CN102149381A - A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivative or its salt, and bisphosphonate - Google Patents
A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivative or its salt, and bisphosphonate Download PDFInfo
- Publication number
- CN102149381A CN102149381A CN2009801335866A CN200980133586A CN102149381A CN 102149381 A CN102149381 A CN 102149381A CN 2009801335866 A CN2009801335866 A CN 2009801335866A CN 200980133586 A CN200980133586 A CN 200980133586A CN 102149381 A CN102149381 A CN 102149381A
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- CN
- China
- Prior art keywords
- hydroxyl
- benzamidine
- amoxy
- phenoxy group
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 208000001132 Osteoporosis Diseases 0.000 title claims abstract description 65
- 150000003839 salts Chemical class 0.000 title claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 10
- 229940122361 Bisphosphonate Drugs 0.000 title abstract description 5
- 150000004663 bisphosphonates Chemical class 0.000 title abstract description 4
- 150000003937 benzamidines Chemical class 0.000 title abstract 3
- -1 bisphosphonate compound Chemical class 0.000 claims abstract description 124
- 238000011282 treatment Methods 0.000 claims abstract description 81
- 239000000203 mixture Substances 0.000 claims abstract description 47
- 230000002265 prevention Effects 0.000 claims abstract description 42
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 541
- 150000001875 compounds Chemical class 0.000 claims description 123
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 55
- 239000001257 hydrogen Substances 0.000 claims description 55
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 42
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 40
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 claims description 27
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 26
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 25
- 239000001177 diphosphate Substances 0.000 claims description 25
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 24
- 235000011180 diphosphates Nutrition 0.000 claims description 24
- 125000002757 morpholinyl group Chemical group 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 claims description 21
- 229960000759 risedronic acid Drugs 0.000 claims description 20
- 229960004343 alendronic acid Drugs 0.000 claims description 19
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 18
- PMZBHPUNQNKBOA-UHFFFAOYSA-N 5-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(C(O)=O)=C1 PMZBHPUNQNKBOA-UHFFFAOYSA-N 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 claims description 14
- 229960003978 pamidronic acid Drugs 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
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- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 claims description 11
- MPBVHIBUJCELCL-UHFFFAOYSA-N Ibandronate Chemical compound CCCCCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O MPBVHIBUJCELCL-UHFFFAOYSA-N 0.000 claims description 10
- 229960002286 clodronic acid Drugs 0.000 claims description 10
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 claims description 10
- 229960005236 ibandronic acid Drugs 0.000 claims description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 8
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 8
- 125000005936 piperidyl group Chemical group 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 230000014509 gene expression Effects 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 150000002460 imidazoles Chemical class 0.000 claims description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- NHNUFAASKXPOQA-UHFFFAOYSA-N (3-acetamido-2-hydroxyphenyl)arsonic acid Chemical compound C(C)(=O)NC=1C(=C(C=CC1)[As](O)(=O)O)O NHNUFAASKXPOQA-UHFFFAOYSA-N 0.000 claims description 3
- LZTBEXFNIKWAAC-UHFFFAOYSA-N 4-[[4-[[4-(5-butyl-2-propan-2-yl-1,3-thiazol-4-yl)phenoxy]methyl]phenyl]methoxy]-n'-hydroxybenzenecarboximidamide Chemical compound S1C(C(C)C)=NC(C=2C=CC(OCC=3C=CC(COC=4C=CC(=CC=4)C(=N)NO)=CC=3)=CC=2)=C1CCCC LZTBEXFNIKWAAC-UHFFFAOYSA-N 0.000 claims description 3
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Landscapes
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- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Abstract
The present invention provides a pharmaceutical composition for preventing or treating osteoporosis, comprising a benzamidine derivative or salt thereof and bisphosphonate for the purpose of using simultaneously, separately, or sequentially as active ingredients. As a prophylactic or therapeutic composition for osteoporosis, the combination treatment of the benzamidine derivative and the bisphosphonate compound exhibits excellent inhibitory effect on osteoclast differentiation than the total effect of each individual treatment, thereby being used for the prevention or treatment of osteoporosis.
Description
[technical field]
The present invention relates to be used to prevent or treat the pharmaceutical composition of osteoporosis, said composition comprises Benzamine derivatives or its salt and diphosphate (bisphosphonate).More specifically, the present invention relates to be used to prevent or treat the pharmaceutical composition of osteoporosis, said composition comprises Benzamine derivatives or its salt and diphosphate, has the effect of improvement than the pharmaceutical composition that comprises formula 1 benzamidine or its salt or diphosphate respectively.
[background of invention]
Bone is the supporter of health skeleton, and is used to preserve necessary bone amount and structure.Bone also plays calcium (Ca
2+) or the storage effect of analog, and in keeping the blood calcium level, play an important role.For this reason, bone carries out successive degraded and moulds.Therefore, bone is in dynamic steady state, and it keeps meticulous balance by carrying out bone resorption and bone formation continuously.When the balance between bone resorption and the bone formation was destroyed, the degree of bone resorption was higher relatively than osteoplastic degree, and it can cause osteoporosis---and cause the symptom that bone density or bone amount reduce, cause bone strength to reduce.This is the disease that frequently betides middle age or old women.
Osteoporosis is such disease: produced by equilibrated destruction between bone resorption and bone formation, and cause by have higher bone resorption degree with respect to the bone formation degree.Osteoporosis reduces the osseous tissue calcification, and reduces the level of tight material in the bone, and it has widened medullary cavity.Along with the osteoporosis development, bone becomes fragile, and fracture can even take place under slight collision easily.Bone is the steady statue structure, and wherein the bone resorption that causes of the bone formation that causes of osteoblast and osteoclast recurs.
Pro-research about osteoporosis mainly concentrates on bone mineral---as the metabolism of calcium and phosphorus.But it is enough about osteoporosis Study on Mechanism result that this research does not provide.
It is relevant with the mortality rate of the rising of suffering from patients with osteoporosis to fracture, and causes serious problem, as the negative effect to patients ' life quality.Therefore, set up multiple strategy can prevent bone density loss and fracture with preparation medicine.
Up to now, diphosphate (fosamax (alendronate), 1-hydroxyl-ethylidene-1, the 1-diphosphate is (according to carrying phosphonate, etidronate)), hormone (raloxifene (raloxifen)), vitamin D, calcitonin, calcium preparation or analog be used as the osteoporosis agent, and Forteo
TM---cause a kind of form of osteoplastic parathyroid hormone, be used to treat the osteoporosis in late period at present.But known these materials have side effect.Particularly, must run through the whole life of patient and give hormone preparation, under the situation of long term administration, can cause side effect, as breast carcinoma, uterus carcinoma, cholelithiasis and thrombosis.Vitamin D preparation costs an arm and a leg, and shows extremely low effectiveness, and calcitonin preparation is also very expensive, and is difficult to give.Calcium preparation has minimum side effect, but its effect is limited to osteoporosis prevention, but not its treatment itself.Forteo
TM---commercial parathyroid hormone have its stimulation of bone formation advantage, but known drug is limited to the prevention of bone resorption.Yet, Forteo
TMShould give with injection every day over a long time, and may increase osteosarcomatous risk.It is used also because high cost and limited.
The diphosphate medicine that following formula is represented, fosamax or Risedronate (risedronate) have been widely used in the treatment of osteoporosis, and demonstrate the inhibitor as bone resorption, bone density improving and prevention fracture.Since oral administration and advantage cheaply, the clinical field that it has been widely used in treating calcium metabolic diseases---comprising osteoporosis---.
But, the low absorbability of diphosphate medicament performance, and can cause esophagitis, thus should advance clothes with enough water gagings in ante cibum.In addition, the patient should wait at least 30 minutes before other beverages of picked-up or food, and avoids lying low the regular hour after administration.It also is reported as the risk that increases hypocalcemia.Recent research asks a question, and the bone turnover rate that causes as excessive inhibition, osteoplastic inhibition, gastrointestinal disease and jawbone necrosis owing to bone resorption reduces.In addition, report that recently it increases the risk of fracture (Andrew S Neviaser etc., Journal of Othopaedic Trauma, 2008,22 (5), 346～350) for a long time.
As mentioned above, current osteoporosis treatment agent is not the therapeutic agent that bone resorption and bone formation are all worked.Therefore, in order to treat osteoporosis, need exploitation such medicine and treatment: cause the bone amount balancedly to increase and improve, thereby reduce the risk of fracturing with bone mass.
In order to overcome above-mentioned defective and to improve clinical efficacy, made big quantity research, the recent therapeutic alliance of researching and proposing bone resorption inhibitor and the osteoplastic commercial parathyroid hormone of promotion.It is described in detail as follows.
By fosamax and estrogen (document-Lindsay etc., J.Clin.Endocrinol.Metab.84,3073-3081 (1999)), fosamax and raloxifene (document-Johnell etc., J.Clin.Endocrinol.Metab.87,985-992 (2002)), fosamax and HRT (hormone replacement therapy) (document-Greenspan etc., JAMA, 289,2525-2533 (2003)) and fosamax and calitriol (WO 01/28564) example the therapeutic alliance of fosamax and other bone resorption inhibitors.These studies have shown that therapeutic alliance its independent increase that demonstrates bone density relatively, but do not reduce the risk of fracture.In addition, even different between its mechanism, comprise that the problem of the bone turnover rate reduction that causes owing to depression effect and osteoplastic inhibition to bone resorption still exists.Therefore, need about the consideration of treatment and further research.
In this respect, the test with the bone formulation stimulant therapeutic alliance is arranged, this therapeutic alliance intention reduces the side effect to osteoplastic depression effect and fosamax.Therapeutic alliance by two pieces of document example fosamax and parathyroid hormone: parathyroid hormone and the fosamax combined effect (document-Black etc. in postmenopausal osteoporosis, N.Eng.J.Med.349,1207-1215, and the combined effect (document-Finkelstein etc. in the male senile patient osteoporosis (2003)), N.Eng.J.Med.349,1216-1226, (2003)).But the document does not prove the increase compared with its bone density that gives separately.In this respect, some researcheres propose such probability: bone strengthening absorption inhibitor---fosamax has been offset the stimulating effect of parathyroid hormone.Subsequently, tested giving in succession of two kinds of medicines, but still required further study, to obtain significant clinical effectiveness.
The inventor discloses the treatment of Benzamine derivatives in osteoporosis at Korean patent No. 705875, Korean patent No. 875596 and Korean Patent Application No. 2008-0073710 and has used.
The inventor also studied by with the prevention that increases formula I benzamidine compound or its salt uniting of other chemical compounds or the method for therapeutic effect, and developed than this compositions that has the effect of raising separately, said composition can be used for osteoporosis prevention and treatment.
[summary of the invention]
[technical problem]
Target of the present invention provides the pharmaceutical composition that comprises Benzamine derivatives or its salt and diphosphate, is used to prevent or treat osteoporosis.
Another target of the present invention provides benzamidine or its salt and the diphosphate that comprises formula 1, the pharmaceutical composition that is used to prevent or treat osteoporosis, when co-administered than individually dosed effect with raising.
Can finish above-mentioned and other targets of the present invention by following explanation of the present invention.
[solution of problem]
According on the one hand, the invention provides the compositions of prevention or treatment osteoporosis, comprise with simultaneously, separately or in succession be the following chemical compound (a) of target and (b) as active component:
(a) by the Benzamine derivatives of following formula 1 expression or its salt and
(b) diphosphate of representing by following formula 2,
[formula 1]
R wherein
1Be C
1～C
6Alkyl, it is not substituted or pyridyl replaces; With straight or branched C
1～C
6Alkyl, its quilt
Replace, should
Be not substituted or replaced by hydroxyl; C
3～C
6Cycloalkyl; Phenyl; Benzyl; Pyridine radicals, it is not substituted or by C
1～C
6Alkyl replaces; Guanidine radicals; NR
6R
7CH
2NR
6R
7Pyridine radicals or
Group, it is by straight or branched C
1～C
6Alkyl replaces;
(wherein A is C
1～C
6Alkyl, m are 2 to 6 integers); Or
Group, it is not substituted or by C
1～C
6Alkyl replaces,
R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; Phenyl; Benzyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholinyl; Thio-morpholinyl; 4-methyl piperazine base; Or straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace;
R
3And R
4Be hydrogen independently of one another; Halogen; Hydroxyl; C
1～C
6Alkyl, it is not substituted or is replaced by halogen; C
3～C
6Cycloalkyl amino; C
1～C
6Alkoxyl; C
1～C
6Alkanoyloxy; C
2～C
6Alkene oxygen base; Phenyl-C
1～C
6Alkoxyl; Phenoxy group; C
2～C
6Alkene acyloxy or phenyl-C
1～C
6Alkanoyloxy; C
3～C
6Cycloalkyloxy, its group that can be selected from carboxyl, esterifying carboxyl group and amidatioon carboxyl replaces; Or aminooxy group;
R
5Be hydrogen or hydroxyl;
R
6And R
7Be hydrogen independently of one another; C
1～C
6Alkyl, it is not substituted or is selected from hydroxyl, C
1～C
6Alkoxyl, pyridine and
Group replace; Phenyl; Benzyl; Pyridine radicals; Carbonyl, it is selected from C
1～C
6Alkyl, hydroxyl, C
1～C
6Alkoxyl, phenyl, benzyl, pyridine and
Group replace; Or C
1～C
6Alkanesulfonyl;
R
8And R
9Be hydrogen independently of one another; C
1～C
6Alkyl, it is not substituted or is selected from hydroxyl, C
1～C
6Alkoxyl, morpholine, imidazoles and NR
6R
7Group replace; C
1～C
6Alkoxyl; C
3～C
6Cycloalkyl; Phenyl; Benzyl; Pyridine radicals; Morpholine; Carbonyl, it is selected from C
1～C
6Alkyl, C
1～C
6Alkoxyl, phenyl, benzyl, pyridine and
Group replace; Carbonyl, it is by C
1～C
6Alkyl replaces, this C
1～C
6Alkyl is selected from halogen, C
1～C
6A group of alkoxyl and imidazoles replaces; Or C
1～C
6Alkanesulfonyl;
R
10And R
11Be hydrogen, C independently of one another
1～C
2Alkyl, C
1～C
3Alkoxyl or halogen;
X
1And X
3Be O independently of one another; S; NH; Or N-C
1～C
6Alkyl, N-C
3～C
6Cycloalkyl, N-benzyl or N-phenyl;
X
2Be C
3～C
7Alkylidene; C
1～C
3Alkylidene-C
2～C
7Alkenylene-C
1～C
3Alkylidene; C
1～C
3Alkylidene-O-C
1～C
3Alkylidene; C
1～C
3Alkylidene-S-C
1～C
3Alkylidene; C
1～C
3Alkylidene-NH-C
1～C
3Alkylidene; C
1～C
3Alkylidene-phenylene-C
1-C
3Alkylidene; C
1-C
3Alkylidene-pyridylidene-C
1-C
3Alkylidene or C
1-C
3Alkylidene-naphthylene-C
1～C
3Alkylidene; C
3～C
7Alkylidene, it is by C
1～C
3Alkyl and hydroxyl replace; C
3～C
7The alkylidene carbonyl; Or C
3～C
7Alkylidene, it is interrupted by piperazine;
Y is O, S, NR
6Or CH
2Group; And
N is an integer 0,1 and 2.
[formula 2]
R wherein
12Be methyl, chlorine, 2-aminoethyl, 3-aminopropyl, 4-ammonia butyl, 5-ammonia amyl group, 4-chlorphenyl sulfo-, 3-pyridylmethyl, (imidazo [1,2-a] pyridin-3-yl) methyl, 2-(N-methyl-N-n-pentyl) aminoethyl, suberyl amino, (1-imidazole radicals) methyl or 1-pyrrolidinyl ethyl
R
13Be hydrogen, chlorine or hydroxyl,
M is hydrogen or sodium, and
Z is any number, preferably 0 to 7 integer.
In formula 1, R
1Specifically be methyl, ethyl, isopropyl, cyclohexyl, phenyl, amino methyl, aminoethyl, amino, pyridine radicals, NR
6R
7, CH
2NR
6R
7,
(wherein A is C
1～C
2Alkyl, and m is 4 to 5 integer);
R
2Be hydrogen; Methyl; Ethyl; Isopropyl; Isobutyl group; Methoxy; Hydroxymethyl; Chloromethyl; Chloroethyl; Cyclopenta; Methyl cyclopentane; Vinyl; By NR
8R
9The methyl or the ethyl that replace; By NR
8R
9The carbonyl that replaces; Quilt
The methyl or the ethyl that replace; By the methyl or the ethyl of pyrrolidine, piperidines or imidazoles replacement;
Piperidines or triazole;
R
3And R
4Be hydrogen, halogen, hydroxyl or methoxyl group independently of one another;
R
5Be hydrogen or hydroxyl;
R
6And R
7Be hydrogen, methyl, ethyl, propyl group, ethoxy, methoxy ethyl, 2-morpholino ethyl, benzyl, pyridin-3-yl, pyridin-4-yl, 2-morpholino ethyl, 4-pyridine radicals carbonyl, 3-pyridine radicals carbonyl, isobutyl group carbonyl, ethylsulfonyl, ethoxy or methoxy ethyl independently of one another;
R
8And R
9Be hydrogen independently of one another; Methyl; Ethyl; Propyl group; Isopropyl; Butyl; Isobutyl group; The tert-butyl group; Cyclopropyl; Cyclohexyl; Ethyl, it is selected from hydroxyl, methoxyl group, 2-morpholino and NR
6R
7Group replace; Propyl group, its group that is selected from 3-isopropoxy and 3-imidazoles replaces; Carbonyl, its group that is selected from 3-pyridine radicals, 4-pyridine radicals and isopropyl replaces;
R
10And R
11Be hydrogen or methyl independently of one another;
X
1And X
3Be oxygen, sulfur, amine or methyl amine group independently of one another;
X
2Be propylidene, butylidene, pentylidene, hexylidene, ethylidene-O-ethylidene, ethylidene-NH-ethylidene, butylidene carbonyl, crotyl, methylene-1,2-phenylene-methylene, methylene-1,3-phenylene-methylene, methylene-1,4-phenylene-methylene or methylene-pyridine radicals-methylene; And
N is an integer 0,1 and 2.
In formula 1 chemical compound of the present invention, R
3And R
4With respect to-X
1-or-X
3-be in an ortho position or a position, and-C (NH
2)=N-R
5Position or para-position between being in.
In one embodiment, R
1Be C
1～C
5Alkyl; The C that is replaced by piperidyl
1～C
5Alkyl; C
3～C
6Cycloalkyl; Phenyl; Pyridine radicals; Guanidine radicals; NR
6R
7By straight chain C
1～C
3Piperidyl or piperazinyl that alkyl replaces; Morpholinyl; Or piperidyl;
R
2Be hydrogen; Be not substituted or by NR
8R
9The straight or branched C that replaces
1～C
4Alkyl; C
3～C
6Cycloalkyl; Benzyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholinyl; Thio-morpholinyl; 4-methyl piperazine base; Or straight or branched C
1～C
3Alkyl, it is by C
1～C
3Alkoxyl, halogen, C
3～C
6Cycloalkyl, morpholinyl, dimethylated morpholinyl, thio-morpholinyl, 4-methyl piperazine base, piperidyl, imidazole radicals or pyrrolidinyl replace,
R
3Be hydrogen,
R
4Be hydrogen, hydroxyl or fluorine,
R
5Be hydrogen or hydroxyl;
R
6And R
7Be hydrogen independently of one another; C
1～C
3Alkyl, it is not substituted or is selected from hydroxyl, C
1～C
3A group of alkoxyl, pyridine radicals, morpholinyl and piperidyl replaces; Benzyl; Carbonyl, it is selected from C
1～C
3Alkyl, the C that is replaced by hydroxyl
1～C
3A group of alkyl and pyridine radicals replaces; Or C
1～C
3Alkanesulfonyl;
R
8And R
9Be hydrogen independently of one another; C
1～C
4Alkyl, it is not substituted or is selected from hydroxyl, C
1～C
3A group of alkoxyl, morpholinyl and imidazole radicals replaces; C
3～C
6Cycloalkyl; Benzyl; Or pyridine acyloxy (pyridinoyl); And
X
1-X
2-X
3Be
In one embodiment, R
1It is methyl; Ethyl; Isopropyl; The tert-butyl group; Amyl group; Piperidines-1-ylmethyl; Cyclohexyl; Phenyl; Pyridin-3-yl; Guanidine radicals; NR6R7; 1-propyl group-piperidin-4-yl; 4-methyl-piperazine-1-base; Morpholine-4-base; Or piperidin-4-yl;
R
2Be hydrogen; Be not substituted or by NR
8R
9The methyl, ethyl, propyl group, isopropyl or the butyl that replace; Cyclopenta; Benzyl; Vinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholine-4-base; Thiomorpholine-4-base; 4-methyl piperazine-1-base; Or straight or branched C
1～C
3Alkyl, it is by methoxyl group, chlorine, cyclopenta, morpholine-4-base, 2, and 6-thebaine-4-base, thiomorpholine-4-base, 4-methyl piperazine-1-base, piperidines-1-base, imidazoles-1-base or pyrrolidine-1-base replaces;
R
6And R
7Be hydrogen independently of one another; Methyl; Ethyl; Propyl group; C
1～C
3Alkyl, its group that is selected from hydroxyl, methoxyl group, pyridin-3-yl, pyridin-4-yl, morpholine-4-base and piperidines-1-base replaces; Benzyl; Carbonyl, its group that is selected from isopropyl, hydroxymethyl, pyridin-3-yl and pyridin-4-yl replaces; Or ethylsulfonyl; And
R
8And R
9Be hydrogen independently of one another; Methyl; Ethyl; Propyl group; Isopropyl; Butyl; Isobutyl group; The tert-butyl group; C
1～C
3Alkyl, its group that is selected from hydroxyl, methoxyl group, isopropoxy, morpholine-4-base and imidazoles-1-base replaces; Cyclopropyl; Cyclohexyl; Benzyl; 3-pyridine acyloxy or 4-pyridine acyloxy.
In one embodiment, R
6And R
7Between to have only a group be hydrogen.
In one embodiment, R
6And R
7All be hydrogen; Or C
1～C
6Alkyl, it is not substituted or is selected from hydroxyl, C
1～C
6A group of alkoxyl and pyridine radicals replaces.
Preferably, R
6And R
7All be hydrogen; Methyl; The methyl that pyridyl replaces; Ethyl; By the ethyl of hydroxyl or methoxyl group replacement; Or propyl group.
In one embodiment, R
6It is methyl; And
R
7Be C
1～C
6Alkyl, it is not substituted or is selected from hydroxyl, C
1～C
6A group of alkoxyl, pyridine radicals and morpholinyl replaces; Benzyl; Or by C
1～C
6The carbonyl that alkyl replaces.
Preferably, R
7Be methyl, it is replaced by pyridin-3-yl or pyridin-4-yl; Ethyl, its group that is not substituted or is selected from hydroxyl, methoxyl group and morpholine-4-base replaces; Benzyl; Carbonyl, it is replaced by isopropyl.
In one embodiment, R
6It is ethyl; And
R
7Be C
1～C
6Alkyl, it is not substituted or is replaced by hydroxyl or morpholinyl; Or benzyl.
Preferably, R
7By the ethyl of hydroxyl or morpholinyl replacement; Or benzyl.
In one embodiment, R
8And R
9Between to have only a group be hydrogen.
In one embodiment, R
8And R
9All are C
1～C
6Alkyl, it is not substituted or is replaced by hydroxyl.
Preferably, R
8And R
9All be ethyl, ethoxy or propyl group.
In one embodiment, R
8Be C
3～C
6Cycloalkyl; And
R
9It is the carbonyl that pyridyl replaces.
Preferably, R
8It is cyclohexyl;
R
9Be 3-pyridine acyloxy or 4-pyridine acyloxy.
In one embodiment, R
1Be C
1～C
6Alkyl, it is not substituted or pyridyl replaces; And
R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholinyl; Or straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
In one embodiment, R
1Be straight or branched C
1～C
6Alkyl, its quilt
Replace, should
Be not substituted or replaced by hydroxyl; And
R
2Be straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,, imidazole radicals or pyrrolidinyl replace.
In one embodiment, R
1Be C
3～C
6Cycloalkyl; And
R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace; Or straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
In one embodiment, R
1Be phenyl or benzyl; And
R
2It is phenyl; Benzyl; Amino; Perhaps straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,, imidazole radicals or pyrrolidinyl replace.
In one embodiment, R
1Be pyridine radicals, it is not substituted or by C
1～C
6Alkyl replaces; And
R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace; Phenyl; Benzyl; C
2～C
6Thiazolinyl; Or straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
In one embodiment, R
1It is guanidine radicals; And
R
2Be straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace.
