# US 8,541,576 B2 · Substituted pyrazolo-quinazoline derivatives as kinase inhibitors

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- Number: US 8,541,576 B2
- Document ID: US8541576B2
- Status: Granted
- Kind: B2
- Application number: 13/327,979
- Filed: 2011-12-16
- Published: 2012-07-26
- Granted: 2013-09-24
- Earliest claimed: 2010-12-17
- Assignees: Nerviano Medical Sciences S.R.L.
- Applicants: Francesco Casuscelli; Claudia Piutti; Antonella Ermoli; Daniela Faiardi
- Inventors: Francesco Casuscelli; Claudia Piutti; Antonella Ermoli; Daniela Faiardi
- Web page: https://patentgrep.com/patent/US8541576B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/08: of the prostate
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to substituted pyrazolo[4,3-h]quinazoline compounds which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular PIM kinases. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing such these compounds or the pharmaceutical compositions containing them.

## Claims

### Claim 1

A compound selected from the group consisting of:
1-(2-hydroxyethyl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-tert-butyl-N-methyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-(2-aminoethyl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
8-(methylsulfanyl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-(2-hydroxyethyl)-8-[4-(4-methylpiperazin-1-yl)phenoxy]-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-tert-butyl-8-[4-(4-methylpiperazin-1-yl)phenoxy]-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-tert-butyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
8-(methylsulfanyl)-1-(piperidin-4-yl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
8-(methylsulfanyl)-1-(piperidin-3-yl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-(4-aminocyclohexyl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
8-(methylsulfanyl)-1-(piperidin-3-ylmethyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
8-methoxy-1-(piperidin-4-yl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-[(3-exo)-8-azabicyclo[3.2.1]oct-3-yl]-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-(4-aminobutan-2-yl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-(1-azabicyclo[2.2.2]oct-3-yl)-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
8-(methylsulfanyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide;
1-[trans-3-(hydroxymethyl)cyclobutyl]-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide; and
1-[cis-3-(hydroxymethyl)cyclobutyl]-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, carrier and/or diluent.