TW201028406A - 5-O-substituted 3-N-aryl-1,3,4-oxadiazolones for medical use - Google Patents

Abstract

The present invention relates to a compound of formula (I), wherein A represents an optionally substituted phenyl or a 5- or 6-membered heteroaromatic ring system containing up to 4 heteroatoms selected from O, S and N, B represents a single bond, O, S or NR1, wherein R1 is selected from hydrogen or a C1-C6-alkyl group; L represents a linker; C represents an amino moiety; n represents 0 or 1; m represents 0, 1, 2, 3, 4, 5 or 6; X represents O or S; and Y represents hydrogen or an optionally substituted carbon moiety; and to stereoisomers, pharmaceutically acceptable salts or esters, or prodrugs thereof. The compounds of the invention are potent FAAH inhibitors.

Description

201028406 VI. Description of the invention: [Technical field to which the invention pertains] The present invention relates to a compound having a 5_〇_substituted 3 n (hetero)aryl-U'W] fine structural unit in a (hetero)aryl group Some have a pendant aliphatic group containing nitrogen. These compounds exhibit an unexpectedly high inhibitory effect of hydrazine (fatty acid amine hydrolase). FAAH is an integral membrane protein (iMp) that hydrolyzes the bioactive guanamine of endogenous cannabinoids (anandamide), which is a cannabinoid receptor such as free fatty acid and ethanolamine and TRPV^^ The synergist of vanilloid prosthesis is described in McKinney Μ·K·, Cravatt BF in the journal “Ann. Rev. Biochem.” No. 74, p. 411 (2005). In view of its ability to regulate the level of anandamide, faah is currently the subject of a drug that has received much attention. Examples of non-selective inhibitors of FAAH include PMSF (phenylmethylsulfonium fluoride), MAFP (methoxyacetoyl tetraalkenylfluorophosphonate), and ATMK (arachidontyltrifluoromethylketone). URB597 ([3-(3-Aminomethylphenyl)phenyl]N-cyclohexylamine phthalic acid vinegar) is widely considered to be the current "golden standard" FAAH inhibitor. In preclinical laboratory tests, 'URB597 increased the production of endogenous cannabinoids, resulting in measurable antidepressant and analgesic effects, as seen in Russo R. et al. in the journal J Pharmacol Exp Ther·, 322(1), pp. 236-42 (2007), ed. FA A Η inhibition is considered to play an important role in many medical conditions, as seen in Pacher et al. (2006, Pharmacol. Rev. 58 3 201028406

Neuropathic pain, including forms associated with age-related viruses and diabetes; migraine, arthritis, rheumatoid arthritis, acute or chronic pain associated with inflammatory diseases, osteoarthritis , spondylitis, gout, (Crohn) disease, stimulating bowel syndrome; acute or chronic peripheral pain; dizziness, vomiting, nausea, especially from chemotherapy; eating disorders, especially anorexia and various properties Cachexia. Neurological and psychiatric disorders: tremor, dyskinesia, dystonia, paralysis, forced paranoia, Tourette syndrome, all forms of depression and anxiety and psychosis of any nature and origin; acute And chronic neurodegenerative diseases: Parkinsin's disease, Alzheimer's disease, Alzheimer's disease, Huntington's chorea, and cerebral ischemia and cranial Lesions associated with bone marrow trauma; epilepsy; sleep disorders, including sleep apnoea; cardiovascular disease 'especially hypertension, arrhythmia, arteriosclerosis, heart Symptoms, cardiac ischemia; renal ischemia; cancer: benign skin tumors, brain tumors and mastoid tumors, prostate tumors, brain tumors (glioblastoma, myeloma, medulloblastoma, neuromuscular Cell tumor, embryogenic tumor, stellate cell tumor, epithelial tumor, 201028406 ependymoma, dendritic glioma, plexiform neoplasm, neuroepithelial neoplasia, pineal body tumor, ependymoma, Malignant meningiomas, sarcoma, malignant melanoma, schwannomas; disorders of the immune system, especially autoimmune diseases: psoriasis, lupus erythematosus, connective tissue disease or collagen disease, Sj0gren syndrome, Ankylosing spondylitis, undifferentiated spondylitis, Behcet's disease, autoimmune hemolytic anemia, multiple sclerosis, amyotrophic lateral sclerosis, amyloidosis, graft rejection, Diseases affecting the fine serum cells; allergic diseases: immediate or delayed allergic reactions, allergic rhinitis or conjunctivitis, contact dermatitis; parasites, diseases Or bacterial infectious diseases: AIDs, meningitis; inflammatory diseases, especially joint diseases; arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, Inflammatory bowel syndrome; Osteoporosis; Ocular condition: Southern eye pressure, glaucoma; Pulmonary condition: respiratory disease, bronchospasm, cough, asthma, chronic bronchitis, chronic airway obstruction, emphysema; gastrointestinal disease : inflammatory bowel syndrome, inflammatory bowel disease, ulcers, diarrhea; urinary incontinence and bladder inflammation. c Summary of the Invention 3 It has now surprisingly been found that the compounds of the present invention have an unexpectedly high FAAH inhibition in vivo, making these compounds potential drug candidates for the treatment or prevention of FAAH-associated medical conditions. In addition, it has also surprisingly been found that the compounds of the present invention are characterized by a superior selectivity for peripheral nerves in vivo than for the meridian system, while avoiding deleterious effects on meridians. Therefore, the compounds of the present invention can be used to treat the secrets mentioned in the rainbow. The invention also encompasses a method of treating such diseases comprising a pharmaceutical composition comprising a compound of the invention in need thereof and a compound comprising two or more compounds of the invention. The best foreseen use of the compounds of the invention is in the treatment of allergic diseases such as immediate or delayed allergic reactions, refractory rhinitis or conjunctivitis, contact dermatitis; inflammatory diseases, ocular conditions such as high intraocular pressure or glaucoma; Department of disease and respiratory diseases, bronchospasm, cough, chronic bronchitis, chronic airway obstruction and emphysema. The term "therapeutic effect" as used herein, and variants thereof, such as "treatment (calling) or "treatment towel", mean any method that can be benefited - human or non-human _ #. The effect may be directed to an existing condition, or may be a prophylactic (preventive) treatment. The therapeutic effect may include a curative, palliative or prophylactic effect. Treatment may prevent or delay the onset of the disease or condition, retard its progression or Improving the symptoms. 'The compounds of the present invention can be used in combination with other pharmaceutically active compounds. The use can be administered simultaneously, for example, in the case of a fixed combination composition containing a combination of pharmaceutically active compounds; or can be administered sequentially 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolone is described in several publications 201028406, such as U.S. Patent No. 5,093,343, U.S. Patent No. 5,236,939, U.S. Patent No. 4,076,824 Patent, WO 03/043997 Al, EP 1263745 Bl, WO 03/072098 Al, WO 01/17981 Al, WO 03/072555 A1 and JP-A 4858140. However, none of the publications relates to FAAH suppression. Role' or about FAAH related Studies of the condition treated Embodiment c:. J based on the present invention having the formula with a compound of ⑴:

(C=X)n — (CHj m—Y (I), wherein A represents a phenyl group or a 5 or 6-shell heteroaromatic ring system containing up to 4 heteroatoms selected from the group consisting of oxygen, sulfur and gas, It is optionally substituted one or more times by the following: CVQ-alkyl, C3-C8, alkyl, C6_Ci. aryl, c6_ci. aryl-cvc8-alkyl, ckv alkoxy 'C6_Ci()_aryloxy , C6_Ci "aryl-cvq-alkoxy, (: 1 < ν alkyl fluorenyl, C6_CiG aryl carboxy, C] - C6 - leumino fluorenyl, C6_CiQj silk based m, Ci C6 sleek The oxy (4) f〇xyl), cvCi 〇 aryl ethoxylates, each of which is optionally substituted one or more times by:

Cl-C6_alkyl; Cl~C6-alkoxy; C6-Cl "aryloxy; C〇2h; 7 201028406 so3h ; conh2 ; so2nh2 ; conh2 or so2nh2, wherein the amino functionality is selected from crc6 Substituting one or more residues of an alkyl, c6-c1 (raryl or c6-c10-aryl-crc4-alkyl group, and wherein the amino functionality substituted with a di-CrCr alkyl group The alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of Ci_C6-alkyl, C6-C] fluorene-aryl, C6-Ci〇-aryl-C1-C4-Hyun Substituent, CrCV alkylcarbonyl, c6-c1()-arylcarbonyl, crc6-alkylsulfonyl and c6-c1 (the residue of the rarylsulfonyl group is substituted with one or more amine groups; thiol group ; hydroxy; nitro; cyano; fluoro; gas; bromo; iodo; CF3 or OCF3; co2h; so3H; amine; selected from crc6-alkyl, c6-c1()- Aryl, c6-c1()-aryl-crc6-alkyl, CVCV alkylcarbonyl, C6-C10-arylcarbonyl, CVCV alkylsulfonyl and c6-c1 (residue of rarylsulfonyl) Substituting one or more amine groups; a disubstituted amine group of the following formula (II): fly

Wherein 0 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and Q-C6-alkyl, and the methylene group in the formula (II) is optionally substituted by CrCV alkyl, fluoro Substituting a gas or a gas group for one or two; conh2; so2nh2; 201028406 CONH2 or SC^NH2, wherein the amino functionality is selected from a Ci_c6 alkyl group, a c:6-c1Q-aryl group or a cvCl (r aryl group) The residue of the _Ci_C6_alkyl group is substituted one or two times, and in the case of an amine functional group substituted with a di-Cl_C6-alkyl group, the alkyl residue may be combined to form a 5- or 6-membered ring; Thiol group; hydroxy group; exact group; cyano group; gas-based base; selected from fluoro, gas, bromo or iodo; cf3; pendant oxy; or 〇cf3; a single bond, CH2, oxygen, sulfur or NR1, wherein: or a CrC6-alkyl group; and oxygen L represents a linker selected from the group consisting of: a) -(CH2)p-, wherein p is b 2, 3 , 4, 5, 6, 7, or 8, b) -(C=0)- or _〇_(c=〇) one, c) -(s〇2)- or -〇-(so2)-, d Phenyl, cyclohexylene or cyclopentylene wherein a) Sd) can be used in combination, and its towel a) sexually with crc 6. Silk, Cl_c6_decyloxy, c〇2H, (10), selected, q-cv alkylamino, bis-Ci_C6-^-amino group, sinomerican saddle 9 201028406 thiol, nitro, cyano , fluoro, carbyl, bromo, decyl, CF3 or OCF3 substituted one or more times; C represents a) NR2R3, wherein R2 and R3 independently of each other represent hydrogen; CVCV alkyl, C3-C8 Cycloalkyl, C6-C10-aryl, saturated, unsaturated or aromatic heterozygous system consisting of up to 10 atoms, C6-C1 〇_ aryl-CVCV alkyl, Q-CV alkane Oxycarbonyl, C6-C1 (r aryloxy-carbonyl, C6-C1()-aryl-CrCV alkoxycarbonyl, Q-CV alkylcarbonyl, C6-Ci〇-aryl thio, C6-Ci -aryl-Ci-Cf alkyl group, CrCV alkyl fluorenylcarbonyl, C3-C8-cycloalkylcarbonylcarbonyl, C6-Ci〇-aryl thiol group, Ci_C6-alkyl base or C6_Ci Anthracene-arylsulfonyl, each of which is selectively subjected to (^-(:6-alkyl, Q-CV alkoxy, C6-C1 (r aryloxy, co2h, so3h, amine, Ci-) CV alkylamino, di-crc6-alkylamino, thiol, hydroxy, decyl, cyano, fluoro, carbyl, thio, acetyl, CF3 Or OCF3 substituted one or more times; and one of R2 and R3 may be fused to B or L to form a 5 or 6 membered ring; or b) NR4R5, wherein R4, R5 and nitrogen form one by at most 10 a saturated, unsaturated or aromatic heterocyclic ring system consisting of an atom, optionally via a cvcv alkyl group, a Q-CV alkoxy group, a C6-C1()-aryloxy group, a co2h, a so3h, an amine group, CrC6-alkylamino, di-CrCV alkylamino, thiol, thiol, cis, cyano, fluoro, chloro, bromo, iodo, CF3 or OCF3 Multiple times; 10 201028406 or C) A disubstituted amine group of the following formula (II):

—N W

Wherein 0 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of hydrogen, Q-CV alkyl, C6-C10-aryl and C6-C10-aryl-Q-CV alkyl, and the chemical formula thereof The methylene group in (II) may be optionally substituted one or two times with a CrCe-alkyl group, a fluoro group or a gas group;

Or d) a hydrazine or hydrazine residue, wherein the residue is optionally substituted by one or more of CrC6-alkyl, C6-C1 (r aryl or C6-Q.-aryl-Q-CV alkyl And wherein the selective substituents may combine to form a 5 or 6 membered saturated, unsaturated or aromatic ring; or one of the isomers of the ruthenium or osmium residue; η represents 0 or 1; m represents 0, 1, 2, 3, 4, 5 or 6;

X represents oxygen or sulfur; and Y represents: a) hydrogen; - alkyl, unit or polyunsaturated C2-C18-alkenyl, C3-C8-cycloalkyl, C6-C10-aryl, C6-C10-aryl -CrCs-alkyl, CrC6-alkoxy, C6_Ci〇_aryloxy, C6-Ci〇-aryl-Ci_C8_alkoxy, Ci-C6_alkoxycarbonyl, c6-c1 (r aryloxy) Carbonyl group, C6-C1()-aryl-CrCV alkoxycarbonyl group, CVC6-alkylcarbonyl group, c6-c1 (r arylcarbonyl group, c6-c1 (r aryl-crc8-alkylcarbonyl group, crc6-alkyl group) Carboxyl, c6-c1()-arylcarboxy, 11 201028406

Cj-CV alkylthiol, c6-c1()-arylhydrothio, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, c6-c1()-aryldecylcarbonyl , CrCV alkyl decyl carboxyl group, c6-c1 (r aryl decyl carboxyl group, crc6-alkyl sulfonyl group, c6-c1 (r aryl sulfonyl group, crc6-alkyl sulfonyloxy group, c6-c10- An aryl oxooxy group or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally substituted one or more times by the following: bl) CrC6-alkyl, C3-C8-cycloalkyl, Q-Ci.-aryl, C6-C10-aryl-Ci-Q-alkyl, CVCV alkoxy, C6-C1()-aryloxy, c6-c1() -Aryl-crc8-alkoxy, crc6-alkoxycarbonyl, C6-Q.-aryloxycarbonyl, C6-C1()-aryl-CVCV alkoxycarbonyl, CrCV alkylcarbonyl, C6-C1 ()-arylcarbonyl, C6-C!-aryl-CkCs-alkylcarbonyl, CVCV alkylcarboxy, C6-C1()-arylcarboxy, Ci-CV alkylthiol, c6-c1 ( Rarylthio group, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, C6-C1D-aryldecylcarbonyl, crc6-alkylindenylcarboxy, c6-c1(rarylfluorene Carboxyl group, Ci_C6-burning base , C6_Ci.-aryl aryl, Ci_C6-alkylsulfonyloxy, c6-c1()-arylsulfonyloxy; each of which is optionally substituted one or more times by: CrCV alkyl ;crc6-alkoxy;CONH2,S02NH2; wherein the amine functionality is substituted by CVCV alkyl one or two conh2 or s〇2nh2; so3h; C02H; amine group; selected from crc6-alkyl, c6- C1()-aryl, c6-c1()-aryl-CrC6-alkyl, CrCV alkylcarbonyl, c6-c1 (rarylcarbonyl, CrCV alkylsulfonyl and c6-c1()-aryl The residue of a sulfonyl group is substituted by a 12 201028406 or a plurality of amine groups; a thiol group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; a chloro group; a bromo group; an iodo group; Wherein a plurality of substituents in bl) may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system;

B2) hydroxy; thiol group; nitro; cyano; fluoro group; gas group; bromo group; iodo group; cf3; co2h; S03H; OCF3; conh2; so2nh2; CONH2 or S02NH2, wherein the amine group The functionality is one or two times substituted with a residue selected from a CVCV alkyl group, a c6-c1 (r aryl group or a c6-c1 (r aryl-CVCV alkyl group, and a bis-Q-C6-alkane thereof) In the case of a substituted amino function, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of CrC6-alkyl, C6-Ci〇-aryl, C6-Ci〇- Residues of aryl-Ci_C8-alkyl, Ci-Ce-carbocarbyl, C6-C10-arylcarbonyl, crc6-alkylsulfonyl and c6-c10-arylsulfonyl are substituted for one or more a second amine group; or a disubstituted amine group of the following formula (II): ———

N/_XW ο (II) wherein ο represents 0 or 1 and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and hexaalkyl, and the methylene group in the formula (II) is selectively a CrC6-alkyl, fluoro or ke group substituted one or two times; or via b3) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally via Replaced one or more times with the following: 13 201028406

CrCV alkyl; CrC6-alkoxy; COOH; so3h; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of CrCe-alkyl, c6-c1()-aryl or c6-c1 ( Substituting one or more residues of an -aryl-CrCV alkyl group, and wherein in the case of a di-CrCe-alkyl substituted amine functionality, the alkyl residue can be combined to form 5 or 6 Member ring; amine group; selected from CrC6-alkyl, C6-C1 (r aryl, C6-C1 (r aryl-CrC4-alkyl, CrQ-alkylcarbonyl, C6-C1()-arylcarbonyl) , a residue of a CrC6-alkylsulfonyl group and a C6-C10-arylsulfonyl group substituted by one or more amine groups; a thiol group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; a chloro group; Bromo group; iodo group; CF3 or OCF3; c) S03H; amine group; selected from the group consisting of crc6-alkyl, c6-c1()-aryl, c6-c10-aryl-CkCV alkyl, CkCV alkyl a carbonyl group, a C6-c1 (rarylcarbonyl group, a CVCV alkylsulfonyl group, and a C6-C1()-arylsulfonyl group residue substituted with one or more amine groups; conh2; so2nh2; CONH2 or S02NH2, wherein The amino functionality is substituted one or two with a residue selected from the group consisting of CVC6-alkyl, C6-C1Q-aryl or c6-c10-aryl-crc6-alkyl And wherein in the case of an amine functionality substituted with a di-CrCV alkyl group, the alkyl residue may combine to form a 5 or 6 membered ring; a thiol group; a hydroxyl group; a nitro group; a cyano group; A fluorenyl group; a halogen selected from a fluoro group, a gas group, a bromo group or an iodo group; CF3; or OCF3; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester or a prodrug. The pharmaceutically acceptable typical salts are known to those skilled in the art, and preferably 201028406 includes hydrochloride, dihydrochloride and trisacetate. The invention also relates to a pharmaceutical composition comprising the above chemical formula (1) a sigma compound or a pharmaceutically acceptable salt thereof or a precursor drug thereof, and a compound having the above chemical formula (1) or a pharmaceutically acceptable salt thereof or a pharmaceutically active amount thereof Precursor, and a method for the disease and condition mentioned in the oral therapy. In the case of the special case, the pharmaceutical composition of the present invention additionally comprises or comprises a plurality of additional active pharmaceutical ingredients. May with one or more additional active pharmacies Dosing together, which may be in the form of a single composition comprising: a chelating compound and/or a plurality of additional active pharmaceutical ingredients, optionally in the form of two or more individual compositions.筚 contained in the composition, and - or a plurality of additional living sequences are contained in one or more individual compositions, for example, for the sulfidation of the above formula (1), Α represents - one containing up to 4 A 5- or 6-membered heteroaromatic ring system selected from the group consisting of oxygen and murine heteroatoms, and preferably a mass of a package and a 1 or 2 money. And clothing is also better to include _Weike. _. The optimal nA a + exhibition is selected from the mouth ratio 疋 0 than the ploughing, shooting, Takou well, three lectures, four brown ^ know, ah, oblique riding two saliva. Miscellaneous, Fu, ten, especially 2-(four), 3♦ and 4♦ fixed materials. Preferably, the system is defined by a mouth, and L preferably represents a linker selected from the group consisting of: a) one (CH2)p-' wherein P is 1, 2, 3, 4, 5, b) ~(c=〇) -or -0-(C=0)-, 7 or 8 ' 15 201028406 c) ~(s〇2)- or ~〇-(so2)-, d) phenyl, cyclohexylene or cyclopentylene . Linkers a) and d) are also preferably via Cl_C6_alkyl, CrC6-alkoxy, co2h, so3h, amine, Ci_C6-alkylamino, bis-Ci_C6_inhocentyl, thiol, hydroxy The nitro group, the cyano group, the fluoro group, the carbyl group, the bromo group, the oxime group, the CF3 group or the hydrazine CF3 are substituted one or more times. Particularly preferred substituents are CVCV alkyl, Cl_c6-alkoxy, amine, Ci_c6-alkylamino, bis-CkC6-alkylamine, hydroxy, fluoro, carbyl, bromo, CF3 And OCF3. Moreover, it is preferred that the number of young to mid-term can also be used in combination. Non-limiting examples of such combinations are -(CH2)p_〇-(c=〇)-, -(CH2)p-〇-(S02)-, and _(ch2)p-(S02)-. In the above formula (I), in the case where C represents NR2R3 and one of R2 and R3 is fused with L to form a 5- or 6-membered ring, nitrogen, a linker and one of R2 and R3 are compared. Preferably forming a pyrrolidine or piperidine moiety and optionally via CrCV alkyl, q-CV alkoxy, amine, CrCV alkylamine, di-CVCV alkylamine, hydroxy, fluoro, The chloro, bromo, CF3 or OCF3 are substituted one or more times. In the above formula (I), in the case where C represents NR2R3 and one of R2 and R3 is fused with B to form a 5- or 6-membered ring, preferably B represents nitrogen and nitrogen of B, NR2R3, and a linkage. And one of R2 and R3 forms a piperene moiety and is selectively CVC6-alkyl, CVCV alkoxy, amine, CrC6-alkylamino, bis-q-CV alkylamine The hydroxy, fluoro, chloro, bromo, CF3 or 〇cf3 are substituted one or more times. In the above chemical formula (I), C represents NR4r5 and 1 and 114 of it and R5 201028406 t become a saturated, unsaturated or aromatic heterogeneous system of 1G atoms. The saturated, unsaturated or aromatic (tetra) compound consisting of up to (7) atoms is preferably a material, hydrazine, fluorene, iso-I-limoline or 3,4-hydroisoquinoline. The ring system may be substituted by Ci_C6 alkyl, CVCV alkoxy, amine, Ci_c6 alkylamino, bis-Ci_C6 alkylamino, light, danyl, carbyl, thiol, CF3 or OCF3 - Or multiple times. In the above formula (I), where c represents a disubstituted amine group of the following formula (11): —|/ ~w °(Π) wherein 0 represents 0 or 1 and w represents oxygen, CH 2 or NR6, R6 is selected from the group consisting of hydrogen, CVCV alkyl, c6-c1 (r aryl and c6_Ci (raryl-Ci_c6-alkyl. The disubstituted amino group preferably represents pyrrolidinyl, piperidinyl, porphyrin) Or a piperidinyl group. In the case of a piperene, the nitrogen may also be substituted by a CrCr alkyl group, a phenyl group or a benzyl group. The methylene group in the formula (II) is also preferably a Cl_Ce_alkyl group, a fluoro group or The gas group is substituted one or two times. In the above formula (I), in the case where (: represents a hydrazine or hydrazine residue, the residue is preferably unsubstituted or substituted by one or more alkyl groups. Preferably, the substituents are also combined to form a 5 or 6 membered saturated, unsaturated or aromatic ring such as a pyrimidine. When C represents a hydrazine or hydrazine residue, the nitrogen bonded to the hydrazone is further preferred. Substituted by an alkyl residue which in turn forms a 5 or 6 membered ring with the linker L. An example of this structure can be found in the compound 5-(2,4-difluorophenoxy)-3- (4-((1-(pyrimidin-2-yl))piperidin -4-yl)methoxy) 17 201028406 Phenyl)-1,3,4-oxadiazole-2(3H) ketone is covered in the present invention. The isomer of the oxime or flank portion is also known as In the connotation of the eye-catching case, the soil is good and good, representing thiol ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl. In the meaning of this application, Cl-C6 The term "hospital base" preferably represents methylethyl, n-propyl, isopropyl, n-butyl, sec-butyl or hexyl.