In one embodiment, R
1Be NR
6R
7Or CH
2NR
6R
7And
R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Or straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
In one embodiment, R
1By straight or branched C
1～C
6Alkyl replaces
Group; And
R
2Be straight or branched C
1～C
6Alkyl, it is not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; Morpholinyl; Thio-morpholinyl; 4-methyl piperazine base; Or straight or branched C
1～C
6Alkyl, it is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
Among formula 1 Benzamine derivatives of the present invention, preferred chemical compound is as follows:
1) N-hydroxyl-4-{5-[4-(2-isopropyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
2) 4-{5-[4-(2-isopropyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
3) N-hydroxyl-4-{5-[4-(2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
4) N-hydroxyl-4-{5-[4-(2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
5) N-hydroxyl-4-{5-[4-(2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
6) N-hydroxyl-4-{5-[4-(2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
7) N-hydroxyl-4-{5-[4-(2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
8) N-hydroxyl-4-{5-[4-(2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
9) N-hydroxyl-4-{5-[4-(2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
10) N-hydroxyl-4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
11) N-hydroxyl-4-{5-[4-(2-ethyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
12) N-hydroxyl-4-{5-[4-(5-methyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
13) N-hydroxyl-4-{5-[4-(5-methyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
14) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
15) N-hydroxyl-4-{5-[4-(5-methyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
16) N-hydroxyl-4-{5-[4-(the 2-tert-butyl group-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
17) N-hydroxyl-4-{5-[4-(5-ethyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
18) N-hydroxyl-4-{5-[4-(2,5-diethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
19) N-hydroxyl-4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
20) N-hydroxyl-4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
21) N-hydroxyl-4-{5-[4-(5-ethyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
22) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
23) N-hydroxyl-4-{5-[4-(5-ethyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
24) N-hydroxyl-4-{5-[4-(2-ethyl-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
25) N-hydroxyl-4-{5-[4-(2,5-diisopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
26) N-hydroxyl-4-{5-[4-(5-isopropyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
27) N-hydroxyl-4-{5-[4-(5-isopropyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
28) N-hydroxyl-4-{5-[4-(5-isopropyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
29) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
30) N-hydroxyl-4-{5-[4-(5-butyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
31) N-hydroxyl-4-{5-[4-(5-butyl-2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
32) N-hydroxyl-4-{5-[4-(5-butyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
33) N-hydroxyl-4-{5-[4-(5-butyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
34) N-hydroxyl-4-{5-[4-(5-butyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
35) N-hydroxyl-4-{5-[4-(5-butyl-2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
36) N-hydroxyl-4-{5-[4-(5-butyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
37) N-hydroxyl-4-{5-[4-(the 5-butyl-2-tert-butyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
38) N-hydroxyl-4-{5-[4-(5-benzyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
39) N-hydroxyl-4-{5-[4-(5-benzyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
40) N-hydroxyl-4-{5-[4-(5-benzyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
41) N-hydroxyl-4-{5-[4-(5-benzyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
42) N-hydroxyl-4-{5-[4-(5-(2-chloro-ethyl)-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
43) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
44) N-hydroxyl-4-{5-[4-(5-isobutyl group-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
45) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
46) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
47) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
48) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
49) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
50) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
51) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
52) 4-{5-[4-(2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
53) 4-{5-[4-(2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
54) 4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
55) 4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
56) 4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
57) N-hydroxyl-4-{5-[4-(2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
58) N-hydroxyl-4-{5-[4-(2-amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
59) N-hydroxyl-4-{5-[4-(2-guanidine radicals-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
60) N-hydroxyl-4-{5-[4-(2-amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
61) N-hydroxyl-4-{5-[4-(2-amino-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
62) N-hydroxyl-4-{5-[4-(2-guanidine radicals-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
63) N-hydroxyl-4-{5-[4-(2-amino-5-butyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
64) N-hydroxyl-4-{5-[4-(5-butyl-2-guanidine radicals-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
65) N-hydroxyl-4-{5-[4-(2-amino-5-benzyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
66) N-hydroxyl-4-{5-[4-(5-benzyl-2-guanidine radicals-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
67) N-hydroxyl-4-{5-[4-(2-amino-5-methyl cyclopentane-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
68) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
69) N-hydroxyl-4-{5-[4-(2-(isobutyryl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
70) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
71) N-hydroxyl-4-{5-[4-(2-amino methyl-5-benzyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
72) N-hydroxyl-4-{5-[4-(5-methyl-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
73) N-hydroxyl-4-{5-[4-(5-isopropyl-2-aminomethyl-1,2,3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
74) N-hydroxyl-4-{5-[4-(5-vinyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
75) N-hydroxyl-4-{5-[4-(5-hydroxymethyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
76) N-hydroxyl-4-{5-[4-(5-methoxy-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
77) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
78) N-hydroxyl-4-{5-[4-(5-vinyl-2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
79) N-hydroxyl-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
80) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
81) N-hydroxyl-4-{5-[4-(2-amino-5-cyclopenta-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
82) N-hydroxyl-4-{5-[4-(5-ethyl-2-aminomethyl-1,2,3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
83) N-hydroxyl-4-{5-[4-(5-isopropyl-2-(piperidines-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
84) N-hydroxyl-4-{5-[4-(2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
85) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
86) N-hydroxyl-4-{5-[4-(5-methyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
87) N-hydroxyl-4-{5-[4-(2-ethylamino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
88) N-hydroxyl-4-{5-[4-(5-methyl-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
89) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
90) N-hydroxyl-4-{5-[4-(2-glycoloyl amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
91) N-hydroxyl-4-{5-[4-(5-methyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
92) N-hydroxyl-4-{5-[4-(5-methyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
93) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
94) N-hydroxyl-4-{5-[4-(2-(2-methoxy ethyl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
95) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
96) N-hydroxyl-4-{5-[4-(5-ethyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
97) N-hydroxyl-4-{5-[4-(5-ethyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
98) N-hydroxyl-4-{5-[4-(5-ethyl-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
99) N-hydroxyl-4-{5-[4-(5-ethyl-2-methoxyl group acetylaminohydroxyphenylarsonic acid 1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
100) N-hydroxyl-4-{5-[4-(5-ethyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
101) N-hydroxyl-4-{5-[4-(5-ethyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
102) N-hydroxyl-4-{5-[4-(5-ethyl-2-(2-methoxy ethyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
103) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
104) N-hydroxyl-4-{5-[4-(2-ethylamino-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
105) N-hydroxyl-4-{5-[4-(5-butyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
106) N-hydroxyl-4-{5-[4-(5-butyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
107) N-hydroxyl-4-{5-[4-(5-benzyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
108) N-hydroxyl-4-{5-[4-(5-benzyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
109) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
110) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
111) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
112) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
113) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
114) N-hydroxyl-4-{5-[4-(5-isopropyl-2-[(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
115) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
116) N-hydroxyl-4-{5-[4-(2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
117) N-hydroxyl-4-{5-[4-(5-ethyl-2-(pyridin-3-yl methyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
118) N-hydroxyl-4-{5-[4-(2-(ethylsulfonyl-methyl-amino)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
119) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
120) N-hydroxyl-4-[5-(4-{2-[(2-ethoxy)-methyl-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
121) N-hydroxyl-4-[5-(4-{2-[ethyl-(2-ethoxy)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
122) N-hydroxyl-4-[5-(4-{2-[two-(2-methoxy ethyl)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
123) N-hydroxyl-4-[5-(4-{5-methyl-2-[methyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
124) N-hydroxyl-4-[5-(4-{2-[ethyl-1-(2-morpholino ethyl)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
125) N-hydroxyl-4-{5-(4-[2-(benzyl-methyl-amino)-5-methyl isophthalic acid, 3-thiazole-4-yl] phenoxy group) amoxy }-benzamidine,
126) N-hydroxyl-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine,
127) N-hydroxyl-4-[5-{4-[2-(benzyl-ethyl-amino)-5-methyl isophthalic acid, 3-thiazole-4-yl] phenoxy group } amoxy]-benzamidine,
128) N-hydroxyl-4-[5-(4-{2-[two-(2-ethoxy)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
129) N-hydroxyl-4-[5-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine,
130) N-hydroxyl-4-[5-(4-{5-ethyl-2-[ethyl-(2-ethoxy)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
131) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
132) N-hydroxyl-4-[5-(4-{5-ethyl-2-[ethyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
133) N-hydroxyl-4-[5-{4-[2-(benzyl-methyl-amino)-5-ethyl-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine,
134) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
135) N-hydroxyl-4-(5-{4-[2-(benzyl-ethyl-amino)-5-ethyl-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine,
136) N-hydroxyl-4-{5-(4-[5-ethyl-2-(ethyl-[pyridin-3-yl methyl] amino)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
137) N-hydroxyl-4-[5-(4-{2-[two-(pyridin-3-yl methyl) amino]-5-ethyl-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
138) N-hydroxyl-4-{5-[4-(2-dipropyl amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
139) N-hydroxyl-4-[5-(4-{2-[two-(2-ethoxy) amino]-5-ethyl-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
140) N-hydroxyl-4-[5-(4-{2-[(2-ethoxy)-methyl-amino]-5-isopropyl-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine,
141) N-hydroxyl-4-[5-(4-{5-isopropyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
142) N-hydroxyl-4-(5-{4-[2-(ethylsulfonyl-methyl-amino)-5-isopropyl-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine,
143) N-hydroxyl-4-[5-(4-{5-butyl-2-[(2-ethoxy)-methyl-amino]-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine,
144) N-hydroxyl-4-[5-(4-{5-butyl-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
145) N-hydroxyl-4-[5-(4-{5-butyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
146) N-hydroxyl-4-{5-[4-(5-butyl-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
147) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
148) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
149) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
150) N-hydroxyl-4-{5-[4-(5-butyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
151) N-hydroxyl-4-{5-[4-(5-butyl-2-ethylmethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
152) N-hydroxyl-4-{5-[4-(5-butyl-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
153) N-hydroxyl-4-[5-(4-{5-cyclopenta-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
154) N-hydroxyl-4-[5-(4-{5-isobutyl group-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
155) N-hydroxyl-4-(5-{4-[5-(2-chloroethyl)-2-dimethylamino-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine,
156) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
157) N-hydroxyl-4-{5-[4-(5-isopropyl-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
158) N-hydroxyl-4-{5-[4-(5-ethyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
159) N-hydroxyl-4-[5-(4-{5-isopropyl-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
160) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
161) N-hydroxyl-4-{5-[4-(5-isopropyl-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
162) N-hydroxyl-4-{5-[4-(5-isopropyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
163) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
164) N-hydroxyl-4-{5-[4-(5-methyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
165) N-hydroxyl-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
166) N-hydroxyl-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
167) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
168) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
169) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
170) N-hydroxyl-4-{5-(4-[5-methyl cyclopentane-2-(4-methyl piperazine generation (piperazino))-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
171) N-hydroxyl-4-{5-[4-(5-vinyl-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
172) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
173) N-hydroxyl-4-{5-[4-(5-isobutyl group-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
174) N-hydroxyl-4-{5-(4-[5-ethyl-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
175) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
176) N-hydroxyl-4-{5-(4-[5-isopropyl-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
177) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine,
178) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-ethyoxyl-ethyoxyl)-benzamidine,
179) N-hydroxyl-4-{3-hydroxyl-5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-3-methyl-amoxy }-benzamidine,
180) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-1-methyl-ethylamino-ethyoxyl)-benzamidine,
181) N-hydroxyl-4-[3-(4-{3-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-propyl group-piperazine-1-yl)-propoxyl group]-benzamidine,
182) N-hydroxyl-4-5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-penta acyloxy-amino-benzamidine,
183) N-hydroxyl-4-({ 5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group }-methyl-amino)-benzamidine,
184) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-2-butylene oxygen base }-benzamidine,
185) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
186) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group]-ethylamino-ethyoxyl)-benzamidine,
187) N-hydroxyl-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
188) 2, N-dihydroxy-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
189) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-3-methoxyl group-benzamidine,
190) N-hydroxyl-2-cyclohexyl amino-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
191) N-hydroxyl-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
192) N-hydroxyl-2-fluoro-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
193) N-hydroxyl-4-{3-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] propoxyl group }-benzamidine,
194) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] butoxy }-benzamidine,
195) N-hydroxyl-3-{5-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine,
196) N-hydroxyl-4-{4-[4-(2-cyclohexyl-5-ethyl-thiazole-4-yl)-phenoxy group]-butoxy }-benzamidine,
197) N-hydroxyl-4-[5-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-thiazole-4-yl } phenoxy group) propoxyl group]-benzamidine,
198) N-hydroxyl-4-[5-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-thiazole-4-yl } phenoxy group) butoxy]-benzamidine,
199) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-thiazole-4-yl phenoxy group) propoxyl group]-benzamidine,
200) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-thiazole-4-yl phenoxy group) butoxy]-benzamidine,
201) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-isopropyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
202) N-hydroxyl-4-{4-[4-(5-butyl-2-isopropyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
203) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-amino-thiazolyl--4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
204) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-amino-thiazolyl--4-yl)-phenoxymethyl]-benzyloxy }-2-fluoro-benzamidine,
205) N-hydroxyl-4-{4-[4-(2-methylamino-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
206) N-hydroxyl-4-{6-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-pyridine-2-base-methoxyl group }-benzamidine,
207) N-hydroxyl-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxy group]-butoxy }-benzamidine,
208) N-hydroxyl-4-{2-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
209) N-hydroxyl-4-{3-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
210) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-cyclohexyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
211) N-hydroxyl-4-{6-[4-(5-isopropyl-2-methyl-thiazole-4-yl) phenoxy group]-hexyloxy }-benzamidine,
212) N-hydroxyl-4-{5-[2-ethyl-5-hydroxyl-4-(2-methyl-thiazole-4-yl) phenoxy group]-amoxy }-benzamidine,
213) N-hydroxyl-4-{5-[2-ethyl-4-(2-methyl-thiazole-4-yl)-5-propoxyl group-phenoxy group]-amoxy }-benzamidine,
214) N-hydroxyl-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
215) 4-(5-{4-[5-(2-isobutyl group aminoethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
216) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-piperidines-1-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
217) N-hydroxyl-4-[5-(4-{2-methyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
218) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
219) N-hydroxyl-4-(5-{4-[5-(2-isopropyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
220) N-hydroxyl-4-[5-(4-{5-[2-(3-isopropoxy-propyl group amino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
221) N-hydroxyl-4-(5-{4-[5-(2-butyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
222) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
223) N-hydroxyl-4-(5-{4-[5-(2-cyclohexyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
224) N-hydroxyl-4-(5-{4-[5-(2-diethylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
225) N-hydroxyl-4-{5-[4-(5-{2-[two-(2-hydroxyl-ethyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
226) N-hydroxyl-4-(5-{4-[5-(2-diisopropylaminoethyl-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
227) N-hydroxyl-4-[5-(4-{5-[2-(2,6-dimethyl-morpholine-4-yl)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
228) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
229) N-hydroxyl-4-(5-{4-[2-amino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
230) N-hydroxyl-4-[5-(4-{5-[2-(2-dimethylamino-ethylamino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
231) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
232) N-hydroxyl-4-[5-(4-{2-methyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
233) N-hydroxyl-4-{5-[4-(5-{2-[two-(2-methoxyl group-ethyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
234) N-hydroxyl-4-(5-{4-[5-(2-tert-butyl group amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
235) N-hydroxyl-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
236) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-pyridin-3-yl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
237) N-hydroxyl-4-[5-(4-{5-[2-(4-methyl-piperazine-1-yl)-ethyl]-2-pyridin-3-yl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
238) N-hydroxyl-4-(5-{4-[2-pyridin-3-yl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
239) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-pyridin-3-yl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
240) N-hydroxyl-4-(5-{4-[2-isopropyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
241) N-hydroxyl-4-[5-(4-{2-isopropyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
242) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-isopropyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
243) N-hydroxyl-4-[5-(4-{2-isopropyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
244) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-isopropyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
245) N-hydroxyl-4-(5-{4-[2-isopropyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
246) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
247) N-hydroxyl-4-[5-(4-{2-cyclohexyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
248) N-hydroxyl-4-[5-(4-{2-cyclohexyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
249) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
250) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dimethylamino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
251) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dipropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
252) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-cyclopropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
253) N-hydroxyl-4-[5-(4-{2-amino-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
254) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-phenyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
255) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
256) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
257) N-hydroxyl-4-(4-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-butoxy)-benzamidine,
258) 4-(5-{4-[2-cyclohexyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
259) 4-(5-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
260) N-hydroxyl-4-(5-{4-[2-methylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
261) N-hydroxyl-4-[5-(4-{2-methylamino-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
262) N-hydroxyl-4-(5-{4-[2-methylamino-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
263) N-hydroxyl-4-[5-(4-{2-methylamino-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
264) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-methylamino-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
265) 4-(5-{4-[2-methylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
266) N-hydroxyl-4-(5-{4-[2-dimethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
267) N-hydroxyl-4-(5-{4-[2-dimethylamino-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
268) N-hydroxyl-4-(5-{4-[2-(isobutyryl-methyl-amino)-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
269) N-hydroxyl-4-(5-{4-[2-[benzyl-(2-morpholine-4-base-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
270) N-hydroxyl-4-(5-{4-[2-diethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
271) N-hydroxyl-4-(5-{4-[2-[two-(2-methoxyl group-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
272) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
273) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
274) N-hydroxyl-4-[5-(4-{5-[2-(4-methyl-piperazine-1-yl)-ethyl]-2-morpholine-4-base-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
275) N-hydroxyl-4-[5-(4-{2-morpholine-4-base-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
276) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-piperidines-1-base-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
277) 4-(5-{4-[2-morpholine-4-base-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
278) N-hydroxyl-4-(5-{4-[5-(2-isobutyryl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
279) N-hydroxyl-4-{5-[4-(5-{2-[isobutyl group-(pyridine-3-carbonyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
280) N-hydroxyl-4-{5-[4-(5-{2-[cyclopropyl-(pyridine-4-carbonyl)-amino]-ethyl-2-isopropyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
281) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-{2-[cyclopropyl-(pyridine-3-carbonyl)-amino]-ethyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
282) N-hydroxyl-4-{5-[4-(5-methylamino formoxyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
283) N-hydroxyl-4-{5-[4-(5-isopropyl carbamoyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
284) N-hydroxyl-4-{5-[4-(5-{3-imidazoles-1-base-propyl group carbamoyl }-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
285) N-hydroxyl-4-{5-[4-(2-amino-5-methylamino formoxyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
286) N-hydroxyl-4-{5-[4-(2-methyl-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
287) N-hydroxyl-4-(5-{4-[2-methyl-5-(4-methyl-piperazine-1-yl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
288) N-hydroxyl-4-{5-[4-(2-amino-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
289) N-hydroxyl-4-(5-{4-[5-(4-methyl-piperazine-1-yl)-2-morpholine-4-base-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
290) N-hydroxyl-4-{5-[4-(2,5-dimorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
291) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-thiomorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
292) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-pyrrolidine-1-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
293) N-hydroxyl-4-{5-[4-(2-methyl-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
294) N-hydroxyl-4-(5-{4-[2-methyl-5-(4-methyl-piperazine-1-ylmethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
295) N-hydroxyl-4-{5-[4-(2-methyl-5-thiomorpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
296) N-hydroxyl-4-{5-[4-(2-methyl-5-piperidines-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
297) N-hydroxyl-4-{5-[4-(5-dimethylamino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
298) N-hydroxyl-4-{5-[4-(5-butyl amino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
299) N-hydroxyl-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
300) N-hydroxyl-4-(5-{4-[5-(tert-butyl group amino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
301) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group amino methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
302) N-hydroxyl-4-[5-(4-{2-methyl-5-[(2-morpholine-4-base-ethylamino)-methyl]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
303) N-hydroxyl-4-[5-(4-{5-[(3-imidazoles-1-base-propyl group amino)-methyl]-2-methyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
304) N-hydroxyl-4-{5-[4-(2-methyl-5-pyrrolidine-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
305) N-hydroxyl-4-{5-[4-(5-imidazoles-1-ylmethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
306) N-hydroxyl-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
307) N-hydroxyl-4-{5-[4-(5-cyclopropyl amino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
308) N-hydroxyl-4-{5-[4-(2-methylamino-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
309) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-4-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
310) N-hydroxyl-4-[5-(4-{2-[(2-hydroxyl-ethyl)-methyl-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
311) N-hydroxyl-4-(5-{4-[2-(ethyl-methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
312) N-hydroxyl-4-(5-{4-[2-(benzyl-methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
313) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
314) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-thiomorpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
315) N-hydroxyl-4-[5-(4-{5-{[two-(2-methoxyl group-ethyl)-amino]-methyl-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
316) N-hydroxyl-4-(5-{4-[2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-(4-methyl-piperazine-1-ylmethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
317) N-hydroxyl-4-[5-(4-{5-(isopropyl amino-methyl)-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
318) N-hydroxyl-4-[5-(4-{5-[(2-methoxyl group-ethylamino)-methyl]-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
319) N-hydroxyl-4-[5-(4-{2-[(2-methoxyl group-ethyl)-methyl-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
320) N-hydroxyl-4-(5-{4-[2-(methyl-propyl group-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
321) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-3-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
322) N-hydroxyl-4-{5-[4-(2-methyl-5-methylamino-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
323) N-hydroxyl-4-[5-(4-{2-methyl-5-[(pyridine-4-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
324) N-hydroxyl-4-[5-(4-{2-methyl-5-[(pyridine-3-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
325) N-hydroxyl-4-[5-(4-{2-phenyl-5-[(pyridine-3-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
326) N-hydroxyl-4-{5-[4-(5-dimethylamino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
327) N-hydroxyl-4-{5-[4-(5-dimethylamino-2-phenyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
328) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-dimethylamino-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
329) N-hydroxyl-4-{5-[4-(2-methyl-5-[1,2,4] triazol-1-yl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
330) N-hydroxyl-4-{5-[4-(5-amino-2-phenyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
331) N-hydroxyl-4-{5-[4-(5-amino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
332) N-hydroxyl-4-{5-[4-(5-amino-2-pyridin-3-yl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
333) N-hydroxyl-4-{5-[4-(5-amino-2-ethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
334) N-hydroxyl-4-{5-[4-(5-amino-2-cyclohexyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
335) N-hydroxyl-4-{5-[4-(2-methylamino-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
336) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine and
337) N-hydroxyl-4-{5-[4-(5-morpholine-4-base-2-piperidines-1-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine.
In formula 1 Benzamine derivatives of the present invention, preferred chemical compound is as follows:
1) 4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
2) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
3) N-hydroxyl-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
4) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
5) N-hydroxyl-4-{5-[4-(2-(2-methoxy ethyl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
6) N-hydroxyl-4-{5-[4-(5-ethyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
7) N-hydroxyl-4-{5-[4-(5-ethyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
8) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
9) N-hydroxyl-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine,
10) N-hydroxyl-4-{5-[4-(2-dipropyl amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
11) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
12) N-hydroxyl-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
13) N-hydroxyl-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
14) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
15) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine,
16) N-hydroxyl-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
17) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-isopropyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
18) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-isopropyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
19) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dipropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
20) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
21) N-hydroxyl-4-(5-{4-[2-[benzyl-(2-morpholine-4-base-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
22) N-hydroxyl-4-(5-{4-[2-diethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
23) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
24) N-hydroxyl-4-{5-[4-(2,5-dimorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
25) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-thiomorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
26) N-hydroxyl-4-{5-[4-(2-methyl-5-piperidines-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
27) N-hydroxyl-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
28) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group amino methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
29) N-hydroxyl-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
30) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-4-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
31) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-thiomorpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine and
32) N-hydroxyl-4-{5-[4-(5-amino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine.
In formula 2 bisphosphonates of the present invention, preferred chemical compound is as follows:
1) etidronic acid,
2) clodronic acid,
3) pamidronic acid,
4) tiludronic acid,
5) risedronic acid,
6) minodronic acid,
7) ibandronic acid,
8) zoledronic acid and
9) alendronic Acid.
Can use formula 1 Benzamine derivatives of the present invention with the form of pharmaceutically acceptable salt.Preferably with the acid-addition salts (acid addition salt) of pharmaceutically acceptable free acid preparation.Be applicable to that free acid of the present invention can be mineral acid or organic acid.Representative examples of mineral pigments can comprise hydrochloric acid, bromic acid, sulphuric acid and phosphoric acid, and organic acid can be by following example: citric acid, acetic acid, lactic acid, tartaric acid, fumaric acid, formic acid, propanoic acid, oxalic acid, trifluoroacetic acid, methanesulfonic acid, benzenesulfonic acid, maleic acid, benzoic acid, gluconic acid, glycolic, succinic acid, 4-morpholino b acid, camphorsulfonic acid, 4-nitrobenzene-sulfonic acid, hydroxyl-O-sulfonic acid, 4-toluenesulfonic acid, galacturonic acid, pounce on acid, glutamic acid and aspartic acid.Preferably, hydrochloric acid or phosphoric acid can be used as mineral acid, can be with methanesulfonic acid as organic acid.
In the present invention, the substituent General Definition of formula 1 and 2 chemical compounds has following meanings:
Term " halogen " means the halogen group atom, comprises chlorine, fluorine, bromine and iodo.
Term " alkyl " means the straight or branched saturated hydrocarbyl with 1 to 6 carbon atom, and the example comprises methyl, ethyl, n-pro-pyl, isopropyl, normal-butyl, sec-butyl and the tert-butyl group.
Term " alkoxyl " means the group with the straight or branched alkyl that is connected to oxygen, and this straight or branched alkyl has 1 to 6 carbon atom, and the example comprises methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, sec-butoxy and tert-butoxy.
Term " cycloalkyl " means the non-aromatic hydrocarbon ring with 3 to 6 carbon atoms, and the example comprises cyclopropyl, cyclobutyl, cyclopenta and cyclohexyl.
Term " thiazolinyl " means the straight or branched unsaturated hydrocarbons with 2 to 6 carbon atoms and one or more pairs of keys.
Term " alkanoyloxy " means such oxy radical: wherein the terminal carbon of alkyl is by carbonyl substituted.
Term " alkene acyloxy (alkenoyloxy) " means such oxy radical: wherein the terminal carbon of thiazolinyl is by carbonyl substituted.
Term " alkene oxygen base (alkenyloxy) " means oxygen containing thiazolinyl.
Term " alkylidene " means has 1 to 7 carbon atom is connected the center with 2 or a plurality of covalent bond straight or branched saturated hydrocarbyl, and the example comprises methylene, ethylidene, methyl ethylidene and isopropylidene.
Term " alkenylene " mean have 2 to 7 carbon atoms, straight or branched unsaturated alkyl that 2 or a plurality of covalent bond connect center and one or more pairs of keys, the example comprises 1,1-ethenylidene (CH
2=C), (CH=CH-) and 1, the 4-butadienyl is (CH=CH-CH=CH-) for vinylene.
Term " carbonyl " means such carbon-based group: wherein 2 in 4 covalent bonds are connected to oxygen atom.
The benzamidine of used formula 1 or its salt can be used as the treatment or the preventive of osteoporosis among the present invention, and bone resorption is had good depression effect, and bone formation is had good stimulating effect.
Can be by the Benzamine derivatives of known method preparation formula 1, this method is disclosed Korean patent No. 705875 and Korean patent No. 875596, and Korean Patent Application No. 2008-0073710.
Term used herein " osteoporosis " means such symptom: though in the structure of remaining bone without any defective, the mineral and the substrate that form bone reduce singularly in a large number, thereby in bone, generate big metering-orifice, make it, and more likely fracture as sponge.It can be called as " minimizing of bone amount ".
The Benzamine derivatives of formula 1 or the dosage of its salt can be depending on patient's body weight, age, sex, health status, diet, administration cycle, route of administration, excretion rate, disease severity, the type or the therapeutic frequency of therapeutic alliance changes.Under situation as treatment or prevention preparation, can be by effective dose usually Benzamine derivatives or its salt of giving construction 1 of each route of administration with the treatment osteoporosis, and those skilled in the art can consider administration purpose, approach, health status and the body weight of object, determine its prescription, dosage or analog at an easy rate.Particularly, can be with about 1 to 1,000mg, preferred 5 to 400mg dosage every day gives Benzamine derivatives or its salt.
In addition, the dosage of the diphosphate of formula 2 can be depending on patient's the type of body weight, age, sex, health status, diet, administration cycle, route of administration, excretion rate, disease severity, therapeutic alliance or therapeutic frequency and changes.Under situation as treatment or preventive, can be by the effective dose usually diphosphate of giving construction 2 of each route of administration with the treatment osteoporosis, and those skilled in the art can consider the health status and the body weight of administration purpose, approach and object, determine its prescription, dosage or analog at an easy rate.Particularly, can be with about 1 to 1,000mg, preferred 1 to 400mg dosage every day gives diphosphate.
In the present invention, can use the benzamidine of formula 1 or the diphosphate of its salt and formula 2 with its combination in any.
In the present invention, can be by the mixed together simultaneously benzamidine of giving construction 1 or the diphosphate of its salt and formula 2, perhaps can be simultaneously or give wherein each in succession respectively, perhaps can give wherein each respectively in the different time.Under situation about giving respectively, can alternately give two kinds of active component, or a kind of active component can give after the finishing of another kind of active component.
In the present invention, the benzamidine of formula 1 or the diphosphate of its salt and formula 2 can be made any pharmaceutical formulation, for example, comprise combination formulations or each unitary agent of two kinds of active component.As used herein, combination formulations means two kinds of active component---and the benzamidine of formula 1 or the diphosphate of its salt and formula 2 are blended in the preparation, and unitary agent means in the preparation and comprises a kind of active component.In the present invention, if two kinds of active component are made into unitary agent, treatment of the present invention and preventive refer to the medicine with its applied in any combination unitary agent.Therefore, each medicine that comprises active component can be made each different preparation.If two kinds of active component are made into unitary agent, then can in a test kit, provide two kinds of preparations.
In addition, can every day or give osteoporosis prevention of the present invention or therapeutic agent off and on, and can give this medicament 1 time on the one or 2～3 times.If each active component is a unitary agent, then it gives frequency and can be same to each other or different to each other.
The diphosphate of the benzamidine of formula 1 of the present invention or its salt and formula 2 can prepare separately or together with following appropriate excipients by known method.The instantiation of preparation can comprise peroral dosage form, as soft capsule, hard capsule, tablet and syrup, and injectable and partial dosage form.
As excipient, pharmaceutically acceptable carrier comprises and is used to prepare known formulations---as sterile liquid, tablet, coated tablet and capsular any standard drug carrier.Generally, this carrier comprises excipient, as the clay of polyvinylpyrrolidone, dextrin, starch, emulsion, sugar, some type, gelatin, stearic acid, Talcum, vegetable oil (for example, edible oil, cotton seed oil, Oleum Cocois, almond oil, Oleum Arachidis hypogaeae semen), the liquid esters---as triglyceride, mineral oil, vaseline (Vaseline), Animal fat, cellulose derivative (for example, crystalline cellulose, hydroxypropyl cellulose, hydroxypropyl emthylcellulose, methylcellulose) and other known excipient.This carrier can also comprise antioxidant, wetting agent, viscosity stabiliser, flavoring agent, color additive and other additives.The compositions that can comprise these carriers by known method preparation.
The compositions of prevention of the present invention or treatment osteoporosis means and will have two types active component of different mechanisms each other---comprising the benzamidine of formula 1 or the diphosphate of its salt and formula 2---use in conjunction, with respect to other independent medicines, provide the good result that improves bone density and intensity.
In order to prevent and treat osteoporosis, separately or combined with surgery, hormone therapy, chemotherapy and other utilize the method for biological response modifier to use prevention of the present invention or therapeutic combination.
[preferred forms of the present invention]
Hereinafter, the present invention is described reference example in further detail.But these embodiment are not that intention limits the present invention by these embodiment only to be exemplified as purpose.
Preparation embodiment 1: the preparation of the Benzamine derivatives of formula 1
According to the Benzamine derivatives of Korean patent No. 705875, Korean patent No. 875596 and the disclosed preparation method preparation formula 1 of Korean Patent Application No. 2008-0073710, incorporate its whole disclosures into as a reference at this.
Identify that prepared chemical compound is as follows.
