KR20100111691A - 5-o-substituted 3-n-phenyl-1,3,4-oxadiazolones for medical use - Google Patents

Abstract

(I)
본 발명은 FAAH(지방산 아미드 가수분해효소)의 억제에 대하여 예상하지 못할 만큼 높은 수준을 갖는 5-O-치환3-N-페닐-1,3,4-옥사디아졸론 구조적 단위를 갖는 화합물에 관한 것이다.(I)

(I)
The present invention relates to compounds having 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone structural units having unexpectedly high levels of inhibition of FAAH (fatty acid amide hydrolase). (I)

Description

5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone for medical use {5-O-SUBSTITUTED 3-N-PHENYL-1,3,4-OXADIAZOLONES FOR MEDICAL USE}

The present invention relates to compounds having 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone structural units having unexpectedly high levels of inhibition of FAAH (fatty acid amide hydrolase). will be.

FAAH is an IMP (intrinsic membrane protein) that hydrolyzes bioactive amides, for example endocannabinoid anandamide, agonists of cannabinoid receptors, and TPRV1 vanilloid receptors of free fatty acids and ethanolamines (e.g. reference 411 (2005)): g., McKinney MK, Cravatt BF, Ann Rev Biochem 74...

Because of its ability to regulate anandamide levels, FAAH is currently an attractive drug target. Examples of inhibitors of FAAH include PMSF (phenylmethylsulfonylfluoride), MAFP (methoxyarachidonylfluorophosphonate) and ATMK (arachidonoyltrifluoromethylketone). URB597 ([3- (3-carbamoylphenyl) phenyl] N-cyclohexylcarbamate) is now widely regarded as the gold standard of FAAH inhibitors. In preclinical laboratory studies, URB597 was found to increase the production of endocannabinoids, which resulted in significant antidepressant and analgesic effects (eg, Russo R., et al,J Pharmacol Exp Ther. 322 (1): 236-42 (2007).

FAAH inhibition has been thought to play an important role in various diseases. (See, eg, Pacher et al Pharmacol . Rev. 58: 389-462 (2006), which document is fully incorporated herein by reference).

FAAH inhibition has been included in the following diseases:

(i) pain, especially acute or chronic neuralgia, such as headaches and neuropathic pain (eg, diabetic neuropathic pain, herpes neuralgia, tertiary neuralgia); Acute or chronic pain associated with inflammatory diseases such as arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease and irritable bowel syndrome; Acute or chronic peripheral neuralgia;

(ii) dizziness, vomiting and nausea, especially due to chemotherapy;

(iii) eating disorders, especially edible and cachexia of various natures;

(iv) neurological and psychiatric pathologies such as tremor, dyskinesia, dystonia, stiffness, obsessive-compulsive disorder, Tourette syndrome, all forms of depression and anxiety of all nature and causes, mood disorders and psychosis;

(v) Parkinson's disease, Alzheimer's disease, senile dementia, Huntington's chorea, cerebral ischemia and disorders associated with skull and bone marrow trauma;

(vi) epilepsy;

(vii) sleep disorders including sleep apnea;

(viii) cardiovascular diseases such as heart failure, high blood pressure, cardiac arrhythmia, arteriosclerosis, heart failure, cardiac ischemia and renal ischemia;

(ix) for example, benign skin tumors, brain tumors and papillomas, prostate tumors, and brain tumors (glioblastoma, medulloblastoma, medulloblastoma, neuroblastoma, tumors of fetal origin, astrocytoma, astrocytoma, cortical covering Cancers such as hematomas, cryptic glioma, reticular tumors, neuroepitheliomas, epiphyseal tumors, glioblastomas, malignant meningiomas, sarcomas, malignant melanoma and neuroencephalopathy);

(x) psoriasis, lupus erythematosus, disease of the connective tissue or collagen, Sjogren's syndrome, ankylosing spondylitis, non-classifiable spondylitis, Behcet's disease, autoimmune hemolytic anemia, multiple sclerosis, Lou Gehrig's disease, amyloidosis, graft rejection, plasma cells Disorders of the immune system, including diseases affecting the sexual line, allergic diseases, immediate or delayed hypersensitivity, allergic rhinitis or conjunctivitis, autoimmune diseases such as contact dermatitis;

(xi) parasitic, viral or bacterial infectious diseases such as AIDS and meningitis;

(xii) inflammatory diseases, especially arthritis such as arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease and irritable bowel syndrome;

(xiii) osteoporosis;

(xiv) eye diseases such as ocular hypertension and glaucoma;

(xv) lung diseases including airway disease, bronchial spasms, coughs, asthma, chronic bronchitis, chronic airway obstruction, and emphysema;

(xvi) gastrointestinal diseases such as irritable bowel syndrome, inflammatory bowel disorder, ulcers, diarrhea, incontinence and cystitis.

Because the compounds containing the 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone constructs were found to have unexpectedly high levels of inhibition of FAAH, these compounds were used to treat FAAH related medical conditions. And promising candidates for drugs for prevention. Furthermore, in vivo experiments have confirmed this activity.

In addition, in these in vivo experiments, compounds comprising a 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone construct show selective FAAH inhibitory activity in the peripheral nerves for activity in the CNS. Application of these compounds is therefore expected to reduce central nervous system side effects seen with FAAH inhibitors that are not selective for peripheral nerves.

That is, the compound of the present invention can be used to prepare the medicament for treating the method as well as to treat the disorder. The present invention also includes methods of treating the disease comprising applying a compound of the invention to a patient in need thereof, as well as a pharmaceutical compound comprising the compound or compounds of the invention.

The most preferred foreseen use for the compounds of the invention is the treatment of pain, in particular:

Treatment of acute or chronic neuralgia, such as, for example, headache and neuropathic pain, including diabetic neuropathic pain, herpes neuralgia, tertiary neuralgia;

-Treatment of acute and chronic pain associated with inflammatory diseases such as arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, irritable bowel syndrome;

-Treatment of acute and chronic peripheral neuropathy.

As used herein, the term treatment and variations thereof such as 'treat' or 'treatment' refer to any curing method that is beneficial to humans or other animals. Treatment may be for an existing disorder or may be prophylactic (prophylactic). Treatment may include efficacy that is effective, palliative or prophylactic for the treatment. Treatment may prevent or delay the onset, delay the progression of the disease, or alleviate signs of the disease or disorder.

5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone is disclosed in U.S. Patent Nos. 5,093,343, 5,236,939, 4,076,824, WO 03/043997 A1, EP 1 263 745 B1, International Patent Publication WO 03/072098 A1, International Patent Publication WO 01/17981 A1 International Patent Publication WO 03/072555 A1, and Japanese Patent Application Publication It is described in various publications such as JP-A 48 58 140. However, no publication is concerned with the inhibition of FAAH or the treatment of a medical condition associated with FAAH.

In one embodiment, the present invention is directed to compounds of formula (I), as shown below:

(I),

Wherein R ¹ to R ⁵ are each independently,

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl-carboxy, C ₁ -C ₆ - Al Kilmer kaeptil _{(C 1 -C 6 -alkylmercaptyl),} C 6 -C 10 - aryl Murray kaeptil, C ₁ -C ₆ -alkylmercaptocarbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercetocarbonyl, C ₁ -C ₆ -alkylmercaptocarbonyl, C _6- C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsulfoxy, C ₆ -C ₁₀ -arylsulfoxy, each above Is optionally substituted one or more times with the functional groups in parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - have one functional group or an amino substituted alkyl, double the selected moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups the alkyl moiety can be bonded to form 5 or 6 membered rings; CONH ₂ or SO ₂ NH ₂ ; amino; C ₁ -C ₆ -alkyl, C ₆ -C _10- Aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ Amino substituted one or more times with a moiety selected from -C ₁₀ -arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or R ⁶ is NR ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, and the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice with alkyl, fluoro or chloro;

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or more times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a moiety selected from C ₁₀ -aryl-C ₁ -C ₆ -alkyl, in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

Wherein any two or more of R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

In which n is 0 or 1; m is 0, 1, 2, 3, 4, 5 or 6;

In which X is O or S;

Wherein Y is represented as follows (a), b), c)):

a) hydrogen;

b) C ₁ -C ₁₈ -alkyl, mono or polyunsaturated C ₂ -C ₁₈ -alkylene, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C _1- C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ -aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - cycloalkenyl Kilmer captopril-carbonyl, C ₆ -C ₁₀ - aryl bots, captopril-carbonyl, C ₁ -C ₆ - Al Kilmer Captocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C _10- Arylsulfoxy, or saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms, each of which (B1), b2), b3)) it is optionally substituted once or several times by:

b1) C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy , C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C _6- C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl carbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril Carbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy; Each of which is optionally C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ , SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ with an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; Or substituted once or several times by OCF ₃ ;

Some of the substituents in b1) above may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

or

b2) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; or

Disubstituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₆ -, and NR ⁶ with R ⁶ selected from alkyl, methylene of formula (II) group is optionally C ₁ - May be substituted once or twice with C ₆ -alkyl, fluoro or chloro;

or

b3) C ₁ -C ₆ -alkyl as a saturated, unsaturated or aromatic heterocyclic ring system of up to 10 atoms; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted once or several times with CF ₃ or OCF ₃ ;

c) SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Thiols; Hydroxyl group; Nitro; Cyano; Fluorosulfonyl; Halogen selected from fluoro, chloro, bromo or iodine; CF _3; Or OCF ₃ ;

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.

Another embodiment relates to the use of the above-described compounds for the inhibition of fatty acid amide hydrolase (FAAH) and also for the treatment of a medical condition positively affected by the inhibition of FAAH. Above all, Pacher et al, Pharmacol . Rev. As pointed out herein by 58: 389-462 (2006), the compound has been specifically pointed out for the treatment of the above-mentioned diseases and medical conditions.

The present invention also relates to a pharmaceutical compound comprising the compound of formula (I) or an enantiomer, a pharmaceutically acceptable salt or a prodrug thereof, and the compound of formula (I), an enantiomer, a pharmaceutical The present invention relates to a method for treating the above-mentioned diseases and conditions by applying a pharmaceutically activated amount of a salt or a prodrug thereof.

Within the scope of the specification, the term C ₁ -C ₄ -alkyl preferably denotes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and tert-butyl.

Within the scope of the present specification, the C ₁ -C ₆ -alkyl term preferably denotes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, and tert-butyl, pentyl or hexyl.

Within the scope of this specification, the C ₁ -C ₁₈ -alkyl term is preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, octyl, decyl , Dodecyl, tetradecyl and octadecyl.

Within the scope of the specification, the term mono or polyunsaturated C ₂ -C ₁₈ -alkylene is preferably ethenyl, n-propenyl, isopropenyl, n- N-butenyl, sec-butenyl, tert-butenyl, pentenyl, hexenyl, octenyl, octenyl, decenyl ), Dodecenyl, tetradecenyl, octadecenyl, octadecenyl, dodecdienyl, tetratradedienyl and octadecdienyl.

Within the scope of the present specification, C ₃ -C ₈ -cycloalkyl preferably denotes cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

Within the scope of this specification, the C ₆ -C ₁₀ -aryl term is preferably phenyl, pentalenyl, indenyl, indanyl, isoindolinyl, chromanyl (chromanyl), naphthyl, fluorenyl, anthryl, anthanthryl or phenanthryl or pyrenyl.

Within the scope of the present specification, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl and C ₆ -C ₁₀ -aryl-C _The term _1- C ₄ -alkyl denotes phenyl or naphthyl, preferably substituted with methyl, ethyl, propyl, or butyl. Particularly preferred residues are benzyl and phenethyl.

Within the scope of the present specification, the C ₁ -C ₄ -alkoxy terms are preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, and tert-butoxy Indicates.

Within the scope of this specification, the C ₁ -C ₆ -alkoxy terms are preferably methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, Pentoxy or hexoxy.

To the extent that the specification is intended, the term C ₆ -C ₁₀ -aryloxy is preferably phenoxy, naphthoxy, indenoxy, fluorenoxy or phenant. Phenanthroxy.

Within the scope of the present specification, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy and C ₆ -C ₁₀ -aryl-C _The term _1- C ₄ -alkoxy preferably denotes benzoxy, phenethoxy, phenpropoxy or phenbutoxy. Particularly preferred residues are benzoxy and phenethoxy.

Within the scope of the specification, the term C ₁ -C ₆ -alkoxycarbonyl preferably refers to methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl or butoxycarbonyl. Indicates.

Within the scope of this specification, the term C ₆ -C ₁₀ -aryloxycarbonyl preferably denotes phenoxycarbonyl or naphthoxycarbonyl.

Within the scope of the present specification, the term C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl preferably denotes benzoxycarbonyl or phenoxycarbonyl.

Within the scope of the specification, the term C ₁ -C ₆ -alkylcarbonyl preferably denotes methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl or butylcarbonyl.

Within the scope of the present specification, the term C ₆ -C ₁₀ -arylcarbonyl preferably denotes phenylcarbonyl or naphthylcarbonyl.

Within the scope of the present specification, the term C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkylcarbonyl preferably denotes benzylcarbonyl or phenethylcarbonyl.

Within the scope of the specification, the C ₁ -C ₆ -alkylcarboxy term preferably denotes methyl carboxy, ethyl carboxy, n-propyl carboxy, isopropyl carboxy, or butyl carboxy.

Within the scope of the specification, the C ₆ -C ₁₀ -arylcarboxy term preferably denotes phenylcarboxy or naphthylcarboxy.

Within the scope of this specification, the term C ₁ -C ₆ -alkylmercaptyl preferably denotes methylmercaptyl, ethylmercaptyl, n-propylmercaptyl, isopropylmercaptyl or butylmercaptyl.

Within the scope of the present specification, the term C ₆ -C ₁₀ -aryl mercaptyl preferably denotes phenylmercaptyl or naphthylmercaptyl.

Within the scope of this specification, the C ₁ -C ₆ -alkylmercaptocarbonyl terms are preferably methylmercaptocarbonyl, ethylmercaptocarbonyl, n-propylmercaptocarbonyl, isopropylmercaptocarbonyl Or butyl mercaptocarbonyl.

Within the scope of the present specification, the C ₃ -C ₈ -cycloalkylmercaptocarbonyl term is preferably cyclopropylmercaptocarbonyl, cyclobutylmercaptocarbonyl, cyclopentylmercaptocarbonyl or cyclohexylmercapto Carbonyl.

Within the scope of the present specification, the term C ₆ -C ₁₀ -aryl mercaptocarbonyl preferably denotes phenylmercaptocarbonyl or naphthylmercaptocarbonyl.

Within the scope of this specification, the C ₁ -C ₆ -alkylmercaptocarboxy term is preferably methylmercaptocarboxy, ethylmercaptocarboxy, n-propylmercaptocarboxy, isopropylmercaptocarboxy or butylmercaptocarboxy. Indicates.

Within the scope of this specification, the term C ₆ -C ₁₀ -aryl mercaptocarboxy preferably denotes phenylmercaptocarboxy or naphthylmercaptocarboxy.

Within the scope of the present specification, the C ₁ -C ₆ -alkylsulfonyl term is preferably methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, n-butylsulfonyl, sec-butylsulfonyl, tert- Butylsulfonyl, pentylsulfonyl or hexylsulfonyl.

Within the scope of the present specification, the term C ₆ -C ₁₀ -arylsulfonyl preferably denotes phenylsulfonyl or naphthylsulfonyl.

Within the scope of the present specification, the C ₁ -C ₆ -alkyl sulfoxy term is preferably methyl sulfoxy, ethyl sulfoxy, n-propyl sulfoxy, n-butyl sulfoxy, sec-butyl sulfoxy or tert- Butyl sulfoxy is shown.

Within the scope of the present specification, the term C ₆ -C ₁₀ -arylsulfoxy preferably denotes phenylsulfoxy or naphthylsulfoxy.

Furthermore, the aforementioned substituents may optionally be selected from C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, CONH ₂ , SO ₂ NH ₂ , Alternative embodiments of the invention which are substituted once or several times with SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ are preferred. . In this definition of optional substituents, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, and C ₆ -C ₁₀ -aryloxy preferably represent the same moieties mentioned above.

Within the meaning of this specification, the term 'optionally substituted once or several times' means not substituted once, substituted once with one or more optional substituents mentioned above, or substituted multiple times. It includes. When substituted several times, the substituents may be selected independently from each other.

Within the scope of the present specification, C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₆ -C ₁₀ -aryl-C _1- C ₆ -alkyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkyl Amino substituted one or more times with residues selected from sulfonyl and C ₆ -C ₁₀ -arylsulfonyl is preferably represented by one or two amino groups, methyl, ethyl for C ₁ -C ₆ -alkyl , n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl or hexyl; Phenyl, benzyl or phenethyl for C ₆ -C ₁₀ -aryl; C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, or C ₆ -C ₁₀ -aryl-C Phenyl, benzyl, or phenethyl for _1- C ₈ -alkyl; Methylcarbonyl, ethylcarbonyl or phenylcarbonyl for C ₁ -C ₆ -alkylcarbonyl and C ₆ -C ₁₀ -arylcarbonyl; And C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl, each independently of one another is substituted by methylsulfonyl, ethylsulfonyl or phenylsulfonyl.

Within the scope of the present specification, "disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or R ⁶ is NR ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, and the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice with alkyl, fluoro or chloro) "is preferably piperidinyl, piperazinyl, pyrrolidinyl, morpholinyl, N-methyl piperazine or 2,2,6 , 6-tetramethyl piperidinyl.

Within the scope of the present specification, C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl or C ₆ -C ₁₀ -aryl-C Having an amino group substituted one or more times with a moiety selected from _1- C ₆ -alkyl, and in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety forms a 5 or 6 molecular ring. CONH ₂ or SO ₂ NH ₂ which may be bonded to is preferably N, N-dimethylamide, N-methylamide, N-ethylamide, N-phenylamide, N, N-dimethylsulfonamide, N-methylsulfonamide And each residue that can be derived from N-ethylsulfonamide, and N-phenylsulfonamide. In the case of alkyl-disubstituted groups of amino functional groups, it is also a preferred alternative that both residues can be combined to form a 5 or 6 molecular ring. Examples of such amino functional groups include, but are not limited to, pyrrolidine and piperidine.

Within the scope of this specification, "saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or more times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a residue selected from C ₁₀ -aryl-C ₁ -C ₄ -alkyl, and in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl residue is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl At least substituted amino; thiol; hydroxyl group; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ ) "The term is preferably one to four selected from N, O or S Saturated, unsaturated, or aromatic heterocyclics up to 10 atoms containing heteroatoms Examples of such saturated, unsaturated or aromatic heterocycles of up to 10 atoms are benzimidazole, benzofuran, benzothiophene, benzoxazole, benzothia Benzothiazole, carbazole, cinoline, dioxin, dioxane, dioxolane, dithiane, dithiazine, dithiazole (dithiazole), dithiolane, furan, imidazole, imidazoline, imidazolidine, indole, indoline, indolizine ( indolizine, indazole, isindole, isoindole, isoquinoline, isoxazole, isothiazole, morpholine, naphthyridine, oxazole (oxazole), oxadiazole, oxathiazole, oxathiazolidine, oxazine zine, oxadiazine, phenazine, phenothiazine, phenoxazine, phenoxazine, phthalazine, piperazine, piperidine, fu Pteridine, purine, pyran, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridolidine, pyridazine, pyridine , Pyrimidine, pyrrole, pyrrolidine, pyrroline, quinoline, quinoxaline, quinoxaline, quinazoline, quinolizine , Tetrahydrofuran, tetrazine, tetrazine, tetrazole, thiophene, thiadiazine, thiadiazole, thiatriazole, thiazine thiazine, thiazole, thiomorpholine, thiianaphthalene, thiopyran, triazine, triazole, and triti Including but not limited to trithiane, their isomeric arrangements are also included. Such heterocycles are C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, CONH _{2 ,} SO ₂ NH _2, (C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl Or an amino group substituted one or more times with a residue selected from C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, and in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group Residues may be combined to form a 5 or 6 molecular ring CONH ₂ or SO ₂ NH ₂ ); Amino, (C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ Amino substituted one or more times with a residue selected from -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl); It may be substituted once or several times with thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ . Particularly preferred optional substituents are methyl, methoxy, amino, hydroxy, nitro, cyano, fluoro, chloro, iodine, CF ₃ or OCF ₃ .

Most preferred saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms consist of 2-pyridine, 3-pyridine and 4-pyridine, all of which are selected from methyl, amino, fluoro, chloro or CF ₃ Optionally substituted one or more times with a residue; And N-linked pyrrole optionally substituted with one or more residues with residues selected from methyl, amino, fluoro, chloro or CF ₃ .

Further embodiments of the present invention, two or more of R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system. Examples of such ring systems include, but are not limited to, benzimidazole, benzofuran, benzothiophene, benzoxazole, and benzothiazole.

In the above formula (I), R ¹ to R ⁵ are each independently represented as follows:

Hydrogen;

Hydroxyl group;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is optionally C ₁ -C ₆ -alkyl, To C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Substituted one or several times by;

Amino;

Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl;

1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, optionally substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, amino, fluoro, chloro or CF ₃ ; or

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice among alkyl, fluoro or chloro);

CONH ₂ ;

SO ₂ NH ₂ ;

CONH ₂ or SO ₂ NH ₂ having amino functional groups, once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;

Fluoro;

Chloro;

Bromo;

CF _3; or

OCF ₃ .

In the above formula (I), still more preferred is when one or more of R ¹ to R ⁵ is hydrogen, fluorine or chlorine. More preferred is when R ¹ or R ⁵ is hydrogen or fluorine. Most preferred is when R ¹ or R ⁵ is fluorine.

In the above formula (I), further preferably, one or more of R ¹ to R ⁵ is hydroxy; C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino , Di-C ₁ -C ₆ -alkylamino, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl), hydroxy, Optionally substituted one or several times with fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ .

More preferably, any one of R ² , R ³ or R ⁴ is hydroxy; C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₄ -alkyl, C ₁ -C _4- Optionally substituted once or twice with alkoxy, amino, C ₁ -C ₄ -alkylamino, di-C ₁ -C ₄ -alkylamino, (C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl Optionally substituted once or several times with CONH ₂ or SO ₂ NH ₂ ), hydroxy, fluoro, chloro or bromo.

In the above formula (I), further preferably, one or more of R ¹ to R ⁵ is amino; Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; Or disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₄ Optionally substituted once or twice with alkyl, fluoro or chloro;

More preferably, any one of R ² , R ³ or R ⁴ is amino; Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; Or a disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, wherein the methylene group in formula (II) is C ₁ -C ₄ Optionally substituted once or twice with alkyl, fluoro or chloro).

More preferably, in formula (I) above, n is 0; m is 0, 1, 2, 3, 4, 5 or 6; And Y is a C ₃ -C ₆ -cycloalkyl or C ₆ -C ₁₀ -aryl optionally substituted one or more times by (a), b), c)), respectively:

a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkoxy, each of which is optionally substituted one or several times by the following parentheses:

Substituted once or twice with (C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl CONH ₂ or SO ₂ NH ₂ ; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C Amino substituted one or more times with a residue selected from ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

or

b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino group substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, and the methylene group of formula (II) is C ₁ -C _4- Optionally substituted once or twice with alkyl, fluoro or chloro;

or

c) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or several times by the following parentheses:

Substituted once or twice with (C ₁ -C ₆ -acyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl CONH ₂ or SO ₂ NH ₂ ; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C Amino substituted one or more times with a residue selected from ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ ).

More preferably, n is 0; m is 0 or 1; And Y is phenyl, 1-naphthyl, 2-naphthyl, 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl ring system.

Even more preferably, Y is C ₁ -C ₄ -alkyl; Phenyl; C ₁ -C ₄ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; CONH ₂ or SO ₂ NH ₂ optionally substituted one or two times with C ₁ -C ₄ -alkyl residues which may be bonded to form a 5 or 6 molecular ring; Or once or several times with amino.

Even more preferably, m is 0 and Y represents phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.

Most preferably, m is 0, Y is in 4-position by fluoro, 4-position by chloro, 2- and 4-position by fluoro, 2- and 4-position by chloro, or phenyl To phenyl substituted at the 4-position.

In the formula (I), particularly preferred, m is 0; n is 0; Y, which is phenyl once or twice substituted by fluoro, chloro or bromo; And any one of R ² to R ⁴ represents OR ⁷ which is R ⁷ selected from hydrogen, C ₁ -C ₄ -alkyl.

In the above formula (I), also very preferably, m is 0; n is 0; Y represents phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, the 2- and 4-position with chloro and in R ² to R ⁴ One represents OR ⁷ which is R ⁷ selected from hydrogen, C ₁ -C ₄ -alkyl.

In the above formula (I), also very preferably, m is 0; n is 0; Y represents phenyl once or twice substituted with fluoro, chloro or bromo and R ³ or R ³ and R ⁴ represent hydroxy.

In the above formula (I), also very preferably m is 0; n is 0; Y represents phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, the 2- and 4-position with chloro and R ³ or R ³ and R ⁴ represents hydroxy.