In the meaning of the present application, Clm-word preferably represents methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, octyl In the meaning of the present application, the unit or polyunsaturated ^7^olefin group-word preferably represents acetyl, n-propyl, isopropyl. Dilute, n-butyl, sec-butenyl, tert-butenyl, pentenyl, hexenyl, octenyl, nonenyl, dodecenyl, tetradecenyl, octadecyl Carbacenyl, dodecadienyl, tetradecadienyl and octadecadienyl.

In the connotation of this application, the term 'C3_C8_ ring-yard base' preferably denotes cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. In the meaning of the present application, the term C6-C] fluorene-aryl preferably represents phenyl, cyclopentadienyl, indenyl, indanyl, isoindolyl, cryptyl, base. , a base, a thiol group, a phenanthryl group or a flower base. In the meaning of the present application, the words CVQo-aryl-CrCV alkyl, c6-c1 (r-square-Ci-C6_alkyl and C6-Ci〇-square-C1-C4-alkyl) are preferred. Represents a stupid or naphthyl group substituted by a methyl 'ethyl, propyl or butyl group. Particularly preferred residue 18 201028406 is a benzyl group and a phenethyl group. In the context of the present application, 'CrC4-alkoxy- The term preferably represents methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy and tert-butoxy. In the context of this application, q The term -C6.alkoxy preferably represents methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentyloxy Or hexyloxy. φ In the meaning of the present application, the term C6-C10-aryloxy preferably represents phenoxy, naphthyloxy, anthracenyloxy, decyloxy or phenanthryloxy. In the connotation of the application, the words 'c6-c10-aryl-CrC8-alkoxy, .C6_Cl(r aryl oxyoxy and CVCnr aryl-CrC4_houseneoxy) preferably represent benzoquinoneoxy, benzene Ethoxy, phenylpropoxy or phenylbutoxy. The most preferred residues are benzoinoxy and phenethyloxy. The term alkoxycarbonyl in the context of the invention preferably represents methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl φ or butoxycarbonyl. In the context of this application, The term C6-C1 (r-aryloxycarbonyl) preferably represents the radical or the ethoxylated group. In the context of the present application, the term 'C6-C1(raryl-CVCs-alkoxycarbonyl) Preferably, it represents a benzhydryloxycarbonyl group or a phenethyloxycarbonyl group. The term 'Ci-CV alkylcarbonyl group' in the context of the present application preferably represents methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, and iso Propylcarbonyl or butylcarbonyl. In the meaning of the present application, the term c6-c 10·arylalkyl preferably represents phenylcarbonyl or naphthylcarbonyl. 19 201028406 In the context of this application, c6- The c10-aryl-crc8-alkylcarbonyl group preferably represents a benzylcarbonyl group or a phenethylcarbonyl group. In the context of the present application, the term 'Ci-C6-alkylcarboxyl preferably represents a decylcarboxy group, an ethyl group. a carboxyl group, a n-propyl carboxyl group, an isopropylcarboxy group or a butylcarboxy group. In the context of the present application, the term c6-c10-arylcarboxy is preferably a stupid base. In the meaning of the present application, the term Cl_c6-alkylthiol preferably represents methylthiomethyl, ethylhydrosulfanyl, n-propylhydrosulfanyl, isopropylhydrogen sulfide. In the meaning of the present application, the term C6_Cl〇_arylhydrosulfanyl preferably represents a strepyl thiol or a naphthyl thiol group. In the meaning of the present application, Cl_C6 The term _alkylmercaptocarbonyl preferably represents methyl-tertyl, ethyl fluorenyl, n-propyl fluorenylcarbonyl, isopropyl fluorenylcarbonyl or butyl fluorenylcarbonyl. The term C3_C8_cycloalkylfluorenylcarbonyl preferably represents cyclopropylhydrazinocarbonyl, cyclobutylhydrazinocarbonyl, cyclopentylfluorenylcarbonyl or cyclohexyldecylcarbonyl. In the meaning of the present application, the term C6-C10-aryldecylcarbonyl preferably represents a styrylcarbonylcarbonyl group or a naphthylfluorenylcarbonyl group. In the meaning of the present application, the term Cl_C6_alkylmercaptocarboxy is preferably substituted for methylmercaptocarboxy, ethylmercaptocarboxy, n-propyldecylcarboxy, isopropylhydrinocarboxy or butyldecylcarboxy. In the context of the present application, the term C6-C10-aryldecylcarboxy preferably represents phenylmercaptocarboxy or naphthylfluorenylcarboxy. 201028406 In the context of this application, the term "Q-C6-alkylsulfonyl" preferably represents fluorenylsulfonyl, ethylsulfonyl, n-propylsulfonyl, n-butylsulfonyl , sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl or hexyl. In the context of this application, the term Q-Cnr arylsulfonyl preferably represents the base or naphthyl fluorenyl. In the meaning of the present application, the term 'Q-CV alkylsulfonyloxy group' preferably means methylsulfonyloxy, ethylsulfonyloxy, n-propylsulfonyloxy, n-butylsulfonate. Alkoxy, sec-butylsulfonyloxy or tert-butylsulfonyloxy. In the meaning of the present application, the term C6-C10-arylsulfonyloxy preferably represents phenylsulfonyloxy or naphthylsulfonyloxy. Further, 'in an optional embodiment of the invention, the substituents mentioned above are preferably selectively substituted by a ^6-alkyl group, a CVCV alkoxy group, a c6_Cl (r aryloxy group, C 〇 2H, S 〇 3H, an amine group, a thiol group, a hydroxyl group, a nitro group, a cyano group, a fluoro group, a carbyl group, a bromo group, an iodo group, a CF3 group or a fluorene cf3 substituted one or more times. In this definition, Ci_C6_alkyl, CrC6_homoyloxy and CVChtaryloxy preferably represent the same residues as mentioned above. In the context of the present application, 'selectively substituted one or more times' The wording is intended to include unsubstituted or mono- or multiple-substitution with one or more of the optional substituents mentioned. In the case of multiple substitutions, the choice of such substituents is independent of each other. In the context of the present application, it is selected from the group consisting of crc6-alkyl, c6-c10-aryl, C6-C10-aryl-CVC4-dynchyl, Crc6-alkyl, C6-C1C)-aryl Substituents of a Crc6-alkylsulfonyl group and a C6-C1Q-arylsulfonyl group are substituted by a 21 201028406 or a plurality of amine groups - preferably 'representing each other independently of each other Substituted- or secondary-amino group: ^_c6., in the case of a base group, via a group of f, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl or Hexyl substitution; in the case of a C6-C10-aryl group and a c6_Ci〇•aryl-Ci_C4·house group, substituted by a phenyl group, a benzyl group or a stupid ethyl group; in the case of a Ci_c6-alkylcarbonyl group and an arylcarbonyl group, Methylcarbonyl, ethylcarbonyl or phenylcarbonyl substituted, in the case of Crcv alkylsulfonyl and C6_Cur arylsulfonyl, methyl thiol, ethyl thiol or phenyl fluorenyl Replace. In the meaning of the present application, "wherein the amino functionality is selected from the group consisting of ❹ <^-(:6-alkyl, C6-C1()-aryl or c6_Ci〇_aryl·Ci_c4_ Substituting a residue one or more times and in the case of an amine functional group substituted with: _C1_Q_alkyl, the alkyl residue may be bonded to form a 5 or 6 membered ring of c〇NH2 or . S〇2NH2 — § 5], preferably derived from N, N dimethyl decylamine, N methyl decylamine, N-ethyl decylamine, N-phenyl decylamine, N, N _: methyl sulfonamide, N methyl Represented by residues of sulfonamide, N-ethylsulfonamide, and N-phenylsulfonamide. In the case of an amine di-alkyl group, the two residues combine to form 5 or 6 members. Rings are also a preferred alternative. Examples of such amine functionalities include, but are not limited to, indole and biting. In the context of this application, "selectively via Ci_c6_alkyl,

Cj-CV alkoxy, COOH, S03H, amine, thiol, hydroxy, nitro, cyano, fluoro, carbyl, bromo, mothyl, cp3 or OCF3 substituted one or more times The term "saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 1 atom" preferably consists of a hetero atom containing from hydrazine to 4 selected from milk, oxygen or sulfur and up to 1 〇 原子 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 2010 , benzopyrene, benzopyrene, stupid and ten-seat, benzopyrene, sin, dioxin, two, f, two, 戍, -, 环, 烧, 二,二Shoot, squat, bite, smell, squat, °m " sit bite, 〇 lead D, 〇 bow Buduo, bow 丨 井, 〇 bow 丨β sit, 丨叫丨 朵喧 喧 、 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 异 喧嗤 喧嗤 喧嗤 喧嗤 萘 萘 萘 萘 萘 萘 萘 萘_, morphine, morphine, sing 0 bottom brown, pie bite, bite, 嘌吟, n 辰 〇, 〇 than speak, than. sit, 〇 than sit 琳 ° than 疋 β 疋, tower whistle ^, D than bite, η close bite, η ratio Luo, hip-hop, β-Hallin, Lin, π, 喹, 喹, 喧, 四, tetrahydrofuran, tetras, tetrazole, thiophene, thiazide, thiadiazole, thiatriazole, Thiacin, thiazole, thioporphyrin, thionaphthalene, thiopyran, tris-sigma well, triazole and trithiazide, and all isomeric configurations thereof. The heterocyclic rings may be selectively Ci-C6-alkyl , Ci_C6_alkoxy, COOH, S〇3H, amine group, thiol group, trans group, moth group, cyano group, fluoro group, gas group, bromo group, mechanical group 'CF34〇Cf3 substituted one Or multiple times. Particularly preferred substituents are methyl, methoxy, amine, hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo, cf3 and 〇CF3 The best aromatic heterocyclic ring system consisting of up to 10 atoms, including a 6-membered heteroaryl 2-° bite, 3-n bite or 4-etb bite, where the owner is selectively Passing one or more residues selected from thiol, amine, fluoro, carbyl or CF3 Substituting; and including pyrrole, which is optionally substituted with one or more residues selected from methyl, amine, milyl, valyl or cf3. In the above formula (I), A preferably represents stupid Base, 2-acridinyl, 3_ 23 201028406 0 than bite group or 4-π ratio bite. A better by CrCV alkyl, C3-C8-cycloalkyl, C6-C1 (r aryl, C6-Ci 〇-aryl-Ci-Cr alkyl, Ci_C6-Hyun "oxy, Ce-Ci.-aryloxy, C6-Ci〇-aryl-Ci-C8_ alkoxy, Ci_C6-alkyl group, C6-Ci〇-方基_carboxy, crc6-alkylmercaptocarboxy, c6-c1()-aryldecylcarboxy, Q-C6-alkylsulfonyloxy, c6-c10-arylsulfonyloxy Substituting one or more times, each of which is optionally substituted one or more times by: CVC6-alkyl; CrCV alkoxy; c6-c1()-aryloxy; co2h; so3h; conh2; so2nh2; conh2 Or so2nh2, wherein the amino functionality is substituted one or more times by a residue selected from the group consisting of crc6-alkyl, c6-c1()-aryl or c6-c10-aryl-crc4-alkyl, and In the case of an amine functional group substituted with a di-Q-CV alkyl group, the alkyl residue may be bonded to form a 5 or 6 membered ring; an amine group; Ci-C6-alkyl, C6-Ci〇-aryl, C6-Ci〇-aryl-C1-C4-Hyun", Q-C6-alkylcarbonyl, c6-c10-arylcarbonyl, crc6-alkane Substituting a residue of a sulfonyl group and a C6-C1G-arylsulfonyl group for one or more amine groups; a thiol group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; a gas group; a bromo group; Iodo, CF3 or OCF3; co2h; so3H; amine; selected from Ci_C6-alkyl, C6-Ci〇-square, C6-Ci〇-square-Ci_C6-alkyl, Q-C6-alkane a residue of a carbonyl group, a c6-c10-arylcarbonyl group, a crc6-alkylsulfonyl group, and a c6-c1()-arylsulfonyl group substituted one or more times; 24 201028406 one having the following chemical formula (π Disubstituted amine groups:

Wherein 0 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of hydrogen and CkCV alkyl, and wherein the methylene group in the formula (II) is selectively Q-CV alkyl, fluoro group Or a gas substituent substituted one or two times; CONH2 ; so2nh2 ;

CONH2 or S02NH2, wherein the amino functionality is substituted one or two times with a residue selected from the group consisting of CrCV alkyl, C6-C1 ()-aryl or c6-c1()-aryl-CrC6-alkyl, and Wherein in the case of an amine functional group substituted with a di-Q-CV alkyl group, the alkyl residue may be bonded to form a 5 or 6 membered ring; a thiol group; a thiol group; a fluorenyl group; a cyano group; Sulfosyl; dentate selected from fluoro, carbyl, bromo or iodo; CF3; pendant oxy; or OCF3. A is more preferably substituted one or more times by a fluoro group, a chloro group, a hydroxyl group or a CrCV alkoxy group. 25 201028406 In the above chemical formula (1) φ Λ ) thousand 'A is more preferably substituted one or more times by a fluoro group or a gas group. In the above chemical + η 八 VIII (I), ’ is optimally substituted by fluorine in the ortho position of the oxadiazolone residue. In the above chemical _ towel, B preferably represents oxygen. In the above chemical formula (1), L more preferably represents (CH2)P in which _, 2, 3 or 4 is selectively substituted by CrC6, benzyl, alkoxy, amine, cvcv amide Substituted or dialkylamino, trans, carbyl, oxo, molybdenum, hydrazine or hydrazine CF3 - or multiple.

In the above formula (1), in the case of L«KCH2)P-, L particularly preferably represents a methylene group, an ethylene group or a propylene group.

In the above formula (1) +, c more preferably represents NR2R3, and the towels R2 and R3 independently of each other represent hydrogen; or CKV filament, c6m, c6_Ci. . Aryl-crc6_& base, Ci_C6 alkyl base, C6_Ci. An aryl aryl group, a C6-C10-aryl-CVCV alkylcarbonyl group, a Ci CV alkylsulfonyl group or a c6_Ct aryl yl group, wherein each of them is selectively C1_C6 alkyl, c]_d oxy, amine Substituted one or more times by a CVQ-alkylamino group, a di- 6-alkylamino group, a trans-group, a fluoro group, a chloro group, a bromo group, a CF3 or OCF3. L is particularly representative of ethylene, and one of r2 and r3 represents a combination with L to form a 5 or 6 membered propylene group. In this embodiment, R2 and R3 preferably further independently of each other represent hydrogen, cvcv alkyl, c6-c1 (r aryl or C6_Ci 〇 _ aryl-Ci-C6-alkyl. In the above formula (1), C More preferably, it represents NR4R5, wherein the rule 4 and the ruler 5 form a saturated, unsaturated or aromatic homocyclic or heterocyclic ring system consisting of up to 10 atoms. The ring systems are also preferably Ci_C6 alkyl, 26 201028406

Cj-CV alkoxy, amine, CrCV alkylamino, di-Crc6-alkylamidino, hydroxy, fluoro, carbyl, bromo, CF3 or OCF3 substituted / or multiple times. In such embodiments, NR4R5 is particularly preferred to form an isoindole ring system selectively via crc6-alkyl, crc6-alkoxy, amine, CrC6-alkylamine, bis-CkCV alkyl The amine group, hydroxyl group, fluoro group, chloro group, bromo group, CF3 or OCF3 are substituted one or more times.

In the above formula (I), C more preferably represents a disubstituted amino group of the following formula (I1):

—f/W °(11) wherein 〇 represents 0 or 1 and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from the group consisting of hydrogen, Ci-C 6-alkyl, C 6 —Ci 〇-aryl and C 6 —Ci 〇-aryl- Ci_C6_ burning base. In these embodiments, 'C particularly preferably represents a pyrrolidinyl group, a piperidinyl group, a porphyrin group or a piperylene group which is optionally N-substituted with a Q-CV alkyl group, a phenyl group or a benzyl group. Moreover, in a particularly preferred embodiment, A represents a phenyl group substituted at least in the ortho position to the oxadiazolone residue. With respect to the 5-oxo-substituent of the °° 坐-ring, it is more preferred that η represents 0 in the above formula (I); m represents 〇, 1, 2, 3, 4, 5 or 6; and γ represents c3- C6-cycloalkyl or C6_C1 (raryl, each of which is optionally substituted one or more times by the following: a) CrC6-alkyl, CVC10-aryl, c6-C10-aryl-QQ-alkyl, Cr C6-alkoxy, c6-c1 (r aryloxy, c6-C1 (raryl-CrC4-alkoxy), each of which is optionally substituted one or more times by: Q-C6-alkyl ; Crc6_ alkoxy; COOH; CONH2; 27 201028406 S〇2NH2; CONH2 or S02NH2 substituted by Crcv alkyl or c6_Ci "aryl group; S03H; amine group; selected from Cl_c6_ alkyl, c6-c1 ()-aryl, C6-C1 (raryl_Ci_c4_alkyl, Ci_c6-alkylcarbonyl, CVCw arylcarbonyl, Ci_c6-alkylsulfonyl and C6-C1()-arylsulfonyl Substituting one or more amine groups for a residue; a thiol group; a trans group; a nitro group; a cyano group; a fluoro group; a gas group; a bromo group; an iodo group; a CF3 or OCF3; or a b) hydroxyl group; Thiol group; nitro group; cyano group; fluoro group; gas group; bromo group; iodo group; CF3; OCF3; c〇2H; S03H; CONH2; So2nh2; CONH24S02NH2, wherein the amino functionality is substituted one or more times by a residue selected from the group consisting of CrC6-alkyl, C6-Ci (r-aryl or C6-C1 (r-aryl-crc4-alkyl) In the case of a di-CrC6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; one or more times substituted with a CrC6-alkyl or phenyl group. Amine group; a disubstituted amine group of the following formula (II): /~Λ

—IM W Η7] 0 (II) wherein 〇 represents 0 or 1 and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and CrC 4 -alkyl, and the methylene group in the formula (II) is optionally Substitution with a C1-C4-alkyl, fluoro or ke group for one or two times, or c) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, the selectivity of which The ground is replaced by one or more of the following: 28 201028406

Ci-Cr system; Ci-C6-alkoxy; COOH; CONH2; S〇2NH2; one or two times of CONH2 or S02NH2 substituted by CrC6_alkyl or CVC1()-aryl; S03H; amine group; Selected from Cl_c6_alkyl, c6-c1 (r aryl, C6-C1 (r aryl-CVCV, s. Substituting a residue of a C1()-aryl fluorenyl group for one or more amine groups; a thiol group; a hydroxy group; a nitro group; a cyano group; a fluoro group; a chloro group; a bromo group; an iodo group; Or OCF3. More preferably η represents 0; m represents 〇 or 1; and γ represents phenyl or a naphthyl group, 2-naphthyl group, 2-» butyl group, 3-" pyridine group or 4-pyridyl group Ring system. Even more preferably, the Y system is substituted one or more times by the following: Crc4_alkyl; phenyl; CVCr alkoxy; hydroxy; fluoro; aldehyde; bromo; eh; OCF3; One or two of CONH2 are optionally substituted with a Q-CV alkyl group, wherein the selective Cl_C4_alkyl residues may be combined to form a 5 or 6 membered ring; or an amine group. More preferably, m represents 0, and Y represent a phenyl group substituted one or two times with a hydroxyl group, a fluoro group, a gas group or a bromo group. Table 〇, and γ represent a fluoro group at the 4-position, a gas group at the 4 position, a fluoro group at the 2- and 4-positions, a chloro group at the 2 and 4 positions, or In the preferred embodiment of the present invention, in the above chemical formula (1), A represents a phenyl group; B represents oxygen; and L represents —(CH2)p-, wherein Is 丨, 2, 3 or 4; c represents NR2R3, wherein r2 represents hydrogen or a CrCV alkyl group, and R3 represents a propylene group fused to L to form a 5 or 6 membered ring. 29 201028406 In this embodiment, In the above chemical formula (i), y is more preferably also represented by a fluoro group or a gas group at the 4_ position, a fluoro group at the 2_ and 4_ positions, or a gas generation at the 2- and 4-positions. In this embodiment, in the above chemical formula (1), A preferably represents a phenyl group substituted with at least fluorine in the ortho position of the ruthenium steel residue. In another aspect, the present invention is also A method for preparing a compound according to the present invention, wherein one of the compounds of the formula (ΙΠ): 〇CLB-A-NN~~^ Η HO-fCH^m-Υ (HI), - /, medium It represents a phenyl group or a 5 or 6-membered heteroaromatic ring system with up to 4 heteroatoms selected from oxygen, sulfur and nitrogen hetero atoms, which is optionally substituted one or more times by the following:

Cl-C6-alkyl, c3_c8_cycloalkyl, c6_Ci (raryl, C6_Ci〇_arylalkyl, Cl-C6_alkoxy, c6_Ci(r aryloxy, c6_Cl『aryl•C]~ C8 · oxo, Q-CV dadyl, c6-c1 ()-aryl chicken, 〇

Cl_C6-alkylmercaptocarboxy, C6_Cl〇_aryldecylcarboxy, CrC6-alkyl R醯oxy, Ce-Cur aryl fluorenyloxy, each of which is optionally substituted one or more times by: ci -c6•alkyl;Cl_C6_alkoxy; C6_C“aryloxy; C〇2H; S〇3H; CONH2; s〇2NH2; CONH2 or S02NH2, wherein the amine functionality is selected from CrC6-alkyl a C6-Cht aryl group or a C6-C10-aryl-Ci-Cr alkyl group substituted one or more times and in the case of an amine functional group substituted with a di-C^-CV alkyl group ' 30 201028406 The alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of CVQ-alkyl, C6-C1()-aryl, C6-C1()-aryl-CrQ-alkane Substituent, Q-C6-alkylcarbonyl, C6-C10-arylcarbonyl, crc6-alkylsulfonyl and c6-c1 (the residue of the rarylsulfonyl group is substituted with one or more amine groups; thiol Base; hydroxyl; nitro; cyano; fluoro; chloro; bromo; iodo; CF3 or OCF3; co2h; so3h;

Amino; selected from the group consisting of crc6-alkyl, c6-c10-aryl, c6-c10-aryl-crc6-alkyl, Ci-CV alkylcarbonyl, c6-c10-arylcarbonyl, crc6-alkyl sulfonate Substituting a residue of a fluorenyl group and a C6-C1Q-arylsulfonyl group for one or more amine groups; a disubstituted amino group having the following formula (II):

—N W Η7] °(ΙΙ) where 〇 represents 0 or 1 and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and

CrC6-alkyl, and the methylene group of the formula (II) thereof, may be optionally substituted one or two times with a Ci-C6-alkyl group, a I group or a gas group; conh2; so2NH2; CONH2 or S02NH2, wherein The amino functionality is substituted one or two times with a residue selected from the group consisting of crc6-alkyl, C6-C1 (r-aryl or C6-C1 (r-aryl-Q-CV alkyl), and In the case of a -G-C6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; 31 201028406 thiol group; thiol; nitro; cyano; fluorosulfonate a dentate selected from the group consisting of fluoro, chloro, bromo or iodo; cf3; pendant oxy;

Or °cf3; B represents a single bond, oxygen, sulfur or NR1, wherein R1 is selected from hydrogen or a CrCV alkyl; L represents a linker selected from the group consisting of: a) -(CH2)p-, wherein p is Bu 2, 3, 4, 5, 6, 7, or 8, b) ~(C=:〇)—or —〇-(c=〇)—,

c) ~(S〇2)_ or _〇_(s〇2)_, d) a stupid group, a cyclohexylene group or a cyclopentylene group, wherein the numbers a) to d) may be used in combination, and And phantom selectively via Ci-C6-alkyl, CVCV alkoxy, co2h, so3h, amine, CVC6-alkylamine, bis-CVCV alkylamine, thiol, thiol, nitrate Substituting one or more times for a cyano group, a cyano group, a fluoro group, a carbyl group, a bromo group, a ruthenium group, a cf3 or a 〇cf3; wherein C represents a hydrogen atom independently of each other; Cl_c6, burns 32 201028406

a c3-c8 cycloalkyl group, a cvcv aryl group, a saturated, unsaturated or aromatic heterocyclic ring system consisting of a polyatomic atom, Q Ci. Aryl-CKV alkyl, Cl-C6-alkoxy, C6_Ci "aryloxy", CVQ "aryl-Cl-CV alkoxycarbonyl, Ci Q alkylcarbonyl, C6-C丨. -arylcarbonyl, cvCi〇_aryl "8-alkylcarbonyl, CrCV alkylcarbonylcarbonyl, C3_C8_cycloalkylcarbonylcarbonyl, CVCur arylsulfonylcarbonyl, CVCe_alkylsulfonyl or C6_Ci〇_aryl Sulfosyl' each of them selectively passes. "alkyl" Ci_c6_ alkoxy, C6-C1 (r aryloxy, c 〇 2H, s 〇 3h, amine, CrQ-alkylamino, di-CrcV alkylamine, thiol, hydroxy , nitro, cyano, fluoro, chloro, bromo, iodo, CF3 or OCF3 substituted one or more times; and one of R2 and R3 may be fused with A or L to form a 5 or 6 member ring; or

b) NR R, wherein R, R and nitrogen form a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 1 atom, optionally via CrCV alkyl, CrC6-alkoxy, C6_CChloroaryloxy, C02H, S03H, Amine, CrQ-Dryyl Amine, Di-Ci_c6_^-Amino, Thiol, Merid, Nitro, Cyano, Fluoryl, Oxygen, Bromine Substituting one or more substituents, mothyl, Cp3 or 〇cf3; or C) a disubstituted amino group of the following formula (II): -n/_Aw Ή7] 33 ° (II) 201028406 where 〇 represents 0 or 1 and w represent oxygen, CH2 or NR6, and R6 is selected from the group consisting of hydrogen, CVQ-hospital, cvci (raryl and C6_Ci〇aryl_C]_C6 alkyl' and the methylene group in the formula (II) The group may be optionally substituted one or two times with a C-C6-alkyl, fluoro or ke group; or d) a hydrazine or hydrazine residue, wherein the residue may be selectively Ci-c^alkyl, CVCht aryl or C6_Ci〇_aryl-Ci_C4 alkyl substituted - or multiple times, wherein the selective substituents may combine to form a 5 or 6 membered saturated, unsaturated or aromatic ring; or the hydrazine or hydrazine One of the isomers; η 〇 or 1 ; m stands for 0, 1, 2, 3, 4, 5 or 6; and Y stands for: ' a) hydrogen; t^CrC!8·alkyl, unit or polyunsaturated C2_Ci8_alkenyl, C3_C8_ ring Hyun, C6-C1G-aryl, C6-C1()-aryl-QQ-alkyl, CrCV alkoxy, C6-C1 (r aryloxy, C6-C1()-aryl-CVCV oxygenated Base, (VCV oxyl group, CVCur aryloxy group, c6-C1()-aryl-CrCV oxyoxycarbonyl, Q-C6-alkylcarbonyl, C6-C1()-arylcarbonyl, C6-C1 (raryl-CrC8-alkylcarbonyl, CrC6-alkylcarboxy, C6-C1()-arylcarboxy,

Ci-C6_alkylthiol, C6-Ci〇-square-based thiol, Ci-Cg-alkyl-based thiol, C3-Cg- ring-based thiol, C6-C1G-aryl酼基基基,

CrC6-alkylmercaptocarboxyl, C6-C10-aryldecylcarboxy, Q-CV alkylsulfonyl, C6-Cnr arylsulfonyl, Q-CV alkylsulfonyloxy, C6-C10- An arylsulfonyloxy group or a saturated 34 201028406 and an unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally substituted one or more times by the following: blKVQ-alkyl , C3-C8-cycloalkyl, C6-C10-aryl, C6-C10-aryl-CkQ-alkyl, Q-CV alkoxy, C6-C1 (r aryloxy, c6-c10-aryl -crc8-alkoxy, crc6-alkoxycarbonyl, C6-Ci〇-aryloxy, C6-Ci〇-aryl-Ci_C8_alkoxy, Q-CV alkylcarbonyl, c6- C1(r arylcarbonyl, c6-c1()-aryl-CrC8-alkylcarbonyl, CVCV alkylcarboxy, C6-C1()-arylcarboxy, Ci_C6-alkylthio group, C6-Ci〇- Arylsulfuryl, Ci_C6-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, C6-C1G-aryldecylcarbonyl, crc6-alkylmercaptocarboxy, c6-c1 (raryldecylcarboxyl) , Ci_C6-alkyl base, C6_C 〇-square rock yellow base, Ci-C6_ alkylsulfonyloxy, c6-c1 (rarylsulfonyloxy; each of which is selectively Column substituted one or more times: CrC6-alkyl; CrCV alkoxy; CONH2, S02NH2; wherein the amine functionality is replaced by crc6-alkyl one or two conh2 or so2nh2; so3h; C02H; amine group; Selected from crc6-alkyl, c6-c1()-aryl, c6-c10-aryl-(VCV alkyl, CVCV alkylcarbonyl, C6-C1()-arylcarbonyl, Q-C6-alkyl sulfonate Mercapto group and c6-c1 (the residue of the r arylsulfonyl group is substituted with one or more amine groups; thiol group; hydroxyl group; nitro group; cyano group; fluoro group; gas group; bromo group; Substituent; CF3; or OCF3; wherein a plurality of substituents in bl) may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or via 35 201028406

B2) hydroxy; thiol group; nitro; cyano; fluoro group; gas group; bromo group; iodo group; cf3; co2h; so3h; OCF3; conh2; so2nh2; CONH2 or S02NH2, wherein the amine group The functionality is substituted one or two times with a residue selected from the group consisting of CVC6-alkyl, c6-c1 (r aryl or c6-c1()-aryl-CkCV alkyl, and in one of the di-Ci-Cr In the case of an alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of CrCV alkyl, c6-c1()-aryl, c6-c1 ( Substituting one or more residues of an -aryl-crc8-alkyl group, a crc6-alkylcarbonyl group, a C6-C1 (rarylcarbonyl group, a CVCV alkylsulfonyl group, and a c6-c10-arylsulfonyl group) An amine group; or a disubstituted amine group of the following formula (II):

Γ~\ -Ν W °(ΙΙ) where Ο represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen

And CrC6-alkyl, and the methylene group in the formula (II) thereof may be optionally substituted one or two times by CVC6-alkyl, fluoro or chloro group; or by b3)-by up to 10 A saturated, unsaturated or aromatic heterocyclic ring system consisting of atoms which are optionally substituted one or more times by: CrCV alkyl; CrC6-alkoxy; COOH; S03H; conh2; so2nh2; conh2 or so2nh2 Wherein the amino functionality is substituted one or more times with a residue selected from the group consisting of alkyl, c6-c1()-aryl or c6-c1()-aryl-CVC4-alkyl, and wherein In the case of a di-CrC6-alkyl substituted amine functionality, the alkyl residue 36 201028406 can be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of CrC6-alkyl, C6-Ci〇-aryl , C6-Ci〇-aryl-C1-C4-alkyl, Ci_C6-alkyl, C6-C1()-arylcarbonyl, Q-CV alkylsulfonyl and C6-C10-arylsulfonate The thiol residue is substituted with one or more amine groups; thiol group; hydroxy group; nitro group; cyano group; fluoro group; chloro group; bromo group; iodo group; CF3 or OCF3; c) S03H; Amine; selected from CrC6-alkyl, CVCi. -aryl, c6-c10-aryl-CkQ-alkyl, crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, Ci-C6-Hyun> base-based base and C6-CiQ-square base The residue of the group is substituted with one or more amine groups; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from a CkCV alkyl group, a c6-c10-aryl group or a c6-c10-aryl group- The residue of the crc6-alkyl group is substituted one or two times, and in the case of an amine functional group substituted with a di-Ci_C6-alkyl group, the alkyl residue can be combined to form a 5 or 6 membered ring; sulfur Alcohol; hydroxy; nitro; cyano; fluorosulfonyl; halogen selected from fluoro, chloro, bromo or iodo; CF3; or OCF3; cyclized to form a bismuth Oxazolone ring system. The cyclization step to form the oxadiazolone ring system is preferably achieved by phosgene, carbonyl di-β m β sit or a carbonated vinegar. Suitable carbonates are, in particular, (^-(: 4-alkyl carbonates). The best reagent for cyclization of phosgene with carbonyl diimidazole. The process may also include the formation of a salt and/or the previous steps. The step of separating any of the salts formed in the following. The present invention is illustrated by the following representative examples: 37 201028406 Example 1: 5-(2,4-Fluorophenyloxy)-3-(4-(2- (Broadcasting small base) ethoxy)phenyl)_ 1,3,4-β咢disal-2(3H)-one dihydrochloride a) at room temperature in 4-decyloxyphenyl Pyridine hydrochloride (6 g, 344 mmol) in a stirred solution of N-methyl-2-pyrrolidone (48 ml), pyridine (13.89 mL, 172 mmol) The resulting solution was cooled to 0 C. Then 2,4-difluorocarbonic acid phenyl ester (7·94 g, 41.2 mmol) was added dropwise. The solution was stirred for 3 minutes and then allowed to return. The mixture was warmed to warmness and stirred for 2 hours. The reaction mixture was poured into ice/water and stirred for hr. hr. The mixture was extracted with ethyl acetate and the organic extracts were washed with 2N hydrochloric acid, water and brine and then dried And filtered to active After stirring for 15 minutes, let the suspension be filtered through a gelatin and diatomaceous earth, and the yellow oil produced by evaporation of the liquid will crystallize from isopropanol to obtain a white solid form of 2 , 4-difluorophenyl 2_(4. methoxyphenyl) hydrazide (3.82 g, 38%) b) 2'4-difluorophenyl 2-(4- at room temperature Methoxyphenyl) 肼_

The ester (3.82 g ' 12.98 mmol) was added dropwise in a solution of Q in a solution of dichloromethane (12 mL). Than the bite (5 46 ml, 67 5 mmol), and cool the resulting solution to (rc. Add phosgene (16 39 ml, 31, 2 mmol) dropwise to the Wei in the stupid Solution: The orange solution produced was given for 30 minutes at 〇 ° C, then allowed to warm to room temperature and mixed for 1 hour. The mixture was purged with nitrogen for 3 minutes, and New Cool was lightly diluted. The phase knife is separated and the organic phase is washed with 2N hydrochloric acid, water and brine, and then dried (sulphuric acid)' and the money is mixed with the rainbow. After the splitting of the seedlings, the suspension 38 201028406 is filtered through a short pad of silicone and diatomaceous earth. The filtrate was evaporated, and the resulting pale yellow solid was crystallised from isopropyl alcohol to give 5,2-difluorophenoxy)-3-(4-methoxyphenyl)-1 as a white solid. , 3,4-indole di-salt-2(3H)-one (1.77 g, 43%). c) 5-(2,4-difluorophenoxy)_3_(4-methoxyphenyl 1,3'4-» and other diindole-2(3H)-one (241 mg, under nitrogen) 0.753 millimolar)

The stirred solution in (5 ml) was cooled to _8 Torr, and boron tribromide (0.142 ml ' 1.505 mmol) was added dropwise. The solution was stirred at -(10) for 5 minutes, then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was then cooled to 〇 C and carefully quenched by the addition of water. The mixture #' was extracted with 30% isopropanol in dioxane, and the combined organic layer was washed with water and brine, then dried (magnesium sulfate), and dried and evaporated. The resulting off-white solid crystallized from isopropanol to give a melting point of 174 5 176. 5-(2,4-Difluorophenoxy)_3_(4-hydroxyphenyl)_U 4 oxadiazole-2(3H)-one (158 mg, 69%). d) 5_(2,4 dioxinoxy) ortho-phenyl)-1,3,4-, di-salt 2 (called _(10) mg, 〇882 mmol) cooled in an ice-water bath Ear), tert-butyl 4-(2-transethyl) travel acid vinegar (244 mg, 〇 59 mmol) and triphenylphosphine (277 mg, 1 fine fine Μ (H) In the solution of (4) in (4 ml), add azodicarboxylate (67 ml, 1.G57 mmol) dropwise, and allow the formed yellow to be colored between the drops. The resulting mixture was removed at room temperature (d) for 3 hours and evaporated under reduced pressure. The residue was chromatographed (1:1 stone_/acetic acid ethyl acetate) to give a butyl group (4-(5-(2,4-difluorophenoxy)) 2oxy group in the form of a color oil. 39 201028406 -U, 4H3 (Liaoji) stupid oxy) ethyl) feed small acid (10) 8 mg, 50%).