1) N-hydroxyl-4-{5-[4-(2-isopropyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.31 (d, 6H), 1.58 (m, 2H), 1.79 (m, 4H), 2.47 (s, 3H), 3.21 (m, 1H), 4.00 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 6.99 (d, 2H), 7.56 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
2) 4-{5-[4-(2-isopropyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.33 (d, 6H), 1.61 (m, 2H), 1.82 (brm, 4H), 2.49 (s, 3H), 3.22 (m, 1H), 4.04 (t, 2H), 4.14 (t, 2H), 7.01 (d, 2H), 7.17 (d, 2H), 7.57 (d, 2H), 7.85 (d, 2H) (DMSO-d
6)
3) N-hydroxyl-4-{5-[4-(2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.78 (brm, 4H), 2.68 (s, 3H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.96 (d, 2H), 7.57 (d, 2H), 7.72 (s, 1H), 7.83 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
4) N-hydroxyl-4-{5-[4-(2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.32 (t, 3H), 1.57 (brm, 2H), 1.77 (brm, 4H), 3.01 (q, 2H), 4.00 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 6.96 (d, 2H), 7.57 (d, 2H), 7.75 (s, 1H), 7.84 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
5) N-hydroxyl-4-{5-[4-(2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.35 (d, 6H), 1.58 (m, 2H), 1.78 (brm, 4H), 3.28 (m, 1H), 4.00 (m, 4H), 5.79 (brs, 2H), 6.91 (d, 2H), 6.97 (d, 2H), 7.58 (d, 2H), 7.76 (s, 1H), 7.84 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
6) N-hydroxyl-4-{5-[4-(2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.80 (brm, 4H), 4.02 (m, 4H), 5.81 (brs, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.51 (m, 3H), 7.58 (d, 2H), 7.96 (d, 2H), 8.01 (m, 3H), 9.49 (s, 1H) (DMSO-d
6)
7) N-hydroxyl-4-{5-[4-(2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (brm2H), 1.80 (brm, 4H), 4.02 (t, 4H), 5.73 (s, 2H), 6.91 (d, 2H), 7.02 (d, 2H), 7.55 (m, 3H), 7.82 (d, 2H), 7.97 (d, 2H), 8.10 (s, 1H), 8.36 (d, 1H), 8.67 (d, 1H), 9.19 (s, 1H), 9.45 (s, 1H) (DMSO-d
6)
8) N-hydroxyl-4-{5-[4-(2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.23 (m, 1H), 1.47 (m, 6H), 1.65 (m, 1H), 1.77 (brm, 6H), 2.06 (m, 2H), 2.99 (m, 1H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.96 (d, 2H), 7.57 (d, 2H), 7.74 (d, 2H), 7.83 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
9) N-hydroxyl-4-{5-[4-(2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (t, 3H), 1.33 (brm, 4H), 1.56 (brm, 2H), 1.73 (brm, 6H), 2.97 (m, 2H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.96 (m, 2H), 7.57 (d, 2H), 7.74 (s, 1H), 7.83 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
10) N-hydroxyl-4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (m, 2H), 1.78 (m, 4H), 2.44 (s, 3H), 2.58 (s, 3H), 4.01 (m, 4H), 5.72 (s, 2H), 6,97 (d, 2H), 7.54 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
11) N-hydroxyl-4-{5-[4-(2-ethyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.27 (t, 3H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.45 (s, 3H), 2.91 (q, 2H), 4.01 (m, 4H), 5.75 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.54 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H). (DMSO-d
6)
12) N-hydroxyl-4-{5-[4-(5-methyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.56 (s, 3H), 4.02 (m, 4H), 5.78 (brs, 2H), 6.91 (d, 2H), 7.03 (d, 2H) .7.49 (m, 3H), 7.58 (d, 2H), 7.65 (d, 2H), 7.91 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
13) N-hydroxyl-4-{5-[4-(5-methyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.59 (m, 2H), 1.79 (m, 2H), 2.58 (s, 3H), 4.02 (m, 4H), 5.72 (s, 2H), 6.91 (d, 2H), 7.03 (d, 2H), 7.52 (m, 1H), 7.58 (d, 2H), 7.66 (d, 2H), 8.26 (d, 1H), 8.64 (d, 1H), 9.09 (d, 1H), 9.45 (s, 1H) (DMSO-d
6)
14) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.26 (m, 1H), 1.43 (brm, 4H), 1.61 (m, 2H), 1.67 (m, 1H), 1.80 (brm, 6H), 2.04 (m, 1H), 2.49 (s, 3H), 2.92 (m, 1H), 4.03 (m, 4H), 5.73 (s, 2H), 6.94 (d, 2H), 7.01 (d, 2H), 7.57 (d, 2H), 7.60 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
15) N-hydroxyl-4-{5-[4-(5-methyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (t, 3H), 1.31 (brm, 4H), 1.58 (m, 2H), 1.68 (m, 2H), 1.78 (brm, 4H), 2.46 (s, 3H), 2.88 (t, 2H), 4.01 (m, 4H), 5.72 (brs, 2H), 6.92 (d, 2H), 6.98 (d, 2H), 7.53 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
16) N-hydroxyl-4-{5-[4-(the 2-tert-butyl group-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.36 (s, 9H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.45 (s, 3H), 4.00 (m, 4H), 5,72 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.55 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
17) N-hydroxyl-4-{5-[4-(5-ethyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.26 (t, 3H), 1.66 (m, 2H), 1.85 (brm, 4H), 2.83 (s, 3H), 2.86 (q, 2H), 4.00 (m, 4H), 4.88 (brs, 1H), 6.87 (d, 2H), 6.91 (d, 2H), 7.46 (d, 2H), 7.52 (d, 2H) (CDCl
3)
18) N-hydroxyl-4-{5-[4-(2,5-diethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1..22 (t, 3H), 1.28 (t, 3H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.85 (q, 2H), 4.01 (m, 2H), 5.73 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
19) N-hydroxyl-4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.22 (t, 3H), 1.31 (d, 6H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.86 (q, 2H), 3.24 (m, 1H), 4.01 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.49 (d, 2H), 7.58 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
20) N-hydroxyl-4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.29 (t, 2H), 1.58 (m, 2H), 1.79 (m, 4H), 2.96 (q, 2H), 4.03 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 7.03 (d, 2H), 7.43 (m, 3H), 7.58 (m, 4H), 7.90 (m, 2H), 9.43 (s, 1H) (DMSO-d
6)
21) N-hydroxyl-4-{5-[4-(5-ethyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.30 (t, 3H), 1.58 (m, 2H), 1.79 (m, 4H), 2.98 (q, 2H), 4.02 (m, 4H), 5.69 (s, 2H), 6.91 (d, 2H), 7.04 (d, 2H), 7.52 (m, 1H), 7.59 (m, 4H), 8.26 (m, 1H), 8.63 (m, 1H), 9.10 (s, 1H), 9.42 (s, 1H) (DMSO-d
6)
22) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.22 (m, 4H), 1.38 (m, 4H), 1.58 (m, 2H), 1.64 (m, 1H), 1.89 (brm, 6H), 2.01 (m, 2H), 2.87 (m, 3H), 4.01 (m, 4H), 5.71 (s, 2H), 6.91 (s, 2H), 6.98 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
23) N-hydroxyl-4-{5-[4-(5-ethyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (t, 3H), 1.21 (t, 3H), 1.32 (brm, 4H), 1.58 (m, 2H), 1.69 (m, 2H), 1.78 (brm, 4H), 2.87 (m, 4H), 4.01 (m, 4H), 5.72 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.48 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
24) N-hydroxyl-4-{5-[4-(2-ethyl-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.26 (m, 9H), 1.57 (m, 2H), 1.79 (brm, 4H), 2.92 (q, 2H), 3.31 (m, 1H), 4.01 (m, 4H), 5.71 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.43 (d, 2H), 7.57 (d, 2H) (DMSO-d
6)
25) N-hydroxyl-4-{5-[4-(2,5-diisopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.24 (d, 6H), 1.32 (d, 6H), 1.56 (brm, 2H), 1.76 (brm, 4H), 3.22-3.27 (m, 1H), 3.34-3.38 (m, 1H), 3.90 (t, 2H), 4.02 (t, 2H), 5.70 (s, 2H), 6.80 (d, 2H), 7.00 (d, 2H), 7.26 (d, 2H), 7.45 (d, 2H), 8.29 (s, 1H) (DMSO-d
6)
26) N-hydroxyl-4-{5-[4-(5-isopropyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.31 (d, 6H), 1.58 (brm, 2H), 1.78 (brm, 4H), 3.44 (m, 1H), 4.02 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 7.03 (d, 2H), 7.47 (m, 3H), 7.56 (m, 4H), 7.90 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
27) N-hydroxyl-4-{5-[4-(5-isopropyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.32 (d, 6H), 1.57 (brm, 2H), 1.78 (brm, 4H), 4.00 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 7.04 (d, 2H), 7.51 (m, 1H), 7.58 (m, 4H), 8.27 (d, 1H), 8.64 (d, 1H), 9.10 (d, 1H), 9.44 (s, 1H) (DMSO-d
6)
28) N-hydroxyl-4-{5-[4-(5-isopropyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.23 (d, 6H), 1.32 (brm, 4H), 1.56 (m, 2H), 1.69 (m, 2H), 1.78 (brm, 4H), 2.88 (m, 2H), 3.36 (m, 1H), 4.01 (m, 4H), 5.73 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.43 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
29) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.91 (t, 3H), 1.57～1.61 (m, 4H), 1.78 (m, 4H), 2.60 (s, 3H), 2.80 (m, 2H), 4.01 (m, 4H), 5.85 (brs, 2H), 6.93 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.58 (d, 2H), 9.51 (s, 1H) (DMSO-d
6)
30) N-hydroxyl-4-{5-[4-(5-butyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 0.83 (t, 3H), 1.30 (m, 2H), 1.53 (m, 4H), 1.78 (brm, 4H), 2.59 (s, 3H), 2.82 (m, 2H), 4.00 (m, 4H), 5.74 (brs, 2H), 6.91 (d, 2H), 7.46 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
31) N-hydroxyl-4-{5-[4-(5-butyl-2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.27 (t, 3H), 1.31 (m, 2H), 1.56 (m, 4H), 1.78 (brm, 4H), 2.83 (t, 2H), 2.92 (m, 2H), 4.01 (m, 4H), 5.72 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.58 (d, 2H), 9.45 (s, 2H) (DMSO-d
6)
32) N-hydroxyl-4-{5-[4-(5-butyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.31 (m, 8H), 1.57 (m, 4H), 1.78 (brm, 4H), 2.83 (m, 2H), 3.24 (m, 1H), 4.01 (m, 4H), 5.74 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
33) N-hydroxyl-4-{5-[4-(5-butyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (t, 3H), 1.33 (m, 2H), 1.61 (m, 4H), 1.80 (m, 4H), 2.92 (t, 2H), 4.01 (m, 4H), 5.72 (brs, 2H), 6.91 (d, 2H), 7.02 (d, 2H), 7.46 (m, 3H), 7.59 (m, 4H), 7.91 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
34) N-hydroxyl-4-{5-[4-(5-butyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (t, 3H), 1.35 (m, 2H), 1.59 (m, 2H), 1.66 (m, 2H), 1.78 (m, 4H), 2.95 (t, 2H), 4.03 (m, 4H), 5.75 (brs, 2H), 6.91 (d, 2H), 7.04 (d, 2H), 7.51 (m, 1H), 7.58 (m, 4H), 8.26 (d, 1H), 8.63 (d, 1H), 9.09 (d, 1H), 9.45 (s, 1H) (DMSO-d
6)
35) N-hydroxyl-4-{5-[4-(5-butyl-2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.28 (brm, 6H), 1,56 (brm, 6H), 1.77 (brm, 6H), 2.00 (m, 2H), 2.83 (t, 2H), 2.90 (m, 1H), 4.01 (m, 4H), 5.72 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
36) N-hydroxyl-4-{5-[4-(5-butyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.85 (m, 6H), 1.31 (m, 6H), 1.58 (m, 4H), 1.69 (m, 2H), 1.78 (brm, 4H), 2,83 (t, 2H), 2.88 (t, 2H), 4.01 (m, 4H), 5.72 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
37) N-hydroxyl-4-{5-[4-(the 5-butyl-2-tert-butyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.31 (m, 2H), 1.36 (s, 9H), 1.57 (brm, 4H), 1.79 (brm, 4H), 2.83 (m, 2H), 4.01 (m, 4H), 5.74 (brs, 2H), 6.91 (d, 2H), 6.97 (d, 2H), 7.48 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
38) N-hydroxyl-4-{5-[4-(5-benzyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.78 (brm, 4H), 2.58 (s, 3H), 4.00 (m, 4H), 4.20 (s, 2H), 5.77 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.17 (d, 2H), 7.22 (m, 1H), 7.30 (m, 2H), 7.52 (d, 2H), 7.57 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
39) N-hydroxyl-4-{5-[4-(5-benzyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.28 (d, 6H), 1.57 (m, 2H), 1.77 (brm, 4H), 3.19 (m, 1H), 4.00 (m, 2H), 4.21 (s, 2H), 5.70 (s, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.19 (m, 3H), 7.30 (m, 2H), 7.53 (d, 2H), 7.56 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
40) N-hydroxyl-4-{5-[4-(5-benzyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.79 (brm, 4H), 4.02 (m, 4H), 4.31 (s, 2H), 5.72 (brs, 2H), 6.91 (d, 2H), 7.03 (d, 2H), 7.24 (m, 3H), 7.32 (m, 2H), 7.46 (m, 3H), 7.58 (d, 2H), 7.64 (d, 2H), 7.89 (m, 2H), 9.44 (s, 2H) (DMSO-d
6)
41) N-hydroxyl-4-{5-[4-(5-benzyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.79 (brm, 4H), 4.02 (m, 4H), 4.34 (s, 2H), 5.73 (brs, 2H), 6.91 (d, 2H), 7.04 (d, 2H), 7.25 (m, 3H), 7.33 (, .2H), 7.49 (m, 1H), 7.58 (d, 2H), 7.66 (d, 2H), 8.25 (d, 1H), 8.63 (d, 1H), 9.08 (s, 1H), 9.45 (s, 1H) (DMSO-d
6)
42) N-hydroxyl-4-{5-[4-(5-(2-chloro-ethyl)-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.65 (m, 2H), 1.86 (m, 4H), 2.72 (s, 3H), 3.30 (t, 2H), 3.67 (t, 2H), 4.02 (m, 4H), 5.70 (s, 2H), 6.92 (m, 4H), 7.45 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
43) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (brs, 6H), 1.77 (brs, 6H), 2.07 (brs, 2H), 2.62 (s, 3H), 3.30 (m, 1H), 3.98 (m, 4H), 6.75～6.92 (m, 4H), 7.39～7.60 (m, 4H) (CDCl
3)
44) N-hydroxyl-4-{5-[4-(5-isobutyl group-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (d, 6H), 1.60 (m 2H), 1.78 (m, 5H), 2.61 (s, 3H), 2.72 (d, 2H), 4.01 (m, 4H), 5.77 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.45 (d, 2H), 7.59 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
45) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.14 (m, 2H), 1.48 (brm 6H), 1.69 (m, 2H), 1.78 (brm, 4H), 2.02 (m, 1H), 2.59 (s, 3H), 2.82 (d, 2H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H), 7.46 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
46) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.11 (m, 2H), 1.27 (t, 3H), 1.52 (brm, 6H), 1.70 (m, 2H), 1.78 (brm, 4H), 2.03 (m, 1H), 2.83 (d, 2H), 2.92 (q, 2H), 4.00 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.46 (d, 2H), 7.79 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
47) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.11 (m, 2H), 1.31 (d, 6H), 1.49 (brm, 6H), 1.78 (brm, 6H), 2.04 (m, 1H), 2.83 (d, 2H), 3.21 (m, 1H), 4.01 (m, 4H), 5.72 (brs, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
48) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.15 (m, 2H), 1.50 (brm, 6H), 1.78 (brm, 6H), 2.11 (m, 1H), 2.92 (d, 2H), 4.01 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 7.02 (d, 2H), 7.46 (m, 3H), 7.58 (m, 4H), 7.91 (dd, 2H), 9.44 (s, 1H) (DMSO-d
6)
49) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.16 (m, 2H), 1.55 (brm, 6H), 1.78 (brm, 6H), 2.12 (m, 1H), 2.96 (d, 2H), 4.02 (m, 4H), 5.71 (brs, 2H), 6.91 (d, 2H), 7.04 (d, 2H), 7.52 (m, 1H), 7.58 (m, 4H), 8.26 (m, 1H), 8.64 (dd, 1H), 9.10 (d, 1H), 9.44 (s, 1H) (DMSO-d
6)
50) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.10 (m, 2H), 1.23 (m, 1H), 1.46 (brm, 11H), 1.77 (brm, 8H), 2.02 (m, 3H), 2.83 (d, 2H), 2.90 (m, 1H), 4.00 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 6.97 (d, 2H), 7.46 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
51) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.85 (t, 3H), 1.10 (m, 2H), 1.31 (brm, 4H), 1.52 (brm, 6H), 1.58 (brm, 4H), 1.70 (brm, 4H), 2.03 (m, 1H), 2.83 (d, 2H), 2.89 (m, 2H), 4.01 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.46 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
52) 4-{5-[4-(2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (brm, 2H), 1.79 (brm, 4H), 2.68 (s, 3H), 4.01 (t, 2H), 4.11 (t, 2H), 6.96 (d, 2H), 7.13 (d, 2H), 7.81 (m, 4H) (DMSO-d
6)
53) 4-{5-[4-(2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.35 (d, 6H), 1.56 (brm, 2H), 1.78 (brm, 4H), 3.30 (m, 1H), 4.02 (m, 4H), 6.95 (m, 4H), 7.77 (s, 1H), 7.83 (m, 4H) (DMSO-d
6)
54) 4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (brm, 2H), 1.79 (brm, 4H), 2.68 (s, 3H), 4.01 (t, 2H), 4.11 (t, 2H), 6.96 (d, 2H), 7.12 (d, 2H), 7.73 (s, 1H), 7.81 (m, 4H) (DMSO-d
6)
55) 4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.32 (d, 6H), 1.59 (m, 2H), 1.79 (m, 4H), 2.47 (s, 3H), 3.21 (m, 1H), 4.02 (t, 2H), 4.09 (t, 2H), 6.98 (d, 2H), 7.09 (d, 2H), 7.55 (d, 2H), 7.74 (d, 2H) (DMSO-d
6)
56) 4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.29 (t, 3H), 1.59 (m, 2H), 1.81 (brm, 4H), 2.95 (q, 2H), 4.04 (t, 2H), 4.11 (t, 2H0,7.03 (d, 2H), 7.15 (d, 2H), 7.47 (m, 3H), 7.59 (d, 2H), 7.84 (d, 2H), 7.91 (m, 2H) (DMSO-d
6)
57) N-hydroxyl-4-{5-[4-(2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.77 (m, 4H), 3.98 (m, 4H), 5.72 (s, 2H), 6.80-6.99 (m, 7H), 7.58 (d, 2H), 7.69 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
58) N-hydroxyl-4-{5-[4-(2-amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (m, 2H), 1.77 (m, 4H), 2.27 (s, 3H), 3.99 (m, 4H), 5.72 (s, 2H), 6.70 (s, 2H), 6.91 (m, 4H), 7.45 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
59) N-hydroxyl-4-{5-[4-(2-guanidine radicals-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.78 (m, 2H), 2.30 (s, 3H), 4.00 (t, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
60) N-hydroxyl-4-{5-[4-(2-amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.15 (t, 3H), 1.57 (m, 2H), 1.76 (m, 4H), 2.68 (q, 2H), 3.99 (m, 4H), 5.69 (s, 2H), 6.72 (s, 2H), 6.91 (m, 4H), 7.39 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
61) N-hydroxyl-4-{5-[4-(2-amino-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.17 (d, 6H), 1.56 (m, 2H), 1.78 (m, 3H), 3.20 (m, 1H), 4.00 (m, 4H), 5.70 (brm, 1H), 6.91 (m, 4H), 7.35 (m, 2H), 7.57 (m, 2H), 9.43 (s, 1H) (DMSO-d
6)
62) N-hydroxyl-4-{5-[4-(2-guanidine radicals-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.17 (d, 6H), 1.56 (brm, 2H), 1.77 (brm, 4H), 3.22 (m, 1H), 4.00 (m, 4H), 5.71 (s, 2H), 6.93 (m, 5H), 7.38 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
63) N-hydroxyl-4-{5-[4-(2-amino-5-butyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.83 (t, 3H), 1.30 (m, 2H), 1.48 (m, 2H), 1.56 (m, 2H), 1.77 (brm, 4H), 2.65 (t, 2H), 3.99 (m, 4H), 5.73 (brs, 2H), 6.72 (s, 2H), 6.91 (m, 4H), 7.38 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
64) N-hydroxyl-4-{5-[4-(5-butyl-2-guanidine radicals-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.83 (t, 3H), 1.28 (m, 2H), 1.53 (m, 4H), 1.78 (m, 4H), 2.69 (m, 2H), 4.00 (m, 4H), 5.73 (brs, 2H), 6.91 (d, 2H), 6.95 (d, 2H), 7.42 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
65) N-hydroxyl-4-{5-[4-(2-amino-5-benzyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.55 (brm,, 2H), 1.77 (brm, 4H), 3.98 (m, 4H), 4.02 (s, 1H), 5.79 (s, 2H), 6.79 (s, 2H), 6.91 (m, 4H), 7.19 (m, 3H), 7.29 (m, 2H), 7.43 (d, 2H), 7.57 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
66) N-hydroxyl-4-{5-[4-(5-benzyl-2-guanidine radicals-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.55 (m, 2H), 1.77 (brm, 4H), 4.99 (m, 4H), 4.05 (s, 2H), 5.71 (s, 2H), 4.92 (m, 4H), 7.19 (m, 3H), 7.29 (m, 2H), 7.45 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
67) N-hydroxyl-4-{5-[4-(2-amino-5-methyl cyclopentane-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.09 (brm, 2H), 1.48 (brm, 4H), 1.56 (m, 2H), 1.69 (m, 2H), 1.77 (brm, 4H), 1.97 (m, 1H), 2.65 (d, 2H), 3.98 (m, 4H), 5.70 (s, 2H), 6.72 (s, 2H), 6.90 (m, 4H), 7.38 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
68) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.11 (m, 2H), 1.43-1.78 (brm, 17H), 2.04 (m, 4H), 2.24 (m, 2H), 2.85 (m, 5H), 4.01 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
69) N-hydroxyl-4-{5-[4-(2-(isobutyryl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.11 (d, 6H), 1.59 (m, 2H), 1.79 (m, 4H), 2.42 (s, 3H), 2.72 (m, 1H), 4.02 (m, 4H), 5.72 (s, 2H), 6.93 (d, 2H), 7.00 (d, 2H), 7.56 (m, 4H), 9.45 (s, 1H), 12.00 (s, 1H) (DMSO-d
6)
70) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.25 (d, 6H), 1.58 (m, 2H), 1.80 (m, 4H), 2.50 (m, 4H), 3.33 (m, 1H), 3.60 (m, 4H), 3.76 (s, 2H), 4.01 (m, 4H), 5.70 (s, 2H), 7.00 (m, 4H), 7.45 (d, 2H), 7.60 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
71) N-hydroxyl-4-{5-[4-(2-amino methyl-5-benzyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.78 (brm, 4H), 3.92 (s, 2H), 4.00 (m, 4H), 4.21 (s, 2H), 5.70 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H), 7.21 (m, 3H), 7.30 (m, 2H), 7.52 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
72) N-hydroxyl-4-{5-[4-(5-methyl-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (t, 3H), 1.42 (m, 2H), 1.56 (m, 2H), 1.67 (m, 2H), 1.78 (brm, 4H), 2.00 (m, 4H), 2.24 (m, 2H), 2.46 (s, 3H), 2.89 (m, 3H), 4.00 (m, 4H), 5.71 (m, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.56 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
73) N-hydroxyl-4-{5-[4-(5-isopropyl-2-aminomethyl-1,2,3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.25 (d, 6H), 1.57 (m, 2H), 1.79 (m, 4H), 3.35 (m, 1H), and 3.96-4.04 (m, 6H), 5.74 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.43 (d, 2H), 7.58 (d, 2H) (DMSO-d
6)
74) N-hydroxyl-4-{5-[4-(5-vinyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.61 (m, 2H), 1.81 (m, 4H), 2.66 (s, 3H), 3.95 (m, 4H), 5.16 (S, 1H), 5.17 (d, 1H), 5.42 (d, 1H), 6.84 (m, 3H), 6.92 (d, 2H), 7.51 (d-d, 4H) (CDCl
3)
75) N-hydroxyl-4-{5-[4-(5-hydroxymethyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.63 (s, 3H), 4.01 (m, 4H), 4.12 (t, 1H), 4.67 (m, 2H), 5.70 (brs, 2H), 6.98 (m, 2H), 7.50 (m, 2H), 7.58 (m, 2H), 8.23 (s, 1H)
76) N-hydroxyl-4-{5-[4-(5-methoxy-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (m, 2H), 1.80 (m, 4H), 2.65 (s, 3H), 3.32 (s, 3H), 4.01 (m, 4H), 4.58 (s, 2H), 6.93 (m, 2H), 7.01 (m, 2H), 7.56 (m, 4H), 9.45 (brs, 1H)
77) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (m, 2H), 1.79 (m, 4H), 3.36 (m, 2H), 3.77 (m, 2H), 4.00 (m, 4H), 5.73 (s, 2H), 6.91 (m, 4H), 7.42 (d, 2H), 7.58 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
78) N-hydroxyl-4-{5-[4-(5-vinyl-2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 4.01 (m, 4H), 6.82-7.75 (m, 11H) (DMSO-d
6)
79) N-hydroxyl-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.59 (m, 2H), 1.81 (m, 4H), 4.05 (m, 4H), 5.44 (d, 1H), 5.71 (d, 1H), 5.85 (brs, 2H), 6.94 (m, 3H), 7.07 (m, 2H), 7.61 (m, 4H), 8.33 (m, 1H), 8.68 (m, 1H), 9.16 (brs, 1H), 9.52 (brs, 1H) (DMSO-d
6)
80) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.60 (m, 2H), 1.81 (m, 4H), 3.44 (m, 2H), 3.94 (m, 2H), 4.02-4.06 (m, 4H), 5.75 (brs, 2H), 6.91 (m, 2H), 7.06 (m, 2H), 7.61 (m, 4H), 8.30 (m, 1H), 8.68 (m, 1H), 9.13 (m, 1H), 9.46 (m, 1H) (DMSO-d
6)
81) N-hydroxyl-4-{5-[4-(2-amino-5-cyclopenta-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.40 (m, 2H), 1.55-1.59 (m, 4H), and 1.77-1.81 (m, 6H), 2.01 (m, 2H), and 3.22-3.31 (m, 1H), 4.00-4.02 (m, 4H), 5.72 (s, 2H), 6.92 (m, 4H), 7.57 (d, 2H), 7.83 (d, 2H) (DMSO-d
6)
82) N-hydroxyl-4-{5-[4-(5-ethyl-2-aminomethyl-1,2,3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.21 (t, 3H), 1.58 (m, 2H), 1.78 (m, 4H), 2.85 (q, 2H), 3.93 (s, 2H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H), 7.48 (d, 2H), 7.58 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
83) N-hydroxyl-4-{5-[4-(5-isopropyl-2-(piperidines-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.25 (d, 6H), 1.57 (m, 2H), 1.80 (m, 4H), 1.91 (m, 2H), 2.17 (m, 2H), 3.05 (m, 2H), 3.37 (m, 4H), 4.02-4.09 (m, 4H), 7.00 (d, 2H), 7.13 (d, 2H), 7.44 (d, 2H), 7.67 (d, 2H) (DMSO-d
6)
84) N-hydroxyl-4-{5-[4-(2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.17 (t, 3H), 1.55 (brm, 2H), 1.77 (brm, 2H), 3.25 (m, 2H), 3.99 (m, 4H), 5.73 (s, 2H), 6.84 (s, 1H), 6.90 (m, 4H), 7.57 (d, 2H), 7.71 (d, 2H) (DMSO-d
6)
85) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.20 (t, 3H), 1.55 (brm, 2H), 1.77 (brm, 4H), 3.02 (q, 2H), 4.00 (m, 4H), 5.77 (brm, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.00 (s, 1H), 7.57 (d, 2H), 7.65 (d, 2H), 9.47 (brs, 1H), 12.86 (s, 1H) (DMSO-d
6)
86) N-hydroxyl-4-{5-[4-(5-methyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.77 (m, 4H), 2.29 (s, 3H), 2.77 (d, 3H), 3.99 (m, 4H), 5.72 (s, 2H), 6.91 (m, 4H), 7.22 (m, 1H), 7.48 (d, 2H), 7.50 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
87) N-hydroxyl-4-{5-[4-(2-ethylamino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.12 (t, 3H), 1.56 (m, 2H), 1.78 (m, 4H), 2.28 (s, 3H), 3.18 (p, 2H), 3.99 (t, 4H), 5.72 (s, 2H), 6.94 (m, 4H), 7.27 (t, 1H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
88) N-hydroxyl-4-{5-[4-(5-methyl-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.89 (t, 3H), 1.54 (m, 4H), 1.78 (m, 4H), 2.28 (s, 3H), 3.12 (m, 2H), 3.99 (m, 4H), 5.72 (s, 1H), 6.92 (m, 4H), 7.32 (t, 1H), 7.47 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
89) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.15 (m, 2H), 1.57 (brm, 6H), 1.77 (brm, 6H), 2.10 (m, 1H), 2.85 (d, 2H), 4.00 (m, 4H), 5.72 (brs, 2H), 6.91 (d, 2H), 7.00 (d, 2H), 7.51 (d, 2H), 7.58 (d, 2H), 7.38 (m, 1H), 8.40 (d, 1H), 8.77 (d, 1H), 9.19 (s, 1H), 9.44 (s, 1H), 12.83 (s, 1H) (DMSO-d
6)
90) N-hydroxyl-4-{5-[4-(2-glycoloyl amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (brm, 2H), 1.78 (brm, 4H), 2.42 (s, 3H), 4.01 (m, 4H), 4.10 (d, 2H), 5.47 (t, 1H), 5.73 (brs, 2H), 6.92 (d, 2H), 6.98 (d, 2H), 7.55 (m, 4H), 9.45 (s, 1H), 11.67 (s, 1H) (DMSO-d
6)
91) N-hydroxyl-4-{5-[4-(5-methyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (brm, 4H), 1.79 (brm, 4H), 2.48 (s, 3H), 4.02 (m, 4H), 5.73 (brm, 2H), 6.91 (d, 2H), 7.01 (d, 2H), 7.58 (m, 4H), 7.98 (dd, 2H), 8.78 (dd, 2H), 9.45 (s, 1H) (DMSO-d
6)
92) N-hydroxyl-4-{5-[4-(5-methyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.46 (s, 3H), 4.01 (m, 4H), 5.74 (s, 2H), 6.91 (d, 2H), 7.00 (d, 2H), 7.57 (m, 4H), 8.41 (d, 1H), 8.77 (d, 1H), 9.20 (d, 1H), 9.46 (brs, 1H), 12.80 (brs, 1H) (DMSO-d