In the above formula (I), particularly preferably, m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; Any one of R ² to R ⁴ is OR ⁷ having R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; And R ¹ is hydrogen or fluorine.

In the above formula (I), particularly preferably, m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, and the 2- and 4-position with chloro; Any one of R ² to R ⁴ is OR ⁷ having R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; And R ¹ is hydrogen or fluorine.

In the above formula (I), particularly preferably, m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; R ³ or R ³ and R ⁴ are hydroxyl groups; And R ¹ is hydrogen or fluorine.

In the above formula (I), particularly preferably, m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, and the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ are hydroxyl groups; And R ¹ is hydrogen or fluorine.

Furthermore, in the above formula (I) also preferably, when n = 0, m = 0 or 1, Y n = 0, m = 0 or 1, Y is C ₆ -C ₁₀ -aryl, preferably phenyl; Benzyl, phenethyl, phenpropyl, phenbutyl or phenhexyl, which is optionally substituted one or more times by (a), b), c)) :

a) C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy , C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, hydroxyl group, CO ₂ H, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxy Carbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ - alkylcarbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ - C ₆ -alkylmercaptocarbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarbonyl, C ₆ -C ₁₀ -Arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy;

Each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl; Optionally substituted once or several times with SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ ;

Some of these optional substituents above may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system; or

b) saturated, unsaturated, or aromatic heterocycles include C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl; Optionally substituted once or several times with SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ ;

c) SO ₃ H, amino, (C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl , C ₆ -C ₁₀ - aryl-carbonyl, C ₁ -C ₆ - alkylsulfonyl, and C ₆ -C ₁₀ - aryl amino substituted on the sulfonyl moiety selected once or several times); One or several substitutions with a residue selected from CONH ₂ , SO ₂ NH ₂ , (C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl CONH ₂ or SO ₂ NH ₂ with an amino functional group; thiol, hydroxyl, nitro, cyano, fluorosulfonyl, (halogen selected from fluoro, chloro, bromo or iodine); CF ₃ , OCF ₃ .

In the above formula (I), it is also very preferably n = 0 and m = 0 or 1.

Also preferably, R ¹ to R ⁵ are each independently hydrogen, hydroxyl, C ₁ -C ₄ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₄ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ - aryl -C ₁ -C ₄ - alkoxy, COOH, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ -aryl Murray kaeptil, C ₁ -C ₆ - alkylsulfonyl, C ₆ -C ₁₀ arylsulfonyl, C ₁ -C ₆ - alkyl sulfonic propoxy, C ₆ -C ₁₀ - aryl epoxy, SO ₃ H, Amino, (C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -Amino substituted one or more times with residues selected from -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl), thiols, hydroxyl groups, nitro, cyano, Fluorosulfonyl; Halogen selected from fluoro, chloro, bromo or iodine; CF ₃ , OCF ₃ ; Or C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or Saturated, unsaturated or aromatic heterocycle optionally substituted one or several times with OCF ₃ .

More preferably, R ¹ to R ⁵ are hydroxyl, methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amino, thiol, hydroxyl, cyano, fluoro, chloro, bromo, nitro , CF ₃ , OCF ₃ , pyridine, CONH ₂ , SO ₂ NH ₂ , tetrazole or triazole.

Also more preferably, any one of R ¹ to R ^{5 may} further comprise a hydroxyl group, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl group, nitro, cyano, fluoro, chloro , Bromo, iodine, phenyl substituted once or several times with CF ₃ or OCF ₃ .

In the above formula (I), also preferably, Y is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, amino, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ represents phenyl or benzyl substituted in the ortho-, meta-, and / or para-position. Even more preferably, Y is ortho- with substituents independently selected from methoxy, ethoxy, tert-butoxy, phenoxy, hydroxy, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ And / or phenyl substituted once, twice or three times in the para-position.

In the above formula (I), and also preferably, when n = 0 and m = 0 or 1, R ¹ to R ⁵ are methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amino, thiol ( thiol), hydroxyl, cyano, fluoro, chloro, bromo, nitro, CF ₃ , OCF ₃ , pyridine, CONH ₂ , SO ₂ NH ₂ , tetrazole, triazole or even C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, nitro, CF ₃ Or phenyl once or more times substituted with OCF ₃ , and Y is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro , Phenyl substituted at the ortho- and / or para-position by chloro or OCF ₃ .

In an alternative embodiment, the invention relates to compounds represented by formula (I)

(I),

In the above formula, R ¹ to R ⁵ are each independently,

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl-carboxy, C ₁ -C ₆ - Al Kilmer kaeptil _{(C 1 -C 6 -alkylmercaptyl),} C 6 -C 10 - aryl Murray kaeptil, C ₁ -C ₆ -alkylmercaptocarbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercetocarbonyl, C ₁ -C ₆ -alkylmercaptocarbonyl, C _6- C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsulfoxy, C ₆ -C ₁₀ -arylsulfoxy, each above Is optionally substituted one or more times with the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - have one functional group or an amino substituted alkyl, double the selected moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups the alkyl moiety can be bonded to form 5 or 6 membered rings; CONH ₂ or SO ₂ NH ₂ ; amino; C ₁ -C ₆ -alkyl, C ₆ -C _10- Aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ Amino substituted one or more times with a moiety selected from -C ₁₀ -arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ or R ⁶ is NR ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, and the methylene group of formula (II) is C ₁ -C ₆ -alkyl Optionally substituted once or twice with fluoro or chloro);

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or more times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a moiety selected from C ₁₀ -aryl-C ₁ -C ₆ -alkyl, in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

Any two or more of the above R ¹ to R ⁵ may combine to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

In which n is 0; m is 0;

Y represents phenyl optionally substituted one or more times by

a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkylcarbonyl, C ₁ -C _6- carboxy alkyl, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - Cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl , C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy;

Each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl Or SO ₂ NH ₂ ; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or more times with CF ₃ or OCF ₃ ;

Some of these optional substituents above may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system; or

b) saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms, C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted once or several times with CF ₃ or OCF ₃ ; or

c) hydroxyl groups; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino group substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or R ⁶ is NR ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, and the methylene group of formula (II) is C ₁ -C _4- Optionally substituted once or twice with alkyl, fluoro or chloro;

Subject to the following (a), b), c), d)):

a) R ² or R ⁴ does not represent a C (= A) -N (B) -SO ₂ -NR ⁶ R ⁷ substituent. Wherein A is O or S, B is hydrogen, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy-alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C _6- alkenyl _{(C 3 -C 6 -alkenyl),} C 3 -C 6 - alkynyl, (C ₃ -C ₆ -alkynyl) or optionally substituted benzyl derivatives, and R ⁶ and R ⁷ are independently hydrogen or an organic one another Represented by a moiety, or organic cyclic structure;

b) when Y represents unsubstituted phenyl, R ¹ to R ⁵ independently of one another do not represent hydrogen, fluoro, bromo, chloro, iodine or alkyl radicals;

c) R ² or R ⁴ does not represent a pyrazol-3-yl-derivative; And

d) a phenyl ring substituted with R ¹ to R ⁵ , and Y not represented by combinations of compounds in the table below:

In the above formula (I), preferably, R ¹ to R ⁵ are independently of each other represented as follows:

Hydrogen;

Hydroxyl group;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Optionally substituted several times or several times;

Amino;

Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; 1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, optionally substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, amino, fluoro, chloro or CF ₃ ; or

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice among alkyl, fluoro or chloro);

CONH ₂ ;

SO ₂ NH ₂ ;

CONH ₂ or SO ₂ NH ₂ having amino functional groups, once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;

Fluoro;

Chloro;

Bromo;

CF _3; or

OCF ₃ .

In the above formula (I), further preferably, R ¹ to R ⁵ One or more of is hydrogen, fluorine or chlorine. Most preferably, R ¹ or R ⁵ is hydrogen or fluorine.

In the above formula (I), still more preferably, one or more of R ¹ to R ⁵ represents:

Hydroxy; or

C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino , Di-C ₁ -C ₆ -alkylamino, (CONH ₂ or SO ₂ NH ₂ ) optionally substituted once or twice with C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl, hydroxy, Optionally substituted one or several times with fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ .

More preferably one of R ² , R ³ or R ⁴ represents:

Hydroxy; or

C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ CONH substituted once or twice with -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, (C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl ₂ or SO ₂ NH ₂ ), optionally substituted one or several times with hydroxy, fluoro, chloro, or bromo.

In the above formula (I), further preferably, one or more of R ¹ to R ⁵ is amino; Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; Or a disubstituted amino of formula (II):

(II)

(II)

(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₄ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) group is optionally C ₁ - May be substituted once or twice with C ₄ -alkyl, fluoro or chloro).

More preferably any one of R ² , R ³ or R ⁴ is amino; Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; Or a disubstituted amino of formula (II):

(II)

(II)

(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₄ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) group is optionally C ₁ - May be substituted once or twice with C ₄ -alkyl, fluoro or chloro).

In the above formula (I), further preferably, Y represents phenyl substituted once or several times by the following (a), b), c)):

a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkoxy, each of which is optionally substituted one or several times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; SO ₃ H; CO ₂ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl -C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Amino substituted once or more by residue; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; OCF ₃ ; or C ₁ CONH ₂ or SO ₂ NH ₂ ) having amino functional groups substituted once or twice with —C ₆ -alkyl;

or

b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Or an amino group substituted once or twice with C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, and di-C _1- In the case of a C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice with alkyl, fluoro or chloro;

or

c) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or several times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH _{2 ;} SO ₂ NH ₂ ; once with C ₁ -C ₆ -alkyl which may be bonded to form a 5 or 6 molecular ring Or CONH ₂ or SO ₂ NH ₂ with two substituted amino functional groups; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C _1- Once with a residue selected from C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Amino substituted or more; thiol; hydroxyl group; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

Even more preferably, Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or selective C ₁ -C _6, which may be combined to form a 5- or 6-ring molecular-alkyl moiety of C ₁ -C ₆ - alkyl with one or two CONH ₂ or SO ₂ NH ₂ which is optionally substituted Phenyl substituted once or several times.

Even more preferably, m is 0 and Y is phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.

Most preferably, m is 0, Y is in 4-position by fluoro, 4-position by chloro, 2- and 4-position by fluoro, 2- and 4-position by chloro, or phenyl Phenyl substituted at the 4-position.

Especially preferably, in formula (I), m is 0; n is 0; Y represents phenyl substituted once or twice with fluoro, chloro, or bromo; One of R ² to R ⁴ represents OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl.

Also very preferably in the formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, or the 2- and 4-position with chloro, and any of R ² to R ⁴ One represents OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl.

Also very preferably in the formula (I), m is 0; n is 0; Y is phenyl once or twice substituted with fluoro, chloro or bromo, R ³ or R ³ and R ⁴ Is hydroxy.

Also very preferably in the formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, or the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ Is hydroxy.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; Any one of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; And R ¹ is fluorine.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, or the 2- and 4-position with chloro; Any one of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; And R ¹ is fluorine.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; R ³ or R ³ and R ⁴ Is hydroxy; And R ¹ is fluorine.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, or the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ Is hydroxy; And R ¹ is fluorine.

Furthermore further preferably in the above formula (I), R ¹ to R ⁵ hydroxyl group, methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amino, thiol, hydroxyl group, cyano, fluoro , Chloro, bromo, nitro, CF ₃ , OCF ₃ , pyridine, CONH ₂ , SO ₂ NH ₂ , tetrazole or triazole.

Also preferably at least one of R ¹ to R ⁵ is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro Saturated, unsaturated or aromatic heterocycle substituted with chloro, bromo, iodine, CF ₃ or OCF ₃ , or Further once or several with C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ Phenyl once substituted.

Alternatively, also preferably at least one of R ¹ to R ⁵ may be CONH ₂ ; SO ₂ NH ₂ ; Or CONH ₂ with an amino function substituted once or several times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl or SO ₂ NH ₂ .

Also preferably in the above formula (I), Y is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, amino, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ Phenyl substituted at the ortho- and / or para-position of.

Even more preferably, Y is ortho- and / with substituents independently selected from methoxy, ethoxy, tert-butoxy, phenoxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ Or phenyl substituted once, twice or three times in the para-position.

Also preferably, Y is ortho- and / or para- with C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ Phenyl substituted at the position.

Also preferably in the above formula (I), R ¹ to R ⁵ are methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amino, thiol, hydroxyl, cyano, fluoro, chloro, Bromo, iodine, CF ₃ , OCF ₃ , pyridine, CONH ₂ , SO ₂ NH ₂ , tetrazole, triazole or even C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino , Thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, phenyl once or several times substituted with CF ₃ or OCF ₃ and Y is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or phenyl substituted at the ortho- and / or para-position by OCF ₃ .

In a further alternative embodiment, the invention is a compound represented by formula (I)

(I)

Wherein R ¹ to R ⁵ are each independently,

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of which is optionally selected once by parenthesis or Is replaced multiple times:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₄ - has one or more substituted amino functional groups selected from the alkyl moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups, the alkyl moiety is CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C _10- Amino substituted one or more times with a residue selected from arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₆ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₆ -alkyl, fluoro or chloro);

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or more times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a residue selected from C ₁₀ -aryl-C ₁ -C ₄ -alkyl, and in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl residue is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

Wherein any two or more of R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

In which n is 0; m is 1;

Y represents phenyl optionally substituted one or more times by (a), b), c)):

a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkylcarbonyl, C ₁ -C _6- carboxy alkyl, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - Cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl , C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy; each of which is optionally substituted one or several times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl) Or SO ₂ NH ₂ ; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF ₃ or OCF ₃ );

Some of these optional substituents may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system; or

b) saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl Or SO ₂ NH ₂ ; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or several times from CF ₃ or OCF ₃ ; or

c) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Disubstituted amino of formula (IV)

(IV)

(IV)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, wherein the methylene group of formula (IV) is C ₁ -C _4- Optionally substituted once or twice among alkyl, fluoro or chloro);

If R ¹ , R ² and R ⁵ are hydrogen, R ⁴ is hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, benzyloxy, phenoxy, Phenyl, 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, R ³ is hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, phenoxy , 4-chlorophenoxy, cyclohexyl, phenyl, morpholinosulfonyl, 3,3,5-trimethylcyclohexylaminosulfonyl, 2,2,6,6-tetramethylcyseridin-4-yl Aminosulfonyl (2,2,6,6-tetramethylpiperidin-4-ylaminosulfonyl), 2- (diisopropylaminoethyl) aminosulfonyl, 4-methylpiperazin-1-yl-sulfonyl (4-methylpiperazin-1 -yl-sulfonyl), 3,3-dimethylpiperidinocarbonyl or 3,5-dichlorophenoxy

If 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, then Y is not unsubstituted phenyl.

Even more preferably, Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once or several times substituted with CONH ₂ or SO ₂ NH ₂ , optionally substituted once or twice with an optional C ₁ -C ₆ -alkyl moiety capable of bonding to form such a 5 or 6 molecular ring. Phenyl.

Even more preferably, m is 0; Y is phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.

Most preferably, m is 0; Y is phenyl substituted in 4-position by fluoro, 4-position by chloro, 2- and 4-position by fluoro, 2- and 4-position by chloro, or 4-position by phenyl .

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; One of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl.

More preferably also in formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro or the 2- and 4-position with chloro; One of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl.

More preferably also in formula (I), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; R ³ or R ³ and R ⁴ Is hydroxy.

More preferably also in formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro or the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ Is hydroxy.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; Any one of R ² to R ⁴ is OR ⁷ having R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; And R ¹ is fluorine.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro or the 2- and 4-position with chloro; Any one of R ² to R ⁴ is OR ⁷ having R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; And R ¹ is fluorine.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro or bromo; R ³ or R ³ and R ⁴ A hydroxyl group; And R ¹ is fluorine.

Especially preferably, in formula (I), m is 0; n is 0; Y is phenyl substituted at the 4-position with fluoro, the 4-position with chloro, the 2- and 4-position with fluoro or the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ A hydroxyl group; And R ¹ is fluorine.

Still more preferably in the above formula (I), R ¹ to R ⁵ are methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amino, thiol, hydroxyl group, cyano, fluoro , Chloro, bromo, nitro, CF ₃ , OCF ₃ , pyridine; CONH ₂ , SO with amino functional groups substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl ₂ NH ₂ ; Tetrazole, triazole is selected from.

Also more preferably, R ¹ to R ⁵ are further C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine , Phenyl substituted once or several times with CF ₃ or OCF ₃ .

Also preferably in formula (I), Y is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, amino, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ By phenyl substituted at the ortho- and / or para-positions.

Even more preferably, Y is ortho- and / with substituents independently selected from methoxy, ethoxy, tert-butoxy, phenoxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ Or phenyl substituted once, twice or three times in the para-position.

Also preferably in formula (I), Y is ortho by C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ -And / or phenyl substituted in the para-position.

Also more preferably in formula (I), R ¹ to R ⁵ are methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amino, thiol, hydroxyl, cyano, fluoro, chloro, Bromo, nitro, CF ₃ , OCF ₃ , pyridine, CONH ₂ , SO ₂ NH ₂ , tetrazole, triazole or even C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino , Thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, phenyl once or several times substituted with CF ₃ or OCF ₃ , Y is C ₁ -C ₆ -alkoxy, C Phenyl substituted at the ortho- and / or para-position by _6- C ₁₀ -aryloxy, hydroxyl, nitro, CONH ₂ , SO ₂ NH ₂ , fluoro, chloro or OCF ₃ .

In a first more preferred embodiment, the present invention relates to a compound represented by the following formula (I):

(I),

(I),

Wherein R ¹ or R ⁵ is hydrogen or fluorine;

Is a hydroxyl group any one of R ² to R ⁴ and the remaining R residues are

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol , Number A group, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF _3;

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

C ₁ -C ₆ -acyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF A saturated, unsaturated, or aromatic heterocyclic ring system of up to 10 atoms optionally substituted once or several times at ₃ ;

And two or more of R ² to R ⁴ may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

n and m are 0; And

Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times,

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.

In a second more preferred embodiment, the invention relates to compounds represented by formula (I)

(I),

(I),

In which R ¹ or R ⁵ is hydrogen or fluorine;

Any one of R ² to R ⁴ is amino and the remaining R residues are

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol , Number A group, nitro, cyano, fluoro, chloro, bromo, search iodine, CF _3, or one or more times, optionally substituted with OCF _3;

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

C ₁ -C ₆ -acyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF A saturated, unsaturated, or aromatic heterocyclic ring system of up to 10 atoms optionally substituted one or several times at ₃ ;

And two or more of R ² to R ⁴ may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

n and m are 0; And

Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times,

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.

In a third more preferred embodiment, the present invention relates to a compound represented by formula (I)

(I),

(I),

In which R ¹ or R ⁵ is hydrogen or fluorine;

One of R ³ or R ⁴ is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy Each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di -C ₁ -C ₆ - alkylamino, thiol (thiol), hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF _3, or is optionally substituted once or several times by OCF3;

The other of R ³ or R ⁴ is C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl , C ₆ -C ₁₀ - aryl-carbonyl, C ₁ -C ₆ - alkylsulfonyl, and C ₆ -C ₁₀ - aryl substituted amino once from sulfonyl residue or a selected number of times;

And R ² is as follows:

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol , Number Group, a nitro, cyano, fluoro, chloro, bromo, iodine, CF _3, or is once or optionally substituted multiple times in the OCF _3;

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

C ₁ -C ₆ -acyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF A saturated, unsaturated, or aromatic heterocyclic ring system of up to 10 atoms optionally substituted once or several times at ₃ ;

n and m are 0; And

Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times,

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.

In all three of these preferred embodiments, even more preferably, Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times.

In all three of these preferred embodiments, even more preferably, Y is phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.

In all three of these preferred embodiments, and even more preferably, Y is in 4-position with fluoro or chloro, 2- and 4-position with fluoro or 2- and 4-position with chloro or phenyl. Phenyl substituted at the 4-position.

All these points of the invention relate to the compound per - se , ie, to be applied in the following:

Compound itself - in the embodiment of the invention relates to (per se), the formula (I) are the following compounds are excluded:

5-dodecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Dodecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-octyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Octyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (3-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (3-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (4- (4-chlorophenoxy) -phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (4- (4-chlorphenoxy) -phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-octyloxy-3-phenyl-3H- (1,3,4) -oxadiazole-2-one

(5-Octyloxy-3-phenyl-3H- (1,3,4) -oxadiazol-2-one)

5-octyloxy-3- (3-fluoro-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Octyloxy-3- (3-fluor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (3-fluoro-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (3-fluor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (3-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (3-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3-phenyl-3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3-phenyl-3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (4-nitro-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (4-nitro-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-hexadecyloxy-3- (4-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Hexadecyloxy-3- (4-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-decyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Decyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-Undecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Undecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-tetradexyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Tetradecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-tridecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-Tridecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (2- (2-hexyloxy-ethoxy) -ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (2- (2-Hexyloxy-ethoxy) -ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-((Z) -octadec-9-enyloxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-((Z) -Octadec-9-enyloxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (Dodecyloxy-ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (Dodecyloxy-ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (2- (4-Fluorophenyl) -ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (2- (4-Fluorphenyl) -ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5-((3ss-cholestan-3-yl) -oxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5-((3ss-Cholestan-3-yl) -oxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (2-Butoxy-ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (2-Butoxy-ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (7-phenyl-heptyloxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (7-Phenyl-heptyloxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (Docosyloxy-ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (Docosyloxy-ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (2- (1-naphthoxy) -ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (2- (1-Naphthloxy) -ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (4-Octylphenoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (4-Octylphenoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (3-Penoxy-phenoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (3-Phenoxy-phenoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (Dodecyloxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (Dodecyloxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (dodecyloxy) -3- (3,4-dichlor-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (Dodecyloxy) -3- (3, 4-dichlor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (Dodecyloxy) -3- (3, 5-dichlor-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (Dodecyloxy) -3- (3, 5-dichlor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (Dodecyloxy) -3- (3-methoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one

(5- (Dodecyloxy) -3- (3-methoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)

5- (dodecyloxy) -3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one;

(5- (Dodecyloxy) -3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one);

An embodiment of the present invention that refers to the compound per - se , which does not represent C ₁ -C ₄ -alkyl when m = 0 and n = 0.

Furthermore, when m = 0 and n = 0, and Y is optionally substituted with a phenyl ring, R ² or R ⁴ is (A is O or S, B is hydrogen, cyano, C ₁ -C _6- Optionally substituted with alkyl, C ₁ -C ₆ -alkoxy-alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₆ -alkenyl, C ₃ -C ₆ -alkynyl or benzyl derivatives, R ⁶ and Each R ⁷ is independently represented by the substituent C (= A) -N (B) -SO ₂ -NR ⁶ R ⁷ which is independently a hydrogen or an organic moiety or a collection of organic cyclic structures; When Y is unsubstituted phenyl, R ¹ to R ⁵ each independently represent no hydrogen, fluoro, bromo, chloro, iodine or alkyl radicals; R ² or R ⁴ is not pyrazol-3-yl-derivative; And the phenyl ring substituted with R ¹ to R ⁵ and Y are not represented by a combination of the compounds of the following table:

Furthermore when n is 0, m is 1, and Y is a optionally substituted phenyl ring, then R ¹ , R ² and R ⁵ are hydrogen and R ⁴ is hydrogen, trifluoromethoxy, trifluorobutoxy , 3,3,5,5-tetramethylcyclohexyloxy, benzyloxy, phenoxy, phenyl, 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, R ³ Divalent hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, phenoxy, 4-chlorophenoxy, cyclohexyl, phenyl, morpholinosulfonyl , 3,3,5-trimethylcyclohexylaminosulfonyl, 2,2,6,6-tetramethylcyseridin-4-ylaminosulfonyl (2,2,6,6-tetramethylpiperidin-4-ylaminosulfonyl), 2 -(Diisopropylaminoethyl) aminosulfonyl, 4-methylpiperazin-1-yl-sulfonyl, 3,3-dimethylpiperidinocarbonyl (3,3 -dimethylpiperidinocarbonyl) or 3,5-dichlorophenoxy

If 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, then Y is not unsubstituted phenyl.

Furthermore, when m = 1, n = 0 and R ³ is trifluoromethoxy, Y is not unsubstituted phenyl.

The compound itself (per - se) in which an alternative embodiment of the present invention that points to, n = 0, m = 0 and when one Y is C ₁ -C ₆ - alkyl, C ₃ -C ₉ - cycloalkyl days Wherein both groups are optionally substituted one or more times with phenyl, C ₁ -C ₄ -alkoxy, SC ₁ -C ₄ -alkyl, N (C ₁ -C ₄ -alkyl) ₂ , and the phenyl is When optionally substituted one or more times with halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkyloxy, nitro, or CF ₃ , R ² to R ⁵ are 2-oxo-pyrrolidine Substituted with phenyl ring by 2-oxo-pyrrolidin-1-yl, 2,5-dimethylpyrrol-1-yl or non-aromatic nitrogen Does not represent.

In some alternative embodiments of the invention that refer to the compound per - se , when n = 0, m = 0, R ¹ or R ⁵ is (at least one of the residues of substituents R ¹ to R ⁵⁾ Represents a substituent selected from halogen, in particular F, Cl, Br, CH ₃ , OCH ₃ , NO ₂ , CN and phenyl representing Y substituted with F, Cl, Br, CH ₃ , OCH ₃ , NO ₂ or CN Ring) in particular F, Cl, NO ₂ , CH ₃ , OCH ₃ or CF ₃ It does not represent a substituent or CN selected from phosphorus halogen.

