# US 8,569,355 B2 · Pyrone-indole derivatives and process for their preparation

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- Number: US 8,569,355 B2
- Document ID: US8569355B2
- Status: Granted
- Kind: B2
- Application number: 13/549,181
- Filed: 2012-07-13
- Published: 2012-11-29
- Granted: 2013-10-29
- Earliest claimed: 2006-02-15
- Assignees: Neurim Pharmaceuticals (1991) Ltd.
- Applicants: Moshe Laudon; Tal Peleg-Shulman
- Inventors: Moshe Laudon; Tal Peleg-Shulman
- Web page: https://patentgrep.com/patent/US8569355B2

## CPC

- C07D 405/12: linked by a chain containing hetero atoms as chain links
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 5/50: for increasing or potentiating the activity of insulin
- A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 13/00: Drugs for disorders of the urinary system
- A61P 13/10: of the bladder
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 15/08: for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A61P 15/10: for impotence
- A61P 17/00: Drugs for dermatological disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/18: Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A61P 25/20: Hypnotics; Sedatives
- A61P 25/22: Anxiolytics
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 25/30: for treating abuse or dependence
- A61P 25/36: Opioid-abuse
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- 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 37/00: Drugs for immunological or allergic disorders
- 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 a method for treating a variety of maladies and conditions; which comprises administering a formulation comprising an effective amount of a pyrone-indole derivative of formula (I): Ar—B—Ar′ (I) wherein Ar represents an indole nucleus ring system: Ar′ represents an alpha-, beta- or gamma-pyrone nucleus ring system: and each of B, R1-4, and R1-2′ are one of the groups as defined herein.

## Claims

### Claim 1

A method for alleviating neuropathy which comprises administering to an animal or human in need of such treatment a formulation comprising an effective amount of a compound having the formula
Ar—B—Ar′ (I)
wherein:
—B— represents:
—X—Y—Z—
wherein
X represents —(CH2)n (wherein n is 0-6);
Y represents oxygen, sulphur, >NH or is absent;
Z represents >C═O, >O or >COO or is absent;
wherein at least one of X, Y and Z must be present;
Ar represents an indole nucleus ring system:
Ar′ represents an alpha-, beta- or gamma-pyrone nucleus ring system:
wherein each of R1-4 substitutes the ring system Ar at any available position (including the N-position) and each of R1′-R2′ substitutes the ring system Ar′ at any available position and wherein each of R1-4 and R1′-2′ independently represents hydrogen, oxygen, halo, halo-C1-5 alkyl, aryl, acyl, a C5-7 heterocyclic group containing 1-3 hetero atoms independently selected from nitrogen, oxygen or sulphur; a C6-8 heteroaryl group containing 1-3 hetero atoms independently selected from nitrogen, oxygen or sulphur, C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl- C1-5 alkyl, aryl- C2-5 alkenyl, aryl-C1-5 alkynyl, hydroxy-C1-5 alkyl, nitro, amino, cyano, cyanamide, guanidine, amidino, acylamido, C1-5 alkylamine, C1-5 alkylamido, hydroxy, thiol, acyloxy, azido, C1-5 alkoxy, carboxy, carbonylamido or styryl; wherein said arylalkyl, arylalkenyl, aralalkynyl, or styryl group optionally can be ring-substituted by one to four substituents independently selected from the group consisting of hydrogen, halo, halo-C1-5 alkyl, aryl, a C5-7 heterocyclic group containing 1-3 hetero atoms independently selected from nitrogen, oxygen and sulphur; a heteroaryl group containing 1-3 hetero atoms independently selected from nitrogen, oxygen and sulphur; C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, aryl-C1-5 alkyl, aryl-C2-5 alkenyl, aryl-C2-5 alkynyl, hydroxy-C1-5 alkyl, nitro, amino, cyano, cyanamido, guanidino, amidino, acylamido, hydroxy, thiol, acyloxy, azido, aikoxy, carboxy, carbonylamido, S-alkyl or alkylthiol;
and either of R3 or R4 further can include or represent a bond to B;
wherein Ar can be bonded to B at any position on the five-membered ring portion of the Ar ring, including the N-position, and Ar′ can be bonded to B at any carbon on the Ar′ ring not substituted by R1′ and R2′; or a salt or stereoisomer thereof.