6)
93) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 0.94 (t, 3H), 1.56 (m, 2H), 1.78 (brm, 4H), 2.18 (s, 3H), 2.98 (q, 2H), 4.01 (m, 4H), 5.73 (s, 2H), 6.90 (d, 2H), 7.01 (d, 2H), 7.38 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H), 12.52 (s, 1H) (DMSO-d
6)
94) N-hydroxyl-4-{5-[4-(2-(2-methoxy ethyl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.30 (s, 3H), 3.26 (s, 3H), 3.39 (m, 2H), 3.37 (m, 2H), 4.01 (m, 4H), 5.71 (s, 2H), 6.90 (d, 2H), 6.96 (d, 2H), 7.48 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
95) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.13 (t, 3H), 1.21 (t, 3H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.59 (q, 2H), 2.99 (q, 2H), 4.01 (m, 4H), 5.70 (s, 2H), 6.90 (s, 2H), 7.01 (d, 2H), 7.35 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H), 12.50 (brs, 1H) (DMSO-d
6)
96) N-hydroxyl-4-{5-[4-(5-ethyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.15 (t, 3H), 1.57 (m, 2H), 1.78 (m, 4H), 2.70 (q, 2H), 2.78 (d, 3H), 3.99 (m, 4H), 5.80 (brs, 2H), 6.92 (m, 4H), 7.25 (q, 1H), 7.42 (d, 2H), 7.58 (d, 2H), 9.48 (s, 1H) (DMSO-d
6)
97) N-hydroxyl-4-{5-[4-(5-ethyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.41 (m, 6H), 1.57 (m, 2H), 1.78 (t, 4H), 2.69 (q, 2H), 3.19 (q, 2H), 3.99 (t, 4H), 5.69 (s, 2H), 6.92 (m, 4H), 7.30 (t, 1H), 7.41 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
98) N-hydroxyl-4-{5-[4-(5-ethyl-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.89 (t, 3H), 1.15 (t, 3H), 1.55 (brm, 4H), 1.77 (brm, 4H), 2.68 (q, 2H), 3.12 (m, 2H), 3.98 (m, 4H), 5.72 (s, 2H), 6.92 (m, 4H), 7.35 (t, 1H), 7.40 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
99) N-hydroxyl-4-{5-[4-(5-ethyl-2-methoxyl group acetylaminohydroxyphenylarsonic acid 1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.23 (t, 3H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.84 (q, 2H), 3.33 (s, 3H), 4.00 (m, 4H), 4.11 (s, 2H), 5.70 (s, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.82 (d, 2H), 9.43 (s, 1H), 11.96 (s, 1H) (DMSO-d
6)
100) N-hydroxyl-4-{5-[4-(5-ethyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.26 (t, 3H), 1.57 (m, 2H), 1.79 (brm, 4H), 2.88 (q, 2H), 4.00 (m, 4H), 5.74 (s, 2H), 6.91 (d, 2H), 7.01 (d, 2H), 7.52 (d, 2H), 7.55 (d, 2H), 7.98 (d, 2H), 8.79 (d, 2H), 9.45 (s, 1H), 12.92 (s, 1H) (DMSO-d
6)
101) N-hydroxyl-4-{5-[4-(5-ethyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.26 (t, 3H), 1.57 (brm, 2H), 1.79 (brm, 4H), 2.88 (q, 2H), 4.00 (m, 4H), 5.71 (brs, 2H), 6.91 (d, 2H), 7.01 (d, 2H), 7.56 (m, 5H), 8.40 (m, 1H), 8.77 (dd, 1H), 9.20 (d, 1H), 9.43 (s, 1H), 12.82 (s, 1H) (DMSO-d
6)
102) N-hydroxyl-4-{5-[4-(5-ethyl-2-(2-methoxy ethyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.14 (t, 3H), 1.60 (m, 2H), 1.78 (m, 4H), 2.69 (m, 2H), 3.26 (s, 3H), 3.40 (m, 2H), 3.38 (m, 2H), 4.02 (m, 4H), 5.67 (s, 2H), 5.75 (s, 1H), 6.90～7.00 (m, 4H), 7.40 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
103) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.17 (d, 6H), 1.56 (brm, 2H), 1.77 (brm, 2H), 2.77 (d, 3H), 3.21 (m, 1H), 5.72 (s, 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.25 (m, 1H), 7.38 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
104) N-hydroxyl-4-{5-[4-(2-ethylamino-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.85 (m, 3H), 1.17 (d, 6H), 1.58 (m, 2H), 1.82 (m, 4H), 3.20 (m, 3H), 4.04 (m, 4H), 6.95 (m, 4H), 7.39 (m, 2H), 7.82 (m, 2H) (DMSO-d
6)
105) N-hydroxyl-4-{5-[4-(5-butyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.83 (t, 3H), 1.30 (m, 2H), 1.48 (m, 2H), 1.56 (m, 2H), 1.77 (m, 4H), 2.67 (t, 2H), 2.78 (d, 3H), 4.01 (m, 4H), 5.72 (brs, 2H), 6.92 (m, 4H), 7.26 (m, 1H), 7.41 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
106) N-hydroxyl-4-{5-[4-(5-butyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.83 (t, 3H), 1.13 (t, 3H), 1.28 (m, 2H), 1.53 (m, 4H), 1.78 (m, 4H), 2.64 (t, 2H), 3.18 (m, 2H), 3.99 (m, 4H), 5.75 (brs, 2H), 6.92 (m, 4H), 7.31 (t, 1H), 7.40 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
107) N-hydroxyl-4-{5-[4-(5-benzyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.55 (m, 2H), 1.76 (brm, 4H), 2.77 (d, 3H), 3.98 (m, 4H), 4.03 (s, 2H), 5.72 (brs, 2H), 6.91 (m, 4H), 7.20 (m, 3H), 7.29 (m, 3H), 7.46 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
108) N-hydroxyl-4-{5-[4-(5-benzyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.14 (t, 3H), 1.55 (m, 2H), 1.77 (brm, 4H), 3.18 (m, 2H), 4.00 (m, 4H), 4.03 (s, 2H), 6.94 (m, 4H), 7.17 (m, 3H), 7.29 (m, 2H), 7.39 (t, 1H), 7.45 (d, 2H), 7.58 (d, 2H), 9.64 (s, 1H) (DMSO-d
6)
109) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.10 (brm, 2H), 1.49 (brm, 4H), 1.56 (m, 2H), 1.69 (m, 2H), 1.78 (m, 4H), 1.97 (m, 1H), 2.66 (d, 2H), 2.78 (d, 3H), 3.99 (m, 4H), 5.71 (s, 2H), 6.92 (m, 4H), 7.25 (m, 1H), 7.40 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
110) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.13 (m, 5H), 1.49 (m, 6H), 1.69 (m, 2H), 1.77 (m, 4H), 1.97 (m, 1H), 2.66 (d, 2H), 3.19 (m, 2H), 3.99 (m, 4H), 5.70 (s, 2H), 6.91 (m, 4H), 7.29 (t, 1H), 7.40 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
111) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.88 (t, 3H), 1.10 (brm, 2H), 1.55 (brm, 8H), 1.77 (brm, 6H), 1.97 (m, 1H), 2.65 (d, 2H), 3.11 (m, 2H), 3.99 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.92 (d, 2H), 7.33 (t, 1H), 7.39 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
112) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.55 (m, 2H), 1.49 (brm, 6H), 1.77 (brm, 6H), 2.10 (m, 1H), 2.86 (d, 2H), 4.00 (m, 4H), 5.74 (s, 2H), 6.91 (d, 2H), 7.01 (d, 2H), 7.51 (d, 2H), 7.58 (d, 2H), 7.97 (d, 2H), 8.79 (d, 2H), 9.46 (s, 1H), 12.91 (s, 1H) (DMSO-d
6)
113) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.89 (t, 3H), 1.55-1.62 (m, 8H), 1.77-1.80 (m, 8H), and 3.31-3.37 (m, 3H), 4.00-4.02 (m, 4H), and 6.90-7.05 (m, 4H), 7.39-7.80 (m, 4H) (DMSO-d
6)
114) N-hydroxyl-4-{5-[4-(5-isopropyl-2-[(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.82 (d, 6H), 1.17-1.25 (m, 2H), 1.78-1.80 (m, 4H), 3.25 (m, 1H), 3.37 (s, 2H), 4.01 (m, 4H), 6.94-7.83 (m, 12H) (DMSO-d
6)
115) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.81 (s, 3H), 3.13 (m, 2H), 3.78 (m, 2H), 4.01 (m, 4H), 5.73 (m, 2H), 6.93 (m, 4H), 7.44 (m, 2H), 7.59 (m, 2H), 9.46 (s, 1H) (DMSO-d
6)
116) N-hydroxyl-4-{5-[4-(2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.57 (m, 2H), 1.77-1.81 (m, 4H), 2.86 (d, 3H), 3.99-4.01 (m, 4H), 5.72 (s, 2H), and 6.88-6.93 (m, 5H), 7.59 (d, 2H), 7.74 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
117) N-hydroxyl-4-{5-[4-(5-ethyl-2-(pyridin-3-yl methyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.24 (t, 3H), 1.57 (m, 2H), 1.79 (m, 4H), 2.87 (q, 2H), 3.79 (s, 2H), 3.91 (s, 2H), 4.02 (m, 4H), 5.74 (s, 1H), 6.94 (d-d, 4H), 7.35 (m, 1H), 7.48 (d, 2H), 7.77 (d, 1H), 7.82 (d, 2H), 8.45 (d, 1H), 8.54 (s, 1H) (DMSO-d
6)
118) N-hydroxyl-4-{5-[4-(2-(ethylsulfonyl-methyl-amino)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.20 (t, 3H), 1.57 (m; 2H), 1.79 (m, 4H), 3.50 (m; 5H), 4.01 (m, 4H), 5.71 (s; 2H), 6.96 (m, 4H); 7.55 (m, 2H), 7.81 (m; 3H), 9.44 (s, 1H) (DMSO-d
6)
119) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.56 (brm, 2H), 1.78 (brm, 4H), 2.43 (m, 4H), 2.55 (m, 2H), 3.05 (s, 3H), 3.52 (m, 4H), 3.60 (m, 2H), 3.99 (brm, 4H), 5.70 (s, 2H), 6.91 (m, 4H), 6.95 (s, 1H), 7.57 (d, 2H), 7.73 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
120) N-hydroxyl-4-[5-(4-{2-[(2-ethoxy)-methyl-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine 1.56 (m, 2H), 1.78 (brm, 4H), 2.31 (s, 3H), 3.02 (s, 3H), 3.44 (t, 2H), 3.59 (q, 2H), 4.00 (t, 4H), 4.79 (t, 1H), 5.71 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
121) N-hydroxyl-4-[5-(4-{2-[ethyl-(2-ethoxy)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine 1.14 (t, 3H), 1.56 (m, 2H), 1.78 (brm, 4H), 2.31 (s, 3H), 3.41 (m, 4H), 3.58 (m, 2H), 4.00 (m, 4H), 4.82 (t, 1H), 5.73 (s, 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
122) N-hydroxyl-4-[5-(4-{2-[two-(2-methoxy ethyl)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine 1.59 (m, 2H), 1.79 (m, 4H), 2.32 (s, 3H), 3.26 (s, 6H), 3.55 (s, 8H), 4.03 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 6.95 (d, 2H), 7.49 (d, 2H), 7.82 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
123) N-hydroxyl-4-[5-(4-{5-methyl-2-[methyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.56 (m, 2H), 1.77 (brm, 4H), 2.32 (s, 3H), 2.41 (brm, 4H), 2.51 (m, 2H), 2.99 (s, 3H), 3.51 (brm, 4H), 3.99 (t, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
124) N-hydroxyl-4-[5-(4-{2-[ethyl-1-(2-morpholino ethyl)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine 1.15 (t, 3H), 1.56 (m, 2H), 1.77 (brm, 4H), 2.31 (s, 3H), 2.42 (brm, 4H), 2.52 (m, 2H), 3.40 (m, 2H), 3.49 (m, 2H), 3.54 (brm, 4H), 3.99 (m, 4H), 5.71 (brs, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
125) N-hydroxyl-4-{5-(4-[2-(benzyl-methyl-amino)-5-methyl isophthalic acid, 3-thiazole-4-yl] phenoxy group) amoxy }-benzamidine 1.57 (m, 2H), 1.77 (brm, 4H), 2.29 (s, 3H), 2.98 (s, 3H), 3.99 (m, 4H), 4.64 (s, 2H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.30 (m, 5H), 7.51 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
126) N-hydroxyl-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine 1.56 (brm, 2H), 1.77 (brm, 4H), 2.33 (s, 3H), 3.00 (s, 3H), 4.00 (m, 4H), 4.68 (s, 2H), 5.71 (s, 2H), 6.90 (d, 2H), 6.95 (d, 2H), 7.36 (m, 1H), 7.51 (d, 2H), 7.57 (d, 2H), 7.72 (d, 1H), 8.48 (d, 1H), 8.55 (s, 1H), 9.44 (s, 1H) (DMSO-d
6)
127) N-hydroxyl-4-[5-{4-[2-(benzyl-ethyl-amino)-5-methyl isophthalic acid, 3-thiazole-4-yl] phenoxy group } amoxy]-benzamidine 1.12 (t, 3H), 1.56 (brm, 2H), 1.77 (brm, 4H), 2,31 (s, 3H), 3.40 (q, 2H), 3.99 (m, 4H), 4.62 (s, 2H), 5.71 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.26 (m, 1H), 7.31 (m, 4H), 7.50 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
128) N-hydroxyl-4-[5-(4-{2-[two-(2-ethoxy)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine 1.57 (m, 2H), 1.80 (m, 4H), 2.24 (s, 3H), 3.0～4.5 (brs, 2H), 3.67 (s, 8H), 4.05 (m, 4H), 5.72 (s, 2H), 7.03 (d, 2H), 7.12 (d, 2H), 7.44 (d, 2H), 7.82 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
129) N-hydroxyl-4-[5-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine 1.17 (t, 3H), 1.57 (m, 2H), 1.78 (brm, 4H), 2.72 (q, 2H), 3.03 (s, 3H), 3.45 (t, 2H), 3.59 (m, 2H), 4.01 (m, 4H), 4.79 (t, 1H), 5.70 (s, 2H), 6.90 (d, 2H), 6.96 (d, 2H), 7.42 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
130) N-hydroxyl-4-[5-(4-{5-ethyl-2-[ethyl-(2-ethoxy)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.15 (m, 6H), 1.56 (brm, 2H), 1.76 (brm, 4H), 2.71 (q, 2H), 3.43 (m, 4H), 4.00 (t, 4H), 4.81 (t, 1H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.42 (d, 2H), 7.81 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
131) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.17 (t, 3H), 1.56 (m, 2H), 1.77 (m, 4H), 2.41 (brm, 4H), 2.51 (m, 2H), 2.72 (q, 2H), 3.00 (s, 3H), 3.53 (brm, 6H), 3.99 (t, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.42 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
132) N-hydroxyl-4-[5-(4-{5-ethyl-2-[ethyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.15 (m, 6H), 1.56 (m, 2H), 1.78 (brm, 4H), 2.42 (brm, 4H), 2.51 (m, 2H), 2.70 (q, 2H), 3.40 (m, 2H), 3.48 (m, 2H), 3.53 (brm, 4H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.42 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
133) N-hydroxyl-4-[5-{4-[2-(benzyl-methyl-amino)-5-ethyl-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine 1.17 (t, 3H), 1.57 (brm, 2H), 1.77 (brm, 4H), 2.74 (q, 2H), 2.98 (s, 3H), 3.99 (m, 4H), 4.64 (s, 2H), 5.71 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.30 (m, 5H), 7.45 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
134) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.18 (t, 3H), 1.56 (m, 2H), 1.77 (brm, 4H), 2.74 (q, 2H), 3.01 (s, 3H), 3.99 (t, 4H), 4.69 (s, 2H), 5.70 (s, 2H), 5.90 (d, 2H), 6.95 (d, 2H), 7.37 (m, 1H), 7.45 (d, 2H), 7.57 (d, 2H), 7.72 (d, 1H), 8.47 (d, 1H), 8.55 (s, 1H), 9.43 (s, 1H) (DMSO-d
6)
135) N-hydroxyl-4-(5-{4-[2-(benzyl-ethyl-amino)-5-ethyl-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine 1.15 (m, 6H), 1.56 (m, 2H), 1.76 (brm, 4H), 2.73 (q, 2H), 3.41 (q, 2H), 3.99 (t, 4H), 4.63 (s, 2H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.25 (m, 1H), 7.32 (m, 4H), 7.44 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
136) N-hydroxyl-4-{5-(4-[5-ethyl-2-(ethyl-[pyridin-3-yl methyl] amino)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine 1.15 (m, 6H), 1.56 (m, 2H), 1.76 (m, 4H), 2.73 (q, 2H), 3.44 (q, 2H), 3.99 (t, 4H), 4.66 (s, 2H), 5.70 (s, 2H), 5.74 (s, 1H), 6.90 (d, 2H), 6.94 (d, 2H), 7.36 (m, 1H), 7.43 (d, 2H), 7.57 (d, 2H), 7.73 (d, 2H), 8.46 (d, 1H), 8.56 (d, 1H), 9.44 (s, 1H) (DMSO-d
6)
137) N-hydroxyl-4-[5-(4-{2-[two-(pyridin-3-yl methyl) amino]-5-ethyl-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.15 (t, 3H), 1.56 (brm, 2H), 1.79 (brm, 4H), 2.73 (q, 2H), 3.99 (t, 2H), 4.09 (t, 2H), 4.91 (s, 4H), 6.95 (d, 2H), 7.14 (d, 2H), 7.41 (d, 2H), 7.67 (d, 2H), 7.82 (m, 2H), 8.26 (m, 2H), 8.73 (m, 2H), 8.79 (s, 2H) (DMSO-d
6)
138) N-hydroxyl-4-{5-[4-(2-dipropyl amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86 (t, 6H), 1.17 (t, 3H), 1.59 (brm, 6H), 1.77 (brm, 4H), 2.71 (q, 2H), 3.30 (m, 4H), 3.99 (m, 4H), 5.71 (brs, 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.42 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
139) N-hydroxyl-4-[5-(4-{2-[two-(2-ethoxy) amino]-5-ethyl-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.17 (t, 3H), 1.57 (brm, 2H), 1.77 (brm, 4H), 2.71 (q, 2H), 3.48 (m, 4H), 3.63 (m, 4H), 3.99 (m, 4H), 4.87 (t, 2H), 5.69 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.41 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
140) N-hydroxyl-4-[5-(4-{2-[(2-ethoxy)-methyl-amino]-5-isopropyl-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine 1.26 (d, 6H), 1.57 (m, 2H), 1.79 (m, 4H), 3.33 (m, 5H), 3.47 (m, 1H), 3.61 (m, 2H), 4.00 (m, 4H), 5.72 (s, 2H), 6.90～7.00 (b, 4H), 7.45 (d, 2H), 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
141) N-hydroxyl-4-[5-(4-{5-isopropyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.20 (d, 6H), 1.56 (m, 2H), 1.79 (m, 4H), 3.01 (s, 3H), 3.24 (m, 1H), 3.32 (s, 2H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (b, 4H), 7.40 (b, 3H), 7.57 (d, 2H), 7.92 (m, 1H), 8.47～8.56 (b, 2H), 9.43 (s, 1H) (DMSO-d
6)
142) N-hydroxyl-4-(5-{4-[2-(ethylsulfonyl-methyl-amino)-5-isopropyl-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine 1.24 (m, 9H), 1.56 (brm, 2H); 1.79 (brm, 4H), 3.41 (s, 3H); 3.46 (q, 2H), 4.00 (m, 4H); 5.74 (s, 2H), 6.91 (d, 2H); 6.95 (d, 2H), 7.45 (d, 2H); 7.57 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
143) N-hydroxyl-4-[5-(4-{5-butyl-2-[(2-ethoxy)-methyl-amino]-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine 0.84 (t, 3H), 1.32 (m, 2H), 1.54 (m, 4H), 1.78 (m, 4H), 2.70 (t, 2H), 3.303 (s, 3H), 3.46 (t, 2H), 3.54 (m, 2H), 4.01 (m, 4H), 5.71 (s, 2H), 6.91 (d, 2H), 6.94 (d, 2H), 7.42 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
144) N-hydroxyl-4-[5-(4-{5-butyl-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 0.83 (t, 3H), 1.30 (m, 2H), 1.53 (m, 4H), 1.77 (brm, 4H), 2.42 (brm, 4H), 2.52 (m, 2H), 2.69 (m, 2H), 2.99 (s, 3H), 3.52 (brm, 6H), 4.00 (m, 4H), 5.72 (s, 2H), 6.92 (m, 4H), 7.41 (d, 2H), 7.57 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
145) N-hydroxyl-4-[5-(4-{5-butyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 0.82 (t, 3H), 1.29 (m, 2H), 1.52 (brm, 4H), 1.76 (brm, 4H), 2.70 (m, 2H), 3.00 (s, 3H), 3.98 (m, 4H), 4.68 (s, 2H), 5.76 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.37 (m, 1H), 7.44 (d, 2H), 7.58 (d, 2H), 7.72 (d, 1H), 8.47 (d, 1H), 8.55 (s, 1H), 9.48 (s, 1H) (DMSO-d
6)
146) N-hydroxyl-4-{5-[4-(5-butyl-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (m, 9H), 1.30 (m, 2H), 1.57 (m, 8H), 1.77 (brm, 4H), 2.68 (m, 2H), 3.33 (m, 4H), 4.00 (m, 4H), 5.70 (s, 2H), 6.90 (d, 2H), 6.94 (d, 2H), 7.41 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
147) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.10 (m, 2H), 1.51 (m, 6H), 1.76 (brm, 6H), 1.99 (m, 1H), 2.71 (d, 2H), 3.00 (s, 3H), 3.99 (t, 4H), 4.68 (s, 2H), 5.72 (s, 2H), 6.90 (d, 2H), 6.95 (d, 2H), 7.36 (m, 1H), 7.43 (d, 2H), 7.57 (d, 2H), 7.72 (d, 1H), 8.48 (d, 1H), 8.55 (s, 1H), 9.45 (s, 1H) (DMSO-d
6)
148) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.11 (brm, 2H), 1.52-1.56 (brm, 6H), 1.77 (brm, 6H), 2.0 (m, 1H), 2.69 (m, 2H), 3.00 (s, 3H), 3.33 (m, 4H), 3.55 (m, 6H), 4.00 (m, 4H), 5.81 (s, 2H), 6.93 (m, 4H), 7.40 (d, 2H), 7.57 (d, 2H), 9.50 (s, 1H) (DMSO-d
6)
149) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.85 (m, 6H), 1.08 (m, 2H), 1.46-1.77 (brm, 16H), 1.99 (m, 1H), 2.67 (d, 2H), 3.30 (m, 4H), 3.99 (m, 4H), 6.04 (s, 2H), 6.90 (d, 2H), 6.93 (d, 2H), 7.41 (d, 2H), 7.59 (d, 2H), 9.60 (s, 1H) (DMSO-d
6)
150) N-hydroxyl-4-{5-[4-(5-butyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84 (m, 3H), 1.14 (t, 6H), 1.30 (m, 2H), 1.55 (m, 4H), 1.77 (m, 4H), 2.69 (m, 2H), 3.40 (m, 4H), 3.98 (m, 4H), 5.73 (s, 2H), 6.92 (d-d, 4H), 7.43 (d, 2H), 7.60 (d, 2H), 9.49 (s, 1H) (DMSO-d
6)
151) N-hydroxyl-4-{5-[4-(5-butyl-2-ethylmethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.85 (t, 3H), 1.12 (t, 3H), 1.30 (m, 2H), 1.53 (m, 4H), 1.78 (m, 4H), 2.70 (m, 2H), 2.96 (s, 3H), 3.42 (m, 2H), 5.74 (s, 2H), 6.93 (m, 4H), 7.43d, 2H), 7.59 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
152) N-hydroxyl-4-{5-[4-(5-butyl-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.81 (t, 3H), 1.25 (m, 2H), 1.52 (m, 4H), 1.76 (m, 4H), 2.67 (m, 2H), 2.97 (s, 6H), 3.97 (m, 4H), 5.70 (s, 2H), 6.91 (d-d, 4H), 7.41 (d, 2H), 7.57 (d, 2H), 9.50 (s, 1H) (DMSO-d
6)
153) N-hydroxyl-4-[5-(4-{5-cyclopenta-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.56-1.59 (m, 6H), 1.73-1.81 (m, 6H), 2.00-2.10 (m, 2H), and 2.38-2.49 (m, 4H), 2.50-2.51 (m, 2H), 3.01 (s, 3H), 3.25 (m, 1H), 3.52--3.55 (m, 6H), 4.00-4.03 (m, 4H), 5.74 (s, 2H), 6.91-6.97 (m, 4H), 7.41 (d, 2H), 7.59 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
154) N-hydroxyl-4-[5-(4-{5-isobutyl group-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 0.88 (d, 6H), 1.78 (m, 2H), 1.80-1.82 (m, 5H), 2.43 (s, 3H), 2.50 (m, 2H), 2.53 (m, 2H), 3.01 (m, 2H), 3.18 (m, 2H), 3.54 (m, 6H), 4.02 (m, 4H), 5.76 (s, 2H), 6.94-6.97 (m, 4H), 7.41 (d, 2H), 7.60 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
155) N-hydroxyl-4-(5-{4-[5-(2-chloroethyl)-2-dimethylamino-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine 1.58-1.66 (m, 2H), 1.78-1.81 (m, 4H), 3.14 (s, 6H), 3.15 (t, 2H), 3.81 (t, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.91-6.98 (m, 4H), 7.46 (d, 2H), 7.59 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
156) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.86-0.88 (m, 6H), 1.58-1.61 (m, 10H), 1.78 (m, 8H), and 3.32-3.39 (m, 5H), 4.02-4.05 (m, 4H), 6.95-7.18 (m, 4H), 7.40 (d, 2H), 7.83 (d, 2H) (DMSO-d
6)
157) N-hydroxyl-4-{5-[4-(5-isopropyl-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.84-0.88 (m, 6H), 1.24 (d, 6H), and 1.57-1.63 (m, 6H), 1.77-1.79 (m, 4H), and 3.28-3.38 (m, 5H), 3.97-4.01 (m, 4H), 5.71 (s, 2H), 6.89-6.95 (m, 4H), 7.41-4.59 (m, 4H), 9.45 (s, 1H) (DMSO-d
6)
158) N-hydroxyl-4-{5-[4-(5-ethyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.15 (t, 3H), 1.23 (t, 6H), 1.58 (m, 2H), 1.79-1.83 (m, 4H), 2.51 (m, 2H), 3.60-3.64 (m, 4H), and 4.08-4.12 (m, 4H), 7.13-7.16 (m, 4H), 7.43 (d, 2H), 7.69 (d, 2H) (DMSO-d
6)
159) N-hydroxyl-4-[5-(4-{5-isopropyl-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine 1.22 (d, 6H), 1.56 (m, 2H), 1.78 (m, 4H), 2.43 (m, 4H), 2.55 (t, 2H), 3.05 (s, 3H), 3.34 (m, 1H), 3.51 (m, 4H), 3.61 (t, 2H), 3.99 (m, 4H), 5.70 (brs, 2H), 6.90 (m, 4H), 7.57 (m, 2H), 7.73 (m, 2H), 9.44 (brs, 1H) (DMSO-d
6)
160) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.12-1.16 (m, 8H), 1.56 (m, 6H), 1.78 (m, 6H), 1.98-2.00 (m, 1H), 2.68 (d, 2H), 3.38-3.40 (m, 4H), 4.00 (m, 4H), 5.89 (s, 2H), 6.91-6.95 (d-d, 4H), 7.42 (d, 2H), 7.59 (d, 2H), 9.53 (s, 1H) (DMSO-d
6)
161) N-hydroxyl-4-{5-[4-(5-isopropyl-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.20 (d, 6H), 1.56 (m, 2H), 1.78 (m, 4H), 2.98 (s, 6H), 3.34 (m, 1H), 3.98-4.01 (m, 4H), 5.77 (s, 2H), 6.90-6.96 (m, 4H), 7.39 (d, 2H), 7.58 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
162) N-hydroxyl-4-{5-[4-(5-isopropyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.14 (m, 6H), 1.20 (d, 6H), 1.56 (m, 2H), 1.78 (m, 4H), 3.30 (m, 1H), 3.40 (m, 4H), 5.84 (s, 2H), 6.91-7.59 (m, 8H), 9.51 (s, 1H) (DMSO-d
6)
163) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.10-1.18 (m, 2H), 1.44-1.57 (m, 6H), 1.70-1.79 (m, 6H), 1.98-2.01 (m, 1H), 2.69 (d, 2H), 2.98 (s, 6H), 3.97-4.02 (m, 4H), 5.77 (s, 2H), 6.90-6.94 (d-d, 4H), 7.42 (d, 2H), 7.59 (d, 2H), 9.48 (s, 1H) (DMSO-d
6)
164) N-hydroxyl-4-{5-[4-(5-methyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.63 (brm, 6H), 1.78 (brm, 4H), 3.60 (brm, 4H), 4.02 (t, 2H), 4.06 (t, 2H), 7.04 (d, 2H), 7.09 (d, 2H), 7.40 (d, 2H), 7.66 (d, 2H) (DMSD-d
6+ TFA-d
1)
165) N-hydroxyl-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.78 (brm, 4H), 2.21 (s, 3H), 3.60 (brm, 4H), 3.74 (brm, 4H), 4.02 (t, 2H), 4.05 (t, 2H), 7.03 (d, 2H), 7.09 (d, 2H), 7.40 (d, 2H), 7.65 (d, 2H) (DMSD-d
6+ TFA-d
1)
166) N-hydroxyl-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.09 (t, 3H), 1.55 (m, 2H), 1.61 (brm, 6H), 1.77 (brm, 4H), 2.56 (q, 2H), 3.59 (brm, 4H), 4.00 (t, 2H), 4.03 (t, 2H), 7.01 (d, 2H), 7.06 (d, 2H), 7.34 (d, 2H), 7.64 (d, 2H) (DMSD-d
6+ TFA-d
1)
167) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.01 (brm, 2H), 1.43 (brm, 4H), 1.56 (brm, 2H), 1.63 (brm, 8H), 1.78 (brm, 4H), 1.94 (m, 1H), 2.56 (d, 2H), 3.61 (brm, 4H), 4.05 (m, 4H), 7.04 (d, 2H), 7.10 (d, 2H), 7.36 (d, 2H), 7.66 (d, 2H) (DMSD-d
6+ TFA-d
1)
168) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.02 (brm, 2H), 1.43 (brm, 4H), 1.56 (brm, 2H), 1.66 (brm, 2H), 1,78 (brm, 4H), 1.94 (m, 1H), 2.58 (d, 2H), 3.61 (brm, 4H), 3.74 (brm, 4H), 4.05 (m, 4H), 7.04 (d, 2H), 7.09 (d, 2H), 7.36 (d, 2H), 7.65 (d, 2H) (DMSD-d
6+ TFA-d
1)
169) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.22 (d, 6H), 1.58 (m, 2H), 1.78 (m, 4H), 3.26 (m, 1H), 3.35 (m, 4H), 3.70 (m, 4H), 4.02 (m, 4H), 5.71 (brs, 2H), 6.95 (m, 4H), 7.40 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
170) N-hydroxyl-4-{5-(4-[5-methyl cyclopentane-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine 1.11 (brm, 2H), 1.52-1.56 (brm, 6H), 1.77 (brm, 6H), 2.00 (m, 1H), 2.50 (m, 2H), 2.69 (m, 2H), 3.00 (s, 3H), 3.33 (m, 4H), 3.55 (m, 6H), 4.00 (m, 4H), 5.81 (brs, 2H), 6.93 (m, 4H), 7.40 (d, 2H), 7.57 (d, 2H), 9.50 (brs, 1H) (DMSO-d
6)
171) N-hydroxyl-4-{5-[4-(5-vinyl-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.55 (m, 2H), 1.79 (m, 4H), 3.17 (d, 1H), 3.35 (m, 4H), 3.42 (m, 2H), 3.72 (m, 4H), 4.01 (m, 4H), 5.74 (s, 2H), 6.92 (m, 4H), 7.60 (d, 2H), 7.77 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
172) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.58-1.60 (m, 7H), 1.74-1.81 (m, 7H), 2.51 (m, 4H), 3.34-3.36 (m, 1H), and 3.69-3.71 (m, 4H), 4.00-4.02 (m, 4H), 5.77 (s, 2H), 6.92-6.98 (m, 4H), 7.42 (d, 2H), 7.59 (d, 2H), 9.48 (s, 1H) (DMSO-d
6)
173) N-hydroxyl-4-{5-[4-(5-isobutyl group-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 0.88 (d, 6H), 1.59 (m, 2H), 1.80 (m, 4H), 2.60 (m, 1H), 3.35 (m, 8H), 3.70 (m, 2H), 4.01 (m, 4H), 5.77 (brs, 2H), 6.94 (m, 4H), 7.44 (m, 2H), 7.59 (m, 2H), 9.48 (brs, 1H) (DMSO-d
6)
174) N-hydroxyl-4-{5-(4-[5-ethyl-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine 1.19 (t, 3H), 1.50-1.59 (m, 2H), 1.80 (m, 4H), 2.21 (s, 3H), 2.41 (m, 4H), 3.36 (m, 6H), 4.01 (m, 4H), 5.71 (brs, 2H), 6.93-6.96 (m, 4H), 7.44 (m, 2H), 7.58 (m, 2H), 9.46 (brs, 1H) (DMSO-d
6)
175) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine 1.56 (m, 2H), 1.77 (m, 4H), 3.42 (m, 8H), 3.98 (m, 4H), 5.73 (brs, 2H), 6.81 (m, 2H), 6.92 (m, 2H), 7.11 (s, 1H), 7.27 (m, 2H), 7.77 (m, 2H), 8.35 (brs, 1H) (DMSO-d
6)
176) N-hydroxyl-4-{5-(4-[5-isopropyl-2-(4-methyl piperazine base)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine 1.23 (d, 6H), 1.58 (m, 2H), 1.77 (m, 4H), 2.21 (s, 3H), 2.40 (m, 4H), 2.21 (s, 3H), 2.40 (m, 4H), 3.33 (m, 1H), 3.35 (m, 4H), 4.00 (m, 4H), 5.71 (s, 2H), 6.93-6.97 (m, 4H), 7.40 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
177) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine 1.23 (d, 6H), 1.52 (m, 2H), 1.60 (m, 2H), 1.75 (m, 2H), 2.60 (s, 3H), 3.03 (m, 2H), 3.32 (m, 1H), 4.00 (t, 2H), 5.52 (s, 2H), 5.79 (m, 1H), 6.51 (d, 2H), 6.99 (d, 2H), 7.37 (d, 2H), 7.42 (d, 2H), 9.19 (s, 1H) (DMSO-d
6)
178) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-ethyoxyl-ethyoxyl)-benzamidine 1.25 (d, 6H), 2.64 (s, 3H), 3.33 (m, 1H), 3.90 (m, 4H), 4.14 (m, 4H), 6.90 (m, 4H), 7.40 (m, 4H) (CDCl
3)
179) N-hydroxyl-4-{3-hydroxyl-5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-3-methyl-amoxy }-benzamidine 1.26 (d, 6H), 1.32 (s, 3H), 2.06 (m, 4H), 2.65 (s, 3H), 3.33 (m, 1H), 4.20 (m, 4H), 5.01 (brs, 1H), 6.86 (d, 2H), 6.92 (d, 2H), 7.43 (d, 2H), 7.50 (d, 2H) (CDCl
3)
180) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-1-methyl-ethylamino-ethyoxyl)-benzamidine 1.10 (d, 3H), 1.23 (d, 6H), 2.59 (s, 3H), 2.96 (m, 2H), 3.05 (m, 1H), 3.32 (m, 2H), 3.90 (m, 2H), 4.04 (m, 2H), 5.71 (s, 2H), 6.92 (d, 2H), 6.99 (d, 2H), 7.43 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
181) N-hydroxyl-4-[3-(4-{3-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-propyl group-piperazine-1-yl)-propoxyl group]-benzamidine 1.23 (d, 6H), 1.85 (m, 4H), 2.40 (brm, 12H), 2.45 (s, 3H), 3.30 (m, 1H), 4.00 (m, 4H), 5.70 (s, 2H), 6.89 (d, 2H), 6.94 (d, 2H), 7.41 (d, 2H), 7.57 (d, 2H), 9.51 (s, 1H) (DMSO-d
6)
182) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-penta acyloxy (pentanoyl)-amino }-benzamidine 1.23 (d, 6H), 1.77 (brs, 4H), 2.40 (m, 2H), 2.60 (s, 3H), 3.33 (m, 1H), 4.02 (brs, 2H), 5.72 (s, 2H), 6.99 (d, 2H), 7.43 (d, 2H), 7.58-7.80 (m, 4H), 9.51 (s, 1H), 10.00 (s, 1H) (DMSO-d
6)
183) N-hydroxyl-4-({ 5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group }-methyl-amino)-benzamidine 1.22 (d, 6H), 1.43 (m, 2H), 1.55 (m, 2H), 1.76 (m, 2H), 2.59 (s, 3H), 2.89 (s, 3H), 3.33 (m, 1H), 3.98 (m, 2H), 5.55 (s, 2H), 6.64 (d, 2H), 6.97 (d, 2H), 7.45 (m, 4H), 9.23 (s, 1H) (DMSO-d
6)
184) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-2-butylene oxygen base }-benzamidine 1.23 (d, 6H), 2.60 (s, 3H), 3.31 (m, 1H), 4.63 (brs, 4H), 5.73 (s, 2H), 6.08 (brs, 2H), 6.94 (d, 2H), 7.01 (d, 2H), 7.44 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
185) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 1.23 (d, 6H), 2.64 (s, 3H), 3.32 (m, 1H), 5.15 (s, 2H), 5.23 (s, 2H), 5.72 (s, 2H), 7.07 (d, 2H), 7.19 (d, 2H), 7.46 (m, 6H), 7.73 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
186) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group]-ethylamino-ethyoxyl)-benzamidine 1.23 (d, 6H), 2.59 (s, 3H), 3.01 (brs, 4H), 3.33 (m, 1H), 4.09 (m, 4H), 5.71 (s, 2H), 6.92 (d, 2H), 7.00 (d, 2H), 7.43 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
187) N-hydroxyl-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.23 (d, 6H), 1.57 (m, 2H), 1.79 (m, 4H), 2.49 (s, 3H), 3.33 (m, 1H), 4.02 (m, 4H), 5.70 (s, 2H), 6.83 (m, 2H), 6.98 (d, 2H), 7.43 (m, 3H), 9.51 (s, 1H) (DMSO-d
6)
188) 2, N-dihydroxy-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.23 (d, 6H), 1.56 (m, 2H), 1.77 (m, 4H), 2.60 (s, 3H), 3.32 (m, 1H), 4.00 (m, 4H), 6.25 (s, 2H), 6.36 (m, 2H), 7.00 (d, 2H), 7.42 (d, 2H), 7.52 (d, 1H), 9.81 (s, 1H), 12.40 (s, 1H) (DMSO-d
6)
189) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-3-methoxyl group-benzamidine 1.24 (d, 6H), 1.58 (m, 2H), 1.80 (m, 4H), 2.61 (s, 3H), 3.35 (m, 1H), 3.77 (s, 3H) 4.02 (m, 4H), 5.77 (s, 2H), 6.98 (m, 3H), 7.26 (m, 2H), 7.46 (d, 2H), 9.48 (s, 1H) (DMSO-d
6)
190) N-hydroxyl-2-cyclohexyl amino-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.23 (m, 12H), 1.54 (m, 2H), 1.65 (m, 2H), 1.76 (m, 4H), 1.78 (m, 2H), 2.60 (s, 3H), 3.34 (m, 2H), 3.99 (m, 4H), 5.66 (s, 2H), 6.09 (m, 2H), 6.97 (d, 2H), 7.31 (d, 1H), 7.43 (d, 2H), 7.70 (d, 1H), 9.48 (s, 1H) (DMSO-d
6)
191) N-hydroxyl-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.17 (d, 6H), 1.57 (m, 2H), 1.79 (brs, 4H), 2.98 (m, 1H), 4.04 (m, 4H), 5.71 (s, 2H), 6.90 (m, 3H), 7.31 (d, 2H), 7.59 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
192) N-hydroxyl-2-fluoro-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.17 (d, 6H), 1.57 (brs, 2H), 1.79 (brs, 4H), 2.98 (m, 1H), 4.05 (m, 4H), 5.73 (s, 2H), 6.82～6.89 (m, 4H), 7.27～7.40 (m, 2H), 9.52 (s, 1H) (DMSO-d
6)
193) N-hydroxyl-4-{3-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] propoxyl group }-benzamidine 1.24 (d, 6H), 2.20 (m, 2H), 2.60 (s, 3H), 3.30 (m, 1H), 4.17 (m, 4H), 5.71 (s, 2H), 6.96 (d, 2H), 7.01 (d, 2H), 7.44 (d, 2H), 7.60 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
194) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] butoxy }-benzamidine 1.26 (d, 2H), 1.89 (m, 4H), 2.60 (s, 3H), 3.30 (m, 1H), 4.06 (m, 4H), 5.72 (s, 2H), 6.92 (d, 2H), 7.00 (d, 2H), 7.44 (d, 2H), 7.60 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
195) N-hydroxyl-3-{5-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine 1.24 (d, 6H), 1.50-1.62 (m, 3H), 1.77-1.79 (m, 2H), 2.65 (s, 3H), 3.02-3.04 (m, 1H), 3.37-3.44 (m, 3H), and 3.99-4.03 (m, 2H), 6.57-6.98 (m, 4H), 7.00 (d, 2H), 7.44 (d, 2H) (DMSO-d
6)
196) N-hydroxyl-4-{4-[4-(2-cyclohexyl-5-ethyl-thiazole-4-yl)-phenoxy group]-butoxy }-benzamidine 1.22 (t, 3H), 1.39-1.44 (m, 3H), 1.59 (m, 1H), 1.77 (m, 2H), 1.89 (m, 4H), 2.03 (m, 2H), 2.90 (m, 3H), 4.18 (m, 4H), 7.00 (m, 4H), 7.49 (m, 2H), 7.60 (m, 2H) (DMSO-d
6)
197) N-hydroxyl-4-[3-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-thiazole-4-yl } phenoxy group) propoxyl group]-benzamidine 1.17 (m, 3H), 2.19 (m, 2H), 2.72 (m, 2H), 3.05 (s, 3H), 3.39-3.79 (m, 4H), 4.16-4.20 (m, 4H), 5.72 (s, 2H), 6.96 (m, 4H), 7.40-7.84 (m, 4H), 9.47 (s, 1H) (DMSO-d
6)
198) N-hydroxyl-4-[4-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-thiazole-4-yl } phenoxy group) butoxy]-benzamidine 1.15 (t, 3H), 1.90 (m, 4H), 2.64 (q, 2H), 3.25 (s, 3H), 3.40-3.80 (m, 4H), and 4.10-4.15 (m, 4H), 7.09-7.15 (m, 4H), 7.42 (d, 2H), 7.73 (d, 2H) (DMSO-d
6)
199) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-thiazole-4-yl phenoxy group) propoxyl group]-benzamidine 1.86 (t, 3H), 2.50 (m, 2H), 2.73 (m, 2H), 3.15 (s, 3H), 4.17-4.25 (m, 4H), 4.96 (s, 2H), 7.01 (d, 2H), 7.17 (d, 2H), 7.44 (d, 2H), 7.73 (d, 2H), 8.06 (m, 1H), 8.54 (d, 1H), 8.87 (d, 1H), 8.94 (s, 1H) (DMSO-d
6)
200) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-thiazole-4-yl phenoxy group) butoxy]-benzamidine 1.19 (t, 3H), 1.79-1.89 (m, 4H), 2.72-2.74 (m, 2H), 3.17 (s, 3H), 4.07-4.15 (m, 4H), 4.98 (s, 2H), 7.00 (d, 2H), 7.14 (d, 2H), 7.44 (d, 2H), 7.72 (d, 2H), 8.05 (m, 1H), 8.55 (d, 1H), 8.87 (d, 1H), 8.95 (s, 1H) (DMSO-d
6)
201) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-isopropyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 1.14 (m, 2H), 1.32 (d, 6H), 1.48 (m, 4H), 1.74 (m, 2H), 2.04 (m, 1H), 2.85 (d, 2H), 3.38 (m, 1H), 5.14 (s, 4H), 5.73 (s, 2H), 7.01 (d, 2H), 7.08 (d, 2H), 7.48 (s, 4H), 7.50 (d, 2H), 7.58 (d, 2H), 9.48 (s, 1H) (DMSO-d
6)
202) N-hydroxyl-4-{4-[4-(5-butyl-2-isopropyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 0.85 (t, 3H), 1.32 (d, 6H), 1.35 (m, 2H), 1.60 (m, 2H), 1.85 (m, 2H), 3.25 (m, 1H), 5.15 (s, 4H), 5.74 (s, 2H), 7.01 (d, 2H), 7.08 (d, 2H), 7.48 (s, 4H), 7.50 (d, 2H), 7.60 (d, 2H), 9.49 (s, 1H) (DMSO-d
6)
203) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-amino-thiazolyl--4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 1.07-1.09 (m, 2H), 1.47-1.50 (m, 4H), 1.70 (m, 2H), 1.99 (m, 1H), 2.34 (s, 6H), 2.62 (d, 2H), 5.18 (s, 2H), 5.25 (s, 2H), 7.17-7.24 (m, 4H), 7.41 (d, 2H), 7.50 (m, 4H), 7.68 (d, 2H) (DMSO-d
6)
204) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-amino-thiazolyl--4-yl)-phenoxymethyl]-benzyloxy }-2-fluoro-benzamidine 1.05 (m, 2H), 1.49 (m, 4H), 1.71 (m, 2H), 2.00 (m, 1H), 2.34 (s, 6H), 2.63 (d, 2H), 5.15-5.26 (d, 4H), 7.05-7.24 (m, 3H), 7.41-7.62 (m, 8H) (DMSO-d
6)
205) N-hydroxyl-4-{4-[4-(2-methylamino-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 2.86 (s, 3H), 5.16 (m, 4H), 6.00 (brs, 2H), 7.02 (m, 4H), 7.48 (m, 4H), 7.60 (s, 1H), 7.76 (m, 4H), 9.57 (brs, 1H) (DMSO-d
6)
206) N-hydroxyl-4-{6-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-pyridine-2-base-methoxyl group }-benzamidine 1.26 (d, 6H), 2.61 (s, 3H), 3.35 (m, 1H), 5.25 (m, 4H), 5.75 (brs, 2H), 7.11 (m, 1H), 7.13 (m, 2H), 7.47 (m, 4H), 7.49 (m, 2H), 7.80-7.90 (m, 2H), 9.49 (brs, 1H) (DMSO-d
6)
207) N-hydroxyl-2-fluoro-4-{4-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxy group]-butoxy }-benzamidine 1.25 (d, 6H), 1.89 (m, 4H), 2.61 (s, 3H), 3.34 (m, 1H), 4.10 (m, 4H), and 6.80-6.90 (m, 2H), 7.02 (m, 2H), 7.46 (m, 3H) (DMSO-d
6)
208) N-hydroxyl-4-{2-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 1.23 (d, 6H), 2.60 (s, 3H), 3.33 (m, 1H), 5.28 (s, 4H), 5.80 (s, 2H), 7.04-7.12 (m, 4H), 7.37 (m, 2H), 7.47 (d, 2H), 7.55 (m, 2H), 7.64 (d, 2H), 9.57 (s, 1H) (DMSO-d
6)
209) N-hydroxyl-4-{3-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 1.23 (d, 6H), 2.60 (s, 3H), 3.31 (m, 1H), 5.14 (s, 2H), 5.15 (s, 2H), 5.72 (s, 2H), 7.00 (d, 2H), 7.08 (d, 2H), 7.42-7.46 (m, 5H), 7.55-7.61 (m, 3H), 9.46 (s, 1H) (DMSO-d
6)
210) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-cyclohexyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine 1.10 (m, 2H), 1.23 (m, 1H), 1.46 (br, 9H), 1.77 (br, 4H), 2.02 (m, 3H), 2.83 (d, 2H), 2.90 (m, 1H), 5.16 (m, 4H), 5.81 (brs, 2H), 7.02 (m, 4H), 7.48 (m, 4H), 7.76 (m, 4H), 9.57 (brs, 1H) (DMSO-d
6)
211) N-hydroxyl-4-{6-[4-(5-isopropyl-2-methyl-thiazole-4-yl) phenoxy group]-hexyloxy }-benzamidine 1.24 (d, 6H), 1.49 (m, 4H), 1.76 (m, 4H), 2.61 (s, 3H), 3.32-3.37 (m, 1H), 3.99-4.02 (m, 4H), 5.81 (s, 2H), 6.91 (d, 2H), 6.99 (d, 2H), 7.44 (d, 2H), 7.59 (d, 2H), 9.49 (s, 1H) (DMSO-d
6)
212) N-hydroxyl-4-{5-[2-ethyl-5-hydroxyl-4-(2-methyl-thiazole-4-yl) phenoxy group]-amoxy }-benzamidine 1.13 (t, 3H), 1.61 (m, 2H), 1.81 (m, 4H), 2.51 (m, 2H), 2.79 (s, 3H), 3.97-4.10 (m, 4H), 6.60 (s, 1H), 7.12 (d, 2H), 7.69-7.86 (m, 4H), 8.81 (s, 1H), 9.26 (s, 1H) (DMSO-d
6)
213) N-hydroxyl-4-{5-[2-ethyl-4-(2-methyl-thiazole-4-yl)-5-propoxyl group-phenoxy group]-amoxy }-benzamidine 1.03 (t, 3H), 1.13 (t, 3H), 1.62 (m, 2H), 1.79-1.85 (m, 6H), 2.55 (m, 2H), 2.69 (s, 3H), 4.01-4.08 (m, 6H), 5.73 (s, 2H), 6.67 (s, 1H), 6.92 (d, 2H), 7.59-7.93 (m, 4H), 9.47 (s, 1H) (DMSO-d
6)
214) N-hydroxyl-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.86 (d, 6H), 1.59 (m, 2H), 1.80 (m, 5H), 2.60 (s, 3H), 2.73 (m, 2H), 2.94 (m, 2H), 3.34 (m, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.93 (m, 4H), 7.49-7.60 (m, 4H), 9.45 (s, 2H) (DMSO-d
6)
215) 4-(5-{4-[5-(2-isobutyl group aminoethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.85 (d, 6H), 1.58 (m, 2H), 1.79 (m, 5H), 2.59 (s, 3H), 2.71 (m, 2H), 2.92 (m, 2H), 3.32 (m, 2H), 4.01 (m, 4H), 6.93 (m, 4H), 7.57 (m, 4H), 9.09 (brs, 3H) (DMSO-d
6)
216) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-piperidines-1-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.52 (m, 2H), 1.58 (m, 6H), 1.79 (m, 4H), 2.50 (d, 2H), 2.60 (s, 3H), 2.98 (d, 2H), 3.38 (m, 4H), 4.02 (m, 4H), 5.73 (s, 2H), 6.93-7.00 (m, 4H), 7.48-7.60 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
217) N-hydroxyl-4-[5-(4-{2-methyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58-1.60 (m, 2H), 1.79-1.81 (m, 4H), 2.31-2.33 (m, 6H), 2.51-2.58 (m, 2H), 2.61 (s, 3H), 2.76 (m, 2H), 2.95 (m, 2H), 3.53 (m, 4H), 4.01-4.04 (m, 4H), 5.73 (s, 2H), 6.94-7.00 (m, 4H), 7.51 (d, 2H), 7.60 (d, 2H) (DMSO-d
6)
218) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.23 (m, 2H), 1.60 (m, 2H), 1.81 (m, 6H), 1.91 (m, 2H), 2.61 (s, 3H), 2.82 (m, 2H), 3.02 (m, 2H), 4.02 (m, 4H), 6.91-7.00 (m, 5H), 7.15 (s, 1H), 7.51 (d, 2H), 7.59 (d, 2H), 7.85 (d, 1H) (DMSO-d
6)
219) N-hydroxyl-4-(5-{4-[5-(2-isopropyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.05 (d, 6H), 1.63 (m, 2H), 1.81-1.85 (m, 4H), 2.65 (s, 3H), 2.85-2.89 (m, 3H), 3.06-3.08 (m, 2H), 3.94-3.97 (m, 4H), 4.84 (brs, 2H), 6.34 (brs, 1H), 6.85-6.89 (m, 4H), 7.46-7.51 (m, 4H) (CDCl
3)
220) N-hydroxyl-4-[5-(4-{5-[2-(3-isopropoxy-propyl group amino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.05 (d, 6H), 1.65 (m, 2H), 1.79-1.84 (m, 6H), 2.64 (s, 3H), 2.77 (t, 2H), 2.91 (t, 2H), 3.15 (t, 2H), 3.40 (t, 2H), 3.50 (m, 1H), 3.94-3.97 (m, 4H), 4.93 (brs, 2H), 6.54 (brs, 1H), 6.84-6.88 (m, 4H), 7.45 (m, 4H) (CDCl
3)
221) N-hydroxyl-4-(5-{4-[5-(2-butyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.85 (t, 3H), 1.29-1.35 (m, 6H), 1.58 (m, 2H), 1.78 (m, 4H), 2.60 (s, 3H), 2.72 (m, 2H), 2.93 (m, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.91-6.97 (m, 4H), 7.49-7.58 (m, 4H) (DMSO-d
6)
222) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.64 (m, 2H), 1.86 (m, 4H), 2.66 (s, 3H), 3.30 (t, 2H), 4.01-4.14 (m, 6H), 6.89-7.77 (m, 11H) (CDCl
3)
223) N-hydroxyl-4-(5-{4-[5-(2-cyclohexyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.98-1.01 (m, 2H), 1.13-1.63 (m, 3H), 1.58-1.70 (m, 5H), 1.78-1.80 (m, 6H), 2.40 (m, 1H), 2.60 (s, 3H), 2.79 (m, 2H), 2.95 (m, 2H), 4.01-4.04 (m, 4H), 5.72 (s, 2H), 6.93-7.00 (m, 4H), 7.50 (d, 2H), 7.60 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
224) N-hydroxyl-4-(5-{4-[5-(2-diethylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.93 (t, 6H), 1.59 (m, 2H), 1.79 (m, 4H), 2.49 (m, 6H), 2.59 (s, 3H), 2.92 (m, 2H), 4.02-4.04 (m, 4H), 5.72 (s, 2H), 6.93-6.70 (m, 4H), 7.48-7.82 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
225) N-hydroxyl-4-{5-[4-(5-{2-[two-(2-hydroxyl-ethyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine 1.59 (m, 2H), 1.79 (m, 4H), 2.55-2.59 (m, 4H), 2.60 (s, 3H), 2.75 (m, 2H), 2.95 (m, 2H), 3.41-3.43 (m, 4H), 4.01-.04 (m, 4H), 5.72 (s, 2H), 6.93-7.00 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
226) N-hydroxyl-4-(5-{4-[5-(2-diisopropylaminoethyl-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.29-1.42 (m, 12H), 1.65 (m, 2H), 1.84-1.89 (m, 4H), 2.71 (s, 3H), 2.93 (m, 2H), 3.52 (m, 2H), 3.64 (m, 2H), 4.00-4.04 (m, 4H), 6.92 (m, 4H), 7.46 (d, 2H), 7.78 (d, 2H) (CDCl
3)
227) N-hydroxyl-4-[5-(4-{5-[2-(2,6-dimethyl-morpholine-4-yl)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.03 (d, 6H), 1.60-1.63 (m, 4H), 1.78-1.80 (m, 4H), 2.47-2.50 (m, 2H), 2.60 (s, 3H), 2.74 (m, 2H), 2.98 (m, 2H), 3.52-3.56 (m, 2H), 4.02-4.04 (m, 4H), 5.72 (s, 2H), 6.93-7.00 (m, 4H), 7.48 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
228) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.78-1.81 (m, 4H), 2.50-2.55 (m, 2H), 2.60 (s, 3H), 2.62 (m, 4H), 2.67 (m, 4H), 2.98 (m, 2H), 4.02-4.04 (m, 4H), 5.72 (s, 2H), 6.93-7.00 (m, 4H), 7.49 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
229) N-hydroxyl-4-(5-{4-[2-amino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.59 (m, 2H), 1.79 (m, 4H), 2.91 (m, 2H), 3.34 (m, 6H), 3.63 (m, 4H), 4.03 (m, 4H), 5.76 (s, 2H), 6.93 (m, 4H), 7.43 (d, 2H), 7.59 (d, 2H), 9.53 (brs, 1H) (DMSO-d
6)
230) N-hydroxyl-4-[5-(4-{5-[2-(2-dimethylamino-ethylamino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.57 (m, 2H), 1.78 (m, 4H), 2.09 (s, 6H), 2.60 (s, 3H), 3.22-3.34 (m, 8H), 4.02 (m, 4H), 6.98 (d, 2H), 7.11 (d, 2H), 7.50 (d, 2H), 7.76 (d, 2H) (DMSO-d
6)
231) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.63 (m, 2H), 1.83 (m, 4H), 2.49 (m, 4H), 2.59 (m, 2H), 2.65 (s, 3H), 3.03 (m, 2H), 3.71 (m, 4H), 3.98 (m, 4H), 4.95 (brs, 1H), 6.85-6.91 (d-d, 4H), 7.44-7.47 (d-d, 4H) (CDCl
3)
232) N-hydroxyl-4-[5-(4-{2-methyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.64 (m, 2H), 1.83 (m, 4H), 2.29 (s, 3H), 2.58-2.63 (m, 10H), 2.64 (s, 3H), 2.99 (m, 2H), 3.96 (m, 4H), 4.85 (brs, 1H), 6.85-6.89 (d-d, 4H), 7.43-7.71 (d-d, 4H) (CDCl
3)
233) N-hydroxyl-4-{5-[4-(5-{2-[two-(2-methoxyl group-ethyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 2.60 (s, 3H), 2.66 (m, 4H), 2.73 (m, 2H), 2.94 (m, 2H), 3.19 (s, 6H), 3.35 (m, 4H), 4.03 (m, 4H), 5.73 (s, 2H), 6.92 (d, 2H), 6.99 (d, 2H), 7.49 (d, 2H), 7.60 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
234) N-hydroxyl-4-(5-{4-[5-(2-tert-butyl group amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.06 (m, 9H), 1.58 (m, 2H), 1.80 (m, 4H), 2.61 (s, 3H), 2.80 (m, 2H), 2.98 (m, 2H), 4.03 (m, 4H), 6.91-7.01 (m, 4H), 7.50-7.82 (m, 4H) (DMSO-d
6)
235) N-hydroxyl-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.86 (d, 6H), 1.59 (m, 2H), 1.80 (m, 5H), 2.60 (s, 3H), 2.73 (m, 2H), 2.94 (m, 2H), 3.34 (m, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.93 (m, 4H), 7.49-7.60 (m, 4H), 9.45 (s, 2H) (DMSO-d
6)
236) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-pyridin-3-yl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.65 (m, 2H), 1.88 (m, 4H), 2.10 (m, 2H), 2.92 (m, 4H), 3.43 (m, 2H), 4.04 (m, 8H), 6.90-7.00 (m, 4H), 7.37 (m, 1H), 7.57-7.60 (m, 4H), 8.24 (d, 1H), 8.63 (d, 1H), 9.14 (s, 1H) (CDCl
3)
237) N-hydroxyl-4-[5-(4-{5-[2-(4-methyl-piperazine-1-yl)-ethyl]-2-pyridin-3-yl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.70 (m, 2H), 1.89 (m, 4H), 2.81 (s, 3H), 2.86 (m, 2H), 3.01-3.22 (m, 8H), 3.46 (m, 2H), 4.05 (m, 4H), 6.95-6.97 (m, 4H), 7.53-7.59 (m, 4H), 7.76 (m, 1H), 8.35 (d, 1H), 8.64 (d, 1H), 9.16 (s, 1H) (CDCl
3)
238) N-hydroxyl-4-(5-{4-[2-pyridin-3-yl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.60 (m, 2H), 1.82 (m, 4H), 2.51-2.93 (m, 4H), 3.35-3.41 (m, 8H), 4.08 (m, 4H), 6.97-7.08 (m, 4H), 7.55 (m, 1H), 7.66-7.85 (m, 4H), 8.31 (d, 1H), 8.68 (d, 1H), 9.13 (s, 1H) (DMSO-d
6)
239) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-pyridin-3-yl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.60 (m, 2H), 1.82 (m, 4H), 3.54 (m, 2H), 4.07 (m, 4H), 4.53 (t, 2H), 6.99-7.17 (m, 5H), 7.53-7.75 (m, 6H), 7.85 (m, 1H), 8.30 (d, 1H), 8.71 (m, 1H), 9.07 (s, 1H) (DMSO-d
6)
240) N-hydroxyl-4-(5-{4-[2-isopropyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.32 (d, 6H), 1.58 (m, 2H), 1.78 (m, 4H), 2.39 (m, 4H), 2.52 (m, 2H), 2.98 (m, 2H), 3.25 (m, 1H), 3.57 (m, 4H), 4.04 (m, 4H), 5.72 (s, 2H), 6.96 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
241) N-hydroxyl-4-[5-(4-{2-isopropyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.32 (d, 6H), 1.56 (m, 2H), 1.80 (m, 4H), 2.22 (s, 3H), 2.49 (m, 10H), 2.97 (m, 2H), 3.22 (m, 1H), 4.04 (m, 4H), 5.72 (s, 2H), 6.96 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
242) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-isopropyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.31 (d, 6H), 1.59 (m, 2H), 1.79 (m, 4H), 3.27 (m, 5H), 4.04 (m, 4H), 5.71 (s, 2H), 6.88 (s, 1H), 6.98 (m, 4H), 7.14 (s, 1H), 7.40 (d, 2H), 7.58 (d, 2H), 7.81 (d, 1H), 9.45 (s, 1H) (DMSO-d
6)
243) N-hydroxyl-4-[5-(4-{2-isopropyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.32 (d, 6H), 1.58 (m, 2H), 1.79 (m, 4H), 2.32 (m, 6H), 2.60 (m, 2H), 2.81 (m, 2H), 2.99 (m, 2H), 3.23 (m, 1H), 3.52 (m, 4H), 4.03 (m, 4H), 5.71 (s, 2H), 6.98 (m, 4H), 7.53 (m, 4H) (DMSO-d
6)
244) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-isopropyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.32 (d, 6H), 1.57 (m, 2H), 1.81 (m, 6H), 2.43 (m, 2H), 2.74 (m, 2H), 2.94 (m, 2H), 3.22 (m, 1H), 4.01 (m, 6H), 5.71 (s, 2H), 6.87 (s, 1H), 6.99 (m, 4H), 7.12 (s, 1H), 7.57 (m, 4H), 7.82 (d, 1H) (DMSO-d
6)
245) N-hydroxyl-4-(5-{4-[2-isopropyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.32 (d, 6H), 1.58 (m, 2H), 1.80 (m, 4H), 2.60 (m, 10H), 2.97 (m, 2H), 3.22 (m, 1H), 4.01 (m, 4H), 5.70 (s, 2H), 6.92 (d, 2H), 6.98 (d, 2H), 7.47 (d, 2H), 7.59 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
246) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.21 (m, 2H), 1.42 (m, 4H), 1.59 (m, 2H), 1.62 (m, 1H), 1.79 (m, 6H), 2.02 (m, 2H), 2.50 (m, 4H), 2.90 (m, 1H), 2.98 (m, 2H), 3.56 (m, 4H), 4.02 (m, 4H), 5.73 (s, 2H), 6.93 (d, 2H), 6.99 (d, 2H), 7.49 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
247) N-hydroxyl-4-[5-(4-{2-cyclohexyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.22 (m, 1H), 1.42 (m, 4H), 1.58 (m, 2H), 1.68 (m, 1H), 1.79 (m, 6H), 2.04 (m, 2H), 2.14 (m, 4H), 2.50 (m, 7H), 2.90 (m, 1H), 2.97 (m, 2H), 3.45 (m, 2H), 4.01 (m, 4H), 5.72 (m, 2H), 6.92 (d, 2H), 6.98 (d, 2H), 7.48 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
248) N-hydroxyl-4-[5-(4-{2-cyclohexyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.23 (m, 1H), 1.42 (m, 4H), 1.57 (m, 2H), 1.68 (m, 1H), 1.79 (m, 6H), 2.02 (m, 2H), 2.33 (m, 6H), 2.60 (m, 2H), 2.80 (m, 2H), 2.91 (m, 1H), 2.98 (m, 2H), 3.52 (m, 4H), 4.02 (m, 4H), 5.72 (m, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.50 (d, 2H), 7.58 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
249) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.25 (m, 1H), 1.42 (m, 4H), 1.58 (m, 2H), 1.67 (m, 1H), 1.79 (m, 6H), 2.01 (m, 2H), 2.56 (m, 2H), 2.60 (m, 4H), 2.67 (m, 4H), 2.90 (m, 1H), 2.96 (m, 2H), 4.01 (m, 4H), 5.72 (s, 2H), 6.91 (d, 2H), 6.99 (d, 2H), 7.47 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
250) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dimethylamino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.21 (m, 2H), 1.42 (m, 4H), 1.57 (m, 2H), 1.67 (m, 1H), 1.78 (m, 6H), 2.02 (m, 2H), 2.15 (s, 6H), 2.45 (t, 2H), 2.90 (m, 1H), 2.93 (t, 2H), 4.01 (m, 4H), 5.73 (s, 2H), 6.93 (d, 2H), 6.98 (d, 2H), 7.49 (d, 2H), 7.58 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
251) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dipropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.79 (m, 6H), 1.22 (m, 1H), 1.32 (m, 4H), 1.35 (m, 4H0,1.58 (m, 2H), 1.66 (m, 1H), 1.76 (m, 7H), 2.00 (m, 2H), 2.33 (m, 3H), 2.60 (m, 2H), 2.92 (m, 3H), 4.01 (m, 4H), 5.72 (s, 2H), 6.90 (d, 2H), 6.97 (d, 2H), 7.47 (d, 2H), 7.57 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
252) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-cyclopropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.20 (m, 2H), 0.33 (m, 2H), 1.22 (m, 2H), 1.42 (m, 4H), 1.58 (m, 2H), 1.65 (m, 1H), 1.79 (m, 6H), 2.04 (m, 3H), 2.80 (s, 2H), 2.96 (m, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.90 (d, 2H), 6.98 (d, 2H), 7.49 (d, 2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
253) N-hydroxyl-4-[5-(4-{2-amino-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 1H), 1.79 (m, 4H), 2.35 (m, 6H), 2.69 (m, 2H), 2.78 (m, 4H), 3.54 (m, 4H), 4.01 (m, 4H), 5.71 (s, 2H), 6.93 (m, 4H), 7.44 (d, 2H), 7.59 (d, 2H) (DMSO-d
6)
254) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-phenyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.57 (m, 2H), 1.79 (m, 4H), 2.41 (m, 4H), 2.55 (m, 2H), 3.06 (m, 2H), 3.59 (m, 4H), 4.02 (m, 4H), 7.01 (m, 4H), 7.57 (m, 7H), 7.92 (m, 2H) (DMSO-d
6)
255) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.28 (t, 3H), 1.59 (m, 2H), 1.79 (m, 4H), 2.39 (m, 4H), 2.49 (m, 2H), 2.92 (q, 2H), 2.98 (t, 2H), 3.56 (t, 4H), 4.01 (q, 4H), 5.70 (s, 2H), 6.92 (d, 2H), 6.98 (d, 2H0,7.49 (d, 2H), 7.57 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
256) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.28 (m, 3H), 1.57 (m, 2H), 1.79 (m, 5H), 2.50 (m, 2H), 2.54 (d, 1H), 2.60 (m, 2H), 2.66 (m, 2H), 2.91 (m, 4H), 3.16 (d, 2H), 4.00 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H0,7.47 (d, 2H), 7.58 (d, 2H), 9.43 (s, 1H) (DMSO-d
6)
257) N-hydroxyl-4-(4-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-butoxy)-benzamidine 1.89 (m, 4H), 2.39 (m, 4H), 2.50 (m, 2H), 2.60 (s, 3H), 2.98 (t, 2H), 3.57 (t, 4H), 4.06 (m, 4H), 5.71 (s, 2H), 6.94 (d, 2H), 6.99 (d, 2H), 7.49 (d, 2H0,7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
258) 4-(5-{4-[2-cyclohexyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.20 (m, 2H), 1.41 (m, 4H), 1.59 (m, 2H), 1.62 (m, 1H), 1.78 (m, 6H), 2.01 (m, 2H), 2.49 (m, 4H), 2.90 (m, 1H), 2.98 (m, 2H), 3.56 (m, 4H), 4.02 (m, 4H), 6.93 (d, 2H), 6.99 (d, 2H), 7.49 (d, 2H), 7.57 (d, 2H), 9.10 (brs, 3H) (DMSO-d
6)
259) 4-(5-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.59 (m, 2H), 1.81 (m, 4H), 2.40 (m, 4H), 2.60 (s, 3H), 2.96 (m, 2H), 3.31 (m, 2H), 3.57 (m, 4H), 4.10 (m, 4H), 6.98 (d, 2H), 7.16 (d, 2H), 7.49 (d, 2H), 7.80 (d, 2H), 9.09 (brs, 3H) (DMSO-d
6)
260) N-hydroxyl-4-(5-{4-[2-methylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.57 (m, 2H), 1.79 (m, 4H), 2.39 (m, 4H), 2.50 (m, 2H), 2.81 (s, 3H), 2.84 (m, 2H), 3.58 (m, 4H), 4.00 (m, 4H), 5.74 (brs, 2H), 6.92 (m, 4H), 7.27 (m, 1H), 7.44 (m, 2H), 7.59 (m, 2H), 9.47 (brs, 1H) (DMSO-d
6)
261) N-hydroxyl-4-[5-(4-{2-methylamino-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.50 (s, 3H), 2.79 (m, 6H), 2.85 (s, 3H), 3.38 (m, 6H), 4.01 (m, 4H), 5.75 (brs, 2H), 6.92 (m, 4H), 7.43 (m, 2H), 7.60 (m, 2H), 9.46 (brs, 1H) (DMSO-d
6)