In some alternative embodiments of the invention that refer to the compound per - se , when n = 0, m = 0, Y does not represent phenyl substituted with phenoxy or C ₆ -C ₁₂ -alkyl. Do not.

In some alternative embodiments of the invention that refer to the compound per - se , when n = 0, m = 1, Y does not represent unsubstituted phenyl.

In some further alternative embodiments of the invention that point to the compound per - se , when m = 0, n = 0, Y is defined when R ¹ to R ⁵ are hydrogen or a halogen atom or a methyl radical No phenyl or lower alkyl radicals.

In some alternative embodiments of the invention that refer to the compound per - se , when n = 0 and m = 0 and Y is (C ₄ -C ₂₀ -alkoxy, C ₆ -C ₁₀ -aryl, Substituted with C ₆ -C ₁₀ -aryloxy or C ₄ -C ₁₂ -alkoxy-C ₂ -C ₄ -alkoxy, C ₇ -C ₂₀ -alkenyl, 3-beta-cholestan-3-yl (3- beta-cholestan-3-yl) or C ₇ -C ₂₂ -alkyl, C ₂ -C ₄ -alkyl, which represents phenyl substituted with phenoxy or C ₆ -C ₁₂ -alkyl, R ² to R ⁵ is hydrogen, halogen, nitro, C ₁ -C ₄ -alkyl, C ₁ -C ₉ -alkyloxy, trifluoromethyl, trifluoromethoxy or C ₆ -C ₁₀ -aryl-C ₁ -C _4- No alkyloxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl, C ₃ -C ₈ -cycloalkyl or OC ₃ -C ₈ -cycloalkyl. In an alternative embodiment of the present invention that refers to the compound per - se , all of these compounds, when aryl, are C ₁ -C ₉ -alkyl, C ₁ -C ₉ -alkyloxy, halogen, and tree Fluoromethyl; C ₁ -C ₄ -alkyl or C ₆ -C ₁₀ -aryl when cycloalkyl; In the case of alkyl it may be substituted once or several times with hydroxyl groups, di-C ₁ -C ₄ alkylamino and fluoro.

In some further alternative embodiments of the invention that refer to the compound per - se , when m = 0, n = 0, Y is alkyl having 1 to 4 carbon atoms; Alkoxy having 1 to 4 carbon atoms; Alkylthio having 1 to 4 carbon atoms; Halogenoalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Halogenoalkoxy having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Or halogenoalkylthio having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Alkylenedioxy having 1 or 2 carbon atoms and having 1 to 4 identical or different halogen atoms; Halogensubstituted alkylenedioxy having 1 or 2 carbon atoms; Cyano; Nitro; Alkylcarbonyl having 2 to 4 carbon atoms; Carbalkoxy having 2 to 4 carbon atoms; Alkylsulphonyl having 1 to 4 carbon atoms; Arylsulphonyl having 6 or 10 aryl carbon atoms; Phenyl, naphthyl, phenoxy, naphthoxy, phenylthio or naphthylthio when R ¹ or R ⁵ is halogen; Alkyl having 1 to 4 carbon atoms; Alkoxy having 1 to 4 carbon atoms; Alkylthio having 1 to 4 carbon atoms; Or halogenoalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Or halogenoalkoxy having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Or halogenoalkylthio having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; And when one or more of the remaining R ¹ to R ⁵ represents hydrogen; Alkyl having 1 to 4 carbon atoms; Alkoxy having 1 to 4 carbon atoms; Alkylthio having 1 to 4 carbon atoms; Halogenoalkyl having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Halogenoalkoxy having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Or halogenoalkylthio having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms; Alkylenedioxy having 1 or 2 carbon atoms; Halogenated-substituted alkylenedioxy having 1 or 2 carbon atoms and having 1 to 5 identical or different halogen atoms; halogen; Cyano; Nitro; Amino; Mono- and dialkylamino having 1 to 4 carbon atoms per alkyl group; Alkylcarbonyl having 2 to 4 carbon atoms; Carbalkoxy having 2 to 4 carbon atoms; Alkylsulphonyl having 1 to 4 carbon atoms; Arylsulphonyl having 6 or 10 aryl carbon atoms; It does not represent phenyl substituted with phenyl, naphthyl, phenoxy, naphthoxy, phenylthio or naphthylthio.

In some further alternative embodiments of the invention that point to the compound per - se , when n is 0 and m is 0, at least one of the residues of the substituents of R ¹ to R ⁵ is halogen, in particular When the substituent is selected from F, Cl, Br, CH ₃ , OCH ₃ , NO ₂ , CN, and when the phenyl ring represents Y substituted with F, Cl, Br, CH ₃ , OCH ₃ , NO ₂ or CN, R ¹ or R ⁵ is not a substituent selected from halogen, in particular F, Cl, NO ₂ , CH ₃ , OCH ₃ or CF ₃ or CN.

In some further alternative embodiments of the invention that refer to the compound per - se (when R ¹ , R ² and R ⁵ are hydrogen or when R ¹ , R ⁴ and R ⁵ are hydrogen), When m = 1 and n = 0, Y is halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkyloxy, nitro, CF ₃ or OC ₁ -C ₄ -alkyl, SC ₁ -C _{4-alkyl, N (C 1 -C 4 -alkyl} ) by a _second one or more times may be substituted with one or phenyl optionally substituted several times with sequentially C ₁ -C ₆ - alkyl or C ₃ -C Does not represent ₉ -cycloalkyl.

The compound itself - points to the (per se) in which an alternative embodiment of the invention, R ¹ Or when R ⁵ is hydrogen and m = 1 and n = 0, Y is halogen, C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkyloxy, nitro, CF ₃ or OC ₁ -C _4- C ₁ -C ₆ -optionally substituted once or several times with phenyl which may be substituted once or several times by alkyl, SC ₁ -C ₄ -alkyl, N (C ₁ -C ₄ -alkyl) ₂ No alkyl or C ₃ -C ₉ -cycloalkyl.

In another aspect, the present invention also relates to the use of the drug action stage of the substance of formula (III)

(III),

(III),

It relates to the preparation of compounds for the inhibition of FAAH and for the treatment of disorders positively affected by the inhibition of fatty acid amide hydrolase (FAAH), in particular for the treatment of the above-mentioned medical instructions.

In still another aspect, the present invention also relates to a compound constituting the pharmacologic action of the substance of the general formula (III)

(III),

(III),

It is intended for the inhibition of FAAH and for the treatment of disorders positively affected by the inhibition of fatty acid amide hydrolase (FAAH), in particular for the treatment of the above-mentioned medical instructions.

To the extent that the specification is intended, a 'pharmacophore' is understood as a molecular sub-unit, or a structure or part of the molecule necessary for interacting with a FAAH enzyme. It is understood that the pharmacodynamic stage of the substance of formula (III) may be substituted more.

In another aspect, the present invention also relates to a process for the preparation of a compound represented by the formula (IV) according to any one of claims 1 to 17, and claims 24 to 79:

(IV)

(IV)

Wherein R ¹ to R ⁵ are each independently,

Hydrogen;

C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl-carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl Nyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol ), Number Group, a nitro, cyano, fluoro, chloro, bromo, search iodine, or CF ₃ with one or optionally substituted several times by the OCF _3;

CO ₂ H;

SO ₃ H;

Amino;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;

Disubstituted amino of formula (II)

(II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice among alkyl, fluoro or chloro);

CONH ₂ ;

SO ₂ NH ₂ ;

Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;

Thiols;

Hydroxyl group;

Nitro;

Cyano;

Fluorosulfonyl;

Halogen selected from fluoro, chloro, bromo or iodine;

CF _{3 ;}

OCF ₃ ; or

Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms include C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, Optionally substituted one or several times with cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ ;

And any two or more of the above R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

m is 0, 1, 2, 3, 4, 5 or 6;

Y is represented as (a), b), c)):

a) hydrogen;

b) C ₁ -C ₁₈ -alkyl, mono or polyunsaturated C ₂ -C ₁₈ -alkylene, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -allyloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C _6- C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - cycloalkenyl Kilmer captopril-carbonyl, C ₆ -C ₁₀ - aryl bots, captopril-carbonyl, C ₁ -C ₆ - Al Kilmer captopril Carboxy, C ₆ -C ₁₀ -allylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -aryl Sulfoxy, or up to 10 atoms, saturated, unsaturated, or aromatic heterocyclic ring systems, each of which is optional Once or several times substituted by a search for a (b1), b2), b3)):

b1) C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy , C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C _6- C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl carbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril Carbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy; Each of which is optionally C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ ; SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ with an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; Or substituted once or several times by OCF ₃ ;

Some of the substituents in b1) above may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

or

b2) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; or

Disubstituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₆ -, and NR ⁶ with R ⁶ selected from alkyl, methylene of formula (II) group is optionally C ₁ - May be substituted once or twice with C ₆ -alkyl, fluoro or chloro;

or

b3) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms, which include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH _{2 ;} SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ with an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted once or several times with CF ₃ or OCF ₃ ;

c) SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Thiols; Hydroxyl group; Nitro; Cyano; Fluorosulfonyl; Halogen selected from fluoro, chloro, bromo or iodine; CF _3; Or OCF ₃ ;

It is cyclized to form an oxadiazolone ring system.

Preferably the cyclization step for the oxadiazolone ring system can be carried out by phosgene, carbonyldiimidazole or a carbonic acid ester.

Suitable carbonic acid esters are especially C ₁ -C ₄ -alkyl carbonic acid esters.

Phosgene and carbonyldiimidazole are the most preferred reagents for obtaining cyclization.

In the formula (IV), preferably, R ¹ to R ⁵ are each independently,

Hydrogen;

Hydroxyl group;

C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl), amino, C ₁ -C ₄ -alkyl Optionally substituted one or several times with amino, di-C ₁ -C ₄ -alkylamino, hydroxy, fluoro, chloro, bromo, CF ₃ or OCF ₃ ;

Amino;

Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl;

Disubstituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₄ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₄ -alkyl, fluoro or chloro;

CONH ₂ ;

SO ₂ NH ₂ ;

CONH ₂ or SO ₂ NH ₂ with amino functional groups optionally substituted one or more times with residues selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;

Fluoro; Chloro; Bromo; CF _3; Or OCF ₃ .

Furthermore, in the above formula (IV), preferably one or more of R ¹ to R ⁵ is fluorine or chlorine. Most preferably R ¹ or R ⁵ is fluorine.

Further from the above formula (IV), preferably one or more of R ¹ to R ⁵ is hydroxy; C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, (C ₁ -C ₆ -alkyl Or CONH ₂ or SO ₂ NH ₂ ) having an amino functional group optionally substituted one or more times with a residue selected from C ₆ -C ₁₀ -aryl; Optionally substituted once or several times with amino, C ₁ -C ₄ -alkylamino, di-C ₁ -C ₄ -alkylamino, hydroxy, fluoro, chloro, bromo, CF ₃ or OCF ₃ .

More preferably, one of R ² , R ³ or R ⁴ is hydroxy; C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₄ -alkyl, C ₁ -C ₄ -alkoxy, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl); Optionally substituted once or several times with amino, C ₁ -C ₄ -alkylamino, di-C ₁ -C ₄ -alkylamino, hydroxy, fluoro, chloro, or bromo.

Further preferably in the above formula (IV), one or more of R ¹ to R ⁵ is amino; Amino substituted with one or more residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or di-substituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₄ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₄ -alkyl, fluoro or chloro).

More preferably, one of R ² , R ³ or R ⁴ is amino; Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; Or a disubstituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₄ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₄ -alkyl, fluoro or chloro).

Further preferably, in the formula (IV), n is 0; m is 0, 1, 2, 3, 4, 5 or 6; And Y represents C ₃ -C ₆ -cycloalkyl or C ₆ -C ₁₀ -aryl, each of which is optionally substituted one or several times by the following (a), b), c)):

a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkoxy,

(Each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl) Or SO ₂ NH ₂ ; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; Or OCF ₃ optionally substituted one or more times);

or

b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with these optional C ₁ -C ₆ -alkyl moieties capable of bonding to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)

(II)

(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₄ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₄ -alkyl, fluoro or chloro;

or

c) Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or several times by the following parentheses:

(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; optional once or twice with these optional C ₁ -C ₆ -alkyl moieties capable of bonding to form a 5 or 6 molecular ring CONH ₂ or SO ₂ NH ₂ substituted with: SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₁ -C ₆ - alkylsulfonyl, and C ₆ -C ₁₀ - aryl with one or more moieties selected from a sulfonyl substituted amino Thiol; hydroxyl group; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ ).

More preferably n is 0; m is 0 or 1; And Y is phenyl, naphthyl or pyridinyl ring system.

Even more preferably Y is C ₁ -C ₄ -alkyl; Phenyl; C ₁ -C ₄ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; CONH ₂ optionally substituted once or twice with this optional C ₁ -C ₄ -alkyl which may be bonded to form a 5 or 6 molecular ring Or SO ₂ NH ₂ ; Or once or several times with amino.

Even more preferably, m is 0 and Y is phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.

Most preferably, m is 0; Y is phenyl substituted in 4-position by fluoro, 4-position by chloro, 2- and 4-position by fluoro, 2- and 4-position by chloro, or 4-position by phenyl .

Particularly preferably in the above formula (IV), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro, bromo; One of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl.

Also preferably in the formula (IV), m is 0; n is 0; Phenyl substituted at the 4-position with Y fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, the 2- and 4-position with chloro and any one of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl.

Also preferably in the formula (IV) m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro, bromo; R ³ or R ³ and R ⁴ Is hydroxy.

Also preferably in the formula (IV) m is 0; n is 0; Phenyl substituted at the 4-position with Y fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, and the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ Is hydroxy.

Particularly preferably in the above formula (IV), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro, bromo; Any one of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; R ¹ is fluorine.

Particularly preferably in the above formula (IV), m is 0; n is 0; Phenyl substituted at the 4-position with Y fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, and the 2- and 4-position with chloro; Any one of R ² to R ⁴ is OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₄ -alkyl; R ¹ is fluorine.

Particularly preferably in the above formula (IV), m is 0; n is 0; Y is phenyl substituted once or twice with fluoro, chloro, bromo; R ³ or R ³ and R ⁴ A hydroxyl group; R ¹ is fluorine.

Particularly preferably in the above formula (IV), m is 0; n is 0; Phenyl substituted at the 4-position with Y fluoro, the 4-position with chloro, the 2- and 4-position with fluoro, and the 2- and 4-position with chloro; R ³ or R ³ and R ⁴ A hydroxyl group; R ¹ is fluorine.

In the following, the invention is illustrated by the following representative examples.

Example 1:

5- Phenoxy -(4-pyridin-3-yl) Phenyl -1,3,4- Oxadiazole -2 (3 H )-won

a) To an ice-cooled and stirred solution of (4-bromophenyl) hydrazine (3.13 g, 14 mmol) mixed with a mixture of NMP (20 mL) and pyridine (6.87 g, 87 mmol) phenyl dropwise under argon Phenyl carbonochloridate (2.412 g, 15.41 mmol) was added. The reaction was stirred at 0 ° C. for 30 minutes, then allowed to heat to room temperature and stirred for 1 hour. The reaction mixture was diluted in water and extracted with EtOAc. The organic phase was washed with water and brine respectively. After drying over MgSO _{4 it} was filtered and evaporated to yield 5.5 g of phenyl-2- (4-bromophenyl) hydrazine carboxylate, a yellow oil crystallized on standing.

b) A toluene solution (22.6 mL, 43 mmol) in which 20% of phosgene was dissolved was added dropwise to an ice cooled mixture of the intermediate (5.5 g) and pyridine (7.37 g, 83 mmol). The reaction mixture was stirred for 30 minutes in a cold state and then for one hour at room temperature. Argon was then passed through the reaction mixture in the form of a bubble and diluted with water at 0 ° C. The two phases were separated and the organic phase was washed with 2N HCl solution, water and brine respectively. The organic phase was stirred for 30 minutes with charcoal and then filtered through a short silica pad. After evaporation of the solvent, the crude is recrystallized from the DCM / IPA mixture to give 3- (4-bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 ( 3H ) -source as a white solid. 1.938 g was calculated. (Yield of two steps: 32.5%)

c) 3- (4-bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one (0.6 g) in dimethoxy ethane (20 mL) and water (3 mL) , 1.8 mmol) was dissolved and pyridine-3-ylboronic acid (0.31 g, 2.52 mmol) and potassium carbonate (0.647 g, 4.68 mmol) were added to the stirred solution. Once the solution was obtained, Pd (PPh ₃ ) ₄ (0.104 g, 0.09 mmol) was added and the mixture was heated at 85 ° C. for 3 hours and then allowed to cool to room temperature. The solvent was removed under reduced pressure and the residue was separated between 20% iPrOH-DCM and water. The mixture was filtered to help separate the layers, the organic phase was washed with water and brine, dried over MgSO ₄ and filtered over activated carbon. After stirring for 10 minutes, the mixture was filtered through a short silica gel / celite plug, and the filtrate was evaporated to leave the green oil solidified on the standing. Recrystallization from ethanol is 5-phenoxy-3- (4-pyridin-3-yl) phenyl-1,3,4-oxadia which is a greenish system powder (0.165 g, 27.7%) with a melting point of 146-147 ° C. Gave a pawn.

Example 2:

5- ( Benzyloxy ) -3- (3- Bromophenyl ) -1,3,4- Oxadiazole -2 (3 H )-won

(5- (Benzyloxy) -3- (3-bromophenyl) -1,3,4-oxadiazol-2 (3 H ) -one)

a) To an ice cooled and stirred solution of pyridine (8.85 g, 112 mmol) and (3-bromophenyl) hydrazine hydrochloride (5.00 g, 22.37 mmol) mixed in NMP (40 mL) benzylchloroformate ( 8.40 g, 24.61 mmol) in 50% dissolved toluene solution was added dropwise. The reaction was stirred at 0 ° C. for 30 minutes, then allowed to heat to room temperature and stirred for 1 hour. The reaction mixture was poured into ice-water; The precipitate was filtered off, washed with water, MgSO ₄ Over EtOAc. Evaporation of the solvent yielded 6.77 g of benzyl-2- (3-bromophenyl) hydrazine carboxylate as a yellow solid. (Yield 94%)

b) An ice-cooled mixture of benzyl-2- (3-bromophenyl) hydrazinecarboxylate (6.77 g) and pyridine (8.57 g, mL, 110 mmol) is a toluene solution (26.6) dissolved in 20% phosgene. mL, 50.6 mmol) was added dropwise. The reaction mixture was stirred for 30 minutes in cold state and then for 1 hour at room temperature. Argon was then bubbled through the reaction mixture and diluted with 0 ° C water. The two phases were separated and the organic phase was washed with 2N HCl solution, water and brine, respectively. The organic phase was stirred with charcoal for 30 minutes. Then filtered with a short silica gel. After evaporation of the solvent, the crude product is recrystallized from ethanol to give a light brown solid 5-benzyloxy-3- (3-bromophenyl) -1,3,4-oxadia having a melting point of 89-90 ° C. The sol-2 ( 3H ) -one (4.76 g) was calculated. (Yield: 65%)

Example 3:

5- (2- Bromopyridine -3- Iloxy ) -3- (4- Methoxyphenyl ) -1,3,4- Oxadiazole -2 (3 H )-won

(5- (2-bromopyridin-3-yloxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazol-2 (3 H ) -one)

a) 2-bromopyridin-3 in an ice-cooled solution of phosgene (52.6 mL, 100 mmol) (20% dissolved in toluene) mixed in DCM (25 mL) -ol) (3.48 g, 20 mmol) and a mixture of pyridine (2.108 g, 26.7 mmol) mixed in DCM (50 mL) were added in portions under nitrogen for 1 hour. The reaction was heated to room temperature and stirred for an additional 2 hours, and then nitrogen passed through the reaction mixture in the form of foam for 30 minutes. It was evaporated to dry in vacuo, azeotroped with 100 mL of toluene under vacuum and evaporated to dry. 2-Bromopyridin-3-yl carbonochloridate is produced in the form of a gray hygroscopic powder. (6.59 g, 93%)

b) 2-bromopyridine-3 in an ice-cooled and stirred solution of pyridine (3.95 g, 50 mmol) mixed with (4-methoxyphenyl) hydrazine hydrochloride (1.746 g, 10.0 mmol) and NMP (15 mL) -Dyl bromide (2-Bromopyridin-3-yl carbonochloridate) (4.23 g, 12.0 mmol) was added in portions under nitrogen. The reaction was stirred at 0 ° C. for 30 minutes, then heated until reaching room temperature and stirred for 1 hour. The reaction mixture was poured into ice water; The mixture was extracted with EtOAc and dried over MgSO ₄ . After evaporation of the solvent, the yellow oil was obtained as a mixture purified by chromatography column with petroleumether: EtOAc = 2: 1, resulting in a white solid, 2-bromopyridine-3-. 1.09 g of il-2- (4-methoxyphenyl) hydrazine carboxylate was calculated. (Yield: 32.2%)

c) bromopyridin-3-yl 2- (4-methoxyphenyl) hydrazinecarboxylate (1.071 g, 3.17 mmol) (2-bromopyridin-3-yl 2- (4-methoxyphenyl) hydrazinecarboxylate) and pyridine (1.303 g) , 16.47 mmol) toluene solution (4.0 mL, 7.6 mmol) in which 20% of phosgene was dissolved was added dropwise. The reaction mixture was stirred for 30 minutes in cold state and then at room temperature for 1.5 hours. Nitrogen is then passed through the reaction mixture in the form of a bubble and diluted with water at 0 ° C. The two phases were separated and the aqueous phase was extracted with DCM. The combined organic phases were dried over MgSO ₄ and filtered. Heterogeneous 5- (2-bromopyridin-3-yloxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 ( 3H )-after evaporation Circle (5- (2-bromopyridin-3-yloxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazol-2 ( 3H ) -one) is petroleum ether: EtOAc = 2: 1 (petroleumether: Purification by chromatography column with EtOAc = 2: 1). (Yield 75 mg light brown flour 6.50%); mp 116.5-117.5 ° C

Example 4:

5- (4- Bromo -2- Methoxyphenoxy ) -3- Phenyl -1,3,4,- Oxadiazole -2 (3 H )-won

(5- (4-Bromo-2-methoxyphenoxy) -3-phenyl-1,3,4-oxadiazol-2 (3 H ) -one)

a) N, N-dimethylaniline (N, N- in an ice-cooled and stirred solution of 4-bromo-2-methoxyphenol (4.06 g, 20 mmol) and phosgene (11.58 mL, 22.00 mmol) A solution of toluene (9 mL) dissolved in dimethylaniline) (2.424 g, 20.00 mmol) was added dropwise. The reaction was stirred at room temperature for 3 hours. Nitrogen was then passed through the reaction mixture in the form of bubbles for 30 minutes; And quench on ice. The organic phase was washed with 1 N HCl solution and water, respectively. After drying in MgSO ₄ , toluene was removed under vacuum and 4-bromo-2-methoxyphenyl carbonochloridate was obtained as an oil. Yield: 4.10 g, 77%.

b) 4-bromo-2-methoxyphenyl chloride (4) in a solution of phenylhydrazine (1.081 g, 10.0 mmol) and pyridine (3.95 g, 50 mmol) mixed with NMP (15 mL) by ice cooling -bromo-2-methoxyphenyl carbonochloridate) (3.19 g, 12.0 mmol) was added in portions. The reaction was stirred at room temperature for 1 hour. Then it was poured into an ice-1N HCl mixture; The precipitate was filtered off, washed with water and dried under vacuum. 4-4-Bromo-2-methoxyphenyl 2-phenylhydrazinecarboxylate was obtained as a white powder ground with petroleum ether. Yield: 3.38 g.

c) Toluene solution in which 20% of phosgene is dissolved in an ice-cooled mixture of 4-bromo-2-methoxyphenyl 2-phenylhydrazinecarboxylate (3.20 g, 9.49 mmol) and pyridine (3.90 g, 49.4 mmol). (11.98 mL, 22.78 mmol) was added dropwise. The reaction mixture was stirred for 15 minutes in the cold and then for 45 minutes at room temperature. Nitrogen was then passed through the mixture in the form of a foam and diluted with water at 0 ° C. The two phases were separated and the organic phase was washed with 1N HCl and water, respectively. After drying with MgSO ₄ the solvent was removed in vacuo. 5- (4-Bromo-2-methoxyphenoxy) -3-phenyl-1,3,4-oxadiazole-2 ( 3H ) -one (5- (4-Bromo-2-methoxyphenoxy)- 3-phenyl-1,3,4-oxadiazol-2 ( 3H ) -one) was purified by column chromatography in a mixture of petroleum ether: EtOAc = 10: 1 ratio. Yield: 1.198 g white powder 34.8%, mp 77-78 ° C.

