soluble guanylate cyclase for the treatment of sickle cell anemia and for the preservation of blood substitutes. The present invention furthermore relates to the use of stimulators and activators of soluble guanylate cyclase in combination with PDE5 inhibitors for the treatment of sickle cell anemia and for the preservation of blood substitutes.

## Claims

### Claim 1

A method of treatment of sickle cell anemia or for the preservation of blood substitutes, comprising administering a stimulator and/or activator of soluble guanylate cyclase to a human or animal in need thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the stimulators and/or activators of soluble guanylate cyclase is selected from a compound of formulae (1) to (25) and (26).

### Claim 3 (depends on 2)

The method of claim 2, wherein the stimulator and/or activator of soluble guanlyate cyclase is one or more compounds selected from the compound of formulae (3), (4), (5), (6), or (7).

### Claim 4

(canceled)

### Claim 5

(canceled)

### Claim 6

(canceled)

### Claim 7

(canceled)

### Claim 8 (depends on 2)

The method of claim 2, further comprising administering the compounds of formulae (1) to (25) or (26), to the human or animal in combination with at least one PDE5 inhibitor selected from the group consisting of:
tadalafil ((6R,12aR)-2,3,6,7,12,12a-hexahydro-2-methyl-6-(3,4-methylenedioxyphenyl)pyrazino(1′,2′:1,6) pyrido(3,4-b)indole-1,4-dione), vardenafil (2-(2-ethoxy-5-(4-ethylpiperazin-1-yl-1-sulfonyl)phenyl)-5-methyl-7-propyl-3H-imidazo(5,1-f)(1,2,4)triazin-4-one), sildenafil (3-[2-ethoxy-5-(4-methylpiperazin-1-yl)sulfonyl-phenyl]-7-methyl-9-propyl-2,4,7,8-tetrazabicyclo[4.3.0]nona-3,8,10-trien-5-one), udenafil 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinylethylamidosulfonyl)phenyl]-methyl-3-propyl-1,6-dihydro-7H-pyrazolo(4,3-d)pyrimidin-7-one, dasantafil (7-(3-bromo-4-methoxybenzyl)-1-ethyl-8-[[(1,2)-2-hydroxycyclopentyl]amino]-3-(2-hydroxyethyl)-3,7-dihydro-1-purine-2,6-dione), avanafil (4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide), mirodenafil, lodenafil, UK 369.003, UK 371.800, SLx 2101 of Surface Logix, and LAS 34179 (triazolo[1,2-]xanthine, 6-methyl-4-propyl-2-[2-propoxy-5-(4-methylpiperazino)sulfonyl]phenyl) or salts, hydrates or hydrates of the salts thereof.

### Claim 9 (depends on 2)

The method of claim 2, wherein a compound of formulae (3), (4), (5), (6), or (7) is administered to the human or animal in combination with vardenafil and/or sildenafil.

### Claim 10

(canceled)

### Claim 11

(canceled)

### Claim 12

(canceled)

### Claim 13

(canceled)

### Claim 14 (depends on 1)

The method of claim 1, wherein the stimulator and/or activator of soluble guanylate cyclase is administered by inhalation.

### Claim 15

(canceled)