262) N-hydroxyl-4-(5-{4-[2-methylamino-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.60 (m, 4H), 2.65 (m, 4H), 2.78 (m, 4H), 3.33 (s, 3H), 5.71 (s, 2H), 6.93 (m, 4H), 7.43 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
263) N-hydroxyl-4-[5-(4-{2-methylamino-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.30 (m, 4H), 2.55 (m, 4H), 2.71 (m, 2H), 2.79 (m, 4H), 3.34 (s, 3H), 3.52 (m, 4H), 4.00 (m, 4H), 5.71 (s, 2H), 6.94 (m, 4H), 7.46 (d, 2H0,7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
264) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-methylamino-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.78 (m, 6H), 2.42 (m, 2H), 2.66 (m, 2H), 2.78 (m, 4H), 3.34 (s, 3H), 4.01 (m, 4H), 5.71 (s, 2H), 6.86 (s, 1H), 6.94 (m, 4H), 7.13 (s, 1H), 7.25 (d, 1H), 7.44 (d.2H), 7.58 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
265) 4-(5-{4-[2-methylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.78 (m, 4H), 2.40 (m, 4H), 2.49 (m, 2H), 2.80 (s, 3H), 2.84 (m, 2H), 3.58 (m, 4H), 4.01 (m, 4H), 6.92 (m, 4H), 7.27 (m, 1H), 7.44 (m, 2H), 7.59 (m, 2H), 9.09 (brs, 3H) (DMSO-d
6)
266) N-hydroxyl-4-(5-{4-[2-dimethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.38 (m, 4H), 2.48 (m, 2H), 2.86 (t, 2H), 3.00 (s, 6H), 3.57 (m, 4H), 4.01 (m, 4H), 5.71 (s, 2H), 6.94 (m, 4H), 7.45 (d, 2H), 7.58 (d, 2H), 9,45 (s, 1H) (DMSO-d
6)
267) N-hydroxyl-4-(5-{4-[2-dimethylamino-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.51 (m, 2H), 2.61 (m, 4H), 2.66 (m, 4H), 2.89 (m, 2H), 3.00 (s, 6H), 4.01 (m, 4H), 5.71 (s, 2H), 6.95 (m, 4H), 7.44 (d, 2H), 7.59 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
268) N-hydroxyl-4-(5-{4-[2-(isobutyryl-methyl-amino)-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.15 (d, 6H), 1.58 (m, 2H), 1.79 (m, 4H); 2.40 (m, 4H), 2.78 (m, 1H), 2.97 (m, 2H); 3.33 (s, 3H), 3.57 (m, 4H), 3.69 (m; 2H), 4.01 (m, 4H), 5.71 (s, 2H); 6.93 (d, 2H), 6.99 (d, 2H), 7.51 (d; 2H), 7.60 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
269) N-hydroxyl-4-(5-{4-[2-[benzyl-(2-morpholine-4-base-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.57 (m, 2H), 1.78 (m, 4H), 2.37 (m, 8H), 2.49 (m, 2H), 2.83 (m, 2H), 3.16 (m, 2H), 3.53 (m, 10H), 3.98 (m, 4H), 4.66 (s, 2H), 5.72 (s, 2H), 6.95 (m, 4H), 7.27 (m, 1H), 7.33 (m, 4H), 7.43 (m, 2H), 7.56 (m, 2H), 9.46 (s, 1H) (DMSO-d
6)
270) N-hydroxyl-4-(5-{4-[2-diethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.15 (m, 6H), 1.57 (m, 2H), 1.79 (m, 4H), 2.38 (m, 4H), 2.48 (m, 2H), 2.83 (m, 2H), 3.40 (m, 4H), 3.57 (m, 4H), 4.02 (m, 4H), 5.71 (s, 2H), 6.94 (m, 4H), 7.45 (d, 2H), 7.58 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
271) N-hydroxyl-4-(5-{4-[2-[two-(2-methoxyl group-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.57 (m, 2H), 1.79 (m, 4H), 2.39 (m, 4H), 2.49 (m, 2H), 2.84 (m, 2H), 3.27 (s, 6H), 3.56 (m, 12H), 4.01 (m, 4H), 5.71 (s, 2H), 6.93 (m, 4H), 7.43 (d, 2H), 7.59 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
272) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.43 (m, 4H), 3.32 (m, 8H), 3.58 (m, 8H), 4.05 (m, 4H), 5.71 (brs, 2H), 6.92 (m, 4H), 7.43 (m, 2H), 7.59 (m, 2H), 945 (brs, 1H) (DMSO-d
6)
273) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.68 (m, 8H), 2.85 (m, 2H), 3.33 (m, 6H), 3.70 (m, 4H), 4.02 (m, 4H), 5.71 (s, 2H), 6.95 (m, 4H), 7.44 (d, 2H), 7.59 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
274) N-hydroxyl-4-[5-(4-{5-[2-(4-methyl-piperazine-1-yl)-ethyl]-2-morpholine-4-base-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.78 (m, 4H), 2.41 (s, 3H), 2.51 (m, 5H), 2.75 (m, 3H), 2.88 (m, 2H), 3.08 (m, 6H), 3.70 (m, 4H), 4.01 (m, 4H), 6.96 (m, 4H), 7.45 (d, 2H), 7.69 (d, 2H) (DMSO-d
6)
275) N-hydroxyl-4-[5-(4-{2-morpholine-4-base-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.59 (m, 2H), 1.79 (m, 4H), 2.30 (m, 4H), 2.50 (m, 4H), 2.97 (m, 2H), 3.37 (m, 4H), 3.50 (m, 6H), 3.71 (t, 4H), 4.01 (t, 4H), 5.70 (d, 2H), 6.94 (m, 4H), 7.42 (d, 2H), 7.51 (d, 2H), 7.58 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
276) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-piperidines-1-base-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.38 (m, 2H), 1.49-1.56 (m, 6H0,1.76 (m, 4H), 2.37-2.49 (m, 8H), 2.98 (m, 2H), 3.54 (m, 4H), 3.67 (m, 2H), 3.99 (m, 6H), 6.90-6.97 (m, 4H), 7.47-7.56 (m, 4H) (DMSO-d
6)
277) 4-(5-{4-[2-morpholine-4-base-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 2.43 (m, 4H), 3.32 (m, 8H), 3.598 (m, 8H), 4.05 (m, 4H), 6.92 (m, 4H), 7.42 (m, 2H), 7.59 (m, 2H), 9.10 (brs, 3H) (DMSO-d
6)
278) N-hydroxyl-4-(5-{4-[5-(2-isobutyryl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.97 (d, 6H), 1.59 (m, 2H), 1.80 (m, 4H), 2.30 (m, 1H), 2.62 (s, 3H), 2.97 (m, 2H), 3.26 (m, 2H), 4.03 (m, 4H), 5.71 (s, 2H), 6.97 (m, 4H), 7.50 (d, 2H), 7.59 (d, 2H), 7.96 (m, 1H), 9.45 (s, 1H) (DMSO-d
6)
279) N-hydroxyl-4-{5-[4-(5-{2-[isobutyl group-(pyridine-3-carbonyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine 0.62 (d, 3H), 0.86 (d, 3H), 1.22 (s, 3H), 1.57 (m, 2H), 1.79 (m, 5H), 2.56 (s, 2H), 2.66 (s, 1H), 2.98 (m, 2H), 3.15 (m, 1H), 3.21 (m, 1H), 3.42 (m, 1H), 3.63 (m, 1H), 4.02 (t, 2H), 4.09 (m, 2H), 5.72 (s, 2H), 6.91 (d, 2H), 6.98 (d, 2H), 7.09 (d, 4H), 7.23 (d, 2H), 8.59 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
280) N-hydroxyl-4-{5-[4-(5-{2-[cyclopropyl-(pyridine-4-carbonyl)-amino]-ethyl-2-isopropyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine 0.37 (m, 2H), 0.44 (m, 2H), 1.33 (d, 6H), 1.58 (m, 2H), 1.79 (m, 4H), 2.70 (m, 1H), 3.24 (m, 2H), 3.35 (m, 2H), 3.68 (m, 1H), 4.00 (m, 4H), 5.72 (s, 2H), 6.90 (d, 2H), 7.00 (m, 2H), 7.35 (m, 2H), 7.59 (m, 4H), 8.63 (m, 2H), 9.45 (s, 1H) (DMSO-d
6)
281) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-{2-[cyclopropyl-(pyridine-3-carbonyl)-amino]-ethyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine 0.36 (m, 2H), 0.47 (m, 2H), 1.22 (m, 1H), 1.43 (m, 4H), 1.57 (m, 2H), 1.66 (m, 1H), 1.78 (m, 6H), 2.02 (m, 2H), 2.77 (m, 1H), 2.95 (m, 1H), 3.27 (m, 2H), 3.70 (m, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.90 (d, 2H), 6.97 (m, 2H), 7.43 (m, 1H), 7.59 (m, 3H), 7.82 (m, 2H), 8.60 (m, 2H), 9.46 (s, 1H) (DMSO-d
6)
282) N-hydroxyl-4-{5-[4-(5-methylamino formoxyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.57 (m, 2H), 1.80 (m; 4H), 2.69 (s, 6H); 4.03 (m, 4H), 5.73 (brs; 2H), 6.97 (m, 4H); 7.61 (m; 4H), 9.46 (brs, 1H) (DMSO-d
6)
283) N-hydroxyl-4-{5-[4-(5-isopropyl carbamoyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.04 (d, 6H), 1.58 (m, 2H); 1.80 (m, 4H), 2.70 (s, 3H); 4.02 (m, 4H), 4.16 (m; 1H), 5.73 (brs, 2H); 6.98 (m, 4H), 7.60 (m; 4H), 9.46 (brs, 1H) (DMSO-d
6)
284) N-hydroxyl-4-{5-[4-(5-{3-imidazoles-1-base-propyl group carbamoyl }-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.57 (m, 2H), 1.77 (m, 6H), 2.11 (brs; 3H), 3.36 (m, 2H), 3.91 (m, 2H); 4.00 (m, 4H), 5.71 (m, 2H), 6.80 (m; 2H), 6.94 (m, 4H), 7.25 (m, 2H); 7.56 (m, 1H), 7.75 (m, 1H); 7.84 (m, 1H), 8.30 (brs, 1H) (DMSO-d
6)
285) N-hydroxyl-4-{5-[4-(2-amino-5-methylamino formoxyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.57 (m, 2H), 1.78 (m; 4H), 2.60 (s, 3H); 4.01 (m, 4H), 5.75 (brs; 2H), 6.914 (m, 4H); 7.46 (m, 2H), 7.58 (m; 2H), 9.48 (brs, 1H) (DMSO-d
6)
286) N-hydroxyl-4-{5-[4-(2-methyl-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.59 (s, 3H), 2.78 (m, 4H), 3.73 (m, 4H), 4.01 (m, 4H), 5.71 (s, 2H), 6.93-6.98 (m, 4H), 7.58 (d, 2H), 8.05 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
287) N-hydroxyl-4-(5-{4-[2-methyl-5-(4-methyl-piperazine-1-yl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.23 (s, 3H), 2.48 (m, 4H), 2.58 (s, 3H), 2.80 (m, 4H), 4.02 (m, 4H), 5.71 (s, 2H), 6.96 (m, 4H), 7.59 (d, 1H), 7.83 (d, 1H), 8.04 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
288) N-hydroxyl-4-{5-[4-(2-amino-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.81 (m, 4H), 2.72 (m, 4H), 3.17 (s, 2H), 3.71 (m, 4H), 4.03 (m, 4H), 6.80 (d, 1H), 6.91 (d, 1H), 6.99 (d, 2H), 7.62 (d, 2H), 7.83 (d, 1H), 8.01 (d, 1H) (DMSO-d
6)
289) N-hydroxyl-4-(5-{4-[5-(4-methyl-piperazine-1-yl)-2-morpholine-4-base-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.23 (s, 3H), 2.49 (m, 4H), 2.77 (m, 4H), 3.36 (m, 4H), 3.70 (m, 4H), 4.02 (m, 4H), 5.72 (s, 2H), 6.94 (m, 4H), 7.59 (d, 2H), 8.05 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
290) N-hydroxyl-4-{5-[4-(2,5-two-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.60 (m, 2H), 1.79 (m, 4H), 2.75 (m, 4H), 3.39 (m, 4H), 3.72 (m, 8H), 4.01 (m, 4H), 5.72 (s, 2H), 6.93 (m, 4H), 7.59 (d, 2H), 8.06 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
291) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-thiomorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.60 (m, 2H), 1.79 (m, 4H), 2.51 (m, 6H), 2.77 (m, 2H), 2.98 (m, 2H), 3.34 (m, 4H), 3.70 (m, 6H), 4.02 (m, 4H), 5.72 (s, 2H), 6.92 (m, 4H), 7.59 (d, 2H), 7.77 (d, 1H), 8.03 (d, 1H), 9.45 (s, 1H) (DMSO-d
6)
292) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-pyrrolidine-1-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 1.89 (m, 4H), 2.91 (m, 4H), 3.36 (m, 4H), 3.70 (m, 4H), 4.02 (m, 4H), 5.72 (s, 2H), 6.93 (m, 4H), 7.48 (d, 2H), 7.94 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
293) N-hydroxyl-4-{5-[4-(2-methyl-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 2.51 (m, 4H), 3.34 (s, 3H), 3.61 (m, 4H), 3.77 (s, 2H), 4.03 (m, 4H), 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.58 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
294) N-hydroxyl-4-(5-{4-[2-methyl-5-(4-methyl-piperazine-1-ylmethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.61 (m, 2H), 1.81 (m, 4H), 2.17 (s, 3H), 2.35 (m, 4H), 2.51 (m, 4H), 3.33 (s, 3H), 3.75 (s, 1H), 3.80 (s, 1H), 4.03 (m, 4H), 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.58 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
295) N-hydroxyl-4-{5-[4-(2-methyl-5-thiomorpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 2.65 (m, 4H), 2.78 (m, 4H), 3.33 (s, 3H), 3.79 (s, 2H), 4.03 (m, 4H), 5.71 (s, 2H), 6.93 (d, 2H), 7.00 (d, 2H), 7.58 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
296) N-hydroxyl-4-{5-[4-(2-methyl-5-piperidines-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.41 (m, 2H), 1.53 (m, 4H), 1.59 (m, 2H), 1.80 (m, 4H), 2.49 (m, 4H), 3.33 (s, 3H), 3.70 (s, 1H), 3.75 (s, 1H), 4.03 (m, 4H), 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.58 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
297) N-hydroxyl-4-{5-[4-(5-dimethylamino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 2.28 (d, 6H), 3.33 (s, 3H), 3.69 (s, 1H), 3.74 (s, 1H), 4.03 (m, 4H), 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.58 (m, 4H), 9.44 (s, 1H) (DMSO-d
6)
298) N-hydroxyl-4-{5-[4-(5-butyl amino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 0.88 (t, 3H), 1.32-1.42 (m, 4H), 1.58 (m, 2H), 1.80 (m, 4H), 2.48 (s, 3H), 2.51 (m, 2H), 3.92 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.91-6.98 (m, 4H), 7.55-7.61 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
299) N-hydroxyl-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.89 (d, 6H), 1.58 (m, 2H), 1.68 (m, 1H), 1.80 (m, 4H), 2.40 (d, 2H), 2.48 (s, 3H), 3.91 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.92 (d, 2H), 7.00 (d, 2H), 7.55-7.60 (m, 4H), 9.45 (s, 1H) (DMSO-d
6)
300) N-hydroxyl-4-(5-{4-[5-(tert-butyl group amino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.08 (s, 9H), 1.58 (m, 2H), 1.81 (m, 4H), 2.47 (s, 3H), 3.88 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.93 (d, 2H), 6.98 (d, 2H), 7.55-7.58 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
301) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group amino methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 0.86 (t, 3H), 1.44-1.46 (m, 2H), 1.58 (m, 2H), 1.80 (m, 4H), 2.48 (s, 3H), 2.51 (m, 2H), 3.91 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.92 (d, 2H), 6.97 (d, 2H), 7.55-7.60 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
302) N-hydroxyl-4-[5-(4-{2-methyl-5-[(2-morpholine-4-base-ethylamino)-methyl]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.35 (m, 2H), 2.40 (m, 4H), 2.48 (s, 3H), 2.70 (m, 2H), 3.56 (m, 4H), 3.95 (s, 2H), 4.01 (m, 4H), 5.72 (s, 2H), 6.93 (d, 2H), 6.99 (d, 2H), 7.55-7.60 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
303) N-hydroxyl-4-[5-(4-{5-[(3-imidazoles-1-base-propyl group amino)-methyl]-2-methyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.59 (m, 2H), 1.78 (m, 4H), 1.85 (m, 2H), 2.48 (s, 3H), 2.51 (m, 4H), 3.91 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.87 (s, 1H), 6.93 (d, 2H), 6.98 (m, 3H), 7.16 (s, 1H), 7.55-7.61 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
304) N-hydroxyl-4-{5-[4-(2-methyl-5-pyrrolidine-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 2H), 1.69 (m, 4H), 1.80 (m, 4H), 2.49 (m, 4H), 2.62 (s, 1.603H), 3.79 (s, 2H), 4.03 (m, 4H), 5.73 (s, 2H), 6.93-7.00 (m, 4H), 7.54-7.58 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
305) N-hydroxyl-4-{5-[4-(5-imidazoles-1-ylmethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.48 (s.3H), 4.03 (m, 4H), 5.54 (s, 2H), 5.72 (s, 2H), 6.94 (m, 3H), 7.02 (d, 2H), 7.29 (s, 1H), and 7.56-7.61 (m, 4H), 7.81 (s, 1H), 9.46 (s, 1H) (DMSO-d
6)
306) N-hydroxyl-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.49 (s.3H), 3.78 (s, 2H), 3.91 (s, 2H), 4.01 (m, 4H), 5.72 (s, 2H) 6.92 (d, 2H), 7.00 (d, 2H), 7.25 (m, 1H), 7.36 (m, 4H) 7.55-7.61 (m, 4H), 9.46 (s, 1H) (DMSO-d
6)
307) N-hydroxyl-4-{5-[4-(5-cyclopropyl amino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 0.30 (m, 2H), 0.39 (m, 2H), 1.59 (m, 2H), 1.80 (m, 4H), 2.20 (m, 1H), 2.48 (s, 3H), 3.96 (s, 2H), 4.02 (m, 4H), 5.72 (s, 2H), 6.92 (d, 2H), 7.00 (d, 2H), 7.58 (m, 4H), 9.45 (s, 1H) (DMSO-d
6)
308) N-hydroxyl-4-{5-[4-(2-methylamino-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.72 (m, 4H), 3.34 (s, 3H), 3.71 (m, 4H), 4.01 (m, 4H), 5.77 (s, 2H), 6.92 (m, 4H), 7.59 (d, 2H), 8.05 (d, 2H), 9.47 (s, 1H) (DMSO-d
6)
309) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-4-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.59 (m, 2H), 1.78 (m, 4H), 2.40 (m, 4H), 3.07 (s, 3H), 3.34 (m, 2H), 3.56 (m, 4H), 4.01 (m, 4H), 4.73-4.80 (m, 2H), 5.72 (brs, 2H), 6.91 (m, 4H), 7.28 (m, 2H), 7.49 (m, 2H), 7.57 (m, 2H), 8.53 (m, 2H), 9.45 (brs, 1H) (DMSO-d
6)
310) N-hydroxyl-4-[5-(4-{2-[(2-hydroxyl-ethyl)-methyl-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.78 (m, 4H), 2.40 (m, 4H), 3.04 (s, 3H), 3.37 (m, 4H), 3.46 (m, 2H), 3.60 (m, 4H), 3.98 (m, 4H), 4.82 (t, 1H), 5.72 (brs, 2H), 6.88 (m, 4H), 7.42 (d, 2H), 7.58 (d, 2H), 9.45 (brs, 1H) (DMSO-d
6)
311) N-hydroxyl-4-(5-{4-[2-(ethyl-methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.12 (t, 3H), 1.58 (m, 2H), 1.79 (m, 4H), 2.50 (m, 4H), 2.97 (s, 3H), 3.01 (m, 2H), 3.35 (m, 2H), 3.44 (m, 4H), 3.98 (m, 4H), 5.72 (brs, 2H), 6.89 (m, 4H), 7.42 (d, 2H), 7.58 (d, 2H), 9.46 (brs, 1H) (DMSO-d
6)
312) N-hydroxyl-4-(5-{4-[2-(benzyl-methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.57-1.60 (m, 2H), 1.77-1.81 (m, 4H), 2.40 (s, 4H), 3.00 (s, 3H), 3.55 (s, 6H), 4.01-4.03 (m, 4H), 4.68 (s, 2H), 5.71 (s, 2H), 6.92 (d, 2H), 6.98 (d, 2H), 7.28-7.37 (m, 5H), 7.52 (d, 2H), 7.59 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
313) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.40 (m, 8H), 2.51 (m, 4H), 3.01 (s, 3H), 3.55 (m, 12H), 3.99 (m, 4H), 5.74 (m, 2H), 6.91 (d, 2H), 6.93 (d, 2H), 7.49 (d, 2H), 7.60 (d, 2H), 9.48 (s, 1H) (DMSO-d
6)
314) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-thiomorpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.59 (m, 2H), 1.77 (m, 4H), 2.41 (m, 4H), 2.51 (m, 2H), 2.63 (m, 8H), 3.01 (s, 3H), 3.54 (m, 8H), 4.00 (m, 4H), 5.74 (m, 2H), 6.93 (m, 4H), 7.47 (d, 2H), 7.61 (d, 2H), 9.49 (s, 1H) (DMSO-d
6)
315) N-hydroxyl-4-[5-(4-{5-{[two-(2-methoxyl group-ethyl)-amino]-methyl-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.43 (m, 4H), 2.50 (m, 2H), 2.63 (m, 2H), 3.01 (s, 3H), 3.18 (m, 4H), 3.36 (m, 8H), 3.55 (m, 6H), 3.74 (m, 2H), 4.01 (m, 4H), 5.72 (s, 2H), 6.92 (m, 4H) 7.42 (d, 2H), 7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
316) N-hydroxyl-4-(5-{4-[2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-(4-methyl-piperazine-1-ylmethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.16 (s, 3H), 2.42 (m, 6H), 3.01 (s, 3H), 3.17 (m, 8H), 3.55 (m, 8H), 4.01 (m, 4H), 5.71 (m, 2H), 6.94 (m, 4H), 7.48 (d, 2H), 7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
317) N-hydroxyl-4-[5-(4-{5-(isopropyl amino-methyl)-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine 0.98 (d, 6H), 1.58 (m, 2H), 1.80 (m, 4H), 2.42 (m, 4H), 2.51 (m, 1H), 3.02 (s, 3H), 3.31 (m, 2H), 3.54 (m, 6H), 3.79 (m, 2H), 4.00 (m, 4H), 5.72 (s, 2H), 6.93-6.96 (m, 4H), 7.49 (d, 2H), 7.58 (d, 2H), 8.32 (s, 1H), 9.45 (s, 1H) (DMSO-d
6)
318) N-hydroxyl-4-[5-(4-{5-[(2-methoxyl group-ethylamino)-methyl]-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.57 (m, 2H), 1.78 (m, 4H), 2.42 (m, 4H), 2.50 (m, 6H), 3.02 (s, 3H), 3.36 (m, 5H), 3.53 (m, 6H), 4.00 (m, 4H), 5.71 (brs, 2H), 6.91 (m, 4H), 7.44 (m, 2H), 7.59 (m, 2H), 9.46 (brs, 1H) (DMSO-d
6)
319) N-hydroxyl-4-[5-(4-{2-[(2-methoxyl group-ethyl)-methyl-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.80 (m, 4H), 2.37 (m, 4H), 3.03 (s, 3H), 3.26 (s, 3H), 3.55 (m, 10H), 4.00 (m, 4H), 5.72 (s, 2H), 6.93-6.97 (m, 4H), 7.49 (d, 2H), 7.59 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
320) N-hydroxyl-4-(5-{4-[2-(methyl-propyl group-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 0.88 (t, 3H), 1.59 (m, 4H), 1.79 (m, 4H), 2.39 (m, 4H), 3.00 (s, 3H), 3.35 (m, 2H), 3.55 (m, 6H), 4.00 (m, 4H), 5.72 (s, 2H), 6.95 (m, 4H), 7.49 (d, 2H), 7.60 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
321) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-3-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine 1.58 (m, 2H), 1.78 (m, 4H), 2.38 (m, 4H), 3.03 (s, 3H), 3.56 (m, 6H), 4.01 (m, 4H), 4.72 (s, 2H), 5.72 (s, 2H), 6.92 (d, 2H), 6.98 (d, 2H), 7.39 (m, 1H), 7.52 (d, 2H), 7.59 (d, 2H), 7.74 (m, 1H), 8.49 (m, 1H), 8.57 (m, 1H), 9.46 (s, 1H) (DMSO-d
6)
322) N-hydroxyl-4-{5-[4-(2-methyl-5-methylamino-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.50 (s, 3H), 2.61 (s, 3H), 4.04 (m, 4H), 5.70 (s, 2H), 6.92 (m, 4H), 7.58 (d, 2H), 7.89 (d, 1H), 7.97 (d, 1H), 9.43 (s, 1H) (DMSO-d
6)
323) N-hydroxyl-4-[5-(4-{2-methyl-5-[(pyridine-4-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.20 (m, 2H), 1.84 (m, 4H), 2.65 (s, 3H), 4.01 (m, 4H), 5.73 (s, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.58 (d, 2H), 7.74 (d, 2H), 7.85 (d, 2H), 8.80 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
324) N-hydroxyl-4-[5-(4-{2-methyl-5-[(pyridine-3-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.78 (m, 4H), 2.64 (s, 3H), 4.01 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 7.02 (d, 2H), 7.58 (m, 3H), 7.78 (d, 2H), 8.29 (d, 1H), 8.77 (d, 1H), 9.10 (s, 1H), 9.43 (s, 1H) (DMSO-d
6)
325) N-hydroxyl-4-[5-(4-{2-phenyl-5-[(pyridine-3-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 4.07 (m, 4H), 7.06 (d, 1H), 7.09 (m, 3H), 7.51 (m, 5H), 7.87 (m, 3H), 7.97 (d, 2H), 8.32 (d, 1H), 8.79 (d, 1H), 9.13 (s, 1H) (DMSO-d
6)
326) N-hydroxyl-4-{5-[4-(5-dimethylamino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.57 (s, 3H), 2.61 (s, 6H), 4.00 (m, 4H), 5.70 (s, 2H), 6.91 (d, 2H), 6.96 (d, 2H), 7.59 (d, 2H), 7.98 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
327) N-hydroxyl-4-{5-[4-(5-dimethylamino-2-phenyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.79 (m, 4H), 2.70 (s, 6H), 4.02 (m, 4H), 5.71 (s, 2H), 6.92 (d, 2H), 7.01 (d, 2H), 7.47 (m, 3H), 7.60 (d, 2H), 7.89 (d, 2H), 8.04 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
328) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-dimethylamino-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.23 (m, 1H), 1.41 (m, 4H), 1.59 (m, 2H), 1.65 (m, 1H), 1.79 (m, 6H), 2.03 (m, 2H), 2.61 (s, 6H), 2.85 (m, 1H), 4.01 (m, 4H), 5.72 (s, 2H), 6.94 (m, 4H), 7.60 (d, 2H), 7.99 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
329) N-hydroxyl-4-{5-[4-(2-methyl-5-[1,2,4] triazol-1-yl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.55 (m, 2H), 1.76 (m, 4H), 2.74 (s, 3H), 3.99 (m, 4H), 5.71 (s, 2H), 6.90 (m, 4H), 7.17 (d, 2H), 7.58 (d, 2H), 8.36 (s, 1H), 8.84 (s, 1H), 9.45 (s, 1H) (DMSO-d
6)
330) N-hydroxyl-4-{5-[4-(5-amino-2-phenyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 2H), 1.80 (m, 4H), 4.02 (m, 4H), 5.73 (s, 2H), 5.88 (s, 2H), 6.94 (d, 2H), 6.98 (d, 2H), 7.40 (t, 1H), 7.42 (d, 2H), 7.59 (d, 2H), 7.74 (d, 2H), 7.76 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
331) N-hydroxyl-4-{5-[4-(5-amino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.77 (m, 4H), 2.44 (s, 3H), 3.99 (m, 4H), 5.34 (s, 2H), 5.71 (s, 2H), 6.92 (m, 4H), 7.59 (d, 2H), 7.67 (d, 2H), 9.44 (s, 1H) (DMSO-d
6)
332) N-hydroxyl-4-{5-[4-(5-amino-2-pyridin-3-yl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.60 (m, 2H), 1.81 (m, 4H), 4.03 (m, 4H), 5.72 (s, 2H), 6.05 (s, 2H), 6.92 (d, 2H), 7.00 (d, 2H), 7.45 (d, 1H), 7.59 (d, 2H), 7.75 (d, 2H), 8.10 (d, 1H), 8.52 (t, 1H), 8.95 (s, 1H), 9.45 (s, 1H) (DMSO-d
6)
333) N-hydroxyl-4-{5-[4-(5-amino-2-ethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.23 (t, 3H), 1.58 (m, 2H), 1.78 (m, 4H), 2.78 (q, 2H), 4.01 (m, 4H), 5.38 (s, 2H), 5.72 (s, 2H), 6.93 (d, 4H), 7.59 (d, 2H), 7.67 (d, 2H), 9.46 (s, 1H) (DMSO-d
6)
334) N-hydroxyl-4-{5-[4-(5-amino-2-cyclohexyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.23 (m, 1H), 1.36 (m, 4H), 1.57 (m, 2H), 1.64 (m, 1H), 1.81 (m, 6H), 1.98 (m, 2H), 2.74 (m, 1H), 4.00 (m, 4H), 5.36 (s, 2H), 5.71 (s, 2H), 6.92 (d, 4H), 7.59 (d, 2H), 7.66 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
335) N-hydroxyl-4-{5-[4-(2-methylamino-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.58 (m, 2H), 1.78 (m, 4H), 2.41 (m, 4H), 2.80 (s, 3H), 3.34 (m, 2H), 3.56 (m, 4H), 4.01 (m, 4H), 5.73 (brs, 2H), 6.92 (m, 4H), 7.36 (m, 1H), 7.49 (d, 2H), 7.59 (d, 2H), 9.46 (brs, 1H) (DMSO-d
6)
336) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.60 (m, 2H), 1.80 (m, 4H), 2.38 (m, 4H), 3.35 (m, 4H), 3.57 (m, 6H), 3.70 (m, 4H), 4.03 (m, 4H), 5.72 (s, 2H), 7.49 (d, 2H), 7.59 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
337) N-hydroxyl-4-{5-[4-(5-morpholine-4-base-2-piperidines-1-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine 1.59 (m, 8H), 1.79 (m, 4H), 2.75 (m, 4H), 3.41 (m, 4H), 3.73 (m, 4H), 4.00 (m, 4H), 5.72 (s, 2H), 6.92 (m, 4H), 7.59 (d, 2H), 8.06 (d, 2H), 9.45 (s, 1H) (DMSO-d
6)
Embodiment 1: etidronic acid (2 μ M) and chemical compound 187,138,119 and 169 separately or associating
Treatment is to the effect of osteoclast differentiation
By utilizing co-culture system to induce osteoclast from Os Mus myelocyte differentiation, and by separately or the treatment of combination formulations estimate the depression effect of medicine to the osteoclast differentiation.Medullary cell and osteoblast that utilization derives from Mus carry out common cultivation.
1. medullary cell and osteoblastic preparation
Medullary cell and osteoblast that utilization derives from Mus carry out common cultivation.
Sterilely excise femur and tibia from 6～8 all big male ddY mices, obtain medullary cell by general method to utilize syringe.Erythrocyte is removed from medullary cell, centrifugal then.Medullary cell is suspended in in the additional α-MEM culture medium of 10% hyclone, calculates eukaryotic quantity in the medullary cell that is obtained, be used for co-culture system then immediately.
Sterilely excise braincap from 1～2 the biggest newborn ICR mice, and the continuous processing of the enzymatic solution by 0.2% collagenase is separated into osteocyte.The cell suspension supernatant is centrifugal, and with the osteoblast predetermined a period of time of breeding in the additional α-MEM culture medium of 10% hyclone that is recovered to.Then, these cell dilutions to required cell quantity, and are used for experiment.
2. measure the osteoclast differentiation by co-culture system
Use with the medullary cell (1 * 10 of the additional α-MEM culture medium of 10% hyclone above-mentioned preparation
5Individual cells/well) and osteoblast (3,000 cells/well) be inoculated in 96 orifice plates.At this moment, with differentiation factor---1 α, 25-dihydroxyvitamin D
3(10
-8M is hereinafter referred to as vitamin D
3) and dexamethasone (10
-8M) add culture medium jointly, thereby induce the osteoclast differentiation.Replaced culture medium with the fresh culture that contains differentiation factor in per 2 to 3 days.