Example 5:

5- (4- Chlorophenoxy ) -3- (4-he Doxyphenyl ) -1,3,4- Oxadiazole -2 (3H) -one

(5- (4-chlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazol-2 (3H) -one)

a) Pyridine in a stirred solution of 4-methoxyphenylhydrazine hydrochloride (6 g, 34.4 mmol) mixed with N-methyl-2-pyrrolidinone (48 mL) (N-methyl-2-pyrrolidinone) at room temperature. 13.89 mL, 172 mmol) was added dropwise, and the resulting solution was cooled at 0 ° C. This was then added dropwise to 4-chlorophenyl carbonate (5.29 mL, 37.8 mmol). The resulting solution was stirred at 0 ° C. for 30 minutes and then heated until reaching room temperature and stirred for 1 hour. The reaction mixture was poured into ice / water and stirred for 1 hour. The precipitate was filtered off, washed with water and dried. Recrystallization from isopropanol yielded 4-chlorophenyl 2- (4-methoxyphenyl) hydrazinecarboxylate (5.74 g, 57%) as a white solid.

b) pyridine (8.25 mL, 102 mmol) in a stirred solution of 4-chlorophenyl 2- (4-methoxyphenyl) -hydrazinecarboxylate (5.74 g, 19.61 mmol) dissolved in dichloromethane (150 mL) at room temperature Was added and the resulting solution was cooled to 0 ° C. Then a toluene solution in which 20% of phosgene was dissolved (24.76 mL, 47.1 mmol) was added dropwise. The mixture was stirred at 0 ° C. for 30 minutes and then heated until reaching room temperature and stirred for 1 hour. Nitrogen was bubbled through the mixture for 30 minutes and then cooled to 0 ° C. and diluted with water. The phases were separated and the organic phase was washed with 2N hydrochloric acid, water, brine respectively, then dried over MgSO ₄ and filtered over activated carbon. After stirring for 15 minutes the suspension was filtered through a short pad of silica and celite. The filtrate was evaporated and the resulting yellow solid crystallized twice from isopropanol to give a white solid of 5- (4-chlorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole -2 (3H) -one (5- (4-chlorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazol-2 (3H) -one) (3.14 g, 50%) was calculated.

c) 5- (4-chlorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one dissolved in dichloromethane (30 mL) under nitrogen. A stirred solution of 3.14 g, 9.85 mmol) was cooled to -80 ° C (suspension) and boron tribromide (1.863 mL, 19.70 mmol) was added dropwise. The resulting bright pink solution was stirred at −80 ° C. for 5 minutes, heated until reaching room temperature and stirred for 2 hours. The reaction mixture was cooled to 0 ° C. and ice / water added carefully. The resulting precipitate was filtered off, washed with water and dried. 5- (4-chlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H), which is recrystallized from isopropanol and has a melting point of 163.5-164.5 ° C. as a white solid. -Won (2.2 g, 73%) was calculated.

Example 6:

3- (3- Aminophenyl ) -5- (2,4- Difluorophenoxy ) -1,3,4- Oxadiazole -2 (3H) -one

(3- (3-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazol-2 (3H) -one)

a) Pyridine (2.13 mL, 26.4 mmol) is added dropwise to a stirred solution of 3-nitrophenylhydrazine hydrochloride (1 g, 5.27 mmol) in N-methyl-2-pyrrolidinone (8 mL) at room temperature It became. The mixture was cooled to 0 ° C and 2,4-difluorophenyl carbonate (1.22 g, 6.33 mmol) was added dropwise. The resulting mixture was stirred at 0 ° C. for 30 minutes and then at room temperature for 1 hour and then poured into ice / water. The mixture was extracted with ethyl acetate and the organic extract was washed with 2N hydrochloric acid, water, brine respectively and then dried over MgSO ₄ , filtered and evaporated to 2,4 as yellow oil (1.6 g, 100%). -Difluorophenyl 2- (3-nitrophenyl) hydrazinecarboxylate was calculated.

b) Pyridine (2.312 mL, 28.6 mmol) in a solution of 2,4-difluorophenyl 2- (3-nitrophenyl) hydrazinecarboxylate (1.7 g, 5.50 mmol) dissolved in dichloromethane (30 mL) at room temperature. It was added dropwise and the solution was cooled to 0 ° C. A toluene solution containing 20% of phosgene (6.94 mL, 13.19 mmol) was added dropwise. The resulting pink suspension was stirred at 0 ° C. for 30 minutes and then heated until reaching room temperature and stirred for 1 hour. Nitrogen passed through the mixture in the form of foam for 30 minutes, which was cooled to 0 ° C. and diluted with water. The phases were separated and the organic phase was washed with 2N hydrochloric acid, water and brine respectively, then dried over MgSO ₄ , filtered and evaporated. The resulting yellow oil was purified by chromatography (petroleum ether / ethyl acetate, 6/1 to 4/1). A small amount of pure product was collected and evaporated to yield a solidified pink oil in a fixed state. It is crystallized from heptane and diethyl ether to give a white solid of 5- (2,4-difluorophenoxy) -3- (3-nitrophenyl) -1,3,4-oxadiazole-2 (3H)- Raw (260 mg, 14%) was calculated.

c) 5- (2,4-difluorophenoxy) -3- (3-nitrophenyl) -1,3,4-oxadiazole-2 dissolved in methanol (20 mL) at room temperature under nitrogen. To a stirred suspension of 3H) -one (251 mg, 0.749 mmol) was added to carbon (25 mg) with 10% palladium. Hydrogen gas was then passed through the reaction mixture in the form of a bubble for 1 hour. The reaction mixture was filtered through a short pad of celite and the precipitate was evaporated. The resulting yellow solid was purified by chromatography column (petroleum ether / ethyl acetate 6/1 to 4/1). The homogeneous portion was collected and evaporated and crystallized from isopropanol to yield the resulting light yellow solid, which was (3-aminophenyl) -5- (2,4-difluorophenoxy, a light yellow solid with a melting point of 122-123 ° C. C) -1,3,4-oxadiazole-2 (3H) -one (128 mg, 56%).

Example 7:

3- (4- (1H-pyrrol-1-yl) Phenyl ) -5- (2,4- Difluorophenoxy ) -1,3,4- Oxadiazole -2 (3H) -one

(3- (4- (1H-pyrrol-1-yl) phenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazol-2 (3H) -one)

3- (4-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one (203 mg, 0.665 mmol) with acetic acid (10 mL 2,5-dimethoxytetrahydrofuran (0.108 mL, 0.832 mmol) dissolved in) was heated to 95 ° C for 1 hour to give a dark red solution. The mixture was cooled to room temperature and the solvent evaporated. Toluene was added to the residue and re-evaporated. The residue was triturated with boiling ethanol, filtered while hot and washed with ethanol. After drying, 3- (4- (1H-pyrrol-1-yl) phenyl) -5- (2,4-difluorophenoxy) -1,3 having a melting point of 181-182 ° C. as a reddish brown solid 4-oxadiazole-2 (3H) -one (109 mg, 46%) (3- (4- (1H-pyrrol-1-yl) phenyl) -5- (2,4-difluorophenoxy) -1,3 , 4-oxadiazol-2 (3H) -one) was obtained.

Example 8:

3- (3'- Methoxybiphenyl -4-yl) -5- Phenoxy -1,3,4- Oxadiazole -2 (3H) -one

(3- (3'-methoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazol-2 (3H) -one)

3- (4-bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -source (526 mg) dissolved in dimethoxyethane (20 mL) and water (10 mL) under nitrogen. , 1.58 mmol), 3-methoxyphenylboronic acid (336 mg, 2.21 mmol) and potassium carbonate (567 mg, 4.10 mmol) in a stirred suspension of tetrakis (triphenylphosphine) palladium (0) triphenylphosphine) -palladium (0)) (91 mg, 0.079 mmol) was added. The resulting mixture was stirred at 85 ° C. for 3 hours and then cooled to room temperature. The solvent was evaporated and the residue was partitioned between layers of dichloromethane and water. The organic phase was separated, washed with water and brine, then dried over MgSO ₄ and filtered over activated carbon. After stirring for 10 minutes, the suspension was filtered through a short silica gel / celite pad and the precipitate was evaporated to leave a solidified oil on the standing. 3- (3'-methoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (white crystal due to recrystallization from dichloromethane / ethanol and melting point 102-103 ° C. 3H) -one (182 mg, 32%) was given.

Example 9:

5- (2,4- Difluorophenoxy ) -3- (4-he Doxyphenyl ) -1,3,4- Oxadiazole -2 (3H) -one

(5- (2,4-difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazol-2 (3H) -one)

a) Pyridine (13.89 mL, 172) in a stirred solution of 4-methoxyphenylhydrazine hydrochloride (6 g, 34.4 mmol) dissolved in N-methyl-2-pyrrolidinone at room temperature mmol) was added dropwise and the resulting solution was cooled to 0 ° C. Then 2,4-difluorophenyl carbononochlorate (7.94 g, 41.2 mmol) was added dropwise. The solution was stirred at 0 ° C. for 30 minutes and then heated to room temperature and stirred for 2 hours. The reaction mixture was poured into ice / water and stirred for 1 hour. The mixture was extracted with ethyl acetate and the organic extract was washed with 2N hydrochloric acid, water and brine respectively and then dried over MgSO ₄ and filtered over activated carbon. It was then stirred for 15 minutes and the suspension was filtered through a short pad of silica gel / felite. The filtrate was evaporated and the resulting yellow oil crystallized from isopropanol to yield 2,4-difluorophenyl 2- (4-methoxyphenyl) hydrazinecarboxylate (3.82 g, 38%) as a white solid.

b) pyridine (5.46 mL, in a stirred solution of 2,4-difluorophenyl 2- (4-methoxyphenyl) hydrazinecarboxylate (3.82 g, 12.98 mmol) dissolved in dichloromethane (120 mL) at room temperature 67.5 mmol) was added dropwise and the resulting solution was cooled to 0 ° C. It was then added dropwise to a toluene solution in which 20% of phosgene (16.39 mL, 31.2 mmol) was dissolved. The resulting orange solution was stirred at 0 ° C. for 30 minutes, then heated to room temperature and stirred for 1 hour. Nitrogen passed through the mixture in the form of foam for 30 minutes and diluted with water. The phases were separated and the organic phase was washed with 2N hydrochloric acid, water and brine respectively and then dried over MgSO ₄ and filtered over activated carbon. After stirring for 30 minutes, the suspension was filtered through a short pad of silica gel / celite. The filtrate was evaporated and the resulting light yellow solid crystallized from isopropanol to give a white solid of 5- (2,4-difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxa Calculate Diazol-2 (3H) -one (1.77 g, 43%).

c) 5- (2,4-difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H dissolved in dichloromethane (5 mL) under nitrogen. The stirred solution of) -source (241 mg, 0.753 mmol) was cooled to -80 ° C, after which boron tribromide (0.142 mL, 1.505 mmol) was added dropwise. The solution was stirred at −80 ° C. for 5 minutes and then heated until reaching room temperature and stirred for 1 hour. The reaction mixture was then cooled to 0 ° C. and carefully quenched by the addition of water. The mixture was extracted with 30% isopropanol and the combined organic layers were washed with water and brine, then dried over MgSO ₄ , filtered and evaporated. What was produced as a white solid was crystallized from isopropanol and melted as a white solid at 174.5-176 ° C. 5- (2,4-difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4- Oxadiazole-2 (3H) -one (158 mg, 69%) was calculated.

Example 10:

5- (4- Chlorophenoxy ) 3- (2- Fluoro -4- Doxyphenyl ) -1,3,4- Oxadiazole -2 (3H) -one

5- (4-chlorophenoxy) -3- (2-fluoro-4-hydroxyphenyl) -1,3,4-oxadiazol-2 (3H) -one

a) Potassium carbonate (15.40 g, 111 mmol) was added in portions to a stirred solution of 3-fluoro-4-nitrophenol (5 g, 31.8 mmol) dissolved in acetone (100 mL) at room temperature, followed by dimethyl sulfonate. Dimethyl sulphate (6.04 mL, 63.7 mmol) was added dropwise. The resulting yellow suspension was stirred for 2 hours at reflux. The reaction mixture was then cooled to room temperature, filtered and the filtrate was evaporated. The resulting yellow liquid was purified by chromatography column (petroleum ether / ethyl acetate, 9/1). The homogeneous portion was collected and evaporated and the resulting yellow oil was crystallized from diethyl ether / petroleum ether to give 2-fluoro-4-methoxy-1-nitrobenzene as light yellow crystals (2.81 g, 52%). .

b) To a stirred solution of 2-fluoro-4-methoxy-1-nitrobenzene (2.76 g, 16.13 mmol) dissolved in methanol (50 mL) at room temperature under nitrogen was added 10% palladium on carbon (276 mg). Added. Hydrogen gas passed through the reaction mixture for 1 hour in the form of a bubble, after which the suspension was filtered through a short pad of celite. The filtrate was evaporated and the resulting red oil solidified with petroleum ether. The resulting orange solid was filtered and dried to give 2-fluoro-4-methoxyaniline (2.2 g, 97%).

c) A stirred solution of 2-fluoro-4-methoxyaniline (2.13 g, 15.09 mmol) dissolved in hydrochloric acid concentrated at -10 ° C (13.97 mL) was dissolved in water (6.96 mL) at -10 ° C. Sodium nitrite (1.121 g, 16.25 mmol) was added dropwise while maintaining the temperature below -10 ° C. The resulting mixture was stirred at -10 ° C for 1 hour. Thereafter, a tin (II) chloride dihydrate solution dissolved in concentrated hydrochloric acid (11.61 mL) was added dropwise while maintaining the temperature below -5 占 폚. The resulting mixture was stirred at −5 ° C. for 1 hour and then heated until it reached room temperature. The light brown suspension was filtered, the filtercake was dissolved in water and the resulting solution was made into a substrate by the addition of 3N aqueous sodium hydroxide solution. The mixture was then extracted with dichloromethane and combined with the extract washed with water and brine and then dried over MgSO ₄ , filtered and evaporated. The resulting dark red-brown solid was crystallized from diethyl ether / petroleum ether to yield the dark pink solid (2-fluoro-4-methoxyphenyl) hydrazine (1.24 g, 53%).

d) pyridine (3.16 mL, in a stirred solution of (2-fluoro-4-methoxyphenyl) hydrazine (1.22 g, 7.81 mmol) dissolved in N-methyl-2-pyrrolidinone (10 mL) at room temperature 39.1 mmol) was added dropwise and the resulting solution was cooled to 0 ° C. Then 4-chlorophenyl carbonate (1.640 mL, 11.72 mmol) was added dropwise. The solution was then stirred at 0 ° C. for 30 minutes and then heated until reaching room temperature and stirred for 1 hour. The reaction mixture was poured into ice / water and stirred for 1 hour. The precipitate was filtered, washed with water and dried to yield 4-chlorophenyl 2- (2-fluoro-4-methoxyphenyl) hydrazinecarboxylate (2.5 g, 100%) as a light brown solid.

e) pyridine (3.38 mL) in a stirred solution of 4-chlorophenyl 2- (2-fluoro-4-methoxyphenyl) hydrazinecarboxylate (2.5 g, 8.05 mmol) dissolved in dichloromethane (40 mL) at room temperature 41.8 mmol) was added dropwise and the resulting solution was cooled to 0 ° C. Then toluene (10.16 mL, 19.31 mmol) in which 20% of phosgene was dissolved was added dropwise. The resulting red suspension was stirred at 0 ° C. for 30 minutes and then heated until reaching room temperature and stirred for 1 hour. Nitrogen was bubbled through the mixture before being cooled to 0 ° C. and diluted with water. The phases were separated and the organic phase was washed with 2N hydrochloric acid, water and brine. The organic layer was dried over MgSO ₄ , filtered over activated carbon and stirred for 30 minutes. The suspension was filtered through a short pad of silica gel and celite. The filtrate was evaporated and the resulting yellow solid crystallized twice from isopropanol to give a light pale brown solid, 5- (4-chlorophenoxy) -3- (2-fluoro-4-methoxyphenyl) -1,3, To yield 4-oxadiazole-2 (3H) -one (1.2 g, 44%).

f) 5- (4-chlorophenoxy) -3- (2-fluoro-4-methoxyphenyl) -1,3,4-oxadiazole-2 dissolved in dichloromethane (40 mL) under nitrogen. The stirred solution of 3H) -one (1.2 g, 3.56 mmol) was cooled to -80 ° C and boron tribromide (0.674 mL, 7.13 mmol) was added dropwise. The solution was stirred at −80 ° C. for 5 minutes, then heated until reaching room temperature and stirred for 5 hours. The reaction mixture was then cooled to 0 ° C. and carefully quenched by the addition of water. A mixture of dichloromethane with 30% isopropanol dissolved was added and the phases separated. The aqueous phase was extracted with dichloromethane and the combined extracts were washed with water and brine. The organic layer was dried over MgSO ₄ , filtered and evaporated. The resulting green solid was dissolved in hot isopropanol and the insoluble material was filtered off. The filtrate was evaporated and the residue crystallized from dichloromethane / petroleum ether to yield a dark pink solid. This solid was dissolved in dichloromethane and added activated carbon. After stirring for 15 minutes the suspension was filtered through a short pad of silica gel and celite. The filtrate was evaporated to low volume and PE added. The resulting solid was filtered, washed with petroleum ether and dried to give 5- (4-chlorophenoxy) -3- (2-fluoro-4-hydroxyphenyl as a grayish white solid with a melting point of 180-182 ° C. ) -1,3,4-oxadiazole-2 (3H) -one (379 mg, 33%) was calculated.

Example 11:

3- (4-amino-3- Methoxyphenyl ) -5- (2,4- Difluorophenoxy ) -1,3,4- Oxadiazole -2 (3H) -membered hydrochloride

a) of 5-fluoro-2-nitrophenol (10 g, 63.7 mmol) and potassium carbonate (17.59 g, 127 mmol) in which methyl iodide (11.94 mL, 191 mmol) is dissolved in acetone (318 mL) at room temperature It was added dropwise to the stirred suspension. The reaction mixture was stirred at room temperature for 4 days, after which the acetone was evaporated under reduced pressure and the residue was left in a separate layer between water and ethyl acetate. The aqueous layer was neutralized with concentrated hydrochloric acid. The organic layer was separated, washed with water and brine, dried over MgSO ₄ , filtered and evaporated to yield a greyish white solid that was recrystallized from isopropanol / dichloromethane and the greyish white solid was 4-fluoro-. 2-methoxy-1-nitrobenzene (9.6 g, 88%).

b) Dropwise in a stirred solution of 4-fluoro-2-methoxy-1-nitrobenzene (7 g, 40.9 mmol) in which hydrazine hydrate (5.96 mL, 123 mmol) was dissolved in ethanol (84 mL) at room temperature. Was added. The solution turned yellow and then bright orange. The reaction mixture was stirred at 100 ° C for 2 hours and then cooled to 0 ° C. The yellow precipitate was separated by filtration and washed with cold ethanol. The mother liquor was evaporated to half the total volume, then cooled to 0 ° C. and more precipitate formed. The precipitate was collected and washed with cold ethanol. The precipitate combined to yield (3-methoxy-4-nitrophenyl) hydrazine (4.18 g, 56%).

c) 2,4-difluorophenyl carbonate (4.63 g, 24.02 mmol) was dissolved (3-methoxy-4-nitrophenyl) hydrazine (4 g, 21.84 mmol) dissolved in NMP (40 mL) at 0 ° C. To the stirred solution of and pyridine (8.83 mL, 109 mmol) was added dropwise. The reaction mixture was stirred at 0 ° C. for 15 minutes and at room temperature for 45 minutes. The solution was then poured into a mixture of ice / 1N hydrochloric acid solution. The product was extracted with ethyl acetate and then with dichloromethane / isopropanol. The combined organic layer was washed with brine and dried over MgSO ₄ , filtered and evaporated to yield an orange oil. Orange, oil / solid 2,4-difluorophenyl 2- (3-methoxy-4-nitrophenyl) using column chromatography (silica, petroleum ether / ethyl acetate 2: 1 then 1: 1) ) Hydrazine carboxylate (5.84 g, 79%) was calculated.

d) 2,4-difluorophenyl 2- (3-methoxy-) dissolved in dichloromethane (115 mL) at 0 ° C. in a toluene solution (21.74 mL, 41.3 mmol) in which 20% of phosgene was dissolved. To the solution of 4-nitrophenyl) hydrazinecarboxylate (5.84 g, 17.21 mmol) and pyridine (7.24 mL, 90 mmol) was added dropwise. The solution turned dark red and stirred at 0 ° C. for 15 minutes and then at room temperature for 45 minutes. Air was bubbled through the solution for 10 minutes and then water was added at 0 ° C. The organic layer was separated and washed with 1 N hydrochloric acid, water and brine respectively, then dried over MgSO ₄ , filtered and evaporated to yield a dark red oil. Column chromatography (petroleum ether / dichloromethane 2: 1 then 1: 1) recrystallized from isopropanol / dichloromethane to yield a yellow solid, which was 5- (2,4-difluorophenoxy) -3- (3-methoxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one (722 mg, 11.5%).

e) 5- (2,4-difluorophenoxy) -3- (3-methoxy-4-nitrophenyl) dissolved in methanol (15 mL) at room temperature in 10% palladium on carbon (18.5 mg) A stirred solution of) -1,3,4-oxadiazole-2 (3H) -one (200 mg, 0.548 mmol) was added. The reaction mixture was stirred for 3 hours under an atmosphere of hydrogen gas at room temperature. Furthermore 10% palladium on charcoal catalyst (9 mg) was added and the reaction mixture was stirred for an additional 2 hours under hydrogen at room temperature. The solution was then filtered through a short celite pad and the celite was washed with ethyl acetate. The filtrate was evaporated and recrystallized from isopropanol to yield a brown solid, to yield a light brown solid (124 mg). Before 2N hydrogen chloride dissolved in ether (2 mL) was added dropwise, it absorbed ethyl acetate (5 mL) and cooled to 0 ° C. The precipitate formed was filtered, washed with ethyl acetate and dried to give 3- (4-amino-3-methoxyphenyl) -5- (2,4-difluorophenoxy, 186-188 ° C., a light brown solid. C) -1,3,4-oxadiazole-2 (3H) -source hydrochloride (120 mg, 90%) was calculated.

Example 12:

3- (4-amino-3- (2- Methoxyethoxy ) Phenyl ) -5- (2,4- Difluorophenoxy ) -1,3,4- Oxadiazole 2 (3H) -one

a) Sodium iodide (0.191 g, 1.273 mmol) is 5-fluoro-2-nitrophenol (4 g, 25.5 mmol) dissolved in DMF (102 mL) at room temperature, potassium carbonate (10.56 g, 76 mmol) and 1 -Chloro-2-methoxyethane (5.10 mL, 56.0 mmol) was added to a stirred suspension. The reaction mixture was stirred overnight at 80 ° C. Further 1-chloro-2-methoxyethane (6.38 mL, 70.0 mmol) was added and the reaction mixture was stirred at 80 ° C. for 4 hours. Water and ethyl acetate were added and the organic layer was separated. The aqueous layer was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The combined organic layer was washed with water, dried over MgSO ₄ , filtered and evaporated to yield a yellow oil. Column chromatography (petroleum ether / ethyl acetate 6: 1) yielded a clean oil, 4-fluoro-2- (2-methoxyethoxy) -1-nitrobenzene (2.26 g, 39%).

b) of 4-fluoro-2- (2-methoxyethoxy) -1-nitrobenzene (2.26 g, 10.50 mmol) in which hydrazine hydrate (1.531 mL, 31.5 mmol) was dissolved in ethanol (21.43 mL) at room temperature. It was added to the stirred solution. The reaction mixture was stirred at 85 ° C. for 3 hours. The solution was then cooled to 0 ° C. to form a precipitate. The solid was separated by filtration and washed with cold ethanol. Mother liquors were evaporated to half the original volume and cooled to 0 ° C. The precipitate formed was separated by filtration and washed with cold ethanol. The combined precipitate (3- (2-methoxyethoxy) -4-nitrophenyl) hydrazine (1.75 g, 73%) is used in the next step without further purification.

c) 2,4-difluorophenyl carbonate (1.631 g, 8.47 mmol) was dissolved in NMP (14 mL) at 0 ° C. (3- (2-methoxyethoxy) -4-nitrophenyl) hydrazine ( 1.75 g, 7.70 mmol) and pyridine (3.11 mL, 38.5 mmol) were added dropwise to a stirred solution. The reaction mixture was stirred at 0 ° C. for 20 minutes and then at room temperature for 1 hour. The solution was poured into 1N hydrochloric acid / ice mixture. After stirring for 30 minutes, ethyl acetate was added and the organic layer was separated and washed with 1N hydrochloric acid, water and brine. The organic layer was then dried over MgSO ₄ and evaporated to leave an orange oil. Column chromatography (petroleum ether / ethyl acetate 2: 1 then 1: 1 then 1: 2) was used to yield an orange oil. The oil was dissolved in ethyl acetate and washed with water. The organic layer was dried over MgSO ₄ , filtered and evaporated to orange foam 2,4-difluorophenyl 2- (3- (2-methoxyethoxy) -4-nitrophenyl) hydrazinecarboxylate (1.54 g, 52 %).

d) 2,4-difluorophenyl 2- (3- (2-meth) dissolved in dichloromethane (27 mL) at 0 ° C. in a 20% toluene solution dissolved in phosgene (5.07 mL, 9.64 mmol). A stirred solution of oxyethoxy) -4-nitrophenyl) hydrazinecarboxylate (1.54 g, 4.02 mmol) and pyridine (1.690 mL, 20.89 mmol) was added dropwise. The dark red solution was stirred at 0 ° C. for 15 minutes and at room temperature for 1 hour. Water was added at 0 ° C. and the organic layer was separated and washed with 1N hydrochloric acid, water and brine, respectively. The organic layer was dried over MgSO ₄ , filtered and evaporated to leave a red oil. Column chromatography (petroleum ether / ethyl acetate 6: 1 then 4: 1) was used to yield a recrystallized brown solid from isopropanol / dichloromethane, which was a light brown solid, 5- (2,4-difluoro Phenoxy) -3- (3- (2-methoxyethoxy) -4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one (539 mg, 33%).

e) 10% palladium in charcoal (35 mg) was dissolved in methanol (18 mL) at room temperature in 5- (2,4-difluorophenoxy) -3- (3- (2-methoxyethoxy) To a stirred solution of -4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one (267 mg, 0.652 mmol). The reaction mixture was stirred under a hydrogen gas atmosphere at room temperature for 1 hour. The reaction was then filtered through a short celite pad and the celite was washed with ethyl acetate. The filtrate was evaporated to yield an orange oil. Column chromatography (petroleum ether / ethyl acetate 4: 1 then 2: 1) was used to yield a crystallized orange oil at room temperature. It is recrystallized from isopropanol / dichloromethane and has a melting point of 3- (4-amino-3- (2-methoxyethoxy) phenyl) -5- (2,4-difluoro which is a light brown solid at 74-75 ° C. Phenoxy) -1,3,4-oxadiazole-2 (3H) -one (118 mg, 45%) was calculated.

