Metal-salen complex compound, local anesthetic and antineoplastic drug

Abstract

A metal-salen complex compound, which exhibits excellent noninvasiveness and can be efficiently transferred to an affected site, a local anesthetic containing this metal-salen complex compound, and an antineoplastic drug containing this metal-salen complex compound are provided. Regarding the metal-salen complex compound, a metal atom part in each of two molecules of a metal-salen complex or a derivative of the metal-salen complex is dimerized via water, and the metal-salen complex compound is mixed with a base to produce an ointment.

1 . An ointment produced by mixing a self-magnetic metal-salen complex compound, in which a metal atom part in each of multiple molecules of a metal-salen complex or a derivative of the metal-salen complex is multimerized via water, with a base. 
     
     
         2 . The ointment according to  claim 1 , wherein the multiple molecules are two molecules and the metal atom part of each of the two molecules is dimerized via water. 
     
     
         3 . An ointment produced by mixing a self-magnetic metal-salen complex compound expressed by any one of the following Formulas (I), (II), and (III) with a base: 
       
         
           
           
               
               
           
         
         where M in all Formulas (I), (II), and (III) represents Fe, Cr, Mn, Co, Ni, Mo, Ru, Rh, Pd, W, Re, Os, Ir, Pt, Nd, Sm, Eu, or Gd and; 
         each of a to f and Y is hydrogen (where M is Fe, excluding a case where all of a to f and Y are hydrogens) or any one of the following (1) to (7): 
       
       
         
           
           
               
               
           
         
         (where R 2  represents a plurality of nucleic acids which are combined together and are formed of adenine, guanine, thymine, cytosine, or uracil); 
       
       (5) —NHCOH, —NH 2 , —NHR 1 , or, —NR 1 R 2  
 (where R 1  and R 2  are alkyl or alkane with the same carbon number or the carbon number from 1 to 6); 
 
       (6) —NHR 3 —, —NHCOR 3 , or, —R 3  
 (where R 3  represents a substituent bound as a result of desorption of a functional group such as hydrogen or a hydroxyl group); and 
 
       (7) halogen atoms such as chlorine, bromine, or fluorine. 
     
     
         4 . The ointment according to  claim 3 , wherein charge transfer of R 3  is less than 0.5 electrons (e). 
     
     
         5 . The ointment according to  claim 3  or  claim 4 , wherein R 3  is any one of compounds represented by the following formulas (1) to (27):
 (1) Ibuprofen piconol, phenylpropionic acid analgesic/anti-inflammatory 
 
       
         
           
           
               
               
           
         
         (2) Mefenamic, anthranilic-acid anti-inflammatory analgesic 
       
       
         
           
           
               
               
           
         
         (3) Drug for treating hyperlipemia 
       
       
         
           
           
               
               
           
         
         (4) Antibacterial 
       
       
         
           
           
               
               
           
         
         (5) Fluorochrome (rhodamine) 
       
       
         
           
           
               
               
           
         
         (6) Hormone (estrogen) 
       
       
         
           
           
               
               
           
         
         (7) Hormone (estrogen) 
       
       
         
           
           
               
               
           
         
         (8) Taxol (paclitaxel) 
       
       
         
           
           
               
               
           
         
         (9) Amino acid (glycine) 
       
       
         
           
           
               
               
           
         
         (10) Amino acid (alanine) 
       
       
         
           
           
               
               
           
         
         (11) Amino acid (arginine) 
       
       
         
           
           
               
               
           
         
         (12) Amino acid (asparagine) 
       
       
         
           
           
               
               
           
         
         (13) Amino acid (aspartic acid) 
       
       
         
           
           
               
               
           
         
         (14) Amino acid (cysteine) 
       
       
         
           
           
               
               
           
         
         (15) Amino acid (glutamic acid) 
       
       
         
           
           
               
               
           
         
         (16) Amino acid (histidine) 
       
       
         
           
           
               
               
           
         
         (17) Amino acid (isoleucine) 
       
       
         
           
           
               
               
           
         
         (18) Amino acid (leucine) 
       
       
         
           
           
               
               
           
         
         (19) Amino acid (lysine) 
       
       
         
           
           
               
               
           
         
         (20) Amino acid (methionine) 
       
       
         
           
           
               
               
           
         
         (21) Amino acid (phynelalanine) 
       
       
         
           
           
               
               
           
         
         (22) Amino acid (proline) 
       
       
         
           
           
               
               
           
         
         (23) Amino acid (serine) 
       
       
         
           
           
               
               
           
         
         (24) Amino acid (threonine) 
       
       
         
           
           
               
               