After 7 days, when observing multinucleated osteoclast, culture medium is removed from the hole, then with containing the PBS of 10% formalin (Formalin) cell fixation.Consider its feature, will resist tartaic acid phosphatase (Tartrate-Resistant Acid Phosphatase) (being hereinafter referred to as TRAP) with marking, to measure sophisticated osteoclast to TRAP dyeing liquor demonstration positive reaction.Preparing the TRAP dyeing liquor by this way: with substrate---naphthols AS-MS phosphate and coloring agent (reddish violet LB salt (Fast Red Violet LB salt)) are dissolved in N, in the dinethylformamide.Contain the tartaric 0.1N NaHCO of 50mM to its adding
3Buffer is being stored in mixture in the cold storage as before the dyeing liquor.Calculate the osteoclast that shows the TRAP-positive reaction with 6-7 or more a plurality of nuclears at microscopically.
3. tester is to the effect of osteoclast differentiation
Carry out the independent treatment of etidronic acid, chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 and the therapeutic alliance of etidronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169, thereby by its effect to the osteoclast differentiation of above-mentioned experimental evaluation.All experiment utilizes with the additional α-MEM culture medium of 10% hyclone and carries out, and this culture medium comprises differentiation factor, vitamin D3 and dexamethasone.
Chemical compound 187, chemical compound 138, chemical compound 119 and chemical compound 169 are dissolved in DMSO with concentration 0.1mM, dilute 1,000 times to ultimate density 0.1 μ M with division culture medium then.Etidronic acid is dissolved in pure water with concentration 2mM, dilutes 1,000 times to ultimate density 2 μ M with culture medium then.In this respect, matched group is remained among the 0.1%DMSO.
As mentioned above, will be diluted to the sample material of desired concn and cell inoculation, and cultivate altogether in 96 orifice plates.At the 3rd day and the 5th day that cultivates, replace culture medium with the fresh division culture medium that contains sample material.At the 7th day that cultivates, carry out TRAP dyeing, thereby calculate by the ripe multinucleated osteoclast that is differentiated to form.Calculate mature osteoclast with 6 or more a plurality of nuclears at microscopically.The result is expressed as quantity percent (%) in the observed mature osteoclast of each experimental group, and this moment, the quantity with mature osteoclast in the matched group (only solvent) was considered as 100%.Experimentize with 4 holes of every experimental group (n=4), and the result is expressed as meansigma methods ± standard deviation.In addition, repeated experiments at least three times, and Student t test is applied to significant difference between experimental group.The result is presented in the following table 1.
[table 1]
Independent or the therapeutic alliance of etidronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is to the effect of osteoclast differentiation
As shown in table 1, when the quantity that shows the multinucleated osteoclast of TRAP-positive reaction in the solvent control group was regarded as 100%, the quantity of the multinucleated osteoclast that obtains in the independent treatment group of chemical compound 187, chemical compound 138, chemical compound 119 and chemical compound 169 was represented as percent.When each material was added co-cultured cell respectively with identical concentration 0.1 μ M, this material showed osteoclast differentiation depression effect, finds that wherein its multinucleated osteoclast relative populations with respect to matched group is respectively 67%, 71%, 66% and 78%.
In addition, in the experimental group for the treatment of with 2 μ M etidronic acids separately, its multinucleated osteoclast relative populations with respect to the solvent control group is measured as 86%.Significantly minimizing like this shows that etidronic acid is the osteoclast differentiation inhibitors.
When the therapeutic alliance of etidronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is carried out simultaneously, find that the multinucleated osteoclast relative populations with respect to the solvent control group is 41% in the therapeutic alliance group of etidronic acid and chemical compound 187.The result shows that this value well below each summation for the treatment of separately, shows the strong depression effect to the osteoclast differentiation.Observe the remarkable result of etidronic acid and chemical compound 138 (40%), chemical compound 119 (38%) or chemical compound 169 (49%) therapeutic alliances equally.In a word, the result proves that the therapeutic alliance of two kinds of materials demonstrates than expected enhanced greatly effectiveness by each summation for the treatment of separately.
Embodiment 2: clodronic acid (1 μ M) and chemical compound 187,138,119 and 169 separately or unite and control
Treatment is to the effect of osteoclast differentiation
Except that substituting with 1 μ M clodronic acid the 2 μ M etidronic acids, experimentize in the mode identical with embodiment 1, thereby estimate clodronic acid and chemical compound 187, chemical compound 138, chemical compound 119 and chemical compound 169 separately or therapeutic alliance effect that osteoclast is broken up.
Clodronic acid is dissolved in pure water with concentration 1mM, dilutes 1,000 times to ultimate density 1 μ M with culture medium then.
The result is presented in the following table 2.
[table 2]
Independent or the therapeutic alliance of clodronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is to the effect of osteoclast differentiation
As described in embodiment 1, in the experimental group for the treatment of with chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 separately, find that its relative populations with respect to the multinucleated osteoclast of solvent control group is very low.In the experimental group for the treatment of with 1 μ M clodronic acid separately, its multinucleated osteoclast relative populations with respect to the solvent control group is measured as 88%, causes remarkable minimizing (table 2).Carry out the therapeutic alliance of these materials in an identical manner.The result, except that the therapeutic alliance group of clodronic acid and chemical compound 187, in the therapeutic alliance group of clodronic acid and chemical compound 138 (54%), chemical compound 119 (47%) or chemical compound 169 (59%), observe the statistically evident increase of osteoclast differentiation depression effect.
Embodiment 3: pamidronic acid (0.1 μ M) and chemical compound 187,138,119 and 169 separately or associating
Treatment is to the effect of osteoclast differentiation
Except that substituting with 0.1 μ M pamidronic acid the 2 μ M etidronic acids, experimentize in the mode identical with embodiment 1, thereby estimate pamidronic acid and chemical compound 187,138,119 and 169 separately or therapeutic alliance effect that osteoclast is broken up.
Pamidronic acid is dissolved in pure water with concentration 0.1mM, dilutes 1,000 times to ultimate density 0.1 μ M with culture medium then.
The result is presented in the following table 3.
[table 3]
Independent or the therapeutic alliance of pamidronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is to the effect of osteoclast differentiation
As shown in table 3, in the experimental group for the treatment of with pamidronic acid (0.1 μ M) separately, its multinucleated osteoclast relative populations with respect to matched group is measured as 82%, causes remarkable minimizing.As mentioned above, carry out the therapeutic alliance of pamidronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 in an identical manner.The result is as follows: the therapeutic alliance 47% of pamidronic acid and chemical compound 187, the therapeutic alliance 42% of pamidronic acid and chemical compound 138, the therapeutic alliance 37% of pamidronic acid and chemical compound 119, and the therapeutic alliance 50% of pamidronic acid and chemical compound 169.Especially, the therapeutic alliance of pamidronic acid and chemical compound 138, chemical compound 119 or chemical compound 169 shows enhanced greatly depression effect, wherein should value than the summation of each independent treatment larger about 10% or bigger.
Embodiment 4: alendronic Acid (0.2 μ M) and chemical compound 187,138,119 and 169 separately or associating
Treatment is to the effect of osteoclast differentiation
Except that substituting with 0.2 μ M alendronic Acid the 2 μ M etidronic acids, experimentize in the mode identical with embodiment 1, thereby estimate alendronic Acid and chemical compound 187,138,119 and 169 separately or therapeutic alliance effect that osteoclast is broken up.
Alendronic Acid is dissolved in pure water with concentration 0.2mM, dilutes 1,000 times to ultimate density 0.2 μ M with culture medium then.
The result is presented in the table 4.
[table 4]
Independent or the therapeutic alliance of alendronic Acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is for the effect of osteoclast differentiation
The alendronic Acid (0.2 μ M) that will show relative value 80% in it is treated is separately united chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 treatments that differentiation has depression effect to osteoclast.Shown the result in the table 4.During the therapeutic alliance that---separately shows relative value 67% in the treatment at it---when carrying out alendronic Acid and chemical compound 187 simultaneously with identical concentration, the quantity of osteoclast significantly reduces and is low to moderate 32%.In the therapeutic alliance of alendronic Acid and chemical compound 138 (32%), chemical compound 119 (29%) or chemical compound 169 (44%), also observe this remarkable result equally, show that the therapeutic alliance of this material demonstrates than expected enhanced greatly effectiveness by each summation for the treatment of separately.
Embodiment 5: risedronic acid (0.1 μ M) and chemical compound 187,138,119 and 169 separately or associating
Treatment is to the effect of osteoclast differentiation
Except that substituting the 2 μ M etidronic acids with 0.1 μ M risedronic acid, experimentize in the mode identical with embodiment 1, thus estimate risedronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 separately or therapeutic alliance effect that osteoclast is broken up.
Risedronic acid is dissolved in pure water with concentration 0.1mM, dilutes 1,000 times to ultimate density 0.1 μ M with culture medium then.
The result is presented in the following table 5.
[table 5]
Independent or the therapeutic alliance of risedronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is to the effect of osteoclast differentiation
Carry out the therapeutic alliance of risedronic acid and four kinds of materials equally, thereby estimate depression effect (table 5) the osteoclast differentiation.In the independent treatment of 0.1 μ M risedronic acid, the relative populations of finding multinucleated osteoclast is about 82%, causes with the solvent control group and compares remarkable minimizing.When risedronic acid binding compounds 187, chemical compound 138, chemical compound 119 or chemical compound 169 are added co-cultured cell, find that the relative populations of multinucleated osteoclast is low to moderate 40%, 35%, 38 and 42% respectively.The result of this result and matched group and independent treatment group has significant difference.
Embodiment 6: ibandronic acid (0.1 μ M) and chemical compound 187,138,119 and 169 separately or associating
Treatment is to the effect of osteoclast differentiation
Except that substituting the 2 μ M etidronic acids with 0.1 μ M ibandronic acid, experimentize in the mode identical with embodiment 1, thus estimate ibandronic acid and chemical compound 187, chemical compound 138, chemical compound 119 and chemical compound 169 separately or therapeutic alliance effect that osteoclast is broken up.
Ibandronic acid is dissolved in pure water with concentration 0.1mM, dilutes 1,000 times to ultimate density 0.1 μ M with culture medium then.
The result is presented in the following table 6.
[table 6]
Independent or the therapeutic alliance of ibandronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is to the effect of osteoclast differentiation
In the independent treatment of ibandronic acid (0.1 μ M), the quantity of observing the multinucleated osteoclast that shows the TRAP-positive reaction significantly reduces (77%).In the therapeutic alliance of ibandronic acid and chemical compound 187, find that the relative populations of multinucleated osteoclast is 42%, cause with each independent treatment and compare remarkable minimizing.As shown in table 6, the therapeutic alliance of ibandronic acid and other chemical compounds also demonstrates the remarkable minimizing of multinucleated osteoclast quantity.
Embodiment 7: zoledronic acid (0.01 μ M) and chemical compound 187,138,119 and 169 separately or connection
Close the effect of treatment to the osteoclast differentiation
Except that substituting the 2 μ M etidronic acids with 0.01 μ M zoledronic acid, experimentize in the mode identical with embodiment 1, thus estimate zoledronic acid and chemical compound 187, chemical compound 138, chemical compound 119 and chemical compound 169 separately or therapeutic alliance effect that osteoclast is broken up.
Zoledronic acid is dissolved in pure water with concentration 0.01mM, dilutes 1,000 times to ultimate density 0.01 μ M with culture medium then.
The result is presented in the following table 7.
[table 7]
Independent or the therapeutic alliance of zoledronic acid and chemical compound 187, chemical compound 138, chemical compound 119 or chemical compound 169 is to the effect of osteoclast differentiation
Carry out zoledronic acid (0.01 μ M) and four kinds of wherein therapeutic alliances of each of material equally, this therapeutic alliance significantly reduces the quantity of osteoclast.In the independent treatment of zoledronic acid, the quantity of observing multinucleated osteoclast significantly reduces (84%).In the therapeutic alliance of zoledronic acid and chemical compound 187, find that the relative populations of multinucleated osteoclast is 43%, far below expecting by each summation for the treatment of separately.This result proves that also therapeutic alliance demonstrates cooperative effect.Same discovery zoledronic acid demonstrates identical effect (table 7) with the therapeutic alliance of other chemical compounds.
Embodiment 8: the independent or therapeutic alliance of the Benzamine derivatives of alendronic Acid (0.1 μ M) and formula 1 is to broken bone
The effect of cell differentiation
By utilizing co-culture system to induce osteoclast from Os Mus myelocyte differentiation, and by separately or the treatment of combination formulations estimate the depression effect of medicine to the osteoclast differentiation.Utilize Os Mus myelocyte and the ST cell that derives from the stromal cell of bone marrow to carry out common cultivation.
1. medullary cell and osteoblastic preparation
Sterilely excise femur and tibia from 6～8 all big male ddY mices, obtain medullary cell by general method to utilize syringe.Erythrocyte is removed from medullary cell, centrifugal then.Medullary cell is suspended in in the additional α-MEM culture medium of 10% hyclone, calculates eukaryotic quantity in the medullary cell that is obtained, be used for co-culture system then immediately.
(RIKEN Cell Bank, Tsukuba Japan) are incubated in the α-MEM culture medium of replenishing with 10% hyclone up to converging with the ST2 cell.Then with these cell dilutions to required cell quantity, be used for experiment.
2. measure the osteoclast differentiation by co-culture system
Use with the medullary cell (1 * 10 of the additional α-MEM culture medium of 10% hyclone above-mentioned preparation
5Individual cells/well) and ST2 cell (3,000 cells/well) be inoculated in 96 orifice plates.At this moment, with differentiation factor---1 α, 25-dihydroxyvitamin D
3(10
-8M is hereinafter referred to as vitamin D
3) and dexamethasone (10
-8M) add culture medium jointly, thereby induce the osteoclast differentiation.Replaced culture medium with the fresh culture that contains differentiation factor in per 2 to 3 days.
After 7 days, when observing multinucleated osteoclast, culture medium is removed from the hole, then with containing the PBS of 10% formalin cell fixation.Consider its feature, will resist tartaic acid phosphatase (being hereinafter referred to as TRAP) with marking, to measure sophisticated osteoclast to TRAP dyeing liquor demonstration positive reaction.Preparing the TRAP dyeing liquor by this way: with substrate---naphthols AS-MS phosphate and coloring agent (reddish violet LB salt (Fast Red Violet LB salt)) are dissolved in N, dinethylformamide.Contain the tartaric 0.1N NaHCO of 50mM to its adding
3Buffer is being stored in mixture in the cold storage as before the dyeing liquor.Calculate the osteoclast of demonstration TRAP-positive reaction with 6-7 or more a plurality of nuclears at microscopically.
3. tester is to the effect of osteoclast differentiation
Alendronic Acid is dissolved in distilled water with concentration 0.1mM, and Benzamine derivatives is dissolved in DMSO with concentration 0.1mM.Respectively it is all diluted 1,000 times to ultimate density 0.1 μ M with division culture medium.In this respect, matched group is remained among the 0.1%DMSO.
As mentioned above, will be diluted to the sample material of desired concn and cell inoculation, and cultivate altogether in 96 orifice plates.At the 3rd day and the 5th day that cultivates, replace culture medium with the fresh division culture medium that contains sample material.At the 7th day that cultivates, carry out TRAP dyeing, thereby calculate by the sophisticated multinucleated osteoclast that is differentiated to form.Calculate mature osteoclast with 6 or more a plurality of nuclears at microscopically.The result is expressed as quantity percent (%) in the observed mature osteoclast of each experimental group, and this moment, the quantity with mature osteoclast in the matched group (only solvent) was considered as 100%.Experimentize with 4 holes of every experimental group (n=4), and the result is expressed as meansigma methods ± standard deviation.In addition, repeated experiments at least twice, and Student t test is applied to significant difference between experimental group.
Embodiment 9: the independent or therapeutic alliance of the Benzamine derivatives of risedronic acid (0.1 μ M) and formula 1 is to broken bone
The effect of cell differentiation
Except that substituting with 0.1 μ M risedronic acid the 0.1 μ M alendronic Acid, experimentize in the mode identical with embodiment 8, thereby estimate risedronic acid and formula 1 Benzamine derivatives separately or therapeutic alliance effect that osteoclast is broken up.
Risedronic acid is dissolved in the distilled water with concentration 0.1mM, dilutes 1,000 times to ultimate density 0.1 μ M with culture medium then.
The result of experiment 8 and 9
The independent treatment of-chemical compound: the quantity that shows the multinucleated osteoclast of TRAP-positive reaction in the solvent control group is considered as at 100% o'clock, and the quantitaes of the multinucleated osteoclast that will obtain in the independent treatment group of the Benzamine derivatives of formula 1 is a percent.When with identical concentration 0.1 μ M each material being added co-cultured cell respectively, these materials demonstrate the different depression effect to the osteoclast differentiation.
The independent treatment of-alendronic Acid or risedronic acid: in the experimental group for the treatment of with 0.1 μ M alendronic Acid or risedronic acid respectively, its relative populations with respect to the multinucleated osteoclast of solvent control group is measured as 76% (alendronic Acid) and 69% (risedronic acid).Remarkable minimizing like this shows that alendronic Acid and risedronic acid are the inhibitor of osteoclast differentiation.
-therapeutic alliance:, estimate the effect of therapeutic alliance to the osteoclast differentiation by comparing with the independent treatment effect of chemical compound and the independent treatment effect of alendronic Acid or risedronic acid.
Result such as following table 8 to 11.
Independent or the therapeutic alliance of the Benzamine derivatives of alendronic Acid or risedronic acid and formula 1 is to the effect of osteoclast differentiation
[table 8]
[table 9]
[table 10]
[table 11]
[commercial Application]
The pharmaceutical composition that comprises benzene carbon amidine (benzmidine) derivative or its salt according to the present invention can be used for prevention and treatment osteoporosis.
Claims (28)
1. the compositions of prevention or treatment osteoporosis comprises with simultaneously, separately or in succession is the following compounds (a) of target and (b) as active component;
(a) by the Benzamine derivatives of following formula 1 expression or its salt and
(b) diphosphate of representing by following formula 2,
[formula 1]
R wherein
1Be C
1～C
6Alkyl, described alkyl are not substituted or pyridyl replaces; Straight or branched C
1～C
6Alkyl, described alkyl quilt
Replace, described
Be not substituted or replaced by hydroxyl; C
3～C
6Cycloalkyl; Phenyl; Benzyl; Pyridine radicals, described pyridine radicals are not substituted or by C
1～C
6Alkyl replaces; Guanidine radicals; NR
6R
7CH
2NR
6R
7By straight or branched C
1～C
6Alkyl replaces
Group; Or
(wherein A is C
1～C
6Alkyl, and m is 2 to 6 integer);
R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, described alkyl are not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; Phenyl; Benzyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholinyl; Thio-morpholinyl; 4-methyl piperazine base; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace;
R
3And R
4Be hydrogen independently of one another; Halogen; Hydroxyl; C
1～C
6Alkyl, described alkyl is not substituted or is replaced by halogen; C
3～C
6Cycloalkyl amino; C
1～C
6Alkoxyl; C
1～C
6Alkanoyloxy; C
2～C
6Alkene oxygen base; Phenyl-C
1～C
6Alkoxyl; Phenoxy group; C
2～C
6Alkene acyloxy or phenyl-C
1～C
6Alkanoyloxy; C
3～C
6The group that cycloalkyloxy, described cycloalkyloxy are selected from carboxyl, esterifying carboxyl group and amidatioon carboxyl replaces; Or aminooxy group;
R
5Be hydrogen or hydroxyl;
R
6And R
7Be hydrogen independently of one another; C
1～C
6Alkyl, described alkyl are not substituted or are selected from hydroxyl, C
1～C
6Alkoxyl, pyridine and
Group replace; Phenyl; Benzyl; Pyridine radicals; Carbonyl, described carbonyl is selected from C
1～C
6Alkyl, hydroxyl, the C that is replaced by hydroxyl
1～C
6Alkyl, C
1～C
6Alkoxyl, phenyl, benzyl, pyridine and
Group replace; Or C
1～C
6Alkanesulfonyl;
R
8And R
9Be hydrogen independently of one another; C
1～C
6Alkyl, described alkyl are not substituted or are selected from hydroxyl, C
1～C
6Alkoxyl, morpholine, imidazoles and NR
6R
7Group replace; C
1～C
6Alkoxyl; C
3～C
6Cycloalkyl; Phenyl; Benzyl; Pyridine radicals; Morpholine; Carbonyl, described carbonyl is selected from C
1～C
6Alkyl, C
1～C
6Alkoxyl, phenyl, benzyl, pyridine and
Group replace; Carbonyl, described carbonyl is by C
1～C
6Alkyl replaces, and described alkyl is selected from halogen, C
1～C
6A group of alkoxyl and imidazoles replaces; Or C
1～C
6Alkanesulfonyl;
R
10And R
11Be hydrogen, C independently of one another
1～C
2Alkyl, C
1～C
3Alkoxyl or halogen;
X
1And X
3Be O independently of one another; S; NH; Or N-C
1～C
6Alkyl, N-C
3～C
6Cycloalkyl, N-benzyl or N-phenyl;
X
2Be C
3～C
7Alkylidene; C
1～C
3Alkylidene-C
2～C
7Alkenylene-C
1～C
3Alkylidene; C
1～C
3Alkylidene-O-C
1～C
3Alkylidene; C
1～C
3Alkylidene-S-C
1～C
3Alkylidene; C
1～C
3Alkylidene-NH-C
1～C
3Alkylidene; C
1～C
3Alkylidene-phenylene-C
1-C
3Alkylidene; C
1-C
3Alkylidene-pyridylidene-C
1-C
3Alkylidene or C
1-C
3Alkylidene-naphthylene-C
1～C
3Alkylidene; By C
1～C
3The C that alkyl and hydroxyl replace
3～C
7Alkylidene; C
3～C
7The alkylidene carbonyl; Or the C that is interrupted by piperazine
3～C
7Alkylidene;
Y is O, S, NR
6Or CH
2Group; And
N is an integer 0,1 and 2,
[formula 2]
R wherein
12Be methyl, chlorine, 2-aminoethyl, 3-aminopropyl, 4-ammonia butyl, 5-ammonia amyl group, 4-chlorphenyl sulfo-, 3-pyridylmethyl, (imidazo [1,2-a] pyridin-3-yl) methyl, 2-(N-methyl-N-n-pentyl) aminoethyl, suberyl amino, (1-imidazole radicals) methyl or 1-pyrrolidinyl ethyl
R
13Be hydrogen, chlorine or hydroxyl,
M is hydrogen or sodium, and
Z is any number, preferably 0 to 7 integer.
2. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein
Described R
1Be C
1～C
5Alkyl; The C that is replaced by piperidyl
1～C
5Alkyl; C
3～C
6Cycloalkyl; Phenyl; Pyridine radicals; Guanidine radicals; NR
6R
7Piperidyl or piperazinyl, it is by straight chain C
1～C
3Alkyl replaces; Morpholinyl; Or piperidyl;
Described R
2Be hydrogen; Straight or branched C
1～C
4Alkyl, described alkyl are not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; Benzyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholinyl; Thio-morpholinyl; 4-methyl piperazine base; Or straight or branched C
1～C
3Alkyl, described alkyl is by C
1～C
3Alkoxyl, halogen, C
3～C
6Cycloalkyl, morpholinyl, dimethylated morpholinyl, thio-morpholinyl, 4-methyl piperazine base, piperidyl, imidazole radicals or pyrrolidinyl replace,
Described R
3Be hydrogen,
Described R
4Be hydrogen, hydroxyl or fluorine,
Described R
5Be hydrogen or hydroxyl;
Described R
6And R
7Be hydrogen independently of one another; C
1～C
3Alkyl, described alkyl are not substituted or are selected from hydroxyl, C
1～C
3A group of alkoxyl, pyridine radicals, morpholinyl and piperidyl replaces; Benzyl; Carbonyl, described carbonyl is selected from C
1～C
3Alkyl, the C that is replaced by hydroxyl and pyridine radicals
1～C
3A group of alkyl replaces; Or C
1～C
3Alkanesulfonyl;
Described R
8And R
9Be hydrogen independently of one another; C
1～C
4Alkyl, described alkyl are not substituted or are selected from hydroxyl, C
1～C
3A group of alkoxyl, morpholinyl and imidazole radicals replaces; C
3～C
6Cycloalkyl; Benzyl; Or pyridine acyloxy; And
Described X
1-X
2-X
3Be
3. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein
Described R
1It is methyl; Ethyl; Isopropyl; The tert-butyl group; Amyl group; Piperidines-1-ylmethyl; Cyclohexyl; Phenyl; Pyridin-3-yl; Guanidine radicals; NR
6R
71-propyl group-piperidin-4-yl; 4-methyl-piperazine-1-base; Morpholine-4-base; Or piperidin-4-yl;
Described R
2Be hydrogen; Methyl, ethyl, propyl group, isopropyl or butyl, described group are not substituted or by NR
8R
9Replace; Cyclopenta; Benzyl; Vinyl (ehthenyl); By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholine-4-base; Thiomorpholine-4-base; 4-methyl piperazine-1-base; Or straight or branched C
1～C
3Alkyl, described alkyl are by methoxyl group, chlorine, cyclopenta, morpholine-4-base, 2, and 6-thebaine-4-base, thiomorpholine-4-base, 4-methyl piperazine-1-base, piperidines-1-base, imidazoles-1-base or pyrrolidine-1-base replaces;
Described R
6And R
7Be hydrogen independently of one another; Methyl; Ethyl; Propyl group; C
1～C
3The group that alkyl, described alkyl are selected from hydroxyl, methoxyl group, pyridin-3-yl, pyridin-4-yl, morpholine-4-base and piperidines-1-base replaces; Benzyl; The group that carbonyl, described carbonyl are selected from isopropyl, hydroxymethyl, pyridin-3-yl and pyridin-4-yl replaces; Or ethylsulfonyl; And
Described R
8And R
9Be hydrogen independently of one another; Methyl; Ethyl; Propyl group; Isopropyl; Butyl; Isobutyl group; The tert-butyl group; C
1～C
3The group that alkyl, described alkyl are selected from hydroxyl, methoxyl group, isopropoxy, morpholine-4-base and imidazoles-1-base replaces; Cyclopropyl; Cyclohexyl; Benzyl; 3-pyridine acyloxy or 4-pyridine acyloxy.
4. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein
Described R
6And R
7Between to have only a group be hydrogen.
5. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein
Described R
6And R
7All be hydrogen; Or C
1～C
6Alkyl, described alkyl are not substituted or are selected from hydroxyl, C
1～C
6A group of alkoxyl and pyridine radicals replaces.
6. the compositions of prevention according to claim 5 or treatment osteoporosis, wherein
Described R
6And R
7All be hydrogen; Methyl; The methyl that pyridyl replaces; Ethyl; By the ethyl of hydroxyl or methoxyl group replacement; Or propyl group.
7. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein
Described R
6It is methyl; And
Described R
7Be C
1～C
6Alkyl, described alkyl are not substituted or are selected from hydroxyl, C
1～C
6A group of alkoxyl, pyridine radicals and morpholinyl replaces; Benzyl; Or by C
1～C
6The carbonyl that alkyl replaces.
8. the compositions of prevention according to claim 7 or treatment osteoporosis, wherein
Described R
7By the methyl of pyridin-3-yl or pyridin-4-yl replacement; The group that ethyl, described ethyl were not substituted or were selected from hydroxyl, methoxyl group and morpholine-4-base replaces; Benzyl; The carbonyl that is replaced by isopropyl.
9. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein
Described R
6It is ethyl; And
Described R
7Be C
1～C
6Alkyl, described alkyl are not substituted or are replaced by hydroxyl or morpholinyl; Or benzyl.
10. the compositions of prevention according to claim 9 or treatment osteoporosis, wherein
Described R
7By the ethyl of hydroxyl or morpholinyl replacement; Or benzyl.
11. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein
Described R
8And R
9Between to have only a group be hydrogen.
12. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein said R
8And R
9All are C
1～C
6Alkyl, described alkyl is not substituted or is replaced by hydroxyl.
13. the compositions of prevention according to claim 12 or treatment osteoporosis, wherein said R
8And R
9All be ethyl, ethoxy or propyl group.
14. the compositions of prevention according to claim 2 or treatment osteoporosis, wherein said R
8Be C
3～C
6Cycloalkyl; And
Described R
9It is the carbonyl that pyridyl replaces.
15. the compositions of prevention according to claim 14 or treatment osteoporosis, wherein said R
9Be 3-pyridine acyloxy or 4-pyridine acyloxy.
16. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein said R
1Be C
1～C
6Alkyl, described alkyl are not substituted or pyridyl replaces; And
Described R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, described alkyl are not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Amino; Dimethylamino; Morpholinyl; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
17. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein said R
1Be straight or branched C
1～C
6Alkyl, described alkyl quilt
Replace, described
Be not substituted or replaced by hydroxyl; And
Described R
2Be straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
18. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein
Described R
1Be C
3～C
6Cycloalkyl; And
Described R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, described alkyl are not substituted or by NR
8R
9Replace; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
19. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein said R
1Be phenyl or benzyl; And
Described R
2It is phenyl; Benzyl; Amino; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
20. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein
Described R
1Be phenyl or benzyl; And
Described R
2It is phenyl; Benzyl; Amino; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
21. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein
Described R
1It is guanidine radicals; And
Described R
2Be straight or branched C
1～C
6Alkyl, described alkyl are not substituted or by NR
8R
9Replace.
22. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein
Described R
1Be NR
6R
7Or CH
2NR
6R
7And
Described R
2Be hydrogen; Straight or branched C
1～C
6Alkyl, described alkyl are not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; C
2～C
6Thiazolinyl; By NR
8R
9The carbonyl that replaces; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
23. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein said R
1By straight or branched C
1～C
6Alkyl replaces
Group; And
Described R
2Be straight or branched C
1～C
6Alkyl, described alkyl are not substituted or by NR
8R
9Replace; C
3～C
6Cycloalkyl; Morpholinyl; Thio-morpholinyl; 4-methyl piperazine base; Or straight or branched C
1～C
6Alkyl, described alkyl is by hydroxyl, C
1～C
6Alkoxyl, halogen, C
3～C
6Cycloalkyl,
Imidazole radicals or pyrrolidinyl replace.