Example 13:

3- (3-amino-4- Methoxyphenyl ) -5- (2,4- Difluorophenoxy ) -1,3,4- Oxadiazole -2 (3H) -one

a) 5- (2,4-difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) in vigorously stirred misting nitric acid cooled to 0 ° C. ) -One (500 mg, 1.561 mmol) was added in portions. The yellow suspension was stirred at 0 ° C. for 5 minutes, then allowed to heat to room temperature and then for 30 minutes. The reaction mixture was poured into ice / water and the resulting precipitate was filtered, washed with water and dried to give a pale yellow solid, 5- (2,4-difluorophenoxy) -3- (4-methoxy-3 -Nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one (533 mg, 93%).

b) 5- (2,4-difluorophenoxy) -3- (4-methoxy-3-nitrophenyl) -1,3,4-oxadiazole-2 (3H in methanol (20 mL) at room temperature) To the stirred suspension of) -one (520 mg, 1.424 mmol) was added 10% palladium on carbon (52 mg). Hydrogen gas was passed through the mixture through the foam for 2 hours, after which the catalyst was removed by filtration through a short pad of celite. The filtrate was evaporated and the resulting pale brown solid dissolved in dichloromethane. Activated carbon was added and the suspension was stirred for 15 minutes before filtration through short pads of silica gel and celite. The filtrate was evaporated and the resulting yellow solid was crystallized from isopropanol to have a melting point of 101 ° C. and an orange solid of 3- (3-amino-4-methoxyphenyl) -5- (2,4-difluorophenoxy). -1,3,4-oxadiazole-2 (3H) -one (280 mg, 59%) was given.

Example 14:

5- (2,4- Difluorophenoxy ) -3- (4- Methoxy -3- (1H- Pyrrole -1 day) Phenyl ) -1,3,4- Oxadiazole -2 (3H) -one

3- (3-amino-4-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one in acetic acid (5 mL) ( 162 mg, 0.483 mmol) and 2,5-dimethoxytetrahydrofuran (0.077 mL, 0.598 mmol) were stirred and heated at 90 ° C. for one hour and then cooled to room temperature. The solvent was removed under reduced pressure and toluene was added to the residue and redevaporated. The residue was taken up in dichloromethane and stirred for 30 minutes with activated carbon before filtration through a short silica / celite pad. The filtrate was evaporated to leave an oil which solidified after the addition of ether. Recrystallization from isopropanol is 5- (2,4-difluorophenoxy) -3- (4-methoxy-3- (1H-pyrrol-1-yl) phenyl) -1, which has a melting point of 136 ° C and is a pale orange solid. , 3,4-oxadiazole-2 (3H) -one (137 mg, 73%) was calculated.

Table 1 further shows compounds prepared in a similar manner. For solid materials, the melting point is given. For oils, NMR data are given in Table 2.

Name m.p. (° C) 5- (benzyloxy) -3- (3-chlorophenyl) -1,3,4-oxadiazole-2 (3H) -one 79-80 3- (4-Bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 109-110 3- (3′-methoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 102-103 5- (benzyloxy) -3-pi-tolyl-1,3,4-oxadiazole-2 (3H) -one 85 5- (benzyloxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 79-80 5- (benzyloxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 61-62 5- (benzyloxy) -3- (4-cyanophenyl) -1,3,4-oxadiazole-2 (3H) -one 118-119 3- (4-cyanophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 100 5- (benzyloxy) -3- (2,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one oil 5- (benzyloxy) -3- (3-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 108-109 3- (3-nitrophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 117 3- (4-methoxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 75-76 5- (benzyloxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 86-87 3- (4-hydroxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 159-160 5-phenoxy-3-phenyl-1,3,4-oxadiazole-2 (3H) -one 93 5-phenoxy-3- (4- (pyridin-3-yl) phenyl) -1,3,4-oxadiazole-2 (3H) -one 146-147 3- (biphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 110-111 3- (3 ', 4'-dimethoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 149-150 5- (benzyloxy) -3- (4-tert-butylphenyl) -1,3,4-oxadiazole-2 (3H) -one 59 5- (benzyloxy) -3- (4-bromophenyl) -1,3,4-oxadiazole-2 (3H) -one 149-150 3- (4-bromophenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 185-186 3- (3-chlorophenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 171-172 5- (4-Chlorophenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 105-106 3- (3-Bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 83-84 3- (biphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 77-78 5-phenoxy-3- (3- (pyridin-3-yl) phenyl) -1,3,4-oxadiazole-2 (3H) -one 81-82 5- (4-methoxyphenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 61-62 5- (benzyloxy) -3- (3-bromophenyl) -1,3,4-oxadiazole-2 (3H) -one 89-90 5- (4-benzyloxy) phenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 99-100 3- (5′-methoxybiphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 69-70 5- (4-hydroxyphenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 176-177 5- (benzyloxy) -3- (biphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 74-75 5- (benzyloxy) -3- (3′-methoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 82-83 5- (4-Chlorophenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 75-76 3- (4′-cyanobiphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 116-117 3- (2-fluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 60-61 3- (3′-cyanobiphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 109-110 3- (4′-cyanobiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 171-172 5- (4-Chlorophenoxy) -3- (2,4-difluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 116-117 5- (benzyloxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 74-75 3- (2,5-Difluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 109-110 3- (2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one oil 5- (benzyloxy) -3- (2,4-difluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 89-90 3- (2-fluorophenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 110-111 5- (4-Chlorophenoxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 129-130 5- (4-Chlorophenoxy) -3- (3 ′, 4′-dimethoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 146-147 3- (3-bromophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 98-99 3- (2,4-Difluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 49-50 3- (2,4-difluorophenyl) -5- (naphthalen-1-yloxy) -1,3,4-oxadiazole-2 (3H) -one 119-120 5- (2-Chlorophenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 61-62 3- (2,4-difluorophenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one oil 5- (4-Bromophenoxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 130-131 3- (2,5-difluorophenyl) -5- (4-fluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 93-94 5- (benzyloxy) -3- (2-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 98-99 3- (2-methoxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 121-122 5- (4-Chlorophenoxy) -3- (2-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 85-86 5- (4-fluorophenoxy) -3- (2-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 96-97 3- (2-Chlorophenyl_-5-phenoxy-1,3,, 4-oxadiazole-2 (3H) -one oil 3- (4-bromophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 139-140 5- (4-Chlorophenoxy) -3- (4′-cyanobiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 191-192 5- (2,4-Difluorophenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 76-77 3- (3-chlorophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 81-82 5- (2,4-difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 90-91 5- (4-Chlorophenoxy) -3- (3 ′, 4′-dimethoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 156-157 3- (5-Bromo-2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 69-70 3- (4-fluoro-4 ′, 5′-dimethoxybiphenyl-3-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H)- won 111-112 3- (3-bromophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 101-102 3- (4-bromophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 90-91 3- (4-fluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 90-91 5- (4-Chlorophenoxy) -3- (4-fluoro-4 ′, 5′-dimethoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 137-138 3- (2-fluoro-4- (pyridin-3-yl) phenyl) -5- (methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 140-141 3- (3-fluoro-4 ', 5'-dimethoxybiphenyl-4-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H)- won 96-97 3- (3-Fluoro-4′-cienobiphenyl-4-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 132-133 3- (4-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 108-109 3- (4-Chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one 89-90 5- (4-methoxyphenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 100-101.5 5- (4-Chlorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 98-99 3- (4 '-(dimethyamino) -3-fluorobiphenyl-4-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) 160-161 5- (4-Chlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 146-147 3- (4-bromophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 114-115 5- (4-Bromo-2-methoxyphenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 77-78 5- (3,5-Dimethoxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 97-98 5- (4-cyanophenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 125-126 3- (2-fluorophenyl) -5- (naphthalen-2-yloxy) -1,3,4-oxadiazole-2 (3H) -one 101-102 3-phenyl-5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 88-89 3- (4- (1H-tetrazol-5-yl) phenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 201-202 3- (5-Bromo-2-fluorophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 107-108 5- (4-fluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 155-156 5- (4- (1H-tetrazol-5-yl) phenoxy) -3-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 153-154 5- (3,4-Dimethoxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 82.5-83 5- (2,4-Difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 174-175 3- (2-fluoro-4- (methylsulfonyl) phenyl) -5- (4-mesoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 95-96 5- (4-fluorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 89-90 5- (biphenyl-4-yloxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 81-81 3- (2-fluorophenyl) -5- (3,4,5-trimethoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 139-140 3- (4-methoxyphenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one 70-71 3- (4-methoxyphenyl) -5- (p-tolyloxy) -1,3,4-oxadiazole-2 (3H) -one 83-84 3- (4-hydroxyphenyl) -5- (p-toloxy) -1,3,4-oxadiazole-2 (3H) -one 159-160 3- (3-Chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one 102-103 3- (4-hydroxyphenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one 167-168 5- (benzyloxy) -3- (3-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 101-102 3- (3-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 84-85 5- (3,5-Dihydroxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 155-156 3- (4-methoxyphenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 79-80 5- (2-Chloro-4-hydroxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 122-123 3- (5-chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 85-86 3- (4-hydroxyphenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 174-175 5- (2,4-Dichlorophenoxy) -3- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 177-178 3- (2-fluorophenyl) -5- (3-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 140-141 3- (2-fluorophenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 63-64 3- (2,4-difluorophenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 89-90 3- (2-fluoro-4- (methylsulfonyl) phenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 100-100 5- (2-Bromopyridin-3-yloxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 116-117 5- (2,4-Di-tert-butylphenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one oil 5- (cyclohexoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 58-59 5- (2,6-dimethylphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 88-89 3- (3-Chloro-2-fluorophenyl) -5- (cyclohexoxy) -1,3,4-oxadiazole-2 (3H) -one 84-85 5- (cyclohexoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 71-72 3- (2,4-difluorophenyl) -5- (2,6-dimethoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 94-95 5- (cyclohexoxy) -3- (3-fluoro-4 ', 5'-dimethoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 101-102 3- (3-hydroxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 116-117 5- (cyclohexoxy) -3- (3-fluoro-3 ′-(trifluoromethoxy) biphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 91-92 5- (4-Chlorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 166-167 5- (4-fluorophenoxy) -3- (3-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 163-164 3- (4-Chloro-2-fluorophenyl) -5-phenethoxy-1,3,4-oxadiazole-2 (3H) -one 52-53 3- (4-hydroxyphenyl) -5-phenethoxy-1,3,4-oxadiazole-2 (3H) -one 148-149 3- (2-fluorophenyl) -5-isobutoxy-1,3,4-oxadiazole-2 (3H) -one oil 3- (4-hydroxyphenyl) -5- (3-phenylpropoxy) -1,3,4-oxadiazole-2 (3H) -one 129-130 3- (4-hydroxyphenyl) -5- (4-phenylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 120-121 3- (4-hydroxyphenyl) -5- (5-phenylpentyoxy) -1,3,4-oxadiazole-2 (3H) -one 128-128 3- (4-hydroxyphenyl) -5- (6-phenylhexoxy) -1,3,4-oxadiazole-2 (3H) -one 107-108 3- (4-aminosulfonylphenyl) -5- (4-fluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 217-218 3- (4-aminosulfonylphenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 191-192 3- (4-hydroxyphenyl) -5- (2-phenoxyethoxy) -1,3,4-oxadiazole-2 (3H) -one 164-165 5- (2-Chlorophenethoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 139-140 3- (4-aminosulfonylphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 227-228 3- (4-aminosulfonylphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 204-205 3-phenyl-5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 50-51 3- (2-fluorophenyl) -5- (4-phenylbutoxy) -1,3,4-oxadiazole-2 (3H) -one oil 3- (4-aminosulfonylphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 143-144 3- (2-fluorophenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one oil 3- (2,4-difluorophenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 40-41 5- (4- (3,4-dimethoxyphenyl) butoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 56-57 3- (2-Chloro-5-fluorophenyl) -5- (5-phenylpentyloxy) -1, 3,4-oxadiazole-2 (3H) -one oil 5- (4- (3,2-dimethoxyphenyl) butoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one oil 5- (2-Chlorophenethoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 79-80 3- (2,4-difluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one oil 3- (4-chloro-2-fluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one oil 3- (3-chloro-2-fluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one oil 3- (4-aminocarbonylphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 226-227 3- (4-aminosulfonylphenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 148-149 3- (2-fluorophenyl) -5- (4- (4-fluorophenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one oil 3- (4-aminocarbonylphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 240-241 3- (4-aminocarbonylphenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 190-191 3- (4-aminocarbonylphenyl) -5- (5- (4-fluorophenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 142-142 3- (4-aminocarbonylphenyl) -5- (5- (4-fluorophenyl) pentyloxy) -1,3,4-oxadiazole-2 (3H) -one 155-156 3- (4-aminocarbonylphenyl) -5- (4-p-tolylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 154-155 3- (4-aminocarbonylphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 150-151 5- (biphenyl-4-yloxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 186-187 5- (4-aminocarbonylphenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 132-133 5- (2-fluorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 64-65 5- (3,4-Difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 86-87 5- (2-fluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 185-186 5- (3,4-difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 152-153 3- (3-aminophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 89-90 3- (3-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 122-123 5- (2-biphenyl-4-yl) ethoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 167-168 5- (2,4-difluorophenoxy) -3- (3,4-dimethoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 97-98 5- (4-Chlorophenoxy) -3- (3,4-dihydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 167-168 5- (2,4-difluorophenoxy) -3- (3,4-dihydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 167-168 5- (2,4-Difluorophenoxy) -3- (3-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 78-79 5- (3,4-dimethoxyphenoxy) -3- (4-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 98-99 5- (3,4-Dihydroxyphenoxy) -3- (4-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 138-139 3- (3-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 139-140 5- (2,4-Difluorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 163-164 5- (2-Chlorophenoxy) -3- (3-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 105-106 3- (4-Chloro-2-fluorophenyl) -5- (4-hydroxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one oil 3- (4-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 130 5- (3,5-Difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 126-127 5- (2-Chlorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 125-126 5- (4-Chlorophenoxy) -3- (2′-hydroxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 160-161 3- (3-chloro-2-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one oil 5- (4-Chlorophenoxy) -3- (2′-methoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 86-87 5- (3,4-Dihydroxyphenoxy) -3- (2-fluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 140-141 5- (4-Chlorophenoxy) -3- (3-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 152-153 5- (2,4-Difluorophenoxy) -3- (2'-methoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 106-107 5- (4-Chlorophenoxy) -3- (2-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 180-182 5- (4-Chlorophenoxy) -3- (2′-hydroxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 112-113 5- (2,4-Difluorophenoxy) -3- (4-hydroxy-3-methylphenyl) -1,3,4-oxadiazole-2 (3H) -one 147-148 5- (4-Chlorophenoxy) -3- (4-hydroxy-3-methylphenyl) -1,3,4-oxadiazole-2 (3H) -one 124-125 5- (2,4-Difluorophenoxy) -3- (2'-hydroxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 161-162 5- (4-Chlorophenoxy) -3- (2′-methoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 108-109 5- (2,4-difluorophenoxy) -3- (4-hydroxy-3,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one 112-113 5- (4-Chlorophenoxy) -3- (4-hydroxy-3,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one 145-146 5- (2,4-difluorophenoxy) -3- (4- (4-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 122 5- (2,4-difluorophenoxy) -3- (4- (3-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 101 5- (4-Chlorophenoxy) -3- (3,5-dihydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 213 5- (2,4-difluorophenoxy) -3- (4- (2-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 75-76 3- (4-benzoyloxyphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 159 3- (4-acetoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 160 3- (4-benzoyloxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 143 3- (4-isobutyroyloxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 89-90 5- (2,4-Difluorophenoxy) -3- (3-methoxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 133 5- (2,4-Difluorophenoxy) -3- (3-hydroxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 129 5- (4-Chlorophenoxy) -3- (3-hydroxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 160-161 5- (2,4-Difluorophenoxy) -3- (7-hydroxynaphthalen-2-yl) -1,3,4-oxadiazole-2 (3H) -one 181 3- (4-amino-3-hydroxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 226-228 3- (4-amino-3-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -membered hydrochloride 200-201 3- (4-amino-3- (2-methoxyethoxy) phenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 79 3- (4-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 152-153 3- (4- (1H-pyrrol-1-yl) phenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 181-182 3- (4-aminophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 112 3- (4-1H-pyrrol-1-yl) phenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 175 3- (3-amino-4-methoxyphenyl) -5- (p-tolyloxy) -1,3,4-oxadiazole-2 (3H) -one 113 3- (3-amino-4-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 101 3- (3-amino-4-methoxyphenyl) -5- (cyclohexyloxy) -1,3,4-oxadiazole-2 (3H) -one hydrochloride 185 5- (2,4-difluorophenoxy) -3- (4-methoxy-3- (1H-pyrrol-1-yl) phenyl) -1,3,4-oxadiazole-2 (3H) -won 136 3- (5-amino-2-fluoro-4-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one hydro Chloride 191-192 reduction. 5- (2,4-Difluorophenoxy) -3- (2-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 135 3- (4-amino-3-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 104-105

The NMR-data obtained from the oil is in Table 2 below. The NMR spectra were recorded on a Bruker Avance DPX400 spectrometer as a solvent used as an internal standard. Data is recorded with the following command: approximate chemical shift (ppm), number of protons, mutilicity (br, broad; d, doublet m, multiplet; s, singlet; t, triplet) and coupling constant (Hz).

Compound NMR data 5- (benzyloxy) -3- (2,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.49-7.40 (5H, m), 7.19 (2H, m), 7.13 (1H, doublet of doublets, J = 1.5 and 7.8), 5.34 (2H, s), 2.35 (3H , s), 2.28 (3H, s) (13C NMR, CDCl 3, 100 MHz) d: 154.9, 149.5, 136.5, 133.3, 133.1, 131.7, 131.0, 129.9, 129.1, 128.6, 128.5, 126.7, 72.6, 20.9, 17.8 3- (2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.48, (1H, dt, J = 1.7, 7.6), 7.38 (1H, m), 7.30 (2H, m, J = 9.3), 7.21 (2H, m), 6.94 (2H, m, J = 9.3), 3.84 (3H, s) (13C NMR, CDCl 3, 100 MHz) d: 157.6, 156.2 (d, J = 254), 154.9, 148.8, 144.7, 130.2 (d, J = 8), 127.0, 124.4 (d, J = 4), 122.6 ( d, J = 12), 120.6, 116.8 (d, J = 19), 114.7, 55.7 3- (2,4-difluorophenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.68 (1H, m), 7.62 (3H, m), 7.50 (1H, m), 6.99 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 162.5 (dd, J = 11 and 252), 156.8 (dd, J = 13 and 257), 153.8, 151.1, 148.6, 132.4 (q, J = 34), 130.6, 128.2 (dd, J = 1 and 10), 123.5 (q, J = 3.5), 122.9 (q, J = 271), 122.8, 118.8 (dd, J = 4 and 12), 116.8 (q, J = 4) , 111.9 (dd, J = 4 and 23), 105.4 (dd, J = 23 and 26) 3- (2-Chlorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.50-7.30 (8H, m), 7.27 (m, 1H) (13C NMR, CDCl 3, 100 MHz) d: 154.1, 151.3, 149.0, 132.0 (2 sig.), 130.7, 130.5, 129.8, 128.9, 127.5, 126.6, 119.3 5- (2,4-Di-tert-butylphenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.48 (1H, m, J = 2 and 8), 7.43 (1H, d, J = 2.5), 7.37 (1H, m), 7.26 (1H, dd, J = 2.5 and 8.6), 7.24-7.16 (3H, m), 1.42 (9H, s), 1.32 (9H, s) (13C NMR, CDCl 3, 100 MHz) d: 156.5 (d, J = 255), 154.8, 149.3, 149.2, 148.2, 139.6, 130.4 (d, J = 7.5), 127.1, 124.7, 124.5 (d, J = 4 ), 124.3, 120.3, 117.0 (d, J = 19.5), 34.9, 34.7, 31.4, 31.3 3- (2-fluorophenyl) -5-isobutoxy-1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.54 (1H, m, J = 2 and 8.3), 7.41 (1H, m), 7.25 (2H, m), 4.15 (2H, d, J = 6.6), 2.18 (1H, m), 1.06 (6H, d, J = 6.6) (13C NMR, CDCl 3, 100 MHz) d: 156.4 (d, J = 254), 155.9, 149.3, 130.2 (d, J = 7.5), 126.9, 124.6 (d, J = 4), 122.9 (d, J = 11.5), 117.0 (d, J = 19.5), 77.2, 27.7, 18.6 3- (2-fluorophenyl) -5- (4-phenylbutoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.53 (1H, m), 7.41 (1H, m), 7.33 (2H, t, J = 7.5), 7.29-7.19 (5H, m), 4.39 (2H, t , J = 6.3), 2.72 (2H, t, J = 7.3), 1.90 (2H, m), 1.80 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 156.4 (d, J = 255), 155.8, 149.3, 141.5, 130.2 (d, J = 8), 128.4 (2 sig.), 126.9, 126.0, 124.6 (d, J = 4), 123.0 (d, J = 11.5), 117.0 (d, J = 20), 71.4, 35.2, 27.8, 27.1 3- (2-fluorophenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.51 (1H, m, J = 2 and 7.8), 7.39 (1H, m), 7.30 (2H, m, J = 7.5), 7.27-7.15 (5H, m) , 4.35 (2H, t, J = 6.6), 2.66 (2H, t, J = 7.3), 1.86 (2H, m), 1.70 (2H, m), 1.50 (2H, m) (13C NMR, CDCl3, 100 MHz) d: 156.4 (d, J = 255), 155.8, 149.3, 142.1, 130.2 (d, J = 8), 128.4, 128.3, 126.9, 125.8, 124.6 (d, J = 4 ), 123.0 (d, J = 11.5), 117.0 (d, J = 19.3), 71.5, 35.7, 30.9, 28.2, 25.1 3- (2-Chloro-5-fluorophenyl) -5- (5-phenylpentyloxy) -1, 3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.53 (1H, dd, J = 2.7 and 6.5), 7.33 (1H, m), 7.30 (2H, t, J = 7.3), 7.23-7.16 (4H, m) , 4.35 (2H, t, J = 6.6), 2.65 (2H, t, J = 7.8), 1.86 (2H, m), 1.70 (2H, m), 1.50 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 156.0, 154.6 (d, J = 255), 148.8, 142.0, 129.8 (d, J = 7.5), 129.5 (d, J = 4), 128.4, 128.3, 126.3, 125.8, 124.0, 118.2 (d, J = 21), 71.7, 35.7, 30.9, 28.2, 25.1 5- (4- (3,4-dimethoxyphenyl) butoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.51 (1H, m, J = 2 and 8), 7.39 (1H, m), 7.27-7.15 (2H, m), 6.81 (1H, d, J = 8) , 6.73 (1H, dd, J = 2 and 8), 6.72 (1H, d, J = 2), 4.37 (2H, t, J = 6.5), 3.89 (3H, s), 3.87 (3H, s), 2.64 (2H, t, J = 7.3), 1.86 (2H, m), 1.78 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 156.4 (d, J = 255), 155.8, 149.3, 148.8, 147.2, 134.1, 130.2 (d, J = 8), 126.8, 124.6 (d, J = 4), 122.9 (d, J = 12), 120.1, 117.0 (d, J = 19), 111.5, 111.1, 71.4, 55.9, 55.8, 34.8, 27.8, 27.3 3- (2,4-difluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.48 (1H, m, J = 5.9 and 8.5), 7.03-6.94 (2H, m), 6.81 (1H, d, J = 8), 6.72 (1H, dd, J = 2 and 8), 6.71 (1H, d, J = 2), 4.35 (2H, t, J = 6.5), 3.88 (3H, s), 3.87 (3H, s), 2.63 (2H, t, J = 7.3), 1.86 (2H, m), 1.77 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 162.5 (dd, J = 10.5 and 252), 157.0 (dd, J = 13 and 258), 155.8, 149.3, 148.8, 147.2, 134.0, 128.2 (dd, J = 1.5 and 10.5), 120.1, 119.4 (dd, J = 4 and 12), 111.9 (dd, J = 4 and 23), 111.5, 111.1, 105.4 (dd, J = 22.5 and 26.5), 71.4, 58.9, 58.8, 34.8 , 27.8, 27.3 3- (4-chloro-2-fluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.44 (1H, t, J = 7.9), 7.25 (1H, d, J = 10.5), 7.22 (1H, m), 6.80 (1H, d, J = 7.9) , 6.72 (1H, dd, J = 2 and 7.9), 6.71 (1H, br), 4.35 (2H, t, J = 6.5), 3.88 (3H, s), 3.86 (3H, s), 2.63 (2H, t, J = 7.5), 1.85 (2H, m), 1.76 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 156.0 (d, J = 258), 155.8, 149.0, 148.8, 147.2, 135.1 (d, J = 9), 134.0, 127.3, 125.0 (d, J = 4), 121.8 (d, J = 12), 120.1, 117.8 (d, J = 22.5), 111.5, 111.1, 71.5, 55.9, 55.8, 34.9, 27.8, 27.3 3- (3-chloro-2-fluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.44 (2H, m), 7.18 (1H, dt, J = 1.7 and 8.1), 6.81 (1H, d, J = 8), 6.73 (1H, dd, J = 2 and 8), 6.72 (1H, br), 4.37 (2H, t, J = 6.3), 3.89 (3H, s), 3.87 (3H, s), 2.64 (2H, t, J = 7.4), 1.87 ( 2H, m), 1.77 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 155.8, 152.3 (d, J = 257), 149.0, 148.8, 147.2, 134.0, 130.5, 124.8, 124.5 (d, J = 5), 124.3 (d, J = 11 , 122.8 (d, J = 16), 120.1, 111.5, 111.1, 71.6, 55.9, 55.8, 34.8, 27.8, 27.3 3- (2-fluorophenyl) -5- (4- (4-fluorophenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.50 (1H, dt, J = 2 and 8.3), 7.39 (1H, m), 7.27-7.19 (2H, m), 7.14 (2H, m, J = 5.5 and 8.5), 6.98 (2H, m, J = 8.7), 4.36 (2H, t, J = 6.4), 2.66 (2H, t, J = 7.5), 1.85 (2H, m), 1.77 (2H, m) (13C NMR, CDCl 3, 100 MHz) d: 161.3 (d, J = 243), 156.4 (d, J = 255), 155.7, 149.3, 137.1 (d, J = 3), 130.2 (d, J = 8) , 129.7 (d, J = 8), 126.8, 124.6 (d, J = 4), 122.9 (d, J = 11.5), 117.1 (d, J = 19.5), 115.1 (d, J = 21.5), 71.3, 34.4, 27.7, 27.3 3- (4-Chloro-2-fluorophenyl) -5- (4-hydroxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.42 (1H, t, J = 8), 7.25 (1H, dd, J = 2.3 and 9.9), 7.23-7.18 (3H, m), 6.87 (2H, m, J = 9), 5.16 (1H, s) (13C NMR, CDCl 3, 100 MHz) d: 156.1 (d, J = 259), 155.3, 154.2, 148.9, 144.8, 135.5 (d, J = 9.5), 127.6, 125.0 (d, J = 4), 120.9, 117.8 (d, J = 22.5), 116.4 3- (3-chloro-2-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one (1H NMR, CDCl3, 400 MHz) d: 7.43 (1H, m), 7.40 (1H, m), 7.23 (2H, m, J = 9), 7.15 (1H, dt, J = 1.5 and 8), 6.86 (2H, m, J = 9), 5.36 (1H, s) (13C NMR, CDCl 3, 100 MHz) d: 155.3, 154.2, 152.5 (d, J = 257), 148.9, 144.9, 130.9, 125.2, 124.5 (d, J = 5), 124.0 (d, J = 12), 122.7 (d, J = 16), 120.9, 116.4