e) tert-butyl 4-(2-(4-(5-(2,4-difluoro)oxy).2_side oxome-U,W bis(3Η)-yl)phenoxy Base ethyl) vinegar (2 Saki '0.405 mmol) in one of three gas acetic acid (1 mL) was stirred at room temperature for an hour and the solvent was removed under reduced pressure. The residue was treated with a stupid and evaporated again. The residue was dissolved in ethyl acetate, cooled in ice water and treated with a mixture of hydrogen and hydrogen. The solid formed is filtered off, washed with cold diethyl ether and ethanol, and dried to give 5-(m-phenoxy)3 (4-(2-(s)- -yl)ethoxy)phenyl)_13,4_n bis(2) (called bismuth salt* salt (114 mg, 57%). 2nd case 5-(2,4-difluorophenoxy) _3·(4_(2_(piperidinyl)ethoxy)phenyl)- 1,3,4-oxadiazole-2(3Η)-one hydrochloride was cooled in an ice-water bath 5_(2 , 4_difluorophenoxy)_3 (4-hydroxyphenyl)-1,3,4-oxadiazole-2(3Η)-one (250 mg, 0.816 mmol), 丨_piperidinium oxime ( Add azobisphthalic acid two dropwise to a stirred solution of 0.141 ml, L060 mmol, and triphenylphosphine (278 mg, 丨〇6〇 mmol) in anhydrous tetrahydrofuran (10 ml) Ethyl ester (〇 168 ml, i 〇 62 mmol). The resulting mixture was stirred at room temperature for 4 hr. And homogenized liquid separation and evaporation. The residue is dissolved in ethyl acetate, cooled in ice water and taken in diethyl ether . The excess hydrogen acidified with 2N vaporized solvent was evaporated under reduced pressure to leave 40 201 028 406 - oily semi-solid, and stirred therein under grant added sequentially isopropanol (1 mL) and acetic mL). The resulting sediment was taken out, washed with B, and dried to give a 5-cm (2 4 difluorophenoxy)-3-(4-(2-( Piece-1-yl)ethoxy)phenyl)diazole_2(3H)-net hydrochloride (160 mg, 43%). Example 3 5((2'4-difluorophenoxy)- 3-(4_(2-(π-rheptidin-1-yl)ethoxy)phenyl)- 1,3,4-oxadiazole-2(3Η)-one hydrochloride ❿ in an ice 'water bath 1_(2,4-bis-phenoxy)-3-(4-pyridylphenyl)l,3,4-w-salt 2 in the middle of cooling (25 〇 mg, 〇 fine millimol ), Bu & red ethyl) scaly 124 ml, j 〇 59 mM) and triphenyl lin (10) Neck,! · _ millimolar) In a solution of anhydrous tetrachloromethane (1 〇 ml), add azobis-diethyl _ 168 ml dropwise! Shim Mo). The resulting mixture was stirred at room temperature for 4 hours and the solvent was evaporated under reduced pressure. The residue was subjected to a simple (purine/ethanol), and a homogeneous liquid was collected and evaporated. The residue was dissolved in diethyl ether (5 mL) and acidified in ice water and with an excess of hydrogen. After the mixing of 30 is known, the solvent is evaporated and the residue is dissolved in ethyl acetate (2 ml). (1) A diethyl test (about 10 ml) is added again, and the resulting precipitate is taken into consideration and (10) Washing and drying to obtain a white 115-shaped 5 (2'4' difluorophenoxy)-3-(4-(2-(pyrrolidin-1-yl)) Oxygen soil) stupid) 1'3,4-〇τ dissuccinyl-2(3H)hydrazine hydrochloride (142 mg, 3. 4th case 41 1 (4_乱乱氧氧)'3~(4' (2-(°Bottom-1-yl)ethoxy)phenyl)-l,3,4-g 201028406 Diazole-2(3H)-one hydrochloride 5-cooled in an ice-water bath (4-Chlorophenoxy)3_(4hydroxyphenylhydrazinyl H,3,4_„f二冬2(3H), _mg,! 313 mmol) and 2_(Niangdi-1-yl)ethanol (0.209 ml, L571 mmol) in a solution of anhydrous tetrahydrogen cough (9) ml), added dropwise triphenyl (10) mg, 1.575 mmol) and azo: (d) diethyl (10) 249 ml, L573 millimolar), after adding the yellow color of the shaft of each drop, add the next drop of the light green solution produced at room temperature overnight, and under reduced pressure: solvent . The residue is chromatographed (acetone), and the pale yellow semi-solid is dissolved in the B-made (1G ml) and cooled in an ice-water bath. 2N ruthenium chloride and acidified. The solid formed is filtered off, and then ethanol is dried and then dried in air. It is called 5-(' Ridge % acetamidine • 2 (10), hydrochloride (10) mg, 45%). Base), '5 melting point. Compound prepared in a similar manner. 5-(2- ϋ* base-~~~ _______ ϋ娘味q-yl)ethoxy)phenyl)-5-(2,4- -Z ^ , ------ ------------ --- — into the defeat -...*· /上^!基)Ethoxy) stupid)-5-(4- £ϊϊί^Γ777ΓΤ~~~-~~~~____ 5 (t -- 二嗤~2(3Η)嗍HCl'(10) mouth small Ethyl)phenyl)13,411 夸~~----^_________________ Melting point (°c) 188-189 180 239-240 193-194 42 201028406 208-209 --based MUM 継193 phenyl)-5 ·(2,4·di-gas phenoxy 253-254 223 181-182 218-219 ^ stupid f jujube ^ (4_(3_(4_笨基°底°井-1-1-ylpropoxy)benzene 203 gas )·3-(4 _(3·(3,4-dione isoindole-2(ex)) yl)propoxy)benzina)-l,3,4-n-deficient alpha-supplemented _2(3Η)-ketohydrochloride Salt 205, alkoxy)phenyl)_201 214 171 5-(1'4ό^·phenoxy)-3-(4-(piperidin-4-ylmethoxy)phenyl^1,3,4 -哼二峻-2(3H)-嗣2,2,2-trifluoroacetate 160-161 5-(4-_phenoxy)-3-(4-(2-(decidinyl)_4_ Ethyl)ethoxy)phenyl)_134_哼二咕-2(3H)-b2,2,2-trigas acetate 162 5-(4-chlorophenoxy)-3-(4-(2 -(piperidin-4-yl)ethoxy)phenyl)-indole, 3- 4-oxadiazole-2(3H)-one hydrochloride/v 196-197 5-(2,4-difluorobenzene Oxy)-3-(4-(2-(piperidin-4-yl)ethoxy)phenyl)· 1,3,4-oxadiazole-2(3H)-嗣2,2,2- Trifluoroacetate 143-144 5-(2,4-difluorophenoxy)-3-(4-(2-(piperidin-4-yl)ethoxy)phenyl)-1,3,4- Oxazol-2(3H)-ketohydrochloride 195 5-(4-Vephenoxy)-3-(4-(root pyridine-4-ylindolyl)phenyl)- m-sodium diazole- 2(3H)-ketohydrochloride 224-226 5-(2,4-difluorophenoxy)-3-(4-(Nylidene-4-ylmethoxy)phenyl)_ 1,3, 4-oxadiazole-2(3H)-one hydrochloride 206 5-(4-Hydroxyphenoxy)-3-(4_(3-(° ate-1-yl)propoxy)phenyl) -1,3,4-噚2 Oxazol-2(3H)-one 2,2,2-trifluoroacetate 175 43 201028406 5-(2,4-difluorophenoxy)-3-(4-(3-(piped-1-yl) Propyloxy)phenyl)- 1,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 143 5_(2,4·difluorophenoxy)-3 -(4-(3-(旅口-1-yl)propoxy) phenyl)_ 1,3,4-oxadiazole-2(3H)-one dihydrochloride 229-230 5-( 4-oxophenoxy)-3-(4-(Bistidin-3-ylmethoxy)phenyl)_ι,3,4-噚-喳-2(3H)-one 2,2,2-three Fluoroacetate - 152 5-(4-oxaphenyloxy)-3-(4-(pyridin-3-ylindolyl)phenyl)-indole, 3,4-indoleazole-2 (3H) -Net hydrochloride-246-248 5-(4-Hydroxyphenoxy)-3-(4-(2-(3,4-dihydroisoquinolin-2(1H)•yl)ethenyl) Phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 193 5-(2,4-difluorophenoxy)-3-(4-(2·(6,7) -Dimethoxy-3,4·dihydroisoindole_2(1Η)-yl)ethoxy)phenyl)-1,3,4-. No.2α-sodium-2(3Η)-amine hydrochloride 217 5-(2,4-difluorophenoxy)-3-(4-(l-pyridin-3-ylmethoxy)phenyl)_丨, 3 n oxazol-2(3H)-one 2,2,2-trifluoroacetate' 153 3-(4-(2-(nodal (indenyl)amino)ethoxy)phenyl)_5_ (2,4-difluorophenoxy)-1,3,4-oxaxadiazole-2(3H)-one hydrochloride 165-166 5-(2,4-difluorophenoxy)-3 -(4-(piperidin-3-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 173 3-(4-(2-(cyclohexyl) (indenyl)amino)ethoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 159- 160 3-(4-(3-(cyclohexyl(methyl)amino)propoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-oxadiazole -2(3H)-ketohydrochloride 167-168 5-(2,4-difluorophenoxy)-3-(4-((1-(pyrimidin-2-yl)piperidin-4-yl))曱oxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 143-144 3-(4-(3-(nodal (methyl)amino)propoxy)benzene 5-(2-(2-(2-(2-(2-(2-(2-(yl)))) (Methyl)amino)ethoxy)phenylphenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 140 5-(4-phenylphenyl)- 3-(2- -4-(2-(slightly -1-yl)ethoxy)phenyl)· 1,3,4-oxadiazole-2(311)-one dihydrochloride 195 5-(2,4- Difluorophenoxy)-3-(4-(2-(isoindolin-2-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 125 5-(2,4-difluorophenoxy)-3-(4-(3-(isoindoline-2-yl)propoxy)phenyl)-1,3,4-oxadiazole- 2(3-Ink-121-122 5-(4-Vinyloxy)-3-(3-fluoro-4-(2-(slightly)) ethoxy)phenyl)·1,3 , 4·oxadiazole-2(3H)-one dihydrochloride 198-199 3-(4-(2-(benzyl)amino)ethoxy)-3-fluorophenyl)- 5-(4-Vephenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 164-165 201028406 3-(4-(2-(benzyl)(methyl)amine Ethyl)phenyl)-5-(2,4-diphenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 182 5-(2,4 -dioxaphenoxy)-3-(4-(2-(piper-1) ethoxy)phenyl)-l,3,4-»f-diazole-2(3H)-one Dihydrochloride 192-193 5-(2,4-difluorophenoxy)-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1,3,4 -oxadiazole-2(3H)-ketohydrochloride 200 5-(2,4-difluorophenyloxy)-3-(4-(2- sulphonylethoxy)phenyl)-1,3 , 4-哼2 j-2(3H)-keto salt Salt 171-172 5-(2,4-dioxaphenyloxy)_3_(4-(2-(piperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole _ 2 (3-Ink-keto hydrochloride 170 5-(2,4-difluorophenoxy)_3_(4-(2-()-pyridin-1-yl)ethoxy)phenyl)-1, 3,4-oxadiazole_2(3H)-one hydrochloride 155-156 5-(2,4-diphenoxy)_3_(4-(2-(isoindoline-2-yl)) Ethoxy)phenyl)-1,3,4-oxadiazole_2(3H)-one 124 5-(2,4-diphenoxy)-3-(4-(2-porphyrin B Oxy)phenyl)-1,3,4-oxadiazole-2(3H)-嗣117 5-(4-gasooxy)·3_(2_fluoro-4-(2-(piperidine)- 1-yl)ethoxy)phenyl)-upper 3,4-oxadiazole-2(3H)-one hydrochloride 174-175 5_(4-phenoxy)_3_(4-(2-( 3,4-Dihydroisoquinoline-2(1H)-yl)ethoxy)-2-fluorophenyl)-l,3,4-oxadiazole-2(3H)-one hydrochloride 221- 222 3-(4-(2-(benzyl(indenyl)amino)ethoxy)-2-fluorophenyl)-5-(4-phenylphenoxy-^)-1,3,4-indole Diazol-2(3H)-one hydrochloride oil 5-(4-phenoxy)-3-(2-fluoro-4-(2-porphyrinethoxy)phenyl H dinet hydrochloride 183 f'(4-gas oxy)-3-(2-fluoro-4-(3-()-l-propyl)propoxy)--di-salt-2(3H)- Ming 2 Hydrochloride 220 5-(4-gas Stupid oxy)_3·(2-fluoro-4-(Butyridin-4-yloxy)phenyl)-1,3,4-fluorene hydrochloride 220-221 5_(4·gasphenoxy )_3_(2-Fluoro-4-(Biridine-4-yloxy)phenyl)-U,4-oxadiazole_^H)-one hydrochloride 194 ^•(2,4-difluorophenoxy Base>3·(2_Fluoro-4-(2-(Big 丼-1-yl)ethoxy)phenyl)-1,3,4·α-diazole_2(3H)-one Hydrochloride 158-160 5·(2,4-difluorophenoxy)-3-(2-fluorodong(3-(indol-1-yl)propoxy)phenyl)- 1,3, 4-oxadiazole_2 (3ΗΊ-keto dihydrochloride 205-206 ^-(2,4-difluoro-p-oxy) each (2_Fluorine (2-(Bistidin-4-yl)ethoxy) Phenyl)-diazole-2(3H)-one 2,2,2-trifluoroacetate 153-154 ^•(2,4-difluoro-p-oxy)-3-(2-fluoro_ 4_(2-(Nylidene-4-yl)ethoxy)phenyl)-i'3,4-», etc. Diazole-2(3H)-one hydrochloride---------- -------1 144-145 45 201028406

5-(2,4-difluorophenoxy)-3-(2-fluoro-4-(piperidin-4-yloxy)phenyl, 3,4-oxadiazole-2(3H)-one Hydrochloride 153-154 5-(2,4-difluorophenoxy)-3-(2-fluoro-4-(piperidin-4-ylmethoxy)phenyl)-1,3,4- Oxadiazole-2 (3 - ketone hydrochloride 203-204 5-(2,4-diphenylbenzene)-3-(2-gas-4-(2-(°) Ethyl)ethyl)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 116-117 3-(4-Amino-3-methoxyphenyl)-5 -(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3H)-one 104-105 5-(2,4-difluorophenoxy)-3-(2 -fluoro-4-(2-(piperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (3-im-ketohydrochloride 121-122 5-(2 ,4-difluorophenoxy)-3-(2-fluoro-4-(2-indolyl ethoxy)phenyl)-1,3,4-oxadiazole-2 (3-indole-hydrochloric acid) Salt 197-198 5-(2,4-difluorophenoxy)-3-(2-fluoro-4-(piperidin-3-ylmethoxy)phenyl)-1,3,4-anthracene Azole-2 (3-acetone hydrochloride 144-145 5-(2,4-difluorophenoxy)-3-(4-(2-(ethylamino)ethoxy)-2-fluoro Phenyl)-1,3,4-oxadiazole-2(311)-ketohydrochloride 158-159 5-(2,4-difluorophenoxy)-3-(4-(2-(B) Amino) ethoxy)phenyl)-1,3/l·oxadiazole-2(3H)-one hydrochloride 222-223 5-(4-Vephenoxy)-3-(4-(piperidin-4-yloxy)phenyl)-1,3,4-"f-diazole-2(3H)-one hydrochloride 228-229 5-(2,4-Difluorophenoxy)-3-(4-(2-(methylamino)ethoxy)phenyl)-1,3,4-oxadiazole-2 (311)-ketohydrochloride 228-229 5-(4-Vinylphenoxy)-3-(4-(2-(indolyl)ethoxy)phenyl)-1,3,4- Oxazol-2(3H)-one hydrochloride 245-246 5-(2,4-diphenoxy)-3-(4-(2-(ethylamino)ethoxy)phenyl )-1,3,4-»-diazole-2(3H)-one 2,2,2-trifluoroacetate 153 5-(2,4-diphenoxy)-3-(4-( 3-(piperidin-1-yl)propoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 230 (decomposition) 5-(4-phenoxybenzene) 3-(4-(2-(ethylamino)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 250 (decomposition) 5- (4-Vephenoxy)-3-(4-(2-(4-methylpiperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (311 )-keto-dihydrochloride 242 (decomposition) 5-(2,4-diphenoxy)-3-(4-(2-(2,6-diindolyl) ethoxy)benzene 1,3,4-oxadiazole-2(311)-ketohydrochloride 182 5-(2,4-diphenoxy)-3-(4-(2-(3,5-) Dimethylpiperidin-1-yl)ethoxy Phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 201 46 201028406 5-(2,4-Difluorophenoxy)-3-(4-(2-( 4-methylpiperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 228 5-(4-phenoxy) 3-(4-(2-(2,6-dimethylphenyl) ethoxy)phenyl)-1,3,4-oxadiazole-2(31 €)-one hydrochloride 211 5-(4-Vephenoxy)-3-(4-(2-(3,5-dimethylpiperidin-1-yl)ethoxy)phenyl)-1,3,4-anthracene Oxazol-2(3H)-one hydrochloride 196 5-(2,4-diphenoxy)-3-(4-(2-(4-methylpiperidin-1-yl)ethoxy) Phenyl)-1,3,4-oxadiazole-2(311)-ketohydrochloride 150 5-(2,4-difluorophenoxy)-3-(4-(2-(4-) 5-piperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 184 5-(4-chlorophenoxy)-3-( 4-(2-(4-indolyl-l-yl-1-yl)ethoxy)phenyl)- 1,3,4-oxadiazole-2(311)-one hydrochloride 193 Using solvent as the above The internal standard of the compound was obtained on a Bruker's Avance DPX400 spectrometer with • 13 C-NMR data. The data are reported in the following order: chemical shift approximation (ppm), multiplicity (br: broad; d: doublet; dd: double bimodal; m: multiplet; q: quartet) and coupling constant (Hz). The NMR spectrum was obtained from DMSO solution except that the compound marked with * was obtained from CDC:: 5-(2-chlorophenylethoxy)-3-(4-(2-(piperidin-1-yl)) Ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 155.1, 154.5,148, 134.4,133.3,131.6, 129.8, 129.4, 128.9, 127.5, 119.7, 115.3, 70.1, 62.7, 54.5, 48.5, 40, 31.7 5-(2-phenoxyethoxy)-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl)- 1,3,4-oxadiazole-2(3H)-one dihydrochloride 157.9, 155.2, 154.7, 148.1, 129.8, 129.7, 121.1, 119.9, 115.4, 114.5, 70, 65, 62.7, 54.6, 48.5, 40 5-(2,4-Difluorophenoxy)-3-(4-(2-(piperidin-1-yl)ethylidyl)phenyl)-1,3,4_〇diazole- 2(3Η)-keto dihydrochloride 160.0 (dd, J=11.0, 246.0 Hz), 155.5, 153.3, 152.7 (dd, J=13.0, 252.0 Hz), 147.9, 134.9 (dd, J= 4.0, 13.0 Hz ), 129.4, 124.1 (d, J = 10.5 Hz), 120.3, 115.4, 112.5 (dd, J = 4.0, 24.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 62.7, 54.6, 48.5, 40.0 47 201028406

5-(4-Vephenoxy)_3-(4-(2-(>»Bottom-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (3H) -ketohydrochloride 155.4, 153.4, 150.2, 148, 130.9, 130.1, 129.5, 121.8, 120.2, 115.3, 62.6, 54.6, 52.6, 22.3, 21.2 5-(2,4-difluorophenoxy)-3- (4-(2-(4-Phenylpiperazin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J =11.0, 246.5 Hz), 155.5, 153.3, 152.7 (dd, J=13.5, 252.0 Hz), 149.6, 147.9, 134.9 (dd, J=4.0, 12.0 Hz), 129.4, 129.2, 124.1 (d, J=10.0) Hz), 120.3, 120, 116, 115.3, 112.5 (dd, J=3.5, 23.5 Hz), 106.1 (dd, J= 22.0, 28.0 Hz), 62.7, 54.3, 51.3, 45.4 5-(2, 4-two Fluorophenoxy)-3-(3-(2-(4-indolylpipen-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one Hydrochloride 160.0 (dd, J = 11.0, 247.0 Hz), 158.1, 153.3, 152.6 (dd, J = 13.5, 252.5 Hz), 149.6, 147.7, 136.8, 134.9 (dd, J = 4.0, 12.0 Hz), 130.6 , 129.2, 124.l (d, J = 10.0 Hz), 120.1, 116, 112.6 (dd, J = 3.5, 23.5 Hz), 111.4, 110.8, 106.1 (dd, J = 22.0, 28.0 Hz), 104.8, 62.6 , 54.4, 51.3, 45.4 3-(4-(2-(4-Piepiperazin-1-yl)ethoxy)benzene -5-(2,4-Difluorophenoxy)-1,3,44-diazole-2(3H)-one hydrochloride 160.0 (dd, J=11.0, 246.5 Hz), 155.5, 153.3, 152.7 (dd, J=13.5, 251.5 Hz), 147.9, 134.9 (dd, J=4.0, 12.0 Hz), 131.4, 129.5, 129.4, 128.8, 124.1 (d, J=10.0 Hz), 120.3, 115.4, 112.5 (dd , J = 4.0, 23.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 62.8, 58.6, 55.1, 54.7, 48.8, 47.8 3-(3-(2-(4-benzyl 〇 bottom σ well - 1-yl)ethoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3Η)-one hydrochloride 160.0 (dd, J= 11.0, 247.0 Hz), 158, 153.3, 152.6 (dd, J = 13.5, 252.0 Hz), 147.6, 136.7 (two single peaks), 134.9 (dd, J = 4.0, 12.0 Hz), 131.4, 130.5, 129.5, 128.8 , 124 (d, J = 10.0 Hz), 112.5 (dd, J = 4.0, 24.0 Hz), 111.6, 110.8, 106.1 (dd, J = 22.0, 28.0 Hz), 104.7, 62.6, 58.6, 54.8, 48.7, 47.8 5-(2,4-difluoro cumyl)-3-(3-(2-(piperidin-1-yl)ethoxytomb)phenyl)-1,3,4-0 two < -2(3H)-one 2,2,2-trifluoroacetate 160.1 (dd, J = 11.0, 247.0 Hz), 158.4 (q, J = 33.0 Hz), 158.4, 153.4, 152.7 (dd, J = 13.0) , 251.0 Hz), 147.7, 136.7, 134.9 (dd, J= 4.0, 12.0 Hz), 130.6, 124.1 (d, J= 10. 2 Hz), 112.6 (dd, J=3.8, 23.8 Hz), 116.7 (q, J= 297.0 Hz), 111.4, 110.6, 106.1 (dd, J=22.0, 28.0 Hz), 104.7, 63.6, 55.3, 49, 41.4 5-(2,4-Difluorophenoxy)-3-(4-(2-(3,4-dihydroisoquinolin-2(111)-yl)ethoxy)phenyl)-1 , 3,4-oxadiazole-2(311)-ketohydrochloride 160.0 (dd, J=10.5, 246.0 Hz), 155.6, 153.3, 152.7 (dd, J=13.5, 251.5 Hz), 148, 134.9 ( Dd, J=4.0, 2.5Hz), 131.3, 129.4, 128.6, 128.4, 127.7, 126.7, 126.6, 124.1 (d, J= 10.0Hz), 120.4, 115.4, 112.5 (dd, J=3.5, 23.5Hz), 106.1 (dd, J=22.0, 28.0 Hz), 62.6, 54, 52.4, 49.3, 24.8 5-(2+-difluoro-p-oxy)-3-(4-(3-(4-phenylpipetro-l) -yl)propoxy)phenyl)-1,3,4-oxadiazole-2 (3 - ketone hydrochloride 160.0 (dd, J = 11.5, 247.0 Hz), 156.3, 153.3, 152.7 (dd, J=13.6, 252.0 Hz), 149.6, 147.9, 134.9 (dd, J=4.0, 12.0 Hz), 129.2, 128.9, 124.1 (dd, J=10.4 Hz), 120.4, 120.1, 116, 48 201028406