           
         
         (25) Amino acid (tryptophan) 
       
       
         
           
           
               
               
           
         
         (26) Amino acid (tyrosine) 
       
       
         
           
           
               
               
           
         
         (27) Amino acid (valine) 
       
       
         
           
           
               
               
           
         
       
     
     
         6 . A local anesthetic having the self-magnetic metal-salen complex compound described in  claim 3 , wherein the self-magnetic metal-salen complex compound is mixed with a base to produce an ointment and R 3  is a compound composed of a substituent represented by any one of the following formulas (28) to (38) obtained as a result of desorption of hydrogen from a compound which has a methyl group and whose charge transfer is less than 0.5 electors (e):
 (28) General name: lidocaine   
       
         
           
           
               
               
           
         
         (29) General name: ethyl aminobenzoic acid 
       
       
         
           
           
               
               
           
         
         (30) General name: oxybuprocaine hydrochloride 
       
       
         
           
           
               
               
           
         
         (31) General name: oxethazaine 
       
       
         
           
           
               
               
           
         
         (32) General name: dibucaine 
       
       
         
           
           
               
               
           
         
         (33) General name: ethylpiperidinoacetylaminobenzoate 
       
       
         
           
           
               
               
           
         
         (34) General name: procaine 
       
       
         
           
           
               
               
           
         
         (35) General name: mepivacaine 
       
       
         
           
           
               
               
           
         
         (36) General name: p-butylaminobenzoyldiethylaminoethanol hydrochloride 
       
       
         
           
           
               
               
           
         
         (37) General name: bupivacaine hydrochloride 
       
       
         
           
           
               
               
           
         
         (38) General name: ropivacaine hydrochloride hydrate 
       
       
         
           
           
               
               
           
         
       
     
     
         7 . An antineoplastic drug having any one self-magnetic metal-salen complex compound described in  claim 3  or  claim 4 , wherein the self-magnetic metal-salen complex compound is mixed with a base to produce an ointment and R 3  is any one of compounds represented by the following formulas (39) to (103), which combines with a main skeleton of the compound of the above formula via a linking group part obtained as a result of desorption of hydrogen (however, with the compound (83), a cyano group (—CN) is the linking group):
 (39) General name: ifosfamide, alkyl antineoplastic drug 
 
       
         
           
           
               
               
           
         
         (40) General name: cyclophosphamide, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (41) General name: dacarbazine, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (42) General name: busulfan, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (43) General name: melphalan, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (44) General name: ranimustine, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (45) General name: estramustine sodium phosphate, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (46) General name: nimustine hydrochloride, alkyl antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (47) General name: enocitabine, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (48) General name: capecitabine, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (49) General name: carmofur, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (50) General name: gimeracil, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (51) General name: oteracil potassium, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (52) General name: cytarabine, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (53) General name: cytarabine ocfosfate, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (54) General name: tegafur, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (55) General name: doxifluridine, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (56) General name: hydroxycarbamide, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (57) General name: fluorouracil, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (58) General name: mercaptopurine hydrate, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (59) General name: fludarabine phosphate, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (60) General name: gemcitabine hydrochloride, antimetabolite antineoplastic drug 
       
       
         
           
           
               
               
           
         
         (61) General name: actinomycin-D, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (62) General name: aclarubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (63) General name: idarubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (64) General name: epirubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (65) General name: zinostatin stimalamer, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         R 1  and R 2  differ from one another and represent the following formulas, 
         respectively, and the same applies to R′ 1  and R′ 2 . 
       
       
         
           
           
               
               
           
         
         A 1 =H or NH 4    
         A 2 , A 3 =H or NH 4  or C 4 H 9    
         (A 2  and A 3  do not represent C 4 H 9  at the same time) 
         M+n: approximately 5.5 on average 
         (66) General name: daunorubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (67) General name: doxorubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (68) General name: bleomycin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (69) General name: peplomycin sulfate, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (70) General name: mitomycin C, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (71) General name: amrubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (72) General name: vibramycin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (73) General name: pirarubicin hydrochloride, antitumor antibiotic 
       
       
         
           
           
               
               
           
         
         (74) General name: docetaxel hydrate, microtubule inhibitor 
       
       
         
           
           
               
               
           
         
         (75) General name: vincristine sulfate, microtubule inhibitor 
       
       
         
           
           
               
               
           
         
         (76) General name: vinblastine sulfate, microtubule inhibitor 
       
       
         
           
           
               
               
           
         
         (77) General name: vinorelbine tartrate, microtubule inhibitor 
       
       
         
           
           
               
               
           
         