FAAH activity in vitro is determined according to the following method:

Cooled brains of Wistar rats (without cerebellum) were used and each brain was homogenized with Potter Elvejhem (500 rpm, 8 strokes) at 15 mL 1 mM MgCl ₂ , 20 nM HEPES pH 7.0. Homogenization was centrifuged at 4 ° C. (Beckman, 70 Ti rotor), 36000 g for 20 minutes. Pellets were resuspended in 15 mL of the buffer and centrifuged under the same conditions. Pellets were resuspended in 15 mL of the buffer and incubated at 37 ° C. for 15 minutes and then centrifuged at 4 ° C., 36000 g for 20 minutes. Each pellet was then resuspended in 15 mL solution dissolved in 3 mM MgCl ₂ , 1 mM EDTA, 50 mM Tris at pH 7.4 and the protein was purified using a standard curve of BSA (50-250 μg / ml). Measured by Biorad Protein Assay (BioRad). The membrane suspension was aliquoted and stored at -80 ° C.

FAAH activity is measured by measuring that by using the AEA (the amine portion of the molecule labeled with ³ H) formed in the substrate and the ³ H- ethanolamine. The reaction mixture (total volume of 200 μl) comprises: 2 μM AEA (2 μM AEA + 5 nM ³ H-AEA) in 1 mM EDTA, 10 mM Tris and 10 μM or 100 mM compound at pH 7.6, 0.1% fatty acid, 5 μg protein without BSA. Stock solutions of compounds for testing (10 mM) were prepared with 100% DMSO and 0.1% of the DMSO concentration for the assay. After a 15 minute pre-incubation period at 37 ° C., the reaction was started by the addition of substrate solution (cold EAE + isotopically labeled EAE + BSA). The reaction was carried out for 10 minutes before termination by the addition of 400 μl of activated charcoal suspension (0.5 M HCI under constant stirring, 8 g of charcoal in 32 mL). After a 30 minute incubation period with stirring at room temperature, the char was precipitated by centrifugation with an experimental centrifuge (10 minutes, 13000 rpm). 200 μl of the supernatant was added to 800 μl of Optiphase Supermix scintillation cocktail, which was previously dispensed into 24-well plates. Counting per minute (cpm) was measured with a MicrobetaTriLux scintillation counter (until 10 minutes counting or σ = 2).

Each assay blank (no protein, usually below 200 cpm) and control (no compound) were present. The results are reported in Table 3 as% of control after blank subtraction.

Compound FAAHi  activity (% Control at  dosage of  100 nM ) 5- (benzyloxy) -3- (3-chlorophenyl) -1,3,4-oxadiazole-2 (3H) -one 8.6 3- (4-Bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 24.81 3- (3'-methoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 11.63 5- (benzyloxy) -3-p-tolyl-1,3,4-oxadiazole-2 (3H) -one 44.47 5- (benzyloxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 12.67 5- (benzyloxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 3.52 5- (benzyloxy) -3- (4-cyanophenyl) -1,3,4-oxadiazole-2 (3H) -one 19.3 3- (4-cyanophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 95.63 5- (benzyloxy) -3- (2,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one 59.02 5- (benzyloxy) -3- (3-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 21.28 3- (3-nitrophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 78.36 3- (4-methoxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 18.49 5- (benzyloxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 21.19 3- (4-hydroxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 28.39 5-phenoxy-3-phenyl-1,3,4-oxadiazole-2 (3H) -one 55.64 5-phenoxy-3- (4- (pyridin-3-yl) phenyl) -1,3,4-oxadiazole-2 (3H) -one 12.2 3- (biphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 16.59 3- (3 ', 4'-dimethoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 12.68 5- (benzyloxy) -3- (4-tert-butylphenyl) -1,3,4-oxadiazole-2 (3H) -one 34.6 5- (benzyloxy) -3- (4-bromophenyl) -1,3,4-oxadiazole-2 (3H) -one 8.01 3- (4-bromophenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 7.3 3- (3-chlorophenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 9.1 5- (4-Chlorophenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 30.9 3- (3-Bromophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 62.21 3- (biphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 32.01 5-phenoxy-3- (3- (pyridin-3-yl) phenyl) -1,3,4-oxadiazole-2 (3H) -one 19.52 5- (4-methoxyphenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 7.44 5- (benzyloxy) -3- (3-bromophenyl) -1,3,4-oxadiazole-2 (3H) -one 8.67 5- (4- (benzyloxy) phenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 18.24 3- (5'-methoxybiphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 27.58 5- (benzyloxy) -3- (biphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 12.74 5- (benzyloxy) -3- (3'-methoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 9.41 5- (4-Chlorophenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 0.64 3- (4'-cyanobiphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 6.27 3- (2-fluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 3.37 3- (3'-cyanobiphenyl-3-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 19.29 3- (4'-cyanobiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 13.52 5- (4-Chlorophenoxy) -3- (2,4-difluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 1.75 5- (benzyloxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 1.12 3- (2,5-Difluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 2.35 3- (2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.29 5- (benzyloxy) -3- (2,4-difluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 4.4 3- (2-fluorophenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 4.48 5- (4-Chlorophenoxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 5.57 5- (4-Chlorophenoxy) -3- (3 ', 4'-dimethoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 0.3 3- (3-bromophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 11.11 3- (2,4-Difluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 3.08 3- (2,4-difluorophenyl) -5- (naphthalen-1-yloxy) -1,3,4-oxadiazole-2 (3H) -one 4.77 5- (2-Chlorophenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 1.82 3- (2,4-difluorophenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one 13.35 5- (4-Bromophenoxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 10.87 3- (2,5-difluorophenyl) -5- (4-fluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 1.85 5- (4-Chlorophenoxy) -3- (2-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 70.37 3- (2-Chlorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 32.63 3- (4-bromophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 11.34 5- (4-Chlorophenoxy) -3- (4'-cyanobiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 6.26 5- (2,4-Difluorophenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 1.29 3- (3-chlorophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 8.98 5- (2,4-difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.26 5- (4-Chlorophenoxy) -3- (3 ', 4'-dimethoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 28.79 3- (5-Bromo-2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.71 3- (4-fluoro-4 ', 5'-dimethoxybiphenyl-3-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H)- won 0.54 3- (3-bromophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 17.69 3- (4-bromophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 8.28 3- (4-fluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 23.33 5- (4-Chlorophenoxy) -3- (4-fluoro-4 ', 5'-dimethoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 2.43 3- (2-fluoro-4- (pyridin-3-yl) phenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.73 3- (3-fluoro-4 ', 5'-dimethoxybiphenyl-4-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H)- won 0.6 3- (3-fluoro-4'-cyanobiphenyl-4-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 2.23 3- (4-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 2.57 3- (4-Chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one 1.07 5- (4-methoxyphenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 1.19 5- (4-Chlorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 1.04 3- (4 '-(dimethylamino) -3-fluorobiphenyl-4-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 5.55 5- (4-Chlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.56 3- (4-bromophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 4.41 5- (4-Bromo-2-methoxyphenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 1.43 5- (3,5-Dimethoxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 5.99 5- (4-cyanophenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 1.88 3- (2-fluorophenyl) -5- (naphthalen-2-yloxy) -1,3,4-oxadiazole-2 (3H) -one 3.03 3-phenyl-5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 46.52 3- (5-Bromo-2-fluorophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 11.63 5- (4-fluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 2.32 5- (3,4-Dimethoxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 14.12 5- (2,4-Difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.31 3- (2-fluoro-4- (methylsulfonyl) phenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.21 5- (4-fluorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 2.08 5- (biphenyl-4-yloxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 1.03 3- (2-fluorophenyl) -5- (3,4,5-trimethoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 69.17 3- (4-methoxyphenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one 3.49 3- (4-methoxyphenyl) -5- (p-tolyloxy) -1,3,4-oxadiazole-2 (3H) -one 4.24 3- (4-hydroxyphenyl) -5- (p-tolyloxy) -1,3,4-oxadiazole-2 (3H) -one 1.23 3- (3-Chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one 0.67 3- (4-hydroxyphenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one 1.07 5- (benzyloxy) -3- (3-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 12.15 3- (3-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 10.52 5- (3,5-Dihydroxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 1.08 3- (4-methoxyphenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 28.19 5- (2-Chloro-4-hydroxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 1.93 3- (5-chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.92 3- (4-hydroxyphenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.42 5- (2,4-Dichlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.38 3- (2-fluorophenyl) -5- (3-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 11.39 3- (2-fluorophenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 38.39 3- (2,4-difluorophenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 48.57 3- (2-fluoro-4- (methylsulfonyl) phenyl) -5- (pyridin-3-yloxy) -1,3,4-oxadiazole-2 (3H) -one 15.98 5- (2-Bromopyridin-3-yloxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 3.36 5- (cyclohexyloxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 2.58 3- (3-Chloro-2-fluorophenyl) -5- (cyclohexyloxy) -1,3,4-oxadiazole-2 (3H) -one 13.54 5- (cyclohexyloxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 45.11 5- (cyclohexyloxy) -3- (3-fluoro-4 ', 5'-dimethoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 30.3 3- (3-hydroxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 14.04 5- (cyclohexyloxy) -3- (3-fluoro-3 '-(trifluoromethoxy) biphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 35.39 5- (4-Chlorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 1.21 5- (4-fluorophenoxy) -3- (3-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 2.95 3- (4-Chloro-2-fluorophenyl) -5-phennetoxy-1,3,4-oxadiazole-2 (3H) -one 10.49 3- (4-hydroxyphenyl) -5-phennetoxy-1,3,4-oxadiazole-2 (3H) -one 24.03 3- (2-fluorophenyl) -5-isobutoxy-1,3,4-oxadiazole-2 (3H) -one 11.63 3- (4-hydroxyphenyl) -5- (3-phenylpropoxy) -1,3,4-oxadiazole-2 (3H) -one 21.68 3- (4-hydroxyphenyl) -5- (4-phenylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 5.49 3- (4-hydroxyphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 3.3 3- (4-hydroxyphenyl) -5- (6-phenylhexyloxy) -1,3,4-oxadiazole-2 (3H) -one 13.56 3- (4-aminosulfonylphenyl) -5- (4-fluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 5.16 3- (4-aminosulfonylphenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 8.32 3- (4-hydroxyphenyl) -5- (2-phenoxyethoxy) -1,3,4-oxadiazole-2 (3H) -one 33.2 5- (2-chlorophennetoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 2.54 3- (4-aminosulfonylphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 5.89 3- (4-aminosulfonylphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 7.61 3-phenyl-5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 47.86 3- (2-fluorophenyl) -5- (4-phenylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 19.62 3- (4-aminosulfonylphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 0.09 3- (2-fluorophenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 18.12 3- (2,4-difluorophenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 43.31 5- (4- (3,4-dimethoxyphenyl) butoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 39.74 3- (2-Chloro-5-fluorophenyl) -5- (5-phenylpentyloxy) -1, 3,4-oxadiazole-2 (3H) -one 9.94 5- (4- (3,4-dimethoxyphenyl) butoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 3.85 5- (2-chlorophennetoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 1.18 3- (2,4-difluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 6.31 3- (4-chloro-2-fluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 3.17 3- (3-chloro-2-fluorophenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 22.32 3- (4-aminocarbonylphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 47.96 3- (4-aminosulfonylphenyl) -5- (4- (3,4-dimethoxyphenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 0.09 3- (2-fluorophenyl) -5- (4- (4-fluorophenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 12.7 3- (4-aminocarbonylphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 9.62 3- (4-aminocarbonylphenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 18.41 3- (4-aminocarbonylphenyl) -5- (4- (4-fluorophenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 1.01 3- (4-aminocarbonylphenyl) -5- (5- (4-fluorophenyl) pentyloxy) -1,3,4-oxadiazole-2 (3H) -one 0.07 3- (4-aminocarbonylphenyl) -5- (4-p-tolylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 0.06 3- (4-aminocarbonylphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 0.09 5- (biphenyl-4-yloxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.97 5- (4-aminocarbonylphenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 14.5 5- (2-fluorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 1.96 5- (3,4-Difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.37 5- (2-fluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 1.1 5- (3,4-difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.46 3- (3-aminophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 52.35 3- (3-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.87 5- (2- (biphenyl-4-yl) ethoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 8.3 5- (2,4-difluorophenoxy) -3- (3,4-dimethoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 1.18 5- (4-Chlorophenoxy) -3- (3,4-dihydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 0.36 5- (2,4-difluorophenoxy) -3- (3,4-dihydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.1 5- (2,4-Difluorophenoxy) -3- (3-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.92 5- (3,4-dimethoxyphenoxy) -3- (4-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 13.95 5- (3,4-Dihydroxyphenoxy) -3- (4-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 57.19 3- (3-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 46.83 5- (2,4-Difluorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.22 5- (2-Chlorophenoxy) -3- (3-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 16.18 3- (4-Chloro-2-fluorophenyl) -5- (4-hydroxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one 8.06 3- (4-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 40.67 5- (3,5-difluorophennetoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 3.9 5- (2-Chlorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 9.36 5- (4-Chlorophenoxy) -3- (2'-hydroxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 2.77 3- (3-chloro-2-fluorophenyl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 22.72 5- (4-Chlorophenoxy) -3- (2'-methoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 0.55 5- (3,4-Dihydroxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 36.2 5- (4-Chlorophenoxy) -3- (3-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 1.05 5- (2,4-Difluorophenoxy) -3- (2'-methoxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 1.86 5- (4-Chlorophenoxy) -3- (2-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 0.01 5- (4-Chlorophenoxy) -3- (2'-hydroxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 6.02 5- (2,4-Difluorophenoxy) -3- (4-hydroxy-3-methylphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.09 5- (4-Chlorophenoxy) -3- (4-hydroxy-3-methylphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.31 5- (2,4-Difluorophenoxy) -3- (2'-hydroxybiphenyl-4-yl) -1,3,4-oxadiazole-2 (3H) -one 1.48 5- (4-Chlorophenoxy) -3- (2'-methoxybiphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 4.91 5- (2,4-difluorophenoxy) -3- (4-hydroxy-3,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.18 5- (4-Chlorophenoxy) -3- (4-hydroxy-3,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one 0.51 5- (2,4-difluorophenoxy) -3- (4- (4-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 0.48 5- (2,4-difluorophenoxy) -3- (4- (3-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 0.2 5- (4-Chlorophenoxy) -3- (3,5-dihydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 2.42 5- (2,4-difluorophenoxy) -3- (4- (2-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 0.27 3- (4-benzoyloxyphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 8.13 3- (4-acetoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.38 3- (4-benzoyloxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.79 3- (4-isobutyroyloxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.26 5- (2,4-Difluorophenoxy) -3- (3-methoxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 52.39 5- (2,4-Difluorophenoxy) -3- (3-hydroxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 51.6 5- (4-Chlorophenoxy) -3- (3-hydroxy-4-nitrophenyl) -1,3,4-oxadiazole-2 (3H) -one 56.4 5- (2,4-Difluorophenoxy) -3- (7-hydroxynaphthalen-2-yl) -1,3,4-oxadiazole-2 (3H) -one 5.45 3- (4-amino-3-hydroxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 13.6 3- (4-amino-3-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -membered hydrochloride 0.3 3- (4-amino-3- (2-methoxyethoxy) phenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.5 3- (4-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.04 3- (4- (1H-pyrrol-1-yl) phenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 7.4 3- (4-aminophenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.51 3- (4- (1H-pyrrol-1-yl) phenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 9.33 3- (3-amino-4-methoxyphenyl) -5- (p-tolyloxy) -1,3,4-oxadiazole-2 (3H) -one 37.03 3- (3-amino-4-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 1.9 5- (2,4-difluorophenoxy) -3- (4-methoxy-3- (1H-pyrrol-1-yl) phenyl) -1,3,4-oxadiazole-2 (3H) -won 0.35 3- (5-amino-2-fluoro-4-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one hydro Chloride 0.35 5- (2,4-Difluorophenoxy) -3- (2-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 0.04 3- (4-amino-3-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 0.31

FAAH inhibitory activity of animal cells modulated with compounds of the present invention in vivo is determined according to the following method:

Animal treatment

The animals used in the experiment were male NMRI rats (weight 27-44 g) obtained from the Harlan Interpow or Iberica Zoo in Barcelona, Spain. Mice were housed 5 per cage under a 12 hour light / dark cycle and environmental conditions controlled at room temperature 22 ± 1 ° C. Food and tap water were fed randomly and the experiment was conducted during the day.

Animals are orally dosed with 30 mg / kg BIA compound (8 mL / kg; compound suspended in 0.5% of carboxymethylcellulose (CMC) or dissolved in water) or by using a stainless steel curve needle to feed the animal ( Perfectum, USA) Dosing 8 ml / kg 0.5% CMC (Control). Fentobarbital (60 mg / kg) is anesthetized intraperitoneally 15 minutes before the animal is sacrificed. Part of the liver, left lobe and cerebellum were removed and placed in a plastic water bottle containing membrane buffer (3 mM MgCl ₂ , 1 mM EDTA, 50 mM Tris HCl pH 7.4). Tissues were stored at -30 ° C until disintegration.

Except for a period of 18 hours or more, the animals were discontinued for one night prior to the infusion of the compound, specifically given no food from the morning of the dosing day and the compound was dosed in the afternoon of the day. Then animals were fed nothing but water.

All animal testing procedures strictly comply with European Directives (86 / 609CEE) and Portuguese law (Decreto-Lei 129/92, Portarias 1005/92 e 1131/97) for the protection of vertebrates used for experimentation and other scientific purposes. Was performed. The number of animals used is the minimum possible in accordance with current regulatory and scientific methods.

Reagents and Solutions

Anandamide [ethanolamine-1- ³ H-] (40-60 Ci / mmol) was obtained from American Radiochemicals. All other reagents were obtained from Sigma-Aldrich. Optiphase Supermix was obtained from Perkin Elmer and activated charcoal was obtained from Sigma-Aldrich.

Organization preparation

Tissue is thawed on ice and Potter-Elvejhem (brain: 500 rpm, 8 strokes) or Heidolph Diax (liver: 30 sec interruption) in 10 volumes of membrane buffer (3 mM MgCl ₂ , 1 mM EDTA, 50 mM Tris HCl pH 7.4) Homogenized using 5 positions of 20 seconds, 2 strokes).

Total protein in tissues was determined using BioRad Protein Assay (BioRad) using BSA (50-250 μg / ml) standard curve.

Enzyme analysis

The reaction mixture (total volume of 200 μl) comprises: 1 mM EDTA at pH 7.6, 2 μM AEA (2 μM AEA + 5 nM ³ H-AEA) at 10 mM Tris, fatty acids without 0.1% BSA, 15 μg (brain), 5 μg (liver) or 50 μg (lung) protein. After a 15-minute pre-incubation period at 37 ° C., the reaction was initiated by the addition of substrate solution (cold AEA + AEA + BSA labeled with radioisotopes). Prior to termination by addition of 400 μl activated charcoal suspension (a solution of 32 mL of 0.5 M HCl and 8 g char under continuous stirring), the reaction is carried out for 10 minutes (brain and lung) or for 7 minutes (liver). ) Was performed. After 30 minutes of incubation with stirring at room temperature, the charcoal is precipitated through centrifugation using an experimental centrifuge (13000 rpm, 10 minutes). 200 μl of the supernatant was added to 800 μl of Optiphase Supermix scintillation cocktail, which was previously dispensed into 24-well plates. Counting per minute (cpm) was measured with a MicrobetaTriLux scintillation counter.

Each assay blanks (without protein) were prepared.

The percentage of activity of the remaining enzyme is measured relative to the control (no compound) and then the blank value is subtracted.