115.1, 112.5 (dd, J=3.8, 23.7 Hz), 106.1 (dd, J=22.0, 28.0 Hz), 65.4, 53, 50.7, 45.4, 23.2 5-(2,4-difluorophenoxy)-3 -(4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one salt Acid salt 160.0 (dd, J = 11.0, 247.0 Hz), 156.3, 153.3, 152.7 (dd, J = 13.0, 251.0 Hz), 147.9, 134.9 (dd, J = 3.9, 12.2 Hz), 131.5, 128.9, 128.6 ( Two single peaks), 127.7, 126.6 (two single peaks), 124.1 (d, J = 10.0 Hz), 120.4, 115.1, 112.5 (dd, J = 3.2, 23.2 Hz), 106.1 (dd, J = 22.0, 28.0 Hz) ), 65.3, 52.7, 51.9, 48.8, 25, 23.6 5-(4-Vephenoxy)-3-(4-(3-(4-phenylpiped-1-yl)propoxy)phenyl )-1,3,4-11 Diazole-2(3H)-one hydrochloride 156.2, 153.4, 150.3, 149.6, 148.1, 130.9, 130.1, 129.2, 129.1, 121.8, 120.2, 120.1, 116, 115.1, 65.4, 53, 50.7, 45.4, 23.3 5-(4-Vephenoxy)-3-(4-(3-(3,4-dihydroisoindolyl-2(1H)-yl)propoxy; benzene -1,3,4-oxadiazole-2(3H)-one hydrochloride 156.2, 153.4, 150.3, 148.1, 131.5, 130.9, 130.1, 129.1, 128.6 (two unimodal), 127.7, 126.7, 126.6 , 121.8, 120.2, 115, 65.3, 52.7, 51.9, 48.8, 25, 23.6 5-(4- Phenoxy)-3-(4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetic acid Salt 158.1 (q, J = 31.0 Hz), 156.4, 153.4, 150.2, 148.1, 130.9, 130.1, 128.9, 121.8, 120.2, 115, 71.4, 42.8, 33.1, 25.2 5-(2,4-difluorophenyloxy) --3-(4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 160.0 ( Dd, J=10.5, 247.0 Hz), 158. l(q, J=31.0 Hz), 156.5, 153.3, 152.7 (dd, J= 13.5, 251.5 Hz), 147.9, 134.9 (dd, J=4.0, 12.3 Hz ), 128.8, 124.l (d, J = 10.3 Hz), 120.4, 115, 112.5 (dd, J = 4.0, 23.5 Hz), 106.1 (dd, J = 22.5, 28.5 Hz), 71.4, 42.8, 33.1, 25.2 5-(4-Gasyloxy)-3-(4-(2-(piperidin-4-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (3H) -ketone 2,2,2-trifluoroacetate 158.1 (q, J = 31.0 Hz), 156.5, 153.4, 150.3, 148.1, 130.9, 130.1, 128.8, 121.8, 120.3, 115, 65.3, 43.2, 34.7, 30.2, 28.4 5-(4-Vephenoxy)-3-(4-(2-(piperidin-4-yl)ethoxy)phenyl)-1,3,4-»diazole-2 (3H )-ketohydrochloride 156.5, 153.4, 150.3, 148.1, 130.9, 130.1, 128.8, 121.8, 120.2, 115, 65.3, 43, 34.7, 30.3, 28.3 5-(2,4-difluoro Stylooxy)-3-(4-(2-(piperidin-4-yl)ethoxy); phenyl)-1,3,4-», etc., two sniff-2(311)-one 2,2,2 -trifluoroacetate 160.0 (dd, J = 11.0, 246.5 Hz), 158.7 (q, J = 33.0 Hz), 156.6, 153.3, 152.7 (dd, J = 13.5, 251.5 Hz), 147.9, 134.9 (dd, J =4.0, 12.0 Hz), 128.6, 124.l (d, J=10.5 Hz), 120.4, 115, 112.5 (dd, J=3.5, 23.5 Hz), 106.1 (dd, J=22.0, 28.2 Hz), 65.3 , 43.2, 34.6, 30.2, 28.4 5-(2,4-Difluorophenoxy)-3-(4-(2-(piperidyl)ethoxytomb)phenyl)-1,3,4-» Quaroxazol-2(3H)-net hydrochloride 160.0 (dd, J = 10.5, 247.0 Hz), 156.6, 153.3, 152.7 (dd, J = 13.5, 252.0 Hz), 147.9, 134.9 (dd, J = 4.0 , 12.0 Hz), 128.6, 124.1 (d, J = 10.5 Hz), 120.4, 115, 112.5 (dd, J = 3.5, 23.5 Hz), 106.1 (dd, J = 22.5, 28.2 Hz), 65.3, 43, 34.7 , 30.3, 28.3 49 201028406 5-(4-Vephenoxy)-3-(4-(Big -4-yloxy)phenyl]-1,3,4-»diazole-2 ( 3H)-ketohydrochloride 156.4, 153.4, 150.3, 148.1, 130.9, 130.1, 128.9, 121.8, 120.2, 115.0, 71.5, 42.6, 33.1, 25.2 5-(2,4-difluorophenoxy)-3- (4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J = 10.8, 246.5 Hz), 156.6, 153.3, 152.7 (dd, J = 13.0, 251.5 Hz), 147.9, 134.9 (dd, J = 4.0, 12.3 Hz), 128.8, 124.l (d, J = 10.2 Hz), 120.4, 115.0, 112.5 (dd, J = 3.5, 24.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 71.5, 42.6, 33.1, 25.1 5-(4-phenoxy) )-3-(4-(3-(Phosin-4-yl)propoxy)phenyl)-1,3,4-^-exclusive"-2(3H)- Brewed 12,2,2- Trifluoroacetate 158.4 (q, J = 33.0 Hz), 156.3, 152.9, 150.1, 147.8, 130.6, 129.7, 128.7, 121.2, 120.3, 114.9, 65.5, 53.4, 48.6, 41.7, 24.7 5-(2,4- Difluorophenoxy)-3-(4-(3-(piped-1-yl)propoxy)phenyl)-1,3,4-indenyl di salpy-2 (3 -2,2,2, 2-tri-1 acetate 670.0 (dd, J = 10.0, 247.0 Hz), 158.7 (q, J = 33.0 Hz), 156.3, 153.3, 152.7 (dd, J = 13.5, 251.5 Hz), 148, 134.9 (dd, J = 4.0, 12.0 Hz), 128.9, 124.1 (d, J = 10.2 Hz), 120.4, 116.9 (q, J = 298.0 Hz), 115, 112.5 (dd, J = 4.0, 23.5 Hz), 106.1 (1H, Dd, J=22.5, 28.0 Hz), 65.2, 53.4, 48.5, 40.9, 24 5-(2,4-difluorophenoxy)-3-(4-(3-(pipe#-1-yl)propene Oxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 160.0 (dd, J=11.0, 246.5 Hz), 156.3, 153.3, 152.7 (dd , J=13.5, 251.5Hz), 147.9, 134.9 (dd, J= 4.0, 12.2Hz), 128.9, 124.l (d, J= 10.5Hz), 120.4, 115.1, 112.5 (dd, J=3.7, 23.7 Hz), 106.1 (dd, J=22.0, 28.0 Hz), 65.1, 53.1, 47.8, 39.9, 23.2 5-(4-carbyloxy)-3-(4-(slightly bit-3-yl-methyl) Phenyl)-1,3,4-» No.2. Sit-2(3Η)-keto 2,2,2-trifluoroacetate 158.1 (q, J=31.0 Hz), 156.2, 153.4, 150.3, 148.1, 130.9, 130.1, 129.1, 121.9, 120.2, 117.3 (q, J=300.0 Hz), 115, 69.5, 45.5, 43.5, 33.3, 24.6, 21.4 5-(4-Vephenoxy)-3-(4-(pyridin-3-ylmethoxy)phenyl)- 1,3,4-"No.2"Sit-2(3Η)-嗣 hydrochloride 156.3, 153.5, 150.3, 148.1, 131, 130.2, 129.1, 121.9, 120.3, 115.1, 69.6, 45.5, 43.4, 33.2 , 24.7, 21.3 5-(4-Vephenoxy)-3-(4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethoxy)phenyl)-l ,3,4-»f oxadiazole-2(3H)-hydrazine hydrochloride 155.4, 153.4, 150.2, 148, 131.3, 130.9, 130.1, 129.5, 128.6, 128.4, 127.7, 126.6, 126.6, 121.8, 120.2, 115.3 , 62.6, 54, 52.3, 49.3, 24.8 5-(2,4--monosyloxy)-3-(4-(2_(6,7--methoxy-3,4-diazaisoindole)咐> -2(1H)-yl)ethoxy)phenyl)-13,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J = 10.9, 246.5 Hz), 155.6, 153.3, 152.7 (dd, J = 13.3, 251.8 Hz), 148.3, 147.9, 147.7, 134.9 (dd, J = 4.0, 12.0 Hz), 129.3, 124.1 (d, J = 10.0 Hz), 123.1, 120.4, 119.8, 115.3, 112.5 (dd, J=3.7, 23.6 Hz), 111.4, 109.6, 106.1 (dd, 5=22.0, 28.0 Hz), 62.7, 55.6, 55.5, 53.8, 52.0, 49.5, 24.4 201028406

ϋ4-Difluoro phenyloxy)-3-(4-(Slightly decylmethoxy)phenyl)-1,3,4-indenyl-2(3H)-one 2,2,2-three Fluoroacetate 160.0 (dd, J = 11.0, 247.0 Hz), 158.0 (q, J = 31.0 Hz), 156.3, 153.3, 152.7 (dd, J = 13.0, 251.0 Hz), 147.9, 134.9 (dd, J = 4.0) , 12.0 Hz), 128.9, 124.l (d, J = 10.0 Hz), 120.4, 115, 112.5 (dd, J = 4.0, 24.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 69.5, 45.5 , 43.5, 33.2, 24.6, 21.4 3-(4-(2-(nodal (indenyl)amino)ethoxy)phenyl)-5-(2,4-difluoro phenyloxy)-1, 3,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J = 11.0, 246.5 Hz), 155.5, 153.3, 152.7 (dd, J = 13.5, 251.5 Hz), 147.9, 134.9 (dd , J=4.0, 12.0Hz), 131.4, 130.1, 129.5, 129.3, 128.9, 124. l(d,J= 10.2Hz), 120.4, 115.3, 112.5(dd, J=3.8, 23.7Hz), 106.1 (dd , J = 22.0, 28.0 Hz), 62.6, 59, 53.2, 39.7 5-(2,4-difluorophenoxy)-3-(4-(pyrylene-3-ylmethoxy)phenyl)- 1,3,4-oxadiazole-2(3Η)-one hydrochloride 160.1 (dd, J = 10.9, 246.7 Hz), 156.3, 153.3, 152.7 (dd, J = 13.7, 252.0 Hz), 147.9, 134.9 (dd, J= 4.0, 12.0 Hz), 128.9, 124_l (d, J = 10.5 Hz), 120.4, 115, 112.5 (dd, J=3.5, 23.5 Hz), 106.1 (dd, J = 21.8, 27.8 Hz), 69.5, 45.4, 43.4, 33.2, 24.6, 21.3 3-(4-(2-(cyclohexyl(methyl)amino)ethoxy)phenyl) -5-(2,4-difluorophenoxy)- 1,3,4-oxadiazole-2(311)-one hydrochloride 160.0 (dd, J = 11.0, 247.0 Hz), 155.5, 153.3 , 152.7 (dd, J = 13.0, 251.0 Hz), 147.9, 134.9 (dd, J = 4.0, 12.0 Hz), 129.3, 124.1 (d, J = 10.3 Hz), 120.4, 115.3, 112.5 (dd, J = 3.5 , 23.8 Hz), 106·l (dd, J= 22.0, 28.0 Hz), 64, 62.9, 51.1, 36.7, 26.3, 25.3, 24.7, 24.5 3-(4-(3-(cyclohexyl)alkyl) Propyloxy)phenyl)-5-(2,4-difluorophenoxy)- 1,3,4-oxadiazole-2 (3-mer-one hydrochloride 160.0 (dd, J=10.5) , 247.0Hz), 156.3, 153.3, 152.7 (dd, J=13.0, 252.0Hz), 147.9, 134.9 (dd, J= 4.0, 12.0Hz), 128.9, 124.1(d, J= 10.5Hz), 120.4, 115 , 112.5 (dd, J = 4.0, 24.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 65.2, 63.2, 49.6, 35.6, 26.5, 25, 24.7, 24.4, 24.3, 23.8 5-(2,4 -diqibenzene-based)-3-(4-((1-(indolyl-2-yl)piperidin-4-yl)methoxy)phenyl)-1,3,4-oxadiazole- 2(3H)-ketone 160.0 (dd, J=10.5, 246.0 Hz), 159.1, 157.7, 156.7, 153.3, 152.7 (dd, J=13.1, 252.0 Hz), 147.9, 134.9 (dd, J=4.0, 12.7 Hz), 128.6, 124.1 (d, J=10.5 Hz), 120.4, 115, 112.5 (dd, J=3.7, 23.6 Hz), 109.6, 106.1 (dd , J=22.3, 28.0Hz), 72, 43.4, 35.5, 28.1 3-(4-(3_(nodal (methyl)amino)propoxy)phenyl)-5-(2,4-difluoro Phenoxy)·1,3,4-codiodiox-2(3H)-one hydrochloride 160.0 (dd, J=11.0, 247.0 Hz), 156.2, 153.3, 152.7 (dd, J=13.0, 252.0 Hz ), 147.9, 134.9 (dd, J= 4.0, 12.5 Hz), 131.3, 130.2, 129.4, 128.9, 128.8, 124.l (d, J = 10.3 Hz), 120.4, 115, 112.5 (dd, J = 3.8, 23.7 Hz), 106.l (dd, J = 22.0, 28.0 Hz), 65.1, 58.1, 51.8, 38.8, 23.4 51 201028406

3-(4-(2-(benzyl)amino)ethoxy)phenyl)-5-(4-oxaphenyl)-, 3,4-oxadiazole-2 (3H) -_HCl 155.4, 153.4, 150.2, 148.0, 131.4, 130.9, 130.1 (two single peaks), 129·6, 129.5, 128.9, 121.8, 120.2, 115.3, 62.5, 59.0, 53.3, 39.5 5-(4- Gaso-oxy)_3·(2-fluoro-4-(2-(piped-1-yl)ethoxy)phenyl)-1,3,4-indenyl-2(3H)- Ming 2 Hydrochloride 159.1 (d, J = 11.0 Hz), 156.9 (d, J = 251.0 Hz), 153.9, 150.1, 149.2, 131.0, 130.1, 129.1, 121.9, 115.7 (d, J = 12.0 Hz), 111.7 (d, J = 2.5 Hz), 103.5 (d, J = 23.0 Hz), 63.3, 54.3, 48.5, 40.0 5-(2,4-difluorobenzoinyl)_3_(4-(2-(iso) 0- oxalin-2-yl)ethoxy)phenyl)_ι, 3,4-0 bis-2(311)-ketone* 160.7 (dd, J=10.5, 250.0 Hz), 156.9, 153.7, 153.5 (dd, J = 12.5, 255.0 Hz), 148, 139.7, 135.1 (m), 129, 126.8, 123.2 (d, J = 10.0 Hz), 122.2, 120.1, 114.9, 111.8 (dd, J = 4.0, 23.0 Hz), 105.9 (dd, J = 21.5, 27.0 Hz), 67.4, 59.6, 54.6 5-(2,4-difluoro-p-oxy)_3_(4-(3-(iso-oxo)poline-2 -yl)propoxy)phenyl) 1,3,4-oxadiazole-2(3H)-one* 160.7 (dd, J = 10.5, 250.0 Hz), 157.1, 153.7, 153.4 (dd, J = 12.5, 255.0 Hz), 148, 140, 135.1 (dd, J = 4.0, 12.0 Hz), 128.8, 126.7, 123.l (d, J = 10.0 Hz), 122.3, 120.1, 114.8, 111.8 (dd, J=4.0, 24.0 Hz), 105.9 (dd, J = 21.5, 27.5 Hz), 66.3, 59.1, 52.6, 28.7 5-(4-phenoxy)-3-(3-fluoro-4) -(2-(Peptidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 153.5, 151.2 (d, J = 246.0 Hz ), 150.2, 147.9, 143.2 (d, J = 11.0 Hz), 131.0, 130.2, 129.7 (d, J = 9.0 Hz), 121.8, 116.0 (br), 114.6 (d, J = 4.0 Hz), 107.0 (d) , J=24.0Hz), 64.3, 54.8, 48.6, 39.5 3-(4_(2-(¥)(methyl)amino)ethoxy)-3-fluorophenyl)-5-(4-benzene Oxy)-1,3,4-oxadiazole-2(311)-one hydrochloride 153.5, 151.3 (d, J = 245.0 Hz), 150.2, 148.0, 143.2 (d, J = 10.5 Hz), 131.4 , 131.0, 130.2, 130.1, 129.7(d), 129.6, 128.9, 121.8, 116.0(d, J=2.0Hz), 114.6(d, J=4.0Hz), 107.1(d, J=24.0Hz), 64.0, 59.1, 53.3, 39.5 3-(4_(2-(nodal (methyl)amino)ethoxy)phenyl)-5-(2,4-diphenoxy)-1,3,4- Oxadiazole-2(3H)-one hydrochloride 155.5, 152.9, 147.9, 145.9, 132, 131.4, 130.4, 130.1, 129.5, 129.3, 129.2, 12 8.8, 125.6, 123.8, 120.3, 115.3, 62.5, 58.9, 53.2, 39.6 5-(2,4-diphenoxy)-3-(4-(2-(petrole)-1-yl)ethoxylate Phenyl)-1,3,4-σ-diazole-2(3Η)-one dihydrochloride 155.5, 152.9, 147.9, 145.9, 132, 130.4, 129.3, 129.2, 125.6, 123.8, 120.3, 115.4 , 62.7, 54.5, 48.5, 39.5 5-(2,4-Difluorophenoxy)-3-(4-(2-(Nentyl-1-yl)ethoxy)phenyl)-1,3, 4-. No. oxazol-2(3H)-one hydrochloride 160.0 (dd, J = 11.0, 246.0 Hz), 155.5, 153.3, 152.7 (dd, J = 13.0, 251.5 Hz), 147.9, 134.9 (dd, J = 4.0 , 12.5 Hz), 129.3, 124.l (d, J = 10.0 Hz), 120.3, 115.3, 112.5 (dd, J=4.0, 23.5 Hz), 106.1 (dd, J=21.8, 28.0 Hz), 62.6, 54.6 , 52.6, 22.3, 21.2 52 201028406

5-(2,4-Difluorophenoxy)-3-(4-(2-porphyrinethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J = 11.0, 247.0 Hz), 155.5, 153.3, 152.7 (dd, J = 13.5, 252.0 Hz), 147.9, 134.9 (m), 129.4, 124.1 (d, J = 10.5 Hz), 120.3, 115.3 , 112.5 (dd, J = 4.0, 23.5 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 63.1, 62.5, 54.8, 51.6 5_(2,4-diphenoxy)-3-(4- (2-(piperidin-1-yl)ethenyl)phenyl)-1,3,4-» bis-2(311)-residual hydrochloride 155.5, 152.9, 147.9, 145.9, 132, 130.4, 129.3, 129.2, 125.6, 123.8, 120.3, 115.3, 62.6, 54.6, 52.6, 22.3, 21.2 5_(2,4-difluorophenoxy)-3-(4-(2-(吼) bite-1 -yl)ethoxy)phenylhydrazine, hydrazine-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J = 10.5, 246.5 Hz), 155.6, 153.3, 152.7 (dd, J = 13.5, 251.5 Hz), 147.9, 134.9 (dd, J= 3.5, 12.0 Hz), 129.3, 124.l (d, J = 10.0 Hz), 120.4, 115.3, 112.5 (dd, J=4.0, 24.0 Hz), 106.1 ( Dd, J = 22.0, 28.0 Hz), 63.6, 53.6, 52.3, 22.6 5_(2,4-dioxaphenyloxy)-3-(4-(2-(iso)poindolin-2-yl) Oxy)phenyl)- 1,3,4-oxadiazole-2(3H)-one 156.6, 152.8, 147.9, 146, 140, 132, 130.4, 129.2, 128.6, 126.6, 125.6, 123.8, 122.1, 120.4, 115,67.1,58.8, 53.8 5_(2,4·diphenoxy)-3-(4-(2- sulphonylethoxy)phenyl )-1,3,4-oxadiazole-2(3H)-steel 156.5, 152.8, 147.9, 146, 132, 130.4, 129.2, 128.6, 125.6, 123.8, 120.4, 115, 66.2, 65.6, 57, 53.6 5 -(4-gasooxy)_3_(2_? 4-(2-(piperidin-1-yl)ethoxy)phenyl)-1,3,4-噚2° sitting_2(311) - hydrazine hydrochloride 159.2 (d, J = 10.5 Hz), 157.0 (d, J = 252.0 Hz), 153.9, 150.1, 149.2, 131, 130.1, 129.1, 121.9, 115.6 (d, J = 12.5 Hz), 111.7 (d, J = 3.0 Hz), 103.4 (d, J = 23.0 Hz), 63.1, 54.4, 52.6, 22.4, 21.2 5-(4-phenoxy)_3_(4-(2-(3,4-) Two $5 啥 _2 (Qiu-based) ethoxylated phenyl)-1,3,4-ef two. -2(3H)-ketohydrochloride 159.2 (d, J = 11.0 Hz), 157.0 (d, J = 252.0 Hz), 153.9, 150.1, 149.2, 131.3, 131, 130.1, 129.1, 128.6, 128.4, 127.7 , 126.7, 126.6, 121.9, 115.6 (d, J = 12.5 Hz), 111.8 (d, J = 3.0 Hz), 103.4 (d, J = 23.0 Hz), 63.2, 53.8, 52.4, 49.4, 24.8 3-(4 -(2-(nodal (indenyl)amino)ethoxy)-2-fluorophenyl)-5-(4-phenoxy)-1,3,4-oxadiazole-2 (3H )-ketohydrochloride 159.1 (d, J = 10.5 Hz), 156.9 (d, J = 251.5 Hz), 153.9, 150.1, 149.2, 131.4, 130.9, 130.1, 130.1, 129.6, 129.1, 128.9, 121.9, 115.6 (d, J = 12.3 Hz), 111.7 (d, J = 3.0 Hz), 103.4 (d, J = 23.0 Hz), 63.1, 58.9, 52.9, 39.6 5-(4-gas 氡 氡)-3- (2-Fluoro-4·(2-咮琳ethoxy)phenyl)-1,3,4-β-Korean-2(3Η)-ketohydrochloride 159.l (d, J=10.5Hz ), 156.9 (d, J = 252.0 Hz), 153.9, 150.1, 149.2, 130.9, 130.1, 129.1, 121.9, 115.6 (d, J = 12.3 Hz), 111.7 (d, J = 3.0 Hz), 103.4 (d, J=23.5 Hz), 63.2, 63.1, 54.6, 51.6 5-(4-Vephenoxy)-3-(2-fluoro-4-(3·(pipe 4-1-yl)propoxy)phenyl )_1,3,4-β-di-salt-2(3Η)-indole dihydrochloride 160.0 (d, J=10.5 Hz), 157.l (d, J=252.0 Hz), 153.9, 1 50.1, 149.3, 131, 130.1, 129.1, 121.9, 115.l (d, J = 12.5 Hz), 111.6 (d, J = 53 201028406 3.0 Hz), 103.0 (d, J = 22.8 Hz), 65.9, 52.9, 47.9, 39.5, 23 5-(4-Vephenoxy)-3-(2-fluoro-4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole- 2(3H)-ketohydrochloride 160.3 (d, J = 10.5 Hz), 157.1 (d, J = 251.0 Hz), 153.9, 150.1, 149.3, 131, 130.1, 129.1, 121.9, 115.0 (d, J = 12.5) Hz), 111.6 (d, J = 2.5 Hz), 102.9 (d, J = 22.5 Hz), 72, 42.6, 32.9, 25.1 5-(4-phenoxy)-3-(2-fluoro-4- (piperidin-4-yloxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 158.4 (d, J = 10.3 Hz), 157.2 (d, J = 252.0 Hz) ), 153.9, 150.1, 149.3, 131.0, 130.1, 129.3, 121.9, 115.3 (d, J = 12.5 Hz), 112.6 (d, J = 3.0 Hz), 104.0 (d, J = 22.5 Hz), 70, 40.5, 26.9 5-(2,4-Difluorophenoxy)-3-(2-fluoro-4-(2-(Phenyl-1-yl)ethoxy)phenyl)-1,3,4- Oxadiazole-2(3H)-one dihydrochloride 160.0 (dd, J = 11.0, 247.0 Hz), 159.2 (d, J = 10.5 Hz), 157.0 (d, J = 252.0 Hz), 153.7, 152.7 ( Dd, J=13.3, 251.5 Hz), 149.1, 134.7 (dd, J=4.5, 12.5 Hz), 129.2, 124.2 (d, J=10.5 Hz), 115.5 (d, J=12.5 Hz), 112.5 (dd, J=4.0, 23.5 Hz), 111.8 (d, J = 3.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 103.5 (d, J = 23.0 Hz), 63.2, 54.2, 48.4, 39.5 5-(2,4- Difluorophenoxy)-3-(2-fluoro-4-(3-( π bottom 0-1-yl)propoxy)phenyl)-1,3,4-oxadiazole-2 (3Η )-keto dihydrochloride 160.l (d, J = 10.5 Hz), 160.0 (dd, J = 10.5, 246.5 Hz), 157.1 (d, J = 252.0 Hz), 153.7, 152.7 (dd, J = 13.0, 251.0 Hz), 149.2, 134.7 (dd, J=4.0, 12.0 Hz), 129.2, 124.2 (d, J = 10.3 Hz), 114.9 (d, J = 12.5 Hz), 112.5 (dd, J = 3.5) , 23.5Hz), 111.6 (d, J=2.5Hz), 106.1 (dd, J=22.0, 28.0Hz), 103.0(d, J=22.5Hz), 65.9, 52.9, 47.8, 39.5, 23.0 5-(2 ,4-difluorophenyloxy)-3-(2-fluoro-4-(2-(piperidin-4-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 ( 3H)-keto 2,2,2-trifluoroacetate 160.5 (d, J = 11.0 Hz), 160.0 (dd, J = 11.0, 247.0 Hz), 158.9 (q, J = 31.0 Hz), 157.2 (d, J=252.0 Hz), 153.7, 152.7 (dd, J=13.0, 251.0 Hz), 149.2, 134.7 (dd, J=4.0, 12.0 Hz), 129.2, 124.2 (d, J=10.0 Hz), 114.7 (d, J = 12.5 Hz), 112.5 (dd, J = 4.0, 24.0 Hz), 111.5 (d, J = 3.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 102.9 (d, J = 22.5 Hz), 66.1, 43.1, 34.4, 30.2, 28.3 5-(2,4- Fluorophenoxy)-3-(2-fluoro-4-(2-(pyridin-4-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (3-im-ketone) Hydrochloride 160.4 (d, J = 10.5 Hz), 160.0 (dd, J = 11.0, 246.0 Hz), 157.2 (d, J = 251.0 Hz), 153.7, 152.7 (dd, J = 13.5, 251.5 Hz), 149.2 , 134.7 (dd, J=4.0, 12.0Hz), 129.2, 124.2(d, J= 10.5Hz), 114.7(d, J=12.5Hz), 112.5(dd, J=4.0, 24.0Hz), 111.5 (d , J=2.4Hz), 106.1 (dd, J=22.0, 28.0Hz), 102.9(d, J=22.5Hz), 66.1,43.1,34.3,30.2, 28.3 54 201028406