24. the compositions of prevention according to claim 1 or treatment osteoporosis, wherein said formula 1 chemical compound is selected from:
1) N-hydroxyl-4-{5-[4-(2-isopropyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
2) 4-{5-[4-(2-isopropyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
3) N-hydroxyl-4-{5-[4-(2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
4) N-hydroxyl-4-{5-[4-(2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
5) N-hydroxyl-4-{5-[4-(2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
6) N-hydroxyl-4-{5-[4-(2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
7) N-hydroxyl-4-{5-[4-(2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
8) N-hydroxyl-4-{5-[4-(2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
9) N-hydroxyl-4-{5-[4-(2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
10) N-hydroxyl-4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
11) N-hydroxyl-4-{5-[4-(2-ethyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
12) N-hydroxyl-4-{5-[4-(5-methyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
13) N-hydroxyl-4-{5-[4-(5-methyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
14) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
15) N-hydroxyl-4-{5-[4-(5-methyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
16) N-hydroxyl-4-{5-[4-(the 2-tert-butyl group-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
17) N-hydroxyl-4-{5-[4-(5-ethyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
18) N-hydroxyl-4-{5-[4-(2,5-diethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
19) N-hydroxyl-4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
20) N-hydroxyl-4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
21) N-hydroxyl-4-{5-[4-(5-ethyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
22) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
23) N-hydroxyl-4-{5-[4-(5-ethyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
24) N-hydroxyl-4-{5-[4-(2-ethyl-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
25) N-hydroxyl-4-{5-[4-(2,5-diisopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
26) N-hydroxyl-4-{5-[4-(5-isopropyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
27) N-hydroxyl-4-{5-[4-(5-isopropyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
28) N-hydroxyl-4-{5-[4-(5-isopropyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
29) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
30) N-hydroxyl-4-{5-[4-(5-butyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
31) N-hydroxyl-4-{5-[4-(5-butyl-2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
32) N-hydroxyl-4-{5-[4-(5-butyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
33) N-hydroxyl-4-{5-[4-(5-butyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
34) N-hydroxyl-4-{5-[4-(5-butyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
35) N-hydroxyl-4-{5-[4-(5-butyl-2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
36) N-hydroxyl-4-{5-[4-(5-butyl-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
37) N-hydroxyl-4-{5-[4-(the 5-butyl-2-tert-butyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
38) N-hydroxyl-4-{5-[4-(5-benzyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
39) N-hydroxyl-4-{5-[4-(5-benzyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
40) N-hydroxyl-4-{5-[4-(5-benzyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
41) N-hydroxyl-4-{5-[4-(5-benzyl-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
42) N-hydroxyl-4-{5-[4-(5-(2-chloro-ethyl)-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
43) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
44) N-hydroxyl-4-{5-[4-(5-isobutyl group-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
45) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
46) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
47) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
48) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
49) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-pyridin-3-yl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
50) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-cyclohexyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
51) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-amyl group-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
52) 4-{5-[4-(2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
53) 4-{5-[4-(2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
54) 4-{5-[4-(2,5-dimethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
55) 4-{5-[4-(5-ethyl-2-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
56) 4-{5-[4-(5-ethyl-2-phenyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
57) N-hydroxyl-4-{5-[4-(2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
58) N-hydroxyl-4-{5-[4-(2-amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
59) N-hydroxyl-4-{5-[4-(2-guanidine radicals-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
60) N-hydroxyl-4-{5-[4-(2-amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
61) N-hydroxyl-4-{5-[4-(2-amino-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
62) N-hydroxyl-4-{5-[4-(2-guanidine radicals-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
63) N-hydroxyl-4-{5-[4-(2-amino-5-butyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
64) N-hydroxyl-4-{5-[4-(5-butyl-2-guanidine radicals-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
65) N-hydroxyl-4-{5-[4-(2-amino-5-benzyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
66) N-hydroxyl-4-{5-[4-(5-benzyl-2-guanidine radicals-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
67) N-hydroxyl-4-{5-[4-(2-amino-5-methyl cyclopentane-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
68) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
69) N-hydroxyl-4-{5-[4-(2-(isobutyryl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
70) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
71) N-hydroxyl-4-{5-[4-(2-amino methyl-5-benzyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
72) N-hydroxyl-4-{5-[4-(5-methyl-2-(1-propyl group-piperidin-4-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
73) N-hydroxyl-4-{5-[4-(5-isopropyl-2-aminomethyl-1,2,3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
74) N-hydroxyl-4-{5-[4-(5-vinyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
75) N-hydroxyl-4-{5-[4-(5-hydroxymethyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
76) N-hydroxyl-4-{5-[4-(5-methoxy-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
77) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
78) N-hydroxyl-4-{5-[4-(5-vinyl-2-amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
79) N-hydroxyl-4-{5-[4-(5-vinyl-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
80) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-(pyridin-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
81) N-hydroxyl-4-{5-[4-(2-amino-5-cyclopenta-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
82) N-hydroxyl-4-{5-[4-(5-ethyl-2-aminomethyl-1,2,3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
83) N-hydroxyl-4-{5-[4-(5-isopropyl-2-(piperidines-3-yl)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
84) N-hydroxyl-4-{5-[4-(2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
85) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
86) N-hydroxyl-4-{5-[4-(5-methyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
87) N-hydroxyl-4-{5-[4-(2-ethylamino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
88) N-hydroxyl-4-{5-[4-(5-methyl-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
89) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
90) N-hydroxyl-4-{5-[4-(2-glycoloyl amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
91) N-hydroxyl-4-{5-[4-(5-methyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
92) N-hydroxyl-4-{5-[4-(5-methyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
93) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
94) N-hydroxyl-4-{5-[4-(2-(2-methoxy ethyl) amino-5-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] amoxy }-benzamidine,
95) N-hydroxyl-4-{5-[4-(2-ethanesulfonamido-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
96) N-hydroxyl-4-{5-[4-(5-ethyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
97) N-hydroxyl-4-{5-[4-(5-ethyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
98) N-hydroxyl-4-{5-[4-(5-ethyl-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
99) N-hydroxyl-4-{5-[4-(5-ethyl-2-methoxyl group acetylaminohydroxyphenylarsonic acid 1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
100) N-hydroxyl-4-{5-[4-(5-ethyl-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
101) N-hydroxyl-4-{5-[4-(5-ethyl-2-(3-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
102) N-hydroxyl-4-{5-[4-(5-ethyl-2-(2-methoxy ethyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
103) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
104) N-hydroxyl-4-{5-[4-(2-ethylamino-5-isopropyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
105) N-hydroxyl-4-{5-[4-(5-butyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
106) N-hydroxyl-4-{5-[4-(5-butyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
107) N-hydroxyl-4-{5-[4-(5-benzyl-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
108) N-hydroxyl-4-{5-[4-(5-benzyl-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
109) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
110) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-ethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
111) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
112) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-(4-pyridine radicals carbonyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
113) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-propyl group amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
114) N-hydroxyl-4-{5-[4-(5-isopropyl-2-[(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
115) N-hydroxyl-4-{5-[4-(5-(2-chloroethyl)-2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
116) N-hydroxyl-4-{5-[4-(2-methylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
117) N-hydroxyl-4-{5-[4-(5-ethyl-2-(pyridin-3-yl methyl) amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
118) N-hydroxyl-4-{5-[4-(2-(ethylsulfonyl-methyl-amino)-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
119) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
120) N-hydroxyl-4-[5-(4-{2-[(2-ethoxy)-methyl-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
121) N-hydroxyl-4-[5-(4-{2-[ethyl-(2-ethoxy)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
122) N-hydroxyl-4-[5-(4-{2-[two-(2-methoxy ethyl)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
123) N-hydroxyl-4-[5-(4-{5-methyl-2-[methyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
124) N-hydroxyl-4-[5-(4-{2-[ethyl-1-(2-morpholino ethyl)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
125) N-hydroxyl-4-{5-(4-[2-(benzyl-methyl-amino)-5-methyl isophthalic acid, 3-thiazole-4-yl] phenoxy group) amoxy }-benzamidine,
126) N-hydroxyl-4-[5-{4-[5-methyl-2-(methyl-pyridin-3-yl-methyl-amino)-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine,
127) N-hydroxyl-4-[5-{4-[2-(benzyl-ethyl-amino)-5-methyl isophthalic acid, 3-thiazole-4-yl] phenoxy group } amoxy]-benzamidine,
128) N-hydroxyl-4-[5-(4-{2-[two-(2-ethoxy)-amino]-the 5-methyl isophthalic acid, 3-thiazole-4-yl } phenoxy group) amoxy]-benzamidine,
129) N-hydroxyl-4-[5-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine,
130) N-hydroxyl-4-[5-(4-{5-ethyl-2-[ethyl-(2-ethoxy)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
131) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
132) N-hydroxyl-4-[5-(4-{5-ethyl-2-[ethyl-(2-morpholino ethyl)-amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
133) N-hydroxyl-4-[5-{4-[2-(benzyl-methyl-amino)-5-ethyl-1,3-thiazoles-4-yl] phenoxy group } amoxy]-benzamidine,
134) N-hydroxyl-4-[5-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
135) N-hydroxyl-4-(5-{4-[2-(benzyl-ethyl-amino)-5-ethyl-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine,
136) N-hydroxyl-4-{5-(4-[5-ethyl-2-(ethyl-[pyridin-3-yl methyl] amino)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
137) N-hydroxyl-4-[5-(4-{2-[two-(pyridin-3-yl methyl) amino]-5-ethyl-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
138) N-hydroxyl-4-{5-[4-(2-dipropyl amino-5-ethyl-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
139) N-hydroxyl-4-[5-(4-{2-[two-(2-ethoxy) amino]-5-ethyl-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
140) N-hydroxyl-4-[5-(4-{2-[(2-ethoxy)-methyl-amino]-5-isopropyl-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine,
141) N-hydroxyl-4-[5-(4-{5-isopropyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
142) N-hydroxyl-4-(5-{4-[2-(ethylsulfonyl-methyl-amino)-5-isopropyl-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine,
143) N-hydroxyl-4-[5-(4-{5-butyl-2-[(2-ethoxy)-methyl-amino]-1,3-thiazoles-4-yl } phenoxy group) amoxy]-benzamidine,
144) N-hydroxyl-4-[5-(4-{5-butyl-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
145) N-hydroxyl-4-[5-(4-{5-butyl-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
146) N-hydroxyl-4-{5-[4-(5-butyl-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
147) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(pyridin-3-yl methyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
148) N-hydroxyl-4-[5-(4-{5-methyl cyclopentane-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
149) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
150) N-hydroxyl-4-{5-[4-(5-butyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
151) N-hydroxyl-4-{5-[4-(5-butyl-2-ethylmethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
152) N-hydroxyl-4-{5-[4-(5-butyl-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
153) N-hydroxyl-4-[5-(4-{5-cyclopenta-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
154) N-hydroxyl-4-[5-(4-{5-isobutyl group-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
155) N-hydroxyl-4-(5-{4-[5-(2-chloroethyl)-2-dimethylamino-1,3-thiazoles-4-yl] phenoxy group } amoxy)-benzamidine,
156) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
157) N-hydroxyl-4-{5-[4-(5-isopropyl-2-dipropyl amino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
158) N-hydroxyl-4-{5-[4-(5-ethyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
159) N-hydroxyl-4-[5-(4-{5-isopropyl-2-[methyl-(2-morpholino ethyl) amino]-1,3-thiazoles-4-yl phenoxy group) amoxy]-benzamidine,
160) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
161) N-hydroxyl-4-{5-[4-(5-isopropyl-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
162) N-hydroxyl-4-{5-[4-(5-isopropyl-2-diethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
163) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-dimethylamino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
164) N-hydroxyl-4-{5-[4-(5-methyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
165) N-hydroxyl-4-{5-[4-(5-methyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
166) N-hydroxyl-4-{5-[4-(5-ethyl-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
167) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-piperidino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
168) N-hydroxyl-4-{5-[4-(5-methyl cyclopentane-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
169) N-hydroxyl-4-{5-[4-(5-isopropyl-2-morpholino-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
170) N-hydroxyl-4-{5-(4-[5-methyl cyclopentane-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
171) N-hydroxyl-4-{5-[4-(5-vinyl-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
172) N-hydroxyl-4-{5-[4-(5-cyclopenta-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
173) N-hydroxyl-4-{5-[4-(5-isobutyl group-2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
174) N-hydroxyl-4-{5-(4-[5-ethyl-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
175) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-1,3-thiazoles-4-yl) phenoxy group] amoxy }-benzamidine,
176) N-hydroxyl-4-{5-(4-[5-isopropyl-2-(4-methyl piperazine generation)-1,3-thiazoles-4-yl] phenoxy group) amoxy }-benzamidine,
177) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine,
178) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-ethyoxyl-ethyoxyl)-benzamidine,
179) N-hydroxyl-4-{3-hydroxyl-5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-3-methyl-amoxy }-benzamidine,
180) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-1-methyl-ethylamino-ethyoxyl)-benzamidine,
181) N-hydroxyl-4-[3-(4-{3-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-propyl group-piperazine-1-yl)-propoxyl group]-benzamidine,
182) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-penta acyloxy-amino }-benzamidine,
183) N-hydroxyl-4-({ 5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amyl group }-methyl-amino)-benzamidine,
184) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-2-butylene oxygen base }-benzamidine,
185) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
186) N-hydroxyl-4-(2-{2-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group]-ethylamino-ethyoxyl)-benzamidine,
187) N-hydroxyl-2-fluoro-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
188) 2, N-dihydroxy-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
189) N-hydroxyl-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-3-methoxyl group-benzamidine,
190) N-hydroxyl-2-cyclohexyl amino-4-{5-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
191) N-hydroxyl-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
192) N-hydroxyl-2-fluoro-4-{5-[3-fluoro-4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
193) N-hydroxyl-4-{3-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] propoxyl group }-benzamidine,
194) N-hydroxyl-4-{4-[4-(5-isopropyl-2-methyl isophthalic acid, 3-thiazole-4-yl) phenoxy group] butoxy }-benzamidine,
195) N-hydroxyl-3-{5-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxy group]-amyl group amino }-benzamidine,
196) N-hydroxyl-4-{4-[4-(2-cyclohexyl-5-ethyl-thiazole-4-yl)-phenoxy group]-butoxy }-benzamidine,
197) N-hydroxyl-4-[3-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-thiazole-4-yl } phenoxy group) propoxyl group]-benzamidine,
198) N-hydroxyl-4-[4-(4-{5-ethyl-2-[(2-ethoxy)-methyl-amino]-thiazole-4-yl } phenoxy group) butoxy]-benzamidine,
199) N-hydroxyl-4-[3-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-thiazole-4-yl phenoxy group) propoxyl group]-benzamidine,
200) N-hydroxyl-4-[4-(4-{5-ethyl-2-[methyl-(pyridin-3-yl methyl) amino]-thiazole-4-yl phenoxy group) butoxy]-benzamidine,
201) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-isopropyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
202) N-hydroxyl-4-{4-[4-(5-butyl-2-isopropyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
203) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-amino-thiazolyl--4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
204) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-amino-thiazolyl--4-yl)-phenoxymethyl]-benzyloxy }-2-fluoro-benzamidine,
205) N-hydroxyl-4-{4-[4-(2-methylamino-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
206) N-hydroxyl-4-{6-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-pyridine-2-base-methoxyl group }-benzamidine,
207) N-hydroxyl-2-fluoro-4-{4-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxy group]-butoxy }-benzamidine,
208) N-hydroxyl-4-{2-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
209) N-hydroxyl-4-{3-[4-(5-isopropyl-2-methyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
210) N-hydroxyl-4-{4-[4-(5-methyl cyclopentane-2-cyclohexyl-thiazole-4-yl)-phenoxymethyl]-benzyloxy }-benzamidine,
211) N-hydroxyl-4-{6-[4-(5-isopropyl-2-methyl-thiazole-4-yl) phenoxy group]-hexyloxy }-benzamidine,
212) N-hydroxyl-4-{5-[2-ethyl-5-hydroxyl-4-(2-methyl-thiazole-4-yl) phenoxy group]-amoxy }-benzamidine,
213) N-hydroxyl-4-{5-[2-ethyl-4-(2-methyl-thiazole-4-yl)-5-propoxyl group-phenoxy group]-amoxy }-benzamidine,
214) N-hydroxyl-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
215) 4-(5-{4-[5-(2-isobutyl group aminoethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
216) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-piperidines-1-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
217) N-hydroxyl-4-[5-(4-{2-methyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
218) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
219) N-hydroxyl-4-(5-{4-[5-(2-isopropyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
220) N-hydroxyl-4-[5-(4-{5-[2-(3-isopropoxy-propyl group amino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
221) N-hydroxyl-4-(5-{4-[5-(2-butyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
222) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
223) N-hydroxyl-4-(5-{4-[5-(2-cyclohexyl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
224) N-hydroxyl-4-(5-{4-[5-(2-diethylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
225) N-hydroxyl-4-{5-[4-(5-{2-[two-(2-hydroxyl-ethyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
226) N-hydroxyl-4-(5-{4-[5-(2-diisopropylaminoethyl-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
227) N-hydroxyl-4-[5-(4-{5-[2-(2,6-dimethyl-morpholine-4-yl)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
228) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
229) N-hydroxyl-4-(5-{4-[2-amino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
230) N-hydroxyl-4-[5-(4-{5-[2-(2-dimethylamino-ethylamino)-ethyl]-2-methyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
231) N-hydroxyl-4-(5-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
232) N-hydroxyl-4-[5-(4-{2-methyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
233) N-hydroxyl-4-{5-[4-(5-{2-[two-(2-methoxyl group-ethyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
234) N-hydroxyl-4-(5-{4-[5-(2-tert-butyl group amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
235) N-hydroxyl-4-(5-{4-[5-(2-isobutylamino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
236) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-pyridin-3-yl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
237) N-hydroxyl-4-[5-(4-{5-[2-(4-methyl-piperazine-1-yl)-ethyl]-2-pyridin-3-yl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
238) N-hydroxyl-4-(5-{4-[2-pyridin-3-yl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
239) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-pyridin-3-yl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
240) N-hydroxyl-4-(5-{4-[2-isopropyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
241) N-hydroxyl-4-[5-(4-{2-isopropyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
242) N-hydroxyl-4-(5-{4-[5-(2-imidazoles-1-base-ethyl)-2-isopropyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
243) N-hydroxyl-4-[5-(4-{2-isopropyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
244) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-isopropyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
245) N-hydroxyl-4-(5-{4-[2-isopropyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
246) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
247) N-hydroxyl-4-[5-(4-{2-cyclohexyl-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
248) N-hydroxyl-4-[5-(4-{2-cyclohexyl-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
249) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
250) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dimethylamino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
251) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-dipropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
252) N-hydroxyl-4-(5-{4-[2-cyclohexyl-5-(2-cyclopropyl amino-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
253) N-hydroxyl-4-[5-(4-{2-amino-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
254) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-phenyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
255) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
256) N-hydroxyl-4-(5-{4-[2-ethyl-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
257) N-hydroxyl-4-(4-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-butoxy)-benzamidine,
258) 4-(5-{4-[2-cyclohexyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
259) 4-(5-{4-[2-methyl-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
260) N-hydroxyl-4-(5-{4-[2-methylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
261) N-hydroxyl-4-[5-(4-{2-methylamino-5-[2-(4-methyl-piperazine-1-yl)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
262) N-hydroxyl-4-(5-{4-[2-methylamino-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
263) N-hydroxyl-4-[5-(4-{2-methylamino-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
264) N-hydroxyl-4-[5-(4-{5-[2-(3-imidazoles-1-base-propyl group amino)-ethyl]-2-methylamino-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
265) 4-(5-{4-[2-methylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
266) N-hydroxyl-4-(5-{4-[2-dimethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
267) N-hydroxyl-4-(5-{4-[2-dimethylamino-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
268) N-hydroxyl-4-(5-{4-[2-(isobutyryl-methyl-amino)-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
269) N-hydroxyl-4-(5-{4-[2-[benzyl-(2-morpholine-4-base-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
270) N-hydroxyl-4-(5-{4-[2-diethylamino-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
271) N-hydroxyl-4-(5-{4-[2-[two-(2-methoxyl group-ethyl)-amino]-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
272) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
273) N-hydroxyl-4-(5-{4-[2-morpholine-4-base-5-(2-thiomorpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
274) N-hydroxyl-4-[5-(4-{5-[2-(4-methyl-piperazine-1-yl)-ethyl]-2-morpholine-4-base-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
275) N-hydroxyl-4-[5-(4-{2-morpholine-4-base-5-[2-(2-morpholine-4-base-ethylamino)-ethyl]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
276) N-hydroxyl-4-(5-{4-[5-(2-morpholine-4-base-ethyl)-2-piperidines-1-base-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
277) 4-(5-{4-[2-morpholine-4-base-5-(2-morpholine-4-base-ethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
278) N-hydroxyl-4-(5-{4-[5-(2-isobutyryl amino-ethyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
279) N-hydroxyl-4-{5-[4-(5-{2-[isobutyl group-(pyridine-3-carbonyl)-amino]-ethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
280) N-hydroxyl-4-{5-[4-(5-{2-[cyclopropyl-(pyridine-4-carbonyl)-amino]-ethyl-2-isopropyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
281) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-{2-[cyclopropyl-(pyridine-3-carbonyl)-amino]-ethyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine,
282) N-hydroxyl-4-{5-[4-(5-methylamino formoxyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
283) N-hydroxyl-4-{5-[4-(5-isopropyl carbamoyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
284) N-hydroxyl-4-{5-[4-(5-{3-imidazoles-1-base-propyl group carbamoyl }-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
285) N-hydroxyl-4-{5-[4-(2-amino-5-methylamino formoxyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
286) N-hydroxyl-4-{5-[4-(2-methyl-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
287) N-hydroxyl-4-(5-{4-[2-methyl-5-(4-methyl-piperazine-1-yl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
288) N-hydroxyl-4-{5-[4-(2-amino-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
289) N-hydroxyl-4-(5-{4-[5-(4-methyl-piperazine-1-yl)-2-morpholine-4-base-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
290) N-hydroxyl-4-{5-[4-(2,5-dimorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
291) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-thiomorpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
292) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-pyrrolidine-1-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
293) N-hydroxyl-4-{5-[4-(2-methyl-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
294) N-hydroxyl-4-(5-{4-[2-methyl-5-(4-methyl-piperazine-1-ylmethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
295) N-hydroxyl-4-{5-[4-(2-methyl-5-thiomorpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
296) N-hydroxyl-4-{5-[4-(2-methyl-5-piperidines-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
297) N-hydroxyl-4-{5-[4-(5-dimethylamino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
298) N-hydroxyl-4-{5-[4-(5-butyl amino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
299) N-hydroxyl-4-(5-{4-[5-(isobutylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
300) N-hydroxyl-4-(5-{4-[5-(tert-butyl group amino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
301) N-hydroxyl-4-{5-[4-(2-methyl-5-propyl group amino methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
302) N-hydroxyl-4-[5-(4-{2-methyl-5-[(2-morpholine-4-base-ethylamino)-methyl]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
303) N-hydroxyl-4-[5-(4-{5-[(3-imidazoles-1-base-propyl group amino)-methyl]-2-methyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
304) N-hydroxyl-4-{5-[4-(2-methyl-5-pyrrolidine-1-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
305) N-hydroxyl-4-{5-[4-(5-imidazoles-1-ylmethyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
306) N-hydroxyl-4-(5-{4-[5-(benzylamino-methyl)-2-methyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
307) N-hydroxyl-4-{5-[4-(5-cyclopropyl amino methyl-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
308) N-hydroxyl-4-{5-[4-(2-methylamino-5-morpholine-4-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
309) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-4-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
310) N-hydroxyl-4-[5-(4-{2-[(2-hydroxyl-ethyl)-methyl-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
311) N-hydroxyl-4-(5-{4-[2-(ethyl-methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
312) N-hydroxyl-4-(5-{4-[2-(benzyl-methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
313) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
314) N-hydroxyl-4-[5-(4-{2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-thiomorpholine-4-ylmethyl-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
315) N-hydroxyl-4-[5-(4-{5-{[two-(2-methoxyl group-ethyl)-amino]-methyl-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
316) N-hydroxyl-4-(5-{4-[2-[methyl-(2-morpholine-4-base-ethyl)-amino]-5-(4-methyl-piperazine-1-ylmethyl)-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
317) N-hydroxyl-4-[5-(4-{5-(isopropyl amino-methyl)-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl-phenoxy group)-amoxy]-benzamidine,
318) N-hydroxyl-4-[5-(4-{5-[(2-methoxyl group-ethylamino)-methyl]-2-[methyl-(2-morpholine-4-base-ethyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
319) N-hydroxyl-4-[5-(4-{2-[(2-methoxyl group-ethyl)-methyl-amino]-5-morpholine-4-ylmethyl-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
320) N-hydroxyl-4-(5-{4-[2-(methyl-propyl group-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
321) N-hydroxyl-4-(5-{4-[2-(methyl-pyridin-3-yl methyl-amino)-5-morpholine-4-ylmethyl-thiazole-4-yl]-phenoxy group-amoxy)-benzamidine,
322) N-hydroxyl-4-{5-[4-(2-methyl-5-methylamino-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
323) N-hydroxyl-4-[5-(4-{2-methyl-5-[(pyridine-4-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
324) N-hydroxyl-4-[5-(4-{2-methyl-5-[(pyridine-3-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
325) N-hydroxyl-4-[5-(4-{2-phenyl-5-[(pyridine-3-carbonyl)-amino]-thiazole-4-yl }-phenoxy group)-amoxy]-benzamidine,
326) N-hydroxyl-4-{5-[4-(5-dimethylamino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
327) N-hydroxyl-4-{5-[4-(5-dimethylamino-2-phenyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
328) N-hydroxyl-4-{5-[4-(2-cyclohexyl-5-dimethylamino-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
329) N-hydroxyl-4-{5-[4-(2-methyl-5-[1,2,4] triazol-1-yl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
330) N-hydroxyl-4-{5-[4-(5-amino-2-phenyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
331) N-hydroxyl-4-{5-[4-(5-amino-2-methyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
332) N-hydroxyl-4-{5-[4-(5-amino-2-pyridin-3-yl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
333) N-hydroxyl-4-{5-[4-(5-amino-2-ethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
334) N-hydroxyl-4-{5-[4-(5-amino-2-cyclohexyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
335) N-hydroxyl-4-{5-[4-(2-methylamino-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine,
336) N-hydroxyl-4-{5-[4-(2-morpholine-4-base-5-morpholine-4-ylmethyl-thiazole-4-yl)-phenoxy group]-amoxy-benzamidine and
337) N-hydroxyl-4-{5-[4-(5-morpholine-4-base-2-piperidines-1-base-thiazole-4-yl)-phenoxy group]-amoxy }-benzamidine.
25. the compositions of prevention according to claim 1 or treatment osteoporosis, the diphosphate of wherein said formula 2 is selected from etidronic acid, clodronic acid, pamidronic acid, tiludronic acid, risedronic acid, minodronic acid, ibandronic acid, zoledronic acid and alendronic Acid.
26. the compositions of prevention according to claim 1 or treatment osteoporosis, the compositions that wherein prepares described prevention or treatment osteoporosis with the form of combination formulations, described combination formulations comprise (a) Benzamine derivatives or its salt and the diphosphate of (b) being represented by following formula 2 by following formula 1 expression.
27. the compositions of prevention according to claim 1 or treatment osteoporosis, the compositions that wherein prepares described prevention or treatment osteoporosis with the form of unitary agent, described unitary agent comprise (a) Benzamine derivatives or its salt and the diphosphate of (b) being represented by following formula 2 by following formula 1 expression.
28. the compositions of prevention according to claim 1 or treatment osteoporosis wherein provides to comprise described (a) by the Benzamine derivatives of following formula 1 expression or its salt with (b) by the diphosphate of following formula 2 expressions each two kinds of a kind of unitary agent wherein in a test kit.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20080075791 | 2008-08-01 | ||
| KR10-2008-0075791 | 2008-08-01 | ||
| KR1020090007774A KR20100014090A (en) | 2008-08-01 | 2009-01-31 | A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivative or its salt, and bisphosphonate |
| KR10-2009-0007774 | 2009-01-31 | ||
| PCT/KR2009/004295 WO2010013975A2 (en) | 2008-08-01 | 2009-07-31 | A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivative or its salt, and bisphosphonate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102149381A true CN102149381A (en) | 2011-08-10 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009801335866A Pending CN102149381A (en) | 2008-08-01 | 2009-07-31 | A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivative or its salt, and bisphosphonate |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP2307016A4 (en) |
| JP (1) | JP2011529876A (en) |
| KR (2) | KR20100014090A (en) |
| CN (1) | CN102149381A (en) |
| CA (1) | CA2732864A1 (en) |
| WO (1) | WO2010013975A2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US9187485B2 (en) | 2007-02-02 | 2015-11-17 | Baylor College Of Medicine | Methods and compositions for the treatment of cancer and related hyperproliferative disorders |
| CN102149380B (en) * | 2008-08-01 | 2012-12-05 | 同和药品株式会社 | A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivatives or their salts, and alendronic acid or its salt |
| JP2016534124A (en) * | 2013-08-29 | 2016-11-04 | ベイラー カレッジ オブ メディスンＢａｙｌｏｒ Ｃｏｌｌｅｇｅ Ｏｆ Ｍｅｄｉｃｉｎｅ | Compositions and methods for the treatment of metabolism and weight related diseases |
| JP6660380B2 (en) | 2014-09-29 | 2020-03-11 | エー１２３ システムズ エルエルシーＡ１２３ Ｓｙｓｔｅｍｓ ＬＬＣ | Method of making prelithiated silicon anode containing PVDF binder |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5451700A (en) * | 1991-06-11 | 1995-09-19 | Ciba-Geigy Corporation | Amidino compounds, their manufacture and methods of treatment |
| CA2278190A1 (en) * | 1997-02-04 | 1998-08-06 | Hong-Suk Suh | 3-amino-1,2-benzoisoxazole derivatives, process for preparation, and use thereof |
| US5998390A (en) * | 1998-09-28 | 1999-12-07 | The Research Foundation Of State University Of New York | Combination of bisphosphonate and tetracycline |
| AR024462A1 (en) * | 1999-07-01 | 2002-10-02 | Merck & Co Inc | PHARMACEUTICAL TABLETS |
| KR100317935B1 (en) * | 1999-10-20 | 2001-12-22 | 유승필 | Pharmaceutical compositions and preparations for treatment of metabolic bone disease |
| KR100454767B1 (en) * | 2001-07-19 | 2004-11-03 | 동화약품공업주식회사 | Use of 4-[(4-thiazolyl)phenoxy]alkoxy-benzamidine derivatives for treatment of osteoporosis |
| JP2003292453A (en) * | 2002-04-02 | 2003-10-15 | Asahi Kasei Corp | Medicinal agent composition for treating bone disease |
| SI1596870T2 (en) * | 2002-12-20 | 2011-07-29 | Hoffmann La Roche | High dose ibandronate formulation |
| JPWO2005002590A1 (en) * | 2003-07-01 | 2006-08-10 | アステラス製薬株式会社 | Bone mass increase inducer |
| JP2007502300A (en) * | 2003-08-13 | 2007-02-08 | カイロン コーポレイション | GSK-3 inhibitor and use thereof |
| US7410977B2 (en) * | 2004-04-28 | 2008-08-12 | Merck & Co., Inc. | Fluorinated 4-azasteroids as androgen receptor modulators |
| AU2005260327B2 (en) * | 2004-07-05 | 2009-10-01 | Dong Wha Pharmaceutical Co., Ltd. | Pharmaceutical composition for the treatment of bone fracture |
| JP5102781B2 (en) * | 2006-01-31 | 2012-12-19 | ドン ファ ファーマシューティカル カンパニー リミテッド | NOVEL BENZAMIDINE DERIVATIVE, PROCESS FOR PRODUCING THE SAME AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME |
| JP2009017222A (en) * | 2007-07-04 | 2009-01-22 | Panasonic Corp | Color adjustment apparatus, color adjustment method, and integrated circuit of color adjustment apparatus |
| MX2010001047A (en) * | 2007-08-02 | 2010-03-03 | Teijin Pharma Ltd | Preventive agent or therapeutic agent for disease caused by abnormal bone metabolism. |
| CN102149380B (en) * | 2008-08-01 | 2012-12-05 | 同和药品株式会社 | A pharmaceutical composition for preventing or treating osteoporosis comprising benzamidine derivatives or their salts, and alendronic acid or its salt |
-
2009
- 2009-01-31 KR KR1020090007774A patent/KR20100014090A/en unknown
- 2009-07-31 CN CN2009801335866A patent/CN102149381A/en active Pending
- 2009-07-31 WO PCT/KR2009/004295 patent/WO2010013975A2/en active Application Filing
- 2009-07-31 KR KR1020090070538A patent/KR20100014174A/en not_active Application Discontinuation
- 2009-07-31 CA CA2732864A patent/CA2732864A1/en not_active Abandoned
- 2009-07-31 EP EP09803180A patent/EP2307016A4/en not_active Withdrawn
- 2009-07-31 JP JP2011521047A patent/JP2011529876A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100014174A (en) | 2010-02-10 |
| WO2010013975A2 (en) | 2010-02-04 |
| KR20100014090A (en) | 2010-02-10 |
| CA2732864A1 (en) | 2010-02-04 |
| JP2011529876A (en) | 2011-12-15 |
| WO2010013975A3 (en) | 2010-06-03 |
| EP2307016A4 (en) | 2011-12-28 |
| EP2307016A2 (en) | 2011-04-13 |
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Application publication date: 20110810 |