The results are reported in Table 4:

Compound FAAHi activity (% control mouse liver (30mg kg 1h)) FAAHi activity (% control mouse brain (30mg kg 1h)) 3- (3'-methoxybiphenyl-4-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 67.58 93.2 5- (benzyloxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 31.12 103.63 3- (3-nitrophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 73.47 87.28 3- (4-hydroxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 46.3 97.32 5- (benzyloxy) -3- (3-bromophenyl) -1,3,4-oxadiazole-2 (3H) -one 70.43 96.92 5- (benzyloxy) -3- (biphenyl-3-yl) -1,3,4-oxadiazole-2 (3H) -one 71.36 71.23 5- (4-Chlorophenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 45.9 76.22 3- (2-fluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 72.15 97 3- (2-fluorophenyl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one 72.04 68.77 5- (benzyloxy) -3- (2,4-difluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 69.86 79.94 5- (4-Chlorophenoxy) -3- (2,5-difluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 70.5 77.59 3- (2,4-Difluorophenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 65.24 86.48 3- (2,4-difluorophenyl) -5- (naphthalen-1-yloxy) -1,3,4-oxadiazole-2 (3H) -one 78.72 94.69 5- (2-Chlorophenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 67.76 106.7 5- (2,4-Difluorophenoxy) -3-phenyl-1,3,4-oxadiazole-2 (3H) -one 39.07 93.97 5- (2,4-difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 52.81 94.15 3- (4-Chloro-2-fluorophenyl) -5- (4-methoxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one 75.9 90.87 5- (4-Chlorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 75.22 92.94 5- (4-Chlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 19.56 37.69 5- (3,5-Dimethoxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 76.19 87.43 5- (4-cyanophenoxy) -3- (2-fluorophenyl) -1, 3,4-oxadiazole-2 (3H) -one 74.33 85.02 5- (4-fluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 30.89 81.63 5- (2,4-Difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 11.94 85.59 5- (biphenyl-4-yloxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 60.42 99.51 3- (4-hydroxyphenyl) -5- (3- (trifluoromethyl) phenoxy) -1,3,4-oxadiazole-2 (3H) -one 69.9 95.5 5- (3,5-Dihydroxyphenoxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 39.57 72.49 3- (4-hydroxyphenyl) -5- (4-nitrophenoxy) -1,3,4-oxadiazole-2 (3H) -one 45 96.3 5- (2,4-Dichlorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 9.17 59.18 5- (cyclohexyloxy) -3- (2-fluorophenyl) -1,3,4-oxadiazole-2 (3H) -one 56.98 77.59 3- (3-hydroxyphenyl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one 33.01 94.66 5- (4-Chlorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 10.26 100.2 5- (4-fluorophenoxy) -3- (3-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 24.27 99.06 3- (2-fluorophenyl) -5-isobutoxy-1,3,4-oxadiazole-2 (3H) -one 26.55 83.52 3- (4-hydroxyphenyl) -5- (3-phenylpropoxy) -1,3,4-oxadiazole-2 (3H) -one 38.45 85.58 3- (4-hydroxyphenyl) -5- (4-phenylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 65.84 95.66 3- (4-hydroxyphenyl) -5- (6-phenylhexyloxy) -1,3,4-oxadiazole-2 (3H) -one 51.19 96.15 5- (2-chlorophennetoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 31.37 92.16 3- (4-aminosulfonylphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 45.73 74.76 3- (4-aminocarbonylphenyl) -5- (4- (4-fluorophenyl) butoxy) -1,3,4-oxadiazole-2 (3H) -one 59.61 106.79 3- (4-aminocarbonylphenyl) -5- (5- (4-fluorophenyl) pentyloxy) -1,3,4-oxadiazole-2 (3H) -one 71.77 105.07 3- (4-aminocarbonylphenyl) -5- (4-p-tolylbutoxy) -1,3,4-oxadiazole-2 (3H) -one 30.46 68.63 3- (4-aminocarbonylphenyl) -5- (5-phenylpentyloxy) -1,3,4-oxadiazole-2 (3H) -one 56.07 84.41 5- (biphenyl-4-yloxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 17.29 62.46 5- (2-fluorophenoxy) -3- (4-methoxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 44.98 88.26 5- (3,4-Difluorophenoxy) -3- (4-methoxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 49.6 85.72 5- (2-fluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 44.44 93.98 5- (3,4-difluorophenoxy) -3- (4-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 17.28 58.22 3- (3-aminophenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 21.63 82.92 5- (4-Chlorophenoxy) -3- (3,4-dihydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 4.94 83.36 5- (2,4-difluorophenoxy) -3- (3,4-dihydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 3.56 65.78 5- (2,4-Difluorophenoxy) -3- (3-hydroxyphenyl) -1,3,4-oxadiazole-2 (3H) -one 11.85 93.77 5- (4-Chlorophenoxy) -3- (3-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 49.56 86.55 5- (4-Chlorophenoxy) -3- (2-fluoro-4-hydroxyphenyl) -1, 3,4-oxadiazole-2 (3H) -one 3.8 64.34 5- (2,4-Difluorophenoxy) -3- (4-hydroxy-3-methylphenyl) -1,3,4-oxadiazole-2 (3H) -one 10.23 48.25 5- (4-Chlorophenoxy) -3- (4-hydroxy-3-methylphenyl) -1,3,4-oxadiazole-2 (3H) -one 37.45 50.01 5- (2,4-difluorophenoxy) -3- (4-hydroxy-3,5-dimethylphenyl) -1,3,4-oxadiazole-2 (3H) -one 7.58 67.44 5- (2,4-difluorophenoxy) -3- (4- (3-methoxybenzyloxy) phenyl) -1,3,4-oxadiazole-2 (3H) -one 45.86 96.03 3- (4-benzoyloxyphenyl) -5- (4-chlorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 108.8 94.4 3- (4-acetoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 73.67 96.55 3- (4-isobutyroyloxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 55.9 90.41 5- (2,4-Difluorophenoxy) -3- (7-hydroxynaphthalen-2-yl) -1,3,4-oxadiazole-2 (3H) -one 79.41 86.37 3- (4-amino-3-methoxyphenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -membered hydrochloride 4.19 9.61 3- (4-amino-3- (2-methoxyethoxy) phenyl) -5- (2,4-difluorophenoxy) -1,3,4-oxadiazole-2 (3H) -one 4.99 6.76

As evidence from the above experiments, the compounds of the present invention are all characterized by 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone structural units and are unexpectedly unexpected for inhibition of FAAH. With high levels, these new compounds are promising candidates for therapeutic drugs or are substances that prevent FAAH-related medical disorders. Furthermore, surprisingly high levels of inhibition of FAAH have been demonstrated in vitro as well as in vivo.

Furthermore, a comparison of experimental data in vivo showed that the FAAH inhibitory activity of compounds with 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone structural units was compared with those in the central nervous system (CNS). It was also derived that characterized by peripheral selectivity when compared.

The data relating to the broad category of compounds activated at high levels represent 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone structural units with the structure represented by formula (III) below,

(III)

(III)

The structure (III) is a pharmacogenetic step for highly effective FAAH inhibition, which serves to increase the degree of diversity with respect to the selection of substituents present on the pharmacogenetic step.

In another aspect, the present invention relates to the following compounds:

5-phenoxy-3- (5- (trifluoromethyl) pyridin-2-yl) -1,3,4-oxadiazole-2 (3H) -one

3- (benzo [d] thiazol-2-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one

3- (benzo [d] oxazol-2-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one

3- (5-bromopyridin-2-yl) -5-phenoxy-1,3,4-oxadiazole-2 (3H) -one

3- (6-Chloropyridin-3-yl) -5- (4-methoxyphenoxy) -1, 3,4-oxadiazole-2 (3H) -one

3- (6-chloropyridin-3-yl) -5- (4-hydroxyphenoxy) -1,3,4-oxadiazole-2 (3H) -one

3- (2-Chloropyridin-3-yl) -5- (4-methoxyphenoxy) -1,3,4-oxadiazole-2 (3H) -membered hydrochloride

5- (benzyloxy) -3- (5- (trifluoromethyl) pyridin-2-yl) -1,3,4-oxadiazole-2 (3H) -one

5- (benzyloxy) -3- (pyridin-2-yl) -1,3,4-oxadiazole-2 (3H) -one.

3- (benzo [d] thiazol-2-yl) -5-benzyloxy-1,3,4-oxadiazole-2 (3H) -one

3- (benzo [d] oxazol-2-yl) -5-benzyloxy-1,3,4-oxadiazole-2 (3H) -one

5- (benzyloxy) -3- (6-chloropyridazin-3-yl) -1,3,4-oxadiazole-2 (3H) -one

It is to be understood that the invention may be modified within the scope of the appended claims.

Claims (90)

Compound represented by the following formula (I):

(I),
In the above formula, R ¹ to R ⁵ are each independently,
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl-carboxy, C ₁ -C ₆ - Al Kilmer kaeptil _{(C 1 -C 6 -alkylmercaptyl),} C 6 -C 10 - aryl Murray kaeptil, C ₁ -C ₆ -alkylmercaptocarbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercetocarbonyl, C ₁ -C ₆ -alkylmercaptocarbonyl, C _6- C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsulfoxy, C ₆ -C ₁₀ -arylsulfoxy, each above Is optionally substituted one or more times with the functional group of the parenthesis:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - have one functional group or an amino substituted alkyl, double the selected moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups the alkyl moiety can be bonded to form 5 or 6 membered rings; CONH ₂ or SO ₂ NH ₂ ; amino; C ₁ -C ₆ -alkyl, C ₆ -C _10- Aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ Amino once or more substituted with a residue selected from -C ₁₀ -arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ )
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or R ⁶ is NR ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, and the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice with alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _3;
OCF ₃ ; or
Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms, optionally substituted one or more times by the compounds of the parenthesis:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a moiety selected from C ₁₀ -aryl-C ₁ -C ₆ -alkyl, in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );
Any two or more of said R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

In which n is 0 or 1; m is 0, 1, 2, 3, 4, 5 or 6;

In which X is O or S;

Wherein Y is represented as follows:
a) hydrogen;
b) C ₁ -C ₁₈ -alkyl, mono or polyunsaturated C ₂ -C ₁₈ -alkylene, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C _1- C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ -aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - cycloalkenyl Kilmer captopril-carbonyl, C ₆ -C ₁₀ - aryl bots, captopril-carbonyl, C ₁ -C ₆ - Al Kilmer Captocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C _10- Arylsulfoxy, or saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms, each of which (B1), b2), b3)) is optionally substituted once or several times by:
b1) C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy , C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C _6- C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl carbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril Carbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy; Each of which is optionally C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ , SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ with an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; Or substituted once or several times by OCF ₃ ;
Some of the substituents in b1) above may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

or
b2) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; or
Disubstituted amino of formula (II)

(II)

(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₆ -, and NR ⁶ with R ⁶ selected from alkyl, methylene of formula (II) group is optionally C ₁ - May be substituted once or twice with C ₆ -alkyl, fluoro or chloro;

or
b3) C ₁ -C ₆ -alkyl as a saturated, unsaturated or aromatic heterocyclic ring system of up to 10 atoms; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted once or several times with CF ₃ or OCF ₃ ;

c) SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Thiols; Hydroxyl group; Nitro; Cyano; Fluorosulfonyl; Halogen selected from fluoro, chloro, bromo or iodine; CF _3; Or OCF ₃ ;

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof, for inhibitors of fatty acid amide hydrolase (FAAH).
The compound of claim 1, wherein R ¹ to R ⁵ are each independently represented as follows:
Hydrogen;
Hydroxyl group;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is optionally C ₁ -C ₆ -alkyl, To C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Substituted one or several times by;
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl;
1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, optionally substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, amino, fluoro, chloro or CF ₃ ; or
Disubstituted amino of formula (II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice among alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
CONH ₂ or SO ₂ NH ₂ having amino functional groups, once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;
Fluoro;
Chloro;
Bromo;
CF _3; or
OCF ₃ .
A compound according to claim 1 or 2, wherein one or more of R ¹ to R ⁵ is hydrogen, fluorine or chlorine.
The compound of claim 3, wherein R ¹ or R ⁵ Is hydrogen or fluorine.
The compound according to claim 1, wherein one or more of R ¹ to R ⁵ represents:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino , Di-C ₁ -C ₆ -alkylamino, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl), hydroxy, Optionally substituted one or several times with fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ .
A compound according to claim 5, wherein one of R ² , R ³ or R ⁴ represents:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ CONH substituted once or twice with -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, (C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl ₂ or SO ₂ NH ₂ ), optionally substituted one or several times with hydroxy, fluoro, chloro, or bromo.
A compound according to claim 1, wherein one or more of R ¹ to R ⁵ represents:
Amino;
Amino substituted one or more of the residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; Or di-substituted amino of formula (II)

(II)

(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₆ -, and NR ⁶ with R ⁶ selected from alkyl, methylene of formula (II) group is optionally C ₁ - Substituted once or twice with C ₆ -alkyl, fluoro or chloro).
8. A compound according to claim 7, wherein any one of R ² , R ³ or R ⁴ represents
Amino;
Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)

Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group in formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro).
The compound of claim 1, wherein n is 0; m is 0, 1, 2, 3, 4, 5 or 6; And Y is each C ₃ -C ₆ -cycloalkyl or C ₆ -C ₁₀ -aryl, optionally substituted one or more times by (a), b), c)):
a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkoxy, each of which is optionally substituted one or several times by the following parentheses:
Substituted once or twice with (C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl CONH ₂ or SO ₂ NH ₂ ; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C Amino substituted one or more times with a residue selected from ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

or
b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino group substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, and the methylene group of formula (II) is C ₁ -C _4- Optionally substituted once or twice with alkyl, fluoro or chloro;

or
c) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or several times by the following parentheses:
Substituted once or twice with (C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl CONH ₂ or SO ₂ NH ₂ ; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C Amino substituted one or more times with a residue selected from ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ ).
The compound of claim 9, wherein n is 0; m is 0 or 1; And Y is phenyl, 1-naphthyl, 2-naphthyl, 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl ring system.
The compound of claim 10, wherein Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once or several times substituted with CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with a C ₁ -C ₆ -alkyl moiety capable of bonding to form a 5 or 6 molecular ring. Compound.
12. The compound of claim 11, wherein m is 0 and Y is phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.
12. The compound of claim 11 wherein m is 0 and Y is 4-position with fluoro or chloro, 2- and 4-position with fluoro, 2- and 4-position with chloro or 4- with phenyl. And is phenyl substituted at the position.
The compound of claim 1, wherein m is 0; n is 0; Y, which is phenyl once or twice substituted by fluoro, chloro or bromo; And any one of R ² to R ⁴ is OR ⁷ which is R ⁷ selected from hydrogen, C ₁ -C ₆ -alkyl.
15. The compound of claim 14, wherein Y is phenyl substituted at the 4-position with fluoro or chloro, the 2-, 4-position with fluoro, or the 2-, 4-position with chloro.
16. The compound of claim 14 or 15, wherein R ¹ or R ⁵ is hydrogen or fluorine.
The compound of any one of claims 14-16, wherein R ² or R ³ and R ⁴ are hydroxy.
18. A compound according to any one of claims 1 to 17 for the treatment of disorders positively affected by the inhibition of FAAH.
19. The method of claim 18, wherein the disorder is pain, dizziness, vomiting and nausea, eating disorders, neurological and psychiatric pathologies, acute and chronic neurodegenerative diseases, epilepsy, sleep disorders, cardiovascular disease, cancer, disorders of the immune system , Parasite, virus or bacterial infection disease, inflammatory disease, osteoporosis, eye disease, lung disease and gastrointestinal disease.
18. Use of a compound according to any one of claims 1 to 17 for the inhibition of FAAH.
18. Use of a compound according to any one of claims 1 to 17 for the treatment of disorders which are positively affected by the inhibition of FAAH.
18. Use of a compound according to any one of claims 1 to 17 for the manufacture of a medicament for the treatment of a disorder positively affected by the inhibition of FAAH.
23. The method of claim 21 or 22, wherein the disorder is pain, dizziness, vomiting and nausea, eating disorders, neurological and psychiatric pathologies, diseases of acute and chronic neurodegeneration, epilepsy, sleep disorders, cardiovascular diseases, cancer, Use of a compound, characterized in that selected from disorders of the immune system, parasites, viral or bacterial infectious diseases, inflammatory diseases, osteoporosis, eye diseases, lung diseases and gastrointestinal diseases.
Compound represented by the following formula (I):

(I)
In the above formula, R ¹ to R ⁵ are each independently,
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of which is optionally selected once by parenthesis or Replaced multiple times:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - has one or more substituted amino functional groups selected from the alkyl moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups, the alkyl moiety is CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C _10- Amino substituted one or more times with a residue selected from arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _3;
OCF ₃ ; or
Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or more times by the following parentheses:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a moiety selected from C ₁₀ -aryl-C ₁ -C ₆ -alkyl, in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );
Any two or more of R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

N is 0 or 1 in the above formula; m is 0, 1, 2, 3, 4, 5 or 6;

Wherein X is O or S;

In the above formula, Y is represented as follows:
a) hydrogen;
b) C ₁ -C ₁₈ -alkyl, mono or polyunsaturated C ₂ -C ₁₈ -alkylene, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C _1- C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ -aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - cycloalkenyl Kilmer captopril-carbonyl, C ₆ -C ₁₀ - aryl bots, captopril-carbonyl, C ₁ -C ₆ - Al Kilmer Captocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C _10- Arylsulfoxy, or saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms, each of which (B1), b2), b3)) is optionally substituted once or several times by:
b1) C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy , C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C _6- C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl carbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril Carbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy; Each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ , SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ with an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; Or optionally substituted one or more times by OCF ₃ ;
Some of the substituents in b1) above may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

or
b2) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; or
Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₆ -, and NR ⁶ with R ⁶ selected from alkyl, methylene of formula (II) group is optionally C ₁ - May be substituted once or twice with C ₆ -alkyl, fluoro or chloro;

or
b3) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms, which include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or more times with CF ₃ or OCF ₃ ;

c) SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Thiols; Hydroxyl group; Nitro; Cyano; Fluorosulfonyl; Halogen selected from fluoro, chloro, bromo or iodine; CF _3; Or OCF ₃ ;

If n is 0 and m is 0, then:
a) R ² or R ⁴ does not represent a C (= A) -N (B) -SO ₂ -NR ⁶ R ⁷ substituent wherein A is O or S and B is hydrogen, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy-alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₆ -alkenyl, C ₃ -C ₆ -alkynyl or optionally substituted benzyl derivatives And R ⁶ and R ⁷ independently represent hydrogen or an organic moiety, or an organic cyclic structure together;
b) when Y represents unsubstituted phenyl, R ¹ to R ⁵ independently of one another do not represent hydrogen, fluoro, bromo, chloro, iodine or alkyl radicals;
c) R ² or R ⁴ does not represent a pyrazol-3-yl-derivative; And
d) a phenyl ring substituted with R ¹ to R ⁵ , and Y not represented by combinations of compounds in the table below:

And furthermore when n is 0 and m is 1, if R ¹ , R ² and R ⁵ are hydrogen, R ⁴ is hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5 Tetramethylcyclohexyloxy, benzyloxy, phenoxy, phenyl, 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, R ³ is hydrogen, trifluoromethoxy, trifluorobutoxy, 3, 3,5,5-tetramethylcyclohexyloxy, phenoxy, 4-chlorophenoxy, cyclohexyl, phenyl, morpholinosulfonyl, 3,3,5-trimethylcyclohexylaminosulfonyl, 2, 2,6,6-tetramethylpiperidin-4-ylaminosulfonyl (2,2,6,6-tetramethylpiperidin-4-ylaminosulfonyl), 2- (diisopropylaminoethyl) aminosulfonyl, 4-methyl Piperazin-1-yl-sulfonyl, 3,3-dimethylpiperidinocarbonyl or 3,5-dichlorophenoxy
If 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, then Y is not unsubstituted phenyl;

And if m = 0, n = 0 then Y is not C ₁ -C ₄ -alkyl as an additional condition;

And with the additional conditions that the compound is not one of the following compounds:
5-phenoxy-3-phenyl- (1,3,4) -oxadiazorin-2-one
(5-phenoxy-3-phenyl- (1,3,4) -oxadiazolin-2-one)
5-dodecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Dodecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-octyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Octyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (3-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (3-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (4- (4-chlorophenoxy) -phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (4- (4-chlorphenoxy) -phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-octyloxy-3-phenyl-3H- (1,3,4) -oxadiazole-2-one
(5-Octyloxy-3-phenyl-3H- (1,3,4) -oxadiazol-2-one)
5-octyloxy-3- (3-fluoro-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Octyloxy-3- (3-fluor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (3-fluoro-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (3-fluor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (3-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (3-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3-phenyl-3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3-phenyl-3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (4-nitro-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (4-nitro-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-hexadecyloxy-3- (4-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Hexadecyloxy-3- (4-benzyloxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-decyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Decyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-Undecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Undecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-tetradexyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Tetradecyloxy-3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-tridecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-Tridecyloxy-3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (2- (2-hexyloxy-ethoxy) -ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (2- (2-Hexyloxy-ethoxy) -ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-((Z) -octadec-9-enyloxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-((Z) -Octadec-9-enyloxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (Dodecyloxy-ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (Dodecyloxy-ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (2- (4-Fluorophenyl) -ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (2- (4-Fluorphenyl) -ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5-((3ss-cholestan-3-yl) -oxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5-((3ss-Cholestan-3-yl) -oxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (2-Butoxy-ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (2-Butoxy-ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (7-phenyl-heptyloxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (7-Phenyl-heptyloxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (Docosyloxy-ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (Docosyloxy-ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (2- (1-naphthoxy) -ethoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (2- (1-Naphthloxy) -ethoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (4-Octylphenoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (4-Octylphenoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (3-Penoxy-phenoxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (3-Phenoxy-phenoxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (Dodecyloxy) -3- (4-trifluoromethoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (Dodecyloxy) -3- (4-trifluormethoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (Dodecyloxy) -3- (3, 4-dichlor-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (Dodecyloxy) -3- (3, 4-dichlor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (Dodecyloxy) -3- (3, 5-dichlor-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (Dodecyloxy) -3- (3, 5-dichlor-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (Dodecyloxy) -3- (3-methoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one
(5- (Dodecyloxy) -3- (3-methoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one)
5- (dodecyloxy) -3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazole-2-one;
(5- (Dodecyloxy) -3- (4-methoxy-phenyl) -3H- (1,3,4) -oxadiazol-2-one);

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.
The method of claim 24, wherein R ¹ to R ⁵ Are each independently a compound having the following characteristics:
Hydrogen;
Hydroxyl group;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is optionally C ₁ -C ₆ -alkyl, To C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Substituted one or several times by;
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl;
1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, which is optionally substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, amino, fluoro, chloro or CF ₃ ;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
CONH ₂ or SO ₂ NH ₂ , having amino functional groups substituted once or twice with residues selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;
Fluoro;
Chloro;
Bromo;
CF _3; or
OCF ₃ .
A compound according to claim 24 or 25, wherein one or more of R ¹ to R ⁵ represent hydrogen, fluorine, chlorine.
27. The compound of claim 26, wherein R ¹ or R ⁵ represents hydrogen or fluorine.
The compound of any one of claims 24-27, wherein one or more of R ¹ to R ⁵ represents:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is optionally C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C _6- Alkylamino, di-C ₁ -C ₆ -alkylamino, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice in C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl), hydr Substituted once or several times by hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ .
The compound of claim 28, wherein any one of R ² , R ³ or R ⁴ represents:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ Optionally substituted once or twice in -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, (C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl Optionally substituted once or several times by CONH ₂ or SO ₂ NH ₂ ), hydroxy, fluoro, chloro, or bromo.
30. A compound according to any one of claims 24 to 29, wherein one or more of R ¹ to R ⁵ represent:
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro).
The compound of claim 30, wherein any one of R ² , R ³ or R ⁴ represents:
Amino;
Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Alkyl, fluoro or chloro may be optionally substituted once or twice).
32. The compound of any one of claims 24-31, wherein n is 0; m is 0, 1, 2, 3, 4, 5 or 6; Y is C ₃ -C ₆ -cycloalkyl or C ₆ -C ₁₀ -aryl, each of which is optionally substituted one or more times by (a), b), c)) :
a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkoxy, each of which is optionally substituted one or several times by the following parentheses:
Substituted once or twice with (C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl CONH ₂ or SO ₂ NH ₂ ; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C Amino substituted one or more times with a residue selected from ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

or
b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino group substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice with alkyl, fluoro or chloro;

or
c) Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or several times by the following parentheses:
Substituted once or twice with (C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl CONH ₂ or SO ₂ NH ₂ ; SO ₃ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C Amino substituted one or more times with a residue selected from ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -acylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ ).
33. The method of claim 32, wherein n is 0; m is 0 or 1; And Y is phenyl, 1-naphthyl, 2-naphthyl, 2-pyridinyl, 3-pyridinyl or 4-pyridinyl ring system.
The compound of claim 33, wherein Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once or several times with CONH ₂ or SO ₂ NH ₂ optionally substituted one or two times with C ₁ -C ₆ -alkyl, an optional moiety that can be bonded to form a 5 or 6 ring ring; Compound which is characterized in that.
35. The compound of claim 34, wherein m is 0 and Y is phenyl substituted once or twice by hydroxy, fluoro, chloro or bromo.
The compound of claim 34, wherein m is 0, Y is 4-position with fluoro or chloro, 2- and 4-position with fluoro, 2- and 4-position with chloro, or 4- with phenyl. A compound characterized by representing a substituted phenyl at the position.
The compound of claim 24, wherein m is 0; n is 0; Y represents phenyl substituted once or twice with fluoro, chloro, or bromo; Any one of R ² to R ⁴ represents OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₆ -alkyl.
38. The compound of claim 37, wherein Y represents phenyl substituted at the 4-position with fluoro or chloro, the 2-, 4-position with fluoro, or the 2-, 4-position with chloro. .
The compound of claim 37 or 38, wherein R ¹ or R ⁵ represents hydrogen or fluorine.
40. The compound of any one of claims 37-39, wherein R ² or R ³ and R ⁴ represent hydroxy.
Compound represented by the following formula (I):