5-(2,4-Difluorophenoxy)-3-(2-fluoro-4-(piperidin-4-yloxy)phenyl)-1,3,4-oxadiazole-2 (3H) - ketohydrochloride 160.0 (dd, J = 11.0, 257.0 Hz), 158.5 (d, J = 10.5 Hz), 157.3 (d, J = 251.5 Hz), 153.7, 152.7 (dd, J = 13.0, 251.5 Hz) , 149.2, 134.7 (dd, J=4.0, 12.0Hz), 129.4, 124.2 (d, J=10.0Hz), 115.l(d, J=12.5 Hz), 112.6(d, J=3.0Hz), 112.5 (dd, J=4.0, 23.0 Hz), 106.l (dd, J=22.0, 28.0 Hz), 104.0 (d, J = 23.0 Hz), 70.0, 40.5, 26.9 5-(2,4-di- benzene Oxy)-3-(2-disorder-4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 160.4 (d , J=10.5Hz), 160.0(dd, J=10.5, 247.0Hz), 157.2(d, J= 251.0Hz), 153.7, 152.7(dd, J=13.4, 251.7Hz), 149.2, 134.7 (dd,4.0 , 12.0 Hz), 129.2, 124.1 (d, J = 10.5 Hz), 114.8 (d, J = 12.0 Hz), 112.5 (dd, J = 3.5, 23.5 Hz), 111.6 (d, J = 2.5 Hz), 106.1 (dd, J=22.0, 28.0 Hz), 102.9 (d, J = 22.5 Hz), 72.0, 42.5, 32.8, 25.0 5-(2,4-difluorophenoxy)-3-(2-fluoro-4) -(2-(indolyl-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J = 11.0, 247.0 Hz ), 159.3 (d, J = 10.5 Hz), 157.0 (d, J = 252.0 Hz), 153.7, 152.7 (dd, J = 13.5, 251.5 Hz), 149.1, 134.7 (dd, J = 4.0, 12.0 Hz), 129.2, 124.1 (d, J = 10.3 Hz), 115.4 (d, J = 12.5 Hz), 112.5 ( Dd, J=3.5, 23.5 Hz), 111.8 (d, J=2.5 Hz), 106.1 (dd, J= 22.0, 28.0 Hz), 103.4 (d, J=23.0 Hz), 64.2, 53.6, 52.2, 22.6 3 -(4-Amino-3-methoxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3H)-one 160.6 (d, d , J = 10.0, 249.5 Hz), 153.5, 153.4 (dd, J = 12.4, 254.5 Hz), 148.1, 147.1, 135.l (m), 134.7, 126.9, 123.l (d, J = 10.0 Hz), 114.3, 112.0, 111.8 (dd, J= 4.0, 23.5 Hz), 105.9 (dd, J=22.0, 27.0 Hz), 102.5, 55.7 5-(2,4-disorganophenyl)-3-(2- Scrambled 4-(2-(piperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 160.1 (dd, J = 10.5, 246.5 Hz), 159.3 (d, J = 10.5 Hz), 157.l (d, J = 251.5 Hz), 153.7, 152.7 (dd, J = 13.3, 251.8), 149.1, 134.7 (dd, J=4.0, 12.0 Hz), 129.3, 124.2 (d, J = 10.5 Hz), 115.4 (d, J = 12.0 Hz), 112.5 (dd, J = 4.0, 24.0 Hz), 111.8 (d, J = 3.0 Hz), 106.1 (dd , J=22.0, 28.0Hz), 103.4(d, J=23.0Hz), 63.2, 54.4, 52.6, 22.4, 21.2 5-(2,4-diphenoxy)-3-(2-chaos-4 -(2-morpholine ethoxy)benzene -1,3,4-oxadiazole-2(3H)-one hydrochloride 160.1 (dd, J = 11.0, 247.0 Hz), 159.3 (d, J = 10.5 Hz), 157.0 (d, J = 252.0) Hz), 153.7, 152.7 (dd, J=13.5, 251.5 Hz), 149.1, 134.7 (dd, J=4.0, 12.0 Hz), 129.3, 124.2 (d, J=10.5 Hz), 115.5 (d, J=12.5) Hz), 112.5 (dd, J=3.5, 23.5Hz), 111.8(d, J=3.0Hz), 106.1(dd, J= 22.0, 28.0Hz), 103.5(d, J=23.0 Hz), 63.2, 63.1 , 54.6, 51.6 55 201028406 5-(2,4·- one gas to be oxy)·3_(2-gas-4_(acridine-3-yloxy)phenyl)134 噚二峻-2(3H) - Ming hydrochloride 160.2 (d, J = 10.0 Hz), 160.0 (dd, J = 11.0, 247.0 Hz), 157.1 (d, J = 251.0 Hz), 153.7, 152.7 (dd, J = 13.5, 252.0 Hz) , 149.2, 134.7 (dd, J= 4.0, 12.0Hz), 129.2, 124.2(d, J= 10.0Hz), 114.9(d, J=12.5Hz), 112.5(dd, J=3.0, 24.0Hz), 111.6 (br), 106.1 (dd, J = 22.0, 28.0 Hz), 103.0 (d, J = 23.0 Hz), 70.1, 45.2, 43.3, 32.9, 24.6, 21.2 5-(2,4-one gas base) 3-(4-(2-(ethylamino)ethoxy)-2-fluorophenyl)-1,3,4-presented di-salt-2(3H)--hydrochloride 160.1 (dd, J =22.0, 28.0 Hz), 159.5 (d, J = 10.0 Hz), 157.0 (d, J = 252.0 Hz), 153.8, 152.7 (dd, J = 13.0, 251.5 Hz), 149.1, 134.7 (dd, J=4.0, 12.5 Hz), 129.3, 124.2 (d, J = 10.3 Hz), 115.4 (d, J = 12.2 Hz), 112.5 (dd, J = 3.8, 23.6 Hz), 111.8 (d, J =3.0 Hz), 106.1 (dd, J=22.0, 28.0 Hz), 103.3 (d, J = 23.0 Hz), 64.4, 45.1, 42.3, 11.0 5-(2,4-difluoro-p-oxy)-3- (4-(2-(ethylamino)ethoxy)phenyl)-1,3,4-indenyl-2(3H)-one hydrochloride 160.0 (dd, J = 10.5, 246.5 Hz) , 155.7, 153.4, 152.7 (dd, J = 13.5, 252.0 Hz), 147.9, 134.9 (dd, J = 4.0, 12.0 Hz), 129.3, 124.l (d, J = 10.3 Hz), 120.3, 115.3, 112.6 (dd, J=4.0, 24.0 Hz), 106.1 (dd, J= 22.0, 28.0 Hz), 63.8, 45.4, 42.4, 11 5-(4-gasooxy)-3-(4-(派咬- 4-yloxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 154.5, 153.4, 150.3, 148.1, 130.9, 130.1, 129.3, 121.8, 120.4, 116.5, 69.4, 40.5, 27.1 5-(2,4-Difluorophenyldry)-3-(4-(2-(methylamino)ethoxy)phenyl)-1,3,4-σ-dioxime- 2(3Η), hydrochloride 160.0 (dd, J=10.5, 246.5Hz), 155.7, 153.3, 152.7 (dd, J=13.0, 252.0Hz), 147.9, 134.9 (dd, J=4.0, 12.5Hz), 129.3, 124.1 (d, J = 10.3 Hz), 120.3, 115.3, 112.5 (dd, J = 4.0, 24.0 Hz), 106.1 (dd, J = 22.0, 28.0 Hz), 63. 6, 47.2, 32.8 5-(4-Vephenoxy)-3-(4-(2-(decylamino)ethoxy)phenyl)-l,3,4-°f two"Sit -2(3H)-_hydrochloride 155.5, 153.2, 150.2, 147.9, 130.7, 129.9, 129.4, 121.5, 120.2, 115.2, 63.6, 47.1, 32.6 5_(2,4_monophenoxy)-3-( 4-(2-(ethylamino)ethoxy)phenyl)-1,3,4-»diazole-2(3H)-indole 2,2,2-trifluoroacetate 155.7, 153, 147.9, 146, 132.1, 130.4, 129.3, 129.2, 125.7, 123.9, 120.3, 115.3, 63.8, 45.5, 42.4, 11 5_(2,4_ 一气本乳基)-3-(4-(3-(略略- 1-yl)propoxy)phenyl)-1,3,4-indenyl-2(3H)-net dihydrochloride 156.3, 152.9, 147.9, 146, 132, 130.4, 129.2, 128.9, 125.6, 123.9, 120.4, 115.1, 65.2, 53.1, 47.9, 39.5, 23.3 5-(4-Vephenoxy)-3-(4-(2-(ethylamino)ethoxy)phenyl)-1, 3,4-oxadiazole-2(3H)-net hydrochloride 155.6, 153.3, 150.2, 147.9, 130.8, 130, 129.4, 121.6, 120.2, 115.2, 63.7, 45.3, 42.3, 10.8 56 201028406

5-(4-Vephenoxy)_3-(4-(2-(4-methylpipene-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 ( 3H)-keto dihydrochloride 155.4, 153.4, 150.3, 148.1, 130.9, 130.1, 129.5, 121.8, 120.2, 115.4, 62.8, 54.8, 49.8, 48.9, 42.1 5-(2,4-diphenoxy) -3-(4-(2-(2,6-dimethyloxalinyl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-indole hydrochloride 155.6, 152.9, 147.9, 146, 132, 130.4, 129.3, 129.2, 125.6, 123.8, 120.4, 115.4, 68.5, 62.2, 55.5, 55, 18.3 5-(2,4-diphenoxy)-3-(4- (2-(3,5-•indolyl)-1-ethoxy)ethoxy)phenyl-1,3,4-»diazole-2(3H)-one hydrochloride 155.6, 152.9 , 147.9, 146, 132, 130.4, 129.3, 129.2, 125.6, 123.8, 120.4, 115.3, 62.4, 57.5, 55, 38.6, 28.3, 18.4 5-(2,4-difluorophenoxy)-3-(4 -(2-(4-hydrazinopipen-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(311)--dihydrochloride 160.0 (dd, J =11.0, 247.0 Hz), 155.5, 153.3, 152.7 (dd, J=12.5, 251.0 Hz), 147.9, 134.9 (dd, J=4.3, 13.0 Hz), 129.3, 124.1 (d, J = 10.0 Hz), 120.3 , 115.4, 112.5 (dd, J=4.0, 24.0 Hz), 106.1 (dd, J=22.0, 28.0 Hz), 62.9, 54 .6, 49.8, 48.9, 42.0 5-(4-Vephenoxy)-3-(4-(2-(2,6-dimethylphenyl)phenyl)ethoxy)phenyl)-1,3 , 4-indole di-salt-2(3H)--hydrochloride 155.4, 153.4, 150.3, 148, 130.9, 130.1, 129.5, 121.8, 120.2, 115.3, 68.4, 62.2, 55.5, 54.9, 18.3 5-(4- Gasooxy)-3-(4-(2-(3,5-dimethylpiperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (3H )-ketohydrochloride 155.4, 153.4, 150.2, 148, 130.9, 130.1, 129.5, 121.8, 120.2, 115.3, 62.4, 57.5, 54.9, 38.6, 28.3, 18.4 5_(2,4-monoxyloxy)-3 -(4-(2-(4-mercaptopiperidin-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 155.5, 152.9, 147.9, 145.9, 132, 130.4, 129.3, 129.2, 125.6, 123.8, 120.4, 115.3, 62.6, 54.8, 52.5, 30.7, 28, 21.2 5-(2,4-difluorophenoxy)-3_(4-( 2-(4-Methylpiperidin-1-yl)ethoxy)phenyl)- 1,3,4-oxadiazole-2(3H)-one hydrochloride 160.0 (dd, J=11.0, 247.0 Hz), 155.5, 153.3, 152.7 (dd, J=13.0, 251.0 Hz), 147.9, 134.9 (dd, J= 4.0, 12.0 Hz), 129.3, 124.1 (d, J = 10.5 Hz), 120.4, 115.3, 112.6 (dd, J=4.0, 24.0 Hz), 106.1 (dd, J= 22.0, 28.0 Hz), 62.6, 54.8, 52 .5, 30.8,28,21.2 5-(4-oxaphenyloxy)-3-(4-(2-(4-methylpiperidin-1-yl)ethoxy)phenyl)-1,3 , 4-oxadiazole-2(3H)-one hydrochloride 155.4, 153.4, 150.3, 148.1, 130.9, 130.1, 129.5, 121.8, 120.2, 115.3, 62.6, 54.8, 52.5, 30.7, 28, 21.2 As an internal standard, Bruker's Avance DPX400 spectrometer obtained an oily sample of 3-(4-(2-(benzyl(indenyl))amino)ethoxy)-2 ih-NMR spectrum of -fluorophenyl)-5-(4-chlorophenyloxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride, and further analysis of characteristic 57 201028406. The data are reported in the following order: chemical shift approximation (ppm), number of protons, multiplicity (br: broad; d: doublet; m: multiplet; s: singlet; t: triple) and coupling constant (Hz): (1H NMR, DMSO, 400 ΜΗζ) δ : 11.02 (1Η, br), 7.68-7.50 (7H, m), 7.46 (3H, m), 4.50 (2H, t, J=5), 4.45-4.28 (2H , m), 3.47 (2H, m), 2.74 (3H, s) FAAH inhibitory activity in animal tissues to which the compound of the present invention is administered is determined according to the following method: Animals used in animal treatment experiments are from Interfauna Ib& Male NMRI mice (body weight 27-44 g) obtained by ica (Spain). Five mice were housed per cage under controlled environmental conditions (12 hour light/dark cycle and room temperature 22; tl 〇 C). Both feed and tap water are freely available, and experiments are conducted during the day. Animals were fed a stainless steel curved injection needle (Perfectum, USA), and 3 mg/kg of BIA compound (8 ml/kg; compound suspended in 〇5% rebellion) was administered to the animals via the oral route. Methylcellulose (CMC) or dissolved in water, or 8 ml/kg 〇5 % CMC (control). Animals were anesthetized by intraperitoneal administration of 6 mg/kg pentobarbital 15 minutes before sacrifice. Remove a portion of the liver, left lobe, and brain that does not include the cerebellum' and place in a plastic bottle containing membrane buffer (3 mM magnesium sulphate, 1 mM EDTA, 5 mM TrisHC1 with a pH of 7.4). Store the tissue before analysis. Animals were fasted overnight until the compound was administered, unless the period exceeded 18 hours; the feed was removed on the morning of the day of administration and the compound was administered on the same afternoon of 201028406. Then only the animals are supplied with water. All animal handling procedures are in strict compliance with the European Vertebrate Protection Act (86/609 CEE) for experimental and other scientific uses and Portuguese law (Decreto-Lei 129/92, Portarias l〇〇5/92e 1131/97). The number of animals used is the least likely to be in line with current legislation and scientific integrity. Reagents and solutions Anandamide [ethyl amide 丨 JH_K40-60Ci / millimolar) was obtained from American Radi Chemicals. All other reagents were obtained from Sigma_Aldrich. The Optiphase Supermix was obtained from Perkin Elmer, Inc., and the activated carbon was obtained from Signia-Aldrich. Tissue preparation was thawed on ice and placed in 10 volumes of membrane buffer (3 mM magnesium sulfide, 1 mM EDTA, 50 mM TrisHCl with a pH of 7.4), homogenized by Potter Elvejhem (brain: 8 hits at 500 rpm) or Heidolph Diax homogenizer (liver: hit 2 times in level 5 for 20 seconds and pause for 30 seconds) for homogenization. Total protein in the tissues was determined by BioRad protein analysis (BioRad) using a standard curve of BSA (50-250 μg/ml). The enzyme assay reaction mixture (total volume 2 〇 0 μl) contains: 2 AEA (2 59 201028406 AEA + 5 nM 3H-AEA); 〇·1% fatty acid-free BSA; 15 μg (brain) in 1 mM EDTA 5 micrograms (liver) or 50 micrograms (lung) protein; 10 mM Tris with a pH of 7.6. After pre-incubation for 15 minutes at 37 ° C, the reaction was initiated by the addition of a substrate solution (cold AEA + radiolabeled AEA + BSA). The reaction was carried out for 10 minutes (brain and lung) or 7 minutes (liver) and then by adding 400 microliters of activated carbon suspension (8 grams of charcoal in 32 ml of 0.5 M hydrochloric acid and in continuous stirring). Stop the reaction. After incubating for 30 minutes at room temperature under stirring, the carbon was precipitated by centrifugation of a microcentrifuge (centrifugation at 13,000 rpm for 1 minute). Add 200 μl of the supernatant to the 800 μl Optiphase Supermix flash coal in a 24-well flat jDL. The count per minute (cpm) was determined in a Microbeta TriLux scintillation counter. A blank group (no protein) was prepared in each analysis. The percentage of residual enzyme activity relative to the control group (no compound) was calculated after subtracting the blank group. The results are published in the second table: Table 3 name control group % small gas liver 30 mg / kg 1 hour control group rat brain 3 〇 mg / kg 1 hour 5- (2- ethoxy ethoxy) -3- ( 4-(2-(〇辰啼-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 41.28 94.88 5-(2- stupid Oxyethoxyethoxy)-3-(4-(2-(piperid-1 -yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)- ---- --- 47.86 ------- 95.96 keto dihydrochloride 5_(2,4-one gas phenyl lactyl)-3-(4-(2-(娘 0 well-1_yl)ethoxy)benzene Base)-1,3,4-codiodin-2(3H)- 5.25 74.12 keto dihydrochloride 201028406