         (78) General name: vindesine sulfate, microtubule inhibitor 
       
       
         
           
           
               
               
           
         
         (79) General name: oxaliplatin, platinum preparation 
       
       
         
           
           
               
               
           
         
         (80) General name: carboplatin, platinum preparation 
       
       
         
           
           
               
               
           
         
         (81) General name: cisplatin, platinum preparation 
       
       
         
           
           
               
               
           
         
         (82) General name: nedaplatin, platinum preparation 
       
       
         
           
           
               
               
           
         
         (83) General name: anastrozole, parahormone drug 
       
       
         
           
           
               
               
           
         
         (84) General name: Afema, parahormone drug 
       
       
         
           
           
               
               
           
         
         (85) General name: exemestane, parahormone drug 
       
       
         
           
           
               
               
           
         
         (86) General name: tamoxifen citrate, parahormone drug 
       
       
         
           
           
               
               
           
         
         (87) General name: toremifene citrate, parahormone drug 
       
       
         
           
           
               
               
           
         
         (88) General name: bicalutamide, parahormone drug 
       
       
         
           
           
               
               
           
         
         (89) General name: flutamide, parahormone drug 
       
       
         
           
           
               
               
           
         
         (90) General name: mepitiostane, parahormone drug 
       
       
         
           
           
               
               
           
         
         (91) General name: estramustine sodium phosphate, parahormone drug 
       
       
         
           
           
               
               
           
         
         (92) General name: medroxyprogesterone acetate, parahormone drug 
       
       
         
           
           
               
               
           
         
         (93) General name: tamibarotene, molecular target therapeutic drug 
       
       
         
           
           
               
               
           
         
         (94) General name: Gefitinib, molecular target therapeutic drug 
       
       
         
           
           
               
               
           
         
         (95) General name: tretinoin, molecular target therapeutic drug 
       
       
         
           
           
               
               
           
         
         (96) General name: imatinib mesylate, molecular target therapeutic drug 
       
       
         
           
           
               
               
           
         
         (97) General name: etoposide, topoisomerase inhibitor 
       
       
         
           
           
               
               
           
         
         (98) General name: sobuzoxane, topoisomerase inhibitor 
       
       
         
           
           
               
               
           
         
         (99) General name: irinotecan hydrochloride, topoisomerase inhibitor 
       
       
         
           
           
               
               
           
         
         (100) General name: nogitecan hydrochloride, topoisomerase inhibitor 
       
       
         
           
           
               
               
           
         
         (101) General name: ubenimex, nonspecific immunopotentiator 
       
       
         
           
           
               
               
           
         
         (102) General name: sizofiran, nonspecific immunopotentiator 
       
       
         
           
           
               
               
           
         
         (103) General name: lenthinan, nonspecific immunopotentiator 
       
       
         
           
           
               
               
           
         
       
     
     
         8 . An antineoplastic drug having any one self-magnetic metal-salen complex compound described in  claim 3  or  claim 4 , wherein the self-magnetic metal-salen complex compound is mixed with a base to produce an ointment and R 3  is composed of any one of compounds represented by the following formulas (104) to (109):
 (104) Product name: Leuplin; and general name: leuprorelin acetate, anti-tumor agent 
 
       
         
           
           
               
               
           
         
         (105) Product name: methotrexate; and general name: methotrexate, anti-tumor agent 
       
       
         
           
           
               
               
           
         
         (106) Product name: Novantrone; and general name: mitoxantrone hydrochloride, anti-tumor agent 
       
       
         
           
           
               
               
           
         
         (107) Product name: photofrin; and general name: porfimer sodium, anti-tumor agent 
       
       
         
           
           
               
               
           
         
         (108) Product name: photofrin; and general name: porfimer sodium, anti-tumor agent 
       
       
         
           
           
               
               
           
         
         (109) Product name: Mylotarg; and general name: gemtuzumab ozogamicin, anti-tumor agent 
       
       
         
           
           
               
               
           
         
       
     
     
         9 . An ointment produced by mixing a self magnetic metal-salen complex compound, in which at least one of positions a, b, c, d, e, f, g, h, i, j, k, and l of the following compound is bonded to another compound and said another compound is magnetized, with a base: 
       
         
           
           
               
               
           
         
         where M represents Fe, Cr, Mn, Co, Ni, Mo, Ru, Rh, Pd, W, Re, Os, Ir, Pt, Nd, Sm, Eu, or Gd. 
       
     
     
         10 . An ointment characterized in that any one of the compounds described in any one of  claim 1  to  claim 9  is mixed at a rate of 0.01 wt % to 10 wt % with a base.