(I),
In the above formula, R ¹ to R ⁵ are each independently,
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of which is optionally selected once by parenthesis or Replaced multiple times:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - has one or more substituted amino functional groups selected from the alkyl moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups, the alkyl moiety is CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C _10- Amino substituted one or more times with a residue selected from arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ - alkyl, C ₆ -C ₁₀ - aryl, C ₆ -C ₁₀ - aryl -C ₁ - C ₆ - alkyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl carbonyl Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₆ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₆ -alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _3;
OCF ₃ ; or
Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are indicated as being optionally substituted one or several times by the following parentheses:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a moiety selected from C ₁₀ -aryl-C ₁ -C ₆ -alkyl, in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

Wherein any two or more of R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

In which n is 0; m is 0;

Y represents phenyl optionally substituted one or more times by (a), b), c)):
a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkylcarbonyl, C ₁ -C _6- carboxy alkyl, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - Cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl , C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy;
Each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl Or SO ₂ NH ₂ ; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or several times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or several times with CF ₃ or OCF ₃ ;
Some of these optional substituents may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system; or

b) saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl Or SO ₂ NH ₂ ; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or several times from CF ₃ or OCF ₃ ; or

c) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Disubstituted amino of formula (IV)

(IV)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, wherein the methylene group of formula (IV) is C ₁ -C _4- Optionally substituted once or twice among alkyl, fluoro or chloro);

Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof;
Subject to
a) R ² or R ⁴ does not represent a substituent C (= A) -N (B) -SO ₂ -NR ⁶ R ⁷ , wherein A is O or S, B is hydrogen, cyano, C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy-alkyl, C ₃ -C ₇ -cycloalkyl, C ₃ -C ₆ -alkenyl, C ₃ -C ₆ -alkynyl or optionally benzyl derivative, and R ⁶ and R ⁷ each independently represent hydrogen or an organic moiety, or all organic cyclic structures;
b) when Y represents unsubstituted phenyl, R ¹ to R ⁵ independently of one another do not represent hydrogen, fluoro, bromo, chloro, iodine or alkyl radicals;
c) R ² or R ⁴ do not represent pyrazol-3-yl-derivatives; And
d) Phenyl ring substituted with R ¹ to R ⁵ and Y do not appear as a combination of compounds in the table below:

The compound of claim 41, wherein R ¹ to R ⁵ are each independently represented by:
Hydrogen;
Hydroxyl group;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of C ₁ -C ₆ -alkyl, C ₁ Once with -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Or optionally substituted many times;
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl;
1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl optionally substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, amino, fluoro, chloro or CF ₃ ;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C _6- Optionally substituted once or twice among alkyl, fluoro or chloro);
CONH ₂ ;
SO ₂ NH ₂ ;
CONH ₂ or SO ₂ NH ₂ having amino functional groups, once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;
Fluoro;
Chloro;
Bromo;
CF _3; or
OCF ₃ .
43. The compound of claim 41 or 42, wherein one or more of R ¹ to R ⁵ represent hydrogen, fluorine or chlorine.
44. The compound of claim 43, wherein R ¹ or R ⁵ represents hydrogen or fluorine.
45. A compound according to any one of claims 41 to 44, wherein one or more of R ¹ to R ⁵ represent:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino , Di-C ₁ -C ₆ -alkylamino, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice in C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl), hydroxy, Fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Optionally substituted one or more times by
The compound of claim 45, wherein any one of R ² , R ³ or R ⁴ represents:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ Optionally one or two substitutions at -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, (C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl Optionally substituted once or several times in the formula CONH ₂ or SO ₂ NH ₂ ), hydroxy, fluoro, chloro, or bromo.
47. A compound according to any one of claims 41 to 46, wherein one or more of R ¹ to R ⁵ represent:
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₆ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₆ -alkyl, fluoro or chloro).
48. The compound of claim 47, wherein one of R ² , R ³ or R ⁴ represents:
Amino;
Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₆ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₆ -alkyl, fluoro or chloro).
49. A compound according to any one of claims 41 to 48, wherein Y represents phenyl substituted once or several times by (a), b), c)):
a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is optionally substituted one or several times by the following parentheses:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; SO ₃ H; CO ₂ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl -C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Amino substituted once or more by residue; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; OCF ₃ ; or C ₁ Amino groups optionally substituted once or twice with -C ₆ -alkyl CONH ₂ or SO ₂ NH ₂ );
or
b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Or an amino group substituted once or twice with C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, and di-C _1- In the case of a C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₆ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₆ -alkyl, fluoro or chloro;
or
c) saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ ; SO ₂ NH ₂ ; CONH ₂ substituted one or two times with C ₁ -C ₆ -alkyl which may be bonded to form a 5 or 6 cyclic ring Or SO ₂ NH ₂ ; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; Or optionally substituted one or several times from OCF ₃ .
The compound of claim 49, wherein Y is phenyl substituted once or several times by parenthesis:
(C ₁ -C ₆ -alkyl; phenyl; C ₁ -C ₆ -alkoxy; hydroxy; fluoro; chloro; bromo; CF ₃ ; OCF ₃ ; amino; or (bonds to form a 5 or 6 molecular ring the optional C ₁ -C _6, which may be -alkyl residues), C ₁ -C ₆ - han an optionally substituted once or twice by alkyl, CONH _2).
51. The compound of claim 50, wherein Y is phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.
51. The phenyl of claim 50 wherein Y is substituted at 4-position with fluoro or chloro, 2-, 4-position with fluoro, 2-, 4-position with chloro, or 4-position with phenyl. The compound characterized by the above-mentioned.
42. The compound of claim 41, wherein Y is phenyl substituted once or twice by fluoro, chloro or bromo; Any one of R ² to R ⁴ represents OR ⁷ with R ⁷ selected from hydrogen and C ₁ -C ₆ -alkyl.
54. The compound of claim 53, wherein Y is phenyl substituted at the 4-position with fluoro or chloro, the 2-, 4-position with fluoro or the 2-, 4-position with chloro.
55. The compound of claim 53 or 54, wherein R ¹ or R ⁵ represents fluorine or hydrogen.
The compound of any one of claims 53-55, wherein R ³ or R ³ and R ⁴ represent hydroxy.
Compound represented by the following formula (I):

(I),
In which R ¹ or R ⁵ is hydrogen or fluorine;
Any one of R ² to R ⁴ is a hydroxyl group and the remaining R residues are represented as follows:
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol , Number Search one or optionally substituted multiple times in a group, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF _3;
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _{3 ;}
OCF ₃ ; or
C ₁ -C ₆ -acyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms optionally substituted once or several times with ₃ ;

And two or more of R ² to R ⁴ may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

n and m are 0; And

Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl residue which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times,
Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.
Compound represented by the following formula (I):

(I),
In which R ¹ or R ⁵ is hydrogen or fluorine;
Any one of R ² to R ⁴ is amino and the remaining R residues are represented as follows:
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol , Number Search one or optionally substituted multiple times in a group, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF _3;
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro);
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _{3 ;}
OCF ₃ ; or
C ₁ -C ₆ -acyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms optionally substituted one or several times with ₃ ;

And two or more of R ² to R ⁴ may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

n and m are 0; And

Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times,
Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.
Compound represented by the following formula (I):

(I),

In which R ¹ or R ⁵ is hydrogen or fluorine;
One of R ³ or R ⁴ is C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy Each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di Optionally substituted one or several times with -C ₁ -C ₆ -alkylamino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ ;
The other of R ³ or R ⁴ is C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl , C ₆ -C ₁₀ - aryl-carbonyl, C ₁ -C ₆ - alkylsulfonyl, and C ₆ -C ₁₀ - aryl with one selected from the sulfonyl moiety or several times substituted amino;
And R ² are represented as follows:
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol , Number Search one or optionally substituted multiple times in a group, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF _3;
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ or hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _{3 ;}
OCF ₃ ; or
C ₁ -C ₆ -acyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms optionally substituted once or several times at ₃ ;

And two or more of R ² to R ⁴ may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

n and m are 0; And

Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or Phenyl substituted several times,
Or stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof.
The compound of any one of claims 57-59, wherein Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; Or once with CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl (which is an optional C ₁ -C ₆ -alkyl moiety which may be bonded to form a 5 or 6 molecular ring) or A compound characterized by representing phenyl substituted several times.
61. The compound of claim 60, wherein Y represents phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.
61. The phenyl substituted according to claim 60, wherein Y is substituted at 4-position with fluoro or chloro, 2-, 4-position with fluoro, 2-, 4-position with chloro or 4-position with phenyl. The compound characterized by the above-mentioned.
Compound represented by the following formula (I):

(I)
Wherein R ¹ to R ⁵ are each independently
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl , C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of which is optionally selected once by parenthesis or Replaced multiple times:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; C ₆ -C ₁₀ -aryloxy; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ - aryl or C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - has one or more substituted amino functional groups selected from the alkyl moiety, di -C ₁ -C ₆ - alkyl-substituted In the case of amino functional groups, the alkyl moiety is CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C _10- Amino substituted one or more times with a residue selected from arylsulfonyl; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ - alkyl, C ₆ -C ₁₀ - aryl, C ₆ -C ₁₀ - aryl -C ₁ - C ₆ - alkyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl carbonyl Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH ₂ or hydrogen, and C ₁ -C ₆ -, and a methylene with an NR ⁶ R ⁶ is selected from alkyl, formula (II) of group optionally C ₁ - Optionally substituted once or twice with C ₆ -alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _{3 ;}
OCF ₃ ; or
Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms are optionally substituted one or more times by the following parentheses:
(C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; SO ₃ H; CONH _{2 ;} SO ₂ NH ₂ ; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C _6- Having at least one amino group substituted with a moiety selected from C ₁₀ -aryl-C ₁ -C ₆ -alkyl, in the case of a di-C ₁ -C ₆ -alkyl-substituted amino functional group, the alkyl moiety is 5 or CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 6 molecular ring; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ Once or as a residue selected from -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl Substituted amino; thiol; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ or OCF ₃ );

Wherein any two or more of R ¹ to R ⁵ may be combined to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

Wherein n is 0; m is 1;

Y represents phenyl optionally substituted one or more times by (a), b), c)):
a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkylcarbonyl, C ₁ -C _6- carboxy alkyl, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - Cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl , C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy;
(Each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl) Or SO ₂ NH ₂ ; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or several times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or several times with CF ₃ or OCF ₃ );

Some of these optional substituents may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system; or

b) saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl Or SO ₂ NH ₂ ; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₄ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or several times from CF ₃ or OCF ₃ ; or

c) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Disubstituted amino of formula (IV)

(IV)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ , which is R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, wherein the methylene group of formula (IV) is C ₁ -C _4- Optionally substituted once or twice among alkyl, fluoro or chloro);

If R ¹ , R ² and R ⁵ are hydrogen, R ⁴ is hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, benzyloxy, phenoxy, Phenyl, 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, R ³ is hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, phenoxy , 4-chlorophenoxy, cyclohexyl, phenyl, morpholinosulfonyl, 3,3,5-trimethylcyclohexylaminosulfonyl, 2,2,6,6-tetramethylcyseridin-4-yl Aminosulfonyl (2,2,6,6-tetramethylpiperidin-4-ylaminosulfonyl), 2- (diisopropylaminoethyl) aminosulfonyl, 4-methylpiperazin-1-yl-sulfonyl (4-methylpiperazin-1 -yl-sulfonyl), 3,3-dimethylpiperidinocarbonyl or 3,5-dichlorophenoxy
If 2-dimethylaminoethyloxy or 3-methylphenoxy-methyl, Y is not an unsubstituted phenyl.
64. The compound of claim 63, wherein R ¹ to R ⁵ are each independently represented as follows:
Hydrogen;
Hydroxyl group;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, C ₁ -C ₆ -alkylcarboxy, C ₆ -C ₁₀ -arylcarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is optionally C ₁ -C ₆ -alkyl, To C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ Substituted one or several times by;
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl;
1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, which is optionally substituted one or more times with a residue selected from C ₁ -C ₆ -alkyl, amino, fluoro, chloro or CF ₃ ;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro;
CONH ₂ ;
SO ₂ NH ₂ ;
CONH ₂ or SO ₂ NH ₂ , having amino functional groups substituted once or twice with residues selected from C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl;
Fluoro;
Chloro;
Bromo;
CF _3; or
OCF ₃ .
65. The compound of claim 63 or 64, wherein one or more of R ¹ to R ⁵ represent hydrogen, fluorine or chlorine.
67. The compound of claim 65, wherein R ¹ or R ⁵ represents hydrogen or fluorine.
The compound of any one of claims 63-66, wherein one or more of R ¹ to R ⁵ represent:
Hydroxy; or
C ₁ -C ₆ - alkoxy, C ₆ -C ₁₀ - aryloxy, C ₆ -C ₁₀ - aryl -C ₁ -C ₆ - alkoxy, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxylic , C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, amino, C ₁ -C ₆ -alkylamino , Di-C ₁ -C ₆ -alkylamino, (CONH ₂ or SO ₂ NH ₂ optionally substituted once or twice with C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl), hydroxy, Optionally substituted one or several times with fluoro, chloro, bromo, cyano, CF ₃ or OCF ₃ .
The compound of claim 67, wherein one of R ² , R ³ or R ⁴ represents:
Hydroxy; or
C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkoxy, each of which is C ₁ -C ₆ -alkyl, C ₁ -C ₆ Optionally substituted once or twice in -alkoxy, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, (C ₁ -C ₆ -alkyl or C ₆ -C ₁₀ -aryl Optionally substituted once or several times by CONH ₂ or SO ₂ NH ₂ ), hydroxy, fluoro, chloro, or bromo.
The compound of any one of claims 63-68, wherein one or more of R ¹ to R ⁵ represents:
Amino;
Amino substituted one or more times with residues selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro).
The compound of claim 69, wherein any one of R ² , R ³ or R ⁴ represents:
Amino;
Amino once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl; or
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice with alkyl, fluoro or chloro).
The compound of any one of claims 63-70, wherein Y represents phenyl substituted one or more times by (a), b), c)):
a) C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy , C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; SO ₃ H; CO ₂ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CONH ₂ ; SO ₂ NH ₂ ; OCF ₃ ; Or optionally substituted once or several times with CONH ₂ or SO ₂ NH ₂ with an amino functional group substituted once or twice with C ₁ -C ₆ -alkyl;
or
b) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; OCF ₃ ; CO ₂ H; SO ₃ H; CONH ₂ ; SO ₂ NH ₂ ; Or an amino group substituted once or twice with C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, and di-C _1- In the case of a C ₆ -alkyl-substituted amino functional group the alkyl moiety may be CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; Amino once or several times substituted with C ₁ -C ₆ -alkyl or phenyl; Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is O, CH ₂ , or NR ⁶ with R ⁶ selected from hydrogen and C ₁ -C ₄ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₄ Optionally substituted once or twice among alkyl, fluoro or chloro);
or
c) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms, which include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH _{2 ;} SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ having amino functional groups once or twice substituted with C ₁ -C ₆ -alkyl which may be bonded to form a 5 or 6 molecular ring; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; Optionally substituted one or more times with CF ₃ or OCF ₃ ;
The compound of claim 71, wherein Y is C ₁ -C ₆ -alkyl; Phenyl; C ₁ -C ₆ -alkoxy; Hydroxy; Fluoro; Chloro; Bromo; CF _3; OCF ₃ ; Amino; The optional C ₁ -C _6, which may be combined to form a 5- or 6-ring molecular-alkyl moiety of C ₁ -C ₆ - once or several times substituted with one or two optionally substituted alkyl, CONH ₂ To represent phenyl.
The compound of claim 71, wherein Y represents phenyl substituted once or twice with hydroxy, fluoro, chloro or bromo.
73. The phenyl of claim 72 wherein Y is substituted at 4-position with fluoro or chloro, 2- and 4-position with fluoro, 2- and 4-position with chloro, or 4-position with phenyl. A compound characterized by the above-mentioned.
64. The compound of claim 63, wherein Y is phenyl once or twice substituted by fluoro, chloro or bromo; And any one of R ² to R ⁴ represents OR ⁷ having R ⁷ selected from hydrogen and C ₁ -C ₆ -alkyl.
76. The compound of claim 75, wherein Y represents phenyl substituted at the 4-position with fluoro or chloro, the 2-, 4-position with fluoro or the 2-, 4-position with chloro.
77. The compound of claim 75 or 76, wherein R ¹ or R ⁵ represents fluorine or hydrogen.
78. The compound of any one of claims 75-77, wherein R ³ or R ³ and R ⁴ represent hydroxy.
A compound for the inhibition of fatty acid amide hydrolase (FAAH), comprising a drug action generating group represented by the following substance (III).

(III)
79. A pharmaceutical composition comprising any compound of any one of claims 24 to 79 and a pharmaceutically acceptable carrier.
80. The compound of any of claims 24-79, which is a drug use.
79. The compound of any of claims 24-78, for the inhibition of fatty acid amide hydrolase (FAAH).
80. A compound according to any one of claims 24 to 79, characterized for the treatment of any disorder positively affected by the inhibition of fatty acid amide hydrolase (FAAH).
84. The method of claim 83, wherein the disorder is pain, dizziness, vomiting and nausea, eating disorders, neurological and psychopathological pathologies, acute and chronic neurodegenerative diseases, epilepsy, sleep disorders, cardiovascular diseases, cancer, disorders of the immune system , Parasite, virus or bacterial infection disease, inflammatory disease, osteoporosis, eye disease, lung disease and gastrointestinal disease.
80. The use of a compound according to any one of claims 24 to 79 for the inhibition of fatty acid amide hydrolase (FAAH).
80. The use of a compound according to any one of claims 24 to 79, wherein the compound is characterized for the treatment of a disorder positively affected by inhibition of FAAH.
Use of a drug action generating group represented by the following structural formula (III) for the preparation of a compound for the treatment of a disorder positively affected by the inhibition of fatty acid amide hydrolase (FAAH).

(III)
Article 86 or 87, wherein the disorder is pain, dizziness, vomiting and nausea, eating disorders, neurological and psychiatric pathologies, acute and chronic neurodegenerative diseases, epilepsy, sleep disorders, cardiovascular diseases, cancer, immunity Use of the system selected from among disorders of the system, parasites, viral or bacterial infectious diseases, inflammatory diseases, osteoporosis, ocular diseases, lung diseases and gastrointestinal diseases.
79. A process for the preparation of a compound according to any one of claims 1 to 17 and 24 to 79, characterized by the compound represented by the following general formula (IV):

(IV)

In the above formula, R ¹ to R ⁵ are each independently,
Hydrogen;
C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C _6- C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkoxycarbonyl, C ₁ -C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl , C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl-carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril carbonyl Nyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy, each of C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -aryloxy, CO ₂ H, SO ₃ H, amino, C ₁ -C ₆ -alkylamino, di-C ₁ -C ₆ -alkylamino, thiol ), Number Group, a nitro, cyano, fluoro, chloro, bromo, search iodine, or CF ₃ with one or optionally substituted several times by the OCF _3;
CO ₂ H;
SO ₃ H;
Amino;
C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl;
Disubstituted amino of formula (II)

(II)
Wherein o is 0 or 1, W is NR ⁶ with R ⁶ selected from O, CH ₂ , or hydrogen, C ₁ -C ₆ -alkyl, wherein the methylene group of formula (II) is C ₁ -C ₆ Optionally substituted once or twice among alkyl, fluoro or chloro);
CONH ₂ ;
SO ₂ NH ₂ ;
Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring;
Thiols;
Hydroxyl group;
Nitro;
Cyano;
Fluorosulfonyl;
Halogen selected from fluoro, chloro, bromo or iodine;
CF _3;
OCF ₃ ; or
Saturated, unsaturated, or aromatic heterocyclic ring systems of up to 10 atoms include C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkoxy, COOH, SO ₃ H, amino, thiol, hydroxyl, nitro, Optionally substituted one or several times with cyano, fluoro, chloro, bromo, iodine, CF ₃ or OCF ₃ ;

And any two or more of R ¹ to R ⁵ may combine to form an fused saturated, unsaturated, or aromatic homo- or hetero-ring system;

m is 0, 1, 2, 3, 4, 5 or 6;

Y is represented as follows (a), b), c)):
a) hydrogen;
b) C ₁ -C ₁₈ -alkyl, mono or polyunsaturated C ₂ -C ₁₈ -alkylene, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy, C ₆ -C ₁₀ -allyloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C _6- C ₁₀ -aryloxycarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ - aryl -C ₁ -C ₈ - alkylcarbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril-carbonyl, C ₃ -C ₈ - cycloalkenyl Kilmer captopril-carbonyl, C ₆ -C ₁₀ - aryl bots, captopril-carbonyl, C ₁ -C ₆ - Al Kilmer captopril Carboxy, C ₆ -C ₁₀ -allylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -aryl Sulfoxy, or up to 10 atoms, saturated, unsaturated, or aromatic heterocyclic ring systems, each of which is optional Once or several times substituted by a search for a (b1), b2), b3)):
b1) C ₁ -C ₆ -alkyl, C ₃ -C ₈ -cycloalkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkoxy , C ₆ -C ₁₀ -aryloxy, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkoxy, C ₁ -C ₆ -alkoxycarbonyl, C ₆ -C ₁₀ -aryloxycarbonyl, C _6- C ₁₀ -aryl-C ₁ -C ₈ -alkoxycarbonyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbonyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl carbonyl, C ₁ -C ₆ - alkyl, carboxy, C ₆ -C ₁₀ - aryl carboxy, C ₁ -C ₆ - Al Kilmer kaeptil, C ₆ -C ₁₀ - aryl Murray kaeptil, C ₁ -C ₆ - Al Kilmer captopril Carbonyl, C ₃ -C ₈ -cycloalkylmercaptocarbonyl, C ₆ -C ₁₀ -arylmercaptocarbonyl, C ₁ -C ₆ -alkylmercaptocarboxy, C ₆ -C ₁₀ -arylmercaptocarboxy, C ₁ -C ₆ -alkylsulfonyl, C ₆ -C ₁₀ -arylsulfonyl, C ₁ -C ₆ -alkylsuloxy, C ₆ -C ₁₀ -arylsuloxy; (Each of which is C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; CONH ₂ ; SO ₂ NH ₂ ; CONH ₂ having an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl or SO ₂ NH ₂ ; SO ₃ H; CO ₂ H; amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C _1- C ₆ - alkylcarbonyl, C ₆ -C ₁₀ - aryl-carbonyl, C ₁ -C ₆ - alkylsulfonyl, and C ₆ -C ₁₀ - aryl with one or more of the selected residues in the amino-substituted sulfonyl; thiol (thiol); hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodine; CF ₃ ; or optionally substituted one or more times by OCF ₃ );
Some of the substituents in b1) above may be combined to form an fused saturated, unsaturated or aromatic homo- or hetero-ring system;

or
b2) hydroxy; Thiols; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF _3; CO ₂ H; SO ₃ H; OCF ₃ ; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; or
Disubstituted amino of formula (II)

(II)
(And wherein o is 0 or 1, W is O, CH _2, or hydrogen, and C ₁ -C ₆ -, and NR ⁶ with R ⁶ selected from alkyl, methylene of formula (II) group is optionally C ₁ - May be substituted once or twice with C ₆ -alkyl, fluoro or chloro;

or
b3) Saturated, unsaturated or aromatic heterocyclic ring systems of up to 10 atoms, which include C ₁ -C ₆ -alkyl; C ₁ -C ₆ -alkoxy; COOH; CONH _{2 ;} SO ₂ NH ₂ ; CONH ₂ or SO ₂ NH ₂ with an amino functional group once or twice substituted with C ₁ -C ₆ -alkyl; SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; Thiols; Hydroxyl group; Nitro; Cyano; Fluoro; Chloro; Bromo; iodine; CF ₃ or OCF ₃ ; Optionally substituted once or several times;

c) SO ₃ H; Amino; C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl, C ₆ -C ₁₀ -aryl-C ₁ -C ₈ -alkyl, C ₁ -C ₆ -alkylcarbonyl, C ₆ -C ₁₀ -arylcarbon Amino substituted one or more times with a residue selected from nil, C ₁ -C ₆ -alkylsulfonyl and C ₆ -C ₁₀ -arylsulfonyl; CONH ₂ ; SO ₂ NH ₂ ; Di-C having an amino function once or twice substituted with a residue selected from C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl or C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl _{In the case of a 1-} C ₆ -alkyl-substituted amino functional group the alkyl moiety can be either CONH ₂ or SO ₂ NH ₂ which may be bonded to form a 5 or 6 molecular ring; Thiols; Hydroxyl group; Nitro; Cyano; Fluorosulfonyl; Halogen selected from fluoro, chloro, bromo or iodine; CF _3; Or OCF ₃ ;

Which is cyclized to form an oxadiazolone ring system;

The obtained product is conditioned on not being the compound required in claim 24.
90. The method of claim 89, wherein said cyclization to said oxadiazolone ring system is achieved by phosgene, carbonyldiimidazole, or carboxylic acid ester.