5-(4-Vephenoxy)-3-(4-(2-(piperidin-1 -yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)- Ketone hydrochloride 12.13 31.85 5-(2,4-difluorophenoxy)-3-(4-(2-(4-phenylpipene-1-yl)ethoxy)phenyl)-1, 3,4-oxadiazole-2(3H)-one hydrochloride 16.87 62.88 5-(2,4-difluorophenoxy)-3-(3-(2-(4-phenylpiped-1) -yl)ethoxy)phenyl H,3,4-oxadiazole-2(3H)-one hydrochloride 37.18 56.99 3-(4-(4-f-phenylpiperidin-1-yl) Ethoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 22.44 85.99 3-(3-(2 -(4-f-piperidine-1-yl)ethoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3H)- Ketone hydrochloride 48.46 87.39 5-(2,4-difluorophenoxy)-3-(3-(2-(piperidin-1-yl)ethoxy)phenyl)-1,3,4- Oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 69.43 107.87 5-(2,4-difluorophenoxy)-3-(4-(2-(3,4-di) Hydrogen isoquinoline-2(1H)-yl)ethoxy)phenyl)-l,3,4-»diazole-2(3H)-one hydrochloride 12.06 64.92 5-(2,4-di Fluorophenoxy)-3-(4-(3-(3,4-dihydroisoquinolin-2(1H)-yl)propoxy)phenyl)-1,3,4-oxadiazole- 2(3H)-ketohydrochloride 52.96 86.86 5-(4-lactyl-phenyl)-3-(4-(3-(4-phenyl)]-1-yl)propoxy)phenyl)-l,3,4-indole Diazole-2(3H)-one hydrochloride 83.35 108.12 5-(4-Vephenoxy)-3-(4-(3-(3,4-dihydroisoquinolin-2(1H)-yl) Propyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 43.01 81.31 5-(4-Chlorophenoxy)-3-(4-(piperidine- 4-yloxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 15.04 92.39 5-(2,4-difluorophenoxy 3-(4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 14.54 99.33 5-(4-Benzylphenyl)-3-(4-(2-(1^03⁄4-4-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2 (3H )-keto 2,2,2-trifluoroacetate 37.98 95.02 5-(4-Phenyloxy!-yl)-3-(4-(2-(pyrylene-4-yl)ethoxy)phenyl) -1,3,4-oxadiazole-2(311)-ketohydrochloride 68.27 92.33 61 201028406 5-(2,4-Difluorophenoxy)-3-(4-(2-(piperidine)- 4-yl)ethoxy)phenyl-1,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 13.11 82.26 5-(2+ Difluorophenoxy --3-(4-(2-(piperidin-4-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 28 .76 87.83 5-(4-Vephenoxy)-3-(4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one Hydrochloride 20.11 80.43 5-(2,4-Difluorophenoxy)-3-(4-(piperidin-4-ylmethoxy)phenyl)-1,3,4-oxadiazole-2 (3H)-ketohydrochloride 6.75 62.47 5-(4-Vephenoxy)-3-(4-(3-(piperidin-1-yl)propoxy)phenyl)-1,3,4 -oxadiazole-2(311)-keto 2,2,2-trifluoroacetate 78 89 5-(2,4-difluorophenoxy)-3-(4-(3-(piperidin-l) -yl)propoxy)phenyl)-l,3,4-oxadiazole-2(3H)-one 2,2,2-trifluoroacetate 7.14 73.68 5-(2,4-difluorophenoxy 3-(4-(3-(3-piperidin-l-yl)propoxy)phenyl)-l,3,4-oxadiazole-2(3H)-one dihydrochloride 7.76 84.65 5 -(4-cyclophenoxy)-3-(4-(piperidin-3-yloxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 2,2, 2-trifluoroacetate 25.17 91.9 5-(4-Vephenoxy)-3-(4-(piperidin-3-yloxy)phenyl)-1,3,4-oxadiazole-2 (3H)-ketohydrochloride 68.86 89.54 5-(4-Vephenoxy)-3-(4-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethoxy) Phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 48.21 94.67 5-(2,4-difluorophenoxy)-3-(4-(2-(6) , 7-dioxane -3,4-Dihydroisoquinoline-2(1H)-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one hydrochloride 52.71 86.57 5-( 2,4-Difluorophenoxy)-3-(4-(piperidin-3-ylindoleoxy)phenyl)-1,3,4-oxadiazole-2 (3 - ketone 2, 2 , 2-trifluoroacetate salt 23.16 99.38 3-(4-(2-(benzyl)amino)ethoxy)phenyl)-5-(2,4-difluorophenoxy)-1 , 3,4-oxadiazole-2(3H)-one hydrochloride 24.42 77.95 5-(2,4-difluorophenoxy)-3-(4-(piperidin-3-ylmethoxy) Phenyl)-1,3,4-oxadiazole-2 (3-ink-ketohydrochloride 11.15 89.76 3-(4-(2-(cyclohexyl(methyl)amino)ethoxy)phenyl) -5-(2,4-difluorophenoxy)-1,3,4-oxadiazole-2(3H)-one salt SIL salt 39.28 92.6 201028406

5-(2,4-difluorophenoxy)-3-(4-((1-(pyrimidin-2-yl)piperidin-4-yl)methoxy)phenyl)-1,3,4 -oxadiazole-2(3H)-one 86.75 89.68 3-(4-(3-(benzyl)amino)propoxy)phenyl)-5-(2,4-difluorophenoxy -1,3,4-oxadiazole-2(3H)-one hydrochloride 31.42 81.94 3-(4-(2-(benzyl)amino)ethoxy)phenyl)- 5-(4-Chlorophenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 65.39 93.28 5-(4-Vephenoxy)-3-(2-fluoro- 4-(2-(piperid-1 -yl)ethoxy)phenyl)-l,3,4-oxadiazole-2(3H)-one dihydrochloride 6.09 85.86 5-(2,4- Difluorophenoxy)-3-(4-(3-(isoindolin-2-yl)propoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 86.58 101.57 5-(4-Vephenoxy)-3-(3-fluoro-4-(2-(pipen-l-yl)ethoxy)phenyl)-l,3,4-oxadiazole- 2(3H)-one dihydrochloride 73.2 102.9 3-(4-(2-(nodal (methyl)amino)ethoxy)-3-fluorophenyl)-5-(4-phenoxybenzene) -1,3,4-oxadiazole-2(3H)-one hydrochloride 89.49 97.96 3-(4-(2-(benzyl)amino)ethoxy)phenyl)- 5-(2,4-Dichlorophenoxy)-1,3,4-oxadiazole-2(3H)-one hydrochloride 46.82 104.27 5-(2,4-di Phenoxy)-3-(4-(2-(piped-1-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one dihydrochloride 6.11 84.39 5-(2,4-Difluorophenoxy)-3-(4-(2-(acridine-l-yl)ethoxy)phenyl)-l,3,4-oxadiazole-2 (3H)-ketohydrochloride 10.11 20.41 5-(2,4-difluorophenoxy)-3-(4-(2- porphyrinethoxy)phenyl)-1,3,4-anthracene Azole-2(3H)-one hydrochloride 14.33 49.96 5-(2,4-Dichlorophenoxy)-3-(4-(2-(piperidin-1-yl)ethoxy)phenyl) -1,3,4-oxadiazole-2(3H)-one hydrochloride 8.83 49.99 5-(2,4-difluorophenoxy)-3-(4-(2-7-pyrrolidine-l- Ethyl)phenyl)-l,3,4-oxadiazole-2(3H)-one hydrochloride 9.21 10.01 5-(2,4-diphenoxy)-3-(4- (2-(Isoindolin-2-yl)ethoxy)phenyl)-1,3,4-oxadiazole-2(3H)-one 60.42 99.37 63 201028406 As apparent from the above biological tests, The compounds of the present invention have an unexpectedly high FAAH inhibition which makes these compounds potential candidates for the treatment or prevention of FAAH-associated medical conditions. Moreover, the comparison of the data also shows that a compound having a 5 〇 substitution 3 N phenyl-1,3,4-SH structure, single το, is characterized in that it is more selective for peripheral nerves in vivo than for the central nervous system (CNS). ). Moreover, when m=l, n=〇 and Y are a selectively substituted phenyl ring, if A represents a meta position of the oxadiazolone ring by 2-dimethylaminoethyloxy 3,3 ,5-trimethylcyclohexylaminosulfonyl, 2,2,6,6-tetramethylpiperidinylsulfonyl, 2-(diisopropylaminoethyl)aminesulfonate Y-substituted by 4-indolyl, 4-methylpiped-1-yl-sulfonyl, 3,3-dimethylpiperidinylcarbonyl or 2-didecylaminoethyloxy, Y does not represent unsubstituted Phenyl. In some optional embodiments of the compounds of the present invention, when A, B and C represent an amine-substituted stupid group, wherein the amine group is N(Ci Cr alkyl) 2 or an amine sulfonyl group Substituting one to three times <^-(:18 alkyl or C2-C18-sweetyl substitution; or cvCht aryl AQ-alkyl-C5-C8-cycloalkyl-CrCV-based substituted by NHSOHVQo-aryl , c5_c8_cycloalkyl, © C6-C1 (raryl-C2-C6-dilute, C6-Ci〇-aryl, diphenyl, diphenyl-CrC4-alkyl, indanyl, γ does not represent Cl_c6_alkyl, c3_C9_cycloalkyl' wherein the two groups are selectively substituted with one or more of phenyl, Ci_C4_alkyloxy, S-CVCV alkyl, N(CrC4_alkyl)2 And, wherein the stupid base is selectively substituted one or more times by spectrinin, CrC4-alkyl, Crc4-alkyloxy, nitro or cF3.

In some optional embodiments of the compounds of the present invention, A 'B 64 201028406 and C do not represent a phenyl group substituted by CVC4 alkyl, CrC:9 alkyloxy or (VC10-aryl-CVCV alkyloxy, CVCs cyclohexyl or 〇-(:3_(:8-cycloalkyl, when n=0 and m=〇, and when γ represents CVC2), substituted by bis-Q-Ct alkylamino group, When C6-C丨〇 aryl, C^-Cio aryloxy or C4-C12-alkoxy-CVC4-alkoxy substituted CVC22 alkyl, cvc4 alkyl, wherein the aryl group may be substituted by the following Multiple phenyl or naphthyl·halogen, Ci_C4_ group, CrCr alkyloxy, nitro or CF3 substituted; or c7_C2() dilute, 3β_ • cholestene-3-yl or phenoxy or c6_Cl2 _Alkyl-substituted phenyl. In still another optional embodiment of the compound of the present invention, all such compounds may be CrC9 alkyl, CrC9 alkyl oxygen, _ s, and trifluoromethyl in the case of an aryl group. Substituted one or more times; and in the case of a cycloalkyl group may be substituted one or more times by a ^-alkyl or a C6-C10 aryl group; and in the case of an alkyl group, may be substituted one or more times by a hydroxy group and a fluoro group [Simple description] (none) _ [Main component symbol description] (none) 65

Claims (1)

201028406 VII. Patent application scope: 1. A compound of formula (I): c—L—B—A—N ^X^-CCH^m-Y (I) wherein A represents a phenyl group or a 5 or 6 membered heteroaromatic ring system containing up to 4 heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, which are optionally substituted by one or more times. Q-Qr alkyl, C3-C8-cycloalkyl, C6-C10-aryl, C6-C10-aryl-CVC8-alkyl, CVCV alkoxy, C6-C1 (r aryloxy, C6-C10 -aryl-CVCs-alkoxy, Q-CV alkylcarboxy, C6-C1 (rarylcarboxy, Crc6-alkylmercaptocarboxy, C6-C1()-aryldecylcarboxy, CKQ-alkyl a sulfonyloxy group, a C6-C1 (rarylsulfonyloxy group, each of which is optionally substituted one or more times by the following: Q-CV alkyl; CVCV alkoxy; C6-C10-aryloxy; Co2h ; so3h ; CONH2 ; S02NH2 ; CONH2 or so2nh2, wherein the amino functionality is selected from the group consisting of crc6-alkyl, C6-C1()-aryl or C6-C1()-aryl-CVC4-alkyl Substituting a residue one or more times, and wherein in the case of a di-CVC6-alkyl substituted amine functionality, the alkyl residue may combine to form a 5 66 201028406 or 6 membered ring; an amine group; It is selected from the group consisting of CrC6-alkyl, C6-C1 (r aryl, C6-C10-aryl-CVCr alkyl, CrC6-alkylcarbonyl, C6-Ci〇-aryl thiol, Ci_C6_alkyl base) Substituting one or more amine groups for a residue of a C6_Ci〇-arylsulfonyl group; a thiol group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; a gas group; a bromo group; Iodo; CF3 or OCF3; co2h; So3H; amine group; selected from CrC6-alkyl, C6-C1 (r aryl, C6-C1 (r aryl-CVC6-alkyl, Q-C6-alkylcarbonyl, C6-C1 (r arylcarbonyl) , CrC6-alkylsulfonyl and c6-c1 (the residue of the rarylsulfonyl group is substituted by one or more amine groups; a disubstituted amine group of the following formula (II): r~\ (II) wherein 0 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and Q-C6-alkyl, and the methylene group in the formula (II) is selectively subjected to Cl-C6 - a calcinyl, fluoro or ke group substituted one or two times; CONH2; so2nh2; conh2 or so2nh2, wherein the amino functionality is selected from the group consisting of crc6-alkyl, C6-C1 (raryl or C6- Wherein the residue of C1 (raryl-CVCV alkyl group is substituted one or two times, and in the case of an amine 67 201028406 group functionality substituted with a di-CrCV alkyl group, the alkyl group may be combined to form 5 Or a 6-membered ring; a thiol-hydroxyl group; a nitro group; a cyano group; a gas fluorescein group; a halogen selected from a fluoro group, a gas group, a bromo group or an iodo group; a CF3; a pendant oxy group; or an OCF3 B represents a single bond, oxygen, sulfur or NR1, wherein R1 is selected from hydrogen or a CrC6-alkyl group; and L represents a linker selected from the group consisting of: f) -(c=o)- or -o-( c=o)-, g) —(S〇2)—or _〇_(S〇2)— 'h) phenyl, cyclohexylene or cyclopentylene wherein a) to d) Can be used in combination, and a) and d) can be selectively subjected to CrC6-alkyl, CVCV alkoxy , co2h, S03H, amine group, CrC6-alkylamino group, di-CrCV alkylamine group, thiol group, hydroxyl group, nitro group, cyano group, fluoro group, chloro group, bromo group, iodo group , CF3 or OCF3 is substituted one or more times; 68 201028406 c represents: a) NR2R3, wherein R2 and R3 independently of each other represent hydrogen; CrC6-alkyl, C3-C8 cycloalkyl, C6-C10-aryl, A saturated, unsaturated or aromatic heterocyclic ring system of up to 10 atoms, C6-C10-aryl-CrC6-alkyl, Q-CV alkoxycarbonyl, C6-C10-aryloxycarbonyl, C6 -C10-aryl-Q-CV alkoxycarbonyl, CrC6-alkylcarbonyl, C6-C1 (rarylcarbonyl, C6-C10-aryl-CVC8-alkylcarbonyl, crc6-alkylmercaptocarbonyl, C3-c8-cycloalkylfluorenylcarbonyl, C6-C1G-aryldecylcarbonyl, CVCV alkylsulfonyl or C6-C1()-arylsulfonyl, each of which selectively passes Q-CV Alkyl, Q-C6-alkoxy, c6-c1()-aryloxy, C02H, S03H, amine, CkCV alkylamine, bis-CkCV alkylamino, thiol, thiol, hydrazine Substituting one or more substituents, nitrogen, fluoro, chloro, bromo, iodo, CF3 or OCF3; One of R2 and R3 may be fused to B or L to form a 5 or 6 membered ring; or b) NR4R5, wherein R4, R5 and nitrogen form a saturated, unsaturated or aromatic group of up to 10 atoms. a heterocyclic ring system selectively substituted by CkCV alkyl, Q-CV alkoxy, C6-C10-aryloxy, CO2H, S03H, amine, CrC6-alkylamine, di-Ci_C6-Hyun Substituted one or more times by an amino group, a thiol group, a thiol group, a thio group, a cyano group, a fluoro group, a carbyl group, a bromo group, an iodo group, a CF3 or an OCF3; 69 201028406 or C) one having the following Disubstituted amine group of formula (II): Wherein 〇 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of nitrogen, Ci_C6-hospital, C6-Ci〇-aryl and C6-Ci〇-aryl-Ci_C6-alkyl, and the chemical formula thereof The methylene group in (II) may be optionally substituted one or two times with a CrCe-alkyl group, a fluoro group or a chloro group; Or d) a hydrazine or hydrazine residue, wherein the residue is optionally substituted one or more times by CVCV alkyl, C6-C1 (r aryl or C6-C10-aryl-CrQ-alkyl, wherein The optional substituents may combine to form a 5 or 6 membered saturated, unsaturated or aromatic ring, or one of the vein or anthracene residue; η represents 0 or 1; m represents 0, 1, 2 , 3, 4, 5 or 6; X represents oxygen or sulfur; and Y represents: a) hydrogen; - alkyl, unit or polyunsaturated C2-C18-alkenyl, C3-C8-cycloalkyl, C6-C1()-aryl, C6-C1 (raryl-CrC8-alkyl, CrC6-alkoxy, C6-C10-aryloxy, C6-C10-aryl-CVCV alkoxy, crc6-alkoxycarbonyl, C6-C1Q-aryloxy Carbonyl, c6-c10-aryl-crc8-alkoxycarbonyl, crc6-alkylcarbonyl, c6-c1 (rarylcarbonyl, c6-c1()-aryl-crc8-alkylcarbonyl, crc6-alkyl Carboxyl group, 70 201028406 C6-C1()-arylcarboxy group, QQ-alkyl thiol group, C6-C1 (r aryl thio group, CVCV alkyl fluorenylcarbonyl group, C3-C8-cycloalkyl fluorenylcarbonyl group, C6 -C1(r aryl fluorenylcarbonyl, CrC6-alkylmercaptocarboxy, C6-C10-aryldecylcarboxy, CrCV alkylsulfonyl, C6-C1G-arylsulfonyl, crc6-alkylsulfonate An oxy group, c6-c1 (rarylsulfonyloxy) or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally substituted one or more times by : MXVCV alkyl, c3-c8-cycloalkyl, c6-c10-aryl, C6-C10-aryl-CVC8-alkyl, CVCV alkoxy, c6-c10-aryloxy, c 6-c1(raryl-crcvalkoxy, crc6-alkoxycarbonyl, C6-C1 (r aryloxycarbonyl, C6-C1()-aryl-CVCV alkoxycarbonyl, crc6-alkylcarbonyl , c6-c1 (rarylcarbonyl, c6-c10-aryl-crc8-alkylcarbonyl, crc6-alkylcarboxy, c6-c10-arylcarboxy, crc6-alkylthiol, C6-C1Q-aryl a thiol group, an ocv alkyl fluorenylcarbonyl group, a c3-c8-cycloalkylcarbonylcarbonyl group, a c6-c1()-aryldecylcarbonyl group, a crc6-alkylindenylcarboxy group, a c6-c10-aryldecylcarboxy group, Crc6-alkylsulfonyl, c6-c10-arylsulfonyl, crc6-alkylsulfonyloxy, c6-c10-arylsulfonyloxy; each of which is optionally substituted by one or more of the following Secondary: CrC6-alkyl; CrC6-alkoxy; CONH2, S02NH2; wherein the amine functionality is replaced by crc6-alkyl one or two conh2 or so2nh2; so3h; C02H; amine; selected from crc6- Alkyl, c6-c1()-aryl, c6-c1 (raryl-CrC6-alkyl, CVC6-alkylcarbonyl, c6-c10-arylcarbonyl, 71 201028406 crc6-alkylsulfonyl and c6 Substituting one or more amino groups for the residue of -c1()-arylsulfonyl; thiol; hydroxy; nitro; cyano; fluoro; Substituents; bromo; iodo; CF3; or OCF3; wherein BL) in a plurality of substituents may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or by B2) hydroxy; thiol group; nitro group; cyano group; fluoro group; gas group; bromo group; iodo group; cf3; C02H; S03H; OCF3; CONH2; S02NH2; CONH2 or S02NH2, wherein the amine group The functionality is substituted one or two times with a residue selected from the group consisting of Ci-C6-alkyl, C6-Ci〇-aryl or c6-c1()-aryl-crc6-alkyl, and wherein In the case of a Ci-CV alkyl-substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of CrCV alkyl, QC!. -aryl, C6-C10-aryl-QQ-alkyl, Q-CV alkylcarbonyl, C6-C1 (rarylcarbonyl, CVC6-alkylsulfonyl and C6-C1Q-arylsulfonyl) Substituting one or more amine groups for a residue; or a disubstituted amine group of the following formula (II): Wherein 〇 represents 0 or 1 and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-C 6 -alkyl, and the fluorenyl group in the formula (II) is optionally subjected to CrC 6 -alkyl, fluorine Substituting a base or a gas radical to replace one or 72 201028406 or B3) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms which is optionally substituted one or more times by the following: Q-CV alkyl; Q-CV alkoxy; COOH ; so3h ; CONH2 ; S02NH2 ; CONH2 or S02NH2, wherein the amino functionality is substituted by a residue selected from the group consisting of CrCV alkyl, C6-C10-aryl or c6-c10-aryl-crc4-alkyl Multiple times, and in the case of an amine functionality substituted with a di-CVCV alkyl group, the alkyl residue may combine to form a 5 or 6 membered ring; an amine group; selected from a Ci-CV alkyl group' C6-c10-aryl, c6-c10-aryl-CVC4-alkyl, crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, crc6-alkylsulfonyl and c6-c1 (raryl Substituting a sulfonyl group for one or more amine groups; thiol group; hydroxy group; nitro group; cyano group; fluoro group; gas group; bromo group; iodo group; CF3 or OCF3; C) S03H Amine; selected from CVCV alkyl, c6-c1 (raryl, C6-Ci〇-aryl-Ci-C8-alkyl, Ci-CV alkyl, C6-Ci〇-arylcarbonyl , crc6-alkylsulfonyl and c6-c1 (the residue of the rarylsulfonyl group is substituted with one or more amine groups; conh2; so2nh2 CONH2 or so2nh2, wherein the amino functionality is substituted one or two times with a residue selected from the group consisting of CrCV alkyl, c6-c1 (r aryl or c6-c1 (raryl-crc6-alkyl), and In the case of a di-crc6-alkyl substituted amine functionality, the alkyl residue can be combined to form a 5 or 6 membered ring; sulfur 73 201028406 alcohol group; trans group; nitro group; cyano group; A halogen-based base; a halogen selected from the group consisting of a gas group, a gas group, a odor group or a moth group; Cf3; or 〇cF3; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester thereof Or a precursor drug. 2. A compound according to claim 1 wherein a represents phenyl, pyridinyl, 3-pyridyl or 4-pyridyl. 3. A compound according to claim 1 or 2, Wherein a is substituted one or more times by a fluoro group, a hydroxy group, a hydroxy group or a CrC6-alkoxy group. 4. A compound according to any one of claims 1 to 3 wherein a is in the diazole The ortho position of the ketone residue is substituted by fluorine. 5. The compound of any one of claims 1 to 4, wherein b represents oxygen. 6. In the scope of claims 1 to 5 A compound of any one, wherein l represents -(CH2)P- wherein p is 1, 2, 3 or 4, which is optionally CVC6-alkyl, CkCV alkoxy, amine, CrC6-alkyl Substituting one or more times with an amine group, a di-Ci_C6-alkylamino group, a thiol group, a gas group, a gas group, a molybdenum group, cf3 or ocf3. The compound of any one of claims 1 to 6, wherein L represents a methylene group, an ethylene group or a propylene group. 8. The compound of any one of claims 1 to 7 wherein C represents NR2R3, wherein R2 and R3 independently of each other represent hydrogen; or CrC6-alkyl, C6-Ci〇-aryl, C6- C10-aryl-Ci_C6_alkyl, C1-C6-alkylcarbonyl, C6-C1Cr arylcarbonyl, C6-C1()-aryl-CrC8-alkylcarbonyl, Q-C6-alkyl base or C6-C1()-aryl fluorenyl group' wherein each of 201028406 is selectively Crc6-alkyl, CrC6-alkoxy, amine, CrCy alkylamino, di-CrC6-alkylamine, hydroxy , fluoro, chloro, > odoro, CF3 or OCF3 are substituted one or more times. 9. A compound according to claim 8 wherein L represents an ethylene group and one of R2 and R3 represents a fused to L to form a 5 or 6 membered ring propylene group. The compound of any one of clauses 8 or 9, wherein R2 and R3 independently of each other represent hydrogen, CrCV alkyl, C6-C1 (raryl or C6-C10-aryl- A compound of any one of claims 1 to 7 wherein C represents NR4R5, wherein R4 and R5 form a saturated, unsaturated or aromatic group of up to 10 atoms. a homocyclic or heterocyclic ring system selectively via Ci-Cr, Cu-C6-alkoxy, amine, Ci_C6-alkylamino, di-CVCV alkylamine, hydroxy, fluoro Substituting a gas group, a bromo group, a cf3 or a cff3 one or more times. 12. A compound according to claim 11 wherein NR4R5 forms an isoindoline ring system selectively via CrC6-alkane Substituted one or more times, q-cv alkoxy, amine, Q-CV alkylamino, di-CrCV alkylamino, hydroxy, fluoro, carbyl, bromo, cf3 or ocf3 A compound according to any one of claims 1 to 7, wherein C represents a disubstituted amino group of the following formula (II): (Π) 75 201028406 wherein 〇 represents 0 or 1 and represents oxygen, ch2 or NR6, and R is selected from the group consisting of hydrogen, CrC6-homo, C6-C10-aryl and C6_Ci〇_aryl-Ci-C6-fluorenyl. 14. A compound according to claim 13 wherein C represents a Bihabitan, piperidinyl, porphyrinyl or a pipeper which is optionally substituted with a fluorene-phenyl, phenyl or benzyl N. Well base. 15. The compound of any one of claims 1-4, wherein η represents 0; m represents 0, 1, 2, 3, 4, 5 or ό; and Υ represents C3-C6-cycloalkyl or C6-C1Q-aryl, each of which is optionally substituted one or more times by the following: a) CrC6-alkyl, c6-C1()-aryl, C6-C1 (r-aryl-CrC4-hospital, Ci-C6-alkoxy, C6_Ci〇-aryloxy, C6-Cl〇-^-C1-C4-alkoxy' each of which is optionally substituted one or more times by: CrCV alkyl; crc6-alkoxy; COOH; CONH2; S〇2NH2, substituted by Ci-C6-alkyl or C6-C10-aryl one or two conh2 or so2nh2; so3h; amine group; CrC6-alkyl, C6-C1 (r aryl, C6-C1 (r aryl-Q-Cr alkyl, CrC6-strandyl, C6-C1()-aryl, q-CV) a thiol group and a C6-C1 (r-aryl group substituted by one or more amine groups; a thiol group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; a gas group; a bromo group; Iodyl; cf3 or 〇cf3; or via b) hydroxy; thiol; nitro; cyano; fluoro; aldehyde; bromo; iodo; cf3; ocf3; co2h; S03H; conh2 ; so2nh2 ; conh2 or so2nh2, wherein the amine group 76 201028406 energy degree is substituted by one or more residues selected from (Vc: 6-alkyl, C6_Cl (r aryl or C6_Ci 〇-aryl-CrCr alkyl) And, in the case of an amine functionality substituted with a di-CrCV alkyl group, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; substituted by a Cl_C6_alkyl or phenyl group Or a plurality of amine groups; a disubstituted amine group of the following formula (11): -N W °(11) wherein 〇 represents 0 or 1 and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CrC 4 -alkyl, and the methylene group in the formula (π) thereof may optionally pass C]-C4 - an alkyl, fluoro or ke group substituted one or two times; or c) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally substituted by One or more times: CVCV alkyl; CVC6-alkoxy; COOH; CONH2; so2nh2; by (^-(:6-alkyl or c6-c10-aryl substituted one or two conh2 or so2nh2; so3h; Amino group; selected from the group consisting of alkyl, C6-Ci〇-^, C6_Ci〇-aryl-C1-C4-dyl, Q-CV alkylcarbonyl, C6-C1 (rarylcarbonyl, crC6-alkyl Substituting thiol and CVCh)-aryl thiol residues to replace one or more amine groups; thiol group; hydroxy group; nitro group; cyano group; fluoro group; gas group; bromo group; Base; cf3 or 〇cf3. 16. A compound of claim 15 wherein η represents 0; m represents 〇 or 1, and Y represents a phenyl group or a 1-naphthyl group, 2-naphthyl group, 2- D is 0 to 77 201028406 base, 3-11 than bite base or 4-turn than bite base ring system. A compound according to claim 16 wherein Y is substituted one or more times by the following: CrC6-alkyl; phenyl; CrC6-alkoxy; hydroxy; fluoro; chloro; bromo; OCF3; an amine group; or alternatively one or two of CONH2 or S〇2NH2 substituted by a CrC6-leunt group, wherein the selective Cl_c6-alkyl residues may combine to form a 5 or 6 membered ring. 18_A compound as claimed in claim 17, wherein !!! represents hydrazine, and γ represents a phenyl group substituted one or two times with a hydroxy, fluoro, valyl or bromo group. 19. A compound according to claim 17, wherein m represents hydrazine, and γ represents a fluoro group or a gas group substituted at the 4-position, and a fluoro group at the 2- and 4-positions, at 2 a stupid group substituted with a 4-position substituted by a gas group or a 4-position at a 4-position. 20_ The compound of claim i, wherein A represents a phenyl group; B represents oxygen; L represents a (CH2)P-, wherein p is 1, 2, 3 or 4; C represents a chemical formula (II) Disubstituted amine groups: Wherein 〇 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of hydrogen, Ci-C6-alkyl, C6-Ci〇-aryl and C6-Ci〇-aryl-CVC6-hospital, and The methylene group in the formula (II) may be optionally substituted one or two times with a crc6-alkyl group, a fluoro group or a gas group. 21. A compound according to claim 1 wherein A represents phenyl; B generation 78 201028406 The milk 'L represents -(CH2)P-' wherein p is 1'2, 3 or 4; C represents NR2R3, wherein R2 represents hydrogen or (:)-(:6-alkyl, and R3 represents a propylene group fused to L to form a 5- or 6-membered ring. 22. A compound according to claim 20 or 21, wherein γ Represents a phenyl group which is substituted by a fluoro group or a gas group at the 4_ position, substituted by a fluoro group at positions 2 and 4, or substituted with a gas group at the 2- and 4-positions. A compound according to any one of items 19 to 22, wherein A represents a phenyl group substituted with fluorine in the ortho position of the oxadiazolone residue. 24 is a compound for inhibiting fatty acid indoleamine hydrolase as claimed in the scope of claim j A compound according to any one of the following 23. 25. A compound which is a drug as claimed in claim 24. 26. A compound for treating a condition as claimed in claim No. It is positively affected by the inhibition of fatty acid indoleamine hydrolase. 27. The compound of claim 26, wherein The condition is selected from pain, particularly neuropathic types of acute or chronic pain, migraine, neuropathic pain, including forms associated with secret viruses and diabetes, acute or chronic pain associated with inflammatory diseases: joints Inflammation, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis, Crohn's disease, stimulating bowel syndrome; acute or chronic peripheral pain; dizziness, vomiting, nausea, especially chemotherapy Eating disorders, especially anorexia and cachexia of various natures; neurological and psychiatric disorders: tremors, dyskinesias, dystonia, paralysis, forced paranoia, Tourette syndrome, all forms of depression And 79 79.28406 A nature and origin of anxiety, mood, psychosis; acute and chronic neurodegenerative diseases: Parkinsin's disease, Alzheimer's disease, Alzheimer's disease, Hang Huntingt〇n chorea, focal cerebral ischemia and cranial and bone marrow trauma; epilepsy; sleep disorders, package Sleep apnea; cardiovascular disease, especially hypertension, dysplasia, suture sclerosis, Qianxin, cardiac ischemia; partial renal deficiency; cancer: benign skin tumor, brain tumor and mastoid tumor, anterior tumor, Domain axis (God to f-blastoma, myeloma, H-blastoma, neuroblastoma, embryogenic tumor, stellate cell tumor, epithelial tumor, ependymoma, oligodendroglioma) , plexus tumor, neuroepithelial neoplasia, pineal tumor, ependytioblastoma, neoencephaloma, sarcoma, malignant melanoma, neuroma); immune system disorders, especially autoimmune diseases; psoriasis, Lupus erythematosus, connective tissue disease or collagen disease, repairing granules, dysentery, undifferentiated vertebral inflammation, Beheet's disease, autoimmune hemolytic anemia, Multiple sclerosis, amyotrophic ridge-sclerosing disease, pure lesions, graft rejection, diseases affecting many cell lines; allergic diseases; immediate or delayed onset, secretive rhinitis or conjunctivitis, contact Sexual dermatitis Insect, viral or bacterial infectious diseases: aids, meningitis; inflammatory diseases, especially joint diseases; osteoporosis; ocular conditions: high intraocular pressure, glaucoma; pulmonary conditions; respiratory diseases, bronchospasm, cough , asthma, chronic bronchitis, chronic airway obstruction, emphysema; gastrointestinal disease; limb disease, material, «, silk ban and bladder 201028406 inflammation. 28. The compound of claim 26, wherein the condition is selected from the group consisting of an allergic disease, an immediate or delayed type allergic reaction, allergic rhinitis or conjunctivitis, contact dermatitis, an inflammatory disease, an ocular condition such as high Intraocular pressure or glaucoma, lung disease, respiratory disease, bronchospasm, cough, asthma, chronic bronchitis, chronic airway obstruction, and emphysema. 29. A process for the preparation of a compound according to any one of claims 1 to 23, wherein a compound of formula (III) is cyclized to form an oxadiazolone ring system: 〇C - L —B —A—NN—^ HH O—CCH^mY (HI), where A represents a phenyl group or a 5 or 6 member heteroaromatic ring system containing up to 4 heteroatoms selected from oxygen, sulfur and nitrogen , which is optionally substituted one or more times by the following: crc6-alkyl, c3-c8-cycloalkyl, c6-c1()-aryl, c6-c1()-aryl-CrC8-alkyl, CVC6 - alkoxy group, C6-C1 (r aryloxy group, C6-C10-aryl-CVC8-alkoxy group, Q-CV alkylcarboxy group, c6-c1 (r arylcarboxy group, CrC6-alkylmercaptocarboxy group, C6-C1 (rarylalkylcarboxyl, (^-(:6-alkylsulfonyloxy, c6-c1()-arylsulfonyloxy), each of which is optionally substituted by one or more of the following Secondary: CrC6-alkyl; CVC6-alkoxy; c6-c1()-aryloxy; co2h; so3h; CONH2; S02NH2; CONH2 or 81 201028406 So2nh2, wherein the amino functionality is substituted one or more times with a residue selected from a CVCV alkyl group, a C6-C1 ()-aryl group or a C6-C1 ()-aryl-CVC4-alkyl group, and In the case of a di-cvc6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 beta ring; the amine group is selected from the group consisting of Ci_C6-alkyl, C6_Ci〇-aryl, Residues of C6-C1()-aryl-CVCV alkyl, CVCV alkylcarbonyl, c6-c10-arylcarbonyl, Q-CV alkylsulfonyl and c6-c10-arylsulfonyl are substituted Multiple amine groups; thiol group; hydroxyl group; nitro group; cyano group; fluoro group; gas group; bromo group; iodo group; CF3 or OCF3; co2h; so3h; amine group; From selected from Ci_C6-alkyl, C6-Ci〇-aryl, C6-Ci〇-square-Ci-Ce-alkyl, CVC6-alkylcarbonyl, c6-c1 (rarylcarbonyl, crc6-alkyl A sulfonyl group and a c6-c1 (an arylsulfonyl group-substituted one or more amine groups; a disubstituted amino group having the following formula (II): -NW ° (11) wherein 0 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and CrC6-alkyl, and the methylene group in the formula (II) thereof can be selectively subjected to (^-(:6-alkyl, fluorine) Substituting a gas or a gas group for one or two times; CONH2; 82 201028406 so2nh2; CONH2 or S02NH2, wherein the amino functionality is selected from the group consisting of Ci-CV alkyl, c6-c10-aryl or c6-c10-aryl a residue of a yl-crc6-alkyl group substituted one or two times, and wherein the ring is in the case of a di-CrC6-alkyl substituted amine functionality; a thiol group, a thiol group; a decyl group; a cyano group; a gas residue; the alkyl residue may be combined to form a 5 or 6 member selected from a fluoro group, a gas group, a bromo group or an iodo group; CF3; a pendant oxy group; or ocf3; a single bond, a CrC6-alkyl group; oxygen, sulfur or NR1, of which R1 is selected From hydrogen or L represents a linker selected from the group consisting of: i) -(CH2)P-, wherein p is 1, 2, 3, 4, 5, 6, 7, or 8, j) -(c=o)- Or -o-(c=o)-, k) -(S02)- or -0-(S02)-, l) phenyl, cyclohexylene or cyclopentylene wherein a) to d) Can be used in combination, and a) and d) optional 83 201028406 Selectively transcentric-仏-alkyl, CVCV alkoxy, C〇2H, S03H, amine, CVCV alkylamine, di-CVC6 -Alkylamino, thiol, hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo, CF3 or OCF3 substituted one or more times; C represents a) NR2R3, wherein R2 and R3 independently of each other represent hydrogen; CrC6-alkyl, C3-C8 cycloalkyl, C6-C10-aryl, saturated, unsaturated or aromatic heterocyclic ring systems consisting of up to 10 atoms, C6-C10-aryl-CrC6-alkyl, CVCV alkoxycarbonyl, c6-c10-aryloxycarbonyl, c6-c10-aryl-crc8-alkoxycarbonyl, crc6-alkylcarbonyl, c6-c1 ()-arylcarbonyl, c6-c10-aryl-Ci-CV alkylcarbonyl, CVCV alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, C6-C1()-aryldecylcarbonyl, CVC6- alkyl Sulfosyl or c6-c1()-arylsulfonyl, each of which is selectively Ci-C6-alkyl, Ci_C6-Hyun*, C6-Ci〇-square, co2h, S03H, amine Base, Q-CV alkylamino, di-crc6-alkylamino, thiol, thio, thio, cyano, fluoro, chloro, bromo, iodo, cf3 or OCF3 is substituted one or more times; and one of R2 and R3 may be fused to A or L to form a 5 or 6 membered ring; or b) NR4R5, wherein R4, R5 and nitrogen form a maximum of 10 atoms a saturated, unsaturated or aromatic heterocyclic ring system consisting selectively of CrC6-alkyl, CVQr alkoxy, C6-C10-aryl 84 201028406 oxy, co2h, so3h, amine, CVCV alkane One or more amino group, bis-Q-C6-alkylamino group, thiol group, hydroxy group, nitro group, cyano group, fluoro group, carbyl group, bromo group, iodo group, cf3 or OCF3 Or; or c) a disubstituted amino group of the following formula (II): Wherein 〇 represents 0 or 1 and W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of nitrogen, Ci_C6_alkyl, C6-Ci〇-aryl and C6-Ci〇-aryl-Ci_C6-alkyl, and the formula thereof The methylene group in II) may be optionally substituted one or two times with a Q-CV alkyl, fluoro or ke group; or d) a hydrazine or hydrazine residue, wherein the residue may be optionally Substituted one or more times by Ci_C6-alkyl, C6-Ci〇-aryl or C6-Ci〇-aryl-C1-C4-alkyl, wherein the selective substituents can be combined to form a 5 or 6 member a saturated, unsaturated or aromatic ring, or one of the isomers of the vein or vein; m represents 0, 1, 2, 3, 4, 5 or 6; and Y represents: a) hydrogen; b) CrC18- Alkyl, unit or polyunsaturated C2-C18-olefin based, C3-C8-cycloalkyl, C6-Ci〇-aryl, C6-Ci〇-aryl-Ci_C8_alkyl, CVC6-alkoxy, c6 -c1(r aryloxy, c6-c10-aryl-crc8-alkoxy 85 201028406 yl, crc6-alkoxycarbonyl, c6-c1 (r aryloxycarbonyl, c6-c10-aryl-CrCV alkoxy Carbonyl group, CrCV alkylcarbonyl group, c6-c1 (rarylcarbonyl group, C6-Ci〇-aryl-Ci-Cf alkyl group, Ci_C6-alkyl group, C6-CiQ- Base group, Ci-Cf alkyl thio group, C6-Ci 〇-aryl sulfenyl group, CrC6-alkyl fluorenylcarbonyl group, C3-C8-cycloalkylfluorenylcarbonyl group, C6-Cnr aryl fluorenyl group Carbonyl group, CrC6-alkylmercaptocarboxyl group, C6-C10-aryldecylcarboxyl group, CkCV alkylsulfonyl group, c6-c1()-arylsulfonyl group, Ci-C6-alkylated base, A C6-Ci-aryl base or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally substituted one or more times by: blKVCV alkane , C3-C8-cycloalkyl, C6-C1 (raryl, C6-C10-aryl-CrCV alkyl, CVC6-alkoxy, c6-c10-aryloxy, C6-C1 (raryl) -CVC8-alkoxy, crc6-alkoxycarbonyl, C6-C1 (r aryloxycarbonyl, C6-C1()-aryl-CrC8-alkoxycarbonyl, crc6-alkylcarbonyl, c6-c1 ( )-arylcarbonyl, c6-c10-aryl-Ci-CV alkylcarbonyl, CVCV alkylcarboxy, c6-c10-arylcarboxy, crc6-alkylthiol, c6-c10-arylthiol , Ci-Ce-alkylmercaptocarbonyl, C3-C8-cycloalkylfluorenylcarbonyl, C6-C1()-aryldecylcarbonyl, CrCV alkyldecylcarboxy, C6-C!-aryldecylcarboxyl ,CrC6- Alkyl sulfonyl, C6-Ci 〇-aryl aryl, Ci_C6 ketone ethoxylate, C6-Ci 〇 arylsulfonyloxy; each of which is optionally substituted by one or more of the following Secondary: CkCV alkyl; crc6-alkoxy; conh2, S02NH2; wherein the amine functionality is substituted by CVCV alkyl one 201028406 or second conh2 or so2nh2; so3h; co2h; amine group; selected from CVC6-alkane a group, c6-c1 (r aryl, c6-c1()-aryl-CVC6-alkyl, Q-CV alkylcarbonyl, c6-c1 (rarylcarbonyl, Q-C6-alkylsulfonyl and Substituent of a c6-c1()-arylsulfonyl group substituted with one or more amine groups; thiol group; hydroxy group; nitro group; cyano group; fluoro group; chloro group; bromo group; iodo group ;cf3 ; or 〇 CF3 ; Wherein a plurality of substituents in bl) may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; B2) hydroxy; thiol group; nitro; cyano; fluoro group; chloro group; bromo group; iodo group; cf3; co2h; so3h; ocf3; conh2; so2nh2; CONH2 or S02NH2, wherein the amine group The functionality is substituted one or two times with a residue selected from the group consisting of CkC-alkyl, C6-C10-aryl or c6-c1()-aryl-crc6-alkyl, and in one of the di-CVC6- In the case of an alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of crc6-alkyl, c6-c10-aryl, c6-c10-aryl Substituting one or more residues of a base-CVQ-alkyl group, a CrC6-alkylcarbonyl group, a C6-C1()-arylcarbonyl group, a CrC6-alkylsulfonyl group, and a C6-C1()-arylsulfonyl group An amine group; or a disubstituted amine group of the following formula (II): 87 (II) 201028406 wherein 〇 represents 〇 or 1 and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CrC 6 -alkyl, and the methylene group in the formula (II) is selectively via CrCV alkyl a fluoro or chloro group substituted one or two times; or a b3)-saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally substituted by the following Multiple times: CrC6-alkyl; CrC6-alkoxy; COOH; so3h; CONH2; S02NH2; CONH2 or S02NH2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, c6-c10-aryl or C6- Substituting a C10-aryl-CrC4-alkyl residue for one or more times, and wherein in the case of a di-CVC6-alkyl substituted amine functionality, the alkyl residue can be combined to form 5 or 6 membered ring; amine group; selected from Ci_C6_alkyl, C6-Ci〇-aryl, C6_Ci〇-aryl-CVC4-alkyl, crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, Substituting one or more amino groups for a residue of a Ci_C6_alkyl group and a C6-Ci〇-aryl group; a thiol group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; Bromo group; iodo group; cf3 OCF3; c)so3h; aminyl; selected from the group consisting of crc6-alkyl, c6-c1()-aryl, c6-c1 (raryl-CrC8-alkyl, CkCV alkylcarbonyl, c6-c1 (r-aryl) Alkylcarbonyl, CVC6-alkylsulfonyl and c6-c1 (the residue of the rarylsulfonyl group is substituted with one or more amine groups; conh2; so2nh2; CONH2 or S02NH2, wherein the amine functionality is selected Substituting one or two times from a residue of a Ci-CV alkyl group, 201028406 C6-C1 (r-aryl or C6-Cicr aryl-CrCV alkyl group, and an amine group substituted with a di-CVC6-alkyl group In the case of functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; thiol; hydroxy; nitro; cyano; fluorosulfonyl; selected from fluoro, chloro, bromo A halogen or a iodine group; a CF3; or an OCF3. 30. The method of claim 29, wherein the cyclization of the oxadiazolone ring system is by phosgene, a stagnation. A carbonated vinegar is achieved. 89 201028406 IV. Designated representative map: (1) The representative representative of the case is: ( ). (none) (2) A brief description of the symbol of the representative figure: 5. If there is a chemical formula in this case, please reveal the chemical formula that best shows the characteristics of the invention: C — Ό —(C=X)n -(Ciym — Y (1) 2